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Shinji Nakao

Publications and source records attributed to Shinji Nakao.

At least 55 records · Page 3Linked to original sources

[Two cases of pulmonary infection by Mycobacterium abscessus in which drug susceptibility testing results conflicted with clinical courses].

We encountered two cases of pulmonary infection by Mycobacterium abscessus (M. abscessus). [Case 1] A 66-year-old man who had been treated for non-tuberculous mycobacterium in the past was admitted because of productive cough. His chest X-ray film showed cavitation and direct microscopy of sputum revealed positive acid-fast bacilli (AFB). He was given rifampicin (RFP), ethambutol (EB), and clarythromycin (CAM), and then his symptoms and radiographic findings improved. [Case 2] A 74-year-old man with multiple myeloma as an underlying disease was admitted because of a cavitation found on chest radiography and a positive result for AFB in his sputum. Standard antituberculous drug therapy with isoniazid (INH), RFP, EB, and pyradinamide (PZA) was initiated and then the chest radiographic findings improved. As M. abscessus was isolated two weeks after the induction of therapy, the therapeutic regimen was changed to another combination therapy consisting of EB, clarithromycin (CAM) and ciprofloxacin (CPFX), and then his symptoms and radiographic findings were further improved. In both cases, the bacilli found in their sputum were identified as M. abscessus by DNA hybridization. They were completely resistant to all anti-tuberculosis agents and many antibiotics with a high value of MIC. However, their symptoms, radiographic abnormalities and the results of sputum examination improved following chemotherapy. The results obtained by MIC measurement were inconsistent with the clinical outcomes. The measurement of the MIC value of antibiotics do not necessarily predict its therapeutic effect.

Aged↗

High incidence of cytomegalovirus reactivation in adult recipients of an unrelated cord blood transplant.

This retrospective analysis of cytomegalovirus (CMV)-seropositive adult transplant recipients showed that CMV antigenemia occurred after transplantation in 10/10 (100%) recipients of unrelated cord blood, 17/39 (43%) recipients of a related matched donor graft, 16/23 (79%) recipients of an unrelated matched donor graft, and 8/12 (67%) recipients of a mismatched related donor graft. These results suggest that unrelated cord blood transplantation itself may be correlated with a high incidence of CMV reactivation.

Adolescent↗

[Non-myeloablative allogenic peripheral blood stem cell transplantation for treatment of advanced renal cell carcinoma].

Non-myeloablative allogenic peripheral blood stem cell transplantation (mini-transplant) is becoming a preferred treatment for those recipients in whom the potential toxicity risk of standard ablative allogeneic therapy may be acceptable. Graft-versus-tumor effect may be generated against epithelial malignancies that are similar to the graft-versus-leukemia activity documented in human hematological malignancies. Renal cell carcinoma has been shown to be responsive to immunotherapy with recombinant human cytokines and may be an ideal model for exploring this novel therapy. Clinical investigations have demonstrated regression of advanced renal cell carcinoma occurs in some patients following non-myeloablative allogenic peripheral blood stem cell transplantation. However, graft-versus-host disease remains a significant toxicity of nonablative transplantation, and directions for further study include the identification of the definitive tumor antigens involved in the graft-versus-tumor effect and means of selecting those patients who will benefit the most from this promising approach with due regard to improve its safety.

Carcinoma, Renal Cell↗

[Reliability of low platelet counts--comparison of microscopic counts with automated hematology analyzer XE-2100].

Sysmex XE-2100 is an automated hematological analyzer with excellent features that can count platelets by both impedance and optical fluorescent method. Particularly, it is notable that platelet counts by optical fluorescent method (PLT-O) are automatically adopted when platelet counts by impedance method (PLT-I) are less than 50 x 10(3)/microl or platelets have abnormal distribution. We compared PLT-I with PLT-O, and also with microscopic counts, using the samples with thrombocytopenia. Regarding reproducibility, mean coefficient of variation values were 5.3% in both PLT-I and PLT-O, when no flags of "PLT Abn Distribution" appeared in the samples with thrombocytopenia. Coefficient of variation values was 10.4% in PLT-I and 5.9% in PLT-O, when flags of "PLT Abn Distribution" appeared in the sample with thrombocytopenia. Correlation among the data obtained by PLT-I, PLT-O and microscopic counts were excellent. When a large difference was observed between PLT-I and PLT-O, PLT-O was more closely consistent with microscopic counts. PLT-O was useful compared with PLT-I, and this system was considered to measure platelet counts more correctly in the samples with thrombocytopenia. Thus, it was suggested that reliable platelet counts could be reported even in the samples with thrombocytopenia by switching system in XE-2100.

