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Biomedical subjects

S Issaragrisil

Publications and source records attributed to S Issaragrisil.

At least 19 recordsLinked to original sources
PubMed2001

Clinical paroxysmal nocturnal hemoglobinuria is the result of expansion of glycosyl-phosphatidyl-inositol-anchored protein-deficient clone in the condition of deficient hematopoiesis.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, clonal hematopoietic stem cell disorder in which PIG-A, gene essential for the biosynthesis of the glycosyl-phosphatidyl-inositol (GPI) anchor, is somatically mutated. Absence of GPI-linked proteins from the surface of blood cells is characteristic of the PIG-A mutant (PNH) clone and is also accountable fo certain manifestations, such as intravascular hemolysis. It is unclear how the PNH clone expands and comes to dominate hematopoiesis. In this study, CD34+ cells--committed progenitors (colony-forming cells) representing immature hematopoietic stem cells--and reticulocytes representing the differentiated erythroid cells were quantitated in peripheral blood of patients with PNH. Compared with normal controls (n = 29), CD34+ cell levels were significantly lower in PNH patients who did not have preexisting aplastic anemia (AA) (n = 12) (2.47+/-1.23 versus 4.68+/-1.05 x 106/L, mean +/- standard error; P = .022). PNH patients with precedent aplastic anemia (AA+/PNH) showed markedly low CD34+ cell levels compared with normal control subjects (0.6+/-0.29 versus 4.68+/-1.05 x 10(6)/L; P = .0001). In addition, colony-forming cells from PNH patients were significantly decreased compared with those from normal volunteers (erythroid burst-forming units, 2.8+/-1.2 versu 25.6+/-6.2/5 x 10(5) mononuclear cells; P = .0006; and granulocyte/macrophage colony-forming units, 1.2+/-0.5 versus 13.3+/-3.0/ 5 x 10(5) mononuclear cells; P = .0006). These findings occur in both aplastic and hemolytic types of PNH, suggesting hematopoietic failure in PNH. On the contrary, the numbers of reticulocytes and the reticulocyte production index of PNH patients were significantly higher than those of normal persons and comparable to those from patients with autoimmune hemolytic anemia, indicating accelerating erythropoiesis in PNH. The degree of reticulocytosis correlated well with the proportion of CD59- (PNH) reticulocytes. All of the findings suggest that in the condition of deficient hematopoiesis, the PNH clone arising from the mutated hematopoietic stem cell expands and maintains a substantial proportion of the patient's hematopoiesis.

Adult↗
PubMed2001

Major hematologic diseases in the developing world- new aspects of diagnosis and management of thalassemia, malarial anemia, and acute leukemia.

The three presentations in this session encompass clinical, pathophysiological and therapeutic aspects of hematologic diseases which impact most heavily on developing world countries. Dr. Victor Gordeuk discusses new insights regarding the multi-faceted pathogenesis of anemia in the complicated malaria occurring in Africa. He describes recent investigations indicating the possible contribution of immune dysregulation to this serious complication and the implications of these findings for disease management. Dr. Surapol Issaragrisil and colleagues describe epidemiologic and clinical characteristics of the thalassemic syndromes. In addition to being considered a major health problem in Southeast Asia, the migration throughout the world of people from this region has caused the disease to have global impact. A unique thalassemia variant, Hb Ebeta-thalassemia, with distinctive clinical features, has particular relevance for this demographic issue. Special focus will be reported regarding recent prenatal molecular screening methods in Thailand which have proven useful for early disease detection and disease control strategies. Dr. Raul Ribeiro describes a clinical model for providing effective treatment for a complex malignancy (childhood acute lymphoblastic leukemia) in countries with limited resources. With the multidisciplinary approach in Central American of the joint venture between St. Jude Children's Research Hospital International Outreach Program and indigenous health care personnel, major therapeutic advances for this disease have been achieved. Given the major demographic population shifts occurring worldwide, these illnesses also have important clinical implications globally. These contributions demonstrate that lessons learned within countries of disease prevalence aid our understanding and management of a number of disorders prominently seen in developed countries. They will show how effective partnerships between hematologists in more and less developed nations may work together to produce important advances for treating major hematologic diseases in less developed regions. A major focus relates to the socio-economic and medical burden of these diseases in developing countries with limited resources. As such, these problems provide a challenge and an opportunity for collaborative interaction between hematologists and policy makers worldwide.

Acute Disease↗
PubMed2000

Immunophenotypic discrepancies between granulocytic and erythroid lineages in peripheral blood of patients with paroxysmal nocturnal haemoglobinuria.

