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Background: This study investigated the effect of adjuvant sublingual immunotherapy (SLIT) on inhaled corticosteroid (ICS) dose in patients with pollinosis-associated asthma., Methods: We retrospectively evaluated patients with cedar pollinosis-associated asthma who initiated pharmacotherapy with or without adjuvant SLIT therapy from December 2014 to December 2016 and who continued treatment for 3 years. Changes in ICS dose (fluticasone propionate or its equivalent), antihistamine use, leukotriene antagonist use and intranasal corticosteroid (INCS) use over the 3-year period were compared., Results: The study included 36 and 35 patients in the add-on SLIT and standard treatment groups, respectively. At 3 years, the add-on SLIT group showed a significant decline in ICS dose (p = 0.024). Although leukotriene antagonist use and INCS use did not differ between the two groups, the percentage of patients using antihistamines at 3 years was significantly lower in the add-on SLIT group than in the standard treatment group (p = 0.009); one in three patients on adjuvant SLIT therapy was able to discontinue ICS treatment. Patients who discontinued ICS treatment were younger (44.6±13.3 years vs. 55.0±14.1 years, p = 0.042), had a higher FEV 1 % predicted (109.9±14.4 vs. 94.8±18.6, p = 0.02), and were on a lower treatment step (2.1±0.7 vs. 3.0±0.8, p = 0.002) than those who did not., Conclusion: The addition of SLIT to standard pharmacotherapy resulted in a significant reduction in ICS dose at 3 years.

Pulmonary Mycobacterium abscessus infection is resistant to many antibiotics and is difficult to treat. We retrospectively analyzed the clinical characteristics of pulmonary infection due to M. abscessus. Eleven cases diagnosed as having pulmonary M. abscessus infection at Osaka Red Cross Hospital from January. 2008, to June, 2012 were enrolled in this study. The average age of the 11 cases was 63 years (all were females). Nine cases showed underlying diseases, comprising 5 cases with Mycobacterium avium complex lung infection, 3 with old pulmonary tuberculosis, and 3 with bronchiectasis. The radiological examination revealed that 10 cases showed the small nodular type, 7 showed the bronchiectatic type, 4 showed a cavity lesion and 4 showed infiltrative shadows. A microbiological definite diagnosis was made from sputum in 10 cases and bronchial lavage fluid in one. As treatment for M. abscessus pulmonary infection, combined multi-drug chemotherapy was carried out in 7 of the 11 cases. No patients were successfully treated with antibiotics alone, whereas 4 patients had no exacerbation of radiological findings without any treatment. One patient received antibiotics including clarithromycin, amikacin and levofloxacin for 2 to 12 months following surgical excision and her sputum cultures have been maintained as negative over the long-term. During the study, none of the 11 patients were known to have died. In this study, we found that M. abscessus pulmonary infection is more common among females, and is found frequently in patients with M. avium complex lung infection. We also found that the clinical course of M. abscessus pulmonary infection was different among patients. We think this is because M. abscessus was shown to comprise three closely related species. M. abscessus is extremely difficult to eradicate, and surgical resection of localized disease or the main lesion or cavity may be significantly effective in preventing the progression of disease.

A 37-year-old woman with acute myeloid leukemia received allogeneic bone marrow transplantation (BMT) after systemic chemotherapy and total body irradiation. Soon after BMT both cutaneous and gastrointestinal graft-versus-host disease (GVHD) developed, but she was successfully treated with corticosteroids and tacrolimus. Thereafter, about 6 months after BMT a dry cough developed, and chest computed tomography (CT) showed a consolidated shadow in the right lower lobe which was resistant to antibiotics, and we finally diagnosed eosinophilic pneumonia based on a bronchoalveolar lavage analysis of the eosinophilia. The eosinophilic pneumonia in this case might have been associated with GVHD, because cutaneous GVHD simultaneously recurred. We report the details of this case because only a few such reports of eosinophilic pneumonia associated with GVHD have been previously described, and such cases may increase with the growing use of transplantations.

