Thisstudy aim tocharacterize melt-derivedbioactive glass and to determinethe bioactive glass (BG) suitability for dental usagethrough proliferative activity assessment of stem cells from human exfoliated deciduous teeth (SHED)when exposed to bioactive glass conditioned medium. Bioglass 45S5 in mole percentages (46.13% SiO2, 26.91% CaO, 24.35% Na2O and 2.60% P2O5)was synthesizedthrough melt-derived and characterized usingX-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR)to confirm and identify its properties.SHEDwere used to evaluate the biocompatibility of 45S5 by exposing the cells to various concentration of BG-conditioned medium (1-10 mg/ml) using alamarBlue assay. The BG produced has an amorphous structureas shown by XRD analysis. TheSi-O-Si bending, asymmetric Si-O stretching and asymmetricSi-O-Si stretchingbands were observed in the BG structure supporting the presenceof silicate network. For alamarBlue assay, SHED cultured in BG-conditioned medium showed high proliferation rate when subjected to minimal powder content in the DMEM cell culture medium.Hence, it can be concluded that SHED cultured in lower powder content of the BG-conditioned media showedhigh proliferative activity suggesting the potential of the BG for dental usage.
We describe the first clinical case of contact lens related corneal ulcer caused by Elizabethkingia meningosepticaregistered in Southeast Asia. A 20-year-old female student who wasa regular soft contact lens wearer, presented with pain, photophobia and blurring of vision of the right eye for 3 days. On slit lamp examination, there was a small paracentral anterior stromal infiltrate with an overlying epithelial defect. Microbiological cultures from corneal scrapings, contact lens and its casing were positive for E.meningoseptica. Due to high likelihood of contact lens contamination causing keratitis, topical fortified gentamicin0.9% and ceftazidime 5% were administered empirically. Topical vancomycin 5% was later added tailoring to the culture and sensitivity of the organism. After 8 weeks of treatment, the keratitis subsided and corneal epithelial defect completely healed with residual corneal opacity. Even though uncommon, contact lens related E.meningosepticakeratitis can occur in healthy immunocompetent individuals with no ocular comorbidities.
Introduction: Methylation of promoter region of p16 leading to gene silencing has been implicated ina wide range of malignancies including lymphomas. In diffuse large B cell lymphoma (DLBCL) particularly, a varying percentage of epigenetic inactivation of p16 promoter region was observed ranging from 16 -54%. However, quantitative analysis of p16 promoter methylation in DLBCL has not been extensively studied in Malaysia. Objective: This study aims to quantitatively analyse p16 methylation in DLBCL samples using pyrosequencing technique. Methods: Genomic DNA was extracted from 16 formalin-fixed paraffin-embedded lymphoma tissue blocks from patients diagnosed with DLBCL. Samples were retrieved from Hospital Tengku Ampuan Afzan, Pahang and Hospital Universiti Sains Malaysia, Kelantan. Primers were designed to amplify bisulfite-treated DNA targeting p16 promoter region. Methylation status of 7 CpG sites was determined by pyrosequencing. Results: All the 16 samples studied showed promoter methylation of p16. The range of mean methylation percentage was between 18 to 81%. Conclusion: The present study has successfully measured the level of methylation of p16 in all 7 CpG sites despite the limitation in sample size. Since p16 methylation is a common event in our series of DLBCL cases, it is worth including a larger sample size in future studies to increase the chance of finding a significant correlation with clinical parameters.
Trisomy 8 is a condition where every cell of an individual presents with an extra copy (three copies of chromosome 8. This disorder occurs when a pair of chromosomes fails to divide evenly, which results in cells containing more than two of this chromosome. Here, we report a case of mosaic trisomy 8 in a Malaysian Malay boy.Although patient in this case confirmed with T8M, he exhibited few of the characteristic features that previously were reported to be associated with T8M. However, the patient’s very young age might explain the lack of clinical presentation of these features.
