Biomedical subjects

Y Ohe

Publications and source records attributed to Y Ohe.

At least 127 records · Page 7Linked to original sources

PubMed1992

In vitro enhancement of fluoropyrimidine-induced cytotoxicity by leucovorin in colorectal and gastric carcinoma cell lines but not in non-small-cell lung carcinoma cell lines.

Leucovorin (LV) increases the cytotoxic effect of fluorouracil (FUra) and 5-fluoro-2'-deoxyuridine (FdUrd) by enhancing the formation of the fluorodeoxyuridine monophosphate (FdUMP) thymidylate synthase (TS) 5,10-methylenetetrahydrofolate (mTHF) ternary complex. To study the difference in the efficacy of this combination against different tumors, we compared the effect of LV (20 microM) on the cytotoxicity of FUra, FdUrd, and 5-fluorouridine (FUrd) in vitro against cell lines of five colorectal carcinomas (CC), five gastric carcinomas (GC), and four non-small-cell lung carcinomas (NSCLC) using the colony-forming assay. At the concentration used in the experiments, LV alone failed to inhibit colony formation in any of the cell lines tested. The NSCLC cell lines were more resistant to FdUrd than were the CC and GC lines. LV modulated the cytotoxicity of FdUrd in all five CC lines and in three of the five GC lines but failed to do so in any of the NSCLC lines. In addition, following 20 h treatment with 1 microM [3H]-FdUrd, formation of the FdUMP/TS/mTHF ternary complex was enhanced by LV in the LV-sensitized CC and GC cell lines but not in the LV-refractory NSCLC lines. These in vitro data corresponded well to the results of clinical trials. Therefore, the colony-forming assay may be useful for the identification of the sensitivity of tumors according to phenotype.

Adenocarcinoma↗

PubMed1992

A prognostic-factor risk index in advanced non-small-cell lung cancer treated with cisplatin-containing combination chemotherapy.

Prognostic factors for response and survival were retrospectively evaluated in 192 previously untreated patients with advanced non-small-cell lung cancer (NSCLC) who had received either vindesine plus cisplatin or mitomycin plus vindesine plus cisplatin as initial treatment. Univariate analysis demonstrated that squamous-cell histology, early stage, and a small number of metastatic sites were favorable prognostic factors for response to chemotherapy. Multivariate analysis using Cox's proportional hazard model indicated that the number of metastatic sites was the only significant pretreatment factor for response (P = 0.0005). Multivariate regression analysis revealed that the number of metastatic sites (P = 0.0002), sex (P = 0.0009), serum albumen levels (P = 0.0018), performance status (P = 0.0026) and lactic dehydrogenase values (P = 0.0026) contributed independently to survival. On the basis of these five prognostic factors, a prognostic index for survival was used to define three prognostic groupings (good, intermediate, and poor) for survival (median survival, 16.5 vs 9.4 vs 4.6 months; P = 0.0001). This particular regression model should aid in the design and analysis of new treatment strategies and may be useful for indirect comparisons of different studies carried out in similar patient populations.

Adenocarcinoma↗

PubMed1992

A new 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for testing macrophage cytotoxicity to L1210 and its drug-resistant cell lines in vitro.

Activated by interferon gamma (IFN gamma)(50 U/ml) and lipopolysaccharide (50 ng/ml), mouse peritoneal macrophages were cocultured with the L1210 parental cell line (L1210/PRT) and its Adriamycin-, cisplatin-resistant cell lines (L1210/ADM, L1210/CDDP) for 24 h at effector: target (E:T) ratios of 10:1, 5:1 and 2:1. The direct 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT)-cleavage assay, a new improved indirect MTT assay, and the colony-formation assay were used to quantify macrophage-mediated suppression of these non-adherent tumour targets. The results showed that the macrophages can produce formazan at a high level, which can interfere with the final results of a direct MTT assay. The new indirect MTT assay can avoid such interference because the effectors are separated from the targets before the assay is performed, so the real viability of the targets is reflected. An indirect MTT assay, as developed in this study, could be better than the direct assay for examining the suppressive effect of activated macrophages on non-adherent tumour cells in vitro. This study also revealed that all the L1210 cell lines can be suppressed significantly by the macrophages at E:T ratios of 10:1 and 5:1 while the two drug-resistant cell lines have lower survival rates at an E:T ratio of 10:1, indicating that they are more susceptible than their parental cell line.

