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  1. Ariffin H, Geikowski A, Chin TF, Chau D, Arshad A, Abu Bakar K, et al.
    Med J Malaysia, 2014 Aug;69(4):193-4.
    PMID: 25500851 MyJurnal
    We report a case of Griscelli Syndrome (GS). Our patient initially presented with a diagnosis of haemophagocytic lymphistiocytosis (HLH). Subsequent microscopic analysis of the patient's hair follicle revealed abnormal distribution of melanosomes in the shaft, which is a hallmark for GS. Analysis of RAB27A gene in this patient revealed a homozygous mutation in exon 6, c.550C>T, p.R184X . This nonsense mutation causes premature truncation of the protein resulting in a dysfunctional RAB27A. Recognition of GS allows appropriate institution of therapy namely chemotherapy for HLH and curative haemotopoeitic stem cell transplantation.
  2. Lum SH, Chin TF, Lau KH, Yap TY, Rajagopal R, Ariffin H
    Int J Hematol, 2014 Mar;99(3):215-6.
    PMID: 24470150 DOI: 10.1007/s12185-014-1515-0
  3. Chin TF, Ibrahim K, Thirunavakarasu T, Azanan MS, Oh L, Lum SH, et al.
    Fetal Pediatr Pathol, 2018 Aug;37(4):243-253.
    PMID: 30273079 DOI: 10.1080/15513815.2018.1492054
    BACKGROUND: Survivors of childhood cancer are at risk of developing a second malignancy. One possible mechanism for neoplastic transformation of cells is through induction of persistent genomic instability. This study aims to seek evidence of chromosomal instability in long-term childhood leukemia survivors (CLS) in one of the largest pediatric academic oncology centers in South East Asia.

    METHODS: 50 asymptomatic (subjects have remained leukemia-free since treatment cessation) CLS and 50 healthy controls were recruited in this cross-sectional study. Of 50 CLS, 44 had acute lymphoblastic leukemia and 6 had acute myeloid leukemia. G-banded karyotyping was performed on unstimulated peripheral blood leukocytes of all subjects.

    RESULTS: CLS had significantly higher occurrence of karyotypic abnormalities compared to controls. Five CLS harbored six nonclonal abnormalities (mostly aneuploidy) while none were found in controls.

    CONCLUSION: Subpopulations with nonclonal chromosomal aberrations were present in peripheral blood leukocytes of our cohort of childhood leukemia long-term survivors.

  4. Chiu CK, Chin TF, Chung WH, Chan CYW, Kwan MK
    Spine (Phila Pa 1976), 2024 Jan 01;49(1):64-70.
    PMID: 37146062 DOI: 10.1097/BRS.0000000000004711
    STUDY DESIGN: Retrospective Study.

    OBJECTIVE: This study aims to investigate variation in the number of thoracic and lumbar vertebrae, the prevalence of lumbosacral transitional vertebra (LSTV) and the prevalence of cervical ribs among surgical patients with adolescent idiopathic scoliosis (AIS).

    SUMMARY OF BACKGROUND DATA: Due to variation in the number of thoracic or lumbar vertebrae, inaccurate identification of vertebral levels has been found to be a contributory factor to wrong-level surgery.

    METHODS: This was a retrospective study on AIS patients who underwent posterior spinal fusion. Demographic and anthropometric data (age, gender, height, weight, and body mass index), radiographic data (Lenke curve type, pre-operative Cobb angle, vertebra numbering of cervical, thoracic, and lumbar spine, presence of LSTV based on the Castellvi classification and the presence of cervical ribs) and clinical data were collected. Data were analysed and reported with mean and standard deviation for quantitative parameters and number and percentage for qualitative parameters. Multinomial logistic regression analyses were performed to identify factors associated with the outcomes of interest.

    RESULTS: A total of 998 patients met inclusion criteria, of which 135 (13.5%) were males and 863 (86.5%) were females. The vertebrae number varied between 23 to 25 total vertebrae with 24 vertebrae considered as the typical number of vertebrae. The prevalence of atypical number of vertebrae (23 or 25) was 9.8% (98 patients). We found a total of 7 different variations in number of cervical, thoracic, and lumbar vertebrae (7C11T5L, 7C12T4L, 7C11T6L, 7C12T5L, 7C13T4L, 7C12T6L, and 7C13T5L) with 7C12T5L considered as the typical vertebrae variation. The total prevalence of patients with atypical vertebrae variation was 15.5% (155 patients). Cervical ribs were found in 2 (0.2%) patients while LSTV were found in 250 (25.1%) of patients. The odds of 13 thoracic vertebrae were higher in males (OR 5.17; 95% CI: 1.25, 21.39) and the odds of 6 lumbar vertebrae were higher in LSTV (OR 3.93; 95% CI: 2.58, 6.00).

