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Biomedical subjects

T Masaoka

Publications and source records attributed to T Masaoka.

At least 37 records · Page 2Linked to original sources

Evaluation of the AMPLICOR CMV, COBAS AMPLICOR CMV monitor and antigenemia assay for cytomegalovirus disease.

The AMPLICOR CMV (qualitative DNA assay by PCR), COBAS AMPLICOR CMV Monitor (quantitative DNA assay by PCR), and antigenemia assay were tested for their ability to diagnose cytomegalovirus (CMV) infection in 115 immunocompromised patients. The AMPLICOR qualitative assay and the antigenemia assay were positive for all nine patients with a clinical diagnosis of CMV disease. The AMPLICOR quantitative assay was negative for one of the nine patients. In 106 patients without CMV disease, the AMPLICOR qualitative test was positive in 22, the quantitative test was positive in 23, and the antigenemia test was positive in 55 patients. The AMPLICOR qualitative and quantitative assays had specificities of 79% and 78% in patients without CMV disease, while that of the antigenemia assay was 48%. Diagnostic efficiencies were 79% for the AMPLICOR qualitative assay, 69% for the AMPLICOR quantitative assay, and 48% for the antigenemia assay. All three tests yielded positive results before, or at the same time as, the onset of CMV disease in most cases, which suggests they can be used to predict disease before the onset of symptoms. During antiviral treatment, test results tended to decrease quantitatively and finally became negative; negative results were followed by remission of symptoms. This suggests that the AMPLICOR quantitative assay and the antigenemia assay could be useful for monitoring therapeutic efficacy. The AMPLICOR qualitative and quantitative assays, as well as the antigenemia assay were considered effective for all of the following: diagnosing CMV disease, predicting the onset of disease, and evaluating the effectiveness of antiviral chemotherapy. The antigenemia assay was at times difficult to perform in the case of severely neutropenic patients, whereas the AMPLICOR assays could be used in such cases.

Antigens, Viral↗

[Early phase II clinical trial of amrubicin hydrochloride in patients with malignant lymphoma].

An early phase II multi-center collaborative study of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, was conducted for malignant lymphoma at 12 institutions nationwide. A total of 41 patients were enrolled in this study between January 1988 and October 1990. Of these, 36 patients, six patients with Hodgkin's disease (HD) and 30 patients with non-Hodgkin's lymphoma (NHL), were eligible for the study. The starting dose of amrubicin hydrochloride was 100 mg/m2 (body surface area) and it was administered once every three weeks, in principle. The efficacy was assessed for 34 patients, excluding two patients: one who has not been followed up adequately and the other violated the dosing schedule (once per week). The overall response rates (CR + PR) were 50.0% (3/6) for HD and 42.9% (12/28) for NHL. Furthermore, a relatively high response rate was noted in 8 (36.4%) of 22 NHL patients who had been treated with other anthracycline derivatives prior to the trial. The safety of amrubicin hydrochloride was assessed for 36 eligible patients. Leukopenia (grade 3 or higher) and thrombocytopenia were noted in 21 patients (58.3%) and 10 patients (27.8%), respectively. Anorexia, nausea/vomiting, fever, alopecia, decrease in hemoglobin and elevations of GOT and GPT levels were observed with a relatively high frequency. Other than myelosuppression, the following adverse reactions (grade 3 or higher) occurred during the course of the trial: diarrhea (two patients), alopecia (two patients), stomatitis (one patient), anorexia (one patient), nausea/vomiting (one patient) and fever (one patient). In conclusion, these results indicate that amrubicin hydrochloride is effective in the treatment of patients with malignant lymphoma.

Aged↗

[Late phase II clinical study of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, for malignant lymphoma].

