Temporal dynamics of visual working memory.

The involvement of the human cerebellum in working memory has been well established in the last decade. However, the cerebro-cerebellar network for visual working memory is not as well defined. Our previous fMRI study showed superior and inferior cerebellar activations during a block design visual working memory task, but specific cerebellar contributions to cognitive processes in encoding, maintenance and retrieval have not yet been established. The current study examined cerebellar contributions to each of the components of visual working memory and presence of cerebellar hemispheric laterality was investigated. 40 young adults performed a Sternberg visual working memory task during fMRI scanning using a parametric paradigm. The contrast between high and low memory load during each phase was examined. We found that the most prominent activation was observed in vermal lobule VIIIb and bilateral lobule VI during encoding. Using a quantitative laterality index, we found that left-lateralized activation of lobule VIIIa was present in the encoding phase. In the maintenance phase, there was bilateral lobule VI and right-lateralized lobule VIIb activity. Changes in activation in right lobule VIIIa were present during the retrieval phase. The current results provide evidence that superior and inferior cerebellum contributes to visual working memory, with a tendency for left-lateralized activations in the inferior cerebellum during encoding and right-lateralized lobule VIIb activations during maintenance. The results of the study are in agreement with Baddeley's multi-component working memory model, but also suggest that stored visual representations are additionally supported by maintenance mechanisms that may employ verbal coding.

Glycogen synthase kinase-3 controls IL-10 expression in CD4(+) effector T-cell subsets through epigenetic modification of the IL-10 promoter.

The serine/threonine kinase glycogen synthase kinase-3 (GSK3) plays an important role in balancing pro- and anti-inflammatory cytokines. We have examined the role of GSK3 in production of IL-10 by subsets of CD4(+) T helper cells. Treatment of naive murine CD4(+) T cells with GSK3 inhibitors did not affect their production of IL-10. However, treatment of Th1 and Th2 cells with GSK3 inhibitors dramatically increased production of IL-10. GSK3 inhibition also led to upregulation of IL-10 among Th1, Th2, and Th17 subsets isolated from human blood. The encephalitogenic potential of GSK3 inhibitor treated murine Th1 cells was significantly reduced in adoptive transfer experiments by an IL-10-dependent mechanism. Analysis of the murine IL-10 promoter in response to inhibition of GSK3 in Th1 cells showed modification to a transcriptionally active state indicated by changes in histone H3 acetylation and methylation. Additionally, GSK3 inhibition increased expression of the transcription factors c-Maf, Nfil3, and GATA3, correlating with the increase in IL-10. These findings are important in the context of autoimmune disease since they show that it is possible to reprogram disease-causing cells through GSK3 inhibition.

Monitoring treatment response in sputum smear positive pulmonary tuberculosis patients: comparison of weight gain, sputum conversion and chest radiograph.

BACKGROUND: 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. METHODS: This was a retrospective study of confirmed positive sputum AFB smear patients from January 1999 to December 2004 who attended the Chest Clinic at Hospital Tengku Ampuan Afzan, Kuantan, Malaysia. Data on weight, chest radiograph and sputum AFB smear from initiation of therapy to end of treatment and follow-up were collected and analyzed. RESULTS: 201 patients were included. At week-4 of anti-tuberculous treatment, only 14.7% had positive sputum smear. At completion of therapy 93.1% had improved chest radiographs. 90% had weight gain, 5% had weight loss and the remaining had no change in weight. Amongst patients with weight loss, there were no significant differences in the underlying illnesses (p=0.376), sputum smear at 4 weeks (p=0.697) and chest X-ray changes (p=0.731). Three patients who initially showed sputum smear conversion had reappearance of positive smear results towards the end of treatment. One of them was diagnosed as treatment failure while the other two remained well after discontinuation of therapy. CONCLUSION: Weight gain is very common among smear-positive tuberculosis patients after treatment even though weight gain does not correlate well with underlying disease, sputum conversion and chest X-ray changes. Reappearance of smear-positive sputum must be interpreted with caution and not to be regarded as treatment failure without other evidence.

Regulation of adaptive immunity; the role of interleukin-10.

