Displaying publications 241 - 260 of 278 in total

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  1. Munkongdee T, Tongsima S, Ngamphiw C, Wangkumhang P, Peerapittayamongkol C, Hashim HB, et al.
    Sci Rep, 2021 05 14;11(1):10352.
    PMID: 33990643 DOI: 10.1038/s41598-021-89641-2
    β-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. A thalassemia severity score has been developed from Mediterranean β-thalassemia patients. However, different ethnic groups may have different allele frequency and linkage disequilibrium structures. Here, Thai β0-thalassemia/HbE disease genome-wild association studies (GWAS) data of 487 patients were analyzed by SNP interaction prioritization algorithm, interacting Loci (iLoci), to find predictive SNPs for disease severity. Three SNPs from two SNP interaction pairs associated with disease severity were identifies. The three-SNP disease severity risk score composed of rs766432 in BCL11A, rs9399137 in HBS1L-MYB and rs72872548 in HBE1 showed more than 85% specificity and 75% accuracy. The three-SNP predictive score was then validated in two independent cohorts of Thai and Malaysian β0-thalassemia/HbE patients with comparable specificity and accuracy. The SNP risk score could be used for prediction of clinical severity for Southeast Asia β0-thalassemia/HbE population.
    Matched MeSH terms: beta-Thalassemia/blood; beta-Thalassemia/diagnosis*; beta-Thalassemia/genetics
  2. Mat MAC, Yaacob LH, Zakaria R
    Malays J Med Sci, 2020 Feb;27(1):124-133.
    PMID: 32158352 MyJurnal DOI: 10.21315/mjms2020.27.1.13
    Introduction: Acceptance of a screening programme for thalassemia is important in managing the disease and its associated complications. The objective of this study was to determine the knowledge of thalassemia and factors associated with thalassemia screening refusal among parents of secondary school children.

    Methods: This cross-sectional study was carried out from May 2017 to October 2017 among parents of fourth form students in three schools in Besut, Terengganu, Malaysia. Parents who are able to read and understand Malay and consented to the study were required to answer a validated questionnaire on their knowledge regarding thalassemia. They were also asked the reason for their acceptance or refusal of the thalassemia screening of their children.

    Results: In total, 273 participants took part in the study. The mean thalassemia knowledge score was 11.8 out of a maximum score of 21. Low knowledge scores (adjusted odds ratio [adj OR] 0.87; 95% confidence interval [CI]: 0.79, 0.95; P = 0.002) and female sex (adj OR 2.60; 95% CI: 1.04, 6.53; P = 0.040) had significant associations with parental thalassemia screening refusal. The main reason for screening refusal was that parents perceived that their children were not at risk for the disease since they did not have a family member with thalassemia.

    Conclusion: The mean thalassemia knowledge score among parents remains unsatisfactory. A high knowledge score is important since it is associated with parental acceptance of thalassemia screening for their children.

