Displaying publications 1 - 20 of 104 in total

  1. Daud, S.S., Ibrahim, K., Ariffin, H.
    JUMMEC, 2007;10(1):11-16.
    We aimed to establish a method for quantitative analysis of mixed haematopoietic chimerism based on microchip electrophoresis of selected molecular markers following PCR amplification for accurate monitoring of graft status post-transplantation. A 12-year-old girl with relapsed acute lymphoblastic leukaemia who underwent allogeneic bone marrow transplantation had qualitative chimerism analysis using short tandem repeat markers at three time points following the procedure. Her archived DNA samples were then used to test the ability to correlate her clinical course with changes in the quantity of donor chimerism at the different time points. Quantitative chimerism analysis was performed on the Agilent 2100 bioanalyser and donor-recipient ratios were calculated from generated electropherograms. Complete donor chimerism (98%) was demonstrated three weeks post- transplantation. Decreasing amount of donor chimerism to 24% was shown after three months and this concurred with clinical relapse. Following a second transplant, full donor chimerism was reestablished where donor chimerism rose to 100%. High resolution microchip electrophoresis could be useful in predicting the occurrence of increasing recipient chimerism which may herald impending relapse in patients while the disease burden is still low. This investigational approach may provide useful information for clinicians to select appropriate intervention strategies to ensure successful transplantation.
  2. Chong LA, Ariffin H
    Med. J. Malaysia, 2009 Dec;64(4):327-9.
    PMID: 20954562 MyJurnal
    We report on an 11 year-old boy with dyskeratosis congenita who presented with dystrophic nails, dysphagia, hyperpigmentation and oral leukoplakia. He had a brother who died 14 years earlier with similar presenting symptoms and aplastic anaemia. Genetic studies of our patient demonstrated the presence of a DKC1 mutation and confirmed our diagnosis. Further genetic screening revealed that his mother and one of his four sisters are heterozygous for the same mutation.
  3. RamaChandran S, Ariffin H
    Pediatr Blood Cancer, 2009 Sep;53(3):488-90.
    PMID: 19434733 DOI: 10.1002/pbc.22063
    Haemophagocytic lymphohistiocytosis (HLH) is an uncommon disease with a high fatality rate. Etoposide is an important component of current HLH treatment regimes. Two patients with HLH developed etoposide-related secondary acute myeloid leukemia (sAML) following therapy for HLH. Etoposide, an epipodophyllotoxin, is a topoisomerase II inhibitor that interacts with DNA to potentiate leukaemogenesis. The risk of developing sAML is estimated to be between 1% and 5%, 2-20 years after exposure to etoposide but may also be related to cumulative drug doses, treatment schedules, host factors and co-administration of other antineoplastic agents.
  4. Nordin, N. I. A. A., Ariffin, H., Hassan, M.A., Ibrahim, N. A., Shirai, Y., Andou, Y.
    The objective of this study was to evaluate the effects of milling methods on tensile properties of polypropylene (PP) / oil palm mesocarp fibre (OPMF) biocomposites. Two types of mills were used; Wiley mill (WM) and disc mill (DM). Ground OPMF from each milling process was examined for its particle size distribution and aspect ratio by sieve and microscopic analyses, respectively. Results showed that DM-OPMF had smaller diameter fibre with uniform particle size compared to the WM-OPMF. Surface morphology study by SEM showed that DM-OPMF had rougher surface compared to WM-OPMF. Furthermore, it was found that PP/DM-OPMF biocomposite had higher tensile strength compared to PP/WM-OPMF, with almost two-fold. Thus, it is suggested that small diameter and uniform size fibre may improve stress transfer and surface contact between the fibre and polymer matrix and cause well dispersion of filler throughout the polymer resulted in better tensile strength of PP/DM-OPMF Compared to PP/WM-OPMF biocomposite. Overall, it can be concluded that disc milling could serve as a simple and effective grinding method for improving the tensile properties of biocomposite.
  5. Mohamed, M., Ariffin, H., Arasu, A., Tuck Soon, S.H., Abdullah, W.A., Lin, H.P.
    Fusarium species is an emerging genus of fungal pathogens which until recently were rare causes of human disease apart from localized infection of the skin and nails. Two cases of fungaemia due to Fusarium sp. in children are described. The first child, an 8-year old girl with acute myeloid leukaemia developed character-sitic pyoderma gangrenosum-like skin lesions before succumbing to disseminated Fusarium infection and acute respiratory distress syndrome. The second child, a 5-month old boy, developed pneumonia associated with a transient erythematous skin rash while on chemother-apy for congenital leukaemia. Both patients had Fusarium isolated from blood. The second child improved after six weeks of treatment with ampho-tericin B and granulocyte-macrophage colony stimulat-ing factor but ultimately she died of the disease follow-ing discharge. Fusarium spp should be recognised as an opportunistic pathogen in immunocompromised patients. Current literature suggests that liposomal amphotericin B in conjunction with leukocyte growth factors are the treatment of choice in this potentially fatal infection.
  6. Sithasanan N, Chong LA, Ariffin H
    Med. J. Malaysia, 2007 Aug;62(3):247-8.
    PMID: 18246918 MyJurnal
