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Biomedical subjects

N Masuda

Publications and source records attributed to N Masuda.

At least 145 records · Page 8Linked to original sources
PubMed1993

[Chemotherapy for small cell lung cancer].

This paper describes the results of a randomized trial comparing alternating chemotherapy with standard chemotherapy and of a trial of dose intensive chemotherapy with or without recombinant human granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC). 1) Between April 1985 and May 1988, the Japan Clinical Oncology Group conducted a randomized phase III trial of cyclophosphamide, doxorubicin and vincristine (CAV) versus cisplatin and etoposide (PE) versus CAV alternating with PE (CAV/PE). Three hundred patients were entered in the study, and 288 of them were eligible for analysis. The response rates for PE (78%) and CAV/PE (76%) were significantly higher than the rate for CAV (55%) (p < 0.01). The median survival time (MST) with CAV/PE (11.8 months) was superior to that with CAV (9.9 months) (p = 0.027) or that with PE (9.9 months) (p = 0.056); however, the survival advantage of CAV/PE disappeared when the data were adjusted for prognostic factors. These results have shown that CAB/PE is a reasonable approach for the management of SCLC. 2) Between May 1989 and September 1991, we carried out a randomized study to determine whether the dose intensity of the weekly CODE (cyclophosphamide, Oncovin, doxorubicin and etoposide) chemotherapy could be increased by the addition of G-CSF support. Sixty-three patients were entered in this study. The use of G-CSF was associated with a reduced incidence of neutropenic fever and an increase in the dose intensity. The MST for the patients treated with CODE plus G-CSF (58 weeks) was significantly longer than that for the patients treated with CODE alone (36 weeks). The results of this study showed that dose intensive weekly chemotherapy may improve the outcome of patients with ED-SCLC.

Aged↗
PubMed1993

[A case of rabbit syndrome--its unique pharmacological feature].

A 61-year-old woman developed cerebellar ataxia as an initial symptom when she was 52 years old. Her neurological symptom was gradually followed by autonomic nervous system disturbance, pyramidal sign, and rigidity. She was diagnosed as suffering from multiple system atrophy (MSA), when she was 53 years old. Magnetic resonance imaging revealed atrophy of the cerebellum and brainstem. She was accompanied by rabbit syndrome (RS), when she was 61 years old. She had not been given any neuroleptics, which might produce RS, before she developed RS. Her regular involuntary movement was localized in lips, and its frequency was about 3 Hz. While sleeping, she did not have the involuntary movement. We had a chance to conduct pharmacological examination on RS. The administration of atropine or trihexyphenidyl did not change her symptom of RS, and the intravenous injection of levodopa deteriorated the movement. Haloperidol, sulpiride, or chlorpromazine was significantly effective on her involuntary movement of RS. These results indicated that our patient had the supersensitivity in her dopamine receptor. Such supersensitivity might result from the denervation in MSA, because she had not been administered any neuroleptics. RS is generally considered to be a kind of extrapyramidal sign, and we have not been aware of any report about RS, which levodopa deteriorated and neuroleptics improved. The mechanism of her symptom is discussed.

Antipsychotic Agents↗
PubMed1993

[Assessment of left ventricular contractility (Emax) and arterial load (Ea) in humans by transesophageal echocardiography and radial artery pressure tracing].

We determined both the slope of the left ventricular end-systolic pressure-volume relation (Emax), which is a measure of contractility independent of loading conditions, and the slope of the arterial end-systolic pressure-stroke volume relation (Ea), which is a measure of arterial load independent of ventricular function, in 10 patients undergoing elective noncardiac surgery. Left ventricular end-systolic volume (Ves) was measured by transesophageal echocardiography and instantaneous left ventricular end-systolic pressure (Pes) was estimated from the dicrotic notch pressure in the radial artery. Emax was calculated during afterload reduction (nicardipine 30 micrograms.kg-1 iv), and the correlation of Emax to either Pes/Ves ratio or MAP (mean arterial blood pressure)/Ves ratio was accomplished in order to investigate whether these indices were clinically useful measurements of ventricular function or not. Ea was also calculated from the data obtained before and 2-3 min after nicardipine iv. The averaged Emax and x-axis intercept (Vo) were 3.11 mmHg.ml-1 and -3.8 ml, respectively. The correlation coefficient obtained between Emax and Pes/Ves was 0.96, and that obtained between Emax and MAP/Ves was 0.97. Ea decreased significantly (P < 0.05) following intravenous nicardipine, demonstrating a decreased arterial load. The direction of changes in Ea was similar to that reported previously in systemic vascular resistance. From these results, we conclude that measurement of Emax (or Pes/Ves, MAP/Ves) and Ea using transesophageal echocardiography and radial artery pressure tracing is feasible and these are a useful tool to estimate left ventricular performance and arterial load during surgery.