The repair process of airway epithelium involves cell migration, spreading, proliferation and re-differentiation. Objective: Cellular and molecular responses to tracheal brush induced injury were investigated using a rabbit model. Methods: Eighteen New Zealand white rabbits were divided into uninjured and injured groups. After tracheal brushing, the animals were maintained in the laboratory before being sacrificed at given time points (1, 12 hours, 3, 7, and 21 days). The trachea of each rabbit was retrieved and preserved before being subjected to haematoxylin and eosin staining and real time PCR. Results: After injury, the remained epithelial cells underwent an instant response by proliferating and migrating into the damaged site. This finding was in accordance with the proliferative and migration activity-related gene expression results (MMP-9, TIMP1, vimentin, and ß-integrin). The increased activity of these genes was crucial at the early time points, as it encouraged the remaining cells to repopulate the damaged area. Conclusions: Continuous regulation of MMP-9, vimentin and ß-integrin plays important roles in promoting cellular homing especially the cells bordering the lesion to migrate and repair of the damaged ECM. Thus, this activation enhanced regeneration and repair of the damaged tracheal epithelium as early as 1 h and complete at 21 d following injury.
Tunnel vision is a classic sign among patients with advanced glaucoma. However, other conditions such as retinitis pigmentosa, optic neuritis and rod-cone dystrophy may be characterized by similar visual field defects. A 52-year-old lady with a family history of glaucoma presented with bilateral gradual loss of peripheral vision for two years. She claimed to have poor night vision about 20 years prior to this presentation. Her visual acuity was 6/7.5 in both eyes. The anterior chamber depth was moderate bilaterally, with Schaffer grading on gonioscopy of grade I to II. The intraocular pressure was 14 mmHg in both eyes. The optic discs appeared normal. Fundus examination showed scattered hypopigmented changes sparing the fovea. Humphrey visual field test revealed bilateral constricted visual fields. She was diagnosed with retinitis punctata albescens (RPA) based on her symptom of poor night vision, supported by the diffuse hypopigmented changes in her fundi. The management of this condition involves careful counselling regarding the genetic nature of the disease and its progressive course. We discuss this case to illustrate the importance of a thorough history taking and careful fundus examination in the workup of patients presenting with tunnel vision.
The aim of this study is to determine the risk factors for retinopathy of prematurity (ROP), and also to screen Norrie Disease Pseudoglioma (NDP) gene mutation in order to determine if mutation in the NDP gene may play a role in the development of ROP among Malay premature infants. This was a case control studyamong Malay premature infants from Hospital Universiti Sains Malaysia (USM) conducted from August 2011 to May 2013. Written consent were taken from their parents before conducting the study. The stage of ROP, systemic risk factors (gestational age and birth weight) and enviromental risk factors (oxygen exposure and duration of ventilation)were reviewed from patients’medical records. DNA was extracted from venous blood and subjected to polymerase chain reaction (PCR) before direct sequencing of NDP gene. A total of 56 Malay premature infants (Case group = 28 ROP premature infants, Controlgroup = 28 non-ROP premature infants)from Hospital USMwere enrolled in this study. Out of 28 premature infants with ROP, 11 (39.3%) premature infants were in stage 3. Only 1 (3.6%) premature infant in stage 4 and 2 (7.2%) premature infants in stage 5. The gestational age (p = 0.010) and birth weight (p = 0.010) were the significant risk factors for ROP. There was no significant difference ofenvironmental risk factors between the two groups. The NDPgene mutation was not detected in Malay premature infants with ROP and also in control group. The gestational age and birth weight were important risk factors of ROP.Although NDPgene mutations were being linked to ROP but NDPgene mutation was not detected in premature infants with ROPas well as premature infants with non-ROP among Malay ethnic background.