Animals↗

PubMed1992

Adult T-cell leukemia/lymphoma (lymphoma type) with remarkable gastric lesions: a case report.

We report a case of a 53-year-old woman with adult T-cell leukemia/lymphoma (ATL) (lymphoma type) with multiple gastric lesions, admitted to our hospital because of systemic lymphadenopathy and epigastralgia. Gastroscopy showed a variety of gastric lesions including thickened folds, ulcerations and polypoid lesions. Biopsy specimens obtained from the stomach and lymph nodes revealed diffuse infiltration of pleomorphic mononuclear cells and the integration of HTLV-1 proviral DNA. We demonstrated through the investigation of 30 previously reported cases of ATL that this is a rare case of the lymphoma type of ATL presenting remarkable gastric lesions.

Blotting, Southern↗

PubMed1992

Circulating tumor-associated antigens detected by monoclonal antibodies against the polypeptide core of mucin--comparison of antigen MUSE11 with CA15-3.

The antigen MUSE11 detected by a monoclonal antibody (MAb) is an adenocarcinoma-associated antigen, while CA15-3 is a representative breast cancer-associated antigen detected by MAbs 115D8 and DF3. MAb MUSE11 showed higher binding activity to a synthetic peptide corresponding to the tandem repeat motif of the mucin core protein than that of MAb DF3, although MAb DF3 also had a significant binding activity indicating that MAbs MUSE11 and DF3 could recognize an identical polypeptide core. The reactivity of MAb DF3 to a breast cancer cell line MRK-neu-1 was completely abolished by neuraminidase treatment whereas that of MAb MUSE11 was partly conserved. The simultaneous measurement of the antigens MUSE11 and CA15-3 in sera from 35 cancer patients demonstrated that the incidence of abnormal serum level of CA15-3 was lower than that of antigen MUSE11. These data suggest that at least a part of the structural basis for the difference between the serum levels of antigen MUSE11 and CA15-3 could be carbohydrate side chains including sialic acids.

Antibodies, Monoclonal↗

PubMed1992

Differential macrophage-mediated cytotoxicity to P388 leukemia cells and its drug-resistant cells examined by a new MTT assay.

After activation by interferon-gamma (INF-gamma) and lipopolysaccharide(LPS), mouse peritoneal macrophages were cocultured with P388 parental cell line (P388/PRT) and its adriamycin (ADM)-, cisplatin(CDDP)-, cyclophosphamide(CPM)-, and mitomycin-C(MMC)-resistant cell lines for one day at effector:target ratios (E:T) of 10:1, 5:1, and 2:1. The direct 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) cleavage assay and a new indirect MTT assay as well as clonogenic assay were used to quantitate activated macrophage-mediated cytotoxicity to these non-adherent leukemia targets. The results revealed that all the P388 cell lines can be suppressed efficiently by activated macrophages, but P388 CPM- and MMC-resistant cell lines (P388/CPM, P388/MMC) were more susceptible than P388/PRT while P388 ADM- and CDDP-resistant cell lines (P388/ADM, P388/CDDP) shared equal level of survival rates with P388/PRT. This study also showed that both non-activated and activated macrophages can produce formazan in a high level, which can interfere with the final results of direct MTT assay. The new indirect MTT assay can avoid such interference by separating the effectors from the targets before performing the MTT assay and reflects the real viability of the targets so the indirect MTT assay developed in this study could be a better way to examine cytostatic and cytotoxic effect of activated macrophages on non-adherent tumor cells in vitro.

Animals↗

PubMed1992

Mechanisms of collateral sensitivity to fluorouracil of a cis-diamminedichloroplatinum(II)-resistant human non-small lung cancer cell line.

