ABSTRACT
BACKGROUND: The aims of our study were to evaluate (i) the relationship between cardiac T2* values and cardiac complications in Asian ß-thalassaemia major (TM) patients, and (ii) the association between cardiac T2* values and other parameters currently used to predict cardiac complications as a result of transfusion iron overload. METHODS: We examined the myocardial iron loads of 88 TM patients from Taiwan with cardiac T2* magnetic resonance imaging (MRI) and assessed the correlation between cardiac T2* values and serum ferritin levels, liver iron concentration and left ventricular ejection fraction (LVEF). We also determined the predictive value of these measurements for the development of arrhythmia. RESULTS AND CONCLUSION: In our group of Taiwanese patients, the relative risk for arrhythmia was 10·36 when cardiac T2* values were less than 10 ms (compared with ≥10 ms) and 1·98 when serum ferritin levels increased >2500 ng mL(-1) (compared with ≤2500 ng mL(-1) ). Serum ferritin levels correlated with cardiac T2* values in patients with abnormal myocardial iron loads (T2* < 20 ms, r = -0·48, P = 0·004, n = 34), but LVEF (measured by echocardiography) gave no indication of excess myocardial iron deposition (r = -0·07, P = 0·52) or of the risk of developing arrhythmia.
Subject(s)
Iron/metabolism , Myocardium/metabolism , beta-Thalassemia/metabolism , Adolescent , Adult , Arrhythmias, Cardiac/diagnostic imaging , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/metabolism , Chelation Therapy , Child , Female , Ferritins/blood , Humans , Magnetic Resonance Imaging , Male , Myocardium/pathology , Radiography , Risk Factors , Taiwan , beta-Thalassemia/complications , beta-Thalassemia/diagnostic imagingABSTRACT
To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid, Acute/therapy , Leukemia, Promyelocytic, Acute/therapy , Stem Cell Transplantation , Adolescent , Child , Child, Preschool , Disease-Free Survival , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Remission Induction , Taiwan , Treatment OutcomeABSTRACT
The clinical and biological features of acute myeloid leukemia (AML) with 11q23/MLL translocations are well known, but the characteristics of AML with partial tandem duplication of the MLL gene have not been explored comprehensively. In this study, MLL duplication was analyzed, in 81 AML patients without chromosomal abnormalities at 11q23, using Southern blotting, genomic DNA polymerase chain reaction (PCR), reverse-transcription PCR and complementary DNA sequencing. Nine patients showed partial tandem duplication of the MLL gene, including eight (12%) of the 68 with normal karyotype. Seven patients showed fusion of exon 6/exon 2 (e6/e2), one, combination of differentially spliced transcripts e7/e2 and e6/e2, and the remaining one, combination of e8/e2 and e7/e2. Among the patients with normal karyotype, children aged 1 to 15 showed a trend to higher frequency of MLL duplication than other patients (2/5 or 40% vs 6/62 or 10%, P = 0.102). The patients with tandem duplication of the MLL gene had a significantly higher incidence of CD11b expression on leukemic cells than did those without in the subgroup of patients with normal karyotype (75% vs 28%, P = 0.017). There were no significant differences in the expression of lymphoid antigens or other myeloid antigens between the two groups of patients. In adults, the patients with MLL duplication had a shorter median survival time than those without (4.5 months vs 12 months, P = 0.036). In conclusion, partial tandem duplication of the MLL gene is associated with increased expression of CD11b on leukemic blasts and implicates poor prognosis in adult AML patients. The higher frequency of MLL duplication in children older than 1 year, than in other age groups, needs to be confirmed by further studies.
