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  1. Abdul Jalil D, Raja Sabudin RZA, Tang YL, Masir N
    Malays J Pathol, 2020 Aug;42(2):273-276.
    PMID: 32860381
    INTRODUCTION: Lymphoblastic leukaemia/lymphoma may present as an isolated extramedullary mass, which includes the musculoskeletal region involvement with normal or near-normal blood counts. The tumour may be in the form of B or T-lymphoblastic leukaemia/lymphoma. The clinical features and histological morphology of extramedullary B-lymphoblastic lymphoma (B-LBL) may mimic mature B-cell neoplasms, thus posing a diagnostic challenge. Arriving at the right diagnosis is crucial because these two diseases differ in their prognosis and management. A high index of suspicion is therefore important so as not to miss the correct diagnosis. The diagnosis may be overlooked because the clinical presentation may not be typical of B-LBL or the blood counts do not show any abnormalities. In this report, we highlight one such case where the diagnosis of B-LBL was missed because of its atypical presentation.
  2. Shamsudin S, Yousuf R, Tang YL, Ding CH, Leong CF
    Malays J Pathol, 2020 Apr;42(1):59-64.
    PMID: 32342931
    INTRODUCTION: Fresh frozen plasma (FFP) is a blood component containing functional quantities of all coagulation factors stored at -18°C or below. FFP has to be thawed and transfused as soon as possible to prevent the loss of certain coagulation factor activities and to minimise microbial contamination.

    MATERIALS AND METHODS: Thirty units of FFP kept at -20°C were thawed using a 37°C water bath and immediately sampled for baseline Factor II (FII), Factor VIII (FVIII) and fibrinogen activity levels and sterility testing. Each unit was then divided into two smaller bags (i.e. Bag I and Bag II) and kept at 4°C. At 6 hours and Day 3, representative samples were taken from Bag I for coagulation factor activity assays, while at Day 5 representative samples were taken from Bag II for coagulation factor activity assays and sterility testing.

    RESULTS: FII activities at the four time points were 73.43%, 73.73%, 71% and 69.8%, respectively, while FVIII activities were 177.63%, 144.37%, 80.8% and 70.97%, respectively. Fibrinogen levels at the four time points were 3.24 g/L, 3.24 g/L, 3.21 g/L and 3.20 g/L, respectively. All samples were free from microbial contamination even at Day 5.

    CONCLUSION: The mean reduction in FII and fibrinogen activities on Day 5 was 5% and 1%, respectively. However, FVIII activity declined significantly by approximately 60% at Day 5. Despite these reductions, thawed plasma stored for up to 5 days at 4°C is still suitable for use as the coagulation factor activity levels still exceed the minimum release criteria recommended in quality assurance regulations.

  3. Lee LH, Cheah YK, Nurul Syakima AM, Shiran MS, Tang YL, Lin HP, et al.
    Genet. Mol. Res., 2012;11(2):1627-41.
    PMID: 22782582 DOI: 10.4238/2012.June.15.12
    Fifty-seven proteobacterium species were successfully isolated from soils of Barrientos Island of the Antarctic using 11 different isolation media. Analysis of 16S rDNA sequencing of these isolates showed that they belonged to eight different genera, namely Bradyrhizobium, Sphingomonas, Methylobacterium, Caulobacter, Paracoccus, Ralstonia, Rhizobium, and Staphylococcus. All isolates were studied for capability of producing antimicrobial and antifungal secondary metabolites using high-throughput screening models. Approximately 23 (13/57) and 2% (1/57) of isolates inhibited growth of Candida albicans ATCC 10231(T) and Staphylococcus aureus ATCC 51650(T), respectively. These results indicated that proteobacterium species isolates from Antarctic could serve as potential source of useful bioactive metabolites. Enterobacterial repetitive intergenic consensus (ERIC)-PCR fingerprinting produced nine clusters and 13 single isolates, with a high D value of 0.9248. RAPD fingerprinting produced six clusters and 13 single isolates, with a relatively low D value of 0.7776. ERIC-PCR analysis proved to have better discrimination capability than RAPD analysis and generated better clustering for all proteobacterium species isolates. We conclude that ERIC-PCR is a robust, reliable and rapid molecular typing method for discriminating different genera of proteobacteria.
  4. Tang YL, Yousuf R, Wan Nawawi WM, Rahman IL, Zainal Abidin J, Rechard Nathan VR, et al.
    Malays J Pathol, 2019 Aug;41(2):161-167.
    PMID: 31427551
    INTRODUCTION: Overnight transfusion (OT) is the blood transfusion taking place from 9pm to 8am. During this period, patients are exposed to increased risk of errors. This cross-sectional study aims to determine the incidence and practice of OT in Universiti Kebangsaan Malaysia Medical Centre.