    CONCLUSION: In this series, we identified a total of 7 different variations in the number of cervical, thoracic, and lumbar vertebrae. The total prevalence of patients with atypical vertebrae variation was 15.5%. LSTV was found in 25.1% of the cohort. It is important to ascertain atypical vertebrae variations rather than the absolute number of vertebrae because variants such as 7C11T6L and 7C13T4L may still have typical numbers of vertebrae in total. However, due to the differences in the number of morphologically thoracic and lumbar vetrebrae, there may still be a risk of inaccurate identification.

  5. Azanan MS, Chandrasekaran S, Rosli ES, Chua LL, Oh L, Chin TF, et al.
    J Pediatr Hematol Oncol, 2020 08;42(6):e394-e400.
    PMID: 32118813 DOI: 10.1097/MPH.0000000000001766
    BACKGROUND: Microvascular endothelial dysfunction is central to the pathogenesis of cardiovascular disease (CVD). The eye offers direct access for endothelial health assessment via the retinal microvasculature. The aim of the study was to investigate whether image-based retinal vessel analysis is a feasible method of assessing endothelial health in survivors of childhood acute lymphoblastic leukemia (cALL).

    MATERIALS AND METHODS: Cardiovascular risk factors (CRFs) were estimated using the 30-year Framingham Risk Score in 73 childhood leukemia survivors (median age: 25; median years from diagnosis: 19) and 78 healthy controls (median age: 23). Radial arterial stiffness was measured using pulse wave analyzer, while endothelial activation markers were measured by soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1). Retinal fundus images were analyzed for central retinal artery/vein equivalents (CRAE/CRVE) and arteriolar-venular ratio (AVR).

    RESULTS: cALL survivors had higher CRF (P<0.0001), arterial stiffness (P=0.001), and sVCAM-1 (P=0.007) compared with controls. Survivors also had significantly higher CRVE (P=0.021) while AVR was significantly lower (P=0.026) in survivors compared with controls, compatible with endothelial dysfunction. In cALL survivors with intermediate risk for CVD, CRAE, and AVR are significantly lower, while sVCAM-1 and sICAM-1 are significantly higher when compared with survivors with low CVD risk after adjusting with covariates (age, sex, and smoking status).

    CONCLUSIONS: cALL survivors have an increased risk of CVD compared with age-matched peers. The survivors demonstrated microvasculopathy, as measured by retinal vascular analysis, in addition to physical and biochemical evidence of endothelial dysfunction. These changes predate other measures of CVD. Retinal vessel analysis may be utilized as a robust screening tool for identifying survivors at increased risk for developing CVD.

  6. Ariffin H, Azanan MS, Abd Ghafar SS, Oh L, Lau KH, Thirunavakarasu T, et al.
    Cancer, 2017 Nov 01;123(21):4207-4214.
    PMID: 28654149 DOI: 10.1002/cncr.30857
    BACKGROUND: Large epidemiologic studies have reported the premature onset of age-related conditions, such as ischemic heart disease and diabetes mellitus, in childhood cancer survivors, decades earlier than in their peers. The authors investigated whether young adult survivors of childhood acute lymphoblastic leukemia (ALL) have a biologic phenotype of cellular ageing and chronic inflammation.

    METHODS: Plasma inflammatory cytokines were measured using a cytometric bead array in 87 asymptomatic young adult survivors of childhood ALL (median age, 25 years; age range, 18-35 years) who attended annual follow-up clinic and compared with healthy, age-matched and sex-matched controls. Leukocyte telomere length (LTL) was measured using Southern blot analysis.

    RESULTS: Survivors had significant elevation of plasma interleukin-2 (IL-2), IL-10, IL-17a, and high-sensitivity C-reactive protein levels (all P 0.8 mg/dL) was related to increased odds of having metabolic syndrome (odds ratio, 7.256; 95% confidence interval, 1.501-35.074). Survivors also had significantly shorter LTL compared with controls (median, 9866 vs 10,392 base pairs; P = .021). Compared with published data, LTL in survivors was similar to that in healthy individuals aged 20 years older. Survivors who received cranial irradiation had shorter LTL compared with those who had not (P = .013).

    CONCLUSIONS: Asymptomatic young adult survivors of childhood ALL demonstrate a biologic profile of chronic inflammation and telomere attrition, consistent with an early onset of cellular processes that drive accelerated aging. These processes may explain the premature development of age-related chronic conditions in childhood cancer survivors. Understanding their molecular basis may facilitate targeted interventions to disrupt the accelerated aging process and its long-term impact on overall health. Cancer 2017;123:4207-4214. © 2017 American Cancer Society.

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