Apolipoprotein E (APOE = gene, apoE = protein) plays a central role in plasma lipoprotein metabolism and in lipid transport within tissues. The APOE shows a genetic polymorphism determined by three common alleles, APOE*2, APOE*3, APOE*4 and the product of the three alleles differs in several functional properties. APOE is involved in the development of certain pathological conditions. In particular, the APOE*4 allele is a risk factor for susceptibility to coronary artery disease (CAD) and Alzheimer's Disease (AD). In the present study we analyzed the APOE allele distribution in the world. The APOE*3 is the most frequent in all the human groups, especially in populations with a long-established agricultural economy like those of the Mediterranean basin (0.849-0.898). The frequency of APOE*4, the ancestral allele, remains higher in populations like Pygmies (0.407) and Khoi San (0.370), aborigines of Malaysia (0.240) and Australia (0.260), Papuans (0.368), some Native Americans (0.280), and Lapps (0.310) where an economy of foraging still exists, or food supply is (or was until the recent past) scarce and sporadically available. The APOE*2 frequency fluctuates with no apparent trend (0.145-0.02) and is absent in Native Americans. We suggest that the APOE*4, based on some functional properties it has and on its distribution among human populations, could be identified as a 'thrifty' allele. The exposure of APOE*4 to the contemporary environmental conditions (Western diet, longer lifespans) could have rendered it a susceptibility allele for CAD and AD. The absence of the association of APOE*4 with CAD and AD in Sub-Saharan Africans, and its presence in African Americans, seems to confirm this hypothesis.
Emerging infectious diseases involving zoonosis have become important global health problems. The 1998 outbreak of severe febrile encephalitis among pig farmers in Malaysia caused by a newly emergent paramyxovirus, Nipah virus, is a good example. This disease has the potential to spread to other countries through infected animals and can cause considerable economic loss. The clinical presentation includes segmental myoclonus, areflexia, hypertension, and tachycardia, and histologic evidence includes endothelial damage and vasculitis of the brain and other major organs. Magnetic resonance imaging has demonstrated the presence of discrete high-signal-intensity lesions disseminated throughout the brain. Nipah virus causes syncytial formation in Vero cells and is antigenically related to Hendra virus. The Island flying fox (Pteropus hypomelanus; the fruit bat) is a likely reservoir of this virus. The outbreak in Malaysia was controlled through the culling of >1 million pigs.
Alzheimer's disease (AD) has become recognised as a major cause of morbidity and mortality in the ageing population worldwide. Over 20 million people worldwide are affected by AD, which ensures that the disease imposes a major economic burden. Alzheimer's disease is a progressive neurodegenerative disorder with characteristic clinical and neuropathological features. Neurofibrillary tangles, neuritic plaques and amyloid angiopathy occur in varying severity in brains of patient's with Alzheimer's disease. Biological markers of AD allowing an early definitive premorbid diagnoses are currently not available. Memory loss for recent events is invariable and often the earliest prominent symptom. Language disorders, difficulties with complex tasks, depression, psychotic symptoms and behavioral changes are other common manifestations of AD. Diagnosis involves the early detection of cognitive decline and ruling out other causes of dementia like vascular dementia, Lewy body dementia, fronto-temporal degeneration or reversible causes like hypothyroidism. Acetylcholinesterase inhibitors have shown to be effective in mild to moderate AD in improving the cognitive function of patients in clinical trials. Caregiver intervention programs have considerable potential to improve both the caregiver and patient quality of life.
A 49 year-old Indian housewife was diagnosed with Hodgkin's disease in 1995. She was given combination chemotherapy comprising Chlorambucil, Vincristine, Procarbazine and Prednisolone. Unfortunately she defaulted after two courses of chemotherapy. One year later, she developed progressive right knee swelling and pain, associated with loss of appetite, loss of weight, intermittent fever, night sweats and pruritus. The right knee swelling measured 15 cm x 20 cm and was warm and tender. A plain radiograph of the right knee revealed osteolytic lesions at the distal end of the right femur and the proximal ends of the right tibia and fibula, associated with gross periosteal reaction and soft tissue swelling. Apart from left cervical lymphoadenopathy, examination of other systems was unremarkable. Pelvic bone marrow biopsy was inconclusive. An open biopsy of the lower end of the right femur was consistent with Hodgkin's disease. She was given salvage combination therapy comprising Chlorambucil, Vincristine, Procarbazine, Prednisolone, Doxorubicin, Bleomycin and Vinblastine. She tolerated the treatment well and responded with significant reduction in the swelling and pain of the right knee. Unfortunately, she again defaulted treatment after 2 courses of chemotherapy. This case illustrates an unusual presentation of Hodgkin's disease in relapse.