Blood Pressure↗
PubMed1993

[Systemic chemotherapy for brain metastasis from small cell lung cancer].

Small cell lung cancer (SCLC) is rapidly progressive, but is sensitive to chemotherapy. The incidence of brain metastasis is high in patients with this disease. The management of brain metastases is an important problem in SCLC patients, because brain tumors have been regarded as being inaccessible to anti-cancer agents due to the blood-brain-barrier (BBB). Of 15 SCLC patients with brain metastasis at diagnosis who were treated with chemotherapy, 3 achieved a complete response (CR) and 4 had a partial response (PR), giving a response rate of 47%. Of 17 SCLC patients with brain metastasis at relapse, 1 achieved a CR and 6 had a PR by chemotherapy, with a response rate of 30%. The response rate of brain metastasis in SCLC patients treated with chemotherapy was similar to those of primary lesions and other metastatic lesions. SCLC patients with brain metastasis at diagnosis had the same response rate and median survival time as other ED-SCLC patient. The BBB may not be an impending factor in systemic chemotherapy of brain metastasis in SCLC. Systemic chemotherapy may be the treatment of choice for SCLC patients with brain metastasis.

Adult↗
PubMed1992

Proton potential-dependent polyamine transport by vacuolar membrane vesicles of Saccharomyces cerevisiae.

Vacuolar membrane vesicles of Saccharomyces cerevisiae accumulated spermine and spermidine in the presence of ATP, not in the presence of ADP. Spermine and spermidine transport at pH 7.4 showed saturation kinetics with Km values of 0.2 mM and 0.7 mM, respectively. Spermine uptake was competitively inhibited by spermidine and putrescine, but was not affected by seven amino acids, substrates of active transport systems of vacuolar membrane. Spermine transport was inhibited by the H(+)-ATPase-specific inhibitors bafilomycin A1 and N,N'-dicyclohexylcarbodiimide, but not by vanadate. It was also sensitive to Cu2+ or Zn2+ ions, inhibitors of vacuolar H(+)-ATPase. Both 3,5-di-tert-butyl-4-hydroxybenzilidenemalononitrile (SF6847) and nigericin blocked completely the spermine uptake, but valinomycin did not. [14C]Spermine accumulated in the vesicles was exchangeable with unlabeled spermine and spermidine. However, it was released by a protonophore only in the presence of a counterion such as Ca2+. These results indicate that a polyamine-specific transport system depending on a proton potential functions in the vacuolar membrane of this organism.

Adenosine Triphosphate↗
PubMed1992

Neurons in the caudal ventrolateral medulla mediate the somato-sympathetic inhibitory reflex response via GABA receptors in the rostral ventrolateral medulla.

In urethane-anesthetized rabbits, stimulation of the sural nerve, consisting of cutaneous afferents (A-fibers), evoked reflex responses consisting of an early small excitatory component followed by a prolonged inhibitory component in renal sympathetic nerve activity. Bilateral injections of GABA antagonist, bicuculline (4 nmol/site), into the rostral ventrolateral medulla (RVLM), where sympatho-excitatory reticulospinal neurons are located, attenuated the inhibitory component in a dose-dependent manner as well as the inhibition evoked by stimulation of the aortic nerve A-fibers (baroreceptor afferents). Bilateral injections of a neurotoxic agent, kainic acid (4 nmol/site, 3 sites/side), into the caudal ventrolateral medulla (CVLM), where sympatho-inhibitory neurons with axonal projection to the RVLM are located, diminished these sympatho-inhibitory responses. Therefore it is concluded that the sympatho-inhibition evoked by activation of somatic afferents was mediated by neurons in the CVLM and by GABA receptors in the RVLM, as was the sympatho-inhibition associated with the arterial baroreceptor reflex. Bilateral injections of kynurenic acid (4 nmol/site, 3 sites/side) into the CVLM did not affect the somato-sympathetic reflex response, but diminished the sympatho-inhibition produced by activation of the baroreceptor afferents. Sympatho-inhibitory neurons in the CVLM were activated by glutamate when baroreceptor afferents were activated, but another excitatory transmitter may participate in the somato-sympathetic reflex in the CVLM.

