Membranous nephropathy in a female patient with X-linked thrombocytopenia.

BACKGROUND: Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by thrombocytopenia and eczema and is caused by a mutation in the WAS gene. WAS has heterogeneous clinical manifestations, and its clinically milder form is called X-linked thrombocytopenia (XLT). Patients with WAS/XLT sometimes have kidney complications, the most common of which is immunoglobulin (Ig)A nephropathy associated with aberrant glycosylation of IgA. CASE DIAGNOSIS/TREATMENT: The patient was a 6-year-old girl who was diagnosed with female XLT at the age of 4 years; she presented with microscopic hematuria and proteinuria at a school urinalysis. Her father had thrombocytopenia and IgA nephropathy while in his 20 s. The patient and her father had the same WAS gene mutations. A kidney biopsy was performed, and no abnormal findings were observed by light microscopy. Immunofluorescence analysis revealed a granular pattern of IgG staining along the capillary wall. Electron microscopy revealed small electron-dense deposits in subepithelial lesions. Consequently, we diagnosed her with membranous nephropathy (MN). Tissue PLA2R and THSD7A were negative, and she was judged unlikely to have secondary MN on the basis of blood test findings and IgG staining. We started the administration of angiotensin-converting enzyme inhibitors, and her proteinuria gradually decreased. CONCLUSION: To our knowledge, this is the first report of MN in a female WAS/XLT patient. WAS protein expression defects affect all immune system cells; however, the mechanisms underlying the occurrence of autoimmunity are not completely understood. In WAS/XLT patients, MN may develop as a result of increased autoantibody production, similar to other types of immunodeficiency.

Single-center survey of prescription trends and appropriate use plans for macrolide antimicrobials.

INTRODUCTION: Macrolides (MCs) are broad-spectrum antimicrobials with activity against many microorganisms. They are widely used, and the development of MC-resistant bacteria is a serious problem in Japan. It is therefore necessary to clarify the purpose and duration of administration, with the aim of promoting appropriate use. METHODS: Patients of all ages, for whom oral MCs were prescribed between 2016 and 2020 were included. They were divided into four groups based on the number of days per prescription. In the long-term treatment group, patients treated with MCs for ≥1000 days were specifically investigated for the purpose of treatment. RESULTS: Macrolide prescriptions increased from 2019 to 2020. Most patients received ≥28 days of treatment based on one prescription. During the study period, 1212 patients (28.6%) received a total of ≥50 days and 152 patients (3.6%) received a total of ≥1000 days of treatment. Approximately a third of long-term administrations were for nontuberculous mycobacterial infections (NTMs), and 18.3% of patients with NTMs were treated with MCs alone. In addition, many MCs were administered for their anti-inflammatory effects on neutrophils. CONCLUSIONS: Owing to their pleiotropic effects, MCs may also be administered for the treatment of noninfectious diseases. In general, the long-term administration of antimicrobials contradicts the strategy for the suppression of resistant bacteria. It is thus important to understand the actual clinical utility of MCs and the purpose and duration of administration. In addition, strategies for the appropriate use of MCs are required for each medical institution.

Obesity and febrile urinary tract infection in young children.

BACKGROUND: Obesity is a risk factor for infectious diseases. However, the relationship between obesity and febrile urinary tract infection (fUTI) is controversial. This study aimed to determine the relationship between obesity and fUTI in young children. METHODS: We analyzed the medical records of children aged <2 years who were admitted to our hospital because of fever between April 2013 to March 2018. The children were categorized into three groups of non-obese, overweight, and obese according to the World Health Organization weight-for-length curves for children aged <2 years. RESULTS: A total of 600 patients were enrolled in this study, of whom 118 were diagnosed with first fUTI. Patients in the fUTI group were younger than those in the control group (patients who were diagnosed with other febrile diseases) (5 ± 5.11 vs 11 ± 6.53 months; P < 0.001). There were no significant differences in the populations of overweight and obese children between the fUTI and control groups. In the fUTI group, the duration of fever, types of pathogen, recurrent rate, the grades of vesicoureteral reflux, and renal scarring were not associated with obesity. The white blood cell count and C-reactive protein levels were not significantly different among the three weight-for-length categories. The same results were obtained when the fUTI group was compared with an age-matched control group (n = 192, 4 ± 2.55 months old; P = 0.261). CONCLUSIONS: Obesity is not a significant risk factor for fUTI in febrile hospitalized young children. Our study suggests that conducting urinalysis for febrile young children without obvious sources, irrespective of obesity, should be considered.

