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Biomedical subjects

N Dobashi

Publications and source records attributed to N Dobashi.

At least 37 records · Page 2Linked to original sources

[Acute vincristine neurotoxicity in a non-Hodgkin's lymphoma patient with Charcot-Marie-Tooth disease].

A 44-year-old, previously healthy man with a diagnosis of non-Hodgkin's lymphoma (NHL, diffuse large B-cell type, stage IIA) was treated with combination chemotherapy including vincristine (VCR). After receiving a cumulative dose of VCR, he experienced rapid and marked weakening which progressed to quadriplegia and bulbar palsy. Prior to this therapy, the patient had no neurological problems, and his siblings were asymptomatic. Physical examination identified pes cavus (hollow foot), and electrodiagnostic studies showed markedly slower nerve conduction velocity of myelinated fibers, with abundant "onion bulb" formations. Chromosomal analysis detected 17p11.2-12 duplication, thus yielding a diagnosis of Charcot-Marie-Tooth (CMT) 1A. CMT disease is a familial neuromuscular disorder, and the incidence is approximately 1 in 2,500. We concluded that if CMT disease is diagnosed, vincristine should be avoided due to the potential severity of neurotoxicity to small doses.

Adult↗

Elevation of cytokeratin 19 fragment in patients with interstitial pneumonia associated with polymyositis/dermatomyositis.

OBJECTIVE: Cytokeratin 19 fragment (CK19) levels in serum have been documented as a useful tumor marker for lung cancer. We hypothesize that CK19 may increase in serum in patients with interstitial pneumonia associated with polymyositis/dermatomyositis (PM/DM) and CK19 might be a useful variable to evaluate the activity of lung injury. METHODS: 1. We measured CK19 in sera in 15 patients diagnosed with PM/DM; 6 had nonspecific interstitial pneumonia (NIP), 4 had acute interstitial pneumonia (AIP), and 5 had no pulmonary involvement. We also measured CK19 in 10 healthy nonsmokers serving as a control group. 2. We evaluated the correlation between CK19 level and individual clinical course in patients with pulmonary involvement associated with PM/DM. RESULTS: CK19 levels in sera of patients with NIP associated with PM/DM were significantly higher versus patients with PM/DM without interstitial pneumonia and healthy nonsmokers. CK19 levels in sera in patients with AIP associated with PM/DM were significantly higher compared with the other groups. CK19 values in sera changed according to the progression or improvement of interstitial pneumonia. Immunohistochemical studies using pulmonary tissues obtained at autopsy from patients with AIP associated with PM/DM revealed that the hyaline membrane was mostly stained by anti-human cytokeratin 19 monoclonal antibody as well as the strong positivity of proliferating type II pneumocytes. CONCLUSION: These results suggest that the measurement of CK19 was a useful variable to evaluate the activity of lung injury in interstitial pneumonia associated with PM/DM.

Adult↗

Detection of anti-cytokeratin 8 antibody in the serum of patients with cryptogenic fibrosing alveolitis and pulmonary fibrosis associated with collagen vascular disorders.

BACKGROUND: It has been suggested that the humoral immune system plays a role in the pathogenesis of cryptogenic fibrosing alveolitis (CFA). Although circulating autoantibodies to lung protein(s) have been suggested, none of the lung proteins have been characterised. The purpose of this study was to determine the antigen to which the serum from patients with pulmonary fibrosis reacted. METHODS: The anti-A549 cell antibody was characterised in a patient with CFA using Western immunoblotting and immunohistochemical staining of A549 cells. As we identified that one of the antibodies against A549 cells was anti-cytokeratin 8, the expression of mRNA of cytokeratin 8 in A549 cells was evaluated. In addition, we attempted to establish an enzyme linked immunosorbent assay to measure the levels of anti-cytokeratin 8 antibody in the serum of patients with CFA and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). RESULTS: Initially two anti-A549 cell antibodies were detected in the serum of patients with pulmonary fibrosis, one of which was characterised as anticytokeratin 8 antibody by Western immunoblotting. We were able to establish an ELISA to measure anti-cytokeratin 8 antibody and found significantly higher levels in patients with CFA and PF-CVD than in normal volunteers, patients with sarcoidosis, pneumonia, and pulmonary emphysema. CONCLUSIONS: One of the anti-A549 cell antibodies in the serum of patients with CFA was against cytokeratin 8. The serum levels of anti-cytokeratin 8 antibody were increased in patients with CFA and PF-CVD. These results suggest that anticytokeratin 8 antibody may be involved in the process of lung injury in pulmonary fibrosis.

