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To evaluate the efficacy and safety of regenerative treatment for tympanic membrane perforation (TMP) using gelatin sponge, basic fibroblast growth factor (bFGF), and fibrin glue.This was a multicenter, non-randomized, single-arm study conducted at tertiary referral centers. Twenty patients with chronic TMP (age 23-78 years, 6 males, 14 females) were registered from three institutions. All treated patients were included in the safety analysis population. The edges of the TMP were disrupted mechanically by myringotomy and several pieces of gelatin sponge immersed in bFGF were placed and fixed with fibrin glue to cover the perforation. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. The main outcome measures were closure or a decrease in size of the TMP, hearing improvement, and air-bone gap evaluated 16 weeks after the final regenerative procedure (FRP). Adverse events (AEs) were monitored throughout the study.Total closure of the TMP at 16 weeks was achieved in 15 out of 20 patients (75.0%, 95% confidence interval [CI]: 50.9%-91.3%) and the mean decrease in size was 92.2% (95%CI: 82.9%-100.0%). The ratio of hearing improvement and the air-bone gap at 16 weeks after FRP were 100% (20/20; 95%CI: 83.2%-100%) and 5.3 ± 4.2 dB (p 0.0001), respectively. Thirteen out of 20 patients (65.0%) experienced at least one AE, but no serious AEs occurred.The results indicate that the current regenerative treatment for TMP using gelatin sponge, bFGF, and fibrin glue is safe and effective.

The first-line treatment for inner ear disorders is usually oral/systemic steroids. Intratympanic steroid therapy is an alternative option; however, it requires multiple office visits owing to the short residence time of steroids in the inner ear (systemic: 24 h, intratympanic: 2-3 h). Therefore, intratympanic injections of higher steroid concentrations could result in longer drug exposure, providing better treatment outcomes. This study aimed to develop a prototype for high-concentration steroids and examine their safety and feasibility in vivo. Using wild-type Institute for Cancer Research mice, high-concentration steroids (50 mg/mL dexamethasone), typical steroid concentrations (3.3 mg/mL dexamethasone), and sterile saline were administrated into the middle ear cavity via tympanic membrane injection. Auditory brainstem response analysis, vestibular function tests, and morphological analyses were performed to examine the safety and utility of High-conc Dex. One month post-injection, the frequency-averaged auditory brainstem response thresholds of high-dose dexamethasone-treated mice were not significantly different from those of low-dose dexamethasone- and saline-treated mice at all tested frequencies. Furthermore, the total points on vestibular function tests were similar between the three groups. Morphologically, no damage to the inner ear/middle ear mucosa was observed in all groups. Two months post-injection, dexamethasone could still be detected in the high-dose dexamethasone group. Altogether, our data successfully demonstrates the feasibility and safety of high-dose dexamethasone for in vivo use in the middle ear and ensure that the drug localizes to the inner ear. Further research is warranted to develop this new treatment strategy and further characterize its effects in vivo.

遺族会は，子どもを亡くした家族を対象に同じ経験を持つ家族が思い出を分かち合い，理解し，支え合い，心の癒しの場となることを目的に，1999年12月に立ち上げ，毎月1回の開催を目標に現在も継続して開催してきた。しかし，参加者が少ないことや子ども以外を亡くした人の参加希望もあり，大切な人を亡くした全ての人に対象を拡大してきた。遺族会の活動は主に語り合いで，参加者が中心となりリーフレットやメモリアルキルトの作成も行った。活動記録から，参加者の語りは「みんなと同じ気持ちだと分かってよかった」「あの子のことだけを考える時間・場所だと思っている」などであった。さらに，遺族会を毎月1回の開催とすることで，遺族はタイムリーに参加し，自由に語ることや，参加しなくてもはがきの案内で故人を想う機会となるなどであった。遺族会を毎月開催し続けることは，遺族が故人を想う機会となること，自由に参加しやすいこと，大切な人を亡くしたという同じ経験を共に語らいながら時間を過ごすことができることから，悲嘆からの回復に寄与できていると考える。今後は，遺族ケアが必要な遺族に遺族会の存在が周知されていない可能性が考えられるので，遺族会について積極的に広報活動を行う必要がある。

