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Biomedical subjects

T Osuga

Publications and source records attributed to T Osuga.

At least 127 records · Page 7Linked to original sources

[Laboratory and clinical studies on 6059-S in children (author's transl)].

Laboratory and clinical studies were performed on 6059-S in the field of pediatrics, a new semi-synthetic 1-oxacephem antibiotic, and results were as follows. 1. MICs of 6059-S were compared with those of cefazolin (CEZ) and cefmetazole (CMZ) on 31 strains of S. aureus, 29 strains of E. coli, 30 strains of K. pneumoniae and 16 strains of P. aeruginosa. With the inoculum size of 10(8) cells/ml an 10(6) cells/ml, the peak of distribution of MICs were S. aureus 6.25, 3.13 micrograms/ml, E. coli 0.2, 0.1 micrograms/ml, K. pneumoniae 0.2, 0.05 micrograms/ml and P. aeruginosa 12.5, 6.25 micrograms/ml, respectively. MICs 6059-S against S. aureus was more less 2 to 3 tubes than CEZ and CMZ, but against E. coli and K. pneunoniae were more higher than 3 to 4 tubes than CEZ and CMZ. 2. The serum concentrations and urinary recovery rate of 6059-S were measured in 5 pediatric patients. 6059-S was given 20 mg/kg by an intravenous injection to 2 cases or a 30 minutes intravenous drip infusion to 3 cases. The mean concentration of the former were 64.3, 44.3, 26.8, 11.7 and 5.0 micrograms/ml at 0.5, 1, 2, 4 and 6 hours, and T 1/2 was 1.51 hours. The urinary recovery rates was 75.0% within 6 hours after the injections. The mean concentration of the latter were 65.3, 86.3, 63.0, 40.3, 17.8 and 8.9 micrograms/ml at 0.25, 0.5, 1, 2, 4 and 6 hours, and T 1/2 was 1.63 hours. The urinary recovery rates was 52.1% within 6 hours after the injection. 3. Eleven cases with acute pneumonia, 1 case with acute bronchitis, 3 cases with acute purulent tonsillitis, 1 case with acute purulent parotitis and 1 case subcutaneous abscess were treated with 6059-S by intravenous injection. All cases were above effective clinically. Five strains of H. influenzae, 3 strains of S. pneumoniae, 2 strains of S. pyogenes and 1 strain of S. aureus were eradicated in all strains. No clinical adverse reaction and abnormal laboratory findings were noted.

Age Factors↗

[Laboratory and clinical studies on cefadroxil in the field of pediatrics (author's transl)].