Automation↗

Kasabach-Merritt syndrome associated with giant liver hemangioma: the effect of combined therapy with danaparoid sodium and tranexamic acid.

n patients with Kasabach-Merritt syndrome (KMS), local activation of coagulation commonly results in disseminated intravascular coagulation (DIC). Progress of DIC is associated with 30-40% mortality as a result of uncontrollable hemorrhage. A 39-year-old woman with an enlarging giant liver hemangioma was diagnosed as having KMS with DIC. To control the hemorrhagic diathesis, we commenced combination therapy for DIC with danaparoid (1,250 Ux2/day, intravenously (IV)) and tranexamic acid (0.5 g x 3/day, peros (PO). Rapid improvement of the bleeding tendency and coagulopathy occurred in response to this treatment - that is, DIC was controlled without removing the giant hemangioma. The therapy did not restrict the behavior of the patient by continuous drip and angiography could be performed without bleeding. Such therapy may be beneficial in chronic DIC with activation of fibrinolysis.

Adult↗

Diazepam-binding inhibitor-related protein 1: a candidate autoantigen in acquired aplastic anemia patients harboring a minor population of paroxysmal nocturnal hemoglobinuria-type cells.

To identify candidate antigens in aplastic anemia (AA), we screened proteins derived from a leukemia cell line with serum of an AA patient and identified diazepam-binding inhibitor-related protein 1 (DRS-1). Enzyme-linked immunosorbent assay (ELISA) revealed high titers of anti-DRS-1 antibodies (DRS-1 Abs) in 27 (38.0%) of 71 AA patients displaying increased paroxysmal nocturnal hemoglobinuria (PNH)-type cells (PNH(+)), 2 (6.3%) of 32 PNH(-) AA patients, 5 (38.5%) of 13 PNH(+) myelodysplastic syndrome (MDS) patients, and none of 42 PNH(-) MDS patients. DRS-1 gene was abundantly expressed in myeloid leukemia cell lines and in CD34(+) cells derived from healthy individuals. Stimulation of T cells from an AA patient displaying high DRS-1 Abs with a putative CD4(+) T-cell epitope (amino acid residues [aa's] 191-204) presented by HLA-DR15, which overlapped with a hot spot (aa's 173-198) of DRS-1 Ab epitopes, gave rise to T cells cytotoxic for L cells (murine fibroblasts) that were transfected with DRB1*1501 and DRS-1. Enzyme-linked immunospot assay demonstrated increased frequency of T-cell precursors specific to the DRS-1 peptide in other HLA-DR15(+) AA patients displaying high DRS-1 Ab titers. These findings indicate that DRS-1 may serve as an autoantigen eliciting immune attack against hematopoietic stem cells in a subset of AA patients characterized by increased PNH-type cells.

Anemia, Aplastic↗

Beneficial effect of low-molecular-weight heparin against lipopolysaccharide-induced disseminated intravascular coagulation in rats is abolished by coadministration of tranexamic acid.

OBJECTIVE: We examined the role of coagulation and fibrinolysis in lipopolysaccharide (LPS) induced disseminated intravascular coagulation (DIC) in rats, studying their contribution to fibrin deposition and organ failure in rats with LPS-induced DIC by concurrent administration of low molecular weight heparin (LMWH) with or without tranexamic acid (TA). METHODS: DIC was induced in male Wistar rats by a 4-h infusion of LPS (30 mg/kg) via the tail vein (LPS group). In the LPS+LMWH group LMWH (200 u/kg) was administered to rats from 30 min before the infusion of LPS for 4.5 h. In the LPS+LMWH+TA group LMWH (200 microg/kg) and TA (50 mg/kg) were administered to rats from 30 min before the infusion of LPS for 4.5 h. RESULTS: In the LPS+LMWH group lower plasma levels of TAT, D dimer, creatinine, and alanine aminotransferase were observed, along with less glomerular fibrin deposition and improved survival over rats administered LPS alone. However, these effects of LMWH were completely eliminated and damage beyond that observed in rats administered LPS alone resulted from combined administration of TA (LPS+LMWH+TA group), except that TAT and D dimer levels remained lower than in the group administered LPS alone. CONCLUSIONS: Suppression of fibrinolysis by TA (despite coadministration of LMWH) resulted in increased organ damage in this study, suggesting that depressed fibrinolysis plays a large role in organ failure resulting from LPS-induced DIC, even though hemostatic activation is moderately suppressed by LMWH.

