Diamond-Blackfan Anemia in Japan: Clinical Outcomes of Prednisolone Therapy and Hematopoietic Stem Cell Transplantation

The epidemiology and treatment outcomes for Diamond-Blackfan anemia (DBA) were surveyed in a cohort of 54 children (M/F = 26:28) registered in Japan from 1988 to 1998. The annual incidence was 4.02 cases per million births, the median age at diagnosis was 60 days, and 59% of the cases presented by 3 months of age. Three patients had a familial occurrence. All patients received prednisolone (PSL), and cyclosporin A (CsA) was added to the therapy in 17 patients. Forty-seven patients received transfusions, and 13 underwent hematopoietic stem cell transplantation (HSCT). The cumulative probabilities of a medication-free or a transfusion-free state prior to HSCT were 36% and 69%, respectively, at more than 5 years after diagnosis. Thirteen patients were weaned from PSL therapy without HSCT, and CsA was not associated with weaning from therapy. Transfusion and medication were stopped at 249 days and 933 days after diagnosis in 34 and 13 patients, respectively, who achieved a state of independence. No initial findings predicted the treatment dependence. More than 20% of patients experienced sustained hemosiderosis and/or adverse effects of PSL. The ages and reticulocyte counts at diagnosis of the patients who underwent HSCT were lower than in the patients who did not. HSCT led to the highest success (85%) of all previous reports, even though 5 alternative donors were included in our study. Two cord blood transplants from unrelated donors failed. These findings suggest the need for developing an integral treatment strategy including selective HSCT for refractory DBA.     

Clinicopathological states of Epstein-Barr virus-associated T/NK-cell lymphoproliferative disorders (severe chronic active EBV infection) of children and young adults

Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disorders (LPD) of children and young adults are sometimes termed as severe chronic active EBV infection (CAEBV), and are associated with an aggressive clinical course. However, these clinicopathological states and the role of EBV have not been clarified. A retrospective study was performed on 43 children and adult patients, who manifested EBV-associated T/NK-cell lymphoproliferative disorders (EBV-T/NK-LPD) and most of whom had experienced general illness with CAEBV for several months or years. Clinicopathologically, 43 patients were classified into four groups: group A (smoldering state) (n=7), morphological non-neoplastic LPD with chronic clinical course (several years); group B (chronic state) (n=10), non-neoplastic LPD with clonal EBV-infected cells and a chronic course; group C (leukemia/lymphoma state) (n=22), neoplastic LPD with a subacute course (years to months); group D (fulminant state) (n=4), neoplastic LPD with a fulminant course (weeks to days). The 43 patients comprised 21 males and 22 females. The median age of group A was 14 years, group B 12 years, group C 17 years, and group D 1 year. Four of 7 patients in group A, 3 of 10 in group B, 12 of 22 in group C, and all 4 in group D have died. Causes of death included hemophagocytic syndrome and/or tumor death. Genotypically and phenotypically, group C was composed of peripheral T-cell lymphoma (PTCL), and NK-cell leukemia/lymphoma (NKLL), and group D comprised cases of PTCL. Groups A and B exhibited increased NK- or T-cells (CD8>CD4), and rare B-cells. Serologic titers of EBV were only modestly elevated or not elevated in almost all cases. EBV early RNA-1 (EBER-1)-expressing EBV-infected cells were frequently encountered in each group, but the number of infected cells varied between the cases. The EBV genotype did not differ between the groups. Our findings support an important pathogenic role for EBV-infected T/NK-cell infection, rather than the EBV state, in CAEBV and consequent EBV-associated NK/T-neoplasia.     

Expansion of trisomy 8 and Sweet syndrome in a prolonged course of aplastic anemia

We describe a 17-year-old boy with aplastic anemia who had Sweet syndrome develop with increasing expansion of trisomy 8. The diagnosis of aplastic anemia was made at 6 years of age. Cytopenias partially responded to danazol therapy. Cytogenetic studies of bone marrow (BM) cells were normal until the detection of trisomy 8 at 14 years of age. This clone increased with the progression of cytopenias. Cell sorting and fluorescence in situ hybridization analysis revealed that trisomy 8 was present only in nonlymphoid elements. When the patient was 17 years of age, Sweet syndrome developed. BM study showed myelodysplastic features, in which trisomy 8 occupied 74% of BM cells with additional chromosomal changes. Trisomy 8 may contribute to the late transformation of myeloid lineages in BM failure.     