Laboratory and clinical investigations were performed in the field of pediatrics with cefadroxil dry syrup, a new semi-synthetic cephalosporin antibiotic. (1) MIC of cefadroxil was measured, to compare with that of cephalexin (CEX), on 30 strains of S. aureus, 30 strains of S. pyogenes and 26 strains of E. coli, all of which were isolated clinically in the field of pediatrics. Two strains of S. aureus showed more than 100 microgram/ml with inoculum size of 10(8) cells/ml, and remaining 28 strains were distributed between 1.56 similar to or approximately 12.5 microgram/ml, while at inoculum size of 10(6) cells/ml, each 1 strain showed 25 microgram/ml and 50 microgram/ml, and the remaining strains were distributed between 1.56 similar to or approximately 3.13 microgram/ml. All 30 strains of S. pyogenes were inhibited the growth by less than 0.2 microgram/ml with inoculum size of both 10(8) cells/ml and 10(6) cells/ml. Three strains of E. coli showed MIC of more than 100 microgram/ml with inoculum size of 10(8) cells/ml, and the remaining 23 strains were distributed between 12.5 similar to or approximately 25 microgram/ml, while with inoculum size of 10(6) cells/ml, 3 strains showed more than 100 microgram/ml, and the remaining strains were distributed between 6.25 similar to or approximately 12.5 microgram/ml. In comparison with the results of CEX, cefadroxil was nearly equal to S. aureus and E. coli, whereas it was 2 grades superior to S. pyogenes. (2) A dose of 10 mg/kg of cefadroxil dry syrup was administered before 30 minutes of breakfast in 3 cases of children, and serum level, urinary level and recovery rate in urine were investigated. Average serum level was 15.2 +/- 2.39 microgram/ml in 1/2 hour, 16.4 +/- 2.3 microgram/ml in 1 hours. 10.1 +/- 2.8 microgram/ml in 2 hours, 3.8 +/- 1.5 microgram/ml in 4 hours and 1.0 +/- 0.4 microgram/ml in 6 hours, and average T 1/2 was 1.24 +/- 0.22 hours. Average urinary level was 857 +/0 232 microgram/ml in 0 similar to or approximately 2 hours, 690 +/- 180 microgram/ml in 2 similar to or approximately 4 hours and 249 +/- 55 microgram/ml in 4 similar to or approximately 6 hours, and average recovery ratio in urine was 86.3 +/- 17.5% within 0 similar to or approximately 6 hours. (3) Cefadroxil dry syrup was administered clinically in 20 cases of acute purulent tonsillitis, 5 cases of acute bronchitis, 14 cases of acute pharyngitis, 5 cases of acute purulent cervical lymphadenitis and 2 cases of acute urinary tract infection. Clinical efficacy, bacteriological effect and its side effect were investigated in total 46 cases of bacterial infection. A dose of 21.1 similar to or approximately 57.1 mg/kg of cefadroxil was administered daily, divided into 3, after each meal for 1 similar to or approximately 10 days, total dose being 0.5 similar to or approximately 11.0 g. Efficacy rate of cefadroxil, including excellent and effective effects, was 90.0% in acute purulent tonsillitis, 60.0% in acute bronchitis, 100.0% in acute pharyngitis, 80...

Age Factors↗

[Laboratory and clinical studies on cefoxitin in pediatric field (author's transl)].

Studies on antimicrobial activity, absorption and excretion and clinical use of cefoxitin in pediatric field were performed. 1. MIC of cefoxitin was compared with that of cefazolin and/or ampicillin for clinical isolates of Staphylococcus aureus (36 strains), Escherichia coli (35 strains), Klebsiella pneumoniae (34 strains) and Haemophilus influenzae (80 strains). MIC of cefoxitin against S. aureus was approximately 1-2 tubes higher than that of cefazolin. Many strains of E. coli and K. pneumoniae that showed high MIC to cefazolin were sensitive to cefoxitin. It is presumed that the results are due to the strong resistance of cefoxitin to beta-lactamase degradation. MIC of cefoxitin against H. influenzae was approximately 1-2 tubes lower than that of cefazolin, but approximately 4 tubes higher than that of ampicillin. 2. Serum level and urinary recovery rate of cefoxitin after one shot i.v. injection of 25 mg/kg were examined. The serum mean levels were 33.8 microgram/ml at 1/2 hour, 7.0 microgram/ml at 1 hour and 2.9 microgram/ml at 2 hours after the injection, respectively, and the drug was not detected in serum at 4 and 6 hours after the injection. The mean half-life of serum level was 27.1 minutes. The mean urinary recovery rate within 6 hours after injection was 96.0% and most of the drug were excreted into urine within 2 hours after the injection. 3. In order to evaluate clinical response, bacteriological response and side effects, cefoxitin was applied to 19 cases, i.e., 12 cases of either acute lobar pneumonia or acute bronchopneumonia, 2 cases of acute pyelitis, 1 case each of acute bronchitis, acute purulent tonsillitis, acute purulent arthritis, acute orbital phlegmon and acute buccal abscess. As for clinical response, the overall efficacy rate (the percentage of cases showed excellent and good efficacy) was 88.9%. As for bacteriological response, among the 13 strains which were determined or supposed to be causative organisms, i.e., 6 strains of Streptococcus pneumoniae, 2 strains of H. influenzae and 1 strain each of streptococcus pyogenes, alpha-Streptococcus, Enterococcus, E. coli and Neisseria sp., all strains were disappeared except for Enterococcus which was reduced by the treatment with cefoxitin. No side effect was observed in any case. Abnormalities of laboratory findings were observed in 3 cases, i.e., 1 case each of reduction of RBC and Hb, elevation of GOT and GPT and elevation of GPT, but all of them returned to normal following completion of the dosage term.