Since the discovery of interleukin-10 (IL-10) in the 1980s, a large body of work has led to its recognition as a pleiotropic immunomodulatory cytokine that affects both the innate and adaptive immune systems. IL-10 is produced by a wide range of cell types, but for the purposes of this review we shall focus on IL-10 secreted by CD4(+) T cells. Here we describe the importance of IL-10 as a mediator of suppression used by both FoxP3(+) and FoxP3(-) T regulatory cells. Moreover, we discuss the molecular events leading to the induction of IL-10 secretion in T helper cell subsets, where it acts as a pivotal negative feedback mechanism. Finally we discuss how a greater understanding of this principle has allowed for the design of more efficient, antigen-specific immunotherapy strategies to exploit this natural phenomenon clinically.

Defaulters among lung cancer patients in a suburban district in a developing country.

INTRODUCTION: This study was carried out to determine the prevalence, patient's characteristic and reasons for defaulting follow-up and treatment among patients with lung cancer. METHODS: Patients with histologically confirmed lung cancer were recruited. Patient's detailed demographic data, occupation, socioeconomic status, and educational level of both the patients and their children were recorded. Defaulters were classified as either intermittent or persistent defaulters. By using Chi-square test, defaulter status was compared with various demographic and disease characteristic factors. The reasons for default were determined. RESULTS: Ninety five patients were recruited. Among them, 81.1% patients were males; 66.3% were Malays. The mean age (SD) was 60 ± 10.5 years. About 46.3% of the patients had Eastern Cooperation Oncology Group (ECOG) functional status 0/1 and 96.8% of the patients presented with advanced stage (Stage 3b or 4). Overall, 20 patients (21.1%) were defaulters (35.0% intermittent defaulters; 65.0% persistent defaulters). Among the intermittent defaulters, 8 patients defaulted once and one patient defaulted 3 times. Among the 20 defaulters, only 2 (10%) patients turned up for the second follow-up appointment after telephone reminder. Two main reasons for default were 'too ill to come' (38.5.5%) and logistic difficulties (23.1%). No correlation was found between patient education, children education, income, ECOG status, stage of the disease, race, and gender with the defaulter rate. CONCLUSION: Defaulter rate among lung cancer patients was 21.1%. Children education level is the only significant factor associated with the defaulter rate.

The bug and the big heart --melioidotic pericardial effusion.

Melioidosis is an infection caused by Gram negative bacterium Burkholderia pseudomallei leading to abscesses in lungs, liver, spleen, musculoskeletal system, prostate and sepsis. We present a rare case of purulent pericardial effusion caused by melioidosis with concomitant pneumonia and splenic abscesses. The patient underwent pericardiocentesis and successfully recovered from cardiogenic and septic shock.

The use of multiplex real-time PCR improves the detection of the bacterial etiology of community acquired pneumonia.

Community-acquired pneumonia (CAP) is still a major cause of morbidity and mortality especially to children and compromised hosts, such as the old and those with underlying chronic diseases. Knowledge of pathogens causing CAP constitutes the basis for selection of antimicrobial treatment. Previous data have shown that etiological agents can be identified in only up to 50% of patients, but this figure can be improved by using polymerase chain reaction (PCR). This study was designed to evaluate multiplex real-time PCR as a method for rapid differential detection of five bacterial causes of CAP (Streptococcus pneumoniae, Burkholderia pseudomallei and atypical bacterial pathogens namely Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila) in CAP patients attending Hospital Tengku Ampuan Afzan (HTAA)/ Kuantan, Pahang, Malaysia. Two previously developed multiplex real-time PCR assays, duplex for the differential detection of S. pneumoniae and B. pseudomallei and triplex for the atypical bacterial pathogens, were used to detect a bacterial cause of CAP in blood and respiratory samples. Thus, 46 blood and 45 respiratory samples collected from 46 adult CAP patients admitted to HTAA were analysed by multiplex real-time PCR assays and conventional methods. The microbial etiology of CAP could be established for 39.1% (18/46) of CAP patients by conventional methods and this was increased to 65.2% (30/46) with the additional use of real-time PCR. The most frequently detected pathogens were S. pneumoniae (21.7% - all by PCR alone), Klebsiella pneumoniae (17.3%), B. pseudomallei (13% - 83% of them positive by PCR alone and 17% by both culture and PCR), Pseudomonas aeruginosa (6.5%), M. pneumoniae (6.5% - all by serology), C. pneumoniae (4.3% - all positive by both PCR and serology), L. pneumophila (2.1% - all by PCR alone), Escherichia coli (4.3%). Haemophilus infuenzae, Acinetobacter lwoffii and Acinetobacter baumannii were detected by conventional methods (2.1% for each).