    Matched MeSH terms: Thalassemia
  3. George E, Jamal AR, Khalid F, Osman KA
    Malays J Med Sci, 2001 Jul;8(2):40-6.
    PMID: 22893759 MyJurnal
    Beta-thalassaemia is characterized by a decrease (β(+)) or absence (β(0)) in the synthesis of β-globin chains of human haemoglobin. The heterozygous state for β(+) or β(0) result in β-thalassaemia trait in which the hallmark is the presence of an elevated level of Haemoglobin (Hb) A(2) (α(2)δ(2)). In the past, the traditional methods such as cellulose acetate electrophoresis with elution and microcolumn chromatrography have been the techniques used by the majority of the laboratories in Malaysia for the estimation of (Hb) A(2) levels. The recommended method currently is high performance liquid chromatography which has only been introduced in a few laboratories in the country.
    Matched MeSH terms: beta-Thalassemia
  4. Noraihan MN, See MH, Raja R, Baskaran TP, Symonds EM
    Med J Malaysia, 2005 Oct;60(4):460-8.
    PMID: 16570708
    The objective of the study is to determine the proportion and different types of birth defects among the children born in Hospital Kuala Lumpur. A cross-sectional study was conducted for a period of 18 months where all consecutively born infants, dead or alive were included. There were total of 34,109 births recorded during this period. The proportion of birth defects in Hospital Kuala Lumpur was 3.1% (n = 1056). The commonest involved were the hematology system, (157.7 per 10,000 births), the central nervous system, genitourinary system and chromosomal anomalies. The proportion was significantly higher in males and in the Chinese (p < 0.001). The commonest abnormalities are Glucose 6 Phosphate Deficiency (157.7/10000), Down's syndrome (12.6/10000), thalassaemia (8.8/10000), cleft lip and/or palate (7.6/10000) and anencephaly (7.3/10000). Neural tube defect is common and ranked second after G6PD deficiency. There is a need for a birth defect registry to assess the extent of the problem in Malaysia.
    Matched MeSH terms: Thalassemia/epidemiology
  5. Hamidah A, Thambidorai CR, Jamal R
    Med J Malaysia, 2005 Oct;60(4):517-9.
    PMID: 16570722
    We describe a patient with HbE-beta thalassaemia and chronic hepatitis C virus infection (genotype 1a) who was treated successfully with peginterferon alfa-2b and ribavirin, following failure to respond to standard interferon and ribavirin therapy. She had sustained virological response for nearly 24 months after completing peginterferon alfa-2b and ribavirin therapy. Transfusion requirements were significantly increased during combination therapy due to ribavirin-induced haemolysis. The adverse effects of interferon were well tolerated. Combination therapy with peginterferon alfa-2b and ribavirin maybe a feasible treatment option for a subset of thalassaemia/HCV infected non-responders to standard interferon-based therapy.
    Matched MeSH terms: beta-Thalassemia/complications*
  6. Hamidah A, Yong JF, Zulkifli HI, Jamal R
    Med J Malaysia, 2002 Sep;57(3):353-6.
    PMID: 12440276
    We describe two cases of transfusion dependent thalassaemics with chronic hepatitis C virus infection whom were treated successfully with interferon and ribavirin, following failure of response or relapse after an initial response to interferon monotherapy. They had sustained virological response for more than twelve months after completing therapy. Transfusion requirements were significantly increased during the combination therapy, probably due to ribavirin-induced haemolysis. Serum ferritin level decreased significantly during the treatment. Combination therapy with interferon alfa and ribavirin may be a feasible treatment option for some nonresponders to prior interferon monotherapy.
    Matched MeSH terms: Thalassemia/complications*
  7. Shukri A, Green S, Bradley DA
    Appl Radiat Isot, 1995 6 1;46(6-7):625.
    PMID: 7633384
    Matched MeSH terms: beta-Thalassemia/therapy
  8. Lie-Injo LE, Herrera AR, Lebo RV, Hassan K, Lopez CG
    Am J Hematol, 1985 Mar;18(3):289-96.
    PMID: 2983536
    Restriction enzyme analysis of the alpha and zeta globin genes was carried out in four cases of Hb Bart's hydrops fetalis, in three patients with Hb H disease without Hb CoSp, in three patients with Hb H disease with Hb CoSp, in 47 individuals with alpha thalassemia trait, and in 47 normal individuals. All four cases of Hb Bart's hydrops fetalis resulted from deletions of alpha 1 and alpha 2 globin genes which did not extend to the psi zeta 1 and zeta 2 globin genes. The same type of deletion was observed in alpha thal1 carriers, but two newborns (one Malay and one of Chinese extraction) had a nondeletion type of alpha thal1 which was confirmed by quantitative alpha globin gene analysis. In addition, two other newborns diagnosed as alpha thal1 trait carriers (one Malay, one Chinese) were shown to have a deletion of both alpha globin genes by quantitative alpha globin gene analysis, but further testing with zeta globin gene probe failed to reveal an abnormal fragment length characteristic of an alpha globin gene deletion. We believe that this last condition is due to a large deletion which includes all alpha globin genes and all zeta globin genes on the same chromosome. On another front, Bgl II restriction analysis of all four Hb Bart's hydrops fetalis cases and the alpha thal1 trait carriers showed a 10.5-kb Bgl II restriction fragment, in the hydrops fetalis as a single band, while in the carriers this 10.5-kb fragment was accompanied by the usual normal 12.5-kb and 11.3-kb fragments. We report that this 10.5-kb fragment, previously thought to be specific for the Southeast Asian alpha thal1 gene deletion, is also common in normal individuals. Nevertheless, digestion with other enzymes can clearly differentiate the alpha thal1 and normal genotypes. We distinguish the findings in the alpha thalassemias from the extensive DNA polymorphism in the region of the alpha and zeta globin genes.
    Matched MeSH terms: Thalassemia/genetics*
  9. Mohd Ibrahim H, Muda Z, Othman IS, Mohamed Unni MN, Teh KH, Thevarajah A, et al.
    BMJ Open, 2020 06 29;10(6):e037974.
    PMID: 32601117 DOI: 10.1136/bmjopen-2020-037974
    OBJECTIVE: Thalassaemia is the most common inherited blood disorder in Malaysia. This study aims to report the current status of thalassaemia in Malaysia and provide a comprehensive understanding of the disease through data obtained from the Malaysian Thalassaemia Registry.