Age Factors↗

[Laboratory and clinical studies of cefoperazone in children (author's transl)].

Experimental and clinical studies on cefoperazone (CPZ), a new synthetic cephalosporin, were performed in the field of pediatrics. 1) The MICs of CPZ against 26 strains of S. aureus, 21 strains of E. coli, 20 strains of K. pneumoniae and 15 strains of H. influenzae which were clinically isolated were estimated and compared with those of CEZ and ABPC. Some strains were found to be high in the MIC of CPZ against S. aureus, E. coli and K. pneumoniae by original inoculation but 88% of S. aureus, 95% of E. coli, 95% of K. pneumoniae and 100% of H. influenzae were under 6.25 mcg/ml by 100 times dilution inoculation. The MIC of CPZ against S. aureus was inferior to CEZ and superior to ABPC, and that against E. coli, K. pneumoniae and H. influenzae was superior to CEZ and ABPC. 2) The serum concentration, urinary concentration and recovery rate from urine were measured in two healthy infants and one infant in the stage of convalescence from cholangiohepatitis after a single intravenous administration of 25 mg/kg of CPZ. The mean serum concentration in the two healthy infants was 88.0 mcg/ml at 30 minutes, 63.0 at 1 hour, 31.4 at 2 hours, 12.2 at 4 hours and 4.2 at 6 hours; the half-life was 1.29 hours, and the recovery rate from urine was 14.5%. 3) The clinical effect of CPZ was examined in 16 cases of acute lobar pneumonia or acute bronchopneumonia, 1 case of acute bronchitis and 4 cases of acute urinary tract infections. All of the cases responded effectively or markedly effectively. Among the causative bacteria in those cases, 2 strains of S. pneumoniae, 1 strain of S. faecalis, 1 strain of H. influenzae and 2 strains of E. coli and 1 strain of K. pneumoniae disappeared following the administration of CPZ. The bacteriological effect against 1 strain of P. aeruginosa was unknown, but clinical effectiveness was observed in this case. No clinical side effects were observed. Laboratory examination carried out before and after the administration revealed a rise of GOT and eosinophilia in each one case, but in both abnormality returned to normal after termination of therapy.

Age Factors↗

Relationships between cholesterol gallstones, biliary function, and plasma lipoproteins in squirrel monkeys.

We used squirrel monkeys (Saimiri sciureus) as models to investigate human sex differences in susceptibility to cholesterol gallstones, biliary function, and plasma lipoproteins. Cholesterol gallstones developed in a large proportion of intact and gonadectomized male and female Brazilian monkeys maintained on a lithogenic diet, but male Bolivian monkeys were completely resistant. Although the gallbladder bile of nearly all monkeys was saturated with cholesterol, the bile of the Bolivian monkeys had a much greater concentration of total lipids (cholesteriol + phospholipid + bile acids) than did bile of the other groups. The male Bolivian monkeys had the highest percentage of gallbladder bile acids as chenodeoxycholic and the lowest as deoxycholic acids. They also had larger total body pools of cholic and chenodeoxycholic acids than any other group. The lithogenic index of all Brazilian squirrel monkeys with gallstones was greater than that of all Brazilian monkeys that were free of stones. The level of HDLs was much lower in the plasma of Bolivian monkeys than in that of any group of Brazilian monkeys, and the differences were restricted to the HDL2 subfraction. Addition of cholesterol (0.9 mg/Kcal) to the regular semipurified diet containing butter resulted in elevations in the LDLs of all groups and a change in the relative compositions of HDL and LDL (a higher percentage of cholesterol and lower percentage of protein). The occurrence of low plasma HDL2 levels in a population of squirrel monkeys resistant to cholesterol gallstones is consistent with the suggested role of that fraction in net transport of cholesterol to the bile.

Animals↗

[Fundamental and clinical studies on sisomicin in children (author's transl)].