A cisplatin(CDDP)-resistant subline of a human lung cancer cell line, PC-7/CDDP, was 4.7-fold more resistant to CDDP than the parent line in a colony-forming assay. The sensitivity of this cell line to anthracyclines, vinca-alkaloid, etoposide, mitomycin C, and bleomycin was similar to that of the parental line, PC-7. However, PC-7/CDDP exhibited 4-fold higher sensitivity to fluorouracil (FUra). Possible mechanisms associated with the collateral sensitivity to FUra were studied in PC-7/CDDP cells. The sensitivity of both cell lines to FUra did not correlate with the effect of FUra on RNA. On the other hand, FUra induced a greater reduction in dTTP pools and more single strand breaks in PC-7/CDDP than in PC-7 cells. These results suggest that the pathway for de novo deoxyribonucleotide synthesis may be a target for FUra in PC-7/CDDP cells. However, inhibition of thymidylate synthase after FUra treatment did not correlate with the DNA-directed activity of FUra. Based on the above findings, the decreased salvage synthesis of dTTP was considered a possible mechanism of the greater reduction of dTTP pools in PC-7/CDDP cells. However, the activity of dThd kinase was the same in both cell lines. In the presence of physiological concentrations of exogenous dThd in the serum, uptake of dThd was less in PC-7/CDDP cells than that in PC-7 cells. Our data suggest that FUra-induced cytotoxicity in PC-7/CDDP cells is associated with the inhibition of dTTP synthesis and that the decreased uptake of dThd is a possible mechanism of the collateral sensitivity to FUra in PC-7/CDDP cells.

Adenocarcinoma↗

PubMed1992

Chemotherapy-induced anemia in patients with primary lung cancer.

To elucidate the factors which influence the value of hemoglobin, the nadir value of hemoglobin, frequency of blood transfusion and prognostic value of blood transfusion in patients with primary lung cancer during intensive chemotherapy, the hematological features of 124 patients entered into a randomized phase III study containing cisplatin were retrospectively analyzed. There was no difference in the percent nadir hemoglobin value of the first course of chemotherapy (% of pretreatment value) in any of the subgroups with respect to sex, body weight loss, performance status, age, stage, number of metastatic sites or treatment arms. The only predictive indicator for the nadir hemoglobin value in the first course of chemotherapy was the pretreatment value of hemoglobin. The equation for the regression line was y = 1.07 + 0.73x (R2 = 0.663, p < 0.001). The lowest nadir hemoglobin value (% of pretreatment value) during all chemotherapy courses was significantly lower in the subgroups older than 60 years and those with body weight loss. There was an inverse correlation between the accumulated dose of cisplatin and the lowest nadir hemoglobin value (p < 0.05). The frequency of blood transfusion in patients with more than two metastatic sites was significantly higher than in those with one or no metastatic sites (p < 0.05). Survival of patients who had required blood transfusion after chemotherapy was significantly shorter than that of patients who had not (p < 0.05).

Adult↗

PubMed1992

Neurotrophic effects of fibroblast growth factors on peptide-containing neurons in culture from postnatal rat hypothalamus.

Basic fibroblast growth factor (bFGF) has been thought to act as a neurotrophic factor during early developmental stages in various brain regions, including the hypothalamus. In the present paper, we have studied the effect of bFGF on peptide-containing neurons cultured from the postnatal (1-3 days and 14 days after birth) rat hypothalamus. The addition of bFGF, or acid FGF (aFGF), to serum-free culture medium increased both survival and neurite growth of growth hormone-releasing factor (GRF)-containing neurons. The potency of bFGF was more than 10 times as great as that of aFGF. Insulin-like growth factor I (IGF-I) did not have any significant effect on the survival of GRF neurons. Further, neither IGF-I nor aFGF modified the survival-promoting effect of bFGF on GRF neurons. bFGF promoted the survival of somatostatin- and vasoactive intestinal polypeptide-containing neurons, too.

Animals↗

PubMed1992

[Induction of tumor immunity by cytokine cDNA transfected Lewis lung carcinoma].

It is difficult to induce anti-tumor immunity in tumors with low antigenicity. In order to develop a more effective method of immunotherapy, we transfected interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6) genes into Lewis lung carcinoma (LLC) cells. Then, 1 x 10(6) LLC-IL-2, LLC-IL-4 or LLC-IL-6 cells were transplanted into C57BL/6 mice subcutaneously. All mice transplanted with LLC-IL2 and half those with LLC-IL-4 rejected the tumor cells. Survival time of LLC-IL-6 transplanted mice was significantly shorter than that of LLC transplanted mice, with no difference in tumor growth. These data suggest that transplantation of IL-2 or IL-4 gene transfected cells could effectively induce immunity against LLC. IL-6 transfection did not induce immunity, but induced cachexia.

