Hyperuricemia in hematologic malignancies is caused by an insufficient urinary excretion.

In order to elucidate the mechanism of hyperuricemia in hematologic malignancies, we have retrospectively investigated the uric acid metabolism in 418 chemotherapy-naïve patients with hematologic malignancies. Hyperuricemia was present in 116 (27.8%) of these patients on initial hospitalization. Among 65 hyperuricemic patients analyzed uric acid metabolism, six (9.2%) had overproduction type, 52 (80.0%) had underexcretion type, and seven (10.8%) had a mixed type. Fourteen patients (3.3%) developed tumor lysis syndrome in 418 patients.

Colonic EBV-Associated Lymphoproliferative Disorder in a Patient Treated with Rabbit Antithymocyte Globulin for Aplastic Anemia.

Epstein-Barr-virus- (EBV-) associated lymphoproliferative disorder (LPD) after immunosuppressive therapy for aplastic anemia (AA), in a nontransplant setting, has not been well described. We report one case of colonic EBV-LPD after a single course of immunosuppressive therapy for AA. The patient developed multiple colonic tumors 3 months after receiving immunosuppressive therapy, which consisted of rabbit antithymocyte globulin (ATG), cyclosporine, and methyl-predonisolone. The histological findings of biopsy specimens revealed that atypical lymphocytes had infiltrated colonic glands. Immunohistochemical staining for CD20 was positive, and in situ hybridization for EBV-encoded small RNAs was also positive. The EBV viral load in peripheral blood was slightly increased to 140/10(6) white blood cells. After the cessation of immunosuppressant, the colonic tumors spontaneously regressed, and the EBV viral load decreased to undetectable levels. This is the first report of the single use of rabbit ATG inducing colonic EBV-LPD. Because a single use of immunosuppressive therapy containing rabbit ATG can cause EBV-LPD, we should carefully observe patients receiving rabbit ATG for AA.

Chronic Myelogenous Leukemia Cells Contribute to the Stromal Myofibroblasts in Leukemic NOD/SCID Mouse In Vivo.

We recently reported that chronic myelogenous leukemia (CML) cells converted into myofibroblasts to create a microenvironment for proliferation of CML cells in vitro. To analyze a biological contribution of CML-derived myofibroblasts in vivo, we observed the characters of leukemic nonobese diabetes/severe combined immunodeficiency (NOD/SCID) mouse. Bone marrow nonadherent mononuclear cells as well as human CD45-positive cells obtained from CML patients were injected to the irradiated NOD/SCID mice. When the chimeric BCR-ABL transcript was demonstrated in blood, human CML cells were detected in NOD/SCID murine bone marrow. And CML-derived myofibroblasts composed with the bone marrow-stroma, which produced significant amounts of human vascular endothelial growth factor A. When the parental CML cells were cultured with myofibroblasts separated from CML cell-engrafted NOD/SCID murine bone marrow, CML cells proliferated significantly. These observations indicate that CML cells make an adequate microenvironment for their own proliferation in vivo.

Markedly increased serum and urinary fructose concentrations in diabetic patients with ketoacidosis or ketosis.

To investigate fructose concentrations in diabetic patients with ketoacidosis or ketosis, serum fructose concentrations and daily urinary fructose excretion were measured in 23 patients with ketoacidosis (n = 16) and ketosis (n = 7) on the first day of admission. Seventeen patients were diagnosed with type 1, one patient with mitochondrial, and 4 patients with atypical diabetes. In 16 of the 23 patients, serum and urinary fructose could be assessed after starting treatments. Mean serum fructose concentration was 71.6 ± 108.1 µmol/l, and mean daily urinary fructose excretion was 352.1 ± 473.7 µmol/day. Serum fructose levels in patients with atypical diabetes were much higher (205.0 ± 213.3 µmol/l) than those in patients with type 1 diabetes (45.1 ± 44.5 µmol/l), while urinary fructose levels in atypical diabetes (249.7 ± 92.4 µmol/day) tended to be lower than those in type 1 diabetes (382.6 ± 533.2 µmol/day). Serum fructose concentrations decreased significantly (P < 0.05) from 88.1 ± 126.3 to 18.0 ± 11.0 µmol/l, and daily urinary fructose excretion also decreased significantly (P < 0.05) from 459.8 ± 530.9 to 75.1 ± 62.0 µmol/day in accordance with glycemic normalization after treatment. Marked and reversible increases in serum and urinary fructose concentrations were observed in diabetics with ketoacidosis and ketosis.

Vascular endothelial growth factor-C and its receptor type-3 expressed in acute lymphocytic leukemia cases with t(1;19).

The vascular endothelial growth factor (VEGF)-C system was analyzed in two cases of acute lymphocytic leukemia (ALL) with TCF3/PBX1 fusion to determine whether the VEGF-C system influences the growth of these ALL blasts. Bone marrow non-adherent mononuclear cells were prepared from the patients, and expressions of VEGFs and VEGF receptors (VEGFRs) were analyzed based on RNA and protein levels. Cell proliferation was also assayed with or without neutralizing antibodies to VEGFs. The patients' leukemic blasts expressed a significant amount of VEGF-C and VEGFR type-3. When anti-VEGF-C antibody was added to the blast cell cultures, cell proliferation was suppressed. These observations indicate that, in our ALL cases with TCF3/PBX1 fusion, VEGF-C autocrine stimulation plays an important role in the proliferation of ALL.

