Xenobiotic substance released in the environment is a concern among the public at large. The example of this xenobiotic release into the environment is xenoestrogens. Xenoestrogens have the capability to bind to the estrogen receptors in the body even at low affinity. Food, pesticides and contraceptive pills are known sources of xenoestrogens. In this study, acute toxicity test was conducted to evaluate toxicity of synthetic estrogen such as estradiol to the embryo-larvae of zebrafish model. Morphological changes in the embryo-larvae of zebrafish were also observed. The parameters that were evaluated in acute toxicity study were half lethal concentration (LC50) and few apical endpoints such as coagulation of embryos, development of pericardial edema, and eyes size. Toxicity effect of the compound was evaluated in term of behavior activity of the larvae. Results showed that certain concentration of estradiol caused toxic effects to the embryo-larvae of the zebrafish (p
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.
The incidence of HbE/beta (HbE/β) thalassaemia is increasing in Asian countries, including Malaysia. HbE/β thalassaemia is widely acknowledged to have a diverse phenotypic spectrum despite having the same primary genetic background [1,2,3]. Thus, there are HbE/β thalassaemia patients who receive unnecessary treatments which leads to side effects [4], reduced quality of life and wasting health care resources. Ideally, the treatment and management of thalassaemia patients are individually tailored in order to minimise side effects and optimise health care costs. Genetic variants have been widely acknowledged to influence the variability of human phenotypes. Presence of unique genetic modifiers are believed to cause the diversity in HbE/β thalassaemia severity. Milder disease course has been found to be highly associated with Xmn1-Gγ polymorphism (rs7482144), a SNP at HBG2 promoter [1,5,6,7]. So far, there is no association study between Xmn1-Gγ polymorphism and HbE/beta thalassaemia disease severity in Malaysia. This study aims to optimise PCR-RFLP technique for detection of Xmn1-Gγ polymorphism, to determine the frequency of Xmn1-Gγ polymorphism in HbE/β thalassaemia patients and finding its association with the severity of HbE/β thalassaemia patients. This hospital-based cross-sectional study was performed using archived genomic DNAs from 58 subjects with their respective research pro formas. Selected datas were extracted from the pro formas in order to classify patients into 3 disease severity groups using the scoring system by Sripichai et al., (2008) based on 6 parameters. The archived genomic DNAs were genotyped employing Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique. The genotypes were categorised into homozygous variant, heterozygous and homozygous wild type. The genotypes detected were then validated using DNA sequencing analysis. Appropriate statistical analysis was used to determine the association of Xmn1-Gγ polymorphism with the clinical severity of HbE/β thalassaemia. This study had successfully optimised the PCR-RFLP technique for detection of Xmn1-Gγ polymorphism. Out of 58 subjects, the Xmn1-Gγ polymorphisms were detected in 40 subjects (69%) with the majority being heterozygous (CT) (n=38, 66%) and there were only 2 (3%) homozygous variant (TT) subjects. Homozygous wild type (CC) were detected in 18 (31%) subjects. There were no significant association of Xmn1-Gγ polymorphism with the severity of HbE/β thalassaemia patients with p-value of 0.65 for genotype and 0.58 for allele, respectively. In conclusion, this study showed no significant association of Xmn1-Gγ polymorphism with milder disease severity of HbE/β thalassaemia patients. This can be a true finding for the patients in North East Malaysia or due to small sample size. Thus we recommend to have a larger study in order to validate the association of Xmn1-Gγ polymorphism with HbE/β thalassaemia severity. In addition, there may be other genetic factors that interact with Xmn1-Gγ polymorphism as it was not possible to consistently predict phenotype and severity from the presence of Xmn1-Gγ polymorphism alone.
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.
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.
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.
Complex chromosome rearrangements (CCRs) are structural aberrations or rearrangements involving three or more cytogenetics breakpoints on two or more chromosomes [1]. Balanced and unbalanced are known to have significant risk of mental retardation and phenotypic anomalies. CCRs are also associated with infertility in males and recurrent abortion in females. Here we report one case of apparently balanced CCR involving three chromosomes 3, 5 and 12 in a child with abnormal features. G banding and FISH were performed to clarify the nature of this complex abnormality.
Early detection and prompt treatment of eye diseases can prevent visual disability. To our knowledge, there is no published data on factors associated with delayed presentation of eye diseases in Malaysia. Our objective is to determine the proportion of patients with eye disease who had a delayed presentation to an ophthalmologist after an initial screening, as well as the factors associated with delay in seeking treatment. This was a retrospective cohort study of patients with eye diseases detected during a Community Eye Survey (CES) program from September 2004 to December 2012 who were referred to the ophthalmologist in Hospital Universiti Sains Malaysia (USM). Delayed presentation of eye disease was defined as patients who came to the eye clinic more than six months after eye screening. Multiple logistic regression was used for analyses. A total of 434 patients who were referred to Hospital USM, Kubang Kerian were included in the study. Their mean (standard deviation) age was 55.65 (21.62) years. The majority of patients (76%) had delayed presentation of eye disease post screening. Type of ocular diseases was not associated with delayed presentation. The factors associated with delayed presentation were unemployment (adjusted odds ratio (OR): 2.51, 95% CI (1.36, 4.64), p
Study site: Hospital Universiti Sains Malaysia (HUSM)
Mutations in the δ globin gene are not pathologically significant [1]. 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.