    MATERIALS & METHODS: Data from all OT in June and mid-July 2017 were collected from recipients' cards, transfusion request forms and patient's case files, regarding discipline involved, indications, time intervals from request of blood transfusion to the completion of OT on patients, monitoring of patients and adverse reactions.

    RESULTS: A total of 1285 transfusion cases were identified during the study period. 216 (16.8%) cases were OT while the 1069 (83.2%) cases were non-OT. Surgery discipline has the highest (30.1%) OT. The indications of OT were acute clinical need: 82.9%, less acute clinical need: 13.9% and no clinical need: 3.2%. A huge delay (average: 5 hours 40 minutes) in starting transfusion after grouping and crossmatching (GXM) completion was noted. Besides, 25.9% cases took <4 hours to complete OT; 83.4% cases did not have proper transfusion monitoring and three transfusion reactions were reported.

    DISCUSSION: Although most of the OT cases had appropriate clinical indications, the transfusion can be commenced earlier at day time rather than overnight. Cases without absolute indication should avoid OT. The poor monitoring of patient during OT had posed risks to patients' life if an adverse transfusion reaction happened. The major reason for OTs was a huge delay in starting transfusion after the GXM completion. The contravention of 4-hour infusion rule increased the patients' risk of developing bacterial sepsis. The practice of OT should be discouraged wherever possible except for clinically indicated cases.

  5. Liau LL, Hassan MNFB, Tang YL, Ng MH, Law JX
    Int J Mol Sci, 2021 Jan 28;22(3).
    PMID: 33525349 DOI: 10.3390/ijms22031269
    Osteoarthritis (OA) is a degenerative joint disease that affects a lot of people worldwide. Current treatment for OA mainly focuses on halting or slowing down the disease progress and to improve the patient's quality of life and functionality. Autologous chondrocyte implantation (ACI) is a new treatment modality with the potential to promote regeneration of worn cartilage. Traditionally, foetal bovine serum (FBS) is used to expand the chondrocytes. However, the use of FBS is not ideal for the expansion of cells mean for clinical applications as it possesses the risk of animal pathogen transmission and animal protein transfer to host. Human platelet lysate (HPL) appears to be a suitable alternative to FBS as it is rich in biological factors that enhance cell proliferation. Thus far, HPL has been found to be superior in promoting chondrocyte proliferation compared to FBS. However, both HPL and FBS cannot prevent chondrocyte dedifferentiation. Discrepant results have been reported for the maintenance of chondrocyte redifferentiation potential by HPL. These differences are likely due to the diversity in the HPL preparation methods. In the future, more studies on HPL need to be performed to develop a standardized technique which is capable of producing HPL that can maintain the chondrocyte redifferentiation potential reproducibly. This review discusses the in vitro expansion of chondrocytes with FBS and HPL, focusing on its capability to promote the proliferation and maintain the chondrogenic characteristics of chondrocytes.
  6. Ding CH, Yusoff H, Muttaqillah NAS, Tang YL, Tan TL, Periyasamy P, et al.
    Malays J Pathol, 2018 Apr;40(1):69-72.
    PMID: 29704387 MyJurnal
    Pneumocystis pneumonia is an important human immunodeficiency virus (HIV)-associated opportunistic infection, and especially so in pregnant HIV-positive patients. We report a case of a 40-year-old woman in her first trimester of pregnancy who initially presented with acute gastroenteritis symptoms but due to a history of high-risk behaviour and the observation of oral thrush, she was worked up for HIV infection. Her retroviral status was positive and her CD4+ T cell count was only 8 cells/µL. She was also worked up for pneumocystis pneumonia due to the presence of mild resting tachypnoea and a notable drop in oxygen saturation (from 100% to 88%) following brief ambulation. Her chest radiograph revealed bilaterally symmetrical lower zone reticular opacities and Giemsa staining of her bronchoalveolar lavage (BAL) was negative for Pneumocystis jirovecii cysts. However, real-time P. jirovecii polymerase chain reaction (PCR) testing on the same BAL specimen revealed the presence of the organism. A course of oral co-trimoxazole plus prednisolone was commenced and her clinical condition improved.
  7. Tang YL, Chia WK, Yap EC, Julia MI, Leong CF, Salwati S, et al.
    Malays J Pathol, 2016 Dec;38(3):315-319.
    PMID: 28028303 MyJurnal
    INTRODUCTION: Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival.

