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Biomedical subjects

C Uotani

Publications and source records attributed to C Uotani.

At least 19 recordsLinked to original sources
PubMed2001

[Gross spreading multiple extramedullary plasmacytomas to the skin in the terminal stage of multiple myeloma].

A 71-year-old woman with an 8-year history of IgG-kappa type multiple myeloma was admitted because of severe lumbago and bone destruction. Her serum IgG level was elevated to 5,565 mg/dl at admission. Despite treatment with doxorubicin, vincristine, dexamethasone, melphalan and interferon-alpha, the response was transient. Nine months later, multiple skin nodules appeared on her chest, abdominal wall and right thigh accompanied by elevation of the serum IgG level. Response to combination chemotherapy with cyclophosphamide, ranimustine, vincristine and prednisolone was also transient. The skin tumors on the bilateral thighs, especially on the left side, acquired chemotherapy resistance and gradually enlarged. Although the serum IgG level was maintained by chemotherapy within the range 1, 790-2,676 mg/dl, the skin tumors on the left thigh had spread very rapidly and appeared "rock-like". The enlarged tumors caused necrosis with erosions and oozing hemorrhage. A skin biopsy from the tumors on the left thigh showed plasmacytoma in which infiltration of large anaplastic plasma cells was observed. The patient died of sepsis 8 months after the skin tumors initially developed. This is a very rare case of multiple myeloma in which multiple large plasmacytomas of the skin developed and grew aggressively at the terminal stage after a long-term indolent course.

Aged↗
PubMed2000

Prognosis of node-positive breast cancer patients who underwent parasternal lymph node biopsy during surgery followed by doxorubicin- or mitoxantrone-containing adjuvant chemotherapy.

The authors examined the survival rates of 60 patients with breast cancer who underwent parasternal lymph node biopsy during surgery with axillary lymph node dissection and had histologically confirmed axillary node metastasis followed by adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy to ascertain whether administration of anthracycline or its analogue improved the prognosis of both axillary and parasternal node-positive patients. The overall survival rate (OS) for the parasternal node-positive patients (n=13, 21.7%) was 30.6%, and relapse-free survival rate (RFS) fell to 0% at the 104-month follow-up. Although the survival rate for all axillary node-positive patients was similar to those in previous reports, the OS and RFS for both axillary and parasternal node-positive patients were significantly worse than that for axillary node-positive and parasternal node-negative patients, despite treatment with adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy. Other intensive adjuvant treatment strategies are needed to reduce distant metastases for high-risk breast cancer patients having both axillary and parasternal nodes positive.

Adult↗
PubMed2000

[Non-Hodgkin's lymphoma in two married couples].

Couple 1: A 74-year-old woman was diagnosed as having diffuse large B-cell lymphoma (DLBL) by left axillary lymph node biopsy. About 6 months later, DLBL was also diagnosed in her 79-year-old husband by right submandibular lymph node biopsy. Although the wife achieved partial remission with chemotherapy, she died due to disease progression. The husband's disease was chemotherapy-resistant, and he died of renal failure. Couple 2: An 86-year-old man was diagnosed as having DLBL by left axillary lymph node biopsy. About 4 years later, DLBL was also diagnosed in his 86-year-old wife by left axillary lymph node biopsy. Both the husband and the wife received chemotherapy. The husband is currently alive in complete remission, and although the wife achieved partial remission, she died due to disease progression. In both of these couples, it was considered unlikely that Epstein-Barr virus or human T-cell lymphotropic virus type I was related to the development of non-Hodgkin's lymphoma, and no environmental factors were confirmed to be involved. It is postulated that other unknown factors or agents may be associated with the development of lymphoma in married couples.

Aged↗
PubMed1999

Adjuvant chemotherapy with a combination of mitoxantrone, methotrexate, 5-fluorouracil for node-positive breast cancer: phase II pilot study.