A late phase II clinical trial of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, was conducted at 14 institutions nationwide, in patients with non-Hodgkin's lymphoma. In this multi-center collaborative study, doxorubicin hydrochloride was replaced by amrubicin hydrochloride in CHOP therapy, a standard regimen for non-Hodgkin's lymphoma consisting of cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisolone. A total of 39 patients were enrolled in this study between January 1996 and March 1998. Among them, 37 patients were eligible for this study. The study drugs were administered to patients with non-Hodgkin's lymphoma according to the following schedule: amrubicin hydrochloride (100 mg/m2, body surface area), cyclophosphamide (750 mg/m2) and vincristine sulfate (1.4 mg/m2, a maximal dose of 2.0 mg/body) were administered intravenously on day one, while prednisolone (60 mg/m2/day) was administered orally on days 1 to 5. This cycle of treatment was repeated every three weeks in principle. The efficacy and safety were assessed for 37 eligible patients. The combined rate for CR + CRu was 70.3% (26/37) and the overall response rate (CR + CRu + PR) was 86.5% (32/37). demonstrating that amrubicin hydrochloride was very effective in the treatment of non-Hodgkin's lymphoma. The most frequent adverse reactions that occurred during the study were myelosuppressions: leukopenia and neutropenia, 100% (37/37); and decreases in hemoglobin levels, 81.1% (30/37). Thrombocytopenia, elevations of serum GOT and GPT levels, anorexia, nausea/vomitting, fever, stomatitis and alopecia were also observed. Although leukopenia and neutropenia of grade 3 or higher were noted in 89.2% (33/37) and 94.6% (35/37), respectively, they were controllable by administrations of G-CSF or solely by follow-up observations. One patient developed intestinal paralysis (grade 4) and another developed hematemesis. In conclusion, these results indicate that amrubicin hydrochloride is an effective agent as a component of combination chemotherapy for non-Hodgkin's lymphoma.

Aged↗

Acute abdomen without cutaneous signs of varicella zoster virus infection as a late complication of allogeneic bone marrow transplantation: importance of empiric therapy with acyclovir.

Two patients complained of severe abdominal pain as the first sign of varicella zoster virus infection about 1 year after allogeneic BMT. In case 1, eruptions, found on the face and chest on admission, became vesicular and dispersed on the third hospital day. Though acyclovir (ACV) was immediately started, he died on the fourth day. In case 2, skin rash was never observed during the clinical course. Laparotomy on the third hospital day revealed many hemorrhagic spots on the liver surface and mucous membrane of the upper GI tract, indicating disseminated visceral disease. Empiric therapy with ACV was successful.

Abdominal Pain↗

Late onset cyclosporine-induced cerebral blindness with abnormal SPECT imagings in a patient undergoing unrelated bone marrow transplantation.

A 23-year-old woman underwent HLA-matched unrelated BMT for CML. She developed cerebral blindness on day 81. Brain magnetic resonance imaging revealed hyperintensity on a T2-weighted image in the white and gray matter of the right frontal and both occipital lobes. Single-photon emission computed tomography (SPECT) was consistent with a decrease in radionuclide uptake in these areas, suggesting a vasoconstrictive mechanism. A diagnosis of CsA-induced encephalopathy was made and CsA was discontinued. Her vision recovered completely after 24 h and abnormal imaging resolved within 2 weeks. This case demonstrates late onset CsA-induced cerebral blindness with the previously unreported abnormalities on SPECT.

Aged↗

Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma in patients with acute graft-versus-host disease after allogeneic bone marrow transplantation.

BACKGROUND: Acute graft-versus-host disease still represents the major factor that limits successful allogeneic bone marrow transplantation. Cytokines released by type 1 T-helper cells are thought to play a pivotal role in acute graft-versus-host disease. OBJECTIVE: This study was performed to investigate whether the serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma were associated with the manifestation of acute graft-versus-host disease. METHODS: Serum cytokine levels were measured by sandwich ELISA in 18 patients who underwent allogeneic bone marrow transplantation. RESULTS: Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma were increased in patients in whom acute graft-versus-host disease developed. However, only serum soluble IL-2 receptor levels were significantly related to disease severity. Serum levels of IL-12 and IL-18, both of which are mainly produced by activated macrophages, were increased in different phases of acute graft-versus-host disease, especially grade I. Serum levels of soluble IL-2 receptor and IFN-gamma were significantly elevated in patients with fever. CONCLUSION: Serum levels of soluble IL-2 receptor were more closely related to the severity of acute graft-versus-host disease than those of IL-12, IL-18, and IFN-gamma.