The use of multiplex real-time PCR improves the detection of the bacterial etiology of community acquired pneumonia

Community-acquired pneumonia (CAP) is still a major cause of morbidity and mortality especially to children and compromised hosts, such as the old and those with underlying chronic diseases. Knowledge of pathogens causing CAP constitutes the basis for selection of antimicrobial treatment. Previous data have shown that etiological agents can be identified in only up to 50% of patients, but this figure can be improved by using polymerase chain reaction (PCR). This study was designed to evaluate multiplex real-time PCR as a method for rapid differential detection of five bacterial causes of CAP (Streptococcus pneumoniae, Burkholderia pseudomallei and atypical bacterial pathogens namely Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila) in CAP patients attending Hospital Tengku Ampuan Afzan (HTAA)/ Kuantan, Pahang, Malaysia. Two previously developed multiplex real-time PCR assays, duplex for the differential detection of S. pneumoniae and B. pseudomallei and triplex for the atypical bacterial pathogens, were used to detect a bacterial cause of CAP in blood and respiratory samples. Thus, 46 blood and 45 respiratory samples collected from 46 adult CAP patients admitted to HTAA were analysed by multiplex real-time PCR assays and conventional methods. The microbial etiology of CAP could be established for 39.1% (18/46) of CAP patients by conventional methods and this was increased to 65.2% (30/46) with the additional use of real-time PCR. The most frequently detected pathogens were S. pneumoniae (21.7% - all by PCR alone), Klebsiella pneumoniae (17.3%), B. pseudomallei (13% - 83% of them positive by PCR alone and 17% by both culture and PCR), Pseudomonas aeruginosa (6.5%), M. pneumoniae (6.5% - all by serology), C. pneumoniae (4.3% - all positive by both PCR and serology), L. pneumophila (2.1% - all by PCR alone), Escherichia coli (4.3%). Haemophilus infuenzae, Acinetobacter lwoffii and Acinetobacter baumannii were detected by conventional methods (2.1% for each).

The introduction, origin and life-history attributes of the non-native cichlid Etroplus suratensis in the coastal waters of Singapore.

Etroplus suratensis, a southern Asian cichlid, has established populations in Singapore. The fish, which was first collected in 1995, was probably introduced via the aquarium trade or through the Johor River in Malaysia. The growth, feeding and reproductive characteristics were found to follow its ecology in its native range in southern Asia, and its establishment in Singapore could be due to the similarity in environment and availability of food. Changes in intestinal length indicated diet shifts from a predominantly herbivorous to an omnivorous one as it matured. Stomach contents did not provide comparable evidence. Diet similarity to two other introduced cichlids may imply that interspecies resource competition exists. Closer monitoring is needed to determine its effects on the local environment.

The man with the boggy head: cranial melioidosis.

Melioidosis is known to cause abscesses in various organs, including the cranium, though less commonly. We present a patient with scalp abscess and subdural empyema that was visible on computed tomography of the brain. The neurosurgical drainage grew Burkholderia pseudomallei. Despite our best effort to treat the patient using parenteral antibiotics and surgical drainage, the patient did not survive.

Pahang melioidosis registry.