    DESIGN: Data were extracted from the Malaysian Thalassaemia Registry, a web-based system accessible to enrolled users through www.mytalasemia.net.my.

    SETTING: The Malaysian Thalassaemia Registry data was recorded from reports obtained from 110 participating government and university hospitals in Malaysia.

    PARTICIPANTS: The patients were those attending the 110 participating hospitals for thalassaemia treatment.

    INTERVENTION: Data were collected from the Malaysian Thalassaemia Registry from 2007 until the fourth quarter of 2018.

    PRIMARY OUTCOME MEASURE: 7984 out of 8681 patients with thalassaemia registered in the Malaysian Thalassaemia Registry were reported alive.

    RESULTS: Majority of the patients were reported in the state of Sabah (22.72%); the largest age group affected was 5.0-24.9 years old (64.45%); the largest ethnic group involved was Malay (63.95%); and the major diagnosis was haemoglobin E/β-thalassaemia (34.37%). From the 7984 patients, 56.73% were on regular blood transfusions and 61.72% were on chelation therapy. A small fraction (14.23%) has undergone splenectomy, while the percentage of patients with severe iron overload (serum ferritin ≥5000 µg/L) reduced over time. However, cardiac complications are still the main cause of death in patients with thalassaemia.

    CONCLUSION: Data gathered into the registry can be used to understand the progression of the disorder, to monitor iron overload management and to improve the outcomes of treatment, to enhance preventive strategies, reduce healthcare burden and improve the quality of life. Sustainability of the Malaysian Thalassaemia Registry is important for surveillance of thalassaemia management in the country and help the national health authorities to develop more effective policies.

    Matched MeSH terms: Thalassemia; beta-Thalassemia
  10. Lee KT, Lim SL, Goh AS
    Med J Malaysia, 2020 01;75(1):33-37.
    PMID: 32008017
    INTRODUCTION: Frequent blood transfusions results in iron overload and lead to multiple endocrine complications. In spite of improvements in iron chelation therapy, a significant number of transfusion dependent thalassaemia (TDT) patients still develop endocrine complications. The aim of this study is to evaluate the prevalence of various endocrine complications in our adult TDT patients and to study the correlation with serum ferritin and liver iron concentration (LIC).

    METHODS: A retrospective review of all TDT patients treated in Haematology Unit, Hospital Pulau Pinang (HPP) was conducted.