Subject(s)
Chromosomes, Human, Pair 11/genetics , DNA-Binding Proteins/genetics , Gene Duplication , Leukemia, Myeloid/genetics , Proto-Oncogenes , Transcription Factors , Acute Disease , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Antigens, Neoplasm/analysis , Blotting, Southern , Child , Child, Preschool , Chromosomes, Human, Pair 11/ultrastructure , DNA, Complementary/genetics , Exons/genetics , Female , Histone-Lysine N-Methyltransferase , Humans , Infant , Karyotyping , Leukemia, Myeloid/classification , Leukemia, Myeloid/mortality , Life Tables , Male , Middle Aged , Myeloid-Lymphoid Leukemia Protein , Phenotype , Prognosis , RNA Splicing , Reverse Transcriptase Polymerase Chain Reaction , Survival Analysis , Treatment OutcomeABSTRACT
OBJECTIVE: To study the prevalence of and risk factors for abnormal glucose tolerance in transfusion-dependent beta-thalassemic patients. RESEARCH DESIGN AND METHODS: A total of 89 transfusion-dependent beta-thalassemic patients were interviewed. Diabetes was previously diagnosed in 14 of them. In the remaining 75 patients, 68 participated in an oral glucose tolerance test. Potential risk factors were identified using the independent t test, chi2 test, and Fisher's exact test. Logistic regression analysis was used to select the independent risk factors that best predicted abnormal glucose tolerance A two-tailed P value of <0.05 was considered to be statistically significant. RESULTS: The prevalence of impaired glucose tolerance was 8.5% (7 of 82) and that of diabetes was 19.5% (16 of 82). Presentation with diabetic ketoacidosis was 31.1% (5 of 16). The risk factors for abnormal glucose tolerance found in transfusion-dependent beta-thalassemic patients were serum ferritin concentration and hepatitis C infection. CONCLUSIONS: The interaction of iron overload and hepatitis C infection worsened the prognosis of thalassemic patients. Aggressive iron-chelation therapy as well as prevention and treatment of hepatitis C infection should be mandatory in managing glucose homeostasis in transfusion-dependent beta-thalassemic patients in Taiwan.
Subject(s)
Blood Transfusion , Glucose Intolerance/epidemiology , beta-Thalassemia/blood , beta-Thalassemia/therapy , Adolescent , Adult , Child , Diabetes Mellitus/epidemiology , Female , Ferritins/blood , Hepatitis B/epidemiology , Hepatitis C/epidemiology , Humans , Iron Chelating Agents/therapeutic use , Male , Patient Compliance , Prevalence , Risk Factors , Taiwan , beta-Thalassemia/complicationsABSTRACT
High-dose therapy followed by peripheral blood stem cell (PBSC) support was performed in 29 patients with primary high-risk (Group I) or chemoresponsive metastatic (Group II) breast cancer patients. Group I patients had received PBSC mobilization within 4 weeks of modified radical mastectomy. Group II patients had to achieve minimal residual disease (MRD) by induction chemotherapy before being considered eligible for PBSC mobilization and high-dose therapy. An innovative FE120C regimen (5-FU 600 mg/m2, i.v., day 1; epirubicin 120 mg/m2, i.v., day 1; cyclophosphamide 600 mg/m2, i.v., day 1) plus G-CSF (300 microg/day, subcutaneous injection for 9 days, from day 4 post-FE120C) was used to mobilize PBSCs. After high-dose CTCb (cyclophosphamide 6,000 mg/m2, thiothepa 500 mg/m2, carboplatin 800 mg/m2, in 4 days), patients received PBSC infusion and daily C-CSF 300 microg subcutaneous injection. There were 19 and 16 patients enrolled into Group I and Group II, respectively. Ten of the Group II patients had achieved minimal residual disease (MRD) after induction chemotherapy. The median numbers of mobilized total CD34 + cells for Group I and Group II patients were 27.3 (9.2 to 114.1) x 10(6)/kg and 17.1 (5.9 to 69.1) x 10(6)/kg respectively. The median time to neutrophil recovery (ANC > or = 500/microL) was 8 and 9 days in Group I and II, respectively. The median time to platelet recovery (> or = 50,000/microL) was 10 and 15 days in Group I and II, respectively. No major treatment-related toxicities were noted. In Group I, 13 out of 19 patients (68.4%; 43-87%, 95% C.I.) remained recurrence-free with a median follow-up of 31 months (6 + to 55 + months). In Group II, 3 out of 10 patients (30%; 7-65%, 95% C.I.) remained progression-free at 33 +, 35 +, 39 + months from induction therapy. We suggest that the FE120C plus G-CSF is an effective and innovative regimen for PBSC mobilization in breast cancer patients, and high-dose CTCb therapy with PBSC support is a safe and well-tolerated treatment modality.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/therapy , Granulocyte Colony-Stimulating Factor/therapeutic use , Adult , Breast Neoplasms/mortality , Clinical Protocols , Cyclophosphamide/administration & dosage , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Mastectomy, Modified Radical , Middle Aged , Radiotherapy, Adjuvant , Recurrence , Survival RateABSTRACT
