Browsing by Author "Chularatana Mahasandana"
Now showing 1 - 14 of 14
- Results Per Page
- Sort Options
Publication Metadata only Carrier detection by DNA linkage analysis in eighty Thai hemophilia A families(2002-08-01) Chularatana Mahasandana; Ajjima Treesucon; Gavivann Veerakul; Pa Thai Yenchitsomanus; Parichat Pung-Amritt; Siripan Petrarat; Sukon Visudhiphan; Mahidol UniversityDNA linkage analysis was performed in Thai hemophilia A families to evaluate its value for carrier detection. Both intragenic and extragenic polymorphic DNA regions of the factor VIII gene, including Bcl I-RFLP in intron 18, microsatellites (CA repeats) in introns 13 and 22, and extragenic St14 (DXS 52) VNTR, were amplified by polymerase chain reaction (PCR) before analyses by appropriate electrophoretic procedures. A total of 80 Thai hemophilia A families (48 with a family history and 32 with a sporadic case), containing 349 DNA samples from 90 hemophilia A patients, 143 parents, and 116 relatives, were analyzed. Heterozygosities in the patients' mothers from both families with a family history and with a sporadic case were observed in 71 out of 80 families (88.75%) for all polymorphic DNA markers analyzed. The carrier status could be identified in 36 females and excluded in 44 females. This result indicates that the DNA linkage analysis can be used for carrier detection or exclusion in the majority of Thai hemophilia A families. It should also be useful for prenatal diagnosis in families at risk of hemophilia A, which is part of the prevention and control of this disease.Publication Metadata only Compound heterozygosity for one novel and one recurrent mutation in a Thai patient with severe protein S deficiency(1999-02-19) Parichat Pung-Amritt; Swibertus R. Poort; Hans L. Vos; Rogier M. Bertina; Chularatana Mahasandana; Voravarn S. Tanphaichitr; Gavivann Veerakul; Suthida Kankirawatana; Vinai Suvatte; Mahidol University; Leiden University Medical Center - LUMCHomozygous or compound heterozygous protein S (PS) deficiency is a very rare disorder in the anticoagulant system, that can lead to life-threatening thrombotic complications shortly after birth. This report describes the results of the genetic analysis of the PROS 1 genes in a Thai girl patient. She was reported in 1990 as the first case with homozygous PS deficiency and neonatal purpura fulminans. In the present report, we identified the mutations in this patient by direct sequencing of PCR products representing all 15 exons of the PROS1 gene and their flanking intronic regions. The patient turned out to be compound heterozygous for two null mutations. One allele contained a novel sequence variation, an A-insertion in an A5-tract covering codon 146 and 147, that results in a frameshift and a stop codon (TAA) at position 155. The other allele contained a nonsense mutation in exon 12 by a transition at codon 410 CGA (Arg) to TGA (stop). Cosegregation of PS deficiency with these two genetic defects was observed in her family.Publication Metadata only Congenital afibrinogenaemia caused by uniparental isodisomy of chromosome 4 containing a novel 15-kb deletion involving fibrinogen Aα-chain gene(2004-11-01) Silvia Spena; Stefano Duga; Rosanna Asselta; Flora Peyvandi; Chularatana Mahasandana; Massimo Malcovati; Maria Luisa Tenchini; Universita degli Studi di Milano; Mahidol UniversityAmong rare inherited deficiencies of coagulation factors, congenital afibrinogenaemia is characterised by the lack of fibrinogen in plasma. In the last few years, several genetic defects underlying afibrinogenaemia (mostly point mutations) have been described in the fibrinogen gene cluster. In this study, the molecular basis responsible for afibrinogenaemia in a Thai proband was defined. Point mutation screening was accomplished by directly sequencing the three fibrinogen genes. The impossibility to amplify fibrinogen Aα-chain gene (FGA) exons 5 and 6 suggested the presence of a homozygous deletion. A specific long-range PCR assay enabled the identification of a novel 15-kb deletion, representing the largest afibrinogenaemia-causing deletion described so far. Direct sequencing of the deletion junction allowed mapping of the breakpoints in FGA intron 4 and in the intergenic region between Aα- and Bβ-chain genes. Since the mutation was inherited only from the mother and nonpaternity was ruled out, a maternal uniparental disomy (UPD) was hypothesised. UPD test, carried out with markers covering the whole chromosome 4, revealed that maternal isodisomy was responsible for homozygosity of the 15-kb deletion in the proband. The apparently normal phenotype of the proband, except for