A phase II pilot study was carried out on 30 patients to ascertain the toxicity and efficacy of combination chemotherapy with mitoxantrone, methotrexate, 5-fluorouracil (NMF) in the adjuvant setting for axillary lymph node-positive breast cancer. The NMF regimen was mitoxantrone 10 mg/m2, methotrexate 40 mg/m2, and 5-fluorouracil 600 mg/m2 administered i.v. on day 1, repeated every 3-4 weeks for 6 cycles. The median nadir WBC count was 2,000/microl; grade 4 leukocytopenia occurred only in 1 patient. Nausea and vomiting appeared as grade 0 and 1 severity in 26/30 patients. Alopecia was extremely mild, appeared as grade 0 and 1 in 29/30 patients. The overall and relapse-free survival rates were 67.8% and 68.4% at the 82-month follow-up, respectively. The overall survival rate in premenopausal patients was significantly better than that in postmenopausal patients (P<0.05). NMF is a well-tolerated combination regimen, suitable as adjuvant chemotherapy for node-positive breast cancer.

Adolescent↗
PubMed1999

[Primary pleural non-Hodgkin's lymphoma without chronic pyothorax].

Most cases of primary pleural malignant lymphoma develop following chronic pyothorax. We report a case of primary pleural non-Hodgkin's lymphoma without chronic pyothorax. A 63-year-old woman was referred and admitted to our hospital with a right pleural effusion that was detected during a routine physical checkup. Her liver, spleen, and superficial lymph nodes were not palpable on physical examination. The massive right pleural effusion and a pleural mass were demonstrated on chest X-ray films and thoracic computed tomograms. Diffuse large B-cell non-Hodgkin's lymphoma was diagnosed by needle biopsy from the pleura, and the clinical stage was IE. Pleural effusion specimens contained no identifiable lymphoma cells, and examinations for Mycobacterium species were also negative. Human herpes virus 8 (HIV-8) DNA was detected in lymphocytes from the peripheral blood and pleural effusion. Epstein-Barr virus-encoded small RNAs and HHV-8 DNA were both negative in biopsied tissue from the pleural mass. Although a complete remission was achieved, the lymphoma relapsed about 8 months later. The patient is currently receiving salvage chemotherapy. Cases of primary pleural non-Hodgkin's lymphoma with massive pleural effusion that are not preceded by chronic pyothorax or Kaposi's sarcoma are very rare.

Chronic Disease↗
PubMed1998

Prothrombin fragment 1 + 2 measures treatment effect in patients with antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis. The anticoagulant management of APS thrombosis remains controversial. Few reports on markers of in vivo activation of coagulation have been reported. To determine whether plasma levels of prothrombin fragment 1 + 2 (F1 +2) correlate with thrombotic risk and treatment effect in patients with APS, plasma F1 + 2 levels were followed in 57 patients with this syndrome for more than 2 years. Clinical findings were also observed in these patients. Plasma levels of F1 + 2 in patients with APS were significantly higher when compared with control subjects (p<.05). These results suggest patients with APS are in a hypercoagulable state. Plasma levels of F1 + 2 significantly decreased following treatment with either aspirin, or aspirin plus warfarin (p<.05 and p<.01, respectively). Recurrent thromboses or spontaneous abortions occurred in all eight patients whose plasma levels of F1 + 2 remained higher than 1 nmol/l after treatment with either aspirin alone or no anticoagulants. These patients were subsequently treated with warfarin as well as aspirin, and plasma levels of F1 + 2 decreased to less than 1 nmol/l, with no additional thrombotic events over the remainder of the 2-year follow-up. No fatal bleeding was observed in treated patients. Our results suggest plasma levels of F1 + 2 are useful indicators of successful treatment. It is also suggested that warfarin plus mini-dose aspirin therapy is effective for patients with APS to protect from recurrent thromboses without harmful side effects. Further, prospective cohort studies are needed to substantiate these associations.

Antiphospholipid Syndrome↗
PubMed1996

Hypercoagulability and high lipoprotein(a) levels in patients with type II diabetes mellitus.