In paroxysmal nocturnal haemoglobinuria (PNH), somatic mutation of the PIG-A gene is thought to result in altered expression of glycosylphosphatidylinositol (GPI)-anchored proteins. This study was performed to determine if there were any heterogeneities of cellular phenotypes between two major peripheral blood cells, erythrocytes and granulocytes. Using CD59-based immunocytometry, the patterns of CD59 expression were shown to be conserved in the circulating erythroid cells (reticulocytes and mature erythrocytes) in all 29 patients with PNH. Twenty-one patients had distinct combinations of PNH type I, II, and III cells in different lineages. Only eight patients exhibited similar patterns of CD59 expression between the two lineages. Approximately one third of the patients had PNH type II cells in either or both of the two lineages indicating variable lineage involvement. The proportion of abnormal granulocytes was higher than those of abnormal reticulocytes and erythrocytes. In patients with appropriate erythropoietic responses to haemolysis (RPI > 2.0), shift reticulocytes display predominantly PNH phenotypes. These immature erythroid cells with altered expression of GPI-anchored proteins may dominate the peripheral blood during periods of increased marrow activity resulting in greater phenotypic mosaicism in such patients. Discrepancies in expression of GPI-anchored proteins in PNH which are highly variable between the two lineages may be the result of their different life spans and the influence of complement-mediated cytolysis. The phenomena also indicated the possible occurrence of more than one PNH clones with variable clonal dominance.

Adolescent↗
PubMed2000

Successful bone marrow transplantation in a child with red blood cell pyruvate kinase deficiency.

We report the first successful use of BMT for the treatment of RBC pyruvate kinase (PK) deficiency in a boy who developed neonatal jaundice and severe transfusion-dependent hemolytic anemia a few months after birth. He received a BMT at the age of 5 from an HLA-identical sister who has normal PK activity after conditioning with busulfan and cyclophosphamide. The post-transplant course was uneventful. At present, 3 years after transplant, he is 8 years old and has a normal hemoglobin level and normal RBC PK activity without evidence of hemolysis. DNA analysis has confirmed full engraftment.

Anemia, Hemolytic↗
PubMed2000

Purification of human hemopoietic stem cells for transplantation in Thailand.

Stem cell transplantation (SCT) has become the therapy of choice for many hematologic and immunologic disorders. At present, only 25% of patients have suitable HLA-identical donors. In an attempt to increase the donor pool for SCT in Thailand and Southeast Asia, we developed a program whereby parents and mismatched siblings can be used as donors. In this preliminary study, after granulocyte-colony-stimulating factor (G-CSF) was given to adult donors, peripheral blood stem cells (PBSC) were collected and CD34+ cells purified using a CliniMACS immunomagnetic device (Miltenyi Biotec, Germany). In seven experiments, purified CD34+ cells could be obtained from G-CSF-stimulated PBSC in large numbers (1.71 +/- 0.19 x 10(8)), with high purity (93 +/- 2.4%) and excellent recovery (64.28% - 85.62%). Immune reactive T and NK cells were adequately depleted to less than 0.2%. The purification procedure can be completed within 3 hours. In conclusion, a clinical stem cell purification program using this novel device is now established in Thailand and for the first time in Southeast Asia. This should allow further development of advanced SCT therapy including haploidentical and mismatched CD34+ SCT for patients' lacking HLA-identical donors in this region.

Adult↗
PubMed2000

TT virus infection in Thailand: prevalence in blood donors and patients with aplastic anemia.

Aplastic anemia has been reported to occur after viral hepatitis of unknown etiology. Recently, TT virus (TTV), a novel DNA virus, was identified in a Japanese patient with posttransfusion non-A-E hepatitis. The prevalence of TTV infection was investigated among blood donors and patients with aplastic anemia in Thailand. Of 99 blood samples from blood donors, 37 tested positive for TTV DNA via semi-nested polymerase chain reaction (PCR) using TTV-specific primers. Seventeen percent of samples from blood donors younger than 20 were positive for TTV DNA, whereas 48% from donors older than 20 were positive. The high prevalence of TTV infection in Thailand is comparable to that reported in China (28%), Mongolia (43%), and Egypt (29%). Forty-two percent of newly diagnosed aplastic anemia patients tested also had TTV DNA in blood. The detection rate of TTV DNA in aplastic anemia patients does not differ significantly from rates in normal blood donors. Our present data thus argue against the role of this novel hepatitis-associated virus in the pathogenesis of aplastic anemia in Thailand. However, larger epidemiological studies may be needed to further evaluate their association.

