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Biomedical subjects

A Kanamaru

Publications and source records attributed to A Kanamaru.

At least 109 records · Page 6Linked to original sources

Successful treatment of severe cytomegalovirus retinitis with foscarnet and intraocular injection of ganciclovir in a myelosuppressed unrelated bone marrow transplant patient.

A female patient with ALL received a bone marrow transplant (BMT) from an unrelated donor with a one locus HLA mismatch. The donor was heterozygous at the HLA-A locus, while the patient was homozygous at this locus. The patient had cytomegalovirus (CMV) antigenemia on day 42 following an intensive preparative regimen that included anti-thymocyte globulin and BU+CY+TBI to prevent graft rejection. Ganciclovir was given initially for the treatment of CMV antigenemia, although the patient soon developed severe myelosuppression. The patient's hematopoietic recovery was poor, and CMV and human herpesvirus-6 (HHV-6) were detectable in the peripheral blood. Severe CMV retinitis was treated with foscarnet and the intraocular injection of ganciclovir. The CMV retinitis improved and the marrow gradually recovered. CMV and HHV-6 were no longer detectable in the peripheral blood. Foscarnet and intraocular injection of ganciclovir appeared to be an effective treatment for CMV retinitis in this myelosuppressed BMT patient.

Adult↗

Human urinary macrophage colony-stimulating factor reduces the incidence and duration of febrile neutropenia and shortens the period required to finish three courses of intensive consolidation therapy in acute myeloid leukemia: a double-blind controlled study.

PURPOSE: To determine whether macrophage colony-stimulating factor (M-CSF) reduces the incidence and duration of febrile neutropenia during three courses of intensive consolidation therapy and whether it shortens time to complete consolidation therapy. PATIENTS AND METHODS: In 198 adult patients with acute myeloid leukemia (AML) in complete remission (CR), M-CSF (8 x 10(6) U/d) or placebo was administered from 1 day after the end of each consolidation chemotherapy for 14 days. RESULTS: The duration and incidence of febrile neutropenia was significantly reduced by 34% (P = .00285) and 17% (P = .02065), respectively, in 88 assessable patients in the M-CSF group compared with those in 94 assessable patients in the placebo group. Patients in the M-CSF group had 565 days and 133 episodes of febrile neutropenia during 7,901 days at risk, while patients in the placebo group had 977 days and 185 episodes during 9,077 days at risk. The median period required to finish the three courses of consolidation therapy was 93 days in the M-CSF group, which was significantly shorter than 110 days in placebo group (P = .0050). In the M-CSF group, the recovery of neutrophils and platelets was significantly faster (P = .0348 and P = 0.0364, respectively), the administration of systemic antimicrobial agents tended to be less (P = .0839), and the frequency of platelet transfusion (P = .0259) and the total volume of transfused platelets (P = .0292) were significantly less. However, there was no significant difference in the disease-free survival. CONCLUSION: M-CSF significantly reduced the incidence and duration of febrile neutropenia during the intensive consolidation therapy, and shortened the time to complete consolidation chemotherapy in AML.

Acute Disease↗

Establishment of a new cell line from a patient with hairy cell leukemia-Japanese variant.

A cell line, JHC-2, was established from the peripheral blood of a patient with hairy cell leukemia (HCL)-Japanese variant. The JHC-2 cells have cytologic features similar to those of the original tumor cells. They displayed hairy cytoplasmic projections by phase contrast and scanning electron microscopy. The tartrate-resistant acid phosphatase reaction was weakly positive. The immunophenotype of the JHC-2 cells was CD5-, CD10-, CD11c+/-, CD19+, CD21+, CD23+, CD24-, CD25+/-, CD38- and FMC-7+. The expression of surface immunoglobulin (IgG, kappa) and the configuration of Ig gene rearrangements in the JHC-2 cells were identical to those in the original leukemic cells, and the JHC-2 cells displayed trisomy 9 on cytogenetic examination. Southern blot analysis for the Epstein-Barr virus (EBV) genome showed that the JHC-2 cells contained the EBV genome, although the freshly isolated leukemic cells did not. These results indicate that the JHC-2 cell line is an EBV spontaneously transformed B cell line originating from HCL cells.

Acid Phosphatase↗

[Clinical evaluation of cefpirome sulfate for severe infections in patients with hematological disorders. Hanshin Study Group of Hematopoietic Disorders and Infections].