Complete blood count (CBC) is used broadly to screen individual's general health status. Some inherited red blood cell (RBC) disorders influence the RBC parameters. Mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) are amongst the important RBC parameters used in thalassaemia-haemoglobinopathy screening [1-2]. Globin chain disorders and Southeast Asian Ovalocytosis (SAO) are common RBC disorders in Southeast Asian countries [3]. We evaluated the RBC parameters in patients with Hb E and those with SAO co-inheritance.
A total of 33 from 1500 Malay patient’s samples that were sent for thalassaemia-haemoglobinopathies screening in Hospital Kuala Lumpur (HKL) were identified and consented (30 cases with Hb E and 3 cases with co-inheritance of Hb E and SAO). The inclusion criteria were Malay patients with MCV and MCH levels less than 78 fL and 27 pg respectively with presence of oval and stomatocytic RBCs in the peripheral blood film. DNA extraction was performed in samples suspected of having co-inheritance of SAO and Hb E. Primers 198 and 199 (AIT biotech Pte Ltd. Singapore) were designed for SAO detection [4], [5]. Hb E mutation was detected using ARMS PCR [6].
SAO was characterised by presence of an in frame 27bp deletion in exon 11 of the band 3 gene. A band of 175bp was observed in normal subjects and two bands, 175bp and 148bp were observed in heterozygous SAO subjects (Fig. 1).
To review the clinical profile of retinal vein occlusion (RVO) in Hospital Universiti Sains Malaysia (USM) from 2011 until 2017. This was a retrospective single-centre case series. The medical records of the patients presented to Ophthalmology Clinic with RVO from 2011 to 2017 were reviewed. A total of 24 patients (26 eyes) with a diagnosis of RVO in Hospital USM were reviewed. There was 91.6% of our patients were aged more than 45 years old with predominantly affected male gender (58.3%). Majority of the patients were Malays (87.5%). Hypertension (70.8%), hyperlipidemia (70.8%) and diabetes mellitus (54.2%) were the common systemic comorbidities in RVO patients. Majority of the patients (87.5%) were non-smoker. Based on type of RVO, there were 38.5% central RVO, 26.9% branch RVO, 19.2% macular branch RVO, and 15.4% hemivein occlusion. RVO was bilateral in 2 patients (8.4%). Based on fundus fluorescein angiography, 3 patients (11.5%) showed ischaemic features. Reduce vision (91.6%) was the main presenting symptoms of RVO while intraretinal haemorrhage (100%) and macular oedema (96.2%) were the most common ocular signs found in RVO. There were 16 eyes (61.5%) have visual acuity equal or better than 6/60 at presentation. Patient who had visual acuity equal or better than 6/60 showed promising improvement in visual acuity post treatment. Elderly with multiple comorbidities complaining of worsening of vision should have high index suspicion of RVO. Presenting visual acuity is associated with final visual outcome post treatment.
A 65-year-old lady complained of occasional flashes of light over her left eye for 2 months. She was referred for ocular assessment after she underwent refractive assessment at the optometrist. On examination, best corrected visual acuity in both eyes was 6/9. Both eyes anterior segments were normal, with normal intraocular pressure. The pupils were equal with no relative afferent pupillary defect. Left eye fundus examination was normal. On the contrary, the "normal" right eye fundus examination revealed a huge, well-circumscribed hypo-pigmented elevated choroidal mass. B scan ultrasonography of the right eye showed a mushroom-shaped intraocular mass. Magnetic resonance imaging showed an intraocular lesion. Comprehensive systemic examination and investigations to rule out distant primary malignancy were unremarkable. A provisional diagnosis of right eye primary choroidal melanoma was made. Despite good vision in the affected eye, she underwent right eye enucleation in view of the large intraocular mass. The diagnosis was confirmed by histopathological examination.
A hemangioma is a benign vascular tumor of the brain, which rarely occurs in the cavernous sinus. We report a rare case of cavernous sinus hemangioma presenting with binocular diplopia. A 23-year-old lady presented with binocular diplopia associated with restricted left lateral gaze for 3 months. Visual acuity of both eyes was 6/6 with normal pupillary reaction. Both anterior and posterior segment were unremarkable. Contrasted computed tomography of brain showed an irregular mass within the left cavernous sinus causing pressure effect on the adjacent bone. Cerebral magnetic resonance imaging (MRI) showed a convexity in the left cavernous sinus, with a well-defined heterogeneous lesion with mixed hypo and hyperintensity in T1WI and T2WI; post gadolinium contrast, it was minimally enhanced. The patient was managed conservatively and at one-year post presentation, her symptoms improved but the lesion morphology and size remained static. We highlight the classic radiological presentation of a hemangioma and discuss the features differentiating it from the more commonly observed meningioma seen in the cavernous sinus.