Adult↗
PubMed1999

Regional patterns in the incidence of aplastic anemia in Thailand. The Aplastic Anemia Study Group.

The annual incidence of aplastic anemia has been determined in a rigorous and standardized epidemiologic study conducted in Thailand. A total of 374 cases were identified over a period of 3-6 years in three geographically defined and distinct regions of the country; Bangkok, Khonkaen in the northeast, and Songkla in the south. The incidence was 3.9 cases per million persons in Bangkok, 3.0 per million in Songkla, and 5.0 per million in Khonkaen. These rates are as high or higher than in any region of Europe or Israel as reported in the International Agranulocytosis and Aplastic Anemia Study, in which the methods and case definition were the same. Rates were stable over the course of the study. There were marked differences in incidence between northern and southern rural regions of Thailand, and among Bangkok suburbs. These differences, together with an unusual peak in the incidence among young people in Bangkok, suggest the possibility of occupational and environmental factors in the etiology of aplastic anemia.

Adolescent↗
PubMed1999

Agranulocytosis in Bangkok, Thailand: a predominantly drug-induced disease with an unusually low incidence. Aplastic Anemia Study Group.

Agranulocytosis, a syndrome characterized by a marked reduction in circulating granulocytes, is strongly associated with medical drug use in Europe and the United States. Unregulated use of common pharmaceutical agents in developing countries has been suspected of causing large numbers of cases of agranulocytosis and deaths, especially among children. To elucidate the incidence and etiology of agranulocytosis in Thailand, a population-based case-control study of symptomatic agranulocytosis that resulted in hospital admission was conducted in Bangkok from 1990 to 1994. An attempt was also made to study the disease in Khonkaen (in northeastern Thailand) and Songkla (in southern Thailand), but there were insufficient cases in the latter regions, and the analysis was confined to subjects from Bangkok. In that region, the overall incidence of agranulocytosis was 0.8 per million per year; there were no deaths. As expected, the incidence was higher in females (0.9 per million), and it increased with age (4.3 per million beyond age 60). Among 25 cases and 529 controls the relative risk estimate for a combined category of all suspect drugs was 9.2 (95% confidence interval = 3.9-21), and the proportion of cases that could be attributed to drug use was 68%. For individual drugs and drug classes the data were sparse; within these limitations, the strongest association appeared to be with antithyroid drugs. One case and three controls were exposed to dipyrone, a drug known to cause agranulocytosis; with such scanty data the risk could not be evaluated. Exposure to pesticides or solvents was not associated with an increased risk. This is the first formal epidemiologic study of agranulocytosis in a developing country. As in the West, most cases are attributable to medical drug use. However, the incidence of agranulocytosis in Bangkok, and apparently, in Thailand as a whole, is unusually low, and the disease does not pose a public health risk.

Adolescent↗
PubMed1999

Epidemiology of aplastic anemia in Thailand. Thai Aplastic Anemia Study Group.

A population-based case-control study of aplastic anemia has been conducted in Thailand since 1989. This is the largest single epidemiologic study of aplastic anemia ever performed. The objectives have been to document the incidence of the disease and to study the etiologic factors in a case-control analysis. The overall incidence of aplastic anemia was 3.9 per million per year in Bangkok, two times higher than in the West; 3.0 per million in Songkla; and 5.0 per million in Khonkaen. A difference appears in the age incidence pattern between Bangkok and the two rural areas, with double incidence peaks at ages 15 to 24 and over 60 in Bangkok, yet a more steady increase in incidence with increasing age in the rural areas. With regard to possible etiologic factors, there is a strong inverse association between incidence of the disease and socioeconomic status as determined by total household income and years of education. There are also significant positive associations with occupational exposure to solvents and agricultural pesticides. Only a few drugs, including thiazide diuretics, sulfonamide, and mebendazole are associated with the disease. There continues to be no evidence of association with chloramphenicol. The etiologic fraction for all associated drugs is lower than 5%. Household pesticide use is not associated with the disease. Exposure to hepatitis A virus is a risk indicator for aplastic anemia and may be a surrogate marker for another enteric infectious agent.

Adolescent↗
PubMed1998

Hematopoietic progenitor cells in the blood and bone marrow in various hematologic disorders.

Hematopoietic progenitor cells are present in the blood and the bone marrow. Changes in the numbers of hematopoietic progenitor cells reflect alteration of pluripotent stem cells. We discuss such changes in common hematologic diseases including aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH) and thalassemia. In aplastic anemia, the numbers of burst forming units-erythroid (BFU-E) and colony-forming units-granulocyte-macrophage (CFU-GM) are much decreased; the decrease still exists after recovery from therapy. In PNH, the numbers of progenitor cells are low, even in the presence of marrow hypercellularity. In thalassemia, the numbers of progenitor cells are much increased; more pronounced in splenectomized patients.