Objective: Populations are aging in many countries, and the proportion of elderly people with severe to profound hearing loss is increasing in parallel with the increasing average life span. The objective of this study was to investigate the outcomes of cochlear implant (CI) surgery in elderly patients compared to those in younger patients. Methods: The outcomes of CI surgery were retrospectively investigated for 81 adults (32 men and 49 women) who underwent CI surgery at our hospital. They were divided according to age at the time of implantation into the younger group (&lt, 75 years of age, n = 49) or elderly group (≥75 years of age, n = 32). Results: The mean sentence recognition score on the CI-2004 Japanese open-set test battery (±standard deviation) was 82.9% ± 24.1 in the younger group and 81.9% ± 23.2 in the elderly group, with no significant difference between the groups (Mann–Whitney U test). The incidence of major complications that required surgical treatment was not significantly different between the groups (4.1% vs. 6.2%, respectively). Thus, there were no severe complications that could affect general health status in either group. Three patients in each group died for reasons unrelated to CI surgery during follow-up. The proportion of patients who were alive and continued to use the CI five years after surgery was 92.8% and 91.5%, respectively. Conclusion: Our results show good speech recognition and a low incidence of major complications in elderly patients. This comprehensive report on the outcomes of CI surgery in elderly patients will be helpful to the elderly with severe to profound hearing loss when deciding whether to undergo CI surgery.

Objective To apply regenerative treatment for tympanic membrane (TM) perforation to patients with severe calcification of the TM, cholesteatomas, or tumors localized to the tympanic cavity. Study design Controlled clinical pilot study. Setting General hospitals. Patients Forty-five patients (age: 8-85; M = 19, F = 26) were selected from patients with or without TM perforation for the regenerative treatment. Twenty-five patients had cholesteatomas, 3 had tumors, and 17 had severe TM calcification. Patients were classified into three groups based on TM perforation size: less than 1/3 of the TM as Grade I (n = 5), 1/3 to 2/3 as Grade II (n = 19), and over 2/3 as Grade III (n = 21). Twenty patients who underwent standard tympanoplasty type I were selected as historical controls. Materials and methods Materials for the TM repair included gelatin sponge with basic fibroblast growth factor and fibrin glue. After lesions were removed through the TM perforation, gelatin sponge immersed in basic fibroblast growth factor was placed over the perforation. Fibrin glue was then dripped onto the sponge. Treatment efficacy was evaluated 6 months posttreatment. Results Complete closure of the TM perforation was achieved in 91% (n = 41/45) of the patients in this regenerative treatment. Improvement in average hearing levels and air-bone gap were much better with this treatment than in the historical control group. Conclusion This new regenerative therapy is useful not only for patients with simple TM perforations but also for those with cholesteatomas, tumors, or severe calcification without requiring conventional surgical procedures. This regenerative therapy is an easy, safe, cost-effective, and minimally-invasive treatment.

Objectives: Examining the pharmacotherapy of patients who have attempted suicide by overdose could be useful in developing treatment and suicide prevention plans. We surveyed the drugs taken by psychiatric prescription overdose patients who received inpatient treatment and sought to determine the characteristics of patients who repeatedly attempt suicide. Methods: Subjects were 116 patients who attempted suicide by overdose with prescription psychiatric drugs and received inpatient treatment at the Intensive Care Unit of the Emergency and Critical Care Center of Teikyo University Hospital from August 2009 to July 2010. We retrospectively surveyed clinical characteristics, including prescriptions prior to hospitalization and psychiatric diagnosis, divided subjects into a first-admission (FA) and repeatadmission (RA) groups, and compared their clinical characteristics. Results: All subjects were prescribed benzodiazepine-receptor agonists (BZDRAs), whereas antidepressants and antipsychotics were prescribed to 58.6% and 49.1% of subjects, respectively. Emotionally unstable personality disorder, borderline-type (EUPD-B) was found to be significantly more common in the RA group. Comparing prescriptions in the FA and RA groups indicated that the prescribed dosage and prescription rate for antipsychotics were significantly higher for RA group patients. Conclusion: This study revealed that repeat-admission attempted suicide patients had a significantly higher rate of EUPD-B and were more frequently using antipsychotic prescription drugs. Further, in these patients, more frequent use of antipsychotics is believed to correspond to patient impulsivity. The excessive prescription of BZDRAs is a serious problem requiring urgent measures. Research on the prescriptions for overdose patients may lead to clinically significant findings and should be promoted in the future.