We investigated the therapeutic efficacy and safety of cefpirome sulfate (CPR) in treatment of hematopoietic disorder-associated infections. A total of 219 patients were admitted to 12 hospitals of Hanshin Study Group of hematopoietic disorders and infections between April 1994 and March 1996 and were enrolled in this study. Most patients received intravenously infused CPR at a dose of 1 or 2 g twice a day for 3 days or more. Twenty nine patients dropped out or were excluded and remaining 190 patients were adopted for the evaluation. A overall response rate was 58.4% (111/190). Among neutropenic patients, the response rate was 50% (8/16) in patients whose peripheral neutrophil counts (PNC) remained less than 100/microliter throughout the observation period and was 53.7% (22/41) in patients with PNC remained less than 500/microliter. In contrast, in patient whose PNC was below 500 before the treatment but exceeded 501/microliter during of at the end of the treatment, the response rate was as high as 78.4% (29/37). When G-CSF was combined, the response rate became significantly (P < 0.05) higher, 68.5% (50/73), as compared with that, 52.1% (61/117), in patients without it. In cases in which the causative organisms could be identified, the organisms were eliminated in 81.8% (9/11) of the patients infected with Gram-positive bacteria, whereas in 100% (12/12) in those infected with Gram-negative bacteria. Skin eruption developed in 6 patients during the treatment with CPR, and vascular pain and parosmia in one each other. These symptoms subsided soon after discontinuation or even without discontinuation of CPR. Abnormal laboratory findings, mainly liver dysfunction, i.e. elevation of slight degree of serum transaminase levels, were observed. The values, however, turned to normal immediately after the cessation or completion of the treatment. In conclusion, CPR is considered to be an antibiotic of value with high efficacy and safety in treatment of hematopoietic disorder-associated infections.

Adolescent↗

Combination of immunoadsorption therapy and high-dose methylprednisolone in patients with lupus nephritis; possible indications in patients with early stage.

OBJECTIVE: Therapeutic protocol and indication of immunoadsorption therapy (IA) for lupus nephritis (LN) have not been established, although it has been reported to be effective in resistant cases. Here, we performed IA and double filtration plasmapheresis (DFPP) in combination with high-dose methyprednisolone in patients with LN, and studied possible indications of IA. METHODS: IA and DFPP were performed in 9 patients each with LN. They were immediately followed by intravenous infusion of 500 mg of methylprednisolone for prevention of rebound phenomenon. After these treatments 1-2 times a week, a total of 4-6 times, clinical findings were observed for 6 months. RESULTS: The effects on clinical findings such as erythema, fever and arthralgia, serum complement activity, mean urinary protein and reduction of dose of adrenocorticosteroids were comparable in both treatments. Serum titers of ADNA decreased by IA more than DFPP (16% in IA, 38% in DFPP in 3 months), while serum immunoglobulins decreased by IA less than DFPP. Responses in urinary protein after IA tended to be better in patients with high titer of serum ADNA and without nephrotic syndrome, and not associated with disease activity of SLE. CONCLUSION: Removal of ADNA was more selective in IA than in DFPP, and the effects of IA were comparable with those of DFPP. Since patients with low titers of serum ADNA and nephrotic syndrome showed poor responses to IA, it might be worth trying rather in patients with early phase of lupus nephritis.

Adolescent↗

Reconstruction of tonic vibration reflex in the biceps brachii reinnervated by transferred intercostal nerves in patients with brachial plexus injury.

The transfer of intercostal nerves to musculocutaneous nerves has been performed to reconstruct elbow flexion in patients with brachial plexus injury. In nine of 15 such patients, 2-3 Hz tapping of the distal tendon of the biceps muscle reinnervated by the transferred intercostal nerves (IC-biceps) induced a mode in the correlogram between tap and EMG pulse of IC-biceps. In five of the mode-positive patients, tapping of various frequencies induced gradual augmentation of integrated EMG of IC-biceps. This reflex was consistent with the tonic vibration reflex (TVR) in normal controls. Conduction velocity and frequency property of the reflex were compatible with the speculation that rapid-conducting muscle afferents (group Ia or II or both) reinnervate mechanoreceptors, such as muscle spindles. The clinical significance of muscle sensory reinnervation is not clear; however, the reconstruction of TVR following this operation is worthy in that it confirms the specific sensory reinnervation of denervated muscle in humans.

