Ruptured dissecting aortic aneurysm more commonly occur in men in the 40 to 70 age group, and most commonly is associated with atherosclerosis. Uncommon causes are previous heart surgery, connective tissue disorders and aortitis. Despite its rarity, Clostridium spp aortitis progresses very rapidly with a mortality rate of approximately 79% in adults, typically occurring within 48 hours of infection. We present a case of sudden death due to clostridial aortitis causing ruptured aortic dissection in an apparently healthy adult female, 7 weeks post-spontaneous vaginal delivery. This case highlights the pathology of aortic dissection and cystic media necrosis as presentations of clostridium spp infection in young female adult.
NK/T cell lymphoma, nasal type is an aggressive and uncommon malignancy. Disease that occurs outside of the aerodigestive tract exhibits an even more aggressive clinical behaviour and does not respond as well to conventional therapy compared to its nasal counterpart. We report such a case of NK/T cell lymphoma, nasal type, that presented as an anterior chest wall mass, arising from the left pectoralis muscle. An interesting feature we wish to highlight is the associated eosinophilia that corresponded to disease activity, exhibiting fluctuations with surgical resection and chemotherapy. To the best of our knowledge this is the third reported case of NK/T cell lymphoma that is associated with peripheral eosinophilia. Our case highlights the role of certain NK cell subsets that play a major role in eosinophilic activation in NK/T lymphomas and calls for more research into further classification of this disease by virtue of its NK cell subsets.
Thalassaemia carriers are common in the Asian region including Malaysia. Asymptomatic patients can be undiagnosed until they present for their antenatal visits. Devastating obstetric outcome may further complicate the pregnancy if both parents are thalassaemia carriers leading to hydrophic fetus due to haemoglobin Bart's disease. However in certain cases where unexplained hydrops fetalis occur in parents with heterozygous thalassaemia carrier,mutated α genes should be suspected. We report a twenty-nine year old woman in her third pregnancy with two previous pregnancies complicated by early neonatal death at 21 and 28 weeks of gestation due to hydrops fetalis. DNA analysis revealed the patient to have heterozygous (--SEA) α-gene deletion, while her husband has a compound heterozygosity for α(3.7) deletion and codon 59 (GGC → GAC) mutation of the α-gene. This mutation, also known as hemoglobin Adana, can explain hydrops fetalis resulting from two alpha gene deletions from the patient (mother) and a single alpha gene deletion with mutation from the father. The third pregnancy resulted in a grossly normal baby boy with 3 α-gene deletions (HbH disease). We postulate that, in view of heterogenisity of the α-thalassaemia in this patient with severely unstable haemoglobin Adana chains from her husband, there will be a 25% possibility of fetal hydrops in every pregnancy.
Prenatal diagnosis is essential in the new era of diagnosis and management of genetic diseases in obstetrics. Multiple ligation-dependent probe amplification (MLPA) is a recent technique for prenatal diagnosis for the relative quantification of 40 different nucleic acid sequences in one single reaction. We had utilized the MLPA technique in detecting aneuploidies in amniotic fluid samples from 25 pregnant women from the Obstetrics and Gynaecology Department UKMMC, versus the quantitative fluorescent polymerase chain reaction (QF-PCR) method. Conclusive results were obtained in 18 cases and all were concordant with that of the QF-PCR. All four cases of trisomies were correctly identified including one case with maternal cell contamination.
The incidence of breast cancer in Malaysia and other Asian countries is on the increase, reflecting lifestyle changes some of which are known risk factors for the development of breast cancer. Most breast cancers are amenable to adjuvant therapies that target hormone receptors or HER2 receptors on the surface of the cancer cells and bring about significant improvement in survival. However, approximately 17% of Malaysian women with breast cancer, present with tumours that are devoid of these receptors and are consequently termed 'triple negative' breast cancers. These triple negative breast cancers typically occur in women of a younger age than receptor positive cancers, are predominantly of high grade tumours and the prognosis is usually poor. There is therefore a pressing need to understand the biological pathways that drive these tumours, in order that effective strategies are developed to treat these aggressive tumours. With the increasing affluence of developing countries, obesity and Type II Diabetes are also on the rise. These diseases are associated with an increased risk of developing a range of cancers including those of the breast. In particular, the metabolic syndrome has been shown to be associated with triple negative breast cancer. This article reviews some of the metabolic pathways and biomarkers which have been shown to be aberrantly expressed in triple negative breast cancer and highlights some of the ongoing work in this area.
