Impact of elevated IgE in protective immunity and immunopathology of dengue.

Dengue is a mosquito-transmitted infection endemic in tropical and subtropical locations of the world where nearly half of the world's population resides. The disease may present as mild febrile illness to severe and can even be fatal if untreated. There are four genetically related but antigenically distinct dengue virus (DENV) serotypes. Immune responses to DENV infection are in general protective but under certain conditions, they can also aggravate the disease. The importance of the cellular immune responses and the antibody responses involving IgG and IgM has been well-studied. In contrast, not much has been described on the potential role of hypersensitivity reactions involving IgE in dengue. Several studies have shown elevated levels of IgE in patients with dengue fever, but its involvement in the immune response against the virus and disease is unknown. Activation of mast cells (MCs) and basophils mediated through dengue-specific IgE could result in the release of mediators affecting dengue virus infection. The present review explores the relationships between the induction of IgE in dengue virus infection, and the potential role of MCs and basophils, exploring both protective and pathogenic aspects, including antibody-dependent enhancement (ADE) of infection in dengue.

Childhood Allergy Disease, Early Diagnosis, and the Potential of Salivary Protein Biomarkers.

Allergic disease has risen to epidemic proportions since the last decade and is among the most common noncommunicable, chronic diseases in children and adolescents worldwide. Allergic disease usually occurs in early life; thus, early biomarkers of allergic susceptibility are required for preventive measures to high-risk infants which enable early interventions to decrease allergic severity. However, to date, there is no reliable general or specific allergy phenotype detection method that is easy and noninvasive for children. Most reported allergic phenotype detection methods are invasive, such as the skin prick test (SPT), oral food challenge (OFC), and blood test, and many involve not readily accessible biological samples, such as cord blood (CB), maternal blood, or newborn vernix. Saliva is a biological sample that has great potential as a biomarker measurement as it consists of an abundance of biomarkers, such as genetic material and proteins. It is easily accessible, noninvasive, collected via a painless procedure, and an easy bedside screening for real-time measurement of the ongoing human physiological system. All these advantages emphasise saliva as a very promising diagnostic candidate for the detection and monitoring of disease biomarkers, especially in children. Furthermore, protein biomarkers have the advantages as modifiable influencing factors rather than genetic and epigenetic factors that are mostly nonmodifiable factors for allergic disease susceptibility in childhood. Saliva has great potential to replace serum as a biological fluid biomarker in diagnosing clinical allergy. However, to date, saliva is not considered as an established medically acceptable biomarker. This review considers whether the saliva could be suitable biological samples for early detection of allergic risk. Such tools may be used as justification for targeted interventions in early childhood for disease prevention and assisting in reducing morbidity and mortality caused by childhood allergy.

α-Thalassemia with Haemoglobin Adana mutation: prenatal diagnosis.

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.

Clinical-Epidemiological Pattern of Primary Immunodeficiencies in Malaysia 1987-2006: A 20 year experience in Four Malaysian Hospitals.

AIM OF STUDY: To determine the clinical and epidemiological characteristics of patients seen with primary immunodeficiencies referred at four Malaysian Hospitals between 1987 to 2007. METHODS: Patient data were retrospectively obtained from patient records and supplemented by information from a standardized questionnaires taken at the time of diagnosis from 4 participating hospitals. The completed data were transferred to document records kept by the first author. The diagnoses made were based on criteria set by WHO Scientific Committee 1986. RESULTS: Fifty one (51) patients with completed records satisfied the criteria of primary immunodeficiencies based on WHO Scientific Committee 1986. Predominant Antibody deficiency (40.4%) is the commonest of the class of primary immunodeficiency (based on modified IUIS classification) followed by phagocytic defect (17.3%), combined immunodeficiencies (15.4%) and other cellular immunodeficiencies (11.5%). The commonest clinical presentation is pneumonia (54%) . A positive Family history with a close family relative afflicted was a strong pointer to diagnosis for PID (52.6%) Primary immnodeficiencies are seen in all the major ethnic groups of Malaysia, predominantly among Malays. As observed in other patient registries, diagnostic delay remains the major cause of morbidity and mortality. CONCLUSION: Primary immunodeficiencies is relative rare but is an emerging disease in Malaysia. Creating awareness of the disease, may reveal more cases within the community. It is sufficient to be a health issue in Malaysia as in other developing countries in the future.