Animals↗

Candida parapsilosis endocarditis that emerged 2 years after abdominal surgery.

A 22-year-old man was hospitalized after 3 months of persistent fever and malaise. He had undergone abdominal surgery 24 months before admission. Echocardiography demonstrated two mobile pedunculated masses in the right ventricle. Multiple blood cultures were positive for Candida parapsilosis. After 4 weeks of miconazole treatment, the two masses were excised via a right atriotomy incision and the transtricuspid value approach. Histological examination revealed that they were fungal vegetation. Antifungal agents were continued for 1 year after surgery. The patient has remained well with no further symptoms for 3 years. This case suggests the necessity for careful evaluation of past history to avoid diagnostic delay in fungal endocarditis.

Adult↗

A guinea pig model for cough variant asthma and role of tachykinins.

Cough variant asthma is known as a major cause of chronic cough. Fundamental features of cough variant asthma are prolonged nonproductive cough responding to bronchodilator therapy, no history of wheezing or dyspnea attack, normal cough sensitivity, and slightly increased bronchial responsiveness. Animal model of cough variant asthma has not been reported. The aim of this study was to establish an animal model for studying detailed pathophysiology of cough variant asthma. Bronchial responsiveness to methacholine and cough reflex sensitivity to capsaicin were measured 72 hours after antigen (ovalbumin, OA) inhalation in actively sensitized guinea pigs. Next, cough number and specific airway resistance (sRaw) were measured during 20 minutes following reinhalation of OA solution, which was carried out 72 hours after the first OA inhalation, and then total cell number and cell differentials in bronchoalveolar lavage fluid (BALE) were measured. Bronchial responsiveness to methacholine, but not cough reflex sensitivity to capsaicin, was significantly increased 72 hours after the first inhalation of OA solution. Number of coughs, sRaw and total cell number in BALF increased significantly by the OA reinhalation, and the cough number and the increase in sRaw were significantly suppressed by beta2 agonist, procaterol. FK224, a specific neurokinin (NK) receptor antagonist, did not significantly influence the OA reinhalation-induced cough and increase in sRaw and total cell number in BALF in this model In conclusion, pathophysiologic feature of this animal model is similar to that of clinical cough variant asthma. Tachykinins may not play an important part in antigen-induced cough associated with bronchoconstriction and airway inflammation in cough variant asthma.

Airway Resistance↗

An idiopathic skin eruption resembling a butterfly rash in a septic patient with disseminated intravascular coagulation following bone marrow transplantation.

A 31-year-old man who underwent chemotherapy and bone marrow transplantation to treat acute myeloblastic leukemia was admitted to our department complaining of high fever and hypotension. His physical examination revealed warm shock state, eruptions resembling that seen in systemic lupus erythematosus on his face and cyanosis in his fingers. We diagnosed septic shock and idiopathic skin eruption on his face. Following treatment with blood transfusion, anticoagulant, antibiotics, respirator and continuous arteriovenous hemofiltration and dialysis, the patient's condition gradually improved. The eruptions on his face first observed at admission progressed with a worsening of his disseminated intravascular coagulation (DIC), and subsided with an improvement in his DIC. A biopsy of the eruption was taken and pathological findings of the eruption revealed multiple micro-fibrin depositions of the dermis. The skin necrosis in purpura fulminans often begins in the distal extremities. But our patient developed this uncommon skin eruption on his face. Patients with an idiopathic skin eruption resembling a butterfly rash in a septic patient should be considered to complicate DIC as in the present case.

Adult↗

Relationship between endothelin and the pathophysiology of tissue factor-induced and lipopolysaccharide-induced disseminated intravascular coagulation in rats: a study examining the effect of an endothelin receptor antagonist.