Follicular lymphoma is characterised by the t(14;18)(q32;q21) chromosomal translocation causing BCL2 protein overexpression. A proportion of follicular lymphomas do not carry the t(14;18) translocation and lacked BCL2 protein expression. We describe a case of a BCL2 protein- and t(14;18)-negative follicular lymphoma that caused diagnostic difficulty. The usefulness of several immunomarkers including Ki67, CD79a and CD21 in aiding the diagnosis is discussed. The patient is a 51-year-old male who presented with gradually enlarging lymphadenopathy. Histopathological examination of the lymph node showed complete architectural effacement by neoplastic follicles containing expanded CD21-positive follicular dendritic cell meshwork. The neoplastic cells expressed pan-B cell markers (CD20, CD79a) and germinal centre marker (BCL6) but not BCL2 and CD10. Of interest are the staining patterns of Ki67 and CD79a. We observed that the Ki67- positive proliferating cells were evenly distributed within the neoplastic follicles without zonation. In addition, CD79a was homogeneously strong within the neoplastic follicles. These staining patterns were distinctly different from that observed in reactive lymphoid follicles. Fluorescent insitu hybridisation (FISH) analysis however showed absence of BCL2 gene rearrangement. Despite the atypical immunophenotype and lack of BCL2 gene rearrangement, the diagnosis of follicular lymphoma was made based on careful observation of the morphology as well as immunoarchitecture of the Ki67, CD79a and CD21 markers.
Monitoring treatment response to anti-tuberculous therapy remains unsatisfactory in resource-limited countries where sophisticated and expensive tests are not readily available. Sputum culture for mycobacterium is desirable, but not obtainable in many developing countries. Sputum acid-fast bacilli (AFB) smear alone can be misinterpreted in the presence of unviable bacilli or non-tuberculous mycobacteria. Hence the search for a cheaper but reliable monitoring tool, or a combination of several tools, continues. Interesting reports from studies in third world nations have considered weight gain/loss as one such monitoring tool. Since pulmonary tuberculosis is endemic in this country, we take the opportunity to evaluate weight gain and chest radiograph, compared to sputum AFB smear in monitoring patient's response.
We report a rare case of homozygous familial hypercholesterolemia (HoFH), a 22-year-old Malay woman who presented initially with minor soft tissue injury due to a cycling accident. She was then incidentally found to have severe xanthelasma and hypercholesterolemia (serum TC 15.3 mmol/L and LDL-C 13.9 mmol/L). She was referred to the Specialized Lipid Clinic and was diagnosed with familial hypercholesterolemia (FH) based on the Simon Broome (SB) diagnostic criteria. There was a family history of premature coronary heart disease (CHD) in that three siblings had sudden cardiac death, and of consanguineous marriage in that her parents are cousins. DNA screening of LDLR and APOB genes was done by Polymerase Chain Reaction (PCR), followed by Denaturing High Performance Liquid Chromatography (DHPLC). Homozygous mutation C255S in Exon 5 of her LDLR gene was found. There was no mutation was found in Exon 26 and Exon 29 of the APOB gene. This report is to emphasize the importance of identifying patients with FH and cascade screening through established diagnostic criteria and genetic studies in order to ensure early detection and early treatment intervention to minimize the risk of developing CHD and related complications.
