Displaying publications 61 - 80 of 607 in total

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  1. Teoh WY, Sim KS, Moses Richardson JS, Abdul Wahab N, Hoe SZ
    PMID: 24369485 DOI: 10.1155/2013/958407
    Gynura bicolor (Compositae) which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water) of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116), one human breast adenocarcinoma cell line (MCF7), and one human normal colon cell line (CCD-18Co) were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay), possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor.
    Matched MeSH terms: Cell Death
  2. Teoh SK, Wong WP
    Med J Malaysia, 1977 Sep;32(1):90-5.
    PMID: 609353
    Matched MeSH terms: Fetal Death
  3. Teh SS, Ee GC, Mah SH, Lim YM, Ahmad Z
    Molecules, 2013 Feb 04;18(2):1985-94.
    PMID: 23381024 DOI: 10.3390/molecules18021985
    The cytotoxic structure-activity relationships among a series of xanthone derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora were studied. Eleven xanthone derivatives identified as mesuarianone (1), mesuasinone (2), mesuaferrin A (3), mesuaferrin B (4), mesuaferrin C (5), 6-deoxyjacareubin (6), caloxanthone C (7), macluraxanthone (8), 1,5-dihydroxyxanthone (9), tovopyrifolin C (10) and α-mangostin (11) were isolated from the three Mesua species. The human cancer cell lines tested were Raji, SNU-1, K562, LS-174T, SK-MEL-28, IMR-32, HeLa, Hep G2 and NCI-H23. Mesuaferrin A (3), macluraxanthone (8) and α-mangostin (11) showed strong cytotoxicities as they possess significant inhibitory effects against all the cell lines. The structure-activity relationship (SAR) study revealed that the diprenyl, dipyrano and prenylated pyrano substituent groups of the xanthone derivatives contributed towards the cytotoxicities.
    Matched MeSH terms: Cell Death/drug effects
  4. Teh CL, Ling GR
    Lupus, 2013 Jan;22(1):106-11.
    PMID: 23112253 DOI: 10.1177/0961203312465780
    Systemic lupus erythematosus (SLE) is a serious autoimmune disease that can be life threatening and fatal if left untreated. Causes and prognostic indicators of death in SLE have been well studied in developed countries but lacking in developing countries. We aimed to investigate the causes of mortality in hospitalized patients with SLE and determine the prognostic indicators of mortality during hospitalization in our center. All SLE patients who were admitted to Sarawak General Hospital from January 1, 2006 to December 31, 2010, were followed up in a prospective study using a standard protocol. Demographic data, clinical features, disease activities and damage indices were collected. Logistic regression and Cox regression analysis were used to determine the prognostic indicators of mortality in our patients. There were a total of 251 patients in our study, with the female to male ratio 10 to 1. Our study patients were of multiethnic origins. They had a mean age of 30.5 ± 12.2 years and a mean duration of illness of 36.5 ± 51.6 months. The main involvements were hematologic (73.3%), renal (70.9%) and mucocutaneous (67.3%). There were 26 deaths (10.4%), with the main causes being: infection and flare (50%), infection alone (19%), flare alone (19%) and others (12%). Independent predictors of mortality in our cohort of SLE patients were the presence of both infection and flare of disease (hazard ratio (HR) 5.56) and high damage indices at the time of admission (HR 1.91). Infection and flare were the main causes of death in hospitalized Asian patients with SLE. The presence of infection with flare and high damage indices at the time of admission were independent prognostic indicators of mortality.
    Matched MeSH terms: Cause of Death
  5. Teh CL, Chan GYL, Lee J
    Int J Rheum Dis, 2008;11(1):24-29.
    DOI: 10.1111/j.1756-185X.2008.00325.x
    Objective: There are limited data on hospitalization of systemic lupus erythematosus (SLE) patients in Asian countries. Our aim of this study is to describe the characteristics and poor prognostic factors in our patients. Method: We performed a retrospective study of SLE hospitalization during a 1-year period (2006) in our centre. Results: There were 125 episodes of hospitalization of 79 patients with SLE. This is the first report of SLE patients from the native population of east Malaysia. The cause of admission was flare of SLE (80.8%), infection (23.2%), renal biopsy (22.4%) and others (4%). There was only one admission for thromboembolism. Patients with both flare of SLE and infection have the longest median length of stay of 11 days (IQR 5,24) requiring more intensive care therapy (P < 0.01). Readmission occurred in 31.4% and was associated with admission for other reasons during the first admission. Flare of SLE was protective against readmission (P < 0.05, OR = 0.36). There were six deaths (4.8% of admissions). The deaths were due to infection in three patients, active SLE in two and acute myocardial infarction in one. The deaths have a higher cumulative prednisolone dose than the survivals (P < 0.01). In multivariate modelling, the only predictor of death was high Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score (P < 0.05, OR = 9.61 per increase of 1 score). Conclusion: Active disease and infection remains the main cause of admission, readmission and death in SLE patients. © 2008 Asia Pacific League of Associations for Rheumatology.
    Matched MeSH terms: Death
  6. Tawfiq Zyoud TY, Abdul Rashid SN, Suppiah S, Abdul Rahim E, Mahmud R
    Med J Malaysia, 2020 07;75(4):411-418.
    PMID: 32724006
    INTRODUCTION: Autopsy is one of the most important approaches to identify clearly the exact cause of death, whether it was due to natural causes, sudden death, or traumatic. Various studies have been done in different countries regarding ways to improve the diagnosis during autopsy. The imaging approach is one of the methods that has been used to complement autopsy findings and to enhance the diagnosis for achieving the most accurate post-mortem diagnosis. The aim of this study is to identify the role of imaging modalities that complement routine autopsy and correlate the findings of diagnostic imaging that can help improve the accuracy of diagnosing the cause of death.