Acute Disease↗

Effects of TAK-044, a nonselective endothelin receptor antagonist, on the spontaneous and indomethacin- or methylene blue-induced constriction of the ductus arteriosus in rats.

We studied the effects of TAK-044, a nonselective endothelin (ET) receptor antagonist, on the indomethacin- or methylene blue-induced constriction of the ductus arteriosus (DA) in rats and compared them with the effects on spontaneous DA constriction. Injection of TAK-044 into 21-day-old fetuses in utero was performed through the uterine wall of laparotomized mother rats under light ether anesthesia. The fetuses were autopsied 3 hr after treatment with TAK-044 (10 mg/kg) in utero and simultaneous administration to the laparotomized mother rats of indomethacin (3 mg/kg, p.o.) or methylene blue (100 mg/kg, i.p.). In the second experiment, pregnant rats were decapitated on day 21 of gestation to obtain newborn rats by cesarean delivery. Newborn rats which were given TAK-044 (2, 10 mg/kg) immediately after or 1 hr before cesarean delivery were autopsied at various times after birth. In both experiments, pups were rapidly frozen in an acetone-dry ice mixture at autopsy to evaluate the DA constriction by the whole-body freezing and shaving method. TAK-044 injection into the fetus 3 hr before autopsy completely inhibited the DA constriction induced by maternal treatment with indomethacin or methylene blue. TAK-044 caused dose-dependent inhibition of the spontaneous closure of the DA after birth. The inhibitory effect was more pronounced in pups which were given TAK-044 in utero 1 hr before birth; however, the inhibitory effect was incomplete in newborn pups. These results, together with the previous finding that BQ-123, an ETA-specific receptor antagonist, inhibits the ductal constriction induced by oxygen in vitro [Coceani et al., 1992], indicate that the ETA receptor plays a significant role in the indomethacin- or methylene blue-induced DA constriction as well as in the spontaneous DA constriction after birth, and also indicate that the inhibition of ETA receptor by TAK-044 was more easily achieved in fetuses than in neonates.

Animals↗

p53 gene mutations occurring in spontaneous benign and malignant mammary tumors of the dog.

Sixty-three cases of benign and malignant canine mammary tumors were analyzed to define the alteration of exons 5-8 for the p53 tumor suppressor gene using polymerase chain reaction direct sequence analysis with paraffin-embedded tissues. Four missense mutations were found in 38 benign mammary tumors (11%), and five missense (one tumor had two missense mutations) and one nonsense mutations were found in 25 mammary carcinomas (20%). These data suggest that the p53 gene alterations might be initiated at an early stage of canine mammary carcinogenesis and p53 mutations might be associated with malignancy. However, there was no evidence of any relationship between the p53 alterations and the histologic types of tumors or breeds of dogs.

Animals↗

[Febrile neutropenia--guideline in Japan].

Fever in neutropenic patients is mostly culture negative, with a rapid progress and high mortality. Due to the necessity of starting treatment early, guidelines for the treatment were first issued by IDSA (Infectious Disease Society of America). We have recently prepared a Japanese version of these guidelines. The criteria for febrile neutropenia are a fever above 38.0 degrees C (in mouth), granulocytes below 1,000. Patients must be checked by blood count, bacterial cultures of blood and urine, and chest X ray. Empiric treatment must be started early before the culture data become available. The first treatment is either single therapy of penem or beta-lactum, or the combination of one of these agents with aminoglucoside. Patients are evaluated after 72 hours. Treatment is modified to add or change to glycopeptide or antifungals. These guidelines still require study for confirmation and to determine the response rates of each treatment arm, as well as to find antibacterial drugs which are effective in culture negative patients with granulocytopenia.

Fever↗

Differences between lymphocyte subsets, after allogeneic bone marrow transplantation, in patients who received tacrolimus and patients who received cyclosporin A.