    RESULTS: Of the 45 adult TDT patients, 22 were males and 23 were females with mean age of 28.8±6.9 years old. Majority of TDT in HPP were beta thalassemia major (71.1%), followed by E-Beta thalassemia (24.4%) and HbH-Constant Spring (4.4%). Frequency of transfusion was 3-4 weekly. 40.0% of adult TDT suffered from at least one endocrine complication. Among the adult TDT patients with endocrine complication, 50% have one endocrinopathy, 38.9% with two types of endocrinopathies and 11.1% of them have three or more types of endocrinopathies. Hypogonadism (22.2%) was the commonest endocrine complication, followed by osteoporosis (20%), hypothyroidism (13.3%), diabetes mellitus (6.7%) and hypocortisolism (4.4%). Patients with endocrine complications were significantly older. Mean serum ferritin level and LIC was higher among patients with endocrine complications but both were not statistically significant.

    CONCLUSION: Endocrinopathy is still prevalent in 40% of adult TDT patients. This leads to higher health-care resource utilization, cost and significant morbidities among patients with TDT. Therefore, regular monitoring and early detection with intensification of chelation therapy is essential.

    Matched MeSH terms: Thalassemia/therapy
  11. Rashid RA, Ankathil R
    Malays J Pathol, 2020 Aug;42(2):171-185.
    PMID: 32860369
    Gene therapy is a method of treatment of disease aimed at its molecular level. The progress of gene therapy, however, was as promising as it was tardy mainly due to the limitations in the resources and financial part of its development as well as owing to the rarity of most diseases it can offer its benefits to. The methods of gene therapy can vary depending on factors such as the physiology of tissue of interest, affinity of vectors to a certain type of cells, depth and accessibility of the tissue of interest, and size of the gene to be replaced or edited. The concept behind gene therapy has inspired scientists and clinicians alike leading to a rapid expansion of its clinical utility that has become so widespread to not only include diseases of monogenic origin, but also polygenic diseases, albeit not so commonly. This article delves into notable success stories of gene therapy which has been regarded as the beacon of medical novelty expected to blossom in the near future to provide a holistic, targeted, precise, and individualistic personalised-medicine as well as laying out the future hopes of gene therapy in the treatment of debilitating diseases such as solid tumours, AIDS, Tuberculosis, Diabetes Mellitus, psychiatric illnesses, which are still at a standstill, from a gene therapy point of view.
    Matched MeSH terms: beta-Thalassemia/therapy
  12. Deris ZZ, Leow VM, Wan Hassan WM, Nik Lah NA, Lee SY, Siti Hawa H, et al.
    Trop Biomed, 2009 Dec;26(3):320-5.
    PMID: 20237446
    Vibrio cholerae infection is mainly caused acute diarrhoea disease. Bacteraemia due to non-O1 V. cholerae is rare and mainly reported in liver cirrhotic patients. We report one case of non-O1 V. cholerae bacteraemia in splenectomised thalassaemic patient who presented with septic shock secondary to abdominal sepsis. She had undergone emergency laporatomy and was managed in the intensive care unit for nine days. She was treated with meropenem and doxycyline and discharged well after fourteen days of admission. The V. cholerae was identified by API 20NE, serotype and polymerase chain reaction showed as non-O1, non-O139 strain. Besides known cholera-like toxin and El Tor hemolysin, with increasing reported cases of V. cholerae bacteraemia, there is possibility of other virulence factors that allow this organism to invade the bloodstream.
    Matched MeSH terms: Thalassemia/complications*
  13. Lie-Injo LE, Lopez CG, Lopes M
    Acta Haematol., 1971;46(2):106-20.
    PMID: 4331171 DOI: 10.1159/000208565