Hematopoietic Cell Transplantation with Reduced Intensity Conditioning Using Fludarabine/Busulfan or Fludarabine/Melphalan for Primary Immunodeficiency Diseases.

PURPOSE: The purpose of our study was to compare the safety and efficacy of hematopoietic cell transplantation (HCT) using fludarabine (Flu)-based reduced intensity conditioning (RIC) with busulfan (BU) or melphalan (Mel) for primary immunodeficiency diseases (PID). METHODS: We retrospectively analyzed transplant outcome, including engraftment, chimerism, immune reconstitution, and complications in 15 patients with severe combined immunodeficiency (SCID) and 27 patients with non-SCID PID. The patients underwent Flu-based RIC-HCT with BU (FluBU: 7 SCID, 16 non-SCID) or Mel (FluMel: 8 SCID, 11 non-SCID). The targeted low-dose BU with therapeutic drug monitoring was set to 30 mg hour/L for SCID. RESULTS: The 2-year overall survival of all patients was 79.6% and that of patients with SCID in the FluBU and FluMel groups was 100% and 62.5%, respectively. In the FluBU group, all seven patients achieved engraftment, good immune reconstitution, and long-term survival. All five patients receiving umbilical cord blood transplantation achieved complete or high-level mixed chimerism and sufficient specific IgG production. In the FluMel group, six of eight patients achieved complete or high-level mixed chimerism. Viral reactivation or new viral infection occurred in one FluBU group patient and four FluMel group patients. In the non-SCID group, 10 of 11 patients (91%) who received FluMel achieved complete or high-level mixed chimerism but had variable outcomes. Patients with WAS (2/2 patients), NEMO deficiency (2/2 patients), and X-linked hyper IgM syndrome (2/3 patients) who received FluBU achieved complete or high-level mixed chimerism and long-term survival. CONCLUSIONS: RIC-HCT with FluBU is a safe and effective strategy for obtaining high-level donor chimerism, immune reconstitution including B cell function, and long-term survival in patients with SCID. In patients with non-SCID PID, the results varied according to the subtype of the disease. Further prospective studies are required to optimize the conditioning regimen for non-SCID PID.

The dynamics of quantitative SARS-CoV-2 antispike IgG response to BNT162b2 vaccination.

Vaccination for SARS-CoV-2 is necessary to overcome coronavirus disease 2019 (COVID-19). However, the time-dependent vaccine-induced immune response is not well understood. This study aimed to investigate the dynamics of SARS-CoV-2 antispike immunoglobulin G (IgG) response. Medical staff participants who received two sequential doses of the BNT162b2 vaccination on days 0 and 21 were recruited prospectively from the Musashino Red Cross Hospital between March and May 2021. The quantitative antispike receptor-binding domain (RBD) IgG antibody responses were measured using the Abbott SARS-CoV-2 IgGII Quant assay (cut off ≥50 AU/ml). A total of 59 participants without past COVID-19 history were continuously tracked with serum samples. The median age was 41 (22-75) years, and 14 participants were male (23.7%). The median antispike RBD IgG and seropositivity rates were 0 (0-31.1) AU/ml, 0.3 (0-39.5) AU/ml, 529.1 (48.3-8711.4) AU/ml, 18,836.9 (742.2-57,260.4) AU/ml, and 0%, 0%, 98.3%, and 100% on days 0, 3, 14, and 28 after the first vaccination, respectively. The antispike RBD IgG levels were significantly increased after day 14 from vaccination (p < 0.001) The BNT162b2 vaccination led almost all participants to obtain serum antispike RBD IgG 14 days after the first dose.