Adult↗

Role of daunorubicin in the induction therapy for adult acute myeloid leukemia.

PURPOSE: To evaluate the relationship of total-dose of daunorubicin (DNR) to the induction therapy and treatment outcome, we have administered individualized doses of DNR during induction treatment to patients with acute myelogenous leukemia (AML). PATIENTS AND METHODS: Ninety-two previously untreated adult patients with AML who entered our hospital were analyzed for the dose of DNR required to achieve complete remission (CR), the CR rate, disease-free survival (DFS), and overall survival (OS). Induction therapy consisted of DNR 40 mg/m2 daily intravenously from day 1 until the marrow was hypoplastic, cytarabine (Ara-C), prednisolone (PRD), and/or 6-thioguanine (6-TG). RESULTS: Eighty-three of 92 patients with adult AML were assessable for this study. Sixty-three (76%) patients achieved CR. Fifty-two of 63 CR patients achieved the CR in the first course of induction therapy, and 11 patients required the second course of induction therapy. The 5-year and 10-year DFS rates were 31.2% and 5-year and 10-year OS rates were 45.1% and 42.3%, respectively. The median total dose of DNR in the induction therapy was 280 mg/m2 (120 to 480 mg/m2). DNR dose did not influence the response to therapy and was not influenced by the initial WBC count or French-American-British (FAB) system classification. CONCLUSION: These results indicated that when the dose was linked to observed tumor response, the optimal dose of DNR in the induction therapy was approximately 280 mg/m2 (40 mg/m2 for 7 days), which is greater than the conventional dose of 40 to 60 mg/m2 for 3 days.

Adolescent↗

[EPOCH therapy for relapsed/refractory lymphoid malignancies].

Patients with refractory or relapsed non-Hodgkin's lymphoma (NHL), acute T-cell leukemia (ATL), ATL lymphoma and acute lymphocytic leukemia (ALL) received EPOCH therapy. All were previously treated with doxorubicin (DOX), vincristine (VCR) and other drugs. The EPOCH treatment schedule is consisted with DOX (10 mg/M2/day, 5 days c.i.v.), VCR (0.4 mg/M2/day, 4 days c.i.v.), etoposide (50 mg/M2/day, 4 days c.i.v.), cyclophosphamide (750 mg/M2/day, day 6 i.v.) and prednisolone (60 mg/M2/day, 5 days p.o.). Twenty-one patients (ALL:10, NHL:8, ATLL:2, ATL:1) were assessable for response and toxicity. Two patients with ALL and NHL, respectively, achieved a complete remission and 3 patients obtained partial remission (NHL:2, ATLL:1). The hematological toxicity (grade > 1) included neutoropenia, anemia and thrombocytopenia, which were observed in 83.3%, 76.7% and 76.7% respectively, of total 30 EPOCH courses. The major non-hematological toxicities were nausea/vomiting, constipation and infection, but most of the toxicity were tolerable with sufficient clinical supportive care. These results indicate that continuous infusion of DOX, VCR and ETP might be effective in patients who were treated with, and presumed to be resistant to the same drugs administrated by bolus infusion.

Adolescent↗

[Primary cardiac non-Hodgkin's lymphoma].

A 69-year-old man who initially presented with lumbago developed heart failure during an MRI scan on the day of admission. A chest X-ray showed cardiomegaly and bilateral pleural effusion. Echocardiogram and computed tomography (CT) scan of the chest revealed a large tumor mass encompassing the heart with much pericardial effusion was demonstrated. The cytology of the effusion obtained by pericardiocentesis was consistent with non-Hodgkin's lymphoma, diffuse large B cell type. As CT scans of the abdomen and pelvis were negative, he was considered to have primary cardiac lymphoma. Although he responded remarkably to therapy with vincristine, cyclophosphamide and prednisolone and, he developed acute respiratory failure on the seventh month after admission. Although incidence of primary cardiac lymphoma is very low, it is necessary to investigate the mechanism of this disease in order to establish appropriate diagnostic and therapeutic approaches.

Aged↗

[Prognostic significance of CD7 expression in adult acute myeloid leukemia].