The subsets of peripheral blood lymphocytes after allogeneic bone marrow transplantation were compared in 20 patients who received tacrolimus and 34 patients who received cyclosporin A (CsA) prophylactically. The phenotypes of CD3, CD4, CD8, and D8/CD57 were analyzed by flow cytometry. The percentage of CD3+ cells in the tacrolimus group (58.8% +/- 21.6%) was significantly lower than in the CsA group (77.2% +/- 12.8%) (P = .0239). The percentage of CD8+CD57+ cells in the patients receiving tacrolimus and developing acute graft-versus-host disease (GVHD) (grade I, 20.1% +/- 10.6%; grade II-IV, 13.2% +/- 6.3%) was significantly higher than in the patients receiving CsA and developing acute GVHD (grade I, 10.7% +/- 5.2%; grade II-IV, 7.7% +/- 4.0%) (grade I, P = .0036; grade II-IV, P = .0255). The absolute number of CD8+CD57+ cells in the patients with grade II-IV acute GVHD was also significantly higher in the tacrolimus group compared with the CsA group. There was no difference in the incidence of acute GVHD in the 2 groups. Recovery from acute GVHD in the tacrolimus group (16.6 +/- 13.6 days) was more rapid than in the CsA group (30.8 +/- 24.8 days) (P = .0124). These results suggest that, compared with CsA, tacrolimus administered prophylactically induces more CD8+CD57+ lymphocytes when acute GVHD occurs and accelerates the recovery from acute GVHD more rapidly.

Adolescent↗

Successful bone marrow transplantation in an adult patient with reactive hemophagocytic syndrome associated with myelodysplastic syndrome.

We report an adult case of reactive hemophagocytic syndrome (RHS) associated with myelodysplastic syndrome (MDS) who received emergency bone marrow transplantation (BMT). Despite methylprednisolone pulse therapy, high-dose gamma-globulin, and chemotherapy containing etoposide, the pancytopenia progressed. After informed consent, the patient underwent syngeneic BMT using melphalan as the conditioning regimen. The patient has been well without relapse of RHS and MDS for more than 2 years after BMT. This result suggests that the above strategy, including BMT, should be considered for the treatment of adult RHS associated with hematological malignancy.

Adult↗

[Transplantation associated alpha herpes virus infection].

Immunosuppression after organ or bone marrow transplantation changes its severity with the time lapse. After bone marrow transplantation, HSV infection occurs in early period and VZV infection, in intermediate period. Aciclovir prophylaxis is effective for preventing HSV in early period and also for elevating the compliance of drug intake. It delays onset of VZV infection on the other hand. VZV infection is usually very severe if it is occurred early, before 100 days after transplant. There was some case of VZV infection with severe abdominal pain without any skin involvement. The incidence of VZV infection in bone marrow recipients was 29%. Even in stable period it caused considerable mental problems in some patient.

Adult↗

A comparative study of administration methods of granisetron injection used to treat nausea/vomiting induced by cancer chemotherapy without cisplatin in tumors of hematopoietic organs. Keihanshin Study Group of Hematological Malignancies.

PURPOSE: The antiemetic effect of granisetron injection at a dose of 40 microg/kg used in the treatment of nausea/vomiting induced by multidrug combined cancer chemotherapy excluding cisplatin in patients with tumors of hematopoietic organs was evaluated by comparing a 30-min infusion and a slow intravenous injection given over 30 s. METHODS: A two-group random-allocation comparative study was performed with the cooperation of multiple institutions using a central registration system. RESULTS: In the treatment of acute clinical symptoms, appetite was described as "similar to that during good health" by 61.1% of patients (55/93) in the instillation group and by 47.3% (44/93) in the slow injection group, a significant advantage in the infusion group. However, no significant differences in the number of episodes of vomiting, the severity of nausea or clinical efficacy were found. In the final clinical evaluation and assessment of usefulness based on the subjective judgement of physicians throughout the entire therapeutic period, no differences were discernible. No side effects were reported for either method and there was no indication of a sex difference concerning efficacy. However, the efficacy in patients with an anemic tendency was slightly inferior. CONCLUSIONS: The maintenance of appetite during the administration of anticancer drugs is very important to maintain patients' daily activities and quality of life. The present results support the usefulness of infusion of granisetron as an administration method during chemotherapy for malignant hemopathy.

Antiemetics↗

Removal of cartilage rings of the graft and omentopexy for extended tracheal autotransplantation.

