Bacteraemia is a common and one of the serious complications in haematopoietic stem cell transplantation (HSCT). To date, there are no published data on antibiotic resistance and clinical outcome among HSCT recipients in Malaysia. The aim of the present study was to analyse the prevalence, antibiotic resistance and clinical outcome of bacteraemia in HSCT recipients, within 100 days following transplantation. We retrospectively analysed the prevalence, antibiotic resistance pattern and mortality rate of early bacteraemia among HSCT recipients in a single centre over a 5-year period (2013-2017). Thirty patients of 85 HSCT recipients developed bacteraemia with 40 positive cultures resulting in prevalence of 47% (40/85). Gram negative bacteria (GNB) accounted for 60.5% of total isolates. Enterobacteriaceae and Coagulase negative Staphylococcus (CoNS) were the commonest pathogens isolated. GNB showed a high resistance rate to ciprofloxacin. Only 30% of recipients responded to first line empirical antibiotics for febrile neutropenia (FN). The mortality rate was 13.3% (4/30), of which 50% was attributed to multi-drug resistance (MDR) Acinetobacter and 25% to extended spectrum beta-lactamase (ESBL) Enterobacteriaceae. Bacteraemia is a frequent and life-threatening early complication among HSCT recipients with MDR GNB being the commonest cause of mortality. The high rate of resistance to ciprofloxacin and failure of the first line empirical antibiotics to treat FN calls for a thorough evaluation of the current antibiotic prophylaxis and empirical treatment protocols. These findings have important clinical implications regarding the use and selection of both prophylactic and empiric antibiotic regimens to treat FN.
Clinacanthus nutans (C. nutans), a well-known ethnopharmacological plant consumed for its medicinal purposes by Southeast Asian communities. C. nutans is said to possess antipyretic, inflammatory, antiedemic as well as analgesic properties and used traditionally in treating various skin ailments, Herpes infection, cancer and diabetes. The young leaves of this C. nutans are consumed in Malaysia for maintaining health. In this study, the proliferative activity of human gingival fibroblast cells (HGF-1, ATCC®CRL-2014™, USA) treated with the ethanol extract obtained from C. nutans leaves at three different concentrations (250, 125 and 62.5 µg/ml) was compared with the untreated cells using alamarBlue assay. The proliferative activity of HGF-1 using alamarBlue assay showed that the cells treated with 62.5 μg/ml of ethanolic extract of C. nutans leaves exhibited increased proliferation compared to the other groups and hence does not exhibit any cytotoxicity on HGF-1.
We report two cases of biphenotypic acute leukaemia diagnosed in Hospital Universiti Kebangsaan Malaysia (HUKM), their clinical, haematological characteristics and response to chemotherapy. Both patients are middle-aged ladies who presented with hepatosplenomegaly and high white cell count, mainly composed of blast cells. Their bone marrow aspirations were hypercellular comprising of more than 90% heterogenous blast cells. Cytochemical analyses show more than 3% positivity towards peroxidase, with smaller blasts showing block positivity towards PAS. Immunophenotypically, the blasts showed dual expression of CD 33 and CD 19, CD 19 and CD34, intra CD22, intra TdT and intraMPO. One of the patients showed presence of the Philadelphia chromosome on cytogenetic analysis which was confirmed by Fluorecsence In Situ Hybridisation (FISH). Molecular analysis also showed presence of the BCR-ABL fusion protein. Both patients were given combination chemotherapy consisting of daunorubicin and cytosine arabinoside.However, the patient with positive Philadelphia chromosome BCR-ABL did not achieve morphological remission after induction chemotherapy. In view of the poor prognosis of this disease, both the patients were planned for upfront peripheral blood stem cell transplantation.
The aim of this study was to determine the genotoxicity of a locally produced nanocomposite by Universiti Sains Malaysia, Malaysia using Comet assay. Stem cells from human exfoliated deciduous teeth (SHED) were treated with the nanocomposite at five different concentrations (0.006, 0.0125, 0.025, 0.05, and 0.1 mg/ml) along with concurrent negative (medium alone) and positive control (zinc sulfate heptahydrate) and incubated at 37°C for 24 hours in an incubator at 5% CO2. The tail moment was used to assess the extent of DNA damage. The tail moment for the group of SHED treated with nanocomposite (for all the five different concentrations) was not statistically significant as compared to the negative control, suggesting that the locally produced dental nanocomposite did not induce any DNA damage. Hence, it can be concluded that the locally produced nanocomposite is non-genotoxic on stem cells from human exfoliated deciduous teeth.