Animals↗

PubMed1992

[Changes in forehead and sole tissue temperature during cardiopulmonary bypass for acquired cardiac disease].

The forehead tissue temperature (FT-T) and the sole tissue temperature (ST-T) were measured and recorded by a deep body thermometer (Terumo Corp.) during open heart surgery. The changes in FT-T and ST-T after cardiopulmonary bypass (CPB) showed two characteristic patterns; the convergence pattern and the dissociation pattern. It is said that the dissociation pattern can notes a poor peripheral circulation. The deverging point of the two patterns was studied in 65 patients with acquired cardiac disease. We divided the patients into two groups taking 3.5 degrees C of the FT-T and ST-T difference (DT) after 2 hour weaning from CPB. The number of the patients in convergence group (group I) was 42, and that in the dissociation group (group II) was 23. The two groups were compared with the DT and the time required for the rise in each temperature from CPB rewarming to CPB weaning. There was no intergroup difference in the DT when the FT-T began to rise upon CPB rewarming. However, the DT was 3.8 +/- 2.3 (mean +/- SD) degrees C in group I and 7.1 +/- 1.8 degrees C in group II when the ST-T began to rise, and 4.2 +/- 2.5 degrees C in group I and 6.9 +/- 1.4 degrees C in group II when the FT-T reached its peak; the figures were significantly lower in group I (P < 0.01). The time required for the rise in ST-T was significantly shorter in group I (14.8 +/- 17.1 min) than in group II (25.8 +/- 14.7 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary Bypass↗

PubMed1991

Phase I study and pharmacological analysis of cis-diammine(glycolato)platinum (254-S; NSC 375101D) administered by 5-day continuous intravenous infusion.

A phase I study of cis-diammine(glycolato)platinum (254-S; NSC 375101D) was conducted in 15 patients with refractory or relapsing malignancy by 5-day continuous i.v. infusion. Three to 5 patients per dose were given 50, 75, 87.5, or 100 mg/m2/120 h (10-20 mg/m2 daily for 5 days). Toxicity evaluation and pharmacokinetic analysis were performed in 15 and 14 patients, respectively. Thrombocytopenia and neutropenia were the dose-limiting toxicities at the maximum tolerated dose of 87.5 mg/m2/120 h (17.5 mg/m2/day); however, nonhematological toxicities including renal toxicity, nausea and vomiting, and peripheral neuropathy were mild and well tolerated. The nadir of platelets and neutrophils was observed 4 and 5 weeks, respectively, after the initiation of drug infusion. Plasma and urine samples were obtained during and after infusion for quantification by atomic absorption spectrophotometry of total and free platinum levels derived from 254-S. The maximum level of total platinum was obtained after 120 h of infusion, whereas the steady state concentration of free platinum in the patients given 75 mg/m2 or more was over 0.1 microgram/ml. Free platinum levels declined monophasically, with half-lives of 0.65-2.56 h/100 mg/m2 dose. The mean area under the concentration versus time curve (AUC) in the patients treated with 75 mg/m2 was 1069 micrograms/ml, which was similar to that obtained in the patients receiving 100 mg/m2 of 254-S by i.v. drip infusion over 30 min. There was a direct correlation between the dose administered and the AUC of platinum (R = 0.757, P = 0.002) or the steady state plasma concentration of free platinum (R = 0.763, P = 0.002). The percentage of platinum excreted in urine 144 h after the initiation of infusion ranged from 73.1 to 100% for each dose level. No significant relationship was established between creatinine clearance in patients before treatment and the AUC or steady state concentration of free platinum. The plasma platinum AUC showed a linear correlation with the percentage of change in leukocytes [formula: see text] (R = 0.736, P = 0.003). In conclusion, the recommended phase II dose for a continuous infusion of 254-S is 75.5 mg/m2/120 h every 6 hours.

Adult↗

PubMed1991

Prediction of the antitumor activity of new platinum analogs based on their ex vivo pharmacodynamics as determined by bioassay.

