New host record of Thelazia callipaeda (Nematoda: Spirurida) with a notably wide host range and shared zoonotic lineage in Japan.

Thelazia callipaeda (Nematoda: Spirurida: Thelaziidae) parasitizes the eyes of dogs, cats, humans, and various wild mammals, and is transmitted by drosophilid flies. In Japan, T. callipaeda is considered an emerging parasite that has expanded its endemic region northward. However, reports of its detection in mammals other than domestic animals and humans are scarce. This study reports the detection of T. callipaeda in Japanese red fox (Vulpes vulpes japonica), masked palm civet (Paguma larvata), Japanese badger (Meles anakuma), Japanese black bear (Ursus thibetanus japonicus), raccoon (Procyon lotor), Japanese raccoon dog (Nyctereutes viverrinus), domestic dog (Canis lupus familiaris), domestic cat (Felis silvestris catus), and human. Of these, the Japanese red fox, masked palm civet, Japanese badger, and Japanese black bear have been reported as novel host records. Sequence analysis of the cytochrome c oxidase subunit I gene of T. callipaeda revealed two unique lineages specific to Japan, with no regional or host species differences. These results suggest a wide host range for T. callipaeda, highlighting the significant role of wildlife as a reservoir for this parasite in Japan.

Relationship between cognitive function affecting motor Functional Independence Measure and hypnotics.

Otsubo H, Kishimoto K, Hirano I, Nakano H, Itaya K, Kumaki R, Osumi H. Relationship between cognitive function affecting motor Functional Independence Measure and hypnotics. Jpn J Compr Rehabil Sci 2022; 13: 4-11. Purpose: The purpose of this study was to examine the relationship between cognitive dysfunction affecting motor Functional Independence Measure (FIM) and hypnotics. Methods: This was a retrospective study involving 509 patients aged ≥ 65 years who were discharged from a convalescent rehabilitation ward. Results: Multiple regression analysis was performed with motor FIM efficiency and motor FIM effectiveness (motor FIM-e) as independent variables and the presence or absence of cognitive dysfunction as the dependent variable. The use of hypnotics in patients with cognitive dysfunction showed a positive relationship with motor FIM efficiency (ß = 0.147, P = 0.019) and motor FIM-e (ß = 0.141, P = 0.026). Multiple regression analyses were performed after further classifying hypnotics by therapeutic class into hypnotics with new mechanisms, non-benzodiazepine (BZ) hypnotics, and BZ hypnotics. Non-BZ hypnotics (ß = 0.141, P = 0.021) showed a positive relationship with motor FIM efficiency. Non-BZ hypnotics (ß = 0.158, P = 0.009) and BZ hypnotics (ß = 0.178, P = 0.003) showed a positive relationship with motor FIM-e, whereas hypnotics with new mechanisms of action did not. In contrast, none of the three combinations of hypnotics showed any significant relationship with either motor FIM efficiency or motor FIM-e in patients without cognitive dysfunction. Conclusion: The results suggested that the use of hypnotics in patients with cognitive dysfunction increases motor FIM efficiency and motor FIM-e.

Epidemiological Study of Pathogenic Leptospira in Raccoons (Procyon lotor) in a Suburb of Tokyo, Japan.

Leptospirosis is a zoonosis that affects humans and animals worldwide. Raccoons (Procyon lotor), adopted in urban environments, may act as potential reservoirs of Leptospira. We investigated the prevalence of pathogenic Leptospira in the kidney and urine samples of raccoons living in Tokyo, as well as anti-leptospiral antibodies in their serum, and aimed to examine the factors that expose raccoons to Leptospira. Polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect leptospiral DNA and anti-leptospiral antibodies, respectively. Thirty-six of 156 raccoons (23.1%) were positive by PCR, and 16 of 165 raccoons (9.7%) were positive by ELISA. The prevalence and seroprevalence rates differed depending on the raccoon dispersal period. We used univariable logistic regression to estimate the environmental factors associated with pathogenic Leptospira and anti-leptospiral antibodies in raccoons. Significant differences were observed in the PCR results for the seasons (spring−summer) (p = 0.01), average monthly temperature (p < 0.01), and average monthly rainfall (p < 0.01). No significant difference was seen in the ELISA results, but raccoons in larger urban areas tended to have higher seroprevalence rates (p = 0.06). We identified a pattern of leptospiral spread in raccoon dispersal and environmental factors that expose raccoons to Leptospira.