University students experience a substantial amount of change where they
progress from the highly controlled setting of school to the self-motivated
environment of the university. Many changes which involve social,
financial, and environment elements, can be a burden to the students putting
them at risk in negative health behaviours. Negative health behaviours
among university students are a cause for concern since they have a
tendency to be carried into adulthood, which may cause the emergence of
chronic disease at a younger age. Spiritual intelligence together with selfefficacy
is seen to promote better health behaviour. Therefore, the purpose
of the study was to investigate the relationship between spiritual intelligence
and self-efficacy on health behaviours among university students in
Universiti Putra Malaysia, Malaysia. A correlational study was conducted
on 400 undergraduate university students living on campus and were chosen
through stratified random sampling technique using closed ended
questionnaires (The Spiritual Self-Report Inventory, General Self Efficacy
Scale and a modified version of Health Style Questionnaire). Pearson
correlation and structural equation modelling were used to explore
association between these aspects. Spiritual intelligence, self-efficacy and
health behaviour were significantly correlated. Self-efficacy showed a
partial mediation effect towards the relationship between spiritual
intelligence and promoting health behaviour (p=0.000). Thus, an association
was found between spiritual intelligence with health behaviour, and selfefficacy
with health behaviour. It is interpreted that spiritual intelligence can
boost positive health behaviour and it is associated with self-efficacy
relevantly gives benefit to health behaviour. Such data have important
implications for both health practice and policy, especially in the context of
higher education institutions.
Salted fish is a locally processed raw food which is used in everyday cooking among Malaysians. Previous studies suggested that salted fish intake was a risk of nasopharyngeal cancer. Hence, this study was carried out to evaluate gene mutation effects through the induction of mutagenic effect of aqueous and methanol extracts of salted fish from Balik Pulau, Pulau Pinang, Malaysia. Balik Pulau was chosen for sampling purpose due to its popularity as a commercial centre for local raw fisheries in Malaysia. Evaluation of mutagenic effect was carried out by hprt Gene Mutation Assay towards V79 lung fibroblast cells. It was found that the aqueous and methanol extracts of salted fish were not cytotoxic towards V79 lung fibroblast cells. It was also found that the extracts of salted fish from Balik Pulau were not mutagenic towards hprt gene of V79 lung fibroblast cells as the mutation frequency of the extracts did not exceed 3 times of the value for negative control mutation frequency. In conclusion, both aqueous and methanol extracts of salted fish from Balik Pulau did not have gene mutation effect towards hprt gene in vitro. However, other toxicological profile could be assessed to determine the mechanism of toxicity of salted fish.
ABSTRACT
Clinacanthus nutans (C. nutans) leaf extracts have been widely used by cancer patients in Malaysia and local practice claims a cure to cancer. There were several studies done to determine the cytotoxicity potency of C. nutans extracts on various types of cells. However, there is still lacking on the knowledge regarding the combination effect of C. nutans with anticancer drugs. Thus, the study was carried out to determine the cytotoxicity potency of C. nutans extracts and paclitaxel (PTX) alone and, in combination on MDA-MB-231 cells. The cells were treated with 100% ethanol extract of C. nutans (CNE) and water extract of C. nutans (CNA), PTX and combination of both extracts and PTX for 72 hours and the cytotoxic activity was determined using SRB assay. Result showed that CNE had little cytotoxic activity, whereas CNA showed no cytotoxic activity on MDA-MB-231 cells. For combination treatment of C. nutans extracts and PTX, only CNE showed significant enhanced PTX-induced cytotoxicity (p < 0.05), meanwhile CNA inhibited PTX-induced cytotoxicity significantly (p < 0.05). As a conclusion, CNE was able to increase PTX potency to inhibit the viability of MDA-MB-231 cells.
Primary nasal lymphomas are rare. One of the most common cellular subtypes in the Asian population is natural killer (NK)/T-cell lymphoma (NKTL) with a high association of EBV. We report a case of a 42-year-old female, who presented with a worsening sore throat, odynophagia, dysphagia to solid food due to oropharyngeal ulcers and bilateral nasal blockage and recurrent fever for the past two weeks prior to admission. Physical examination revealed ulcers over the soft palate with nasopharyngeal slough. Computerized Tomography (CT) scan of the neck showed nasopharyngeal abscess with bilateral maxillary ethnoidal sinusitis. The diagnostic and management challenge is discussed.