We report the predictive model for the clinical response of new platinum analogs against lung cancer by a bioassay using human lung-cancer cell lines including small-cell (SCLC) and non-small-cell lung cancer (NSCLC). Exponentially growing cells of six different SCLC and six NSCLC lines were exposed to different concentrations of the three platinum compounds, cisplatin, carboplatin, and 254-S in a double-agar colony-forming cell assay. The concentrations inhibiting 50% of colony formation (IC50 value) for cisplatin, carboplatin and 254-S in SCLC cell lines were significantly lower than those in NSCLC cell lines. A total of 15 patients entered the pharmacological study. In all, 80 mg/m2 cisplatin, 450 mg/m2 carboplatin, and 100 mg/m2 254-S were each given to five patients by intravenous drip infusion. Bioassay as well as chemical assay was achieved by clonogenic techniques using NCI-H-69 (SCLC cell line) and PC-9 (NSCLC cell line) as target cells. Biological comparison of antitumor activity was performed on the basis of the antitumor activity of patients' plasma using the antitumor index (ATI), which was defined as the area under the percentage of colony suppression versus time curve obtained by bioassay and calculated by the trapezoidal rule. When NCI-H-69 and PC-9 were used as target cells for bioassay, colony-inhibitory activity was revealed by the ATIs. The ATIs obtained by bioassay showed better correlation than the AUCs obtained by chemical assay with the clinical response for cisplatin and carboplatin against SCLC and NSCLC, according to the following equation: [Reported Response (%)] = 11.5668 + 0.0014 x [ATI] (r = 0.97). The response rates for 254-S against SCLC and NSCLC were predicted by this formula to be 40%-65% and 14%-16%, respectively. 254-S is prospectively suspected of having the same, if not more, activity then carboplatin against SCLC and of having almost the same activity as cisplatin against NSCLC.

Antineoplastic Agents↗

PubMed1991

A randomised clinical trial of vindesine plus cisplatin versus mitomycin plus vindesine and cisplatin in advanced non-small cell lung cancer.

This trial was carried out to evaluate the therapeutic benefit of the addition of mitomycin to vindesine plus cisplatin (80 mg/m2) in 126 previously untreated non-small cell lung cancer (NSCLC) patients. 124 patients were evaluable for toxicity and survival and 122 for response. No patient achieved complete response. The partial response rate (PR) in the vindesine plus cisplatin (VP) and mitomycin plus vindesine and cisplatin (MVP) groups were 23% (14/62) vs. 35% (21/60) (P = 0.13) with a median duration of response of 23 vs. 37 weeks (P = 0.071), respectively. Time to progression (TTP) and survival time (ST) were similar for both treatment arms [median TTP; 14 vs. 21 weeks (P = 0.10), median ST; 9.1 vs. 10.5 months (P = 0.94), respectively]. No difference in the frequency of side-effects was observed except that WHO grade 3 and 4 leukopenia was higher in the MVP group. In multivariate analysis, the significant predictors of survival were serum albumin, sex, performance status, lactate dehydrogenase and stage. In conclusion, the addition of mitomycin to the VP regimen appears to have limited value in advanced NSCLC.

Adult↗

PubMed1991

Late toxicities and complications in three-year survivors of small cell lung cancer.

123 patients with small cell lung cancer (SCLC) presented to the National Cancer Center Hospital (Tokyo) between 1978 and 1986. 22 of 71 patients with limited stage disease (LD) and none of 52 patients with extensive disease (ED) survived for 3 years. 15 of the 22 three year survivors had significant late complications. All patients received chemotherapy and either thoracic irradiation, resection or both. No prophylactic cranial irradiation was given. 4 patients developed cardiac failure, 2 with a dilated cardiomyopathy, despite the fact that no patient received over 420 mg/m2 of doxorubicin. 12 patients of the 17 who received thoracic irradiation developed radiation pneumonitis and 3 required hospitalisation for severe haemoptysis (2) or cavity formation (1). 1 patient who received nimustine developed a fatal myelodysplastic syndrome and 2 additional patients developed second primary tumours in the oesophagus (1) and stomach (1). Mild peripheral neuropathy (WHO grade 1) was persistent in 3 patients and asymptomatic azotemia (WHO grade 1) in 7. Despite advances in the treatment of SCLC there are very few asymptomatic long-term survivors.

Adult↗

PubMed1991

A retrospective analysis of patients receiving surgery after chemotherapy for small cell lung cancer.