Online reporting system for transfusion-related adverse events to enhance recipient haemovigilance in Japan: a pilot study.

BACKGROUND: A surveillance system for transfusion-related adverse reactions and infectious diseases in Japan was started at a national level in 1993, but current reporting of events in recipients is performed on a voluntary basis. A reporting system which can collect information on all transfusion-related events in recipients is required in Japan. METHODS: We have developed an online reporting system for transfusion-related events and performed a pilot study in 12 hospitals from 2007 to 2010. RESULTS: The overall incidence of adverse events per transfusion bag was 1.47%. Platelet concentrates gave rise to statistically more adverse events (4.16%) than red blood cells (0.66%) and fresh-frozen plasma (0.93%). In addition, we found that the incidence of adverse events varied between hospitals according to their size and patient characteristics. CONCLUSION: This online reporting system is useful for collection and analysis of actual adverse events in recipients of blood transfusions and may contribute to enhancement of the existing surveillance system for recipients in Japan.

[High-dose methotrexate followed by whole-brain irradiation for primary central nervous system lymphoma patients--a retrospective study in a single institute].

This study analyzed retrospectively the clinical efficacy of combined therapy consisting of high-dose methotrexate (MTX), administered at a dose of 4 g/m2 every 2 weeks (maximum of 4 courses), followed by whole-brain irradiation for newly diagnosed primary central nervous system lymphoma (PCNSL) patients. Fifteen patients (median age: 59 years old; range: 26-79) were diagnosed by histological examinations or imaging techniques in our hospital. Of 15 patients, 12 (6: complete response; 6: partial response) achieved objective response, and the response rate was 80% (95% CI, 51.9-95.7%). The median follow-up time was 20 (range: 3-81) months, and the 3-year survival rate was 76%. The overall survival time was 71 months (95% CI, 23. 7-118.3 months), and the progression free survival was 15 months (95% CI, 0-43.8 months). The major toxicity (grade>or=3) of high-dose MTX included cytopenia (20%), acute respiratory distress syndrome (6.7%), and liver damage (6.7%). No patient evidenced complicated leukoencephalopathy in the follow-up time. The combined therapy of high-dose MTX followed by whole-brain irradiation showed a substantial antitumor efficacy in PCNSL patients. Prospective studies are required to determine the suitable treatment schedule for MTX and irradiation.

Gemtuzumab ozogamicin (GO) in relapsed/refractory patients with acute myeloid leukemia.

OBJECTIVE: Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 antibody, linked to calicheamicin, which has been approved in Japan recently. We conducted to evaluate the efficacy and toxicity of GO in our patients with relapsed or refractory AML retrospectively. PATIENTS AND METHODS: Data were collected between March 1, 2000, and March 1, 2006, on 10 patients with relapsed or refractory AML(excluding FAB: M3). Scheduled treatment was two doses of GO monotherapy, 14-28 days apart. RESULTS: Of the 10 assessable patients, two patients achieved CR. CR duration of one patient lasted for 52 months with post-remission treatment. Grade 4 neutropenia occurred in 9 patients, and the incidence of grade 3 or 4 thrombocytopenia was 100%, with no severe bleeding events. Two patients developed infusion-related adverse events that included grade 3 allergic reaction with shock status. Liver damage (grade 3 or 4) were observed in 40% of patients after GO treatment. No patient developed hepatic veno-occlusive disease including 2 patients who underwent HSCT. CONCLUSION: GO is a valuable new treatment option for relapsed or refractory AML patients, however, the benefit from single agent appears insufficient. On going clinical trials including combination with other antileukemic agents might better define the role of GO.

Current risks in blood transfusion in Japan.

Over the past decades, the incidence of transfusion-transmitted diseases has been dramatically reduced. These reductions have been due to a multifocal approach to the collection, processing, and release of blood components. The estimated risks of transfusion-transmitted hepatitis viruses are now extremely small, but the possibility of infections with emerging pathogens always exists because preventive measures may not be available for all cases. Thus, some patients may be harmed before preventive measures are introduced. Beside transfusion-transmitted infections (TTI), unsolved residual risks such as transfusion-related acute lung injury or incompatible blood components transfusion still exist as major concerns. Continuous efforts toward research on and the prevention of adverse reaction-related blood components must be made to ensure blood safety. The purpose of this article is to introduce the concept of the current risks of transfusion including TTI, review the preventive measures already implemented, and discuss future visions for transfusion safety in Japan.