We investigated the relationship between endothelin, a potent vasoconstrictor peptide, and the pathophysiology of disseminated intravascular coagulation (DIC), using two models of DIC. Experimental DIC was induced by sustained infusion of 50 mg/kg lipopolysaccharide (LPS), or 3.75 U/kg thromboplastin, for 4 h via the rat tail vein. The effect of administration of a non-selective endothelin receptor antagonist (TAK-044) (2, 10, or 50 mg/kg, from -0.5 to 4 h) on thromboplastin-induced DIC was not significant. However, LPS-induced elevation of alanine aminotransferase, creatinine and glomerular fibrin deposition was significantly suppressed by co-administration of TAK-044 in a dose-dependent manner, although no effect of TAK-044 was observed on the platelet count, fibrinogen concentration or the level of thrombin-antithrombin complex. Moreover, plasma levels of D-dimer, which reflect the grade of fibrinolysis of cross-linked fibrin, were significantly increased by co-administration of each dose of TAK-044 in the LPS-induced DIC model in rats. Our results suggest that vasoconstriction, as well as depressed fibrinolysis, contribute to severe organ dysfunction in LPS-induced, but not thromboplastin-induced, DIC, and that endothelin plays a role in the development of organ injury in LPS-induced DIC in rats.

Alanine Transaminase↗

Antithrombotic role of nitric oxide in rats under physiological conditions.

Although sepsis-induced release of nitric oxide (NO) is known to have an antithrombotic effect, it is unknown if NO exerts this same effect under physiological conditions. We have there-fore attempted to determine whether or not NO protects against thrombus formation in normal Wistar rats injected with various amounts (0.8, 4.0, 20.0 and 100 mg/kg/4 hr) of L-NAME (N (omega)-nitro-l-arginine methyl ester), an NO synthase inhibitor, via the tail vein. Plasma levels of D-dimer fragments of fibrin were significantly increased in rats receiving L-NAME (0.21+/-0.04, 0.22+/-0.05, 0.26+/-0.07, 0.59+/-0.17 micro g/mL, means+/-SE; p<0.05, 0.05, 0.05, 0.01: L-NAME 0.8, 4, 20, 100, respectively, compared with control levels: <0.06 micro g/mL), and thrombin-anti-thrombin complex (TAT) levels were significantly increased in rats receiving 20mg/kg/4 hr or greater doses of L-NAME (4.5+/-1.1, 4.7+/-1.4, 18.7+/-4.9, 42.5+/-4.0 ng/mL, NS, NS, p<0.05, 0.01, respectively, compared with control levels: 3.8+/-1.2 ng/mL). Glomerular fibrin deposition was increased in a dose-dependent manner in rats receiving L-NAME (6.8+/-1.5, 13.9+/-1.6, 32.4+/-2.6, 49.2+/-5.2%, p<0.05, 0.05, 0.01, 0.01, respectively, com-pared with control levels: 0.0+/-0.0%). Renal dysfunction and hepatic dysfunction were observed in rats receiving 20mg/kg/4 hr or greater, or 100mg/kg/4 hr, doses of L-NAME, respectively. Mean blood pressure was also elevated in rats receiving L-NAME in a dose-dependent manner. These findings suggest that NO, in addition to regulating blood pressure, is involved in prevention of thrombus formation under physiological circumstances.

Animals↗

Significance of decreased plasma D-dimer levels following lipopolysaccharide-induced disseminated intravascular coagulation in rats.

Plasma D-dimer (DD) is considered to be one of the most useful markers in the diagnosis and assessment of disseminated intravascular coagulation (DIC). The present study was performed to clarify the role of DD in a rat model of lipopolysaccharide (LPS)-induced DIC in which low-molecular-weight heparin (LMWH) and tranexamic acid (TA) were used. We investigated whether a relationship exists between plasma DD levels and severity of DIC. Experimental DIC was induced in rats by a sustained 4-hour infusion of 30 mg/kg LPS administered via the tail vein (LPS group). Rats received either LPS alone (LPS group) or LPS combined with 200 U/kg LMWH (LPS+LMWH group) or 50 mg/kg TA (LPS+TA group) from -30 minutes to 4 hours. Blood was drawn from each rat at 4, 8, and 12 hours. Plasma levels of thrombin-antithrombin complex (TAT) and creatinine were suppressed in the LPS+LMWH group, and less glomerular fibrin deposition was observed compared with the LPS group. On the other hand, an increased level of creatinine and increased glomerular fibrin deposition were observed in the LPS+TA group compared with the LPS group. LMWH demonstrated a protective effect against LPS-induced DIC, resulting in increased survival at 12 hours, whereas TA had the opposite effect. From these results, it appears that LMWH protects against LPS-induced DIC, but TA exacerbates LPS-induced DIC. It was interesting that plasma levels of DD were almost completely suppressed by concurrent administration of either TA or LMWH in this LPS-induced DIC model. This finding suggested that plasma levels of DD were suppressed by inhibition of coagulation (reduced deposition of fibrin) in the LPS+LMWH group and that DD levels were also suppressed by inhibition of fibrinolysis (reduced degradation of fibrin by plasmin) in the LPS+TA group. Thus care should be taken when evaluating the significance of plasma DD levels, because suppressed levels can occur with progressive fibrin deposition and worsening organ dysfunction or improvement in the course of DIC.