BACKGROUND: One of the serious problems in longer-size tracheal transplantation is infection or severe stenosis of the graft, probably caused by an inadequate blood supply even with omentopexy. For obtaining an appropriate blood supply, we experimentally developed a new technique that included removal of some cartilage rings of the graft and omentopexy. METHODS: Twenty-one adult mongrel dogs were used. In group A (n = 11), a nine-cartilage ring length of the trachea in which six of nine rings were removed, leaving one cartilage ring at each end of the graft and another in the center, was autotransplanted with omentopexy. Two artificial tracheal rings outside the graft were used for maintaining the lumen. In group B (n = 10), a nine-cartilage ring length of the trachea was autotransplanted with omentopexy. RESULTS: In group A, all dogs survived until being sacrificed, whereas 5 group B dogs died of graft infection and mediastinitis (p<0.05 versus group A). Mucosal blood flow of the graft in group A was normal and higher than in group B (p<0.05). Grade of the graft stenosis at death or sacrifice was 14%+/-1% in group A and 58%+/-25% in group B (p<0.05). CONCLUSIONS: Removal of some cartilage rings improved blood supply to the graft and resulted in satisfactory survival and nonsignificant tracheal stenosis in extended tracheal autotransplantation.

Animals↗

Induction of autologous graft-versus-host disease after autologous peripheral blood stem cell transplantation.

BACKGROUND: Autologous graft-versus-host disease has been reported after the administration of cyclosporine in patients who have received autologous bone marrow transplantation. OBJECTIVE: The purpose of this study was to determine whether autologous graft-versus-host disease could be induced in recipients of autologous peripheral blood stem cell transplantation and whether tacrolimus induced the disease instead of cyclosporine. METHODS: Twelve patients with acute leukemia and 5 patients with malignant lymphoma received either cyclosporine (1 mg/kg/day) or tacrolimus (0. 05 mg/kg/day) orally after autologous bone marrow or peripheral blood stem cell transplantation. RESULTS: Autologous graft-versus-host disease of the skin, confirmed by histopathologic criteria, occurred in 40% of the patients at 8 to 25 days after transplantation and lasted 3 to 15 days. The frequency of autologous graft-versus-host disease was approximately the same (40%) irrespective of the source of the graft (bone marrow cells or peripheral blood stem cells) and the drug used for induction (cyclosporine or tacrolimus). CONCLUSIONS: This pilot study suggests that autologous graft-versus-host disease can be induced in recipients of autologous peripheral blood stem cell transplantation by cyclosporine or tacrolimus.

Acute Disease↗

A phase II study employing combination regimens containing KRN8602 in drug-resistant acute myeloid leukemia and acute lymphoblastic leukemia. KRN8602 Leukemia Study Group.

We conducted a phase II multicenter study in order to evaluate the efficacy and toxicity of two combination regimens containing KRN8602 (MX2) for drug-resistant acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). AML was treated with KRN8602, 15 mg/m2 i.v. push for 5 days, and cytarabine (AraC), 100 mg/m2 by 24 h coutinuous infusion for 7 days. ALL was treated with KRN8602, 15 mg/m2 i.v. push for 5 days, vincristine (VCR), 1.4 mg/m2 i.v. push, once weekly, and prednisolone (PSL), 40 mg/m2, 3 h infusion for 5 days. In AML and ALL, the complete remission (CR) rate was 36.4% (16 of 44) and 24.1% (seven of 29), and the overall response rate (CR+PR) was 52.3% (23 of 44) and 51.7% (15 of 29), respectively. Among the 29 relapsed cases of AML, a higher CR rate, 51.7% (15 of 29), was obtained. A high incidence of nausea/vomiting and anorexia was observed, and some patients experienced central nervous system disorders and peripheral neuropathy. There was a low incidence of severe neurotoxicities; all other toxicities were manageable. KRN8602 was found to overcome drug resistance clinically, confirming results based on the preclinical studies. We conclude that KRN8602 is an effective novel anthracycline for drug-resistant acute leukemias.

ATP Binding Cassette Transporter, Subfamily B, Mem↗