Search PubMed⌕ Search

Biomedical subjects

M Yanai

Publications and source records attributed to M Yanai.

At least 127 records · Page 7Linked to original sources

Comparison of intermittent or continuous methotrexate plus 6-mercaptopurine in regimens for standard-risk acute lymphoblastic leukemia in childhood (JCCLSG-S811). The Japanese Children's Cancer and Leukemia Study Group.

From 1981 to 1983, 131 previously untreated patients with acute lymphoblastic leukemia (ALL) standard-risk group were entered to the protocol JCCLSG-S811. Of 119 eligible patients, 115 (96.6%) attained complete remission by treatment with prednisone (PRD) plus vincristine (VCR) or vindesine (VDS). After preventive central nervous system (CNS) therapy including 18 Gy cranial irradiation and three doses of intrathecal methotrexate (MTX), the patients were assigned randomly to the two maintenance chemotherapies, Regimen A and Regimen B. Regimen A (intermittent regimen) consisted of PRD (120 mg/m2/day by mouth for 5 days) plus 6-mercaptopurine (6MP) (175 mg/m2/day by mouth for 5 days) plus VCR (2.0 mg/m2 intravenously) alternating biweekly with MTX (225 mg/m2 intravenously). Regimen B (continuous regimen) consisted of 6MP (50 mg/m2/day by mouth) plus MTX (20 mg/m2/week by mouth) combined with pulses of PRD and VCR (the same dosages as Regimen A) every 4 weeks. As the late intensification therapy (LIT), five courses of high-dose MTX (2000 mg/m2 per dose per week intravenously for three doses every 12 weeks) with leucovorin rescue were administered to all patients who were in continuous complete remission (CCR) for more than 2 years. Sixty and 55 patients, respectively, were registered in Regimen A and B. The CCR rates in Regimen A and B were 75.1% +/- 5.8% (mean +/- 1 SE) and 49.7% +/- 7.3% (P less than 0.01) at 4 years, and 72.1% +/- 6.3% and 49.7% +/- 7.3% (P less than 0.05) at 5 years, respectively. In Regimen B, CNS and testicular relapses increased after 3 years of CCR. In addition, the patients in Regimen B had a much higher incidence of infections than Regimen A. The LIT did not seem to have important effects on the duration of CCR. From these data we conclude that the intermittent cyclic regimen of 6MP and MTX may be more effective as compared to the continuous administration of these drugs in the maintenance chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Serial distribution of bronchoconstriction in normal subjects. Methacholine versus histamine.

We compared the relative sites of airway responses to methacholine and histamine aerosols in normal subjects by simultaneous assessment of respiratory resistance (Rrs) and anatomic dead space (VD). Methacholine (12.5 mg/ml) or histamine (12.5 mg/ml) was continuously inhaled during tidal breathing until a nearly twofold increase in Rrs was observed. Large airway response was determined by VD, and overall airway response was determined by Rrs. Small airways response was inferred from Rrs when the change in VD was slight. Inhalation of methacholine and histamine increased Rrs with decreased VD, but the decrease in VD was significantly greater with methacholine than with histamine for an equivalent change in Rrs (p less than 0.01). Inhalation of atropine (5 mg/ml) decreased Rrs with a simultaneous increase in VD. After inhalation of atropine, time required for a twofold increase in Rrs by histamine inhalation was prolonged, and histamine did little decrease VD. These results suggest that the predominant site of cholinergically mediated constriction is the large airways, and that histamine constricts the large airways in part via a cholinergic reflex mechanism and constricts the small airways via its direct action in normal subjects.

Adult↗

Partitioning of large and small airway resistance in human measured by an anterograde catheter with a tip micromanometer.

We measured lateral pressure in airways 3 mm in internal diameter in three normal subjects using an anterograde catheter with a tip micromanometer. The pressure was used to partition total pulmonary resistance into a large airway resistance component between the mouth and the pressure sensor and a small airway resistance component between the pressure sensor and alveoli. Large airway resistance and small airway resistance during inspiration were 2.3 +/- 0.4 and 0.9 +/- 0.2 cmH2O/liter/sec (mean +/- S.E.), respectively, and small airway resistance was 29% of the total pulmonary resistance. We suggest that the present technique may be useful for determining the localization of airway resistance in human subjects.

Adult↗

[Pharmacokinetic and clinical studies of sultamicillin fine granules in children].