Deaths due to blunt force trauma to the head as a result of assault are some of the most common cases encountered by the practicing forensic pathologist. Previous studies have shown inflicting injury to the head region is one of the most effective methods of murder. The important factors that determine severity of trauma include the type of weapon used, type and site of skull fracture, intracranial haemorrhage and severity of brain injury. The aim of this study was to determine the characteristics of blunt force trauma to the skull produced by different instruments. Nine adult monkeys (Macaca fascicularis) skulls were used as models. Commonly found blunt objects comprising of Warrington hammer, hockey stick and open face helmet were used in this study. A machine calibrated force generator was used to hold the blunt object in place and to hit the skulls at forces of 12.5N and 25N. Resultant traumatic effects and fractures (linear, depressed, basilar, comminuted, and distastic) were analyzed according to type of blunt object used; surface area of contact and absolute force (N/cm(2)) delivered. Results showed that all investigated instruments were capable of producing similar injuries. The severity of trauma was not related to the surface area of contact with the blunt objects. However, only high absolute forces produced comminuted fractures. These findings were observational, as the samples were too small for statistical conclusions.
Alpha (Α) thalassaemia is the most common inherited disorder in Malaysia. The clinical severity is dependant on the number of Α genes involved. Full blood count (FBC) and haemoglobin (Hb) analysis using either gel electrophoresis, high performance liquid chromatography (HPLC) or capillary zone electrophoresis (CE) are unable to detect definitively alpha thalassaemia carriers. Definitive diagnosis of Α-thalassaemias requires molecular analysis and methods of detecting both common deletional and non-deletional molecular abnormailities are easily performed in any laboratory involved in molecular diagnostics. We carried out a retrospective analysis of 1623 cases referred to our laboratory in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) for the diagnosis of Α-thalassaemia during the period October 2001 to December 2012. We examined the frequency of different types of alpha gene abnormalities and their haematologic features. Molecular diagnosis was made using a combination of multiplex polymerase reaction (PCR) and real time PCR to detect deletional and non-deletional alpha genes relevant to southeast Asian population. Genetic analysis confirmed the diagnosis of Α-thalassaemias in 736 cases. Majority of the cases were Chinese (53.1%) followed by Malays (44.2%), and Indians (2.7%). The most common gene abnormality was ΑΑ/--(SEA) (64.0%) followed by ΑΑ/-Α(3.7) (19.8%), -Α(3.7) /--(SEA) (6.9%), ΑΑ/ΑΑCS (3.0%), --(SEA)/--(SEA) (1.2%), -Α(3.7)/-Α(3.7) (1.1%), ΑΑ/-Α(4.2) (0.7%), -Α(4.2)/--(SEA (0.7%), -Α(3.7)/-Α(4.2) (0.5%), ΑΑ(CS)/-- SEA) (0.4%), ΑΑ(CS)/ΑΑ(Cd59) (0.4%), ΑΑ(CS)/ΑΑ(CS) (0.4%), -Α(3.7)/ΑΑ(Cd59) (0.3%), ΑΑ/ΑΑ(Cd59) (0.1%), ΑΑ(Cd59)/ ΑΑ(IVS I-1) (0.1%), -Α(3.7)/ΑΑ(CS) (0.1%) and --(SEA) /ΑΑ(Cd59) (0.1%). This data indicates that the molecular abnormalities of Α-thalassaemia in the Malaysian population is heterogenous. Although Α-gene deletion is the most common cause, non-deletional Α-gene abnormalities are not uncommon and at least 3 different mutations exist. Establishment of rapid and easy molecular techniques is important for definitive diagnosis of alpha thalassaemia, an important prerequisite for genetic counselling to prevent its deleterious complications.