Patients with severe hypophosphatasia (HPP) develop osteogenic impairment with extremely low alkaline phosphatase (ALP) activity, resulting in a fatal course during infancy. Mesenchymal stem cells (MSCs) differentiate into various mesenchymal lineages, including bone and cartilage. The efficacy of allogeneic hematopoietic stem cell transplantation for congenital skeletal and storage disorders is limited, and therefore we focused on MSCs for the treatment of HPP. To determine the effect of MSCs on osteogenesis, we performed multiple infusions of ex vivo expanded allogeneic MSCs for two patients with severe HPP who had undergone bone marrow transplantation (BMT) from asymptomatic relatives harboring the heterozygous mutation. There were improvements in not only bone mineralization but also muscle mass, respiratory function, and mental development, resulting in the patients being alive at the age of 3. After the infusion of MSCs, chimerism analysis of the mesenchymal cell fraction isolated from bone marrow in the patients demonstrated that donor-derived DNA sequences existed. Adverse events of BMT were tolerated, whereas those of MSC infusion did not occur. However, restoration of ALP activity was limited, and normal bony architecture could not be achieved. Our data suggest that multiple MSC infusions, following BMT, were effective and brought about clinical benefits for patients with lethal HPP. Allogeneic MSC-based therapy would be useful for patients with other congenital bone diseases and tissue disorders if the curative strategy to restore clinically normal features, including bony architecture, can be established.

Background Rearrangements of chromosome 8q24/MYC (8q24/MYC-r), resulting from t(8;14)(q24;q32), t(2;8)(p11;q24), or t(8;22)(q24;q11), are mainly associated with Burkitt lymphoma/leukemia (BL) and rarely observed in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The characteristics of BCP-ALL with 8q24/MYC-r are poorly understood. Procedure A retrospective nationwide study of data from patients with pediatric BCP-ALL with 8q24/MYC-r in Japan was conducted to clarify the clinical and biological characteristics associated with 8q24/MYC-r BCP-ALL. Results Ten patients with BCP-ALL with 8q24/MYC-r, including three with double-hit leukemia (DHL) (two with t(8;14)(q24;q32) and t(14;18)(q32;q21) and one with t(8;14) and t(3;22)(q27;q11)), were identified. Patients with BCP-ALL with 8q24/MYC-r had higher median age and uric acid and lactate dehydrogenase levels, than those without 8q24/MYC-r. All patients were initially treated with ALL-type chemotherapy; however, four, including one with DHL, were switched to BL-type chemotherapy, based on cytogenetic findings. One patient relapsed after standard-risk ALL-type chemotherapy, and two patients with DHL did not attain complete remission with chemotherapy; all three died within 11 months. The other seven patients treated with BL-type or high-risk ALL-type chemotherapy are alive without disease. Conclusions The clinical and laboratory features of BL with IG-MYC rearrangement, displaying a BCP immunophenotype (Wagener et al. and Herbrueggen et al. termed it as pre-BLL), are similar to those of BCP-ALL with 8q24/MYC-r. Low-risk ALL-type chemotherapy may not be appropriate for them, and further studies are required to establish an adequate therapeutic strategy. Further studies of DHL to identify new treatment strategies are also needed.