Sultamicillin (SBTPC) is a semi-synthesized beta-lactam antibiotic consisted of ampicillin (ABPC) and a beta-lactamase inhibitor, sulbactam (SBT), linked with an ester linkage. Pharmacokinetic and clinical studies using SBTPC 10% fine granules were performed in pediatric patients with a variety of infections. 1. Pharmacokinetic investigation: SBTPC was given at 30 minutes after meal at a dose of 10 mg/kg. Peak serum levels were attained at 1 hour after dosing with average levels of 3.83 +/- 0.27 micrograms/ml for ABPC and 2.73 +/- 0.30 micrograms/ml for SBT. The average half-life of ABPC was 1.52 +/- 0.25 hours and that of SBT was 1.13 +/- 0.09 hours. The urinary recovery rate of ABPC during 6 hours after dosing was 58.2 +/- 4.9% and that of SBT was 59.7 +/- 6.4%. 2. Clinical investigation: Enrolled in the study were a total of 26 patients including 12 with tonsillitis, 6 with pharyngitis, 5 with urinary tract infections, and 1 each with bronchitis, with Salmonella enteritis and a case with fever of unknown case. Responses were excellent in 15 patients, good in 8, fair in 2 and poor in 1 with an efficacy rate of 88.5%. In the assessment of the bacteriological efficacy, 11 out of 14 strains of organisms isolated previous to the treatment were eradicated, 1 strain was found reduced in number and 2 strains remained unchanged with an eradication rate of 78.6%. One patient (3.8%) out of the 26 had diarrhea as side effects and 3 patients (16.7%) of 18 showed eosinophilia in laboratory examinations.

Adolescent↗

Effect of a previous voluntary deep breath on laryngeal resistance in normal and asthmatic subjects.

We studied changes in both laryngeal resistance (Rla) and respiratory resistance (Rrs) after a voluntary deep breath in 7 normal and 20 asthmatic subjects. Rla was measured using a low-frequency sound method (Sekizawa et al. J. Appl. Physiol. 55: 591-597, 1983) and Rrs by forced oscillation at 3 Hz. In normal subjects, both Rla and Rrs significantly decreased after a voluntary deep breath (0.05 less than P less than 0.01). During methacholine provocation in the normal subjects, a voluntary deep breath significantly decreased Rrs (0.05 less than P less than 0.01, but Rla was significantly increased (0.05 less than P less than 0.01). In 10 asthmatic subjects in remission, a voluntary deep breath significantly increased Rrs (0.05 less than P less than 0.01) but significantly decreased Rla (0.05 less than P less than 0.01). In another 10 asthmatic subjects during spontaneous mild attacks, a voluntary deep breath significantly increased both Rrs and Rla (0.05 less than P less than 0.01). The present study showed that without obvious bronchoconstriction, Rla decreased after a voluntary deep breath in both normal and asthmatic subjects but, with bronchoconstriction, Rla increased in both groups. Subtraction of the change in Rla from Rrs gives the change in Rrs below the larynx (Rlow). Rlow changed little or decreased in normal subjects and increased in asthmatic subjects, irrespective of base-line bronchomotor tone. These results suggest that airway response below the larynx after a voluntary deep breath differentiates patients with bronchial asthma from normal subjects.

Adult↗

Late asthmatic response to Ascaris antigen challenge in dogs treated with metyrapone.

We developed an experimental dog preparation that shows a biphasic bronchoconstriction after allergen exposure. After anesthetization, the dogs were intubated with endotracheal tubes and manually ventilated. Respiratory resistance (Rrs) was measured by the forced oscillation method at 3 Hz. Ascaris suum, diluted from 10(-5) to 10(-2) of the extract, was inhaled during tidal breathing for 5 min. One hour before antigen challenge, 10 dogs received 70 mg/kg of metyrapone (cortisol synthesis inhibitor), and 2 h after antigen challenge 35 mg/kg of metyrapone were injected intravenously. In another 10 dogs, metyrapone was not administered. After the maximal increase in Rrs had been assessed (immediate asthmatic response), Rrs increased again 4 to 6 h after antigen challenge in 8 of the 10 dogs treated with metyrapone (late asthmatic response, 443 +/- 282% mean +/- SD of initial Rrs), which was significantly higher than Rrs 6 h after antigen challenge (124 +/- 41%) in dogs without metyrapone (p less than 0.01). In another 5 dogs, ragweed challenge with metyrapone caused no change in Rrs. Bronchoalveolar lavage at the time of the late response revealed a significant correlation between late asthmatic response and neutrophil accumulation (p less than 0.01) in all dogs. We conclude that cortisol depletion augments the occurrence of the late response. The present dog model may be a useful tool for study of the late response in bronchial asthma.

Airway Resistance↗

[Fundamental and clinical studies of flomoxef in the pediatric field].