Clinacanthus nutans or locally known as Belalai Gajah in Malaysia has been used in China in various manners to treat inflammatory conditions like hematoma, contusion, strains and rheumatism. Recently, C. nutans has become popular for the treatment of cancer among Malaysian. Thus, the aim of this present study is to prove the anti cancer activity of C. nutans extracts in a treatment of cervical cancer as claimed by local people. Aqueous and methanol extracts were extracted from the leaves of C. nutans and phytochemical screening was performed for determination of secondary metabolites. The cytotoxic activities of both aqueous and methanol extracts were investigated against HeLa cell by using MTT assay. The mode of cell death was examined by Hoechst 33258 nuclear staining. The secondary metabolite constituents detected in C. nutans aqueous extract are terpenoids and flavonoids, whereas methanol extract contains terpernoids, alkaloids and flavonoids. Results also showed that C. nutans aqueous extract exerted a significant cytotoxic effect on HeLa cells (IC50=13±0.82 μg/ml) but no IC50 was detected by methanol extract. No significant cytotoxic activities (IC50 = not detected) were observed in normal kidney cell line, Vero, treated with both aqueous and methanol extracts of C. nutans which showed the cytoselective property of the extracts. However, HeLa and Vero cells treated with control drug, tamoxifen showed a significant cytotoxicity effects with IC50 values of 3.8±0.19 μg/ml and 2.2±0.029 μg/ml respectively. Hoechst 33258 stained showed the aqueous extract of C. nutans induced cell death on HeLa cells via apoptosis. Thus, suggesting C. nutans aqueous extract as a potential promising alternate therapeutic substance for cancer prevention and treatment especially for cervical cancer treatment.
Muscular dystrophy is a group of diseases that result in progressive muscle weakness and atrophy. Duchenne Muscular Dystrophy (DMD) is classified as dystrophinopathy and is an X-linked recessive disease. It is caused by alterations in the dystrophin gene at Xp21.2 encoding 79 exons . It is characterised by progressive muscle wasting that begins at 3 to 5 years, delay in motor development and eventually wheelchair confinement followed by premature death at about 30 years from cardiac or respiratory complications . Genetic etiology of cases of DMD in Malaysia are still scarcely reported. Here, we report the genetic cause in the case of an 11-year-old Kelantanese Malay boy who has progressive muscle weakness since 5 years old. He has difficulty in getting up from sitting and supine position also in climbing up stairs until 1st floor. He has a strong family history of DMD and musculoskeletal problems. His younger brother was diagnosed with DMD by molecular analysis and his maternal uncle died at the age of 16 with musculoskeletal problems but was never investigated. Physical examination revealed no dysmorphic features, positive Gower sign with absent tounge fasciculation. On neurological examination, tendon reflexes and muscle tone for limbs were normal. Muscle power for bilateral upper limbs were normal, however, bilateral lower limbs showed slight reduction in muscle power with calf hypertrophy.
The molecular biology knowledge in β-thalassaemia is limited due to the involvement of various erythropoeitic processes where the genetic information is lack due to nucleus ejection throughout the maturation of red blood cell activities concurrence with the accumulation of haemoglobin. Nucleated red blood cells (NRBCs) are typically found in peripheral blood (PB) of β-thalassaemia transfusion dependent patients and abundant in post splenectomy (Fig. 1A) . The presence of NRBCs will provide further understanding on the molecular aspect of ineffective erythropoiesis in β-thalassaemia patients. Therefore, the objectives of this study were to isolate the NRBCs using CD71 magnetic beads from PB of β-thalassaemia patients and to compare the quantity of NRBCs enriched between non-splenectomised transfusion dependent and post-splenectomised transfusion dependent β-thalassaemia patients.
The large clinical spectrum of Haemoglobin E (HbE)/β-thalassaemia leads to identification of modifiers that cause the complexity1. IGSF4, a member of the immunoglobulin superfamily 4 is known as a thalassaemia-related gene that plays an important role in globin synthesis. Methylation of IGSF4 was reported to interrupt the process of globin synthesis through its interaction with other genes in the regulation network of globin expression2. Specific cells isolation is needed in order to study the methylation profile as the interaction between various haematopoietic cells including nucleated red blood cells (NRBCs) in whole blood could impact the methylation results3. Therefore, the objective of this study was to describe the pattern of DNA methylation at the promoter region of IGSF4 gene that may involve in the alteration of globin synthesis in HbE/β-thalassaemia patients.
HRQOL is referring to patients' perceptions that is related to physical and mental of thalessemia patients. HRQOL measurement is crucial in assessing the extent of impact that this chronic disease has affected the thalassaemia patients’ lives. HRQOL measurement also includes identifying the effects of the treatment and disease towards wellbeing of the patients. Quality of Life (QOL) of individuals with thalassaemia major are affected by many influence factors such as the effect of diagnosis and treatment, chronic conditions state, appearances, treatment’s components such as frequent hospital visits for the transfusion, nightly mixture of subcutaneous, late arrival or absence, sexual development and complications from the disease[1-2].