Despite otological surgical progress improving clinical congenital ossicular malformation management, some cases remain inadequately treated. We report 27 cases of congenital ossicular malformation, focusing on reasons for remaining or delayed postoperative hearing loss evaluated in 27 congenital ossicular malformation cases in Kyoto Prefecture from 2002 to 2008. Overall success was 93% (25/27) 6 months postoperatively. Two ears had no hearing improvement and three delayed hearing loss 8 to 48 months postoperatively. The first two ears underwent small fenestration stapedotomy with malleus attachment piston, and the other three tympanoplasty type III using an autologous ossicle or total ossicular replacement prosthesis (TORP) as a columella. We discuss problems and solutions using a malleus attachment piston or prosthesis, preoperative audio-and radiological findings, and operative findings including facial nerve anomaly and congenital cholesteatoma.

Since 1970, many hemophilia centers have been opened in the United States and Western Europe. In these centers, nurse coordinators (NCs) play an important role as key persons in improving the QOL of hemophiliacs with a variety of problems. On the other hand, NCs have not been stationed in most Japanese hemophilia centers, although many doctors and nurses in charge of hemophilia care desire that NCs participate in hemophilia treatment. Therefore, a survey of hemophiliacs and their families was conducted to clarify the role of the nurse in Japanese hemophilia care. The results obtained from the analysis of responses concerning 393 patients indicated that about two thirds of the respondents had never consulted with nurses in regard to their disease. Although the total number of items of care and support which were offered by nurses to the patients was 739, the total number of these items which were expected to be offered from nurses to the patients was 1078. These results indicate that the introduction of NCs is necessary for hemophilia care in Japan.

Acquired thrombotic thrombocytopenic purpura (TTP), characterized by widespread thrombus formation in the microcirculation, is a ponderous complication of antiphospholipid syndrome. Recently, von Willebrand factor-cleaving protease (VWF-CPase) activity has been reported as a possible determinant for the occurrence of TTP. To clarify the role of VWF-CPase in the thrombus formation associated with antiphospholipid syndrome, we investigated plasma VWF-CPase activity in patients of collagen diseases with lupus anticoagulant (LA). Decreased plasma VWF-CPase activity less than 50% of the normal activity was observed in 25.7% (n = 18) in 70 patients with collagen diseases and 7 (10%) cases of them showed more lower VWF-CPase activity less than 25%. The IgG fractions obtained from 2 patients with the low VWF-CPase activity strongly inhibited the proteolytic reaction of normal VWF-CPase. There was no significant relationship between LA and plasma VWF-CPase activity. Thrombotic episodes, especially arterial thrombosis, were more frequently observed in LA-positive patients with low VWF-CPase activity. These results suggest that decreased activity of VWF-CPase, partly due to IgG type inhibitor to the enzyme activity may be an additional risk factor for arterial thrombosis in collagen disease patients with antiphospholipid antibodies.

Antiphospholipid antibodies(APA) have been reported to be a heterogeneous family of immunoglobulins. Some APA can be detected via phospholipid dependent coagulation assays when they present as an aspecific coagulation inhibitor, lupus anticoagulant(LA), other antibodies can be measured via immunological assays mostly via their capability to bind to immobilized cardiolipin (anticardiolipin antibody; aCL). Despite their name, APA associated with antiphospholipid syndrome(APS) do not bind phospholipids, but are directed at plasma proteins bound with anionic phospholipids. The antigenic targets of these antibodies include beta 2 glycoprotein I(beta 2 GP I), prothrombin, high- and low-molecular-weight kininogens, annexin V, protein C and protein S. In this article, the current knowledge on the methods of detection and their functional properties are reviewed, and the interaction of these antibodies and acquired activated protein C resistance are discussed.