[Acute myelogenous leukemia developed at the 26th week of gestation].

We report here a 35-year-old pregnant woman with acute myelogenous leukemia (AML). She was diagnosed with AML (M2) in August 2009, coinciding with the 26(th) week of pregnancy. She underwent a cesarean section at 27 weeks gestation, delivering a very low birth weight male infant (1,066 g). One week later, she received induction chemotherapy with idarubicin and cytarabine. She achieved complete remission after two courses of chemotherapy. The incidence of acute leukemia during pregnancy is low. Chemotherapy after the 2(nd) trimester is not associated with an increased rate of fetal malformation. However, there are some reports that in utero exposure to chemotherapy during any trimester of pregnancy carries a significant risk for an unfavorable outcome including low birth weight, fetal or neonatal death, and intrauterine growth retardation. Decision on the choice of treatment for acute leukemia during pregnancy should be case-dependent. If an infant has grown sufficiently to be viable outside uterus and the patient does not demonstrate a severe bleeding tendency, delivery by cesarean section preceding chemotherapy is one option.

Successful unrelated bone marrow transplantation for a human immunodeficiency virus type-1-seropositive acute myelogenous leukemia patient following HAART.

The availability of highly active anti-retroviral therapy (HAART) has greatly improved the outcome of human immunodeficiency virus type-1 (HIV-1) infection and disease. We report here on a case of an HIV-1-seropositive patient with acute myelogenous leukemia who underwent a successful allogeneic unrelated bone marrow transplantation following HAART. A 40-year-old Japanese HIV-seropositive man underwent allogeneic unrelated bone marrow transplantation using a myeloablative pretransplant-conditioning regimen. Neutrophil engraftment occurred on day +18, and donor chimerism was achieved on day +27. During pre- and post- transplantation, the HAART was not interrupted. Over 1 year after transplantation, the patient is alive and in continuous complete remission with undetectable levels of HIV-1 RNA. HAART can lead to a successful hematopoietic stem cell transplantation without severe opportunistic infections.

[Examination about utility of a Streptococcus pneumoniae capsular antigen swiftness search kit urine in a pneumonia patient].

We investigated the usefullness of Binax NOW urine antigen test, an immunochromatographic assay that binds any soluble Streptococcus pneumoniae antigen (C polysaccharide) for the diagnosis of penumoniae form September 2003 to March 2005. We used 372 samples form the patinets with pneumoniae diagnosed for blood or sputum cultuter or gram-stained sputum smear. Out of 24 culture positive specimens, Binax NOW urine antigen test, showed positive in 18 (75%) specimens. The sensitivity of sputum and blood culture was 71.7% and 83.3%, respectively. Binax NOW urine antigen test was seemed false positives in 55 samples, false negatives in 6 samples. The specificity of Binax NOW urine antigen test was evaluated 84.1%. Overall agreement among tests was 83.6%. When compared to culture, false negative urine antigen may be the result of colonizing S. pneumoniae in sputum or pneumonia caused by an agent other than S. pneumoniae. CRP values for cases were both urine antigen and culture were positive ranged from 40 mg/dl to 10 mg/dl while urine antigen and culture negative cases were predominantly less than 10 mg/dl. Positive blood and pleural fluid culture cases were consistently associated with strongly positive urine antigen tests. Non-agreement between urine antigen, culture, and microscopy may be the result of specimen quality, labile nature of S. pneumoniae and antimicrobial therapy.

[Study of resistance mechanism on cefotaxime resistant Proteus mirabilis isolated from clinical specimens and its clinical background].

Over a 6-year period (1997 to 2002), 56 strains of Proteus mirabilis (12% of the total number of P. mirabilis isolates obtained) resistant to ampicillin, piperacillin, cefazolin and cefoperazone by routine antimicrobial testing method, were isolated in Saitama Medical School Hospital. Of the 56 strains resistant to 4 beta-lactams, 12 strains were studied and were found to produce extended-spectrum beta-lactamases, identified as CTX-M-10 group and Toho-1 group in 8 and 2 strains, respectively. Susceptibility testing showed that 12 strains were resistant to cefotaxime, and cepodoxime, and ceftriaxon but susceptible to ceftazidime. Moreover, all of the beta-lactamases were inhibited by clavulanic acid. Of the 12 strains, one strain showed resistance to cephamycins such as cefoxitin, cefmetazole and cefotetan. Four of the twelve patients had infections caused by ESBL producing P. mirabilis, and eight patients were colonized, as confirmed by clinical and laboratory findings. The infections were urinary tract infections (two episodes), pneumonia (one episode), and sepsis (one episode). These patients had a favorable response to antibiotic therapy including cephalosporin. From these findings, CTX-M-type beta-lactamase producing P. mirabilis strains were confirmed from clinical specimens in our hospital.