Accumulated cytokines in stored autologous blood do not cause febrile nonhemolytic transfusion reactions.

Accumulated inflammatory cytokines are considered to be a cause of febrile nonhemolytic transfusion reactions (FNHTRs) of platelet transfusions. Inflammatory cytokines have been found in red cell components stored at 4 degrees C; however, their relationship to FNHTRs has not been clearly demonstrated following red cell transfusions. We measured cytokine levels in stored blood, and determined whether inflammatory marker concentrations were elevated in subjects infused with autologous blood stored for 5 weeks. In conclusion, cytokines accumulated in blood stored at 4 degrees C, but their increases were small. No changes were seen in recipients' inflammatory markers after blood transfusion. Our results indicate that cytokines in stored autologous blood are not responsible for FNHTRs.

Elevated serum levels of human matrix metalloproteinase-9 (MMP-9) during the induction of peripheral blood stem cell mobilization by granulocyte colony-stimulating factor (G-CSF).

To investigate the role of matrix metalloproteinases (MMPs) in the mobilization of peripheral blood stem cells stimulated by granulocyte colony-stimulating factor (G-CSF), we analyzed MMP serum levels in 11 healthy donors and 9 patients who had hematological malignancies or germ cell tumors. A dose of 5-10 microg/kg per day of G-CSF (lenograstim) was administered for 4-8 days to each subject. The serum levels of MMP-2, and MMP-9; interleukin-3, -6, -8, and -10; stem cell factor; interferon-gamma; and tumor necrosis factor-alpha were measured both before and during G-CSF administration. MMP-9 was found to be increased in both the cancer patients and the healthy donor group. In contrast, the levels of each of the other factors tested were unchanged. No significant positive correlation was observed between the MMP-9 levels and the number of CD34+ cells. Hence, we found no significant role for MMPs during the mobilization of peripheral blood stem cells stimulated by G-CSF.

Long-term follow-up of autologous stem cell transplantation for patients with aggressive non-Hodgkin lymphoma who had bone marrow involvement at initial diagnosis in the pre-rituximab era.

BACKGROUND: High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is an important treatment option for selected patients with aggressive non-Hodgkin lymphoma; however, the effectiveness of HDT for patients with bone marrow (BM) involvement of lymphoma cells is not well defined. PATIENTS AND METHODS: Between February 1991 and December 2001, 57 patients with aggressive non-Hodgkin lymphoma were treated with HDT and ASCT. Thirteen of 57 patients who had BM infiltration at initial diagnosis were analyzed. RESULTS: Median follow-up was 11.5 years. Eleven of 13 patients (85%) exhibited complete remission after HDT. The overall survival (OS) at 10 years was 49%, and the median survival time was 74.3 months. Meanwhile, the probability of OS at 10 years for 44 patients who did not have BM disease was 60%. There was no significant difference in OS (P=0.895) between patients with or without BM disease at initial diagnosis. CONCLUSION: High-dose therapy treatment followed by ASCT might save some groups of patients with lymphoma regardless of BM involvement at initial diagnosis.

Carcinoembryonic antigen-producing multiple myeloma detected by a transcription-reverse transcription concerted reaction system.

Multiple myeloma is a disease involving the clonal evolution of plasma cells that produce monoclonal immunoglobulin; however, other products, such as ammonia and amylase, reportedly are secreted by neoplastic plasma cells. We describe a patient with immunoglobulin A (IgA) myeloma who showed a high serum level of carcinoembryonic antigen (CEA) that correlated well with disease status and IgA level. We detected CEA-specific messenger RNA in plasma cells by means of a recently introduced rapid and quantitative RNA-amplification system, the transcription-reverse transcription concerted reaction system. This report is the first of a patient with a diagnosis of CEA-producing multiple myeloma.

Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia.

We investigated the significance of the platelet indices, mean platelet volume (MPV), platelet size deviation width (PDW), and platelet-large cell ratio (P-LCR), in the diagnosis of thrombocytopenia by comparing these levels in 40 patients with hypo-productive thrombocytopenia (aplastic anaemia; AA) and 39 patients with hyper-destructive thrombocytopenia (immune thrombo-cytopenia; ITP). The sensitivity and specificity of platelet indices to make a diagnosis of ITP were also compared. All platelet indices were significantly higher in ITP than in AA, and platelet indices showed sufficient sensitivity and specificity. The area under the curve (AUC) of the receiver operating characteristics curve of platelet indices was large enough to enable the diagnosis of ITP. P-LCR and PDW had the largest AUCs, which indicated that these values were very reliable for immune thrombocytopenia. Our results suggest that these indices provide clinical information about the underlying conditions of thrombocytopenia. More attention should be paid to these indices in the diagnosis of thrombocytopenia.