Upshaw-Schulman syndrome (USS) is a congenital form of thrombotic thrombocytopenic purpura (TTP) associated with loss-of-function mutations in the ADAMTS13 gene, possibly leading to aberrant complement activation and vascular injury. However, USS is extremely rare, and there have been no systematic studies correlating histopathological severity with local ADAMTS13 expression and complement activation.Here, we compared histopathological features, ADAMTS13 immunoreactivity, and immunoreactivity of complement proteins C4d and C5b-9 among renal biopsy tissues from five USS cases, ten acquired TTP cases, and eleven controls.Pathological analysis revealed chronic glomerular sclerotic changes in the majority of USS cases (4 of 5), with minor glomerular pathology in the remaining case. In two of these four severe cases, more than half of the glomerular segmental sclerosis area was localized in the perihilar region. The average number of ADAMTS13-positive cells per glomerulus was significantly lower in USS cases than controls (p 0.05). Conversely, C4d staining was significantly more prevalent in the glomerular capillary walls of USS cases than controls (p 0.05), while C5b-9 staining did not differ significantly among groups.These findings suggest that the severity of glomerular injury in USS is associated with deficient ADAMTS13 expression and local complement activation, particularly in vascular regions with higher endothelial shear stress. We suggest that C4d immunostaining provides evidence for complement-mediated glomerular damage in USS.

Rotavirus and norovirus are common pathogens associated with gastroenteritis in children. Although rotavirus occasionally induces central nervous system disease, only 3 cases with rotavirus-induced acute myositis have been reported in the English literature. We recently treated a female patient with acute myositis associated with gastroenteritis induced by concurrent infection with rotavirus and norovirus. Having suffered from gastroenteritis for 3 days, she suddenly developed myositis affecting her lower extremities with concomitant creatine kinase elevation. Herein, we present our patient and review the previous cases including those reported in the Japanese literature.

Bone marrow (BM) transplantation (BMT) is one of the treatment strategies for congenital metabolic disease, but leukemia secondary to intensive cytoreductive treatment is a major concern. Besides BM cells, mesenchymal stem cells (MSC) are also used for transplantation. An 8-month-old girl with hypophosphatasia underwent transplantation of haploidentical BM cells followed by two transplants of MSC obtained from her father to facilitate osteogenesis. Fludarabine(Flu)/cyclophosphamide (CPA)/anti-thymocyte globulin were used for myeloablative conditioning, but the patient developed therapy-related leukemia harboring t(9;22)(q34;q11.2); minor BCR-ABL (t-leukemia with Ph) at the age of 32 months. At the age of 40 months she underwent a second BM and third MSC transplant from the same donor. Thereafter, she achieved complete histological and molecular remission. The present case suggests that the combination of cytotoxic agents (Flu/CPA) and MSC led to t-leukemia with Ph as a consequence of chromosome instability and suppression of host anti-tumor immunity.

We report on two cases of auditory ossicular anomaly and one case of traumatic ossicular dislocation evaluated with three-dimensional images using MDCT (multidetector-row CT). The first patient was an 18-year-old female, who had noticed hearing impairment in her right ear since she was a child. The second patient was a 32-year-old male, complaining of hearing loss in his right ear after a head injury. The third patient was a 27-year-old female who had hearing impairment in her right ear probably from birth. The first and the second patients underwent surgery, and their congenital ossicular anomaly and traumatic ossicular disarticulation were identified intraoperatively, which were almost corresponding to the findings shown by three-dimensional computed tomography (3D-CT). In both cases, the additional information provided by 3D-CT, together with conventional cross-sectional CT images, improved the ability to evaluate and diagnose the auditory ossicular lesions preoperatively. Although the third patient did not undergo surgery because she preferred observation, 3D-CT clearly showed the abnormality of her ossicles compared with conventional CT images, which helped her and her family to understand the reason for her hearing impairment. Our cases indicate that 3D-CT is useful not only for surgeons to optimize surgical planning but also for patients to understand the condition of their middle ear.

Intraosseous hemangiomas are rare, comprising only 0.5% to 1% of all osseous neoplasms. The most common locations are the vertebral column and the skull bones; nevertheless, the maxillary bone is quite a rare location and only a few cases have been described in the literature thus far. We describe a case of a 48-year-old woman who was referred to our hospital with a suspected maxillary tumor incidentally discovered on (18) F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging performed during a general medical examination. Computed tomography (CT) demonstrated a 3 cm bony tumor with a honeycomb appearance occupying the left maxillary sinus. Complete surgical resection via the Caldwell-Luc procedure was performed for the purpose of diagnosis and treatment. Histological examination revealed that the tumor was an intraosseous cavernous hemangioma originating from the maxillary bone. Although preoperative angiography and embolization were not performed, intraoperative-blood loss was minimal. No recurrence has been seen in a follow-up period of 3 years.