The study aims to assess the Health Related Quality of Life (HRQoL) among thalassaemia patients and identify the significant factors that contribute to HRQoL in thalassaemia patients in Malaysia. A cross sectional based study was conducted at Kedah Thalassaemia Society Club in Kedah, Malaysia. The HRQoL was measured using a Short form survey version 2 (SF-36). Descriptive study was used to describe the demographic and disease related to the thalassaemia patients. The HRQoL was compared using the Mann-Whitney and Kruskal-Wallis test. The analyses were performed using the Quality Metric Health Outcomes Scoring software for SF-36 and SPSS v 22. Three hundred and ninety thalassaemia patients were enrolled in the study. The majority of the participants (n = 221, 58.5%) were categorized in the age group of 18-27 years (25.40 ± 10.2). The HRQoL measure of less than 50 for the physical component summary (PCS) and mental component summary (MCS) among thalassaemia patients were rated as poor. Patients with higher education levels were significantly associated with PCS (p=0.002) and showed higher mean scores for PCS (52.0) compared to the others. Age, marital status, employment status, monthly income, health check-ups before screening of thalassaemia and medical insurance was associated with PCS levels compare to the others. The type of thalassaemia, the medical treatment received and the side effects of the conventional treatment were significantly associated with p-values of less than 0.001 and PCS and MCS scores of below 50.
Mutations in the δ globin gene are not pathologically significant . However, coinheritance of β and δ thalassaemia can mask the diagnosis of β thalassaemia trait as it causes HbA2 level to be lowered [2,3]. Here, we reported 5 unrelated cases of compound heterozygous β0 Filipino ~ 45 kb deletion and codon 67 (GTG>ATG) HbA2 Deventer in Sabahan population.
Cases of β°-thalassemia traits with unusual low HbA2 were reviewed. These cases were initially referred to our laboratory for definitive diagnosis of β-thalassemia trait. Haematological parameters and Hb analysis were carried out at the referral hospital. Genomic DNA was extracted from the peripheral blood. Multiplex ARMS and Gap PCR were done to detect common point mutations and deletions for both alpha and beta globin genes. Sanger sequencing was performed to detect mutations in delta globin gene.
Patients’ consist of 4 males and 1 female aged between 25-38 years old. All of them are indigenous Sabahan (2 Kadazans, 1 Murut, 1 Dusun and 1 Sungai). Their haemoglobin level ranges between 10.8 – 12.8g/dl. Hb analysis findings of HbA2 and HbF level ranges between 2.9 – 4.0 and 2.2 – 9.4g/dl respectively. Molecular findings revealed heterozygous state of (β)º-thal, Filipino ~45Kb deletion, NG_000007.3:g.[66258_184734del];[66258_184734=] and heterozygous state of Codon 67 [GTG>ATG] Hb A2-Deventer mutation, NG_000007.3:g.[63512G>A];[63512G=] (Figure 1 and 2).
Detection of 5 unrelated cases of HbA2 Deventer may suggest that this delta variant is common among indigenous Sabahan. Since beta thalassaemia is also common in the population, more attention should be paid during diagnosis. Identification of delta variant in beta thalassaemia carrier is important because coinheritance of beta and delta thalassaemia results in a less elevated HbA2 level. Therefore, molecular testing of thalassemia carrier state in the case of borderline HbA2 is warranted to avoid misdiagnosis of beta thalassaemia carriers.