From 1984 to 1989, 20 of 142 patients with small cell carcinoma of the lung received surgery after intensive chemotherapy alone or chemotherapy combined with thoracic irradiation. All patients giving informed consent and having an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 were included in the present retrospective study. Ages ranged from 37-74 (median 58) years. All patients received 1-10 cycles of chemotherapy intravenously every three or four weeks (PVP: 80 mg cisplatin/m2, 100 mg etoposide/m2 x 3; CAV: 800 mg cyclophosphamide/m2, 50 mg doxorubicin/m2, 1.4 mg vincristine/m2, and other combinations) and were evaluated for surgery 1-27 months after the initial systemic chemotherapy. Clinically, two, three, eleven and for patients were diagnosed as having stages I, II, III and IV disease, respectively at the beginning of treatment. At the time of reevaluation after chemotherapy or chemotherapy plus chest radiotherapy there were one (5%) complete responder, 17 (85%) partial responders, and two (10%) with stable disease. Twenty patients underwent thoracotomy consisting of nine lobectomies and 11 pneumonectomies. Eighteen of the 20 had resectable lesions. According to postoperative pathological findings, there were six, one, seven and two patients with stages I, II, III and IV disease, respectively. In two patients no tumor was demonstrated pathologically. Small cell carcinoma was detected in 15 specimens and three had non-small cell carcinoma. Two of the 20 patients survived for more than five years. The median survival of the 20 patients was 22 months. It would appear that resection is applicable in only a selected subset of patients with small cell carcinoma of the lung.

Adult↗

PubMed1991

Analysis of three-year survivors among patients with advanced inoperable non-small cell lung cancer.

Among 238 patients with advanced inoperable non-small cell lung cancer (NSCLC), we evaluated the characteristics of three-year survivors and analyzed them to determine whether or not there were any specific pretreatment prognostic factors which could make it possible to discriminate this group the rest. All patients received chemotherapy according to the protocol for phase II or III trials at the National Cancer Center, Japan, between 1980 and 1987. Eighteen (8%) patients survived for over three years. Five of the 18 responded to initial therapy, seven received thoracic irradiation and five surgical resection after chemotherapy. No patient achieved a complete response by chemotherapy. Among five disease-free survivors, two received surgery after completion of chemotherapy. Their clinical stage was IIIA. Three patients received radiation therapy, but they could not be evaluated. Although some radiologically detectable shadows remained, these patients survived for more than three years with no active lesion, indicating the difficulty in diagnosing a complete response to treatment. Thirteen patients survived for more than three years with disease. Some unknown biological factors might influence survival in this group. Pulmonary fibrosis, as treatment toxicity, was observed in six of the 18. The pretreatment prognostic factors that discriminated three-year survivors from the rest were Eastern Cooperative Oncology Group performance status (PS) (P = 0.0015), clinical T factor (P = 0.0093), and serum LDH (P = 0.0317) by means of univariate analysis, and PS (P = 0.0134) and clinical T factor (P = 0.0117) by means of multivariate analysis with a logistic regression procedure.

Adult↗

PubMed1991

[Clinical study on the priming principle of muscle relaxants: comparison of pancuronium with vecuronium].

The priming principle of non-depolarizing muscle relaxants was treated in this study. The subjects were 48 patients. We administered divided doses (p) and single dose (s) using pancuronium (P) and vecuronium (V), and compared the 4 groups (Pp, Ps, Vp, Vs). Pp and Vp groups received intravenous injection of 0.02 mg.kg-1 first, and 0.08 mg.kg-1 after 5 minutes. Ps and Vs groups received intravenous injection of 0.1 mg.kg-1. Relaxograph was used for monitoring muscle relaxation. First-twitch (T1) and train-of-four ratio (TR) were recorded, and the time intervals required to decrease T1 to 25% (T1-25) and 5% (T1-5) were determined. T1-25 (sec) was 126.2, 153.1, 82.7, and 132.7 in Pp, Ps, Vp, and Vs group, respectively; and T1-5 (sec) was 192.8, 229.8, 112.7, and 165.2 in Pp, Ps, Vp, and Vs group, respectively. As these values suggest, there were no significant differences between Pp and Ps group, while significant differences were noted between Vp and Vs group. The following conclusions were obtained. Clinical usefulness of the priming principle was not shown with pancuronium, but was noted with vecuronium. However, the action of vecuronium appeared rapidly after single dose, and some patients complained of dyspnea during priming. Consequently, the priming principle was not considered to be clinically beneficial.

Adult↗