The introduction and success of imatinib mesylate (IM) has become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, the high efficacy of IM has been hampered by the issue of clinical resistance that might due to pharmacogenetic variability. In the current study, the contribution of three common single nucleotide polymorphisms (SNPs) of ABCB1 (T1236C, G2677T/A and C3435T) and two SNPs of ABCG2 (G34A and C421A) genes in mediating resistance and/or good response among 215 CML patients on IM therapy were investigated. Among these patients, the frequency distribution of ABCG2 421 CC, CA and AA genotypes were significantly different between IM good response and resistant groups (P=0.01). Resistance was significantly associated with patients who had homozygous ABCB1 1236 CC genotype with OR 2.79 (95%CI: 1.217-6.374, P=0.01). For ABCB1 G2677T/A polymorphism, a better complete cytogenetic remission was observed for patients with variant TT/AT/AA genotype, compared to other genotype groups (OR=0.48, 95%CI: 0.239-0.957, P=0.03). Haplotype analysis revealed that ABCB1 haplotypes (C1236G2677C3435) was statistically linked to higher risk to IM resistance (25.8% vs. 17.4%, P=0.04), while ABCG2 diplotype A34A421 was significantly correlated with IM good response (9.1% vs. 3.9%, P=0.03). In addition, genotypic variant in ABCG2 421C>A was associated with a major molecular response (MMR) (OR=2.20, 95%CI: 1.273-3.811, P=0.004), whereas ABCB1 2677G>T/A variant was associated with a significantly lower molecular response (OR=0.49, 95%CI: 0.248-0.974, P=0.04). However, there was no significant correlation of these SNPs with IM intolerance and IM induced hepatotoxicity. Our results suggest the usefulness of genotyping of these single nucleotide polymorphisms in predicting IM response among CML patients.
A case control study was carried out to investigate associations between breast cancer risk, antioxidant status and oxidative stress among women in Klang Valley and Selangor. A total of 57 newly diagnosed cases aged 30 to 66 years old participated and were matched for age and ethnicity with 139 controls with no diagnosis of cancer or other chronic diseases. An interview based questionnaire designed to collect information on demographic and socioeconomic status, as well as reproductive, medical and dietary history was used. Anthropometric measurements including weight, height, waist and hip circumference were made and a 10 ml fasting venous blood sample was taken for glucose testing and analysis of plasma vitamin antioxidants and malondialdehyde. Hair and toenail samples were taken for selenium analysis. Results showed that the mean intake of vitamin A, vitamin E and selenium among cases (606.8 +/- 334.8 microg/d, 6.1 +/- 2.4 g/d, 56.9 +/- 16.2 microg/d) was lower than controls (724.7 +/- 414 microg/day, 6.9 +/- 3.0 g/d, 60.8 +/- 17.5 microg/d, respectively) (p<0.05 for all parameters). A similar trend was noted for plasma vitamin A and E and also selenium in hair and toenails. Poor antioxidant status as indicated by low plasma vitamin A (<284.3 microg/l or <366.3 microg/l) increased risk of breast cancer by approximately two fold, whilst low plasma vitamin E (<2.5 mg/dl, <2.8 mg/dl and <3.1 mg/dl) increased the risk by two to three fold [Adjusted OR 2.97 (95% CI 1.38-3.48), 2.32 (95% CI 1.07-2.41) and 2.12 (95% CI 1.00-4.21)]. Cases had a greater level of malondialdehyde 4.4 +/- 1.1 mmol/g protein), an indicator of oxidative stress, as compared to controls (3.2 +/- 1.7 mmol/g protein) (p<0.05). A high level of MDA (> or = 4.8 mmol/g protein) was associated with breast cancer [Adjusted OR 6.82 (95% CI 1.95-23.9)]. It is concluded that a poor antioxidant status and high oxidative stress are associated with breast cancer risk. Thus, it is essential for Malaysian women to obtain a good antioxidant status by consuming a diet rich in vitamins A and E as well as selenium and adopt healthy behaviour to reduce oxidative stress in order to prevent breast cancer.
Peripheral blood stem cells (PBSC) mobilised with growth factor with or without chemotherapeutic regimens, are used increasingly in both autologous and allogeneic transplantation. Previously, many PBSC harvests are used directly without ex vivo manipulation, and these PBSC have been shown to be contaminated with tumour cells, which may contribute to subsequent relapses post transplantation. Therefore, requirement for purging of malignant cells from the harvest has initiated the use of various methods to reduce tumour cell contamination of the graft by the positive selection of CD34+ progenitor cells or negative selection of tumour cells using other cell-specific antigens. We report here our local experience with the CliniMACS (magnetic-activated cell separation system) in eight adult patients with haematologic malignancies.
