Noninvasive diagnosis of nasopharyngeal carcinoma: nasopharyngeal brushings reveal high Epstein-Barr virus DNA load and carcinoma-specific viral BARF1 mRNA

Nasopharyngeal carcinoma (NPC) is the most prevalent ENT-tumour in Indonesia. We investigated the primary diagnostic value of Epstein-Barr virus (EBV) DNA load and mRNA detection in noninvasive nasopharyngeal (NP) brushings, obtained prospectively from consecutive Indonesian ENT-patients with suspected NPC (N=106) and controls. A subsequent routine NP biopsy was taken for pathological examination and EBER-RISH, yielding 85 confirmed NPC and 21 non-NPC tumour patients. EBV DNA and human DNA load were quantified by real-time PCR. NP brushings from NPC patients contained extremely high EBV DNA loads compared to the 88 non-NPC controls (p<0.0001). Using mean EBV DNA load in controls plus 3 SD as cut-off value, specificity, sensitivity, positive and negative predictive values were 98, 90, 97 and 91%, respectively. Epstein-Barr nuclear antigen 1 (EBNA1) and the carcinoma-specific BARF1 mRNA were detected by nucleic acid sequence based amplification and found in 86 and 74% of NP brushings, confirming NPC tumour cell presence. EBV RNA positivity was even higher in fresh samples stored at -80 degrees C until RNA expression analyses (88% for both EBNA1 and BARF1). EBV RNA-negative NP brushings from proven NPC cases had the lowest EBV DNA loads, indicating erroneous sampling. No EBV mRNA was detected in NP brushings from healthy donors and non-NPC patients. In conclusion, EBV DNA load measurement combined with detection of BARF1 mRNA in simple NP brushings allows noninvasive NPC diagnosis. It reflects carcinoma-specific EBV involvement at the anatomical site of tumour development and reduces the need for invasive biopsies. This procedure may be useful for confirmatory diagnosis in large serological NPC screening programs and has potential as prognostic tool.     

Four dengue virus serotypes found circulating during an outbreak of dengue fever and dengue haemorrhagic fever in Jakarta, Indonesia, during 2004

Periodic outbreaks of dengue have emerged in Indonesia since 1968, with the severity of resulting disease increasing in subsequent years. In early 2004, a purported dengue outbreak erupted across the archipelago, with over 50,000 cases and 603 deaths reported. To confirm the disease aetiology and to provide an epidemiological framework of this epidemic, an investigation was conducted in ten hospitals within the capital city of Jakarta. Clinical and laboratory findings were determined from a cohort of 272 hospitalised patients. Exposure to dengue virus was determined in 180 (66.2%) patients. When clinically assessed, 100 (55.6%) of the 180 patients were classified as having dengue fever (DF), 31 (17.2%) as DF with haemorrhagic manifestations and 49 (27.2%) as dengue haemorrhagic fever (DHF). Evidence from haemagglutination inhibition assays suggested that 33/40 (82.5%) of those with DHF from which laboratory evidence was available suffered from a secondary dengue infection. All four dengue viruses were identified upon viral isolation, with DEN-3 being the most predominant serotype recovered, followed by DEN-4, DEN-2 and DEN-1. In summary, the 2004 outbreak of dengue in Jakarta, Indonesia, was characterised by the circulation of multiple virus serotypes and resulted in a relatively high percentage of a representative population of hospitalised patients developing DHF.     