Animals↗
PubMed1992

Mitomycin C, vindesine, and cisplatin in advanced non-small-cell lung cancer. A phase II study.

Between August 1985 and June 1986, 49 previously untreated patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) were treated with the combination of cisplatin 80 mg/m2 i.v. on day 1, vindesine 3 mg/m2 i.v. on days 1 and 8, and mitomycin-C 8 mg/m2 i.v. on day 1 (MVP), repeating after an interval of 4 weeks, and thereafter every 6 weeks. The median age for all patients was 62 years, with a range of 21 to 77 years. All patients had a performance status of 0, 1, or 2 (ECOG scale) and measurable disease. Histologic types included squamous cell carcinoma (22 patients), adenocarcinoma (22 patients), and large-cell carcinoma (6 patients). Forty-eight patients were evaluable for response. Out of 48 patients, one (2%) achieved a complete response and 24 patients (50%) achieved a partial response, resulting in an overall response rate of 52% (95% confidence interval, 38-68%). The response rates were 52% for squamous cell carcinoma, 45% for adenocarcinoma, and 80% for large-cell carcinoma, respectively. The median duration of response was 4.2 months and the median duration of survival for all patients was 10.6 months. The major toxicity was myelosuppression. Leukopenia and thrombocytopenia of grade 3 or 4 occurred in 85% and 33%, respectively. One patient died of sepsis associated with leukopenia. Other toxicities were manageable and reversible. In conclusion, the MVP regimen was active and tolerable in patients with advanced NSCLC. Prospective randomized study comparing the MVP regimen with the two-drug combination of vindesine and cisplatin is warranted.

Adult↗
PubMed1992

Weekly dose-intensive chemotherapy in patients with small-cell lung cancer: a pilot study.

The study was aimed to evaluate the feasibility of dose-intensive chemotherapy given on a weekly basis for 12 weeks. Seventeen [7 with limited disease (LD) and 10 with extensive disease (ED)] previously untreated patients with small-cell lung cancer (SCLC) were treated with the cisplatin, vincristine, doxorubicin, and etoposide (CODE) regimen. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was given to eight patients for the purpose of increasing the dose intensity. Overall response rate was 88%, with a 29% complete response. The median survival times were greater than 20.5 months for LD patients and 8.1 months for ED patients. Overall actual dose intensity was 88% of planned protocol. The major toxicity was myelosuppression. Fifteen patients (88%) had grade 3 or 4 leukopenia. Other problems were weight loss and worsening of performance status during the treatment. RhG-CSF significantly reduced leukopenic nadirs and shortened the neutropenic period. Our preliminary results indicate that 12 cycles of the CODE regimen on a weekly schedule is effective for SCLC, but is also associated with significant toxicity.

Adult↗
PubMed1992

Cross-resistance to meropenem, cephems, and quinolones in Pseudomonas aeruginosa.

Multiple-drug-resistant mutants were isolated from Pseudomonas aeruginosa PAO1 on agar plates containing ofloxacin and cefsulodin. These mutants were four to eight times more resistant to meropenem, cephems, carbenicillin, quinolones, tetracycline, and chloramphenicol than the parent strain was. In contrast, these mutants showed no significant changes in their susceptibilities to all carbapenems except meropenem. In these mutants, the amounts of an outer membrane protein with an apparent molecular weight of 49,000 (designated OprM) were increased compared with the amount in PAO1. Multiple-drug-resistant mutants of this type were also isolated from PAO1 on agar plates containing meropenem. Approximately 5% of clinical isolates showed cross-resistance to meropenem, cephems, and quinolones, concomitant with overproduction of OprM. Moreover, these two phenotypes, i.e., multiple-drug resistance and overproduction of OprM, were cotransferable by transduction. These data suggest that overproduction of OprM is associated with cross-resistance to meropenem, cephems, and quinolones in P. aeruginosa. The ofloxacin-cefsulodin-resistant mutant required higher concentrations of meropenem to induce beta-lactamase than PAO1 did, indicating the possibility that this mutation involves decreased outer membrane permeability to meropenem.