Clinical validation of an immunochromatographic SARS-Cov-2 IgM/IgG antibody assay with Japanese cohort.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a major health threat. To overcome COVID-19, appropriate diagnosis methods are urgently needed. The aim of this study was to clinically evaluate the colloidal gold immunochromatography assay for SARS-Cov-2 IgM/IgG antibody (Ab). METHODS: Patients confirmed COVID-19 (n = 51) were recruited prospectively from the Musashino Red Cross hospital and Tokyo Medical and Dental University Medical Hospital, between March and May 2020. And the analytical specificity was assessed with serum samples of patients without COVID-19 (n = 100) collected between August to September 2019 before SARS-CoV-2 was first reported in China. RESULTS: Among COVID-19 patients, a total of 87 serum samples were tested for SARS-Cov-2 IgM/IgG Ab assay. IgM was detected 71.0 %, 86.9 %, and 83.3 % at day8-14, 15-28, >29 after symptom onset and IgG was detected in 81.6 %, 87.0 %, and 94.4 %, respectively. The sensitivity of IgM and IgG Ab after day8 assay was significantly higher than before day7, respectively (p=0.0016, 0.0003). There were no positive results in 100 serum samples from patients without COVID-19. CONCLUSION: The SARS-Cov-2 IgM/IgG Ab assay had 79.7% / 86.1% sensitivity (the 8 days after from onset) and 100% specificity in this population.

The effectiveness of prescription support and treatment reporting system on the appropriate usage of oral third-generation cephalosporins.

INTRODUCTION: Preauthorization and prospective audit and feedback system are reported to be effective for the achievement of appropriate use of intravenous antimicrobials, but few reports on oral antimicrobials are available, especially for adults. METHODS: The prescription of oral third-generation cephalosporins (oral 3rd Ceph) for inpatients and outpatients from 2013 to 2018 was investigated. The study period was divided into three phases. First, prescription support to suggest discontinuation of antimicrobials for unnecessary prescriptions, and alternative antimicrobials for inappropriate prescriptions were provided. Next, we continued prescription monitoring, and observed the trends of antimicrobial prescription without support. Finally, we have introduced prescription reporting system to promote the appropriate use of oral 3rd Ceph. In each phase, we evaluated days of therapy per 1000 patient-days and prescriptions per 1000 visits as an index of effectiveness of our interventions. RESULTS: The total annual amount of oral 3rd Ceph usage decreased significantly over time between phases, respectively. During the same period, the incidence rate of methicillin-resistant Staphylococcus aureus (MRSA), extended spectrum ß-lactamase (ESBL)-producing bacteria, and AmpC ß-lactamase (AmpC)-producing bacteria was not changed significantly, indicating that oral 3rd Ceph usage was reduced without a concomitant increase of the drug-resistant bacteria. Simultaneously, the annual usage of other broad-spectrum antimicrobial agents such as oral fluoroquinolones and oral macrolides also decreased, which indicated these antimicrobials were not prescribed as an alternative for oral 3rd Ceph. CONCLUSIONS: The combination of prescription support activity and treatment reporting system for oral antimicrobial agents is an effective method for promoting appropriate oral antimicrobial use.

Differences in the Central Energy Metabolism of Cancer Cells between Conventional 2D and Novel 3D Culture Systems.

The conventional two-dimensional (2D) culture is available as an in vitro experimental model. However, the culture system reportedly does not recapitulate the in vivo cancer microenvironment. We recently developed a tissueoid cell culture system using Cellbed, which resembles the loose connective tissue in living organisms. The present study performed 2D and three-dimensional (3D) culture using prostate and bladder cancer cell lines and a comprehensive metabolome analysis. Compared to 3D, the 2D culture had significantly lower levels of most metabolites. The 3D culture system did not impair mitochondrial function in the cancer cells and produce energy through the mitochondria simultaneously with aerobic glycolysis. Conversely, ATP production, biomass (nucleotides, amino acids, lipids and NADPH) synthesis and redox balance maintenance were conducted in 3D culture. In contrast, in 2D culture, biomass production was delayed due to the suppression of metabolic activity. The 3D metabolome analysis using the tissueoid cell culture system capable of in vivo cancer cell culture yielded results consistent with previously reported cancer metabolism theories. This system is expected to be an essential experimental tool in a wide range of cancer research fields, especially in preclinical stages while transitioning from in vitro to in vivo.

Long non-coding RNA MANCR is a target of BET bromodomain protein BRD4 and plays a critical role in cellular migration and invasion abilities of prostate cancer.

Androgen receptor (AR)-negative castration-resistant prostate cancer (CRPC) is highly aggressive and is resistant to most of the current therapies. Bromodomain and extra terminal domain (BET) protein BRD4 binds to super-enhancers (SEs) that drive high expression of oncogenes in many cancers. A BET inhibitor, JQ1, has been found to suppress the malignant phenotypes of prostate cancer cells, however, the target genes of JQ1 remain largely unknown. Here we show that SE-associated genes specific for AR-negative CRPC PC3 cells include genes involved in migration and invasion, and that JQ1 impairs migration and invasion of PC3 cells. We identified a long non-coding RNA, MANCR, which was markedly down-regulated by JQ1, and found that BRD4 binds to the MANCR locus. MANCR knockdown led to a significant decrease in migration and invasion of PC3 cells. Furthermore, RNA sequencing analysis revealed that expression of the genes involved in migration and invasion was altered by MANCR knockdown. In summary, our data demonstrate that MANCR plays a critical role in migration and invasion of PC3 cells.