We have identified a putative protein kinase gene from both Plasmodium falciparum cDNA and genomic DNA libraries. The nucleotide sequence contains an open-reading frame of 2646 bp, which codes for a predicted protein of 882 amino acid residues. Comparison of the predicted amino acid sequence with those in GenBank suggests that this gene codes for a protein similar to the mitogen-activated protein (MAP) kinase of other organisms. This MAP kinase-related protein, named PfMRP, contains the TDY dual phosphorylation site upstream of the highly conserved VATRWYRAPE sequence in subdomain VIII. PfMRP contains an unusually large and highly charged domain within its carboxyl-terminal segment, which includes two repetitive sequences of either a tetrapeptide or octapeptide motif. PfMRP gene is located on chromosome 14. Northern blot analysis of total RNA reveals the presence of a single mRNA transcript approximately 4.2 kb in length, which is predominantly expressed in gametocytes and gametes/zygotes.
Subject(s)
Calcium-Calmodulin-Dependent Protein Kinases/genetics , Plasmodium falciparum/enzymology , Plasmodium falciparum/genetics , Protozoan Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , DNA Primers/genetics , DNA, Complementary/genetics , DNA, Protozoan/genetics , Gene Expression Regulation, Developmental , Genes, Protozoan , Molecular Sequence Data , Plasmodium falciparum/growth & development , Sequence Homology, Amino AcidABSTRACT
Flame atomic absorption spectrophotometric methods were developed for the determination of zinc, copper, arsenic, iron and selenium in blood samples. Data from blackfoot disease patients in five clinical stages were compared with those from healthy controls. Copper concentrations were the same for all clinical stages. Arsenic increased in the initial three stages but decreased thereafter, although arsenic was previously considered to be the major causative agent of the disease. The decrease of arsenic in the later stages was attributed to the antagonistic effect of selenium, and the decrease of iron during the progress of the disease is thought to be due to the antagonistic effect of arsenic in the initial stages and the loose of haemoglobin in the later stages.
Subject(s)
Peripheral Vascular Diseases/metabolism , Trace Elements/blood , Aged , Arsenic/blood , Copper/blood , Female , Humans , Iron/blood , Male , Middle Aged , Peripheral Vascular Diseases/etiology , Selenium/blood , Spectrophotometry, Atomic/methods , Taiwan , Zinc/bloodABSTRACT
Dacryocystography has been widely used in the assessment of the nasolacrimal duct system, particularly in patients with epiphora. Our study was undertaken to evaluate image quality and level of patient discomfort during examinations with water-soluble contrast agents (iohexol [Omnipaque 240], iopamidol [Isovue 200 and 300], and 52.7% diatrizoate meglumine and 26.9% iodipamide meglumine [Sinografin]) compared with the iodized oil-based contrast agent Lipiodol. Fifty-five dacryocystograms were obtained from 41 consecutive patients. The procedure was performed first with a water-soluble contrast agent, then repeated with Lipiodol. A distention technique was used with conventional radiography. Patients were asked to evaluate their level of discomfort (none, mild, moderate, severe). The images were evaluated separately by two radiologists, blinded to which water-soluble agent was employed, and the images were graded on a five-point scale. Images obtained with Lipiodol were significantly better than those with other agents (P less than .02), and image quality deteriorated as iodine concentration decreased. Use of Isovue 300 and Sinografin produced significantly more patient discomfort (P less than .03) than the use of other agents. The authors conclude that, in most instances, Lipiodol is the contrast agent of choice with regard to both highest level of patient comfort and greatest conventional radiographic image quality among the agents compared.