CD2+ tetraploid acute promyelocytic leukemia variant with double (15;17) translocations.

We report a patient with a variant form of CD2+ acute promyelocytic leukemia (APL) who had double translocations (15;17) in a single leukemic cell. The patient presented with severe neutropenia, thrombocytopenia, and disseminated intravascular coagulation. The bone marrow showed marked hyperplasia with large leukemic cells that had bizarre nuclear configuration and basophilic, hypogranular cytoplasm. Leukemic cells were positive for CD2, 13, 33, 34, and 56 and negative for HLA-DR. The karyotype of the abnormal clone was characterized as 92,XXYY, t(15;17)(q22;q21)x2. No other additional abnormal clone was found, and the patient's condition was diagnosed as tetraploid APL variant. Fluorescence in situ hybridization assay revealed 2 promyelocytic leukemia and retinoic acid receptor alpha (PML/RARA) fusion signals, and reverse transcription-polymerase chain reaction assay revealed short-form PML/RARA fusion transcript. Tetraploidy in APL is a very rare abnormality. Double translocations were an additional abnormality in this case, and this patient's karyotype might have had some influence on morphological characteristics, expression of CD2, and poor clinical outcome.

Th1/Th2 lymphocyte balance in patients with aplastic anemia.

Activated T cell plays an important role in the pathogenesis of aplastic anemia (AA). CD4+ T cells are divided into Th1 cells producing hematopoietic inhibitory cytokines like interferon-gamma and Th2 cells producing interleukin-4. We investigated the Th1/Th2 cell ratio in the peripheral blood of AA patients treated with immunosuppressive therapy (IST). There were 10 patients who responded well to IST (responders) and 3 patients who were refractory to IST (non-responders). Th1 cells were lower in responders than in non-responders (16.2+/-2.4% vs. 28.8+/-5.5%, respectively, p<0.05), whereas Th2 cells did not differ. The Th1/Th2 ratio was also significantly lower in responders than in non-responders, being 13.2+/-1.5 and 40.4+/-5.1 (p<0.001), respectively. In three responders, the Th1/Th2 ratio was declined according to the hematological recovery (from 10.6 to 8.3, 16.3 to 10.9 and 11.8 to 9.5). Our results suggest that Th1 lymphocytes are more predominant in AA, and it may be very useful to monitor the Th1/Th2 ratio during IST.

Serum soluble interleukin-2 receptor in eosinophilia.

The relationship between soluble interleukin-2 receptor (sIL-2R) levels and clinical characteristics was evaluated in patients with eosinophilia. Thirty-eight out of 60 patients showed sIL-2R levels of more than 800 U/ml. In these patients, sIL-2R was closely related to the eosinophil count, but not the IgE level. Their underlying diseases were heterogeneous, including neoplasms and collagen diseases. In patients with lower sIL-2R levels, there was no relationship to the eosinophil count, but sIL-2R was correlated with the IgE level. These findings indicate that patients with eosinophilia and higher sIL-2R levels tend to have underlying diseases other than allergy, and might be more severely ill than patients with lower sIL-2R levels. sIL-2R may be a good marker for evaluating patients with eosinophilia, as an indicator of the probable etiology and severity of their diseases.

Successful immunosuppressive therapy with cyclosporine A for posthepatitis B-cell deficiency with activated cytoplasmic interferon--gamma-positive T-lymphocytes.

We describe a patient with transient disappearance of B-cells, hypogammaglobulinemia, and mild pancytopenia after acute hepatitis. Both HLA-DR+CD8+ and intracellular interferon-gamma+/interleukin-4- cell levels were markedly increased, resulting in an increase in the cytotoxic T-cell (T(C))1/Tc2 and helper T-cell (T(H))1/T(H)2 ratios. After immunosuppressive therapy with cyclosporine A, these parameters of T-cell activation were clearly decreased, and hematologic recovery, including an increase in B-lymphocytes and immunoglobulin concentration, was obtained. These results suggest that there had been suppression of B-cells by activated T-cells. Some patients with common variable immunodeficiency show similar activation of T-cell function, and the present findings suggest the possibility of immunosuppressive therapy for such patients.