afibrinogenaemia, suggests that UPD for chromosome 4 is clinically silent. This represents the first case of a documented complete isodisomy of chromosome 4 causing the phenotypic expression of a recessive disorder. In silico analyses of the regions surrounding the breakpoints suggested that the 15-kb deletion might have originated from an inappropriate repair of a double-strand break by the nonhomologous end joining mechanism. © 2004 Nature Publishing Group All rights reserved.Publication Metadata only Frameshift mutations with severe and moderate clinical phenotypes in Thai hemophilia A patients(2000-01-01) Varaporn Akkarapatumwong; Sorasak Intorasoot; Sumalee Oranwiroon; Prapaporn Thano-otarakul; Parichat Pung-amritt; Gavivann Veerakul; Chularatana Mahasandana; Sakol Panyim; Pa Thai Yenchitsomanus; Mahidol UniversitySix frameshift mutations in exon 14 of the factor VIII gene were identified in Thai hemophilia A patients. Although all these mutations created premature stop codons and expected to cause severe disease, the molecular defects and clinical severity were in discrepancy in some patients. Four mutations (delT3490, delACAC3618-21, delGA4429-30, and delA4658) were found in the patients with the severe clinical phenotype while two (delA3629-37 and insA4372-9) were observed in the patients who had moderate severity, with FVIII:C of 4.2 and 2.8%. The frameshift mutations in these two patients were due to deletion and insertion of an 'A' nucleotide in the stretches of 9As and 8As in codons 1191-4 and 1439-41, respectively. This indicates that deletion or insertion in the stretches of poly A nucleotides in exon 14 of the factor VIII gene is a likely cause of the moderate clinical severity in some cases of Thai hemophilia A patients. Copyright 2000 Wiley-Liss, Inc.Publication Metadata only Gaucher's disease;thirty-two years experience at Siriraj Hospital(1999-12-01) Voravarn S. Tanphaichitr; Vinai Suvatte; Chularatana Mahasandana; Prasit Sachapong; Gavivann Veerakul; Suthida Kankirawatana; Pornswan Wasant; Mahidol UniversityGaucher's disease, a lysosomal disorder, is not a common disease in Thailand. During the period 1966-1998 we saw 20 patients with Gaucher's disease at the Department of Pediatrics, Siriraj Hospital. The patients came from different regions of the country but mostly from the central part of Thailand. There were 8 males and 12 females from 13 families of Thai, Thai-Chinese, Thai-Laos and Chinese-Chinese in origin. A history of consanguinity was present in 2 families. The age of onset was 2 months-4 years and the age when they were diagnosed was 4 months-15 years. The most common clinical features included splenomegaly, hepatomegaly, growth retardation, pallor, bleeding disorders and neurological abnormalities. The diagnosis was made by the clinical manifestations, hematologic complications and demonstration of Gaucher cells in the bone marrow and/or other tissues. In one family, the diagnosis was confirmed by evaluation of glucocerebrosidase activities in skin fibroblasts. The management of these patients was symptomatic ie packed red cell and platelet transfusion, splenectomy and other supportive measures. Most patients died of bleeding or infection at an early age.Publication Metadata only Linear growth in homozygous β-thalassemia and β-thalassemia/hemoglobin E patients under different treatment regimens(2001-07-01) Vip Viprakasit; Chularatana Mahasandana; Lerlugsn Suwantol; Suthida Kankirawatana; Vinai Suvatte; Voravarn S. Tanphaichitr; Amara Assteerawatt; Gavivann Veerakul; Parichat Pung-Amritt; Mahidol UniversityThe effects on linear growth and development among thalassemic patients under different treatment regimens were compared. Twelve homozygous β-thalassemia (homozygous β-thal) and 36 β-thalassemia/Hb E (β-thal/Hb E) were studied longitudinally between 1977 and 1998. Eighteen cases (10 homozygous β-thal and 8 β-thal/Hb E) received hypertransfusion with iron chelation by desferrioxamine. Another 30 cases (2 homozygous β-thal and 28 β-thal/Hb E) were given a low transfusion (depending on their clinical requirement). Their heights were measured serially and are presented as a standard deviation score (SDS). There was no significant difference in initial basic hematological data and ferritin levels between either group. However, the hypertransfused group, seemed to be clinically more severely affected than the other group as evidenced by early age at initial transfusion, the early onset of anemia and diagnosis and also their large acquired iron load after a period of transfusion. The average height SDS of the hypertransfused patients was within the 50thpercentile ± 1 