Melioidosis has a high annual incidence and mortality rate in Pahang, Malaysia. We initiated the first melioidosis registry in the country on 1st July 2005 to improve the management of melioidosis in the state. Continuous medical education on melioidosis was carried out in all hospitals in the state to highlight the magnitude of the disease and to educate the doctors on the treatment of the disease. All culture confirmed cases were registered and analysed. During the one-year study period from 1st July 2005 till 30th June 2006, a total of 63 patients had positive culture for Burkholderia pseudomallei. The calculated annual incidence of melioidosis in Pahang state was 4.3 per 100,000 population per year (Adult, 6.0 per 100, 000 population per year and paediatric, 1.6 per 100,000 population per year). There were 55 Malays (87.3%), three Chinese (4.8%), four aborigines (6.3%) and one Indonesian. Nine (14.3%) were less than 18 years old. The median age was 49 years (range: 1-68 years). Only one patient (1.6%) had a previous history of confirmed melioidosis. With this programme, we had observed a decline in adult mortality from 54% to 44%, although this was not statistically significant. However, culture-confirmed relapses had dropped from 19% to nil. Several measures need to be taken to decrease mortality from melioidosis in endemic countries.

Melioidotic prostatic abscess in Pahang.

Melioidosis is caused by Burkholderia pseudomallei, a Gram-negative bacillus. Melioidosis can affect many organs, including the prostate. However, prostatic abscess due to melioidosis is uncommon. We describe five cases of melioidosis with prostatic abscess. Four of five patients had diabetes mellitus and had more than one organ involvement. The diagnosis of prostatic abscess in our patients was only made with computed tomography of the abdomen and pelvis. None of our patients underwent surgical drainage and all remained well after treatment with antibiotics, except for one mortality secondary to severe septicaemia.

A mimicry of melioidosis by Klebsiella ozaenae infection.

Klebsiella ozaenae is a Gram negative bacillus. It has been described as a colonizer of oral and nasopharyngeal mucosa and is a cause of atrophic rhinitis. Klebsiella ozaenae has seldom been isolated from serious infections. However, several reports have stated that Klebsiella ozaenae may cause invasive infections and even mortality. We report a 55-year-old man with Klebsiella ozaenae infection causing abscesses involving the right eye and left kidney and possibly also in the brain, lungs and prostate. The isolates were sensitive to ceftazidime, ciprofloxacin, chloramphenicol, gentamicin and sulfamethoxazole-trimethoprim but resistant to ampicillin. He responded well to 4 weeks of i.v. ceftazidime and i.v. amoxycillin-clavulanic acid. To our knowledge, such a multiorgan infection has not been reported previously for this organism.

Transbronchial needle aspiration of mediastinal lymph node.

In Malaysia, transbronchial needle aspiration (TBNA) is a relatively new procedure performed only in a handful of respiratory centres. We reviewed TBNA of mediastinal lymph node performed in Hospital Tengku Ampuan Afzan (HTAA) to determine the yield and its complications. Data was retrieved from endoscopy databases and patients' records, CT thorax images and all cytological and histological slides were reviewed. Twenty-five patients had TBNA performed. TBNA was positive in 15 patients (60%). Overall, 80% had confirmed malignancy after bronchoscopy. Only four patients had documented bleeding after TBNA and in two of them, bleeding stopped spontaneously and another two patients required diluted adrenaline to stop the bleed. No mortality was reported from this procedure. Hence, TBNA is a safe procedure.

The urine bag used in pneumothorax.

Pneumothorax is the presence of air in the pleural cavity. It can be classified into spontaneous, traumatic or iatrogenic. The majority of pneumothorax cases are spontaneous, which can be further classified into primary spontaneous pneumothorax (PSP) or secondary spontaneous pneumothorax (SSP), defined by the absence or presence of obvious underlying lung disease respectively. The treatment of spontaneous pneumothorax includes simple aspiration, intercostal tube drainage or surgical intervention. When intercostal tube drainage is used, it is usually attached to an underwater-seal system. Mobile chest drains, such as the Heimlich valve, replace the underwater-seal and allow outpatient management of spontaneous pneumothoraces. The Heimlich valve however, is costly and not readily available in many local hospitals. Cheaper and easily obtainable alternatives which are also safe are being sought. This is a case report describing the use of the urine bag in the management of a patient with spontaneous pneumothrax.

Transbronchial needle aspiration of mediastinal lymph node.