Purpose: This was a preliminary study to assess surgical construction and regeneration of mastoid air cells in the treatment of cholesteatoma. Methods: Two-stage tympanoplasty with mastoidectomy was performed in four cases of unilateral cholesteatoma with sclerotic mastoid. During the first-stage operation, small fragments of autologous cortical bone were inserted into the cavity after mastoidectomy to form a honeycomb-like structure. Reconstruction of the lateral wall of the mastoid cavity was performed using the mastoid cortical bony plate. Pre- and postoperative mastoid volume was evaluated by three-dimensional reconstruction based on high-resolution computed tomography (HR-CT) images. Results: HR-CT images after the first-stage operation showed that mastoid volume had increased in all subjects. Macroscopic inspection during the second-stage operation revealed that the honeycomb-like structure made of bony fragments and covered by thin mucosa in the mastoid cavity was stable, with no evidence of effusion or granulation tissue. No retraction of the eardrum, middle ear effusion or recurrence of cholesteatoma was observed, and the hearing level on a pure-tone audiogram was improved in any subject 60 - 94 months after the second-stage operation. Conclusion: Surgical construction and regeneration of mastoid air cells using autologous cortical bone can be useful in treatment of cholesteatoma with arrested mastoid pneumatization.

Background Diamond-Blackfan anemia is a rare, clinically heterogeneous, congenital red cell aplasia: 40% of patients have congenital abnormalities. Recent studies have shown that in western countries, the disease is associated with heterozygous mutations in the ribosomal protein (RP) genes in about 50% of patients. There have been no studies to determine the incidence of these mutations in Asian patients with Diamond-Blackfan anemia. Design and Methods We screened 49 Japanese patients with Diamond-Blackfan anemia (45 probands) for mutations in the six known genes associated with Diamond-Blackfan anemia: RPS19 , RPS24 , RPS17 , RPL5 , RPL11 , and RPL35A. RPS14 was also examined due to its implied involvement in 5q- syndrome. Results Mutations in RPS19 , RPL5 , RPL11 and RPS17 were identified in five, four, two and one of the probands, respectively. In total, 12 (27%) of the Japanese Diamond-Blackfan anemia patients had mutations in ribosomal protein genes. No mutations were detected in RPS14 , RPS24 or RPL35A . All patients with RPS19 and RPL5 mutations had physical abnormalities. Remarkably, cleft palate was seen in two patients with RPL5 mutations, and thumb anomalies were seen in six patients with an RPS19 or RPL5 mutation. In contrast, a small-for-date phenotype was seen in five patients without an RPL5 mutation. Conclusions We observed a slightly lower frequency of mutations in the ribosomal protein genes in patients with Diamond-Blackfan anemia compared to the frequency reported in western countries. Genotype-phenotype data suggest an association between anomalies and RPS19 mutations, and a negative association between small-for-date phenotype and RPL5 mutations.

A girl, aged 19 months, presented with a sacrococcygeal tumor that developed at 5 months after birth and gradually enlarged. Serum tumor marker levels were negative. Ultrasound imaging showed abundant blood flow in the tumor. However, neither computed tomography (CT) nor magnetic resonance imaging (MRI) showed contrast agent incorporation. The surgically resected tumor consisted of immature cells with myxoid stroma and proliferating small blood vessels. Immunostaining showed extensive vimentin expression. However, smooth muscle actin, muscle-specific actin, and S-100 protein expression was negative. Neither the ETV6-NTRK3 fusion gene nor the FUS gene rearrangement was detected. Thus, the patient was diagnosed with a primitive myxoid mesenchymal tumor of infancy. This tumor primarily consisted of a mucosal stroma with a low absorption on CT, a low signal on T1-weighted MRI, and a high signal on T2-weighted MRI. A diagnosis of primitive myxoid mesenchymal tumor of infancy should be considered in cases of soft tissue tumors in infants that show prominent vascularity but little contrast enhancement on MRI or CT.