    Phaeohyphomycosis consists of a group of mycotic infections characterized by the presence of dematiaceous (dark walled) septate hyphae. Splenic abscess and spontaneous rupture is an infrequent complication in children with haematological malignancies and can be life threatening. To the best of our knowledge this is the first report of a case of splenic rupture following the development of multiple abscesses secondary to infestation by this rare fungal species.
  7. Chong LA, Josephine P, Ariffin H
    Med. J. Malaysia, 2006 Jun;61(2):236-8.
    PMID: 16898320 MyJurnal
    We report a case of a child with severe congenital neutropenia (Kostmann's syndrome) who was treated with daily prophylactic subcutaneous granulocyte colony-stimulating factor (G-CSF) from the age of eight to sixteen years before being discontinued for poor haematological and clinical response. She did not have a HLA-matched sibling to enable bone marrow transplantation. She subsequently developed acute megakaryoblastic leukemia at the age of 17 years and succumbed during induction chemotherapy. The role of G-CSF in the pathogenesis of her malignant transformation to AML is complicated as this disorder has a propensity for myelodysplasia or AML as part of its natural history.
  8. Ariffin H, Navaratnam P, Lin HP
    Int. J. Clin. Pract., 2002 May;56(4):237-40.
    PMID: 12074201
    We prospectively studied the type, frequency and outcome of infections in 513 patients with 762 consecutive episodes of febrile neutropenia (FN) over a five-year period between 1995 and 1999 in a single paediatric oncology unit. The findings were then compared with a similar study carried out in our unit between 1990 and 1994. The types of bacterial isolates and sensitivity patterns were also studied to identify trends and to gauge the suitability of antibiotics chosen for empirical therapy. Bacteraemia was documented in 35.4% of FN episodes, although 70% of patients did not have an obvious site of sepsis. The majority of isolates (61.9%) were gram-negative bacteria, a consistent finding throughout the study period. Resistance to ceftazidime, amikacin and imipenem among gram-negative bacteria was 26.3%, 21.2% and 0.7%, respectively. Methicillin resistance among gram-positive bacteria was 26.3%, while no vancomycin-resistant bacteria were encountered. There were 36 sepsis-related deaths. Factors associated with a fatal outome were prolonged capillary refill time, hypotension, fever above 39 degrees C and pneumonia. Rapid neutrophil recovery was associated with a good prognosis. A change to our current choice of empirical antibiotics for FN, comprising ceftazidime/ceftriaxone and amikacin appears necessary because of the relatively high resistance rates found.
  9. Ariffin H, Ariffin W, Peng LH, Parasakthi N
    J. Trop. Pediatr., 1997 10;43(5):279-81.
    PMID: 9364125 DOI: 10.1093/tropej/43.5.279
    Infectious complications are the major cause of morbidity and mortality in children with malignancy. Empirical antimicrobial therapy in the management of fever of unknown origin should be tailored to local bacteriological data and antibiotic sensitivity patterns. Five-hundred-and-fifty-nine cases of culture-proven septicaemia occurring in pediatric cancer patients between 1990 and 1994 were retrospectively analysed and compared with a similar study done in our centre between 1976 and 1979. A wide spectrum of organisms was isolated. Staphylococcus epidermidis, Staphylococcus aureus, and Klebsiella pneumoniae were the most common and consistent bacteria isolated during the 5 year period. More than 70 per cent of the staphylococci were sensitive to methicillin and universally sensitive to vancomycin. However, a worrying trend of ceftazidime-resistance amongst gram-negative organisms was found. In these situations, the use of imipenem is recommended as resistance to this antimicrobial agent was exceedingly rare.
  10. Madhloom HT, Kareem SA, Ariffin H
    J Med Syst, 2012 Aug;36(4):2149-58.
    PMID: 21399912 DOI: 10.1007/s10916-011-9679-0
    An important preliminary step in the diagnosis of leukemia is the visual examination of the patient's peripheral blood smear under the microscope. Morphological changes in the white blood cells can be an indicator of the nature and severity of the disease. Manual techniques are labor intensive, slow, error prone and costly. A computerized system can be used as a supportive tool for the specialist in order to enhance and accelerate the morphological analysis process. This research present a new method that integrates color features with the morphological reconstruction to localize and isolate lymphoblast cells from a microscope image that contains many cells. The localization and segmentation are conducted using a proposed method that consists of an integration of several digital image processing techniques. 180 microscopic blood images were tested, and the proposed framework managed to obtain 100% accuracy for the localization of the lymphoblast cells and separate it from the image scene. The results obtained indicate that the proposed method can be safely used for the purpose of lymphoblast cells localization and segmentation and subsequently, aiding the diagnosis of leukemia.
  11. Chong SY, Chong LA, Ariffin H
    Am J Emerg Med, 2010 Jun;28(5):603-6.
    PMID: 20579557 DOI: 10.1016/j.ajem.2009.02.006
    The aim of this study is to formulate an accurate estimate of the spinal needle depth for a successful lumbar puncture in pediatric patients.
  12. Parasakthi N, Vadivelu J, Ariffin H, Iyer L, Palasubramaniam S, Arasu A
    Int. J. Infect. Dis., 2000;4(3):123-8.
    PMID: 11179914
    OBJECTIVES: To describe the epidemiology, antimicrobial susceptibility, genomic profiles, and control of a nosocomial outbreak of multidrug-resistant Klebsiella pneumoniae (MRKP) that occurred in the pediatric oncology unit of the University of Malaya Medical Centre in Kuala Lumpur.