Recently, a new fibrinogen/fibrin degradation products(FDP) test using monoclonal antibodies against FDP(LPIA FDP-P: FDP-P) has been developed, which is able to measure FDP directly in plasma. The objective of this study is to clarify clinical significance of the test in the diagnosis of fibrinogenolysis and fibrinolysis in comparison with a conventional FDP test using polyclonal antibodies against fibrinogen(FDP-S) and D-dimer test using monoclonal antibodies against D-dimer(D-D). The monoclonal antibodies used in FDP-P test was shown to recognize fragment X, Y and D1 derived from fibrinogen digested by urokinase, and was also to recognize XDP fragments, D-dimer and D derived from cross-linked fibrin digested by tissue plasminogen activator using SDS-PAGE and immunoblotting analysis. There was a good correlation of FDP levels between FDP-P test and FDP-S test. However, levels of FDP in both tests were discrepant in several samples. There was a tendency that the levels of FDP were higher in FDP-S test than in FDP-P test. Such discrepancy was suggesting that soluble fibrin monomer complex(FM) was recognized by the antibodies used in FDP-S test, but not recognized by the antibodies used in FDP-P test. There was also a good correlation of FDP levels between FDP-P test and D-D test. However, the levels of FDP in both tests were discrepant in several samples. The levels of FDP were higher in FDP-P test than in D-D test. These discrepant samples had lower levels of antiplasmin and higher levels of plasmin antiplasmin complex(PIC), and also showed XDP fragments, D-dimer, X, Y, and D1 by using SDS-PAGE. These observations suggest that D-D test measures only fibrinolytic fragments, while FDP-P test measures fibrinogenolytic fragments as well as fibrinolysis. In results, the FDP-P test was confirmed to be a useful tool to examine fibrinogenolysis as well as fibrinolysis more specifically than the conventional FDP test.

Our group conducted a national survey of patients who had died of acquired immunodeficiency syndrome (AIDS) after being infected with human immunodeficiency virus type 1 (HIV-1) by contaminated blood coagulation factor products. A total of 1446 hospitals, clinics, and other health-care institutions throughout Japan were enrolled in the study, which was supported by the Japanese government Ministry of Health and Welfare with a health sciences grant for research on HIV/AIDS. Of the 1434 registered patients who had been infected with HIV-1 by contaminated blood coagulation factor products, 493 (34%) had died as of Oct. 30, 1997. Most were hemophiliacs. The average CD4+ cell count was 25/microliter for the 398 who died of complications from AIDS, compared to an average of 158/microliter for those who died of other causes. Pneumocystis carinii pneumonia, cytomegalovirus infection, and atypical mycobacterial disease were the main causes of death in patients with AIDS. The annual death rate for AIDS patients in Japan dropped dramatically in 1997, 1 year later than a similar trend observed in the United States. The introduction and widespread adoption of new and effective drugs and treatment regimens for HIV-1 and opportunistic infections will be essential life-saving measures.

Factor VIII (IX) inhibitors represent one of the most serious problems for the treatment of patients with hemophilia. The Blood Products Research Organization (Japan) has supported a study group for treatment of hemophiliacs with inhibitors. In 1995 the study group started a prospective matched control study of hemophiliacs with and without inhibitors and compared such factors as quality of life and economic cost. Each inhibitor patient was matched with a control patient in terms of age, type of hemophilia, and severity of hemophilia. A total of 136 patient-pairs were enrolled. Bleeding episodes were more frequent in the control group than in the inhibitor group. Days of hospitalization, days in wheelchairs, and the number of impaired joints were significantly higher for the inhibitor group. Number of blood-product infusions, days of bed rest at home, and days of brace use were the same for both groups. Blood-product expenditures were significantly higher for the inhibitor group than for the control group (yen 10,872,283/patient/year vs. yen 4,327,542/patient/year). Our study highlighted the higher cost of treatment and lower quality of life for hemophiliaes with Factor VII inhibitors.