SD during the first decade of life in both sexes and both genotypes. Whereas, in patients who were transfused infrequently, the SDS was always below the -1 SD and decreased gradually. In severe β-thal/Hb E cases, their growth SDS showed no difference from those with homozygous β-thal. Normal linear growth in those with homozygous β-thal and severe β-thal/Hb E was only seen in the group that underwent hypertransfusion and this regimen contributed to normal growth during the first ten years of life. However, adequate iron chelation and hormonal treatment in these patients were also required in order to achieve normal adult height.Publication Metadata only Malignancies in HIV-infected children at Siriraj Hospital(2002-08-01) Kleebsabai Sanpakit; Worapant Kriengsuntornkij; Voravarn S. Tanphaichitr; Gavivann Veerakul; Kulkanya Chokephaibulkit; Chularatana Mahasandana; Mahidol UniversityBackground: Some malignancies such as Kaposi's sarcoma, non-Hodgkin's lymphoma (NHL) are one of the acquired immunodeficiency syndrome (AIDS) - defining illnesses. With the improving survival of patients with AIDS due to better prevention and treatment of infectious complications, there may well be an increase in AIDS-related malignancies. Objective: To study malignancies in human immunodeficiency virus (HIV)-infected children in view of demographic data, HIV disease status, characters of malignancies, and treatment outcome. Method: Retrospective study was performed in HIV-infected children with malignancies at Siriraj Hospital from January 1995 to October 2001. Results: During the 6 year and 10 month period, there were 7 HIV-infected children (2 boys, 5 girls) with malignancies. Mean age at diagnosis of malignancies was 3 years 7 months (2 years 6 months - 5 years). Hepatomegaly and lymphadenopathy were the most common presenting symptoms. All patients had NHL stage III or IV. Burkitt's lymphoma was the predominant type. Six patients were treated with appropriate chemotherapy and one patient also received antiretroviral therapy. Only one patient with large cell lymphoma stage IV who received both antiretroviral and chemotherapy has survived to date. Five patients died during chemotherapy treatment and one patient died before receiving chemotherapy. Causes of death of these patients were infections. One of them with Burkitt's lymphoma stage III also had central nervous system (CNS) relapse at the time of death. Mean survival time after diagnosis with malignancies was 11 months (15 days - 3 years 1 month). Conclusion: NHL is the most common malignancy in HIV-infected children at Siriraj Hospital. Age at presentation of NHL in these children is younger than their non-HIV counterpart. Outcome of treatment is poor. Adjustment protocol for treatment of malignancy in HIV-infected children combined with antiretroviral therapy for controlling HIV infection should be studied further.Publication Metadata only Malignant lymphoma in Thailand: Changes in the frequency of malignant lymphoma determined from a histopathologic and immunophenotypic analysis of 425 cases at Siriraj Hospital(1998-09-15) Sanya Sukpanichnant; Dhira Sonakul; Anong Piankijagum; Wanchai Wanachiwanawin; Gavivann Veerakul; Chularatana Mahasandana; Voravarn S. Tanphaichitr; Vinai Suvatte; Mahidol UniversityBACKGROUND. Analysis of malignant lymphoma in a single institution at different periods of time can determine the changing status of the disease in the region. METHODS. To compare with the large series of 1095 lymphoma cases reported between 1957-1971 at Siriraj Hospital, the largest hospital in Thailand, a similar study was performed through histopathologic evaluation of 425 lymphoma cases diagnosed consecutively at the same institution between August 1993 and October 1995. Phenotypic analysis was performed by paraffin section-immunoperoxidase studies. RESULTS. A striking increase in lymphoma cases was noted from 73 cases/year in the first series to 189 cases/year in the second series (an increase of 158.9%). Lymphoma occurred in all age groups, with a peak incidence at the seventh decade of life. The male to female ratio decreased from 2:1 in 1957-1971 to 1.3:1 in the more recent series. The incidence of Hodgkin's disease (HD) was found to have decreased from 28.9% to 8.5%. There were 36 Cases (8.5%) of HD and 389 cases (91.5%) of non-Hodgkin's lymphoma (NHL) reported in the second series. The subtypes of HD included 16 cases of mixed cellularity, 13 cases of nodular sclerosis, 6 cases of lymphocyte depletion, and 1 case of lymphocyte predominance. According to the Working Formulation, the 389 NHL cases included low grade (14.1%), intermediate grade (57.3%), high grade (11.3%), and miscellaneous groups (17.2%). They were classified as small lymphocytic (9.5%), follicular (11.1%), diffuse (50.9%), immunoblastic (4.1%), small noncleaved (4.4%), lymphoblastic (2.8%), anaplastic large cell (9.0%), mycosis fungoides (1.8%), hairy cell leukemia (0.3%), true histiocytic (0.5%), and extramedullary plasmacytoma (1.0%). The immunophenotypes of the 359 NHL cases available for paraffin section-immunoperoxidase studies were B-cell (71.0%), T-cell (24.5%), histiocyte (0.6%), and undetermined phenotypes (3.9%). CONCLUSIONS. The incidence of malignant lymphoma is increasing in Thailand, with a high frequency of intermediate to high grade NHL of B-cell phenotype reported.Publication Metadata only National survey of patients with hemophilia and other congenital bleeding disorders in Thailand(2004-06-01) Ampaiwan Chuansumrit; Chularatana Mahasandana; Yingyong Chinthammitr; Boonchu Pongtanakul; Vichai Laosombat; Weerasak Nawarawong; Yuchinda Lektakul; Somporn Wangruangsatid; Ladda Sriboriboonsin; Ponlapat Rojnakarin; Pantep Angchaisuksiri; Theera Ruchutrakool; Malai Wongchanchailert; Pattra Thanarattanakorn; Issarang Nuchprayoon; Panya Seksarn; Arunee Jetsrisuparb; Chittima Sirijirachai; Triroj Krutvecho; Roongroj Pimchaipong; Patcharat Kittiwattanawan; Yuthasak Osodthanakarn; Apichat Apiwattanaporn; Nittaya Visanuyothin; Piyapan Ruthirago; Kulthida Sawatdee; Songchat Siriyothinphan; Pempak Sornchai; Saroj Suntayakorn; Sombat Navarattara; Suebsuk Sirithorn; Sutin Krongapiradee; Suwapee Buranawanich; Wanpen Sataworrawong; Mahidol University; Prince of Songkla University; Chiang Mai University; Sappasitthiprasong Hospital; Buddhachinaraj Hospital; Lampang Hospital; Chulalongkorn University; Khon Kaen Regional Hospital; Khon Kaen University; Phramongkutklao College of Medicine; Udon Thani Center Hospital; Buriram Hospital; Uttaradit Hospital; Maharaj Nakhon Ratchasima Hospital; Trang Hospital; Nakhon Nayok Hospital; Prachuap Khiri Khan Hospital; Nakhonping Hospital; Prapokklao Hospital; Bhumipol Adulyadej Hospital; Pranakornsiayutthaya Hospital; Paholpolayuhasena Hospital; Chonburi Regional HospitalA national survey of patients with hemophilia and other congenital bleeding disorders in Thailand was conducted in the years 2000 to 2002. Questionnaires were sent to physicians working at hospitals throughout the country. Although the overall response rate to the questionnaires was 19%, the two highest rates of 80% and 73.7% were found at university and regional hospitals, respectively, where most of the patients received their diagnosis and treatment. A total of 1,450 patients comprised of hemophilia 1,325 cases, von Willebrand disease, 69 cases, congenital factor VII deficiency, 15 cases, hereditary platelet dysfunction, 22 cases, and undefined causes of congenital bleeding disorders, 19 cases. Most were pediatric patients <15 years of age. Treatment was mainly given on demand for a bleeding episode, while only 8.6% received additional home treatment for early bleeding episodes. Replacement therapy primarily relied on fresh frozen plasma, cryoprecipitate and cryo-removed plasma. Factor concentrate was seldom used because of the high price. As a result, hemophilia care services in Thailand should be strengthened by providing comprehensive education for medical personnel, making available simple laboratory kits to determine hemophilia A and B, ensuring an adequate supply of blood components and affordable factor concentrate, and establishing home care treatment.Publication Metadata only Neonatal purpura fulminans associated with homozygous protein S deficiency(1990-01-06) Chularatana Mahasandana; Vinai Suvatte; Richard A. Marlar; Marilyn J. Manco-Johnson; Linda J. Jacobson; William E. Hathaway; Mahidol University; University of Colorado School of MedicinePublication Metadata only A novel Asn344 deletion in the core domain of coagulation factor XIII a subunit: Its effects on protein structure and function(1998-07-15) Sasichai Kangsadalampai; Gareth Chelvanayagam; Rohan T. Baker; Pa Thai Yenchitsomanus; Parichat Pung-amritt; Chularatana Mahasandana; Philip G. Board; Australian National University; Mahidol UniversityIn this study a previously undescribed 3 bp deletion, AAT1030-1032, in the factor XIII A subunit gene, has been detected in a Thai patient. The inframe deletion results in the translation of a factor XIII A subunit that lacks Asn344. This is the first inframe deletion to be identified in the factor XIII A subunit gene because six previously reported deletions have all caused frameshifts. The deletion has been introduced into a factor XIII A subunit cDNA