    METHODS: We sourced articles from Scopus, Ovid and PubMed databases for journal publications related to post-mortem diagnostic imaging. We highlight the most relevant full articles in English that explain the type of modality that was utilised and the added value it provided for diagnosing the cause of death.

    RESULTS: Minimally invasive autopsies assisted by imaging modalities added a great benefit to forensic medicine, and supported conventional autopsy. In particular the role of post mortem computed tomography (PMCT), post mortem computed tomography angiography (PMMR) and positron emission tomography computed tomography (PMCTA) that have incremental benefits in diagnosing traumatic death, fractures, tissue injuries, as well as the assessment of body height or weight for corpse identification.

    CONCLUSION: PMCT and PMMR, with particular emphasis on PMCTA, can provide higher accuracy than the other modalities. They can be regarded as indispensable methods that should be applied to the routine autopsy protocol, thus improving the findings and accuracy of diagnosing the cause of death.

    Matched MeSH terms: Cause of Death*
  7. Taufiq Hidayat, Zahoor Iqbal, Ariffin Nasir, Norsarwany Mohamad, Fahisham Taib
    MyJurnal
    Food is considered as a social responsibility of caregivers to their children. It has cultural connotation for all races notwithstanding their background and religious belief; that social responsibility should not be separated even in terminally ill patients. We recorded a case scenario of a terminally ill child who faced difficult end of life with inability to take oral fluids or food due to mechanical obstruction of duodenum by the pelvic rhabdomyosarcoma. From cultural context, the physical act of giving food and fluids to a sick person is considered “a display of one’s affection”. It is understandable that, once the dying phase has reached, and the body starts to shut down, administering fluids may not be useful despite it is deemed necessary from cultural point of view. This case illustrates an ethical dilemma in managing a child with end stage metastatic disease with multiple systemic complications, compounded with futility of medical care and complex social circumstances. It is quite challenging for physicians and relatives to provide good end of life care to patients in palliative care setting. Ensuring good quality of care, quality of life and quality of death are paramount to avoid suffering and distress among the patients and family members.
    Matched MeSH terms: Death
  8. Tang SP, Lim SC, Arkachaisri T
    J Clin Med, 2021 Feb 03;10(4).
    PMID: 33546120 DOI: 10.3390/jcm10040559
    Childhood onset systemic lupus erythematosus is a rare disease that is more common amongst Southeast Asian children compared to the West. It is typified by a peripubertal onset and a female preponderance, which increases with advancing age. Organs commonly involved at diagnosis include haematological, renal, and mucocutaneous. Fever, malar rash, and cutaneous vasculitis are common. Lupus nephritis is typically proliferative especially Class IV and contributes to both disease activity and damage. Antinuclear antibody and anti-dsDNA positivity are both prevalent in this region. Disease activity is higher than Western cohorts at onset but responds to therapy reducing to low disease activity by six months. However, organ damage occurs early and continues to accumulate over the time, a consequence of both active disease (neurological and renal systems) and steroid-related complications especially in the eye (cataract and glaucoma) and musculoskeletal systems (avascular necrosis). Infections remain the leading cause of death and mortality in this region is highly variable contributed by the heterogeneity in social economic status, healthcare access, and availability of paediatric rheumatology expertise in the region.
    Matched MeSH terms: Cause of Death
  9. Tanaka KI, Shimoda M, Chuang VTG, Nishida K, Kawahara M, Ishida T, et al.
    Int J Pharm, 2018 Jan 15;535(1-2):140-147.
    PMID: 29122608 DOI: 10.1016/j.ijpharm.2017.11.012