To evaluate the sensitivity and specificity of confirmatory assays for LA detection, we performed the platelet neutralization procedure (PNP), diluted Russell's viper venom time (dRVVT) confirmatory assay (the ratio of LA-screen and LA-confirm:S/C), and specific hexagonal phase neutralization test (StaLA) on, plasma samples 43 LA-positive in either the ratio of dilute APTT and APTT(dAPTT/APTT) or dRVVT(LA-screen). The sensitivity and the specificity were evaluated by 4 different analyses based on, 1) maximal plasma dilution, 2) correlation between the screening assays and these confirmatory assays, 3) ratio of LA-positive in the confirmatory assays, and 4) receiver operation characteristic (ROC) method. All 4 analyses showed that sensitivity was in the order of PNP > S/C > Staclot-LA. However, the order of the specificity evaluated by the ROC method was Staclot-LA > S/C > PNP. The APTT-based confirmatory assay, PNP can detect LA of the plasma samples that were all positive in the dAPTT/APTT ratio, while the LA-positive plasma samples in dRVVT-confirm were all positive in the dRVVT-screen assay. Our findings suggest that confirmatory assays should be based on the method giving an abnormal screening assay. Accordingly, we recommend the following combinations of screening and confirmatory assays in terms of specificity; 1) dAPTT/APTT ratio and Staclot-LA as the APTT-based assay, and 2) LA-screen and LA-confirm as the dRVVT-based assay.

Age-related changes of 27 items in serum chemistry were investigated in Sprague-Dawley rats of both sexes from 6 to 30 weeks of age. The following 12 items were shown as an increase in those values during growth and maturity, i.e., total protein, albumin (female only), glucose, total cholesterol, triglyceride, phospholipid (female only), beta-lipoprotein, cholinesterase (female only), asparate aminotransferase (female only), creatinine, direct-bilirubin and total-bilirubin. However, the following 4 items decreased with aging, i.e., asparate aminotransferase, alkaline phosphatase, creatine phosphokinase and inorganic phosphorus. No age-related changes were found in the values for calcium, sodium and chloride in both sexes and for alanine aminotransferase, cholinesterase and albumin in males. The sex differences were shown in the following 12 items: higher values in males were alkaline phosphatase, creatinephosphokinase, glucose and inorganic phosphorus, and higher values in females were cholinesterase, albumin, phospholipid, non-esterified fatty acid, urea nitrogen, direct-bilirubin, total-bilirubin and serum iron. No sex-related differences were found in the values for calcium, sodium, chloride and total cholesterol.

TJ-114 (Tsumura Sairei-to) is a powdered extract made from 12 Chinese herbal drugs. TJ-114 is used against various nephrotic diseases and used as an inhibitory treatment for the side effects of glucocorticoids. We expected that TJ-114 would increase the survival ratio of rats given a high dose of glucocorticoid. Therefore, in this study, we investigated the combined effects of glucocorticoid and TJ-114 in rats. An ointment containing fluocinolone acetonide (FA) was applied on the back of 7-week-old Wistar male rats for various periods. TJ-114 was administered orally at the doses of 0.5, 1.0 or 2.0 g/kg simultaneously. The combination with TJ-114 suppressed the loss of body weight by FA. The survival ratio of the FA group was 50%, but it was 83% for the group treated with FA in combination with 0.5 g/kg TJ-114 and no deaths were observed in the other drug combined group. With a lower dose of FA, we investigated its hematological effects and determined the white blood cell (WBC) count. Although the lymphocytes were decreased by FA, the combination with TJ-114 depressed this decrease of lymphocytes significantly. Furthermore, TJ-114 significantly suppressed the insulin increase elicited by FA. Macroscopic observations showed atrophy and decreases in the weights of the thymus, spleen and adrenal, all being target organs of glucocorticoid. The combination with TJ-114 decreased these effects of FA. Moreover, microscopic examinations revealed that FA induced the degeneration of lymphocytes and lymphocyte depletion in the cortex of the thymus, caused atrophy of the white pulp, decreased the extramedullary hematopoiesis of the spleen, and caused the atrophy of zona fasciculata in the adrenal cortex. The combination with TJ-114 depressed these effects significantly. These results suggest that TJ-114 suppresses the adverse side effects of gucocorticoids.

Further modification of the previously reported peroxidase staining method for von Willebrand factor (vWF) multimer is described in this article. The alteration are as follows: affinity purified anti-human vWF rabbit IgG was replaced by commercial anti-human vWF rabbit IgG, and washing and reaction steps were shortened markedly. Despite these modification, the resolution of vWF multimers on the nitrocellulose membrane remains comparable to the autoradiography. However, unlike autoradiography, results produced by this method can be obtained in a day. The features of this method are especially useful in clinical laboratories where both time and equipments are limited.