Murder is the most notorious crime that violates religious, social and cultural norms. Examining the types and number of different killing methods that used are pivotal in a murder case. However, the psychological traits underlying specific and multiple killing methods are still understudied. The present study attempts to fill this gap in knowledge by identifying the underlying psychological traits of different killing methods among Malaysian murderers. The study adapted an observational cross-sectional methodology using a guided self-administered questionnaire for data collection. The sampling frame consisted of 71 Malaysian male murderers from 11 Malaysian prisons who were selected using purposive sampling method. The participants were also asked to provide the types and number of different killing methods used to kill their respective victims. An independent sample t-test was performed to establish the mean score difference of psychological traits between the murderers who used single and multiple types of killing methods. Kruskal-Wallis tests were carried out to ascertain the psychological trait differences between specific types of killing methods. The results suggest that specific psychological traits underlie the type and number of different killing methods used during murder. The majority (88.7%) of murderers used a single method of killing. Multiple methods of killing was evident in 'premeditated' murder compared to 'passion' murder, and revenge was a common motive. Examples of multiple methods are combinations of stabbing and strangulation or slashing and physical force. An exception was premeditated murder committed with shooting, when it was usually a single method, attributed to the high lethality of firearms. Shooting was also notable when the motive was financial gain or related to drug dealing. Murderers who used multiple killing methods were more aggressive and sadistic than those who used a single killing method. Those who used multiple methods or slashing also displayed a higher level of minimisation traits. Despite its limitations, this study has provided some light on the underlying psychological traits of different killing methods which is useful in the field of criminology.
Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) contribute in the development of preeclampsia and are suggested as prediction markers in healthy pregnant women but limited data is available in women with major preeclampsia risk factors. This study aimed to determine the role of sFlt-1 and PlGF in predicting preeclampsia among high risk pregnant women. This was a prospective study and samples were collected for a period of ten months. Blood samples were obtained from 84 pregnant women who had at least one risk factor for preeclampsia at 25 to 28 weeks and at 29 to 36 weeks of gestation. SFlt-1 and PlGF concentrations were determined by immunoassay method. There were significantly higher median sFlt-1 and sFlt-1:PlGF ratio at gestational interval 25 to 28 weeks and sFlt-1:PlGF ratio at 29 to 36 weeks in high risk women who developed preeclampsia. Significant lower median serum PlGF levels at 25 to 28 weeks and 29 to 36 weeks were observed in this group of women. In conclusion, the concentrations of these markers were altered in high risk preeclamptic women, a similar pattern seen in low risk preeclamptic women. However the predictive value of these markers could not be established clearly.
Experiments involving short-term space flight have shown an adverse effect on the physiology, morphology and functions of cells investigated. The causes for this effect on cells are: microgravity, temperature fluctuations, mechanical stress, hypergravity, nutrient restriction and others. However, the extent to which these adverse effects can be repaired by short-term space flown cells when recultured in conditions of normal gravity remains unclear. Therefore this study aimed to investigate the effect of short-term spaceflight on cytoskeleton distribution and recovery of cell functions of normal human osteoblast cells. The ultrastructure was evaluated using ESEM. Fluorescent staining was done using Hoechst, Mito Tracker CMXRos and Tubulin Tracker Green for cytoskeleton. Gene expression of cell functions was quantified using qPCR. As a result, recovered cells did not show any apoptotic markers when compared with control. Tubulin volume density (p<0.001) was decreased significantly when compared to control, while mitochondria volume density was insignificantly elevated. Gene expression for IL-6 (p<0.05) and sVCAM-1 (p<0.001) was significantly decreased while alkaline phosphatase (p<0.001), osteocalcin and sICAM (p<0.05) were significantly increased in the recovered cells compared to the control ones. The changes in gene and protein expression of collagen 1A, osteonectin, osteoprotegerin and beta-actin, caused by short-term spaceflight, were statistically not significant. These data indicate that short term space flight causes morphological changes in osteoblast cells which are consistent with hypertrophy, reduced cell differentiation and increased release of monocyte attracting proteins. The long-term effect of these changes on bone density and remodeling requires more detailed studies.
Ewing sarcoma (ES)/ primitive neuroectodermal tumour (PNET) is an aggressive malignant neoplasm affecting mainly children and young adults. The tumour is included with other primitive neoplasms under the category of small round cell tumour. Cytokeratin expression in ES/PNET has been described in sporadic case reports as well as a few systemic series. We studied this feature in Malaysian patients diagnosed in University Malaya Medical Centre on the basis of typical morphology and immunohistochemical assays. Immunohistochemical staining for AE1/AE3 and MNF116 were performed in 43 cases. Cytokeratin was expressed in 17 cases (39.5%) in focal, intermediate or diffuse patterns. There was no significant association between cytokeratin immunoreactivity and the following parameters: patient age, sex, skeletal and extraskeletal primary location as well as primary, metastastic or recurrent tumours or chemotherapy treatment. A significant association between cytokeratin and neuron specific enolase (NSE) expression was demonstrated. Our study supports evidence of epithelial differentiation in ES/PNET and emphasizes that the expression of cytokeratin does not exclude ES/PNET in the differential diagnosis of small round cell tumours.
