Intermittent heparin infusion in children with ischemic heart disease caused by Kawasaki disease.

We determined change in serum hepatocyte growth factor (HGF), one of the most potent angiogenic factors, after intravenous infusion of heparin in children and reported successful improvement of cardiac ischemia after regular intravenous heparin infusion in an infant with ischemic heart disease (IHD) caused by Kawasaki disease (KD). Intravenous infusion of 50 units/kg of heparin significantly increased serum HGF from 0.8+/-0.6 to 8.4+/-3.4 at 5 min, 8.3+/-2.5 at 30 min, and 4.9+/-1.5 ng/ml at 60 min, respectively. Subsequently, a 16-month-old infant with IHD caused by KD had received regular intravenous infusion of heparin, 100 IU/kg twice a day for 1 month and once a week for subsequent 2 months. With this treatment, his perfusion defect on myocardial scintigraphy disappeared. In conclusion, regular heparin infusion alone can improve myocardial ischemia caused by KD, probably due to facilitated production of HGF.

Myofibrosarcoma of the nasal bone.

Myofibrosarcoma is a recently recognized rare tumor that mainly occurs in adults. These tumors are composed of a collagenous stroma and pleomorphic stellate to spindle-shaped cells that resemble smooth muscle cells with eosinophilic cytoplasm and tapered nuclei. We present a case of myofibrosarcoma of the nasal bones in a 4-year-old girl who showed rapid enlargement of a painless glabellar swelling. Computed tomography and magnetic resonance imaging revealed an expanding solid mass with erosion of the surrounding nasal bones. After excision and histopathological examination, this tumor was identified as a myofibrosarcoma. This is the first report of such a tumor localized to the glabellar region. This case report contributes to better awareness of an extremely rare type of glabellar lesion in children.

Case of B-cell lymphoma with rearrangement of the BCL1, BCL2, BCL6, and c-MYC genes.

We managed a peculiar case of lymphoma showing immunohistochemical overexpression of cyclin D1. At initial examination the patient had meningeal lymphomatosis and general lymphadenopathy. Histologic examination of biopsy specimens of inguinal lymph nodes showed tumor cells and vague nodular growth resembling lymphoblasts. The results of flow cytometric analysis were positive for CD10, CD20, CD103, and immunoglobulin G (IgG) and Ig kappa and were negative for CD5, CD23, and terminal deoxynucleotidyl transferase activity. Results of immunohistochemical analysis of paraffin-embedded specimens were positive for cyclin D1 and Bcl2 in the tumor cells. Sixty percent of tumor cells had positive results for MIB1/Ki67. Cytogenetic and molecular studies revealed tumor cells simultaneously had t(14;18)(q32;q21), t(11;22)(q13;q11), t(8;14)(q24;q32), and t(3;14)(q27;q32) with the rearrangement of BCL1, BCL2, BCL6, and c-MYC genes. Lymphadenopathy showed a quick and complete response to doxorubicin-containing systemic chemotherapy with rituximab, but the central nervous system disease progressed and killed the patient.

[The monitoring of residual disease for chronic myelogenous leukemia patients treated with imatinib mesylate: detection of T315I mutation in ATP binding site of BCR/ABL gene].

Imatinib Mesylate, a specific inhibitor of BCR/ABL tyrosine kinase, was developed as a molecularly targeted drug for the treatment of patients with chronic myelogenous leukemia. We evaluated effectiveness of the drug on cytogenetic response for monitoring residual disease using fluorescence in situ hybridization(FISH), reverse transcription-nested-polymerase chain reaction(RT-nested-PCR) and competitive PCR strategy. Of 9 patients in chronic phase, 7 achieved major cytogenetic response(CR) and 2 achieved minor CR by FISH. In 3 out of 6 patients with complete CR, no BCR/ABL gene was detected by RT-nested-PCR in peripheral blood or bone marrow specimens. Of 4 patients in accelerated phase, 1 achieved complete CR but 3 developed blast crisis. Despite high efficacy of Imatinib, 5 out of 13 patients showed resistance to the drug. To clarify the mechanism of resistance, we have newly developed a method for investigating a point mutation of T315I in tyrosine kinase domain of BCR/ABL gene using RT-PCR restriction digested analysis. None of them showed T315I mutation. The sensitivity of the method was as low as 10 copies of mutant gene. The method is useful for screening the mutation when there are many clinical samples or low copy number of BCR/ABL gene. BCR/ABL value obtained by FISH was of use to predict cytogenetic response when residual disease was above 2 to 3%. Below this level, the routine use of RT-nested-PCR was suffices to monitor minimal residual disease.

A case of acute myeloid leukemia with t(7;11)(p15;p15) mimicking myeloid crisis of chronic myelogenous leukemia.

The chromosome aberration t(7;11)(p15;p15) is uncommon but recurrent in leukemia. We experienced a case of acute leukemia with t(7;11)(p15;p15), the hematological appearance of which mimicked myeloid crisis in chronic myeloid leukemia (CML). This case showed splenomegaly, a decreased neutrophil alkaline phosphatase (NAP) score, increased vitamin B12 value, and cells at all stages of neutrophilic maturation in both bone marrow and peripheral blood. We initially had difficulty differentiating acute myeloid leukemia (AML) M2 with marked myeloid differentiation from myeloid crisis of Philadelphia chromosome (Ph)-negative CML. Immature myeloid cells in the peripheral blood disappeared and cytogenetic analysis indicated that marrow cells changed to the normal karyotype after remission induction therapy. Therefore, this case was thought not to be myeloid crisis but AML M2 subtype. The NUP98/HOXA9 fusion transcript was detected by reverse transcription-polymerase chain reaction (RT-PCR) at exon A but not exon B of NUP98.