    Zinc (Zn) is a co-factor for a vast number of enzymes, and functions as a regulator for immune mechanism and protein synthesis. However, excessive Zn release induced in pathological situations such as stroke or transient global ischemia is toxic. Previously, we demonstrated that the interaction of Zn and copper (Cu) is involved in the pathogenesis of Alzheimer's disease and vascular dementia. Furthermore, oxidative stress has been shown to play a significant role in the pathogenesis of various metal ions induced neuronal death. Thioredoxin-Albumin fusion (HSA-Trx) is a derivative of thioredoxin (Trx), an antioxidative protein, with improved plasma retention and stability of Trx. In this study, we examined the effect of HSA-Trx on Cu2+/Zn2+-induced neurotoxicity. Firstly, HSA-Trx was found to clearly suppress Cu2+/Zn2+-induced neuronal cell death in mouse hypothalamic neuronal cells (GT1-7 cells). Moreover, HSA-Trx markedly suppressed Cu2+/Zn2+-induced ROS production and the expression of oxidative stress related genes, such as heme oxygenase-1. In contrast, HSA-Trx did not affect the intracellular levels of both Cu2+ and Zn2+ after Cu2+/Zn2+ treatment. Finally, HSA-Trx was found to significantly suppress endoplasmic reticulum (ER) stress response induced by Cu2+/Zn2+ treatment in a dose dependent manner. These results suggest that HSA-Trx counteracted Cu2+/Zn2+-induced neurotoxicity by suppressing the production of ROS via interfering the related gene expressions, in addition to the highly possible radical scavenging activity of the fusion protein. Based on these findings, HSA-Trx has great potential as a promising therapeutic agent for the treatment of refractory neurological diseases.
    Matched MeSH terms: Cell Death
  10. Tan, Toong Seng, Yap, Wei Boon, Sharifah Syed Hassan
    MyJurnal
    The occasional influenza pandemics and the seasonal influenza epidemics have destroyed millions of lives since
    the last century. It is therefore necessary to understand the virus replication patterns as this provides essential
    information on the virus infectivity, pathogenicity and spread patterns. This study aimed to investigate the replication
    of avian influenza A virus H5N1 (A/Chicken/Malaysia/5858/2004) in MDCK cells. In this study, the TCID50 (50% tissue
    culture infectious dose) of AIV H5N1 was first determined. The MDCK cells were then infected with AIV H5N1 at TCID50
    for 0-48 h. The CPE (cytopathic effect) was observed and cell death was determined hourly. The virus-infected cells
    and media were subsequently collected for gene analysis. The results showed that the TCID50 of AIV H5N1 was 10-9
    dilution. The CPE percentage showed a strong and positive correlation with the infection period (r = 1.0, n = 9, p <
    0.01). The amount of a highly conserved influenza viral gene, M2 gene amplified from infected media (r = 0.471, n =
    9, p= > 0.05) and infected cell (r = 0.73, n = 9, p < 0.05) were also positively correlated with the infection period. In
    conclusion, although CPE started to be observed in the early time points of infection, however, the M2 gene was only
    amplified from the infected media and cells after 48 h and 24 h, respectively. This signifies that AIV H5N1 used in this
    study is pathogenic and it is able to cause severe cytopathology to host cells even at low virus load.
    Matched MeSH terms: Cell Death
  11. Tan YY, Yap PK, Xin Lim GL, Mehta M, Chan Y, Ng SW, et al.
    Chem Biol Interact, 2020 Sep 25;329:109221.
    PMID: 32768398 DOI: 10.1016/j.cbi.2020.109221
    Cancer continues to be one of the most challenging diseases to be treated and is one of the leading causes of deaths around the globe. Cancers account for 13% of all deaths each year, with cancer-related mortality expected to rise to 13.1 million by the year 2030. Although, we now have a large library of chemotherapeutic agents, the problem of non-selectivity remains the biggest drawback, as these substances are toxic not only to cancerous cells, but also to other healthy cells in the body. The limitations with chemotherapy and radiation have led to the discovery and development of novel strategies for safe and effective treatment strategies to manage the menace of cancer. Researchers have long justified and have shed light on the emergence of nanotechnology as a potential area for cancer therapy and diagnostics, whereby, nanomaterials are used primarily as nanocarriers or as delivery agents for anticancer drugs due to their tumor targeting properties. Furthermore, nanocarriers loaded with chemotherapeutic agents also overcome biological barriers such as renal and hepatic clearances, thus improving therapeutic efficacy with lowered morbidity. Theranostics, which is the combination of rationally designed nanomaterials with cancer-targeting moieties, along with protective polymers and imaging agents has become one of the core keywords in cancer research. In this review, we have highlighted the potential of various nanomaterials for their application in cancer therapy and imaging, including their current state and clinical prospects. Theranostics has successfully paved a path to a new era of drug design and development, in which nanomaterials and imaging contribute to a large variety of cancer therapies and provide a promising future in the effective management of various cancers. However, in order to meet the therapeutic needs, theranostic nanomaterials must be designed in such a way, that take into account the pharmacokinetic and pharmacodynamics properties of the drug for the development of effective carcinogenic therapy.