Partial nucleotide sequences of 1D gene of 38 isolates of foot-and-mouth disease virus (FMDV) of serotypes O, A and Asia 1 originating from various parts of India were determined. Field materials were subjected straight to RNA extraction, reverse transcription - PCR (RT-PCR) and sequencing. Also 3 FMDV vaccine strains, IND R2/75 (serotype O), IND 63/72 (serotype Asia 1) and IND 17/77 (serotype A) were included in the analysis. The seqences were compared mutually as well as with available corresponding sequences of other FMDV isolates, and their phylogenetic relationships were calculated. The deduced amino acid sequences showed that the serotype O isolates were relatively conserved as compared to serotype Asia 1 or A isolates from India. In phylogenetic analysis, the serotype O viruses clustered in two genotypes, one including the European vaccine strain (O1/K) and the other represented by the isolates from Bangladesh, India, Nepal and Turkey. The serotype Asia 1 viruses clustered in two groups of single genotype where the prototype strain from Pakistan (PAK 1/54) formed one group and the other was formed by the isolates from Bangladesh, Bhutan, India, Israel and Nepal. In serotype A viruses three well-differentiated genotypes were observed. The isolates from Azerbaijan, Bangladesh, Malaysia and India formed the first genotype. The second genotype was formed by isolates from Iran, Saudi Arabia and Turkey, while two recent Iranian isolates represented the third genotype. In India, the prevalence of at least one genotype could be identified in each serotype. This evolutionary clustering of isolates from the neighbor countries is not surprising, since these countries share border with India. The genetic relatedness between sequences of isolates from India and those from distant places is indicative of spread of the virus between the countries. Of importance is the fact that clinical materials proved useful for rapid generation of sequences and subsequent studying of molecular epidemiology of the disease.
From available studies, there appears to be a racial preponderance of coronary artery disease (CAD) among Indians when compared to other ethnic groups. We found that this racial difference exists even in a young Asian population with premature atherosclerosis. In this small series, these racial differences could not be explained by the commonly known risk factors for coronary artery disease--smoking, hypertension, diabetes and hypercholesterolaemia, findings similar to those found in older patients elsewhere. Only fasting triglyceride levels were significantly higher among young Indians compared to non Indians (p less than 0.02) although the importance of this finding as a risk factor for CAD remains controversial. The majority of these young patients were treated medically and their one year survival was good.
Since dengue was first documented in Malaysia in 1902 and made notifiable in 1973, the disease pattern has changed from major outbreaks every four years to one of increasing trend yearly. The largest outbreak was seen in 1996 with 14,255 dengue cases reported and 32 deaths. The case fatality rate varied from a high of 10.43% in 1985 when dengue type 3 was the predominant type to a low of 1.29% when dengue type 1 predominated. Severe disease patterns have been observed with dengue 2 and 3 serotypes in the country. The clinical spectrum has also been changing and multisystem involvement with more severe manifestations are being seen. Liver involvement has been documented since 1987. Fulminant hepatitis with encephalopathy can resemble Reye's syndrome. Dengue type 3 has been isolated from liver biopsy specimens. Neurological manifestations can very from irritability, convulsions, coma to peripheral neuritis. The isolation of dengue viruses from cerebrospinal fluids recently strongly suggests that dengue viruses can be neurovirulent. Adult respiratory distress syndrome was seen in three children admitted with shock. Deaths were more frequent in children in the early period but since 1982, over 50% of deaths have occurred in patients over the age of 15 years.
An invasive aspergillosis model in rabbits was attempted using 3 concentrations of A. fumigatus conidia. Conidia concentrations of 1 x 10(6), 1 x 10(7) and 1 x 10(8) were inoculated intravenously into rabbits. The severity of infection was directly proportional to the inoculum size of the conidia. Aspergillus fumigatus was isolated from livers, kidneys, spleens, hearts and lungs of infected rabbits at a rate of 82%, 75%, 57%, 54% and 32% respectively. Cultures of urine specimens taken by bladder tap were positive for A. fumigatus in 30% of the rabbits tested. Blood cultures using the Bactec Fungal System (Becton Dickinson Corp., USA) failed to isolate A. fumigatus in 20 rabbits with biopsy-proven invasive apergillosis. Active infection with high fungal tissue burden occurred between 2-4 days after infection in rabbits inoculated with 1 x 10(7) conidia.