Anemia, Aplastic↗
PubMed1998

Bone marrow, peripheral blood and cord blood stem cell transplantation in children: ten years' experience at Siriraj Hospital.

Stem cell transplantations were performed in 69 children at Siriraj Hospital over a ten year period. The source of stem cells was bone marrow (60), peripheral blood (3), or cord blood (6). The diseases treated included 35 thalassemias, 11 Burkitt's lymphoma, five non-Hodgkin's lymphoma, five aplastic anemia, eight acute leukemia, and one each of neuroblastoma, severe combined immunodeficiency, Wiskott-Aldrich syndrome, myelodysplastic syndrome, and pyruvate kinase deficiency. The success rate of stem cell transplantation in Thai children varied according to the underlying diseases of the patients, ranging from 50% in acute leukemia to 100% in aplastic anemia. The outcome of stem cell transplantation in 35 thalassemic children revealed 23 (79.4%) were cured, whereas three (10.3%) remain alive with disease and the other three (10.3%) died. The incidence of graft-versus-host disease was low hen compared with that of Western countries. It is concluded that bone marrow, peripheral blood and cord blood stem cell transplantation will be the treatment of choice and will be widely used in the future to cure many hematologic and malignant disorders in children.

Adolescent↗
PubMed1997

Low drug attributability of aplastic anemia in Thailand. The Aplastic Anemia Study Group.

From 1989 to 1994, a population-based, case-control study of aplastic anemia was conducted in Thailand, including the regions of Bangkok, Khonkaen in the northeast, and Songkla in the south. An annual incidence in Bangkok of 3.7 cases per million population, about twice as high as in Western countries, has been reported. To evaluate the etiologic role of drugs, 253 subjects were compared with 1,174 hospital controls. With multivariate adjustment for confounding, a significant association was identified for exposure 2 to 6 months before admission to thiazide diuretics (relative risk estimate 7.7; 1.5 to 40). There were crude associations with sulfonamides (relative risk estimate, 7.9; P = 0.004) and mebendazole (6.3; P = 0.03) (there were insufficient data for multivariate adjustment). Excess risks for the three drugs were in the range of 9 to 12 cases per million users. There was no significant association with chloramphenicol, although the multivariate relative-risk estimate was elevated (2.7; 0.7 to 10). Other drugs that have been reported to increase the risk of aplastic anemia, such as nonsteroidal anti-inflammatory drugs and anticonvulsants, were not commonly used. There were no associations with commonly used drugs, including benzodiazepines, antihistamines, oral contraceptives, and herbal preparations. For all associated drugs, the overall etiologic fraction (the proportion of cases attributable to an exposure) was 5%, compared with 25% in Europe and Israel. Drugs are uncommon causes of aplastic anemia in Thailand, and their use does not explain the relatively high incidence of the disease in that country.

Adolescent↗
PubMed1997

Association of seropositivity for hepatitis viruses and aplastic anemia in Thailand.

Aplastic anemia is more common in the Orient than in western countries, with an incidence in Thailand that is 2- to 3-fold higher than in Europe. Aplastic anemia after hepatitis is a well characterized clinical entity, and clinical hepatitis is also prevalent in the Far East. We performed a prospective case-control study to determine risk factors for aplastic anemia in Bangkok and two rural regions during 1989 to 1994. A total of 375 cases were identified, along with 1,174 hospital controls matched for age and sex. Historical data were collected by trained interviewers. Sera from a subset of cases (N = 177) and controls (N = 183) were tested for antibodies to hepatitis viruses A, B, and C and hepatitis B surface antigen. There was no evidence of association of aplastic anemia with hepatitis B or hepatitis C. Previous exposure to hepatitis A, as determined by immunoglobulin G (IgG) seropositivity, was significantly associated with aplastic anemia: the relative risk adjusted for confounding was 2.9 (95% confidence interval 1.2-6.7). The same association also existed for persons under age 25 years, in whom the prevalence of hepatitis A IgG was lower than in the total population. However, no patients showed evidence of recent infection with hepatitis A (immunoglobulin M [IgM] seropositivity). These results indicate that exposure to a hepatitis virus is a risk indicator for aplastic anemia in Thailand, and while itself unlikely to be etiologic, hepatitis A may be a surrogate marker for another enteric microbial agent.

Adult↗
PubMed1997

Use of household pesticides and the risk of aplastic anaemia in Thailand. The Aplastic Anemia Study Group.