    CASE REPORT: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He achieved a second remission for the next 11 years. During a follow-up later, his full blood picture showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia in less than four months, complicated with severe pneumonia. Despite aggressive treatment with antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis.

    DISCUSSION AND CONCLUSION: Diagnosis of t-MN should be suspected in patients with a history of receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to address the optimal management for patients with t-MN.

  8. Yousuf R, Mustafa AN, Ho SL, Tang YL, Leong CF
    Asian J Transfus Sci, 2017 3 21;11(1):62-64.
    PMID: 28316444 DOI: 10.4103/0973-6247.200770
    The G antigen of Rh blood group system is present in almost all D-positive or C-positive red cells but absent from red cells lacking D and C antigens. The differentiation of anti-D and anti-C from anti-G is not necessary for routine transfusion; however, during pregnancy, it is important because anti-G can masquerade as anti-D and anti-C with initial antibody testing. The false presence of anti-D will exclude the patient from receiving anti-D immunoglobulin (RhIG) when the patient actually is a candidate for RhIG prophylaxis. Moreover, patients with positive anti-D or anti-G are at risk of developing hemolytic disease of the fetus and newborn and need close monitoring. Thus, proper identification allows the clinicians to manage patients properly. This case report highlights a rare case of anti-G together with anti-D and anti-C in a pregnant woman. This report disseminates knowledge on identification of anti-G and its importance in pregnant women.
  9. Mansor NA, Yusof N, Tang YL, Ithnin A, Azma RZ, Tumian NR, et al.
    Malays J Pathol, 2018 Aug;40(2):191-197.
    PMID: 30173238 MyJurnal
    INTRODUCTION: Essential thrombocythaemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterised by persistent thombocytosis. It is an indolent disorder but transformation to myelofibrosis (MF), acute myeloid leukaemia (AML) or myelodyplastic syndrome (MDS) has been reported.

    CASE REPORT: We described a patient with ET whose disease evolved into MDS with fibrosis and complex karyotype after 15 years of stable disease. She was asymptomatic and was on hydroxyurea (HU) treatment until recently when she presented with worsening anaemia. Physical examination showed mild splenomegaly. Full blood picture showed leukoerythroblastic picture with presence of 3% circulating blasts and background of dysplastic features such as hypogranular cytoplasm and nuclear hyposegmentation of neutrophils. The bone marrow aspiration was haemodiluted but revealed presence of 6% blast cells, trilineage dysplasia and predominant erythroid precursors (60%). Trephine biopsy showed no excess of blast cells and normal quantity of erythroid precursors, but there was increased in fibrosis (WHO grade 2) and presence of dysmegakaryopoeisis such as nuclear hypolobation, multinucleation and micromegakaryocytes. Cytogenetic study showed complex karyotype; monosomy of chromosome 2, chromosome 5, chromosome 18 and presence of a marker chromosome (42~44, XX,-2,-5,-18,+mar). Fluorescence in situ hybridisation (FISH) showed 5q deletion (CSF1R and EGR1).

    CONCLUSION: The findings were consistent with transformation of ET to MDS with fibrosis and complex karyotype. ET progression to MDS is considered rare. The presence of complex karyotype and fibrosis in MDS are associated with unfavourable outcome.