Tuberculosis, an ancient disease, still thrives today as the leading infection caused by Mycobacterium tuberculosis. Diagnosis of ocular tuberculosis poses a great challenge due to the varied clinical presentations. We report 3 cases of primary ocular tuberculosis with varied presentations: conjunctival abscess, sclera-uveitis and occlusive vasculitis. There were no symptoms suggestive of pulmonary tuberculosis in all cases. All patients presented with acute, unilateral painful red eye. The first case had good visual acuity (VA) OD (6/9) with a swollen upper lid, localized perilimbal-hemorrhagic conjunctival swelling superiorly, keratic precipitates and mild anterior chamber reaction. The posterior segment was normal. The second case had a VA of 6/60 OD. There was presence of conjunctival injection, keratic precipitates, posterior synechiae and anterior chamber reaction of 1+. A few days later, there was a progression to vitritis OU and hyperemic optic disc OD with choroidal folds, cystoid macula edema and a positive T sign on B scan ultrasonography. The third case had VA of 6/6 OU, AC reaction of 2+ OD. There was multiple peripheral choroiditis with peripheral vasculitis seen in the posterior segment OU. Fundus fluorescein angiography (FFA) showed peripheral periphlebitis in all 4 quadrants OU. All 3 cases had positive Tuberculin Skin Test (Mantoux test) results which were more than 20mm. Anti-tuberculous treatment was promptly started and all patients showed significant clinical improvement. This case series highlights the diverse clinical presentations of ocular tuberculosis. A high clinical index of suspicion led to prompt initiation of anti-tuberculous therapy which resulted in good clinical outcomes for all cases.
Hb Malay was first described in 1989 following an investigation of anaemia in a 22-year-old Malay gentleman who was homozygous for this chain variant. This Hb variant is caused by AAC AGC mutation at codon 19 of the globin gene resulting in the substitution of serine for asparagine [1]. The mutation creates cryptic RNA splice site in exon 1 of the -globin gene leading to an abnormal RNA processing. Thus, this mutation not only produces variant haemoglobin but also a mild + thalassemia phenotype [2].
Cornea bee sting is a rare condition with mild to severe complications. We report a case series of three patients with cornea bee sting presented to a tertiary center. All patients sustained embedded stingers in the cornea stroma and presented within a few hours of injuries. All patients received topical antibiotics, topical steroids and removal of stingers. However, techniques of stinger removal and administration of the medications are among factors that contributed to different outcomes in these patients
Breast cancer in young pregnancy is a breast cancer diagnosed in a young lady at the age of less than 30 years old during pregnancy. Diagnosis and treatment of breast cancer during pregnancy are challenging as both maternal and fetal outcome must be considered in terms of their short and long-term effects. It requires multidisciplinary treatment. Instead, pregnancy should be preserved whenever possible, while treating the underlying breast cancer. It is important not to compromise the treatment of breast cancer because of the pregnancy. The overall therapeutic concept basically depends on timing of delivery, staging of the underlying disease, treatment mode and the impacts of treatment recommended as well as foetal outcome in relation to treatment that administered to the mother during pregnancy. We present a case of young pregnant lady at the age of 23 with breast cancer as it is a rare event and the challenges encountered in managing her and to highlight the treatment options for the patient and the baby.
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.
Toxoplasmic optic neuropathy is rare and usually occurs monoocularly. This case report demonstrates a rare presentation of bilateral
juxtapapillary retinochoroiditis (Jensen disease) due to toxoplasma infection in
a young healthy patient. A 20-year-old lady presented with bilateral painless
blurring of central vision for 5 days duration. It was preceded by fever, upper
respiratory tract symptoms and headache. There was no history of contact or
being scratched by a cat. Visual acuity was counting fingers for the right eye
and 6/45 for the left eye. There was presence of relative afferent pupillary
defect in the right eye. Optic nerve functions were impaired bilaterally which
was severe in the right eye. Both eyes showed the presence of mild anterior
segment inflammation and vitritis. Fundus examination revealed juxtapapillary
retinochoroiditis bilaterally with swollen optic disc. Optical coherence
tomography (OCT) showed presence of intra-retinal and sub-retinal fluid at
macular area bilaterally. Serology for anti-toxoplasma Immunoglobulin G (IgG)
was positive with titre of 1450 IU/ml. Computed tomography scan (CT scan) of
brain and orbit was normal. A diagnosis of bilateral juxtapapillary
retinochoroiditis or Jensen disease was made. Oral azithromycin 500 mg daily
and guttae prednisolone 4 hourly for 6 weeks was commenced. Oral
prednisolone 50 mg daily (1 mg/kg/day) was added after completion of 1 week
of antibiotic and was tapered down within 5 weeks. There was improvement of
vision as early as 3 weeks post initiation of the treatment. Upon 6 weeks
completing the treatment, her vision has improved to 6/7.5 on both eyes with
resolution of optic disc swelling and sub-retinal fluid. Early recognition and
initiation of treatment in toxoplasma infection associated with juxtapapillary
retinochoroiditis usually result in good visual prognosis.