The effects of spaceflight on cardiovascular health are not necessarily seen immediately after astronauts have returned but can be delayed. It is important to investigate the long term effects of spaceflight on protein and gene expression of inflammation and endothelial activation as a predictor for the development of atherosclerosis and potential cardiovascular problems. The objectives of this study were to investigate the (a) protein and gene expression of inflammation and endothelial activation, (b) expression of nuclear factor kappa B (NFκB), signal transducer and activator of transcription-3 (STAT-3) and endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVEC) 3 months post-space flight travel compared to ground controls. HUVEC cultured on microcarriers in fluid processing apparatus were flown to the International Space Station (ISS) by the Soyuz TMA-11 rocket. After landing, the cells were detached from microcarriers and recultured in T-25 cm(2) culture flasks (Revived HUVEC). Soluble protein expression of IL-6, TNF-α, ICAM-1, VCAM-1 and e-selectin were measured by ELISA. Gene expression of these markers and in addition NFκB, STAT-3 and eNOS were measured. Spaceflight induced IL-6 and ICAM-1 remain elevated even after 3 months post spaceflight travel and this is mediated via STAT-3 pathway. The downregulation of eNOS expression in revived HUVEC cells suggests a reduced protection of the cells and the surrounding vessels against future insults that may lead to atherosclerosis. It would be crucial to explore preventive measures, in relation to atherosclerosis and its related complications.
The presence of antiphospholipid antibodies (aPLs) is closely associated with thrombotic events and pregnancy complications such as recurrent pregnancy loss, preeclampsia and placental insufficiency. We investigated the presence of aPLs and its frequency among female patients with a history of fetal loss in a Malaysia population. Serum samples were collected from 108 patients who had (1) one or more unexplained deaths of morphologically normal fetuses at or beyond the 22nd week of gestation, or (2) one or more premature births of morphologically normal neonates at or before the 24th week of gestation due to eclampsia or preeclampsia, or recognized features of placental insufficiency, or (3) three or more unexplained, consecutive, spontaneous miscarriages before the 20th week of gestation. Serum was tested for aPLs subtypes: anticardiolipin (aCL), anti-beta-2- glycoprotein I (aβ2GPI), anti-beta-2-glycoprotein I dependent cardiolipin (aβ2GPI dependent CL), anti-phosphatidylcholine (aPC), anti-phosphatidylethanolamine (aPE), anti-phosphatidylinositol (aPI), anti-phosphatidylserine (aPS) and anti-sphingomyeline (aSph) by using the enzyme-linked immunosorbent assay (ELISA) method. The mean age of patients was 30±5. Four patients (3.7%) were found positive for at least one aPLs subtype. Four aPLs subtypes were detected. The most common subtypes was aβ2GPI dependent CL (3.7%), followed by aCL (2.7%), aβ2GPI (0.9%), and aPE(0.9%). In conclusion, frequency of aPLs among women with fetal loss (3.7%) in Malaysia was low with subtype aβ2GPI dependent CL being the most prevalent aPLs.
Leptospirosis is an endemic disease in Malaysia and recently has received increasing attention mainly due to several recent incidents that have resulted in human mortality which have alarmed health professionals in Malaysia. The increasing incidence of leptospirosis in forested regions is associated with the bacteria infecting small wild mammals other than rats. Infection in wildlife could result in the introduction of new serovars to humans and domesticated animals. More research on leptospirosis and the screening of wildlife and humans near wildlife habitats is required to have a better understanding of the involvement of wildlife in the disease.