Hodgkin's disease (HD) in association with pregnancy is rarely reported. Thus, the data in the management of pregnancy complicated by HD is limited. We report here the management of advanced HD in pregnancy that was treated successfully with chemotherapy.
Ripeness classification of oil palm fresh fruit bunches (FFBs) during harvesting is important to ensure that they are harvested during optimum stage for maximum oil production. This paper presents the application of color vision for automated ripeness classification of oil palm FFB. Images of oil palm FFBs of type DxP Yangambi were collected and analyzed using digital image processing techniques. Then the color features were extracted from those images and used as the inputs for Artificial Neural Network (ANN) learning. The performance of the ANN for ripeness classification of oil palm FFB was investigated using two methods: training ANN with full features and training ANN with reduced features based on the Principal Component Analysis (PCA) data reduction technique. Results showed that compared with using full features in ANN, using the ANN trained with reduced features can improve the classification accuracy by 1.66% and is more effective in developing an automated ripeness classifier for oil palm FFB. The developed ripeness classifier can act as a sensor in determining the correct oil palm FFB ripeness category.
The aim of this study was to evaluate the in vitro cytotoxicity of biomaterials; Hydroxyapatite (HA), Natural coral (NC) and Polyhydroxybutarate (PHB). Three different materials used in this study; HA (Ca10(PO4)6(OH)2), NC (CaCO3) and PHB (Polymer) were locally produced by the groups of researcher from Universiti Sains Malaysia. The materials were separately extracted in the complete culture medium (100mg/ml) for 72h and introduced to the osteoblast cells CRL-1543. The viability of osteoblast CRL-1543 cultivated with these extraction materials after 72h incubation period was compared to negative control with neutral red assay by using spectrophotometer at 540nm. The results showed the non-cytotoxicity of the materials. After 72h of incubation period, HA showed 123% viable cells, NC was 99.43% and PHB was 176.75%. In this study, cytotoxicity test dealt mainly with the substances that leached out from the biomaterial. The results obtained showed that the materials were not toxic and also promoted cells growth in the sense of biofunctionality.
Chronic Myeloid Leukaemia (CML) is a disease characterised by a distinctive marker that is the Philadelphia Chromosome and an ability to transform into blast phase, which confers a poor prognosis. The median survival was reported to be between three to six months in correlation to blast phase. Extramedullary involvement with CML to sites such as pleural, meningeal and bones have been reported. We report a case of 41-year-old man who was diagnosed with CML in blast phase and presented with ascites. Ultrasound of abdomen showed coarse echotexture of liver suggestive leukaemic infiltration to the liver. The liver profile was severely deranged and associated with coagulopathy. Flow cytometry analysis of the peritoneal fluid revealed presence of myeloblasts consistent with CML in blast crisis with leukaemic ascites. Bone marrow biopsy also confirmed disease transformation. He received standard induction chemotherapy for acute myeloid leukaemia with dose modifications based on liver enzymes performance. Our case highlights an unusual presentation of CML in blast crisis with leukaemic ascites and the challenges in managing cytotoxic treatments due to the liver infiltration.
Activation of immunoregulatory T lymphocyte subsets has been observed in dengue viral infection, being more evident in dengue hemorrhagic fever (DHF) than in classical dengue fever (DF). There are, however, as yet no well-defined host markers to determine which patients with dengue viral infection will develop severe complications during the acute febrile stage of the disease. A study was performed to compare the cellular immune status in DHF, DF and non-dengue viral infections (NDF) in order to determine the value of these parameters in distinguishing DHF from classic DF and other viral infections during the acute febrile stage of the disease. This study involved 109 febrile patients admitted because of suspected DHF. Fifty patients were serologically confirmed cases of dengue infection, of which 25 had grade 1 or 2 DHF. There was a reduction in total T (CD3), CD4 and CD8 cells in DHF and demonstrated that a low level of CD3, CD4, CD8 and CD5 cells discriminated DHF from DF patients during the febrile stage of the illness. In contrast, B (CD19) cells and natural killer (NK) cells did not appear to be discriminatory in this study. Receiver operating characteristic (ROC) curve analysis showed that a combination of CD3 cell of < or = 45% and CD5 cell of < or = 55% was the best marker to identify DHF patients (sensitivity = 84% and specificity = 52% for CD3 cell of < or = 45%; sensitivity = 92% and specificity = 71% for CD5 cell of < or = 55%). CD4 cell of < or = 25% and CD8 cell < or = 30% were equally good in discriminating DHF from DF patients. On the other hand, the ROC curves indicated no clear difference between the immunoregulatory cell counts in DF from NDF Lymphopenia, atypical lymphocytosis and thrombocytopenia were significantly more evident in dengue compared to non-dengue infection but did not appear to be discriminatory among DHF and DF patients. The reduction in CD3, CD4, CD8, CD5 cells correlated with the degree of thrombocytopenia in DHF (p < 0.05) which suggests that these cells probably participate in a common pathogenetic mechanism.