44-year-old Malay lady presented with drooping of the right eyelid and worsening of left eye vision for one week duration. There was associated headache, periorbital discomfort and diplopia on left gaze. She previously had a history of recurrent optic neuritis affecting both eyes over a period of 12 years. On examination, there was right-sided partial ptosis and left exotropia. The adduction, abduction, elevation and depression of the right eye was limited. Left eye extraocular movements were full. The right eye visual acuity was 6/9, while the left eye visual acuity was perception to light, with a positive relative afferent papillary defect and a pale optic disc. The right optic disc was normal. There was reduced sensation in the trigeminal nerve distribution over the right side of the face. Neurological examination was otherwise normal. Magnetic resonance imaging of the brain and orbit revealed meningeal thickening with involvement of the right orbital apex and cavernous sinus. Blood investigations for infectious and autoimmune causes were unremarkable. She was diagnosed to have idiopathic hypertrophic cranial pachymeningitis and treated with systemic corticosteroids. The right eye extraocular motility improved, while the left eye visual acuity improved to counting finger. This case demonstrates that idiopathic hypertrophic cranial pachymeningitis may present as recurrent optic neuritis in the early phase, before radiological evidence of the disease is present. A high index of suspicion for the underlying cause is essential to prevent irreversible optic nerve damage due to recurrent optic neuritis.
Chromosomal abnormalities (CA) can affect numerical or structural compositions of chromosomosal DNA leading to a diversity of clinical phenotypic presentations. Awareness of prenatal diagnosis and genetic counselling have improved with advancing medical research but CA remain prevalent as its aetiology is unknown. The objective of this study is to determine the frequencies of various CA in the principle region of north-western Malaysia and compare this data to previous reports to ascertain if statistical differences exist. Karyotype analyses performed at the Genetics Laboratory, Advanced Diagnostic Laboratory (ADL) during the first 5-years of cytogenetic services, totalling 1461 cases, were assessed in this report. Cases suspected of CA were initially diagnosed by clinicians and detailed clinical and family histories were recorded. Peripheral blood lymphocytes of patients were collected and cultured in vitro for acquisition of karyotype by standardized G-banding technique. Fluorescence in situ hybridization (FISH) was conducted in cases suspected of to be DiGeorge, Prader-Willi, Angelman and Williams syndrome. Of the total samples (1805) received and cultured, 1669 (92.46%) successfully yielded results. Abnormal outcomes were observed in 495 cases (29.66%) whereby pronounced majority of cases 299 (68.42%) were Down syndrome. This is followed by Edward, Turner and Patau syndrome, in order of frequency. Numerical CA appears to be prevalent accounting for 85.86% of cases. Structural CA accounted for 14.14% of total positive cases whereby the most common was deletions (34.29%) followed by translocations (20%), ring chromosomes (5.71%), Fragile X syndrome (4.29%), duplications (5.71%) and marker chromosomes (7.14%). The remainder of cases (22.86%) consisted of derivative chromosomes and other complex aberrations. The number of polymorphic variant cases were 27 (1.62%). The number of peripheral blood samples received has significantly increased from 14.3 per month in 2006 to 32.17 per month in 2011. Comparative analysis of our study to previous reports reveal statistical differences in the occurrence of several CA including Edward, Patau, Klinefelter and Fragile-X syndrome. Our experience with peripheral blood samples for cytogenetic analysis demonstrated a success rate of 92.46%. This showed an increase in clinicians validating patients’ diagnoses with karyotyping which is essential in confirming genetic anomalies with the goal to substantiate genetic counselling.
nfectious endophthalmitis is a devastating and potentially sight-threatening condition.The objective is toanalyse the microbiological profile and visual outcome of culture positive endophthalmitis seen in Hospital Universiti Sains Malaysia. All patients with endophthalmitis admitted to Hospital Universiti Sains Malaysia over a 7-year period from January 2007 until December 2013 were recruited into this study. Retrospective review of medical and microbiology records was conducted among patients clinically diagnosed with endophthalmitis in Hospital Universiti Sains Malaysia from January 2007 until December 2013. Sixteen patients were admitted with endophthalmitis during this study period. Seven (43%) were culture-positive, in which five (71%) cases were from vitreous culture and two (29%) from blood specimens. The mean age for culture positive patients of presentation was44 years. The most common bacterial isolate was Pseudomonas spp., while the most common fungus was Candida spp. Other organisms isolated were Fusariumsp., Aspergillus sp., Staphylococcus sp.and Enterococcus sp. The risk factors for culture-positive cases were ocular trauma, corneal keratitis, ocular chemical injury, severe urinary tract infection and retropharyngeal abscess. Only three of the affected eyes could be salvaged. The final visual acuity waspoor in all the culture-positive eyes. Two cases underwent evisceration while one case underwent enucleation. As a conclusion,Culture-positive endophthalmitis in this study were mainly attributed to Pseudomonas spp. and Candida spp. The visual outcome of culture-positive endophthalmitis was poor.