    MATERIALS AND METHODS: A prospective epidemiologic and microbiologic study was conducted of MRKP isolated from the blood and wound of a boy with necrotizing fasciitis after a 7-day course of ceftazidime and amikacin. In the following 2 weeks, phenotypically similar MRKP were isolated from the blood cultures of four other patients and rectal swabs of another three patients and two liquid soap samples located in the same ward.

    RESULTS: Antimicrobial profiles demonstrated that all the isolates were resistant to ceftazidime, sensitive to imipenem and ciprofloxacin, and confirmed to be extended-spectrum beta-lactamase producers. Plasmids of varying molecular weights were present in all isolates. In eight of these isolates, which included four from blood, there were common large molecular weight plasmids ranging from 80 kb to 100 kb. Pulsed-field gel electrophoresis analysis using XbaI demonstrated six different DNA profiles, A to F. Profile A was shared by two blood culture isolates and were related by 91%. Profile B was found in one rectal swab isolate and one isolate from liquid soap and were related by 94%. Profile C was shared by one blood isolate and one liquid soap isolate and showed 100% relatedness. Profiles D, E, and F each were demonstrated by one blood isolate and two rectal swab isolates, respectively. These showed only 65% relatedness.

    CONCLUSIONS: The MRKP strains in this outbreak were not clonal in origin. The decline of the outbreak after 4 weeks was attributed to the reemphasis of standard infection control procedures and the implementation of a program that addressed sites of environmental contamination.

  13. Lum SH, How SJ, Ariffin H, Krishnan S
    Med. J. Malaysia, 2016 02;71(1):28-9.
    PMID: 27130741
    Immune thrombocytopenia is the most common diagnosis of isolated thrombocytopenia. The dilemma encountered by paediatricians is missing diagnosis of acute leukaemia in children with isolated thrombocytopenia. We demonstrated childhood ITP could be diagnosed using a four point clinical criteria without missing a diagnosis of acute leukaemia. Hence, bone marrow examination is not necessary in children with typical features compatible with ITP prior to steroid therapy. This can encourage paediatricians to choose steroid therapy, which is cheaper and non-blood product, as first line platelet elevating therapy in children with significant haemorrhage.
  14. Oh L, Hainaut P, Blanchet S, Ariffin H
    BMC Cancer, 2020 Feb 10;20(1):110.
    PMID: 32041553 DOI: 10.1186/s12885-020-6599-8
    BACKGROUND: TP53 mutations occur in only about 3% of primary and 10-20% of relapse B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). However, alternative mechanisms may contribute to functionally impairing the p53 pathway in the absence of a mutation. Candidate mechanisms include overexpression of p53 mRNA variants encoding either dominant-negative p53 protein isoforms such as Delta40p53 and Delta133p53, or modulatory isoforms such as p53beta, which counteract the effects of Delta133p53 on replicative senescence in T-lymphocytes.

    METHODS: We used semi-quantitative reverse-transcriptase PCR (RT-PCR) and Western blot to investigate the expression of full length p53 (TAp53), Delta40p53, Delta133p53 or p53beta in diagnostic marrow from a clinical cohort of 50 BCP-ALL patients without TP53 mutation (29 males and 21 females, age range 2-14 years) and in the bone marrow cells of 4 healthy donors (used as controls).