A traditional Chinese herbal medicine, Kampo medicine, maoto, has been widely used in the treatment of febrile symptoms caused by viral infection. This herbal extract granule for oral use, however, is not well accepted by infants or young children due to its unpleasant taste and odor. Therefore, we prepared Kampo medicine, maoto, suppository and investigated the pharmaceutical and clinical efficacy of the suppository. Kampo medicine, maoto, granules were micro-pulverized and homogeneously dispersed into Hosco-H15 to prepare suppositories containing 0.25 to 1.0 g herbal extract by the conventional fusion method. Content of l-ephedrine, an index compound of Kampo medicine, maoto, in the extract granules and suppositories was determined by using a high performance liquid chromatographic method. Physicochemical experiments revealed that the suppository containing 0.5 g herbal extract had the most suitable melting point of 34 degrees C. Contents of l-ephedrine in the suppository were constant, 93-96% of those in the same amount of the extract granules in different three lots. Upper and lower portions of the suppository had the same content of l-ephedrine. The suppository maintained more than 95% of l-ephedrine content through 6 months at 4 degrees C, room temperature and 40 degrees C, although maldistribution of the extract constituent was observed after storage at 40 degrees C. The suppository was administered to 21 pediatric febrile patients at a dose of 1/3 to 2 full pieces depending on their body weight and physical status. Significant reduction (p

The present study evaluated the incidence of otitis media with effusion (OME) after head and neck surgery in patients who had been free from OME preoperatively.The subjects were 47 patients (90 ears; 22 males, 25 females; mean age 46.8 years; range 16-85 years) who had undergone head and neck surgery in our department. All ears had been free from middle ear diseases preoperatively. The operations were performed under general anesthesia in 42 cases, including 40 cases of nitrous oxide (N2O) anesthesia, and local anesthesia in 5 cases. Surgical sites were the middle ear in 2 cases, the nose in 9, the throat in 17, and the neck in 19. Otomicroscopic findings and tympanograms were evaluated three times; on the day before surgery, 1-2 days and 5-9 days after surgery.At the first-postoperative inspection of the ear drums, middle ear effusion was observed in 6 ears (6.7%). Effusion disappeared in all ears at the second-postoperative inspection. Tympanograms, which were type A in all ears before surgery, changed to type B in one ear (1.1%), type C1 in 8 ears (8.9%) and type C2 in 9 ears (10.0%) at the first-postoperative testing. All ears returned to type A except in one ear (from type C2 to type C1) at the second-postoperative testing. The average of intratympanic pressure was -17.5±2.2daPa (mean±SEM) and -59.6±8.4daPa in preoperative and the first-postoperative testing, respectively (p

A rare case of large vocal cord polyp causing dyspnea is reported. A 55-year-old man with thrombocytopenia visited our department complaining of dyspnea and hoarseness. Laryngeal endoscopy showed a large mass located between the vocal cords, which moved up and down in accordance with breathing. The upper airway was very narrow because of the mass. Tracheostomy was performed under local anesthesia and then the mass was resected under general anesthesia using a laryngomicrosurgery technique. The patient's dyspnea and hoarseness disappeared after surgery. The histopathological findings indicated a diagnosis of vocal cord polyp. We consider that tracheostomy is the safest and most useful procedure to guarantee the upper airway in cases of large vocal cord polyp showing dyspnea.