    A study of 23 patients with Hb H disease and their 82 relatives in 17 families showed that 2 types of this condition exist. One is associated with the presence of a small slow-moving component, which we tentatively called the X component and which was invariably present in one parent. Some siblings also had it. The other type was not associated with this component. Two patients without X component had a newborn with Bart’s haemoglobin without X component. None of the parents of 20 newborns with Hb Bart’s without the X component had the X component. It was present in only one parent of each of 2 newborns with Hb Bart’s and the X component. They are thought to represent Hb H disease in the newborn period. We suggest that at least 3 abnormal genes may lead to Hb H disease, which results when 2 of the 3 combine. Severity of clinical and haematological symptoms depends upon which abnormal gene is present and which 2 are involved in any particular combination.
    Key Words: a-Thalassaemia; Haemoglobin Bart’s; Haemoglobin H disease; Haemoglobinopathies
    Matched MeSH terms: Thalassemia/epidemiology
  14. Hoe TS, Deng CT, Khuzaiah R
    PMID: 8160075
    Matched MeSH terms: beta-Thalassemia/complications*
  15. Jamal R, Fadzillah G, Zulkifli SZ, Yasmin M
    PMID: 10772566
    Regular blood transfusions for patients with thalassemia have improved their overall survival although these transfusions carry a definite risk of the transmission of certain viruses. Infection with hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) leads to complications which contribute to the morbidity and mortality of patients with thalassemia. We analyzed the blood samples taken from 85 transfusion dependent thalassemics receiving treatment at the day care center in Hospital Universiti Kebangsaan Malaysia and found that the seroprevalence rates for HBV, HCV and CMV were 2.4%, 22.4% and 91.8% respectively. None of the patients tested positive for HIV. Those positive for HBV and HCV will require further tests and treatment if chronic hepatitis is confirmed.
    Matched MeSH terms: beta-Thalassemia/therapy; beta-Thalassemia/virology*
  16. Lim WF, Muniandi L, George E, Sathar J, Teh LK, Gan GG, et al.
    Blood Cells Mol. Dis., 2012 Jan 15;48(1):17-21.
    PMID: 22079025 DOI: 10.1016/j.bcmd.2011.10.002
    The alpha haemoglobin stabilising protein (AHSP) acts as a molecular chaperone for α-globin by stabilising nascent α-globin before transferring it to waiting free β-globin chains. Binding of AHSP to α-globin renders α-globin chemically inert whereby preventing it from precipitating and forming reactive oxygen species byproducts. The AHSP has been actively studied in the recent years, particularly in its relation to β-thalassaemia. Studies have shown that AHSP is a modifier in β-thalassaemia mice models. However, this relationship is less established in humans. Studies by some groups showed no correlation between the AHSP haplotypes and the severity of β-thalassaemia, whereas others have shown that certain AHSP haplotype could modify the phenotype of β-thalassaemia intermedia patients. We investigated the expression of AHSP in relation to selected demographic data, full blood count, HPLC results, HbE/β-thalassaemia genotype, Xmn-1 Gγ polymorphism, α-globin, β-globin and γ-globin expression. We found that AHSP expression was significantly correlated to mean cell haemoglobin level, HbF %, α-globin, β-globin and excess α-globin expression. We concluded that AHSP could be a secondary compensatory mechanism in red blood cells to counterbalance the excess α-globin chains in HbE/β-thalassaemia individuals.
    Matched MeSH terms: beta-Thalassemia/genetics*
  17. Toman HA, Nasir A, Hassan R, Hassan R
    Eur J Orthod, 2011 Dec;33(6):700-4.
    PMID: 21282284 DOI: 10.1093/ejo/cjq147
    Thalassaemia is a public health problem in Malaysia. It is known to cause skeletal deformity. The purpose of this study was to compare the skeletal, dentoalveolar, and soft tissue features of Malay transfusion-dependent thalassaemia (TDT) patients with a Malay control group. Lateral cephalometric radiographs of 30 Malay (14 males and 16 females aged 6.4-21.8 years) TDT patients and 60 normal Malays matched for chronological age and gender were analysed and compared using an independent t-test. The TDT group showed a similar sagittal relationship to the control group but with a significantly increased (P < 0.01) mandibular plane inclination. They also showed a significantly shorter (P ≤ 0.001) mandibular body, ramus length, and posterior face height and consequently a smaller ratio of posterior to anterior face height (P < 0.01). The upper and lower lips were significantly procumbent (P < 0.001) in the TDT group together with a significantly smaller nasolabial angle (P < 0.05). Dentoalveolar measurements showed less proclined maxillary teeth in the TDT group compared with the controls (P < 0.05). The cephalometric features of Malay TDT patients were characterized by a mild Class II skeletal pattern, prominent vertical growth direction of the mandible, and protruded upper and lower lips.