Fundamental and clinical studies of flomoxef (FMOX, 6315-S) were conducted and the obtained results are summarized as follows. For the pharmacokinetic investigation, FMOX at 10 or 20 mg/kg was administered by intravenous drip infusion over 30 minutes. In the 10 mg/kg group, the maximum blood concentration was reached just after completion of the drip infusion with the mean concentration of 30.3 +/- 4.5 micrograms/ml, and the mean half-life was 0.734 +/- 0.196 hour. The 6-hour urinary excretion rate was 72.3%. In the 20 mg/kg group, which also showed the peak concentration immediately after completion of the drip infusion, the mean peak blood concentration was 54.3 +/- 9.7 micrograms/ml and the mean half-life was 0.628 +/- 0.185 hour. The 6-hour urinary excretion rate was 69.3%. The urinary recovery tended to be lower in children than in adults. Between 10 mg/kg and 20 mg/kg, a definite correlation was observed between dose levels and blood concentrations. In the clinical investigation conducted with a total of 30 patients (22 with respiratory tract infection, 3 with lymphadenitis, 2 each with urinary tract infection and cellulitis, and 1 with acute osteomyelitis), FMOX was found to be excellent in 14 cases, good in 9, fair in 1, poor in 1, and not evaluable in 5. The efficacy rate was, therefore, 92.0%. In the bacteriological evaluation, 8 out of 12 clinically isolated strains were eradicated, 2 unchanged and 2 unknown. The elimination rate was 80.0%. Regarding side effects, no abnormal clinical symptoms were observed. As abnormal laboratory values, eosinophilia, prolongation of APTT, increased platelet count, and a slight elevation of GOT were observed.

Adolescent↗

Effects of magnesium and sodium ions on the outer membrane permeability of cephalosporins in Escherichia coli.

Both Mg2+ and Na+ stimulated the outer membrane permeation of negatively charged cephalosporins in Escherichia coli without any significant alteration of the permeation of a zwitterionic cephalosporin. Such stimulation was not observed in an E. coli mutant lacking porins. The stimulation was caused by the direct interaction between the cations and the porin pores, which resulted in a decrease in cation selectivity of both the Omp F and Omp C porin pores.

Bacterial Outer Membrane Proteins↗

Control of larynx during loaded breathing in normal subjects.

We examined laryngeal resistance (Rla) in six normal subjects in control and four kinds of loaded breathing: hypercapnia, chest strapping, added external resistance, and inhaled methacholine. Rla was measured with a low-frequency sound methed (Sekizawa et al., J. Appl. Physiol. 55: 591-597, 1983). In control and the four kinds of loaded breathing, changes in Rla were tightly coupled with ventilation and Rla decreased during inspiration and increased during expiration. Hypercapnia and chest strapping significantly decreased Rla in both inspiration and expiration in all subjects. Added external resistance decreased inspiratory Rla in all subjects, but decreased expiratory Rla in three subjects, did not change it in two subjects, and increased it in one subject. Inhaled methacholine increased Rla in both inspiration and expiration in all subjects. The present study suggests that although laryngeal movement is tightly coupled with ventilation, laryngeal aperture may be determined by the complex competition of dilating and constricting mechanisms associated with the activity of the respiratory center and neural reflexes from the airway.

Adult↗

Central and peripheral airways as determinants of ventilatory function in patients with chronic bronchitis, emphysema, and bronchial asthma.

We studied central and peripheral airways as determinants of ventilatory function in patients with chronic bronchitis (CB), bronchial asthma (BA), and emphysema (CPE), which were identified using the selective alveolobronchogram (SAB) (see reference 14). First, the relationship between SAB and morphologic findings in the airway was examined in 16 autopsy lungs. The irregularity indices of both central (C-II) and peripheral airways (P-II), obtained from SAB, showed a significant correlation with pathologic abnormalities in both airways (p less than 0.01). Second, SAB were obtained in 38 CB, 25 BA, and 62 CPE patients in whom pulmonary function tests were performed. In CB, C-II were significantly correlated with P-II (p less than 0.001). In CB, inspiratory lung resistance (RL) was significantly correlated with P-II (p less than 0.001) and with C-II (p less than 0.01), and FEV/VC% was significantly correlated with P-II (p less than 0.0001) but not with C-II. In BA and CPE, little correlation was observed between any SAB parameter and RL or FEV/VC%. We conclude that the present SAB parameters represent morphometric abnormalities of the central and peripheral airways, and that in CB, peripheral airway abnormalities correlated well with chronic airway obstruction.

Adult↗