Tropical pulmonary eosinophilia (TPE) is considered to be a variant of human filarial infection. The pulmonary manifestations of TPE have been well described. Extra-pulmonary features of the disease, although not commonly seen, have been reported previously. A 9-year-old Malay girl with a history of recurrent cough and wheezing was admitted because of cardiac failure. Physical examination revealed a very sick girl with tachypnoea, central cyanosis, finger clubbing, elevated jugular venous pulse, generalized crackles and rhonchi in the chest, a loud second heart sound and hepatosplenomegaly. A chest radiograph showed cardiomegaly and right pleural effusion. Laboratory investigations revealed hypochromic, microcytic anaemia with persistent blood eosinophilia (absolute eosinophil counts varied from 1.9 to 5.5 x 10(9)/1). The ELISA test for antifilarial IgG antibodies was strongly positive. She responded promptly to treatment with diethylcarbamazine. In summary, this is a patient with TPE who presented with cor pulmonale, probably due to late-stage interstitial pulmonary fibrosis. In order to prevent the long term morbidity of cardiorespiratory disability, the early signs of TPE should be recognized and the infection treated.
Central nervous system involvement in melioidosis is rare. We describe a 48 year old woman who developed septicaemia and a brain abscess due to Pseudomonas pseudomallei. Since there is a continuing practical problem in bacteriological confirmation of the aetiological agent, diagnosis of melioidosis has to be made on clinical suspicion.
Two episodes of El Tor cholera outbreak occurred in Tumpat, Kelantan between the 13th of January and the 16th of May 1990. Every case and carrier reported were investigated to determine the source and mode of transmission and to identify specific preventive measures to break the chain of transmission. There were 109 cases and 85 carriers involved in this study. The first episode of one case only was of Inaba serotype while the second episode was caused by the imported Ogawa serotype. Two foci of spread were identified from cluster occurrence but the majority of infection had no discernible link between them. The outbreak became both explosive and protracted indicating poor basic sanitation and personal hygiene. Person-to-person transmission via food and water was the main mode of spread. The Kelantan river water and river clams were confirmed sources of reservoir during the outbreak. Recommendations for prevention are intensified surveillance throughout the year,urgent upgrading of potable water supply and concerted effort in public health education especially against the use of river water and the consumption of raw food.
Matched MeSH terms: Disease Outbreaks*; Disease Reservoirs/statistics & numerical data
The clinical, biochemical and immunological features of 180 patients with hyperthyroid Graves' disease managed at the Universiti Kebangsaan Malaysia (UKM) Endocrine Clinic from 1983 to 1987 were examined. The prevalence of the disease is highest in Chinese and lowest in Indians. The female: male ratio is 2.8:1. Hypokalaemic periodic paralysis and hypercalcaemia were present in 5.0% and 1.7% of the cases respectively. Pretibial myxoedema was extremely rare. Thyrotropin - binding inhibitory immunoglobulins, anti-thyroglobulin and anti-microsome antibodies were positive in 61.5%, 25.8% and 42.3% of the patients respectively. A eumetabolic state could be achieved in the majority of patients with antithyroid drugs alone. Definitive therapy with subtotal thyroidectomy or radioiodine were needed in 31.3% of cases.
In a prospective case-control study over a two-year period involving 1006 women, 264 women with acute myocardial infarction (AMI), 305 with non-infarct acute coronary syndromes (CAD) were compared with 437 women with no coronary heart disease (Controls), to determine the relationship between cigarette smoking and other risks factors with coronary heart disease. A history of current cigarette smoking was strongly associated with the risk of coronary events for both AMI And CAD (p less than 0.001). 23.9% of patients with acute coronary syndromes were current smokers, compared with only 12.8% among controls. Overall, women smokers had about a two-fold increase in risk for all coronary events. Younger women smokers (less than 40 years) and those between 61-70 years had particularly higher risks (10.3 and 2.7 times respectively (p less than 0.01, p less than 0.02). A dose-response pattern of increased AMI risks (from 2.0 to 2.9 times) among women smokers was also found, corresponding to the number of cigarettes smoked per day (p less than 0.05). Other significant coronary risk factors established were: postmenopausal status (OR 6.5), diabetes mellitus (OR 5.1), hypertension (OR 1.6), family history of premature coronary heart disease less than 50 years (OR 1.3) and use of oral contraceptive pills (OR 1.4). Our results thus emphasize that cigarette smoking is an important determinant of acute coronary events even among Malaysian women.