There is compelling evidence for the involvement of hypothalamic-pituitary-adrenal (HPA) axis abnormalities in depression. Growing evidence has suggested that the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test is highly sensitive to detect HPA axis abnormalities. We organized a multicenter study to assess the DEX/CRH test as a state-dependent marker for major depressive episode in the Japanese population. We conducted the DEX/CRH test in 61 inpatients with major depressive episode (Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV)) and 57 healthy subjects. In all, 35 patients were repeatedly assessed with the DEX/CRH test on admission and before discharge. The possible relationships between clinical variables and the DEX/CRH test were also examined. Significantly enhanced pituitary-adrenocortical responses to the DEX/CRH test were observed in patients on admission compared with controls. Such abnormalities in patients were significantly reduced after treatment, particularly in those who underwent electroconvulsive therapy (ECT) in addition to pharmacotherapy. Age and female gender were associated with enhanced hormonal responses to the DEX/CRH test. Severity of depression correlated with DEX/CRH test results, although this was explained, at least in part, by a positive correlation between age and severity in our patients. Medication per se was unrelated to DEX/CRH test results. These results suggest that the DEX/CRH test is a sensitive state-dependent marker to monitor HPA axis abnormalities in major depressive episode during treatment. Restoration from HPA axis abnormalities occurred with clinical responses to treatment, particularly in depressed patients who underwent ECT.

The authors report a 4-year-old girl who developed brain stem glioblastoma. Meningeal irritation was present at onset. Magnetic resonance imaging revealed intracranial and intraspinal leptomeningeal dissemination, which progressed faster than the original tumor. Multiple large cysts developed at the interhemispheric and prepontine cisterns, resulting in progressive obstructive hydrocephalus. The patient survived only 5 months after presentation. Histology was verified by autopsy.

Familial hemophagocytic lymphohistiocytosis (FHL) is a disorder of immune homeostasis characterized by fever, cytopenias, hepatosplenomegaly, and coagulopathy. We studied the outcomes of 13 FHL patients who underwent the first unrelated cord blood transplantation (UCBT) after non-myeloablative conditionings. The major regimen consisted of fludarabine (FLU; n = 12)+melphalan (MEL; n = 11)± low-dose total body irradiation (TBI 2-4 Gy; n = 6). The median age at presentation and period to UCBT were 6 and 5 months, respectively. Central nervous system (CNS) disease developed in one infant at diagnosis, and in two others until UCBT. HLH activity was controlled in all but one at the time of UCBT. Ten patients had early engraftment on median day 21 with no grade >2 treatment-related toxicity and two controllable grade >2 acute GVHD. Two patients with early rejection successfully underwent subsequent UCBT after myeloablative conditioning. Two others had late graft failure following mixed donor chimerism. Two deaths occurred from HLH; early liver failure and late CNS disease. Of 11 FLU+MEL-conditioned patients, the frequency of disease-free complete engraftment was higher for MEL (≥120 mg/m(2) )+TBI, or high-dose MEL (180 mg/m(2) ) than for others (83% vs. 25%, p = 0.036). The FLU+MEL-based non-myeloablative regimen was acceptable for FHL infants undergoing UCBT, although further studies will be needed for confirmation.

Linezolid (LZD)-induced myelosuppression has been reported in adults; however, LZD-induced pure red cell precursor toxicity rarely occurs. A 2-year-old boy diagnosed with infective endocarditis by Streptococcus mitis received LZD after developing resistance to multiple antibiotics. Although his infective symptoms were improved by LZD, progressive anemia was noticed 2 weeks after LZD therapy. Four weeks after LZD administration, his hemoglobin level was 6.5 g/dL and reticulocytes less than 0.1%. Bone marrow examination revealed markedly decreased erythropoiesis with cytoplasmic vacuolation of erythroblasts. Anemia recovered 19 days after cessation of LZD. Elevated protoporphyrin and a high LZD level in the blood suggested that mitochondrial disturbance by high-dose and long-term treatment with LZD may have been responsible for LZD-induced pure red cell precursor toxicity.

We describe neuroblastoma (NB) in monozygotic twins whose ages at the onset of the disease had a 3-year interval. The primary tumor site of twin 1 was the adrenal gland, whereas that of twin 2 was the jejunum/mesentery. MYCN amplification, DNA index, ALK mutation, and copy number alterations of DNA were different between each primary tumor. NB in ectopic sites may have resulted from twin-to-twin metastasis through vascular anastamoses in the placenta. The pathogenesis of this NB involved a premalignant stage of NB during the fetal development and subsequent molecular alterations after birth, resulting in NBs that were phenotypically similar but genetically different.