Anti-Bacterial Agents↗
PubMed1992

CODE chemotherapy with or without recombinant human granulocyte colony-stimulating factor in extensive-stage small cell lung cancer.

CODE therapy demonstrated high antitumor activity in extensive-stage small cell lung cancer (SCLC). Toxicity was acceptable in a regimen with a nine-cycle schedule. The results obtained in this study suggest that CODE therapy improves the outcome of patients with extensive-stage SCLC. The use of recombinant human granulocyte colony-stimulating factor may well reduce the duration and degree of neutropenia during CODE chemotherapy and increase the dose intensity, leading to further improvement of outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small-cell lung cancer.

PURPOSE: Camptothecin-11 (CPT-11) is a new semisynthetic derivative of CPT, and has been shown to inhibit DNA topoisomerase I and to have a strong antitumor activity with low toxicity in murine tumors. To evaluate the effectiveness of CPT-11 in patients with non-small-cell lung cancer (NSCLC), a phase II study was conducted between April 1989 and February 1990. PATIENTS AND METHODS: Seventy-three patients were entered onto the study. All patients had had no previous therapy and had measurable disease. Their median age was 67 years (range, 34 to 75 years). Fifty-four patients had a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale, and 19 had a PS of 2. CPT-11 was given at a dose of 100 mg/m2 by intravenous 90-minute infusion once a week. The dose of CPT-11 was modified based on the WBC count obtained on the day of drug administration. RESULTS: Of 72 assessable patients, 23 (31.9%) showed a partial response (95% confidence interval, 20.2% to 43.6%). Of 40 patients with a stage IV disease, 13 (32.5%) responded. Response rates for patients with PS 0 or 1 and those with PS 2 did not differ (34.0% and 26.3%, respectively). The median duration of response in patients showing a PR was 15 weeks. The median survival time for all patients was 42 weeks. The major toxicities were leukopenia and diarrhea. Grade 3 or 4 leukopenia and diarrhea occurred in 18 patients (25%) and 15 patients (21%), respectively. These toxicities were unpredictable. Other toxicities of greater than or equal to grade 3 included nausea/vomiting (22%), anemia (15%), alopecia (4%) and pneumonitis (3%). One patient died of pulmonary toxicity (interstitial pneumonitis). CONCLUSIONS: CPT-11 is a very active agent for NSCLC with acceptable toxicities. Further trials in combination with other agents for this disease are warranted.

Adult↗
PubMed1992

CPT-11 in combination with cisplatin for advanced non-small-cell lung cancer.

PURPOSE: The purpose of this study was to determine the maximum-tolerated dose and the dose-limiting toxicities of CPT-11, a new derivative of camptothecin, in combination with a fixed dose of cisplatin in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-seven previously untreated patients with stage IIIB or IV NSCLC were assessable for toxicity, and 26 were assessable for response. The initial dose of CPT-11 was 30 mg/m2 given as a 90-minute intravenous (IV) infusion on days 1, 8, and 15 in combination with cisplatin (80 mg/m2 IV on day 1) given every 4 weeks. The dose of CPT-11 was escalated in increments of 10 mg/m2 until severe or life-threatening toxic effects were observed. RESULTS: Significant toxicity was infrequent up to 60 mg/m2 of CPT-11. The maximum-tolerated toxicity was reached at a dose of 70 mg/m2. Three of six patients either had leukocyte count nadirs of less than 2,000/microL or experienced grade 4 diarrhea during the first cycle of therapy at 70 mg/m2. The major toxic effects were leukopenia and diarrhea. There were 14 partial responses (54%) among the 26 patients. CONCLUSIONS: A combination of CPT-11 and cisplatin seems to be effective against NSCLC with acceptable toxicities. The recommended dose for phase II studies is 60 mg/m2 of CPT-11 on days 1, 8, and 15, and 80 mg/m2 of cisplatin on day 1 every 4 weeks.

Adult↗
PubMed1992

CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer.