A six-week-old male infant was admitted for investigation of cholestasis and pale stools. He became lethargic and apnoeic with prolonged seizures after a percutaneous liver biopsy. Subsequent investigations showed conjugated hyperbilirubinaemia, elevated liver enzymes, and hypoglycaemia. The radinuclide hepatobiliary scintigraphy was non-excretory. After an operative cholangiogram, the infant developed Addisonian-like crisis with bradycardia, hypotension, respiratory distress, metabolic acidosis, hypoglycaemia, hyponatraemia, and hyperkalaemia. Blood investigations confirmed congenital hypopituitarism. Hormone replacement therapy with L-thyroxine and cortisone acetate resulted in dissolution of jaundice and the reduction of the liver size.
Leigh syndrome (LS) is one of the most puzzling mitochondrial disorders, which is also known as subacute necrotizing encephalopathy. It has an incidence of 1 in 77,000 live births worldwide with poor prognosis. Currently, there is a poor understanding of the underlying pathophysiological mechanisms of the disease without any available effective treatment. Hence, the inevitability for developing suitable animal and cellular models needed for the development of successful new therapeutic modalities. In this short report, we blocked FOXRED1 gene with small interfering RNA (siRNA) using C57bl/6 mice. Results showed neurobehavioral changes in the injected mice along with parallel degeneration in corpus striatum and sparing of the substantia nigra similar to what happen in Leigh syndrome cases. FOXRED1 blockage could serve as a new animal model for Leigh syndrome due to defective CI, which echoes damage to corpus striatum and affection of the central dopaminergic system in this disease. Further preclinical studies are required to validate this model.
The process of software development life cycle (SDLC) is an important element of development phases to develop the application. In fact, there are needs to upgrade the sequence of methodology in software development. Thus, the SDLC is very crucial in order for them to ensure the quality of skills is placed accordingly in the workflow. This research contributes to the development of a new approach in system development workflow with the aim to properly manage system development projects. It started by providing some background data related to the previous mode of operation in the teamwork samples as shared by the stakeholders of the transformation projects and the new proposed Analysis System Development Framework (ASDF) method team members. Then, the key findings related to steps of software development such as (1) input for User Requirement Specification (URS) and (2) System Requirement Specification (SRS), (3) process for module, (4) process for database, (5) process for User Acceptance Testing (UAT) (6) output for Final Acceptance Testing (FAT) and empowerment for the whole level based on ASDF method. This paper contribution significantly to support the perception of high quality of skills in a teamwork, results in better performance of software development.
Foot-and-mouth disease (FMD) is a major threat to the livestock industry worldwide. Despite constant surveillance and effective vaccination, the perpetual mutations of the foot-and-mouth disease virus (FMDV) pose a huge challenge to FMD diagnosis. The immunodominant region of the FMDV VP1 protein (residues 131-170) displayed on phage T7 has been used to detect anti-FMDV in bovine sera. In the present study, the functional epitope was further delineated using amino acid sequence alignment, homology modelling and phage display. Two highly conserved regions (VP1145-152 and VP1159-170) were identified among different FMDV serotypes. The coding regions of these two epitopes were fused separately to the T7 genome and displayed on the phage particles. Interestingly, chimeric phage displaying the VP1159-170 epitope demonstrated a higher antigenicity than that displaying the VP1131-170 epitope. By contrast, phage T7 displaying the VP1145-152 epitope did not react significantly with the anti-FMDV antibodies in vaccinated bovine sera. This study has successfully identified a smaller functional epitope, VP1159-170, located at the C-terminal end of the structural VP1 protein. The phage T7 displaying this shorter epitope is a promising diagnostic reagent to detect anti-FMDV antibodies in vaccinated animals.
Neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by progressive neuronal loss and pathological accumulation of some proteins. Developing new biomarkers for both diseases is highly important for the early diagnosis and possible development of neuro-protective strategies. Serum antibodies (AIAs) against neuronal proteins are potential biomarkers for AD and PD that may be formed in response to their release into systemic circulation after brain damage. In the present study, two AIAs (tubulin and tau) were measured in sera of patients of PD and AD, compared to healthy controls. Results showed that both antibodies were elevated in patients with PD and AD compared to match controls. Curiously, the profile of elevation of antibodies was different in both diseases. In PD cases, tubulin and tau AIAs levels were similar. On the other hand, AD patients showed more elevation of tau AIAs compared to tubulin. Our current results suggested that AIAs panel could be able to identify cases with neuro-degeneration when compared with healthy subjects. More interestingly, it is possible to differentiate between PD and AD cases through identifying specific AIAs profile for each neurodegenerative states.