    Matched MeSH terms: Cause of Death
  12. Tan XW, Bhave M, Fong AY, Matsuura E, Kobayashi K, Shen LH, et al.
    Oxid Med Cell Longev, 2016;2016:6943053.
    PMID: 27239253 DOI: 10.1155/2016/6943053
    This study was aimed at preliminarily assessing the cytoprotective and antioxidative effects of rice bran extracts (RBEs) from a Sarawak local rice variety (local name: "BJLN") and a commercial rice variety, "MR219," on oxidative stress in rat H9c2(2-1) cardiomyocytes. The cardiomyocytes were incubated with different concentrations of RBE and hydrogen peroxide (H2O2), respectively, to identify their respective IC50 values and safe dose ranges. Two nonlethal and close-to-IC50 doses of RBE were selected to evaluate their respective effects on H2O2 induced oxidative stress in cardiomyocytes. Both RBEs showed dose-dependent cytotoxicity effects on cardiomyocytes. H2O2 induction of cardiomyocytes pretreated with RBE further revealed the dose-dependent cytoprotective and antioxidative effects of RBE via an increase in IC50 values of H2O2. Preliminary analyses of induction effects of RBE and H2O2 on cellular antioxidant enzyme, catalase (CAT), also revealed their potential in regulating these activities and expression profile of related gene on oxidative stress in cardiomyocytes. Pretreated cardiomyocytes significantly upregulated the enzymatic activity and expression level of CAT under the exposure of H2O2 induced oxidative stress. This preliminary study has demonstrated the potential antioxidant effects of RBE in alleviating H2O2-mediated oxidative injuries via upregulation in enzymatic activities and expression levels of CAT.
    Matched MeSH terms: Cell Death/drug effects
  13. Tan WN, Lim JQ, Afiqah F, Nik Mohamed Kamal NNS, Abdul Aziz FA, Tong WY, et al.
    Nat Prod Res, 2018 Apr;32(7):854-858.
    PMID: 28782393 DOI: 10.1080/14786419.2017.1361951
    Garcinia atroviridis Griff. ex T. Anders. is used as a medication agent in folkloric medicine. The present study was to examine the chemical composition of the stem bark and leaf of G. atroviridis as well as their cytotoxic effects against MCF-7 cells. The constituents obtained by hydrodistillation were identified using GC-MS. The stem bark oil (EO-SB) composed mainly the palmitoleic acid (51.9%) and palmitic acid (21.9%), while the leaf oil (EO-L) was dominated by (E)-β-farnesene (58.5%) and β-caryophyllene (16.9%). Treatment of MCF-7 cells using EO-L (100 μg/mL) caused more than 50% cell death while EO-SB did not induce cytotoxic effect. EO-L has stimulated the growth of BEAS-2B normal cells, but not in MCF-7 cancerous cells. The IC50 of EO-L in MCF-7 and BEAS-2B cells were 71 and 95 μg/mL, respectively. A combination treatment of EO-L and tamoxifen induced more cell death than the treatment with drug alone at lower doses.
    Matched MeSH terms: Cell Death
  14. Tan ML, Muhammad TS, Najimudin N, Sulaiman SF
    J Ethnopharmacol, 2005 Jan 15;96(3):375-83.
    PMID: 15619555
    Epipremnum pinnatum (L.) Engl. hexane extract produced a significant growth inhibition against T-47D breast carcinoma cells and analysis of cell death mechanisms indicated that the extract elicited a non-apoptotic programmed cell death. T-47D cells exposed to the extract at EC(50) concentration (72 h) for 24 h failed to demonstrate typical DNA fragmentation associated with apoptosis, as carried out using a modified TUNEL assay. In addition, acute exposure to the extract produced an insignificant regulation of caspase-3 and p53 mRNA expression but increased in the c-myc mRNA expression. Ultrastructural analysis using transmission electron microscope demonstrated distinct vacuolated cells, which strongly indicated a Type II non-apoptotic cell death although the changes in chromatin were also detected. The presence of non-apoptotic programmed cell death was then reconfirmed with annexin-V and propidium iodide staining. These findings suggested that up-regulation of c-myc mRNA expression may have contributed to the growth arrest and Type II non-apoptotic programmed cell death in the Epipremnum pinnatum (L.) Engl. hexane extract-treated T-47D cells.
    Matched MeSH terms: Cell Death/drug effects
  15. Tan LN, Cheung KW, Philip I, Ong S, Kilby MD
    Fetal Diagn Ther, 2019;45(5):285-294.
    PMID: 30554214 DOI: 10.1159/000494616
    BACKGROUND/PURPOSE: We report a case study of jejunal atresia and the results of a systematic literature review of all reported cases of bowel complications occurring after fetoscopic laser ablation (FLA) for the treatment of twin-to-twin transfusion syndrome (TTTS).