Fundamental and clinical studies on sisomicin, a new aminoglycoside antibiotic were carried out and the following results were obtained. 1. Antibacterial activity of sisomicin was superior to that of gentamicin, amikacin, cefazolin and ampicillin against S. aureus and Ps. aeruginosa. Against E. coli and K. pneumoniae, it was superior to that of amikacin, cefazolin, ampicillin and equal or slightly superior to that of gentamicin. 2. Mean serum levels of sisomicin were 18.0 +/- 0.5 microgram/ml, 15.7 +/- 1.3 microgram/ml, 9.6 +/- 0.6 microgram/ml, 3.2 +/- 0.4 microgram/ml, 1.7 +/- 0.2 microgram/ml and 0.95 microgram/ml at 1/2, 1, 2, 4, 6 and 8 hours after a single intramuscular administration of sisomicin 2.0 mg/kg to 3 children. Mean half-life time was 1.6 +/- 0.2 hours. Mean urinary recovery was 60.4 +/- 7.5% within 6 hours after administration of sisomicin 1.6-2.1 mg/kg to 4 children. 3. Sisomicin was given intramuscularly to 13 children with acute pyelitis (11), acute cystitis (1) and stomatitis gangrenosa and cervical lymphadenitis (1). The daily dose was 2.0 -4.2 mg/kg, divided into twice. Clinical response was excellent in 8 and good in 5. In bacteriological examinations, 13 pathogens (E. coli 9, K. pneumoniae 2, Ps. aeruginosa 2) were eradicated after administration. No adverse reactions were observed.

Acute Disease↗

[Laboratory and clinical studies of cefamandole in children (author's transl)].

Laboratory and clinical studies of cefamandole (CMD), a new semisynthetic cephalosporin, were investigated and following results were obtained. 1) Absorption and excretion study following 25 mg/kg intravenous administration was carried out in pediatric patients. In 6 cases, mean serum levels of 116.7 +/- 24.0 micrograms/ml, 62.1 +/- micrograms/ml, 12.2 +/- 2.7 micrograms/ml, 2.9 +/- 1.1 micrograms/ml, 0.6 +/- 0.6 micrograms/ml and 0.1 +/- 0.2 micrograms/ml obtained after 15, 30 minutes, 1, 2, 4 and 6 hours administration. In 4 cases, mean urinary recovery of 68.2 +/- 17.2% (0 approximately 8 hours) was obtained. The mean half life of serum level was 0.36 +/- 0.08 hours. 2) The transfer of cefamandole was poor in infants with meningitis. 3) Cefamandole was given to 22 children with acute pyelitis (1 case), acute pneumonia (19 cases), and meningitis (2 cases). The dosage was 80.0 approximately 284.2 mg/kg/day, and it was divided into 4 approximately 6 times and given intravenous or intravenous drip. The duration of administration was from 3 to 17 days. The overall efficacy rate in 22 cases was 95.2%, i.e., excellent in 5, good in 15, poor in 1, and unknown in 1. In bacteriological examination, there were eradication of the organisms in 9 (52.9%), decrease in 4, unchange in 4 out of 17 strains. 4) Any noticeable adverse reaction was not observed.

Adolescent↗

[Study of cefuroxime in pediatric field (author's transl)].