ERp29 induces breast cancer cell growth arrest and survival through modulation of activation of p38 and upregulation of ER stress protein p58IPK

Endoplasmic reticulum protein 29 (ERp29) is an ER luminal protein that has a role in protein unfolding and secretion, but its role in cancer is unclear. Recently, we reported that overexpression of ERp29 significantly inhibited cell proliferation and prevented tumorigenesis in highly proliferative MDA-MB-231 breast cancer cells. Here, we show that ERp29-induced cancer cell growth arrest is modulated by the interplay between the concomitant phosphorylation of p38 and upregulation of the inhibitor of the interferon-induced, double-stranded RNA-activated protein kinase, p58(IPK). In this cell model, ERp29 overexpression significantly downregulates modulators of cell proliferation, namely urokinase plasminogen activator receptor, β(1)-integrin and epidermal growth factor receptor. Furthermore, ERp29 significantly (P<0.001) increases phosphorylation of p38 (p-p38) and reduces matrix metalloproteinase-9 secretion. The role of ERp29 in upregulating cyclin-dependent kinase inhibitors (p15 and p21) and in downregulating cyclin D(2) is demonstrated in slowly proliferating ERp29-overexpressing MDA-MB-231 cells, whereas the opposite response was observed in ERp29-knockdown MCF-7 cells. Pharmacological inhibition of p-p38 downregulates p15 and p21 and inhibits eIF2α phosphorylation, indicating a role for p-p38 in this process. Furthermore, p58(IPK) expression was increased in ERp29-overexpressing MDA-MB-231 cells and highly decreased in ERp29-knockdown MCF-7 cells. This upregulation of p58(IPK) by ERp29 suppresses the activation of p-p38/p-PERK/p-eIF2α by repressing eIF2α phosphorylation. In fact, reduction of p58(IPK) expression by RNA interference stimulated eIF2α phosphorylation. The repression of eIF2α phosphorylation by p58(IPK) prevents ERp29-transfected cells from undergoing ER-dependent apoptosis driven by the activation of ATF4/CHOP/caspase-3. Hence, the interplay between p38 phosphorylation and p58(IPK) upregulation has key roles in modulating ERp29-induced cell-growth arrest and survival.     

Development of SOVAT: a numerical-spatial decision support system for community health assessment research

INTRODUCTION: The development of numerical-spatial routines is frequently required to solve complex community health problems. Community health assessment (CHA) professionals who use information technology need a complete system that is capable of supporting the development of numerical-spatial routines. BACKGROUND: Currently, there is no decision support system (DSS) that is effectively able to accomplish this task as the majority of public health geospatial information systems (GIS) are based on traditional (relational) database architecture. On-Line Analytical Processing (OLAP) is a multidimensional data warehouse technique that is commonly used as a decision support system in standard industry. OLAP alone is not sufficient for solving numerical-spatial problems that frequently occur in CHA research. Coupling it with GIS technology offers the potential for a very powerful and useful system. METHODOLOGY: A community health OLAP cube was created by integrating health and population data from various sources. OLAP and GIS technologies were then combined to develop the Spatial OLAP Visualization and Analysis Tool (SOVAT). RESULTS: The synergy of numerical and spatial environments within SOVAT is shown through an elaborate and easy-to-use drag and drop and direct manipulation graphical user interface (GUI). Community health problem-solving examples (routines) using SOVAT are shown through a series of screen shots. DISCUSSION: The impact of the difference between SOVAT and existing GIS public health applications can be seen by considering the numerical-spatial problem-solving examples. These examples are facilitated using OLAP-GIS functions. These functions can be mimicked in existing GIS public applications, but their performance and system response would be significantly worse since GIS is based on traditional (relational) backend. CONCLUSION: OLAP-GIS system offer great potential for powerful numerical-spatial decision support in community health analysis. The functionality of an OLAP-GIS system has been shown through a series of example community health numerical-spatial problems. Efforts are now focused on determining its usability during human-computer interaction (HCI). Later work will focus on performing summative evaluations comparing SOVAT to existing decision support tools used during community health assessment research.     

Laryngeal tuberculosis: an important issue

In developing countries like Indonesia, pulmonary tuberculosis still ranks among the major health problems and the prevalence of laryngeal tuberculosis are therefore still high. It is important for physicians and otolaryngologist to recognize the cardinal sign and symptoms of laryngeal tuberculosis in order to make an early diagnosis. An illustration of four cases with laryngeal tuberculosis is reported. All cases presented with hoarseness and diagnosis of laryngeal and pulmonary tuberculosis were made at ENT department.