Diabetes mellitus is associated with disturbances in hemostasis that could contribute to the development of diabetic vascular disease. We investigated the changes in parameters of blood coagulation and the fibrinolytic system and in plasma levels of lipoprotein(a)(Lp(a)) in 124 patients with type II diabetes mellitus and 44 healthy control subjects matched for age and body mass index (BMI) to determine whether hemostatic disturbances may lead to increased cardiovascular mortality. Median levels of fibrinogen (P < 0.0001), thrombin-antithrombin III complex (TAT) (P < 0.005), and plasminogen activator inhibitor-1 (PAI-1) activity (P < 0.05) in plasma were significantly elevated in diabetic patients compared with controls. The median concentration of Lp(a) was significantly higher in diabetic patients than in normal controls (18.2 vs. 12.6 mg/dl. P < 0.0005). Lp(a) levels tended to be elevated in patients with a prolonged history of diabetes. There was no evidence that Lp(a) levels were affected by metabolic control or by type of treatment. Twenty-two diabetics with coronary heart disease (CHD) had significantly higher levels of fibrinogen (P < 0.05), TAT (P < 0.05), and Lp(a) (24.7 vs. 13.7 mg/dl, P < 0.01) than the 51 patients without diabetic angiopathy. Our data indicate that impaired hemostatic balance in diabetes may cause hypercoagulability and may thus contribute to the increased cardiovascular mortality in diabetes.

Aged↗
PubMed1996

Protective effects of DX-9065a, an orally active, novel synthesized and selective inhibitor of factor Xa, against thromboplastin-induced experimental disseminated intravascular coagulation in rats.

We investigated the protective effects of DX-9065a, an orally active, newly synthesized, and specific inhibitor of factor Xa, against experimental disseminated intravascular coagulation (DIC) in rats. Experimental DIC was induced by a 4 hour sustained infusion of thromboplastin at a dose of 2.5 mg/kg. The rats were orally administered DX-9065a at 10, 30, 100 mg/kg 30 minutes before thromboplastin injection. In this DIC model, DX-9065a showed a protective effect against DIC, at all doses and in all parameters, including fibrin(ogen) degradation products, fibrinogen level, thrombin-antithrombin III complex level, prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, and the number of renal glomeruli with fibrin thrombi. When DX-9065a was orally administered at 100 mg/kg without thromboplastin, no significant changes were seen in hemostatic parameters except PT and APTT, and no fibrin thrombi or abnormal bleeding were seen in renal specimens. These findings suggested that the new oral anti-Xa drug, DX-9065a, has a protective effect against thromboplastin-induced DIC model with little risk of bleeding.

Administration, Oral↗
PubMed1996

Hypercoagulability and high lipoprotein(a) levels in patients with aplastic anemia receiving cyclosporine.

There is some clinical evidence that cyclosporine A (CyA) is associated with thrombotic complications of bone marrow and renal transplantation. We investigated plasma concentrations of lipoprotein(a) [Lp(a)], a potentially atherothrombotic lipoprotein, and hemostatic and vascular status in ten patients with aplastic anemia receiving CyA, eleven patients not taking it, and 38 age-matched healthy controls. Patients receiving CyA had significantly higher concentrations of plasma fibrinogen (P < 0.05), prothrombin fragment 1 + 2 (F1 + 2; P < 0.05), plasminogen activator inhibitor-1 (PAI-1; P < 0.05), and von Willebrand factor antigen (P < 0.05) than did patients not taking CyA. Plasma concentrations of Lp(a) were higher in CyA-treated patients than those not receiving it (P < 0.05) or healthy controls (P < 0.05). The difference in the Lp(a) concentration between controls and patients who did not receive CyA-treatment was not significant. Our results suggest that hypercoagulability is likely to occur during CyA therapy. Further, the presence of high concentrations of Lp(a) may accelerate the process of atherosclerosis and increase thrombotic events in patients receiving long-term CyA.

Adult↗
PubMed1996

[Analysis of behaviors of plasma tissue factor and tissue factor pathway inhibitor in patients with various diseases].