Veneering technique for a Ti-6Al-7Nb framework used in a resin-bonded fixed partial denture with a highly filled indirect composite

This article presents a veneering technique for fixed partial denture frameworks made from a Ti-6Al-7Nb alloy. The fixed partial denture framework was prepared with a magnesia-based mold material and a centrifugal casting machine. An esthetic veneer was fabricated with a highly filled dual-polymerized composite material and a metal-conditioning agent. This technique can be applied as a standardized veneering procedure for the titanium alloy, for which porcelain fusing is currently difficult.     

Antimicrobial activity of hinokitiol against Legionella pneumophila

Antimicrobial activity of hinokitiol (beta-thujaplicin), which is a major component of the essential oil of Chamaecyparis obtuse, against Legionella pneumophila was investigated experimentally. The quantitative antibacterial assay of hinokitiol was carried out by the disk-diffusion method. The test concentrations of hinokitiol were 0.39 to 25.0 micrograms/disk, and the lowest concentrations of hinokitiol that showed growth inhibition against L. pneumophila were 1.56 micrograms/disk on B-SYE agar and 0.39 microgram/disk on B-SYE agar without iron.     

High-dose-rate brachytherapy with local injection of bleomycin for N0 oral tongue cancer--possibilities of the control of tumor implant by inserting applicators and the decrease in tumor dose

Twenty-eight patients with N0 oral tongue cancer were treated with high-dose-rate (HDR) interstitial brachytherapy combined with local injection of bleomycin between December 1997 and June 2001 at the Department of Radiology, National Kyushu Medical Center Hospital. A median dose of 5 mg of bleomycin was injected locally, and 16-20 Gy was delivered to the area surrounding applicators for control of the tumor implant during the initial two days. The two-year local recurrence-free survival rate was 96% [T1, 2: 100% (8/8, 15/15), T3: 80% (4/5)]. The two-year secondary neck node metastasis rate was 7.1% [T1: 12.5% (1/8), T2: 6.7% (1/15), T3:0% (0/5)]. There were no tumor implants in any patients. We tried to decrease the minimal tumor dose step by step. The groups with median minimal tumor doses of 60 Gy, 50 Gy, and 40 Gy had local recurrence rates of 12.5% (1/8), 0% (0/14), and 0% (0/6), respectively. Local recurrence rates were not increased by decreasing the minimal tumor dose. Two patients (7%) had secondary neck node metastasis. Late adverse effects were tongue ulcer: 11% (3/28), oral floor ulcer: 4% (1/28), and osteonecrosis: 4% (1/28). These results suggest that control of the tumor implant and the decrease in minimal tumor dose below 60 Gy may be possible with the local injection of bleomycin and delivery of doses to the area surrounding the applicators when NO tongue cancer is treated using 192Ir-HDR brachytherapy.     

Inhibitory effects of angiotensin-converting enzyme (ACE) inhibitors on oxygen radicals produced by bronchoalveolar lavage cells in young and aged guinea pigs

We examined the effect of angiotensin-converting enzyme (ACE) inhibitors and age on oxygen radical formation by bronchoalveolar lavage (BAL) cells. Lung-free cells, including pulmonary alveolar macrophages, were harvested from young (4-month-old) and aged (28-month-old) male guinea pigs using BAL. The oxygen radicals produced by BAL cells were measured by a lucigenin-dependent chemiluminescence method using a photon counter. Although spontaneous oxygen radical production by BAL cells from young and aged guinea pigs did not differ, the oxygen radical generation after maximal stimulation with phorbol-myristate acetate (PMA) was greater than that produced without PMA stimulation in both young and aged animals. ACE inhibitors with and without an SH-group (alacepril and lisinopril, respectively) were tested for their effect on oxygen radical formation by BAL cells; both ACE inhibitors inhibited oxygen radical production and generation by BAL cells from both young and aged guinea pigs in a dose-dependent manner. However, the alacepril concentration giving 50% inhibition (IC50) of oxygen radical generation by BAL cells was smaller than the IC50 of lisinopril in both young and aged guinea pigs. These results indicate that ACE inhibitors, in particular those with an SH-group, effectively reduce oxygen radical production by BAL cells from young and aged guinea pigs, and suggest that treatment with ACE inhibitors may be useful for ameliorating oxidant-associated pulmonary disorders in young and aged patients.