Adolescent↗

Optical imaging of respiratory burst activity in newborn rat medullary block preparations.

We report on the optical imaging of excitation propagation induced by electrical stimulation of the nucleus tractus solitarius (NTS) area and subsequent inspiratory burst activity in the ventrolateral medulla (VLM) of a medullary block preparation. A medullary block preparation with a thickness of 1.0-1.4 mm was made from brainstems isolated from 0- to 4-day-old rats and stained with a fluorescent voltage-sensitive dye, RH795. Neuronal responses in the VLM evoked by electrical stimulation were recorded as a fluorescence change using an optical recording apparatus with a 128 x 128 photodiode array and a maximum time resolution of 0.6 ms. Motoneuronal activity was simultaneously recorded at the contralateral hypoglossal nerve roots. Neuronal excitation evoked by stimulation of the NTS area propagated to the VLM through the intermediate reticular zone (IRt). In contrast, caudal VLM stimulation induced excitation which propagated to the rostral VLM without any detectable excitation propagation in the IRt toward the NTS area from the VLM. NTS stimulation also induced an inspiratory burst activity in the hypoglossal nerve root activity with a 150-200 ms delay. Fluorescence changes corresponding to the inspiratory burst activity were observed in the VLM which coincided with the area in which the localization of many respiratory neurons had been demonstrated in previous studies using whole-brainstem preparations. The present results show the feasibility of using optical recordings for the analysis of respiratory neuron activity as well as for analysis of the transmission pathway of afferent and/or efferent information in the medulla.

Animals↗

Myelodysplastic changes in three cases within 100 days after allogeneic bone marrow transplantation.

Three patients with severe aplastic anemia, acute promyelocytic leukemia (M3) and chronic myelogenous leukemia, developed myelodysplastic changes with trilineage morphological abnormalities in a few months following allogenic bone marrow transplantation (BMT). Morphologically dysplastic changes associated with moderate-severe anemia, leukopenia and/or thrombocytopenia appeared on day 40, day 62 and day 68 after BMT. A ferrokinetics study clearly showed ineffective erythropoiesis in one patient. Hematopoietic cells were shown to be of donor-origin in all three cases. The levels of vitamin B12 and folic acid were normal. Laboratory tests showed no signs of hemolysis or fragmentation of red blood cells. Although the cause of aberrant hematopoiesis compatible with MDS within 100 days post-BMT remains to be determined, cytomegalovirus infection, ganciclovir and/or graft-versus host disease (GVHD) might be associated with this myelodysplasia following allogeneic BMT.

Adolescent↗

Feasibility of salvage chemotherapy for refractory or relapsed non-Hodgkin's lymphoma with two topoisomerase II inhibitors, MST-16 and VP-16. MST-16 Study Group.

A feasibility study was carried out on the treatment for refractory and relapsed non-Hodgkin's lymphomas with a combination of two oral topoisomerase II inhibitors, MST-16 and VP-16. On the basis of the synergistic activity in preclinical studies and the schedule dependency in these drugs, low-dose and long-term administration was planned. For the anticipated myelosuppression, two different regimens were designed as an open label trial in this study. In Regimen I, 400 mg of MST-16 combined with 25 mg of VP-16 was administered daily. With this regimen, the response rate (RR)/median time to tumor progression (TTP) in all evaluable patients was 50% (2/4)8.5 months in low grade (indolent) lymphoma and 60% (6/10)/5.2 months in intermediate/high grade (aggressive) lymphomas. In Regimen II, 400 mg of MST-16 combined with 25 mg of VP-16 was administered intermittently (3 days a week or every other day). With this regimen, there was an RR/median TTP of 60% (3/5)/7.0 months in indolent lymphoma and 33.3% (4/12)/1.1 months in aggressive lymphoma. A major side effect in both of these regimens was myelosuppression, with the incidence of grades 3 and 4 toxicity being higher in Regimen I than in Regimen II. The other side effects were uncommon and not severe. These findings indicated that two regimens were tolerated well and were promising for refractory and relapsed aggressive non-Hodgkin's lymphomas. To define the anti-tumor activity and safety of these regimens precisely, large-scale prospective randomized trials are necessary.

Adolescent↗

Vibration-induced finger flexion reflex and inhibitory effect of acupuncture on this reflex in cervical spinal cord injury patients.