Religiousness, religious coping methods and distress level among psychiatric patients in Malaysia.

BACKGROUND: Patients having psychiatric diagnoses often experience high level of distress. Religiousness is often used by them as part of their coping mechanism and problem-solving strategies. OBJECTIVE: To determine the level of religious commitment and coping methods in psychiatric patients and its relationship with distress level. METHODS: Religious commitment and coping patterns were measured with the Duke University Religious Index (DUREL) and Brief RCOPE, respectively. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS) and distress level was assessed with the Depressive, Anxiety and Stress Scale (DASS). Social support and experiences of recent threatening events were measured with the Multidimensional Scale of Perceived Social Support (MSPSS) and Life Threatening Events (LTE). RESULTS: A total of 228 patients were included in this study with a mean age of 40.2 years. The majority were male, Malay, Muslim, single and with psychotic disorder. The subjects had a high level of religious commitment and had used more positive coping methods. Negative religious coping, psychiatric symptoms and diagnosis of anxiety disorder or major depression were significantly associated with high distress level. Higher religious commitment was significantly associated with lower distress (p < .05). CONCLUSION: Psychiatric patients were religiously committed and used more positive religious coping methods. Practices of negative religious coping, severe psychiatric symptoms and anxiety/depression were associated with higher distress.

Validation of the Malay version of the Multidimensional Scale of Perceived Social Support (MSPSS-M) among a group of medical students in Faculty of Medicine, University Malaya.

OBJECTIVE: The aim of this study was to validate the Malay version of the Multidimensional Scale of Perceived Social Support (MSPSS-M) among a group of medical students in Faculty of Medicine, University Malaya. METHODS: 237 students participated in the study. They were given the Malay version of MSPSS, medical outcome study (MOS) social support survey, Malay version of General Health Questionnaire (GHQ), Malay version of Beck Depression Inventory (BDI) and English version of MSPSS. A week later, these students were again given the Malay version of MSPSS. RESULTS: The instrument displayed good internal consistency (Cronbach's alpha=0.89), parallel form reliability (0.94) and test-retest reliability (0.77) (Spearman's rho, p<0.01). The negative correlation of the total and subscales of the instrument with the Malay version of GHQ and BDI confirmed its validity. Extraction method of the 12 items MSPSS using principle axis factoring with direct oblimin rotation converged into three factors of perceived social support (Family, Friends and Significant Others) with reliability coefficients of 0.88, 0.82 and 0.94, respectively. CONCLUSION: The Malay version of the MSPSS demonstrated good psychometric properties in measuring social support among a group of medical students from Faculty of Medicine, University Malaya and it could be used as a simple instrument on young educated Malaysian adolescents.

Investigation on mechanical properties of contemporary metallic bone plates: towards the development of composite bone plates.

This study aims at investigating the mechanical properties of the contemporary metallic bone plates determining the effect of their length, width and thickness on the properties and compares with the composite bone plates. Three-points bending test was performed over the stainless steel plates of different length, width and thickness. The test results showed that different plates had different mechanical properties. However, the properties are still much higher than that of particular bones intended to be treated. Therefore, the reported findings strongly encourage developing composite bone plates with biocompatible polymers/fibers that would have modulated properties according to the requirements.