Retrospective analysis of children with high-risk acute myeloid leukemia who underwent allogeneic hematopoietic stem cell transplantation following complete remission with initial induction chemotherapy in the AML-05 clinical trial.

In the AML-05 clinical trial conducted by the Japanese Pediatric Leukemia/Lymphoma Group from 2006 to 2010, children with high-risk acute myeloid leukemia (HR AML) received allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1). The aim of this study was to investigate the impact of allo-HSCT on the outcome of HR AML. Patients with either monosomy 7, 5q-, t(16;21), Ph1, FLT3-ITD, or induction failure after the first course of chemotherapy were eligible for transplant. Of 53 children with HR AML, 51 received allo-HSCT-45 in CR1, five in CR2, and one with non-CR. t(8;21), t(9;11), and t(16;21) abnormalities were identified in eight, five, and four patients, respectively. The stem cell sources varied-bone marrow in 30 patients, peripheral blood in three, and cord blood in 18. The median follow-up was 62 months. The overall survival (OS) rates at 3 years were 73% and 25% for patients who received transplant at CR1 and ≥CR2, respectively. Multivariable analysis showed that patients with chronic graft-versus-host disease (cGVHD) had better OS. This study supports that allo-HSCT is a suitable treatment for HR AML in CR1. The favorable outcome associated with cGVHD indicates that a graft-versus-leukemia effect might be occurring.

The location of the bladder neck in postoperative cystography predicts continence convalescence after radical prostatectomy.

BACKGROUND: This study was conducted to determine whether the location of the bladder neck in postoperative cystography predicts recovery of continence after radical prostatectomy. METHODS: Between 2008 and 2015, 203 patients who underwent laparoscopic radical prostatectomy (LRP, n = 99) and robot assisted radical prostatectomy (RARP, n = 104) were analyzed. The location of the bladder neck was visualized by postoperative routine cystography, and quantitative evaluation of the bladder neck position was performed according to the bladder neck to pubic symphysis (BNPS) ratio proposed by Olgin et al. (J Endourol, 2014). Recovery of continence was defined as no pad use or one security pad per day. To determine the predictive factors for recovery of continence at 1, 3, 6 and 12 months, several parameters were analyzed using logistic regression analysis, including age (≤68 vs. > 68, BMI (≤23.4 vs. > 23.4 kg/m2), surgical procedure (LRP vs. RARP), prostate volume (≤38 vs. > 38 mL), nerve-sparing technique, vesico-urethral anastomosis leakage, and BNPS ratio (≤0.59 vs. > 0.59). RESULTS: The mean postoperative follow-up was 1131 days (79-2880). At 1, 3, 6 and 12 months after surgery, continence recovery rates were 25, 53, 68 and 81%, respectively. Although older age (> 68) and RARP were significant risk factors for incontinence within 3 months, neither was significant after 6 months. A high BNPS ratio (> 0.59) was the only significant risk factor for the persistence of incontinence at all observation points, up to 12 months. CONCLUSIONS: A lower bladder neck position after prostatectomy predicts prolonged incontinence.

Intravesical bacillus Calmette-Guerin therapy after second transurethral resection for primary T1 bladder cancer.

BACKGROUND: To evaluate the effect of intravesical bacillus Calmette-Guerin (BCG) instillation therapy after second transurethral resection (TUR) on primary T1 bladder cancer. METHODS: The subjects were 180 patients diagnosed with T1 bladder cancer at our university and at affiliated hospitals between January 1990 and December 2015. Tumor residual rate, intravesical recurrence rate, and risk factors for intravesical recurrence were investigated. RESULTS: The median follow-up period was 26 (1-175) months. Of the 180 patients, 78 (43%) underwent a second TUR. Residual tumors were detected in 42 patients (53.8%), and no up-staging cases were observed. Within the whole group, 42 patients were treated with intravesical BCG therapy following a second TUR (group 1), 36 were treated with second TUR alone (group 2), 28 were treated with intravesical BCG therapy alone (group 3), and 74 were treated without second TUR or intravesical BCG therapy (group 4). The 1- and 5-year recurrence-free survival rates of the four groups were 80.7 and 59.7% (group 1), 69.0 and 26.3% (group 2), 76.3 and 56.6% (group 3), 64.6 and 48.6% (group 4), respectively. There was no significant difference between group 1 and group 3 (p = 0.401). Intravesical BCG therapy was the only factor preventing intravesical recurrence (p = 0.013). CONCLUSIONS: Intravesical BCG therapy alone showed a significant preventive effect with regard to intravesical recurrence. In our cohort, however, second TUR did not improve recurrence-free survival in those individuals who underwent BCG instillation.