Animals↗

Efficacy and safety of imatinib mesylate for patients in the first chronic phase of chronic myeloid leukemia: results of a Japanese phase II clinical study.

Imatinib mesylate is a relatively new drug that targets the BCR-ABL chimeric protein, the molecular basis of chronic myeloid leukemia (CML). A phase II clinical trial in 39 Japanese patients in the first chronic phase of CML was conducted with imatinib mesylate at a dose of 400 mg/day. Hematologic complete response was obtained in 92.3% of the patients, complete cytogenetic response (CR) was obtained in 43.6%, and major partial CR was obtained in 20.5% of the patients. Although 29 of 39 patients required an adjustment of dosing because of grade 3 or 4 adverse events, most of the events were reversible, and 25 of the 29 patients were able to resume therapy. Between day 15 and day 35, grade 3 or 4 neutropenia and/or leukocytopenia occurred in 13 patients, and grade 3 thrombocytopenia occurred in 5 patients. Overall, nonhematologic grade 3 adverse events occurred in 28.2% of the patients. These data support the use of imatinib mesylate as the treatment of choice for chronic-phase CML patients.

Adult↗

Chronic hypersensitivity pneumonitis caused by Aspergillus complicated with pulmonary aspergilloma.

A 57-year-old man consulted our hospital with a history of the gradual onset of dyspnea and a productive cough. Chest computed tomographic (CT) scans showed a nodular shadow in a cavity lesion, and reticulonodular, cystic, and ground-grass opacities in the bilateral lung fields with honeycombing. He was diagnosed as having pulmonary aspergilloma and idiopathic pulmonary fibrosis (IPF). As an outpatient, he suffered from dyspnea upon physical exertion with exacerbation of the high-resolution CT (HRCT) opacities. An inhalation provocation test for Aspergillosis fumigatus was positive and chronic hypersensitivity pneumonitis (CHP) caused by Aspergillus was finally diagnosed. Insidious CHP is sometimes misdiagnosed as IPF. The diagnosis of insidious CHP should be made on the basis of a detailed history, specific HRCT findings, and lymphocyte-dominant bronchoalveolar lavage fluid cell findings.

Alveolitis, Extrinsic Allergic↗

[Transient liver injury caused by gefitinib].

Gefitinib blocks epidermal growth factor receptor autophosphorylation and subsequently the signal transduction pathways implicated in proliferation, metastasis, invasion, and angiogenesis. Reported adverse reactions to gefitinib include liver injury that is not fully understood. Liver injury was observed in 5 (12.2%) of 41 patients with non-small cell lung cancer who received gefinitib monotherapy. Onset of liver injury was seen between 28 and 56 days after initiation of administration. Two patients had Grade 2 liver injury and 3 patients, Grade 3. In 4 patients, liver injury was temporary, lasting during a period of continuous gefitinib administration. In another patient, gefitinib was discontinued because of the onset of liver injury, which improved when gefitinib administration was restarted. Gefitinib is necessary in most patients whose lung cancer is refractory to cytotoxic chemotherapy, because no other treatment regimens are available at present. The rate of liver injury in cases treated with gefitinib is high, and so it is necessary to observe liver function carefully, but the liver injury due to this drug is often transient. However, the use of gefitinib in many cases appears to be a necessity.

Adult↗

Reduced-intensity allogeneic stem cell transplantation for renal cell carcinoma: in vivo evidence of a graft-versus-tumor effect.

We report the cases of 3 patients with advanced renal cell carcinoma who underwent reduced-intensity allogeneic stem cell transplantation. In 2 partial responders, histologic analyses of metastases revealed prominent accumulation of CD8+ T cells and degenerative changes of clear cell carcinoma, suggestive of induction of tumor-specific cytotoxic T lymphocytes.

Aged↗