Charged particle therapy with carbon ions has advantages over conventional radiotherapy using x-ray beams. The application of charged particle therapy has rapidly increased over the last decades. This is due to its characteristic Bragg peak which has relatively low entrance doses and favourable doses distribution. In this research work, Geant4 based Monte Carlo simulation (MC) method has been used to calculate the radiation transportation and dose distributions in tissue-like media. The main objective of the work was to compare the Geant4 simulated depth dose distributions with experimental measurements and verify the capability of the geant4 simulation toolkit. The carbon ion beams for the therapeutic energy of 350 MeV/u and 400 MeV/u respectively were simulated, with the same settings as the experimental work carried out at the treatment room at Heavy Ion Medical Accelerator (HIMAC), National Institute of Radiological Sciences (NIRS), Chiba, Japan. The simulation results were verified with measurements data. The work was to measure the accuracy and quality of the dose distributions by Geant4 MC methods. The results show that the Bragg peak and spread out Bragg peak (SOBP) distributions in simulation has fairly good agreement with measurements.
Medicinal plants have healing properties and are able to synthesize various chemical compounds. These chemicals (also known as phytochemical compounds) play vital roles in determining the pharmacological properties existing in certain plants. The phytochemical compounds present in plants are associated with primary and secondary constituents. Most of the time, the secondary constituents exhibit the bioactivities in plants such as antimicrobial, antioxidant, antidiabetic, antibacterial and anti-inflammatory properties. Some common medicinal plants that have been used in curing various diseases by traditional practitioners in Malaysia are Ficus deltoidea Jack, Andrographis paniculata, Curcuma longa, Clinacanthus nutans and Eurycoma longifolia Jack. This review discusses the morphology, phytochemical compounds and phytochemical properties of selected medicinal plants in Malaysia. The plants of focus have been found to possess anti-cancer and anti-diabetic effects. This review, it is hoped will enable Malaysian researchers to explore further on the potential of these plants in investigating new and novel drugs in the future.
We report a case of cavernous sinus thrombosis in a post-splenectomy male with underlying Haemoglobin E Thalassemia major. A 35-year-old man presented with a first episode of sudden onset of diplopia on lateral gaze for 1 week. He had no other ocular and systemic symptoms. There was no history of trauma or recent infection. However, he admitted that he was not compliant to his oral penicillin V and aspirin, which was prescribed to all post splenectomy patients. Unaided visual acuity in both eyes was 6/6. On examination, there was limited abduction over the left eye, suggestive of left lateral rectus palsy. Full blood count revealed leucocytosis with thrombocytosis. Magnetic resonance imaging, magnetic resonance angiography and magnetic resonance venography of the brain showed bulging of the left cavernous sinus, with a persistent focal filling defect, in keeping with left cavernous sinus thrombosis (CST). He was diagnosed with left isolated sixth nerve palsy secondary to aseptic cavernous sinus thrombosis with pro-thrombotic state post-splenectomy. He was started on subcutaneous fondaparinux and oral warfarin. His diplopia fully resolved after 1 month of treatment with complete resolution of CST on computed tomography venogram.
We report a case of dural carotid cavernous fistula (CCF) pose a diagnostic dilemma with initial symptoms of the arteriovenous shunt. A 56 year-old man presented with right eye diplopia, thensubsequently developed ptosis, congestion of conjunctiva, dilated episcleral vessels, and gradual rise in intraocular pressure. Initial diagnosis of pseudotumour was made based on negative finding of CCF by computed tomography angiography (CTA). In view of persistent clinical manifestations in spite of steroid therapy, and with the presence of new ocular signs; cock-screw conjunctival vessels, dilated retinal veins, and proptosis, digital subtraction angiography (DSA) was performed and confirmed the diagnosis of dural CCF.The ocular symptoms resolved completely post embolization of the fistula.