    METHODS: A systematic literature review was performed of bowel complications after FLA for TTTS according to PRISMA guidelines.

    RESULTS: There are 11 published cases of small bowel atresia, 5 cases of necrotising enterocolitis (NEC), and 2 cases with foetal bowel perforations. Recipient twins were more likely to be affected by small bowel atresia (7 recipient and 4 donor cases) and NEC (3 recipient and 2 donor twins). Prenatal ultrasonographic abnormalities were demonstrated in 7 out of 9 cases with bowel atresia and in both cases of bowel perforation. The overall survival rate for neonates with bowel complications after FLA is 72%, but is much lower for co-twins at 22%. The survival rates for jejunoileal atresia and NEC are 91 and 40%, respectively.

    CONCLUSIONS: It is uncertain as to whether these bowel anomalies are due to bowel ischaemia associated with TTTS, the treatment with FLA, or a combination of both. Cases with prenatal abdominal ultrasonographic abnormalities after FLA should have close prenatal and postnatal assessment to detect bowel complications.

    Matched MeSH terms: Fetal Death
  16. Tan LJ, Othman MS, Hiu J, Wong KT, Lai SK
    Malays J Pathol, 2021 Apr;43(1):81-85.
    PMID: 33903310
    BACKGROUND: Small bowel volvulus is defined as the torsion of the small intestine, potentially leading to bowel obstruction, gangrene and perforation. It is a rare condition, especially in adults.

    CASE PRESENTATION: A 30-year-old man was retrieved from the jungle with severe weight loss and abdominal symptoms. He succumbed to death despite 22 days of intensive medical treatment. An autopsy revealed a ruptured gangrenous ileal volvulus with peritonitis and subdiaphragmatic abscess. Further laboratory analysis detected systemic Candida tropicalis and intestinal gramnegative bacterial sepsis, systemic Zika virus viremia, leptospirosis complicating rhabdomyolysis and disseminated intravascular coagulopathy, Type I Herpes Simplex virus infection of the tongue and upper gastrointestinal tract. The cause of death was the ruptured ileal volvulus, complicated with upper gastrointestinal bleeding due to Herpes simplex virus esophagitis in a malnourished patient with resolving leptospirosis and underlying Zika virus co-infection.

    CONCLUSION: Rare clinical scenarios of adult-onset intestinal volvulus with concomitant multiple infections precludes clinical diagnosis and early treatment, leading to devastating consequences of clinical outcome. The positive clinical and postmortem correlation is a good learning lesson in many disciplines of medicine and science.

    Matched MeSH terms: Cause of Death
  17. Tan JT, Letchuman Ramanathan G, Choy MP, Leela R, Lim BK
    Med J Malaysia, 2013 Oct;68(5):384-8.
    PMID: 24632866 MyJurnal
    INTRODUCTION: Paraquat is a quaternary nitrogen herbicide which is highly toxic to human. Death is usually from respiratory failure and may occur within days up to a month after exposure. It is easily available and commonly abused to commit suicide.

    METHODOLOGY: This is a retrospective study describing the demographic characteristics, clinical features and outcomes of paraquat poisoning cases admitted to Hospital Taiping from 1st January 2008 to 30th October 2011. Medical records of 79 patients were reviewed.