BACKGROUND: Aplastic anaemia is a severe blood dyscrasia that is more common in Thailand than in Western countries. Its a etiology remains poorly understood. METHODS: A case-control study was conducted in Bangkok and two rural regions of Thailand. The effect of household pesticides was evaluated among 253 incident cases of aplastic anaemia and 1174 hospital controls. RESULTS: A total of 54% of the cases and 61% of the controls were exposed 1-6 months previously. For most individual household pesticides and for groups classified according to chemical type (organophosphates, pyrethrins, and organochlorines), the relative risk (RR) estimates approximated 1.0; upper 95% confidence limits were below 2.0 for many comparisons. A significant association was observed for exposure to combination products containing dichlorvos and propoxur, with an overall RR estimate of 1.7 (95% confidence interval [CI]: 1.1-2.6); the estimate for regular use was 1.6 (95% CI: 0.9-2.9). CONCLUSIONS: The absence of a higher risk for the regular use of dichlorvos/propoxur reduces the credibility of the apparent association, which could well have been an artefact of multiple comparisons. We conclude that most household pesticides used in Thailand do not appear to increase the risk of aplastic anaemia.

Adult↗
PubMed1997

Aplastic anemia in rural Thailand: its association with grain farming and agricultural pesticide exposure. Aplastic Anemia Study Group.

OBJECTIVES: A population-based case-control study was conducted to elucidate the incidence and etiology of aplastic anemia in Thailand. METHODS: Case patients and hospital control patients were enrolled in three regions from 1989 to 1994; data were collected by interview. RESULTS: Forty-six percent of 81 case patients and 19% of 295 control patients from Khonkaen were grain farmers (estimated relative risk [RR] = 2.7, 95% confidence interval [CI] = 1.4, 5.2). Sixteen percent of case patients and 6% of control patients used agricultural pesticides (estimated RR = 2.7, 95% CI = 1.1, 6.6). The association with grain farming remained among those not exposed to pesticides. In Songkla, 16% of 43 case patients and 2% of 181 control patients were grain farmers (crude RR estimate = 11, 95% CI = 3.4, 35). CONCLUSIONS: The relation of aplastic anemia to grain farming may partly explain the high incidence of aplastic anemia in Thailand.

Adult↗
PubMed1996

Drugs in the aetiology of agranulocytosis and aplastic anaemia.

Agranulocytosis and aplastic anaemia are rare but serious conditions known to be caused by numerous drugs. Most of what is known or suspected about the aetiology is based on case reports, with only a few formal epidemiological studies that provide quantitative estimates of risk. Updated results have been obtained from a combined analysis of data from 3 case-control studies that used similar methods: the International Agranulocytosis and Aplastic Anemia Study (IAAAS), conducted in Israel and Europe; a study conducted in the northeast US; and a study conducted in Thailand. Totals of 362 cases of agranulocytosis, 454 cases of aplastic anaemia and 6458 controls were included in the analyses. The IAAAS and Thai study were population-based, providing estimates of the incidence of the 2 dyscrasias. The overall annual incidence of agranulocytosis in the ambulatory population was 3.4/10(6) in the IAAAS and 0.8/10(6) in Thailand; by contrast the incidence of aplastic anaemia was 2.0/10(6) in the IAAAS and 4.1/10(6) in Thailand. A total of 21 compounds were significantly associated with an increased risk of agranulocytosis in the IAAAS and US studies. Excess risks ranged from 0.06 to 13 cases/10(6) users/wk; the most strongly associated drugs were procainamide, anti-thyroid drugs and sulphasalazine. An association with drugs that had previously been suspected was also seen in Thailand. The overall aetiologic fractions of agranulocytosis due to drug use were 62% in the IAAAS, 72% in the US and 70% in Thailand. Eleven drugs were significantly associated with an increased risk of aplastic anaemia, with excess risks ranging from 1.4 to 60 cases/10(6) users in a 5-month period. The most strongly associated drugs were penicillamine, gold and carbamazepine. Aetiologic fractions were 27% in the IAAAS, 17% in the US and 2% in Thailand, which paralleled the prevalence of use of associated drugs in the 3 populations. The present results confirm that agranulocytosis is largely a drug-induced disease, with similar proportions accounted for in 3 disparate geographic regions. By contrast, although many of the expected associations were observed for aplastic anaemia, most of the aetiology is not explained by drugs. For all associated drugs, the excess risks are sufficiently low that blood dyscrasias should not figure prominently in the balancing of risks and benefits.

Agranulocytosis↗