Shosaiko-to-go-keishikashakuyaku-to (TJ-960) is an extract of nine herbal drugs (Paeoniae radix, Cinna momi cortex, Bupleuri radix, Zingiberis rhizoma, Glycyrrhizae radix, Ginseng radix, Scutellariae radix, Pinelliae tuber and Zizyphi fructus) that has a potent anticonvulsant action. The rat fetuses treated orally with TJ-960 during the organogenesis period (days 7-17 of gestation) revealed no anomalies (up to 3000 mg/kg/day). When TJ-960 was co-administered with sodium valproate (VPA, 400 mg/kg) during the organogenesis period, embryonic resorption, fetal body weight, ossification and skeletal variation or anomalies induced by VPA were markedly reduced. The maternal plasma and embryonic concentration of VPA with TJ-960, however, were not significantly different from VPA alone. These results suggest that TJ-960 has protective effects against the teratogenicity of VPA.

We evaluated a new automated biopsy device for percutaneous renal biopsies under ultrasound guidance, which was recently introduced in Japan for prostate biopsies. This device (Biopty-Gun: Bard Biopty Instrument Uppsala, Sweden) employs a Tru-Cut type smaller needle (18 gauge). We were able to obtain one or two renal tissues in all 57 cases with great ease and in little time. The length of specimen was sufficient (5-17 mm), but the width was thinner than the samples with the Vim-Silverman or Tru-Cut needles. We could achieve a definitive pathological diagnosis in 54 of 57 cases (94.7%), but now, we try to obtain two pieces of tissue for taking more adequate tissue. Only three patients had perirenal hematomas noted by computerized tomography or ultrasonography. We believe that this new automated technique offers a safer and more effective means of obtaining renal tissue.

Experiments were performed to investigate the effects of TJ-41 on spermatogenic disorders under current treatment with adriamycin (ADR). Male ICR mice were intraperitoneally injected with ADR at the dose of 0.15 mg/kg, twice a week for 5 weeks. Simultaneously, these mice were orally administered TJ-41 at the dose of 1, 2 or 4 g/kg for 12 weeks. The effects of TJ-41 were evaluated by histological analysis of germ cells in the testis at 7 weeks after the last injection of ADR. TJ-41 at a dose of 4 g/kg significantly inhibited the decrease of testis weight in mice treated with ADR. TJ-41 at doses of 1 and 4 g/kg significantly decreased the proportion of seminiferous tubules without germ cells as compared with the ADR-treated group. On the other hand, TJ-41 at doses of 1 and 4 g/kg significantly increased the proportion of normal seminiferous tubules and the Sertoli cell ratio of spermatocytes as compared with the ADR-treated group. These results indicate that TJ-41 may qualitatively and quantitatively protect against the decrease of germ cells in the testis of mice treated with ADR.

We reported a case of TMD with transient increase of tetrasomy-21 cells in a phenotypically normal newborn. The patient was admitted to the St. Marianna University Hospital due to hepatosplenomegaly on the 7th days after birth. Hematological findings on admission revealed remarkable leukocytosis (168,300/microliters) with 79% blasts. Immunological studies of the blasts showed a positive reaction for platelet associated antigens, KOR-P77, AN50, TP80 and a pan-T antigen, TP40. Cytochemically blasts were strongly positive for acid phosphatase, positive for alpha NAE and weakly positive for PAS. The platelet peroxidase reaction was observed in rough endoplasmic reticulum of blast cells. Both immunological and cytochemical findings suggested that the blasts were of megakaryocyte lineage. Chromosomal analysis of the blasts showed 48, XX, + 21, +21 (21 tetrasomy). After chemotherapy with PSL and 6MP, bone marrow showed a complete remission. But we thought it was spontaneous remission because PSL and 6MP were not effective to acute megakaryocytic leukemia (AMKL). Bone marrow cells were karyotypically normal on the 67th day of life when abnormal blasts were not observed in the bone marrow.