Acute leukaemia may rarely present as diffuse papules, nodules and plaques forming leonine facies. Leukaemia cutis generally carries a poor prognosis, and responds less well to chemotherapy. We described a case of acute myelomonocytic leukaemia presenting as leonine facies as a result of extensive cutaneous infiltration. The patient did not achieve haematological remission following standard induction chemotherapy and succumbed 6 weeks after the diagnosis was made.
Three cases of diffuse panbronchiolitis (DPB) occurring in two Malaysian Chinese patients and one Malay patient are reported. They had similar clinical, radiological and physiological features which are characteristic of DPB. The diagnosis in one of the cases was confirmed histologically by transbronchial lung biopsy. These could be the first three cases identified in Malaysia.
Allogeneic haemopoietic stem cell transplantation was initially considered as a means of delivering supralethal doses of chemotherapy with or without total body irradiation for the treatment of malignancy. However, it has become clear that this mode of therapy does not eradicate the malignancy in many patients and its benefit is largely due to the immune mediated graft versus malignancy effect. This has led to development of alternative strategy to utilize a less intensive preparative regimen pre-transplantation that provides sufficient immunosuppression to achieve engraftment of an allogeneic stem cell graft, thus allowing the evolution of a graft versus malignancy effect post-transplantation. Since September 1999, we had carried out 10 cases of allogeneic peripheral blood stem cell transplantation: one case of aplastic anaemia, four cases of acute myeloid leukemia (AML) in first remission, and five cases of chronic myeloid leukemia (CML) in chronic phase. The preparative regimen was non-myeloablative comprising Fludarabine with Cyclophosphamide or Busulphan. Recovery from transplantation was rapid with no or brief period of neutropenia or thrombocytopenia. Engraftment was established by determining donor's short tandem repeats in the recipient's bone marrow at day 30, 60 and 100 post-transplantation. Seven cases (70%) show partial or complete donor's chimerism by day 30 indicating successful engraftment. No treatment mortality was noted at day 100. Graft versus host disease was generally limited. Up to the date of reporting, two patients with CML had graft failure, one was successfully re-transplanted later. Two patients with AML had since relapsed and passed away. The others remain alive and well. The cost of transplantation on average was estimated to be about a quarter of that using a myeloablative regimen. It appears that this treatment strategy is a promising approach for the management of blood disorders.
The standard treatment of open wounds via the direct usage of therapeutic agents is not without limitations with respect to healing. Small peptides can create a favorable milieu for accelerating the healing of wounds. This study presents the potential of a novel fatty acid conjugated tetrapeptide (palmitic acid-glycine-aspartic acid-proline-histidine; Palmitoyl-GDPH) in alleviating wound healing. Tetracycline was employed as a standard control drug following its significance in wound healing including biologically active and antimicrobial effects. The peptide in liquid form was applied on to a 4 cm2 full thickness wound surgically induced at the dorsum of Sprague Dawley (SD) rats. The in vivo wound treatment with Palmitoyl-GDPH for eighteen days, histologically demonstrated an almost perfect healing exhibited by increased re-epithelialization, enhanced collagen deposition, and diminished scar formation compared to the controls. In addition, the well-developed epidermal-dermal junction and ultimate stimulation of hair follicle-growth in the Palmitoyl-GDPH treated group indicated the wound to have healed as functionally viable tissues. In general, the much lower hemogram values in the Palmitoyl-GDPH group indicated that the ongoing healing is en route to an earlier recovery. Additionally, the liver, kidney, and pancreas function biomarkers being within normal limits indicated the relatively non-toxic nature of Palmitoyl-GDPH at the used dosage. These results indisputably supported the great potential of this newly synthesized Palmitoyl-GDPH to be used as an effective therapeutic agent for wound healing (this actually means creating a new wound).