Effect of reduced-intensity conditioning and the risk of late-onset non-infectious pulmonary complications in pediatric patients.

OBJECTIVE: Late-onset non-infectious pulmonary complications (LONIPCs) contribute to higher morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, we investigated the risk factors of LONIPCs in pediatric patients. METHOD: Between 2001 and 2011, 74 pediatric patients (range, 7 months to 22.7 years old; median 6.5 years old), including 29 with a primary immunodeficiency, underwent 80 allo-HSCTs at our institution. Sixty-seven patients who survived more than 3 months after allo-HSCT were analyzed retrospectively. The median follow-up period was 1 973 days (range, 126-5 145 days). RESULTS: Nine patients (13.4%) developed LONIPCs between 90 and 3 578 days after allo-HSCT. A myeloablative conditioning (MAC) regimen and chronic GVHD were determined as significant risk factors of LONIPCs. None of 18 patients who received the reduced-intensity conditioning (RIC) regimen developed LONIPCs, although there was no difference in overall survival between the MAC and RIC regimen. Notably, two immunodeficient patients who received busulfan-based MAC regimen under 2 years old developed LONIPC with no history of chronic GVHD after 5 years and 10 years from SCT, respectively, suggesting the direct toxicity of busulfan. CONCLUSION: Our study's findings indicate that the RIC regimen reduces the risk of LONIPCs in pediatric patients.

Severe neonatal CMV infection complicated with thrombotic microangiopathy successfully treated with ganciclovir.

We report a neonate of severe cytomegalovirus (CMV) infection who presented vomiting, severe thrombocytopenia and thrombotic microangiopathy (TMA). He showed occasional vomiting at 3 weeks of age and visited us with systemic petechiae at 29 days old. Platelet was markedly decreased to 18,000/µL and fragmented red blood cells were increased in the peripheral blood. Intravenous ganciclovir (GCV) administration was started at 35 days old after detection of CMV in the peripheral blood. His normal values of T-cell receptor excision circles (TREC) and signal joint kappa-deleting recombination excision circles (sjKREC) excluded the possibility of severe immunodeficiency. Congenital CMV infection was denied later, when CMV of the dried blood spot obtained for neonatal mass-screening at 4 days old was proved negative. We provided 6-week treatment with no side effect such as myelosuppression. The left hearing abnormality found at first was improved along with other symptoms. GCV seems to be effective and safe for severe neonatal CMV infection.

The Effect of D-Aspartate on Spermatogenesis in Mouse Testis.

Spermatogenesis is controlled by hormonal secretions from the hypothalamus and pituitary gland, by factors produced locally in the testis, and by direct interaction between germ cells and Sertoli cells in seminiferous tubules. Although the mammalian testis contains high levels of D-aspartate (D-Asp), and D-Asp is known to stimulate the secretion of testosterone in cultured Leydig cells, its role in testis is unclear. We describe here biochemical, immunohistochemical, and flow cytometric studies designed to elucidate developmental changes in testicular D-Asp levels and the direct effect of D-Asp on germ cells. We found that the concentration of D-Asp in mouse testis increased with growth and that fluctuations in D-Asp levels were controlled in part by its degradative enzyme, D-aspartate oxidase expressed in Sertoli cells. In vitro sperm production studies showed that mitosis in premeiotic germ cells was strongly inhibited by the addition of D-Asp to the culture medium. Moreover, immunohistochemical analysis demonstrated that d-Asp accumulated in the differentiated spermatids, indicating either transport of D-Asp to spermatids or its de novo synthesis in these cells. Such compartmentation seems to prevent premeiotic germ cells in mouse testis from being exposed to the excess amount of D-Asp. In concert, our results indicate that in mouse testis, levels of D-Asp are regulated in a spatiotemporal manner and that D-Asp functions as a modulator of spermatogenesis.