    RESULTS: Irrespective of isoforms, levels of p53 mRNA were low in controls but were increased by 2 to 20-fold in primary or relapse BCP-ALL. TAp53 was increased in primary BCP-ALL, Delta40p53 was elevated in relapse BCP-ALL, whereas Delta133p53 and p53beta were increased in both. Next, mRNA levels were used as a basis to infer the ratio between protein isoform levels. This inference suggested that, in primary BCP-ALL, p53 was predominantly in active oligomeric conformations dominated by TAp53. In contrast, p53 mostly existed in inactive quaternary conformations containing ≥2 Delta40 or Delta133p53 in relapse BCP-ALL. Western blot analysis of blasts from BCP-ALL showed a complex pattern of N-terminally truncated p53 isoforms, whereas TAp53beta was detected as a major isoform. The hypothesis that p53 is in an active form in primary B-ALL was consistent with elevated level of p53 target genes CDKN1A and MDM2 in primary cases, whereas in relapse BCP-ALL, only CDKN1A was increased as compared to controls.

    CONCLUSION: Expression of p53 isoforms is deregulated in BCP-ALL in the absence of TP53 mutation, with increased expression of alternative isoforms in relapse BCP-ALL. Variations in isoform expression may contribute to functional deregulation of the p53 pathway in BCP-ALL, specifically contributing to its down-regulation in relapse forms.

  15. Oh L, Hafsi H, Hainaut P, Ariffin H
    Curr Opin Oncol, 2019 03;31(2):84-91.
    PMID: 30585860 DOI: 10.1097/CCO.0000000000000504
    PURPOSE OF REVIEW: Childhood blastomas, unlike adult cancers, originate from developing organs in which molecular and cellular features exhibit differentiation arrest and embryonic characteristics. Conventional cancer therapies, which rely on the generalized cytotoxic effect on rapidly dividing cells, may damage delicate organs in young children, leading to multiple late effects. Deep understanding of the biology of embryonal cancers is crucial in reshaping the cancer treatment paradigm for children.

    RECENT FINDINGS: p53 plays a major physiological role in embryonic development, by controlling cell proliferation, differentiation and responses to cellular stress. Tumor suppressor function of p53 is commonly lost in adult cancers through genetic alterations. However, both somatic and germline p53 mutations are rare in childhood blastomas, suggesting that in these cancers, p53 may be inactivated through other mechanisms than mutation. In this review, we summarize current knowledge about p53 pathway inactivation in childhood blastomas (specifically neuroblastoma, retinoblastoma and Wilms' tumor) through various upstream mechanisms. Laboratory evidence and clinical trials of targeted therapies specific to exploiting p53 upstream regulators are discussed.

    SUMMARY: Despite the low rate of inherent TP53 mutations, p53 pathway inactivation is a common denominator in childhood blastomas. Exploiting p53 and its regulators is likely to translate into more effective targeted therapies with minimal late effects for children. (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/COON/A23).

  16. Loh KB, Ramli N, Tan LK, Roziah M, Rahmat K, Ariffin H
    Eur Radiol, 2012 Jul;22(7):1413-26.
    PMID: 22434420 DOI: 10.1007/s00330-012-2396-3
    OBJECTIVES: The degree and status of white matter myelination can be sensitively monitored using diffusion tensor imaging (DTI). This study looks at the measurement of fractional anistropy (FA) and mean diffusivity (MD) using an automated ROI with an existing DTI atlas.

    METHODS: Anatomical MRI and structural DTI were performed cross-sectionally on 26 normal children (newborn to 48 months old), using 1.5-T MRI. The automated processing pipeline was implemented to convert diffusion-weighted images into the NIfTI format. DTI-TK software was used to register the processed images to the ICBM DTI-81 atlas, while AFNI software was used for automated atlas-based volumes of interest (VOIs) and statistical value extraction.

    RESULTS: DTI exhibited consistent grey-white matter contrast. Triphasic temporal variation of the FA and MD values was noted, with FA increasing and MD decreasing rapidly early in the first 12 months. The second phase lasted 12-24 months during which the rate of FA and MD changes was reduced. After 24 months, the FA and MD values plateaued.

    CONCLUSION: DTI is a superior technique to conventional MR imaging in depicting WM maturation. The use of the automated processing pipeline provides a reliable environment for quantitative analysis of high-throughput DTI data.

    KEY POINTS: Diffusion tensor imaging outperforms conventional MRI in depicting white matter maturation. • DTI will become an important clinical tool for diagnosing paediatric neurological diseases. • DTI appears especially helpful for developmental abnormalities, tumours and white matter disease. • An automated processing pipeline assists quantitative analysis of high throughput DTI data.

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