To evaluate the prognostic significance of CD7 expression in de novo acute myeloid leukemia (AML), we studied 63 patients with AML who had been admitted to our hospital between September 1989 and January 1996. Even of the patients were later eliminated from the study (9 due to insufficient surface marker analyses, and 2 due to early death). The remaining 52 patients (median age: 42.5 years) were evaluated for morphologic subtype, immunophenotypic classification, complete remission (CR), disease-free survival (DFS) and overall survival (OS). All 52 patients were grouped by the French-American-British classification system: 10 as M1, 16 as M2, 11 as M3, 8 as M4, 5 as M5, and 2 as M6. Ten of the patients expressed CD7 on their leukemia cells (positive rate > or = 25) and were classified as CD7(+)AML, with morphological subtypes as follows: 3 as M1, 6 as M2, and 1 as M3. Thirty-three of the 42 patients with CD7 + AML (78.6%) and 6 of the 10 patients with CD7 + AML (40%) achieved CR. DFS and OS rates for the patients with CD7(+)AML were 22.1% and 35.4%, respectively; those for the CD7(+)AML patients were 53.3% and 44.4%, respectively. No significant differences in gender hematological findings, clinical manifestations such as hepatosplenomegaly, lymphadenopathy, or incidence of central nervous system involvement, CR rate, and DFS distinguished patients with CD7(+)AML from those with CD7(+)AML. These suggest that CD7 expression is unlikely to be a prognostic factor in AML.

Adolescent↗

[Chemotherapy for non-Hodgkin's lymphoma].

This review highlights the role of chemotherapy for intermediate grade non-Hodgkin's lymphoma (NHL) including immunoblastic large cell lymphoma and low grade NHL. The combined modality treatment (CMT) consisting of chemotherapy including adriamycin (ADM) and involved-field irradiation (IFI) is considered standard therapy for localized intermediate grade NHL since a superior outcome (long-term disease-free survival rate is about 80%) can be obtained by CMT. However, developing dose-intensified regimens in initial chemotherapy will change the role of IFI. The phase II study using second and third generation regimens for advanced intermediate grade NHL showed a better outcome than first generation regimen CHOP. Unfortunately, the recent phase III intergroup trial concluded that none of the second or third generation treatment was superior to CHOP, and this regimen is now considered to be standard chemotherapy. However, the cure rate of the CHOP regimen (about 30%) is not satisfactory, and efforts should be underway to develop promising regimens with significantly increased dose intensity. While radiotherapy such as IFI, extended-field irradiation and total lymph node irradiation for localized low grade NHL obtained a more than 50% disease-free survival rate, the role of chemotherapy remains controversial. To date, many randomized trials of single agent chemotherapy regimen, combination chemotherapies with or without ADM, and CMT have shown no overall survival benefit for advanced low grade NHL, so there is no standard therapy for it.

Antineoplastic Combined Chemotherapy Protocols↗

Haemodynamic changes during induced hypotension--comparison of trimethaphan with prostaglandin E1 assessed using transoesophageal echocardiography.

Haemodynamic changes during induced hypotension depend upon the hypotensive agent used. We investigated if, using transoesophageal echocardiography (TEE), we could identify the haemodynamic differences between trimethaphan and prostaglandin E1. Twenty-nine patients undergoing total hip replacement were selected for study. Hypotension was induced to a mean arterial pressure of 8.0-9.3 kPa with either trimethaphan (5-20 micrograms.kg-1.min-1) or prostaglandin E1 (0.5-2.0 micrograms.kg-1.min-1). The left atrial dimension, cardiac output, fractional shortening, pulmonary venous flow and mitral valve flow were evaluated using TEE. During induced hypotension, left atrial dimension decreased in both trimethaphan and prostaglandin E1 groups (P < 0.05). In the trimethaphan-treated patients systolic velocity in pulmonary venous flow decreased from 41.9 +/- 4.8 cm.sec-1 before induced hypotension to 27.8 +/- 4.2 cm.sec-1 by 30 min after stable hypotension had been established (P < 0.01). The late/early ratio of peak velocity in mitral blood flow decreased in prostaglandin E1 treated patients. Cardiac output increased from 4.2 +/- 0.5 L.min-1 to 5.3 +/- 0.4 L.min-1 during 30 min hypotension with prostaglandin E1 administration (P < 0.05), but cardiac output decreased from 5.0 +/- 0.5 to 3.5 +/- 0.4 L.min-1 with trimethaphan (P < 0.01). The differences in haemodynamic variables could be attributed to the venule dilatation effect of trimethaphan. We conclude that it was possible to detect the haemodynamic differences between trimethephan and prostaglandin E1 using TEE.

Adult↗

[Antitumor effect of SN-38, active form of CPT-11, on human colorectal cancer cell line].