A family history study of chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterized by unexplained, disabling fatigue and is associated with high rates of comorbid depression. While the aetiology is unknown, findings from recent twin surveys suggest that genetic factors may be relevant to prolonged fatigue states (> 1 month). To date, however, there has been no exploration of the role of familial/genetic factors in operationally defined CFS. The aims of the present study were: (i) to examine whether CFS is familial by comparing the rates of CFS in the first-degree relatives of CFS cases and medical control subjects; and (ii) to determine whether the high rate of comorbid depression in CFS is reflected in a greater familial loading for affective disorder. Twenty-five CFS cases and 36 medical control subjects were assessed for fatigue symptoms based on the Centre for Disease Control (CDC) criteria for CFS, and for lifetime psychiatric symptoms using the Schedule for Schizophrenia and Affective Disorders-Lifetime Version. Informant family history was obtained regarding first-degree relatives using the CDC criteria and the Family History Research Diagnostic Criteria. In addition, informant history was supplemented by sending a questionnaire to first-degree relatives. There were significantly higher rates of CFS in the relatives of CFS cases compared with the relatives of control subjects. The rate of depression in the CFS cases was similar to previous studies but did not appear to reflect a greater familial loading for depression when compared with control subjects. However, these analyses were complicated by higher than expected rates of depression in the control group. These findings suggest that familial factors are important in the aetiology of chronic fatigue syndrome.

Neonatal meningitis and septicaemia caused by Burkholderia pseudomallei.

We report a case of meningitis and one of fatal septicaemia in neonates due to Burkholderia pseudomallei and review the literature on neonatal melioidosis. Pneumonia was the primary presentation and was complicated by shock in the latter case. The epidemiological findings suggest that the cases reported from Malaysia were community-acquired in contrast with those from the USA and Thailand.

Autosomal dominant thrombocytopenia with microthrombocytes: a family study.

A family demonstrating autosomal dominant thrombocytopenia is described. A 28-year-old Malay housewife was found to have a platelet count of 40 x 10(9)/l with a low mean platelet volume (6.8 fl) while being investigated prior to ovarian cystectomy. The bone marrow was consistent with immune thrombocytopenia but she failed to respond to appropriate therapy. Five siblings, one parent and one nephew have easy bruising and platelet counts of 39-82 x 10(9)/l. Platelet aggregation studies excluded a major functional defect. Survival of homologous platelets in the circulation was normal. Familial thrombocytopenias are rare but important to differentiate from the common acquired thrombocytopenias in order to spare the patient unnecessary treatments.

Puerperal acquired factor VIII inhibitor causing a von Willebrand-like syndrome in a patient with anti-DNA antibodies.

A 30-year-old Malay lady, with no previous or family history of bleeding, presented with severe gum bleeding 25 days post-partum. The factor VIII:c was 0.03 iu/ml with evidence of a slow-acting factor VIII inhibitor. Von Willebrand factor antigen (VWF:age) varied from less that 0.05 to 0.17 iu/ml, and there was absent ristocetin-induced platelet aggregation. Anti-nuclear and anti-DNA antibodies were present, but there were no other features of systemic lupus erythematosus. There was some clinical response to cryoprecipitate and tranexamic acid, and slight improvement with corticosteroid. Fifteen months later, the patient has no active bleeding problem, and her VWF-ag is increasing spontaneously. However, factor VIII:c is less than 0.01 iu/ml and her factor VIII inhibitor titre is still > 20 Bethesda units/ml.

Oral disopyramide for the prevention of arrhythmias in patients with acute myocardial infarction admitted to open wards.

Patients with acute myocardial infarction admitted to open wards of three hospitals were given either oral disopyramide (100 mg four times daily) or matching placebo, prophylactically, for seven days. The drug was associated with a significant reduction in mortality (p = 0-0025) and in incidence of extension of infarction (p = 0-01), ventricular fibrillation (p = 0-05), and ventricular tachycardia (p = 0-01). Disopyramide was not associated with any particular complication or side-effect. Unitl information is available to the contrary, oral disopyramide should be given for the first seven days after myocardial infarction to all patients not managed in an intensive-care unit.