and the deleted polypeptide expressed in yeast. The mRNA encoding the mutant enzyme appears to have normal stability but the translated protein is subject to premature degradation. In addition, the mutated enzyme exhibited very little transglutaminase activity compared with the wild-type enzyme. Structural modeling of the deleted enzyme suggests that the absence of Asn344 would have a potent impact on the catalytic activity by reorienting the residues associated with the catalytic center. Thus, the Asn344 deletion strongly confirms the significance of the residues surrounding the catalytic center of the factor XIII A subunit.Publication Metadata only Pyruvate kinase deficiency in an alpha-thalassemia family: First case report in Thailand(1997-12-01) Voravarn S. Tanphaichitr; Vinai Suvatte; Chularatana Mahasandana; Gavivann Veerakul; Parichat Pung-amritt; Kalya Tachavanich; Hiroshi Ideguchi; Mahidol University; Fukuoka University; Faculty of Medicine, Siriraj Hospital, Mahidol UniversityIn Thailand, the most common cause of chronic hemolytic anemia is thalassemia hemoglobinopathy. We report here a 10-year-old girl with pyruvate kinase. (PK) deficiency who was initially diagnosed to have Hb H disease, like her sister. The patient had a history of neonatal jaundice which required blood exchange transfusion twice and phototherapy. She became anemic and regular blood transfusion was required since the age of 2 1/2 months. She was very anemic compared to her sister and was transfusion dependent. Besides, she never had red cell inclusion bodies, thus re-evaluation was performed The diagnosis of red cell pyruvate kinase deficiency and the exclusion of Hb H disease was achieved after cessation of blood transfusion for 3 months The family study also confirmed the diagnosis. The patient is now on high transfusion and iron chelation. She is doing well with mild splenomegaly.Publication Metadata only Successful prophylaxis of intracranial hemorrhage in infants with severe congenital factor VII deficiency(2000-12-01) Suthida Kankirawatana; Chularatana Mahasandana; Gavivann Veerakul; Julin Seeloem; Lerlugsn Suwantol; Voravan Tanphaichitr; Vinai Suvatte; Mahidol UniversityDuring the period 1984-1992. 2 severe cases (1 male, 1 female) of congenital F VII deficiency with intracranial hemorrhage (ICH) were referred to the Department of Pediatrics, Siriraj Hospital Bangkok, Thailand at the ages of 1 and 3 months old. They both responded very well to fresh frozen plasma (FFP) transfusion therapy. Subsequently, both had repeated episodes of ICH (repeated ICH) 5 and 6 times, despite the 10-14 days of replacement therapy for each episode and eventually died at the ages of 11 and 13 months. Since September 1996, another 2 severe cases (2 females) of congenital F VII deficiency who had ICH within their first month of life were referred to us. In order to prevent repeated ICH, we started a prophylactic regime after the second episode of ICH, by giving FFP 10 ml/kg twice a week. The average duration of follow up was 21 months (at 8 and 34 months). All of them (aged 14, and 38 months old) are doing well at this time and free from repeated ICH. From this observation, if there is FFP available, this regime is an effective way to prevent repeated ICH in infants with severe congenital Factor VII deficiency.Publication Metadata only Thrombotic complications during induction chemotherapy of acute childhood lymphoblastic leukemia(2002-08-01) Suthida Kankirawatana; Kleebsabai Sanpakit; Patraporn Akkabutr; Chularatana Mahasandana; Gavivann Veerakul; Voravarn S. Tanphaichitr; Lerlugsn Suwantol; Mahidol UniversityThe incidence of thrombosis during induction chemotherapy of acute childhood lymphoblastic leukemia (ALL) patients was 6 found to be in 105 (5.7%). There were 4 cerebral infarctions, 1 superior vena cava (SVC) obstruction and I deep vein thrombosis. Among these, 2 of them died. A prospective study was further conducted of the change in coagulation and anticoagulation factors during 6 weeks of induction chemotherapy. It was found that the activated partial thromboplastin time (aPTT) was within normal range in all cases throughout 6 weeks, while prothrombin time (PT) and thrombin time (TT) were slightly prolonged, especially during the first 3 weeks of this phase. The natural anticoagulant panels which included protein C (PC), protein S (PS) and antithrombin III (AT III) and also fibrinogen level, were lower during the first 3 weeks and reached its nadir during the second and third week. The lower level of natural anticoagulants might be an important predisposing factor for the occurrence of thrombosis in these patients.