The vibration-induced finger flexion reflex (VFR) and the inhibitory effect of acupuncture on this reflex were studied in five cervical spinal cord injury patients (C-SCIs). VFR, which is a tonic finger flexion reflex induced by vibratory stimulation on the finger tip, was induced before and after acupuncture was carried out on the same hand. A stainless steel needle was inserted to the Hoku point. As in healthy subjects, VFR was performed and it was significantly inhibited by acupuncture in the C-SCIs; mean maximum VFR was 204.2 +/- S.E. 68.6 g before and 119.8 +/- S.E. 42.2 g after acupuncture. The present results suggest that at least part of the reflex center for VFR is located in the spinal cord and that part of VFR inhibition by acupuncture may be mediated via the spinal cord.

Acupuncture Therapy↗

Second transplantation with CD34+ bone marrow cells selected from a two-loci HLA-mismatched sibling for a patient with chronic myeloid leukaemia.

A 43-year-old man with chronic myeloid leukaemia underwent a second transplant with CD34+ bone marrow cells selected from his two-loci HLA-mismatched sibling after rejection of the first graft from an HLA-matched unrelated donor. By immunomagnetic positive selection, CD34+ marrow cells at 0.95 x 10(6)/kg with 97% purity and CD3+ T lymphocytes at 1.3 x 10(4)/kg were collected and transplanted. Engraftment was confirmed to be of CD34+ cell-donor origin. The patient developed only grade I acute graft-versus-host disease (GVHD) and no chronic GVHD to date. These observations suggest that allogeneic CD34+ bone marrow cells are capable of reconstituting haemopoiesis and that CD34+ selection could be applicable to T-cell depletion.

Adult↗

Randomized trials between behenoyl cytarabine and cytarabine in combination induction and consolidation therapy, and with or without ubenimex after maintenance/intensification therapy in adult acute myeloid leukemia. The Japan Leukemia Study Group.

PURPOSE: We analyzed complete remission (CR), disease-free survival (DFS), and event-free survival (EFS) rates in two groups of patients treated with either N4-behenoyl-1-beta-D-arabinosylcytosine (BHAC) or cytarabine, and analyzed DFS with or without ubenimex, a biologic response modifier. PATIENTS AND METHODS: Newly diagnosed patients with acute myeloid leukemia (AML) were randomized to receive either BHAC or cytarabine as remission-induction combination chemotherapy and two courses of consolidation therapy. After maintenance/intensification therapy, patients in CR were randomized to receive either ubenimex and no drug. RESULTS: Of 341 patients registered, 326 were assessable. The age of assessable patients ranged from 15 to 82 years (median, 48). The overall CR rate was 77%: 72% in the BHAC group and 81% in the cytarabine group, and there was a significant difference between the two groups (P = .035, chi 2 test). The predicted 55-month EFS rate of all patients was 30%: 23% in the BHAC group and 35% in the cytarabine group, with a significant difference between groups (P = .0253). The predicted 55-month DFS rate of all CR patients was 38% and that of CR patients less than 50 years of age was 47%. There was no significant difference in DFS between the ubenimex group and the group that did not receive ubenimex. CONCLUSION: Analyses of our clinical trial showed that the use of BHAC in remission-induction therapy and in consolidation therapy resulted in poorer CR and EFS rates in adult AML patients compared with the use of cytarabine at the doses and schedules tested. Immunotherapy with ubenimex after the end of all chemotherapy did not improve DFS.

Acute Disease↗

[Urgent allogeneic bone marrow transplantation using a preparative regimen of cyclophosphamide anti-human thymocytes rabbit globulin in a patient with severe aplastic anemia with pneumonia].

A 16-year-old girl was diagnosed as having severe aplastic anemia (SAA) had received emergency complicated by sever pneumonia. She had an HLA-identical younger brother and been urgently transplantation with her brother's marrow following a preparative regimen of CY+rabbit antithymocyte globulin (ATG). Granulocyte transfusions carried out before and after the transplant prevented exacerbation of the pneumonia. The pneumonia was cured in association with the hematopoietic recovery after BMT. No signs or symptoms of acute or chronic graft-versus-host disease were recognized and her hematological data are normal. The rabbit ATG was thought to be effective in preventing rejection and could be used in the preparative regimen instead of total body irradiation.

Adolescent↗

[Paroxysmal nocturnal hemoglobinuria].