    RESULT: Majority were of the Indian ethnicity (72.2%) followed by Chinese (13.9%) and Malay (10.1%). Majority was male (73.4%) and between 20 to 29 years old (34.2%). The median age of the patients was 30 years old. The mean length of stay was 6.2 days. Most exposures were intentional (69.6%) and presented to the hospital early at less than 6 hours after exposure (72.2%). Patients with positive urine paraquat result had significantly higher mortality rate compared to patients with negative results (47.4% vs 15.2% respectively). We found that neither hemofiltration nor immunosuppressive therapies help to improve survival.

    CONCLUSION: The non-survivor characteristics of patients with paraquat poisoning are intentional exposure, delay from exposure to hospital admission, urine paraquat positivity and manifestation of respiratory failure. The demographic characteristics, reasons for exposure and mortality rate are similar to previous reports. Urine paraquat may be used to assess severity of the exposure as well as prognosis. Hemofiltration and immunosuppression therapy do not improve patients' survival and paraquat remains a lethal killer.
    Matched MeSH terms: Death
  18. Tan JL, Nordin S, Besari AM
    Malays J Med Sci, 2017 Oct;24(5):119-123.
    PMID: 29386980 MyJurnal DOI: 10.21315/mjms2017.24.5.14
    Introduction: Tuberculosis is the second leading cause of death under the category of infectious diseases, after the human immunodeficiency virus (HIV). Tuberculous meningitis (TBM) constitutes about 5% of all extrapulmonary disease worldwide. This report describes a case of Tuberculous meningitis with rare presentation in a 28-year-old woman, who was treated based on a collection of her social background, clinical findings and Multiplex PCR of tuberculosis.

    Case presentation: A 28-year-old Malay woman with no significant medical history presented to HUSM with one month history of on and off fever, two weeks history of generalised limbs weakness and one week history of dysphagia. She was reported to have experienced visual hallucination and significant weight loss. Her laboratory result is significant for leukocytosis, elevated ESR and hypernatremia. Non-enhanced and contrast CT scan of the brain showed severe bilateral frontal cerebral atrophy. Cerebral spinal fluid (CSF) for multiplex PCR for Mycobacterium tuberculosis complex was positive. She was promptly started on anti-TB regime combined with dexamethasone. Subsequent follow-up showed significant improvement.

    Conclusion: This is a rare clinical manifestation of Tuberculous meningitis that demonstrates the importance of recognising and initiating the treatment early to reduce disabilities and improve clinical outcome.

    Matched MeSH terms: Cause of Death
  19. Tan HY, Yong YK, Shankar EM, Paukovics G, Ellegård R, Larsson M, et al.
    J Immunol, 2016 05 15;196(10):4052-63.
    PMID: 27076678 DOI: 10.4049/jimmunol.1502203
    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) complicates combination antiretroviral therapy (cART) in up to 25% of patients with HIV/TB coinfection. Monocytes and IL-18, a signature cytokine of inflammasome activation, are implicated in TB-IRIS pathogenesis. In this study, we investigated inflammasome activation both pre- and post-cART in TB-IRIS patients. HIV/TB patients exhibited higher proportions of monocytes expressing activated caspase-1 (casp1) pre-cART, compared with HIV patients without TB, and patients who developed TB-IRIS exhibited the greatest increase in casp1 expression. CD64(+) monocytes were a marker of increased casp1 expression. Furthermore, IL-1β, another marker of inflammasome activation, was also elevated during TB-IRIS. TB-IRIS patients also exhibited greater upregulation of NLRP3 and AIM2 inflammasome mRNA, compared with controls. Analysis of plasma mitochondrial DNA levels showed that TB-IRIS patients experienced greater cell death, especially pre-cART. Plasma NO levels were lower both pre- and post-cART in TB-IRIS patients, providing evidence of inadequate inflammasome regulation. Plasma IL-18 levels pre-cART correlated inversely with NO levels but positively with monocyte casp1 expression and mitochondrial DNA levels, and expression of IL-18Rα on CD4(+) T cells and NK cells was higher in TB-IRIS patients, providing evidence that IL-18 is a marker of inflammasome activation. We propose that inflammasome activation in monocytes/macrophages of HIV/TB patients increases with ineffective T cell-dependent activation of monocytes/macrophages, priming them for an excessive inflammatory response after cART is commenced, which is greatest in patients with TB-IRIS.
    Matched MeSH terms: Cell Death
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