The in vitro sensitivity testing for four human colorectal cancer cell lines to seven chemotherapeutic drugs including CPT-11, derivative of camptothecin, and its active form SN-38 were determined. MTT assay revealed that SN-38 was the most active for all four cell lines tested and its IC50's were very close to its clinically achievable plasma concentration. Relationship between exposure time and cytocidal effect of SN-38 was also investigated using MTT assay, topoisomerase-I (Topo-I) immunoblot analysis and DNA relaxation-assay, showing that IC50 value, Topo-I protein and Topo-I activity were decreased soon after the administration of SN-38 and reached to the plateau level at 24 hours. We conclude that SN-38 is very potent for colorectal cancer and the optimal schedule of CPT-11 can be the more continuous form of administration capable of as long as 24 hours exposure of its active metabolite, SN-38.

Antineoplastic Agents, Phytogenic↗

[Myocardial hemorrhage due to high-dose cyclophosphamide treatment in a case of non-Hodgkin's lymphoma].

43-year-old male with non-Hodgkin's lymphoma which was resistant to standard treatment received high-dose chemotherapy followed by autologous stem cell transplantation. He had a past history of nephrectomy due to renal cell carcinoma. He had received adriamycin at a total dose of 280mg/m2, but had no episode of heart disease. His chest radiograph, electrocardiogram and serum creatinine were within normal ranges at the start of high-dose chemotherapy. He was given 120 mg/kg of cyclophosphamide (CPM) over two days. Serum creatinine levels elevated two days before transplantation, and he felt discomfort of the chest followed by severe arrhythmia. He died of heart failure one day after the transplantation. Postmortem examination revealed diffuse myocardial hemorrhage with degeneration and necrosis of the heart muscle. CPM is one of the useful antitumor alkylating agents for the treatment of malignant neoplasms. Although conventional doses of CPM can be used without adverse cardiac effects, high-dose CPM has been reported to induce cardiotoxicity in a few cases. Patients often develop fatal acute heart failure. For the safe use of high-dose CPM, we must consider about the dosing schedule, early detection of adverse cardiac effects, and patient risk factors.

Adult↗

[Spontaneous splenic rupture in a case of non-Hodgkin's lymphoma].

A 58-year-old man admitted to hospital as an emergency with pain in the left hypochondrium. The initial physical examination revealed hypotension, giant splenomegaly and ascites but no lymphadenopathy was found. Laboratory findings at admission included hemoglobin level of 9.2g/dl, leucocyte count of 22, 100/microliters with 2% of lymphoma cell and platelets count of 66,000/microliters. A presumptive diagnosis of ruptured spleen was made. Splenectomy was performed after 7 hours from admission. The spleen was infiltrated by malignant lymphoma. Three weeks after surgery, left neck and abdominal lymphoadenopathy were recognized, therefore systemic chemotherapy was started. The leukemic change was one of important factors for the mechanisms of spontaneous splenic rupture in malignant lymphoma.

Antineoplastic Agents↗

[Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine. 14. Effect on epidural pressure].

We studied effect of total intravenous anesthesia using ketamine, fentanyl and droperidol (DFK) on epidural pressure as an index for cerebrospinal fluid pressure in six surgical patients who underwent gastrectomy. The epidural catheter was inserted on the previous day. The epidural puncture was made at Th7-12 and the tip of the catheter was located 5 cm cephalad. The epidural pressure was measured before, just after and 30 minutes after the induction. The induction dose of fentanyl was 5 micrograms.kg-1 and that of ketamine was 1 mg.kg-1. The epidural pressure at the induction decreased in significantly by 19% as compared with that before the induction. The result suggested that DFK would not increase cerebrospinal fluid pressure when the doses of ketamine and fentanyl were changed.

Adult↗

[Treatment of priapism with intracavernous injection of etilefrine hydrochloride].

A case of priapism following epidural anesthesia was reported. A 67 year old man received epidural anesthesia for the transurethral resection of a malignant bladder tumor. Epidural anesthesia which he had wanted to receive was given through the L3 to L4 intervertebral space with 18 ml of 2% lidocaine. The penile erection occurred while he was prepared and draped. Additional 8 ml of 1% lidocaine failed to overcome it and the operation cancelled. After this episode, he had anesthesia on 5 occasions in 2 years. General anesthesia was given 3 times without penile erection, but epidural block was tried on 2 occasions, which was followed by penile erection. For the penile erection, intracavernous injection of etilefrine hydrochloride was effective and surgical procedure could be done smoothly. The mechanism of priapism remained unclear but imbalance of the autonomic nervous system may be a involved. This case suggests that intracavernous injection of etilefrine hydrochloride is effective for treatment of penile erection during transurethral surgery.

Aged↗