We measured plasma levels of tissue factor (TF), total tissue factor pathway inhibitor (TFPI) and free TFPI antigen in patients with diabetes mellitus (DM), hyperlipidemia and disseminated intravascular coagulation (DIC). The mean TF, total TFPI and free TFPI antigen concentrations were significantly higher in patients with DM than in controls and the plasma TF concentration was significantly higher in patients with retinopathy or nephropathy than in DM with no complications. The mean TF, total TFPI and free TFPI antigen concentrations were significantly higher in patients with hyperlipidemia than in controls. There was a significant positive correlation between levels of total TFPI and total cholesterol. In patients with hyperlipidemia, the level of total TFPI was significantly decreased compared to base line level by cholesterol lowering drug, however, free TFPI concentration did not change by cholesterol lowering drug. The TF and total TFPI concentrations were significantly higher in patients with DIC than in controls.

Anticoagulants↗
PubMed1995

Role of tissue factor in disseminated intravascular coagulation.

We examined plasma antigen levels of tissue factor (TF) in 95 cases of disseminated intravascular coagulation (DIC), to investigate the role of TF in DIC. A significant elevation of plasma antigen levels of TF was observed in cases of DIC associated with cancer. However, no such significant elevation was observed in cases of DIC associated with acute promyelocytic leukemia (APL), acute leukemia except APL, blastic crisis of chronic myelogenous leukemia, non-Hodgkin lymphoma (NHL), sepsis or fulminant hepatitis. No significant elevation of TF was observed in patients without DIC, except 4 cases of cancer who developed DIC thereafter. Plasma antigen levels of TF were higher in both cases of DIC with renal failure and chronic renal failure without DIC than its levels in those without renal failure. Therefore, plasma antigen levels of TF in DIC patients with renal failure were considered to be carefully estimated. The levels of TF were decreased with the clinical improvement in some cases of DIC but were further increased or remained at high levels in patients who showed no improvement of DIC. Thus, plasma antigen levels of TF is an important marker to predict the development and/or prognosis of DIC, especially in patients with cancer.

Adult↗
PubMed1995

Relationship between elevation in the plasma concentration of elastase-alpha 1 proteinase inhibitor complex (E-alpha 1 PI) and haemostatic parameters during haemodialysis.

To investigate the relationship between changes in plasma concentrations of polymorphonuclear elastase (PMN-E) and haemostatic effects during haemodialysis (HD), changes in the plasma concentrations of elastase-alpha 1 proteinase inhibitor complex (E-alpha 1 PI) and fibrinogen (Fbg), cross-linked fibrin degradation products (XDP), thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC) and soluble thrombomodulin (TM) in 49 patients with end-stage chronic glomerulonephritis maintained on chronic HD were measured. Plasma concentrations of TAT, PIC, TM and E-alpha 1 PI significantly increased during a single HD. There was a statistically significant correlation between change in plasma E-alpha 1 PI concentration and changes in plasma concentrations of TAT, PIC and TM during a single HD, as well as between changes in plasma concentrations of TM and TAT during a single HD. These observations suggested that activation of coagulation and fibrinolysis, endothelial cell damage, and activation of polymorphonuclear cells occur during HD. Activation of polymorphonuclear cells may induce activation of coagulation and fibrinolysis, leading to endothelial cell damage, augmented by release of proteases such as elastase.

Adult↗
PubMed1995

Recombinant hirudin for the treatment of disseminated intravascular coagulation in patients with haematological malignancy.

The purpose of this pilot study was to determine the effect of recombinant hirudin (r-hirudin) on coagulopathy and the relationship between concentrations of thrombin-antithrombin III (ATIII) complex (TAT) and thrombin-hirudin complex (THC) in patients with disseminated intravascular coagulation (DIC). Five patients with haematological malignancy associated with DIC were studied. r-Hirudin was administered by continuous intravenous infusion at a dose of 0.005 mg/kg/h for 4-9 days to each patient. Fibrin/fibrinogen degradation products (FDP), D-dimer, TAT and plasmin-alpha 2 antiplasmin complex (PAP) concentrations decreased after treatment with r-hirudin in four patients studied. However, in one patient, serum creatinine increased to 1.7 mg/dl and aPTT was prolonged to 74.4s. Statistical analysis disclosed significant positive correlations between plasma concentrations of hirudin and THC, and between concentrations of THC and TAT. The concentrations of THC were much higher than those of TAT. In conclusion, these findings indicate that r-hirudin more strongly inhibited thrombin than did ATIII without heparin, and that administration of r-hirudin to renal insufficiency required individual adjustment of dosage. The present findings also suggest that r-hirudin can be considered a new agent for the treatment of DIC.