  10. Tang YL, Raja Sabudin RZ, Leong CF, Ko CC, Chia WK, Salwati S, et al.
    Malays J Pathol, 2015 Dec;37(3):275-9.
    PMID: 26712675 MyJurnal
    A rare case of double Philadelphia chromosome-positive B Acute lymphoblastic Leukaemia (B-ALL) is reported here. A 60-year-old lady presented with one month history of fever, submandibular lymphadenopathy, loss of appetite and weight loss. Physical examination revealed multiple palpable cervical lymph nodes. Blood film showed leucocytosis with 72% blasts. Bone marrow assessment confirmed a diagnosis of B-ALL with presence of double Philadelphia (Ph) chromosomes. As she was very ill, she was initially treated with an attenuated regimen of induction chemotherapy consisting of rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP) along with intrathecal chemotherapy comprising methotrexate, cytarabine and hydrocortisone. Bone marrow examination post-induction chemotherapy showed >5% blasts. She was subsequently re-induced with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) along with intrathecal chemotherapy, following which she went into complete remission. Consolidation chemotherapy consisting of methotrexate, methylprednisolone, cytarabine, intrathecal chemotherapy and imatinib was subsequently administered followed by maintenance chemotherapy consisting of vincristine, prednisolone and imatinib (IDEAMOP). She developed spontaneous bruises and relapsed four months into her maintenance chemotherapy with 90% blasts in the bone marrow which was treated with fludarabine, cytarabine and granulocyte colony stimulating factor (FLAG). Unfortunately she developed neutropenic sepsis which was complicated by invasive lung aspergillosis. Bone marrow examination post-FLAG showed 80% blasts. Despite aggressive antifungal therapy, her lung infection worsened and she finally succumbed to her illness 13 months after the initial diagnosis. We highlight a rare case of elderly B-ALL with double Ph chromosomes which carries a poor prognosis despite aggressive treatment for the disease and its complications.
  11. Lee LH, Cheah YK, Sidik SM, Xie QY, Tang YL, Lin HP, et al.
    Int J Syst Evol Microbiol, 2013 Jan;63(Pt 1):241-248.
    PMID: 22389286 DOI: 10.1099/ijs.0.038232-0
    Three novel actinobacteria, strains 39(T), 40 and 41, were isolated from soil collected from Barrientos Island in the Antarctic. The taxonomic status of these strains was determined using a polyphasic approach. Comparison of 16S rRNA gene sequences revealed that strain 39(T) represented a novel lineage within the family Dermacoccaceae and was most closely related to members of the genera Demetria (96.9 % 16S rRNA gene sequence similarity), Branchiibius (95.7 %), Dermacoccus (94.4-95.3 %), Calidifontibacter (94.6 %), Luteipulveratus (94.3 %), Yimella (94.2 %) and Kytococcus (93.1 %). Cells were irregular cocci and short rods. The peptidoglycan type was A4α with an L-Lys-L-Ser-D-Asp interpeptide bridge. The cell-wall sugars were galactose and glucose. The major menaquinone was MK-8(H(4)). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphoglycolipid, two glycolipids and one unknown phospholipid. The acyl type of the cell-wall polysaccharide was N-acetyl. The major cellular fatty acids were anteiso-C(17 : 0) (41.97 %), anteiso-C(17 : 1)ω9c (32.16 %) and iso-C(16 : 0) (7.68 %). The DNA G+C content of strain 39(T) was 68.4 mol%. On the basis of phylogenetic and phenotypic differences from other genera of the family Dermacoccaceae, a novel genus and species, Barrientosiimonas humi gen. nov., sp. nov., is proposed; the type strain of the type species is 39(T) (=CGMCC 4.6864(T) = DSM 24617(T)).
  12. Lee LH, Cheah YK, Mohd Sidik S, Ab Mutalib NS, Tang YL, Lin HP, et al.
    World J Microbiol Biotechnol, 2012 May;28(5):2125-37.
    PMID: 22806035 DOI: 10.1007/s11274-012-1018-1
    The present study aimed to isolate actinobacteria from soil samples and characterized them using molecular tools and screened their secondary metabolites for antimicrobial activities. Thirty-nine strains from four different location of Barrientos Island, Antarctica using 12 types of isolation media was isolated. The isolates were preceded to screening of secondary metabolites for antimicrobial and antifungal activities. Using high-throughput screening methods, 38% (15/39) of isolates produced bioactive metabolites. Approximately 18% (7/39), 18% (7/39), 10% (4/39) and 2.5% (1/39) of isolates inhibited growth of Candida albicans ATCC 10231(T), Staphylococcus aurues ATCC 51650(T), methicillin-resistant Staphylococcus aurues (MRSA) ATCC BAA-44(T) and Pseudomonas aeruginosa ATCC 10145(T), respectively. Molecular characterization techniques like 16S rRNA analysis, Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), Random amplified polymorphic DNA (RAPD) and composite analyses were used to characterize the actinobacteria strains. Analysis of 16S rRNA sequences is still one of the most powerful methods to determine higher taxonomic relationships of Actinobacteria. Both RAPD and ERIC-PCR fingerprinting have shown good discriminatory capability but RAPD proved to be better in discriminatory power than ERIC-PCR. Our results demonstrated that composite analysis of both fingerprinting generally increased the discrimination ability and generated best clustering for actinobacteria strains in this study.
  13. de Leon J, Schoretsanitis G, Smith RL, Molden E, Solismaa A, Seppälä N, et al.
    Pharmacopsychiatry, 2021 Dec 15.
    PMID: 34911124 DOI: 10.1055/a-1625-6388
    This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
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