Clinical features and hematopoietic stem cell transplantations for CD40 ligand deficiency in Japan.

BACKGROUND: The long-term outcome of X-linked hyper-IgM syndrome (XHIM) caused by mutations in CD40LG is poor, and the only curative treatment is hematopoietic stem cell transplantation (HSCT). OBJECTIVE: We sought to determine the clinical features and factors affecting outcomes in patients with XHIM. METHODS: We enrolled and retrospectively analyzed data from 56 Japanese patients with XHIM, including 29 patients who received HSCT. RESULTS: The long-term survival rate was poor in those not undergoing HSCT (overall survival rate at 40 years of age, 28.2%). The overall survival rate of patients undergoing HSCT (n = 29) was significantly higher than that of those not undergoing HSCT (n = 27, P = .0231). Moreover, event-free and disease-free survival rates were significantly greater in patients 5 years old or younger at the time of transplantation (n = 14) than in older patients (n = 15). CONCLUSION: On the basis of these results, we concluded that HSCT improved the outcomes of patients with XHIM and that an age of 5 years or younger was optimal for the timing of HSCT because persistent infections and severe organ damage were frequently observed in patients older than 6 years.

ENDOSCOPIC SHIELDING OF RECTOURETHRAL FISTULA AFTER LAPAROSCOPIC RADICAL PROSTATECTOMY; REPORT OF A CASE.

Rectourethral fistulais a relatively rare complication of radical prostatectomy but is extremely difficult to treat. We report a case with post-laparoscopic radical prostatectomy rectourethral fistula, treated with only endoscopic shielding.A 75-year-old man had undergone laparoscopic radical prostatectomy for prostate cancer, cT2cN0M0. Although there was no finding of rectal injury during the operation, pneumaturia, pyuria and diarrhea appeared at postoperative day 21 and diagnosed rectourethral fistula by colonoscopy and amidotrizoic acid enema. The fistula did not close spontaneously. Four months after the prostatectomy, we treated with endoscopic shielding by use of polyglycolic acid sheets and fibrin glue. The fistula have not recurred for 20 months after the endoscopic procedure.This method is simple and less-invasive for patients. We think it is worth trying this method before surgical management for narrow rectourethral fistula following radical prostatectomy.

Principles of dielectric blood coagulometry as a comprehensive coagulation test.

Dielectric blood coagulometry (DBCM) is intended to support hemostasis management by providing comprehensive information on blood coagulation from automated, time-dependent measurements of whole blood dielectric spectra. We discuss the relationship between the series of blood coagulation reactions, especially the aggregation and deformation of erythrocytes, and the dielectric response with the help of clot structure electron microscope observations. Dielectric response to the spontaneous coagulation after recalcification presented three distinct phases that correspond to (P1) rouleau formation before the onset of clotting, (P2) erythrocyte aggregation and reconstitution of aggregates accompanying early fibrin formation, and (P3) erythrocyte shape transformation and/or structure changes within aggregates after the stable fibrin network is formed and platelet contraction occurs. Disappearance of the second phase was observed upon addition of tissue factor and ellagic acid for activation of extrinsic and intrinsic pathways, respectively, which is attributable to accelerated thrombin generation. A series of control experiments revealed that the amplitude and/or quickness of dielectric response reflect platelet function, fibrin polymerization, fibrinolysis activity, and heparin activity. Therefore, DBCM sensitively measures blood coagulation via erythrocytes aggregation and shape changes and their impact on the dielectric permittivity, making possible the development of the battery of assays needed for comprehensive coagulation testing.

Transient abnormal myelopoiesis in non-Down syndrome neonate.

We encountered a case of neonatal acute megakaryoblastic leukemia not associated with Down syndrome (DS). Molecular cytogenetic analysis of leukemic blast cells indicated that increased blast cell status was caused by transient abnormal myelopoiesis with trisomy 21 and GATA1 mutation. Based on these molecular cytogenetic data, intensive chemotherapy was avoided, and the patient was successfully cured with low-dose cytarabine. Morphologically, leukemic blast cells of acute megakaryoblastic leukemia in a non-DS neonate are indistinguishable from a blast cell of transient abnormal myelopoiesis. The possibility of transient abnormal myelopoiesis should be carefully considered before intensive chemotherapy is adopted.