Acute Disease↗
PubMed1995

Haemostatic and fibrinolytic parameters in septic patients with leukopenia or leukocytosis.

Induction of leukocytopenia by cytotoxic drugs protects against the generalized Shwartzman reaction induced by endotoxin. To elucidate the relationship between leukocyte number and in haemostatic and fibrinolytic disturbances in human sepsis, we studied 32 septic patients with abnormal leukocyte counts. Twenty patients had sepsis in the setting of leukopenia after chemotherapy for haematological malignancies. Twelve patients with leukocytosis developed sepsis associated with benign disorders. Concentrations of thrombin-antithrombin III complex (TAT), plasminogen activator inhibitor-1 (PAI-1) and plasma thrombomodulin (TM) in the leukocytosis group of (12.0 +/- 11.0, 40.2 +/- 27.0 and 5.5 +/- 2.3 ng/ml, respectively) were significantly elevated compared to the leukopenia group of (3.8 +/- 2.3, 18.0 +/- 15.0 and 3.1 +/- 1.0 ng/ml, respectively) and controls (3.3 +/- 0.4, 10.5 +/- 5.3, 3.0 +/- 0.5 ng/ml, respectively). On the other hand, there were no significant differences in these values between leukopenia group and controls. Thus leucocytes may play important roles in thrombin generation, PAI-1 release and injury to endothelial cells.

Adult↗
PubMed1994

Study of the balance between coagulation and fibrinolysis in disseminated intravascular coagulation using molecular markers.

Plasma levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC) and active plasminogen activator inhibitor (PAI) were assayed in 66 cases of disseminated intravascular coagulation (DIC). Significant elevation of both TAT and PIC was observed in all cases of DIC. Most elevated levels of TAT were seen in DIC with acute promyelocytic leukaemia (APL) and sepsis. The highest levels of PIC were seen in DIC with APL but were much lower in sepsis. A significant elevation in active PAI was observed in DIC due to acute leukaemia (apart from APL), chronic myeloid leukaemia and sepsis, but not in APL, non-Hodgkin lymphoma and cancer. Active PAI was higher in patients with multiple organ failure (MOF) than in those without MOF while PIC was lower in patients with this complication. Thus, the balance of coagulation and fibrinolysis varied according to the underlying cause of DIC; APL had more dominant activation of fibrinolysis, while sepsis had greater activation of coagulation. It is suggested that the inhibition of secondary fibrinolytic activation plays an important role in the progression of MOF by the disturbance of the microcirculation.

Antifibrinolytic Agents↗
PubMed1994

Effects of DX-9065a, an orally active, newly synthesized and specific inhibitor of factor Xa, against experimental disseminated intravascular coagulation in rats.

We investigated the protective effects of DX-9065a, an orally active, newly synthesized and specific inhibitor of factor Xa, against two kinds of experimental disseminated intravascular coagulation (DIC) in rats. Endotoxin-induced experimental DIC was induced by a 4-h sustained infusion of endotoxin at a dose of 100 mg/kg. Thromboplastin-induced experimental DIC was induced by a bolus injection of thromboplastin at a dose of 150 mg/kg. The rats were orally administered DX-9065a at 10, 30 or 100 mg/kg 30 min before endotoxin or thromboplastin injection. In both DIC models, DX-9065a showed a protective effect against DIC, at all doses and in all parameters, including fibrin/fibrinogen degradation products (FDP), fibrinogen level, prothrombin time, activated partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi. When DX-9065a was orally administrated at 100 mg/kg without endotoxin or thromboplastin, no significant changes were seen in hemostatic parameters except PT and APTT, and no fibrin thrombi or abnormal bleeding were seen in renal specimens. These findings suggest that the new oral anti-Xa drug, DX-9065a, has an effect in reducing the severity of DIC. However, further dose-finding and safety studies of this drug have still to be assessed.

Administration, Oral↗