PURPOSE: To evaluate the activity of CPT-11, which is a new derivative of camptothecin, against refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Sixteen patients with refractory or relapsed SCLC were entered onto a prospective, non-randomized, single-institution phase II trial. All 16 patients had been pretreated heavily with some form of cisplatin-based combination chemotherapy. Five patients had received previous chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide (CODE) as an induction therapy. Six patients had been treated with concurrent cisplatin and etoposide plus chest x-ray. The median time off chemotherapy was 7.3 months (range, 1.9 to 15.1 months). Patients were treated with a CPT-11 starting dose of 100 mg/m2 body surface given as a 90-minute intravenous (IV) infusion every week with subsequent doses based on toxicity. Fifteen patients were assessable for toxicity, response, and survival. RESULTS: Seven patients (47%; 95% confidence limits for an overall response rate, 21.4% to 71.9%) responded to CPT-11 with a median duration of response of 58 days. The major toxicities were myelosuppression (predominantly leukopenia), diarrhea, and pulmonary toxicity. CONCLUSION: CPT-11 is an active agent against refractory or relapsed SCLC and deserves to be studied more closely as both a single agent and in combination with other drugs to treat patients with SCLC.

Adult↗
PubMed1992

Coronary artery disease in patients with arteriosclerosis obliterans of the lower extremities or aortic aneurysm.

Routine coronary angiography was performed in order to determine the incidence and clinical condition of coronary artery disease in 37 patients with arteriosclerosis obliterans or aortic aneurysm. Coronary angiography demonstrated significant stenosis in 12 (57%) of 21 patients with arteriosclerosis obliterans and in 7 (44%) of 16 patients with aortic aneurysm. The prevalence of risk factors for arteriosclerosis was similar for patients with arteriosclerosis obliterans and those with aortic aneurysm, and similar for patients with and without coronary artery stenosis. But coronary artery disease is often silent in patients with arteriosclerosis obliterans.

Aged↗
PubMed1992

[A case-control study on factors relating to discontinuation of domiciliary care for the bedridden elderly in a metropolitan area].

A case-control study was conducted to examine factors relating to discontinuation of domiciliary care for the bedridden elderly in Shinagawa-ku, Tokyo. Cases were bedridden residents aged 65 years and over who had abandoned home care and applied for admission to live in a special nursing home for the aged between April and September in 1990 after being recipients of welfare allowances for disabled elderly. Controls were bedridden residents who continued to be given home care and matched to cases by sex, age and beginning month of the receiving of allowances. Among 50 cases and 94 controls interviewed, we obtained responses from 31 cases (62%) and 60 controls (64%). The main results were as follows: 1. During the home-care period, ADL (activities of daily living) of cases, especially walking ability, deteriorated more severely than in controls. Night delirium also appeared more frequently in cases. 2. The primary caregivers of cases were older than those of controls. Remarkable differences between cases and controls were observed in the family structure, the number of family members and the number of sub-caregivers. Cases tended to live alone or live with a spouse only, and with smaller number of family members and caregivers. 3. Case lived more frequently in houses with small numbers of rooms and without rooms of their own. 4. As regards utilization of domiciliary care services, cases used dispatch of home helpers more frequently and used day services less frequently.

Aged↗
PubMed1992

[Prognosis of small cell lung cancer with ipsilateral pleural effusion].

A total of 184 patients with small cell lung cancer (SCLC) including 18 patients with ipsilateral pleural effusion as the only evidence of metastasis beyond the primary tumor site (PL), 84 patients with limited disease (LD), and 82 patients with extensive disease (ED) were treated at the Osaka Prefectural Habikino Hospital between December 1982 and June 1990. The median survival time for patients with PL was 51 weeks; for the patients with LD, 51 weeks; and for the patients with ED, 34 weeks. The survival of PL patients was significantly better than that of ED patients (P less than 0.05), and did not differ from that of LD patients. The response rate of PL patients was not significantly different from the response rates observed in LD- and ED-patients. There was no significant difference in survival or response rate between patients with cytologically positive and those with cytologically negative PL. Ipsilateral pleural effusion was not found to be a independent prognostic factor for survival from multivariate analysis in LD patients. These results indicate that the classification of limited disease small cell lung cancer should include patients with ipsilateral pleural effusion, as suggested by the consensus report at the International Association for the Study of Lung Cancer (IASLC) Workshop in 1989.

Adult↗