In Malaysia, transbronchial needle aspiration (TBNA) is a relatively new procedure performed only in a handful of respiratory centres. We reviewed TBNA of mediastinal lymph node performed in Hospital Tengku Ampuan Afzan (HTAA) to determine the yield and its complications. Data was retrieved from endoscopy databases and patients' records, CT thorax images and all cytological and histological slides were reviewed. Twenty-five patients had TBNA performed. TBNA was positive in 15 patients (60%). Overall, 80% had confirmed malignancy after bronchoscopy. Only four patients had documented bleeding after TBNA and in two of them, bleeding stopped spontaneously and another two patients required diluted adrenaline to stop the bleed. No mortality was reported from this procedure. Hence, TBNA is a safe procedure.

An unusual cause of haemoptysis and headache: cryptococcosis.

Pulmonary cryptococcosis can be clinically silent in non-HIV infected patients but can also present as nodules and masses on the chest radiograph, which can be mistaken for tuberculosis or lung cancer. Common symptoms include fever and cough, and uncommonly haemoptysis. This report illustrates a non-HIV infected patient whose main complaint was haemoptysis and headache. He was diagnosed with pulmonary cryptococcosis from biopsy of an endobronchial mass found on flexible bronchoscopy. Disseminated cryptoccoccal infection should be considered as a differential diagnosis in non-HIV infected patients presenting with haemoptysis and headache. Early recognition and administration of appropriate therapy will improve clinical outcome in these patients.

Medical thoracoscopy: Pahang experience.

Medical thoracoscopy has gain its popularity in Malaysia recently. This paper presents our early experience in thoracoscopy using semi-rigid fiberoptic thoracoscope. All thoracoscopy records since October 2006 were retrieved. The patients' records, thoracocentesis investigations results, thoracoscopic findings and all pleural biopsy results were reviewed. Twenty-four thoracoscopic procedures on 22 patients in whom two patients had repeated thoracoscopy. Ten patients were confirmed carcinoma. Eight patients had inconclusive thoracoscopic pleural biopsy results. Three patients underwent pleurodesis for malignant effusion. One patient had adhesiolysis for empyema. There was no procedure-related deaths or intraoperative accidents. Thoracoscopy is a relatively safe procedure.

Glycoprotein D-independent spread of pseudorabies virus infection in cultured peripheral nervous system neurons in a compartmented system.

The molecular mechanisms underlying the directional neuron-to-epithelial cell transport of herpesvirus particles during infection are poorly understood. To study the role of the viral glycoprotein D (gD) in the directional spread of herpes simplex virus (HSV) and pseudorabies virus (PRV) infection, a culture system consisting of sympathetic neurons or epithelial cells in different compartments was employed. We discovered that PRV infection could spread efficiently from neurons to cells and back to neurons in the absence of gD, the viral ligand required for entry of extracellular particles. Unexpectedly, PRV infection can also spread transneuronally via axo-axonal contacts. We show that this form of interaxonal spread between neurons is gD independent and is not mediated by extracellular virions. We also found that unlike PRV gD, HSV-1 gD is required for neuron-to-cell spread of infection. Neither of the host cell gD receptors (HVEM and nectin-1) is required in target primary fibroblasts for neuron-to-cell spread of HSV-1 or PRV infection.

Role of pseudorabies virus Us3 protein kinase during neuronal infection.

The pseudorabies virus (PRV) Us3 gene is conserved among the alphaherpesviruses and encodes a serine/threonine protein kinase that is not required for growth in standard cell lines. In this report, we used a compartmented culture system to investigate the role of PRV Us3 in viral replication in neurons, in spread from neurons to PK15 cells, and in axon-mediated spread of infection. We also examined the role of Us3 in neuroinvasion and virulence in rodents. Us3 null mutants produce about 10-fold less infectious virus from neurons than wild-type virus and have no discernible phenotypes for axonal targeting of viral components in cultured peripheral nervous system neurons. After eye infection in rodents, Us3 null mutants were slightly attenuated for virulence, with a delayed onset of symptoms compared to the wild type or a Us3 null revertant. While initially delayed, the symptoms increased in severity until they approximated those of the wild-type virus. Us3 null mutants were neuroinvasive, spreading in both efferent and afferent circuits innervating eye tissues.