    Matched MeSH terms: Thalassemia/therapy*
  18. Lai MI, Garner C, Jiang J, Silver N, Best S, Menzel S, et al.
    Twin Res Hum Genet, 2010 Dec;13(6):567-72.
    PMID: 21142933 DOI: 10.1375/twin.13.6.567
    Cytotoxic precipitation of free α-globin monomers and its production of reactive oxygen species cause red cell membrane damage that leads to anemia and eventually ineffective erythropoiesis in β-thalassemia. Alpha hemoglobin stabilizing protein (AHSP) was found to bind only to free α-globin monomers creating a stable and inert complex which remains soluble in the cytoplasm thus preventing harmful precipitations. Alpha hemoglobin stabilizing protein was shown to bind nascent α-globin monomers with transient strength before transferring α-globin to β-globin to form hemoglobin tetramer. A classical twin study would be beneficial to investigate the role of genetics and environment in the variation of alpha hemoglobin stabilizing protein expression as this knowledge will enable us to determine further investigations with regards to therapeutic interventions if alpha hemoglobin stabilizing protein is to be a therapeutic agent for β-thalassemia. This study investigates the heritability influence of alpha hemoglobin stabilizing protein expression and factors that may contribute to this. Results indicated that a major proportion of alpha hemoglobin stabilizing protein expression was influenced by genetic heritability (46%) with cis-acting factors accounting for 19% and trans-acting factors at 27%.
    Matched MeSH terms: beta-Thalassemia/genetics*
  19. Taher AT, Origa R, Perrotta S, Kourakli A, Ruffo GB, Kattamis A, et al.
    Am J Hematol, 2017 May;92(5):420-428.
    PMID: 28142202 DOI: 10.1002/ajh.24668
    Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption. The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged ≥10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes. One hundred seventy-three patients were randomized 1:1 to DT (n = 86) or FCT (n = 87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study. Patient-reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload-related complications.
    Matched MeSH terms: Thalassemia/drug therapy*
  20. Delatycki MB, Alkuraya F, Archibald A, Castellani C, Cornel M, Grody WW, et al.
    Prenat Diagn, 2020 02;40(3):301-310.
    PMID: 31774570 DOI: 10.1002/pd.5611
    Reproductive carrier screening started in some countries in the 1970s for hemoglobinopathies and Tay-Sachs disease. Cystic fibrosis carrier screening became possible in the late 1980s and with technical advances, screening of an ever increasing number of genes has become possible. The goal of carrier screening is to inform people about their risk of having children with autosomal recessive and X-linked recessive disorders, to allow for informed decision making about reproductive options. The consequence may be a decrease in the birth prevalence of these conditions, which has occurred in several countries for some conditions. Different programs target different groups (high school, premarital, couples before conception, couples attending fertility clinics, and pregnant women) as does the governance structure (public health initiative and user pays). Ancestry-based offers of screening are being replaced by expanded carrier screening panels with multiple genes that is independent of ancestry. This review describes screening in Australia, Cyprus, Israel, Italy, Malaysia, the Netherlands, Saudi Arabia, the United Kingdom, and the United States. It provides an insight into the enormous variability in how reproductive carrier screening is offered across the globe. This largely relates to geographical variation in carrier frequencies of genetic conditions and local health care, financial, cultural, and religious factors.
    Matched MeSH terms: Thalassemia/genetics
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