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.

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 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.

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.

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.

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.

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.

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.

An in vitro system to study trans-neuronal spread of pseudorabies virus infection.

The neuronal spread of infection of alpha herpesviruses is controlled by unknown mechanisms. In the natural host, primary infection always leads to invasion of the peripheral nervous system, but rarely results in extensive invasion of the central nervous system. After reactivation of latent infection in the peripheral nervous system, virions are produced and shed from epithelial surfaces, but rarely invade the central nervous system. We have been studying two aspects of the general problem. First, using GFP and mRFP fusion proteins, we have used video confocal microscopy to assess mechanisms that influence spread of pseudorabies (PRV) virion components within axons. Second, and the subject of this report, is the development of a new in vitro cell culture system that enables the study of trans-neuronal spread of infection from neurons to non-neuronal cells similar to what happens after reactivation and spread to epithelial surfaces. We have developed a tissue culture system involving tri-chamber Teflon rings that enables facile analysis of trans-neuronal spread. The system duplicates all the known in vivo correlates of trans-neuronal spread and provides the opportunity to do both quantitative and qualitative assessment of spread of PRV infection from infected neurons to non-neuronal cells.

Evaluation of recommendations for replication-competent retrovirus testing associated with use of retroviral vectors.

With input from the gene therapy community, CBER is actively examining the recommendations for RCR testing during retroviral vector production, production of ex vivo-transduced cells, and in patients who receive such material. Our initial recommendations were made at a time when our experience with RCR detection assays and clinical use of retroviral vectors was limited. As the gene therapy field has matured, there is an increasing amount of data available on RCR detection assays and from monitoring of patients in clinical trials. The cumulative data give assurance that RCR detection assays in use are of sufficient sensitivity to provide a margin of safety to patients: no patients to date have evidence of RCR infection. However, CBER encourages members of the gene therapy community to continue to submit data to the FDA or to publish data that will enhance the cumulative data base on RCR testing assays, experience with different VPC, and patient monitoring. Based on the analysis of data accumulated to data, and ongoing discussions with members of the gene therapy community, CBER is proposing to discuss changes to the current RCR testing recommendations, as summarized below. RCR testing during production of retroviral vector and ex vivo-transduced cells. Development of characterized standards for RCR testing of supernatant and cells should allow comparison of assay sensitivity. One proposal under consideration is to apply statistical methods to determine how much material needs to be tested independent of the size of the production lot. Data and discussion are still needed to define a limit concentration and a value for probability of detection for RCR testing, while maintaining an appropriate margin of safety. These modifications of RCR testing strategies could lead to improvements in assay sensitivity. Additional discussion and data are also needed to evaluate the current recommendations of the testing for ex vivo-transduced cells: should both cells and supernatant be tested in all cases? RCR testing during patient follow-up. The time points required for RCR testing during patient follow-up need examination. One proposal under consideration is to sample and assay at three time points during the first year of treatment (e.g., 4-6 weeks, 3 months, and 1 year post-treatment). Further discussion is needed to define appropriate additional follow-up. Choice of assays to detect surrogate markers for RCR infection (i.e., serologic or PCR-based assays) should consider mode of vector administration and the patient population. Positive results with such assays should be pursued by direct culture assay to obtain and characterize the infectious viral isolate. These proposals will be the focal point for the discussion at the Retroviral Vector Breakout Session at the 1997 FDA/NIH Gene Therapy Conference. After the 1997 FDA/NIH Gene Therapy Conference, CBR plans to propose revised recommendations for RCR testing for public comment.

Pigmented central neurocytoma: case report and literature review.

A case of pigmented central neurocytoma is reported. The tumor showed histologic, immunophenotypic, and ultrastructural features of central neurocytoma. The pigment consisted of an intimate association of lipofuscin and neuromelanin. Pigmented neuroepithelial tumors are rare, and the pigments may be neuromelanin or melanin. Pigmented central neurocytoma has not been described to date. The low proliferation rate of the tumor suggests a delayed turnover of tumor cells as a possible cause of lipofuscin accumulation. Autocatalytic peroxidation of lipofuscin is a possible mechanism of neuromelanin formation.

Encephalopathy and neuropathy following ingestion of a Chinese herbal broth containing podophyllin.

Two patients developed podophyllin intoxication following ingestion of a broth of the Chinese herb guijiu. The neurological manifestations are described and the pathology of the peripheral neuropathy is fully documented with ultrastructural and quantitative studies.

An unusual complication of silastic dural substitute: case report.

A case is presented in which a patient developed an unusual complication after the use of Silastic dural substitute. In 1983, the patient underwent removal of a meningioma with the involved dura. Five years later, he developed around the graft material a very thick connective tissue capsule, which simulated a recurrent meningioma clinically and radiologically.

Sparganosis of the spinal cord. Case report.

Sparganosis of the spinal cord is a rare disease: only two cases have previously been described. A third case of spinal sparganosis is reported in which a sparganum was removed from the central canal of the patient's spinal cord. The clinical presentation and pathology are described. A brief review of the life cycle of the Spirometra is given and the possible mode of infestation is discussed.

Spinal meningioma arising from a lumbar nerve root. Case report.

A case is reported of cauda equina compression from an intradural meningioma arising from the L-5 nerve root in a young man.

An epithelial cyst in the cerebellopontine angle. Case report.

A case of a benign epithelial cyst in the posterior cranial fossa is described. It had the unique histological feature of a double-layered cuboidal epithelial lining. Detailed immunohistochemical and electron microscopic studies supported an endodermal origin. The differential diagnosis and the histogenesis of epithelial cysts in the central nervous system are discussed.