Paroxysmal Nocturnal Hemoglobinuria (PNH) is an acquired hemolytic anemia characterized by chronic hemolysis, deep thrombosis, and hypoplastic marrow, and thought to be a clonal hematopoietic stem cell disorder. Affected blood cells are deficient in glycosylphosphatidylinositol (GPI)-anchored cell surface proteins. Recent investigations revealed that the PIG-A gene, which participates the biosynthesis of the GPI-anchor, was identified and the mutations were detected in the patients with PNH. Here we discuss the following problems related to the PIG-A gene; (1) the inconsistency of the expression of the GPI-anchored proteins and the mutations of the PIG-A gene, (2) the existence of the multiple PNH clones bearing different PIG-A mutations in a single patient, (3) aplastic anemia-PNH syndrome and PIG-A gene.

Animals↗

Establishment and molecular characterization of a novel leukemic cell line with Philadelphia chromosome expressing p230 BCR/ABL fusion protein.

The cell line AR230 was established from the peripheral blood mononuclear cells of a patient with chronic myeloid leukemia and t(9;22) translocation bearing a variant type of BCR/ABL rearrangement. AR230 expresses a BCR/ABL fusion protein with a molecular mass of 230 kilodaltons (kDa) due to the insertion of 180 amino acids encoded by 3' exons of BCR (b4 to c3). An immune complex kinase assay showed that the 230-kDa BCR/ABL protein ahd autophosphorylation activity. Immunoprecipitation analysis revealed a stable complex of GRB2 and 230-kDa BCR/ABL proteins, indicating that the Ras activation pathway is involved in the process of transformation. AR230 expressed another short transcript consisting of a BCRc2/ABL junction, which is associated with a stop signal shortly after the junction. To our knowledge, this is the first cell line expressing a 230-kDa fusion product of BCR/ABL. AR230 will be useful for studying the biological function of divergent BCR/ABL proteins.

Amino Acid Sequence↗

All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic leukemia. Japan Adult Leukemia Study Group.

We conducted a multicenter trial of treatment with all-trans retinoic acid (ATRA) for newly diagnosed acute promyelocytic leukemia (APL) in the AML-92 study and compared it with our previous study with standard intensive chemotherapy, the AML-89 study, in the view of complete remission (CR) rate, incidence of early death, and event-free survival (EFS). Patients were scheduled to receive oral ATRA 45 mg/m2 daily until CR. If patients had leukocyte counts above 3 x 10(9)/L at the start of therapy, they received daunorubicine (DNR) 40 mg/m2 for 3 days and behenoyl cytosine arabinoside (BHAC) 200 mg/m2 for 5 days in addition to ATRA. During the ATRA therapy, if patients showed myeloblast plus promyelocyte counts higher than 1 x 10(9)/L in the peripheral blood, they received additional DNR and BHAC in the same schedule, as well. A total of 110 patients were entered into the study. Median age was 43 years (range, 16 to 74). Twenty-eight (26%) of 109 patients (one died before the start of therapy) received ATRA alone. Ninety-seven patients (89%) achieved CR; 48 of 49 (98%) aged less than 40 years, 44 of 52 (84%) aged between 40 and 69, and 5 of 8 (63%) aged above 70 achieved CR, respectively; 25 of 28 (89%) with ATRA alone, 46 of 51 (90%) with ATRA plus initial chemotherapy and 26 of 30 (87%) with ATRA plus later chemotherapy attained CR, respectively. Nine (8%) patients died within 28 days after the start of therapy. In contrast, 44 of 62 patients (71%) attained CR, and 13 (21%) died within 28 days in the AML-89 study with the combination of DNR, BHAC, 6-mercaptopurine and prednisolone. Seven developed retinoic acid syndrome and one died of it in the present study. Other toxicities associated with this drug included cheilitis, desquamation, muscle pain, and hypertriglyceridemia. Predicted 23 months EFS for all ATRA-treated patients and disease-free survival (DFS) in the CR cases were 75% and 81%, respectively, in a median follow-up period of 21 months. Compared to the AML-89 study, there was a highly significant difference in remission rate (P = .004), EFS (P = .0007), and also early mortality rate (P = .02). Present results demonstrated that ATRA with or without chemotherapy gives a statistical improvement in CR rate and early mortality rate, as well as superior survival in newly diagnosed APL.

Adolescent↗