1. Cefuroxime (CXM) was studied for absorption and excretion in 4 pediatric patients given one shot intravenous injection of 20 approximately 25 mg/kg. The following serum levels were determined: 24.5 approximately 38.0 micrograms/ml at 30 minutes (mean 33.3 +/- 6.1 micrograms/ml), 10.0 approximately 17.0 micrograms/ml at 1 hours (mean 13.9 +/- 3.3 micrograms/ml), 3.4 approximately 7.6 micrograms/ml at 2 hours (mean 5.2 +/- 1.9 micrograms/ml, 0.7 approximately 2.1 micrograms/ml at 4 hours (mean 1.3 +/- 0.6 micrograms/ml, 0.1 approximately 0.3 microgram/ml at 6 hours (mean 0.2 +/- 0.1 microgram microgram/ml). Half-life (T 1/2) was 0.65 approximately 0.88 hour (mean 0.75 +/- 0.10 hour). Urinary levels were 1,280 approximately 7,100 micrograms/ml at 0 approximately 2 hours, 96 approximately 3,400 micrograms/ml at 2 approximately 4 hours, 68 approximately 250 micrograms/ml at 4 approximately 6 hours. Urinary recovery rate at 0 approximately 6 hours was 54.1 approximately 74.4% (mean 61.8 +/- 9.4%). 2. From the study on spinal fluid concentration in pediatric patients with Haemophilus influenzae-induced meningitis, the dose of CXM 52.2 mg/kg was given to 1 pediatric case with this disease by one shot intravenous injection. Spinal fluid levels were presumed as 9.0 micrograms/ml at 30 minutes, 6.8 micrograms/ml at 1 hour, 3.8 micrograms/ml at 2 hours and 1.2 micrograms/ml at 4 hours. 3. CXM was studied in 19 pediatric patients with bacterial infection for clinical efficacy, bacteriological effect and side effect. Clinical result was found good in 1 with purulent meningitis; excellent in 9 out of 15 with acute lobar pneumonia or acute bronchopneumonia, and good in remaining 6 cases; good in 2 with acute bronchitis; excellent in 1 with acute pyelonephritis. This represents efficacy ("excellent" plus "good") rate of 100%. Of 5 strains of H. influenzae presumed as causative organisms, 4 were disappeared and 1 was reduced. Two strains of Streptococcus pneumoniae and 1 strain of Escherichia coli were disappeared. No side effect was noted in terms of clinical symptom. Laboratory examination showed elevation of GOT and GPT in 1 case, but these elevated values returned to normal after the end of the CXM treatment.

Bacteria↗

Continuous-flow determination of bile acids in serum, and its clinical application.

We describe a highly sensitive and accurate automated continuous-flow method for determining bile acids in serum. The bile acids are first liberated from serum protein by dialysis at alkaline pH and then measured fluorometrically after the following enzymic reaction. Bile acids are converted to 3-oxo bile acids with 3alpha-hydroxysteroid dehydrogenase (EC 1.1.1.50) with concomitant reduction of NAD+ to NADH. The hydrogen in the generated NADH is transferred by diaphorase (EC 1.6.4.3) to resazurin to yield resorfin, the fluorophore. Only 100 microliter of serum is required and 40 determinations can be done per hour. The CV for 20 replicate determinations in serum with a mean bile acid concentration of 9.8 mumol/liter was 2.6%. The CV for day-to-day variation for another serum on 27 successive days was 3.0% (mean concentration, 10.0 mumol/liter). We applied this method to 826 sera from various diseases; 29% exceeded the upper limit of normal, 10 mumol/liter, and abnormally high values (greater than 20 mumol/liter) were almost exclusively limited to sera from hepatobiliary and enteric disorders.

3-Hydroxysteroid Dehydrogenases↗

Evaluation of fluorimetrically estimated serum bile acid in liver disease.

Fasting serum bile acid (SBA) was measured by the enzymic fluorimetric method coupled with the NAD-resazurin system in 23 controls, 35 asymptomatic carriers of HIs antigen including 4 e antigen carriers and 91 patients with various liver diseases. All GHBs and e antigen carriers showed SBA within the normal range. SBA was most significantly correlated with serum bilirubin (gamma=0.74) and was a more sensitive index for impaired liver function than bilirubin or alkaline phosphatase in 164 radomly chosen samples from the liver disease group. In serial determinations of SBA with reference to GOT, GPT, changing patterns of these two parameters were classified into the parallel type and the discrepant type. Thirty two out of 40 cases with chronic liver disease belonged to the parallel type. SBA remained abnormal even after the normalization of transaminase in 12 out of 20 resolving episodes in cases of the parallel type, regardless of diagnosis. Since SBA changes according to the stage of the disease activity, serial and simultaneous estimation of SBA and GOT, GPT was found to be helpful in the observation of liver diseases. Maximum values of SBA elevation in an endogenous bile acid tolerance test after eating two egg yolks were higher than controls in 4 out of 7 cases with liver disease, who were associated with normal fasting SBA.

Alanine Transaminase↗

A simple and sensitive assay of total serum bile acids.

A simple and sensitive method was developed for the quantification of serum total 3alpha-hydroxy bile acids. 0.1 ml of serum was mixed with tris(hydroxymethyl) aminomethane hydrochloric acid buffer and heated at 67 degrees C for 30 min. To the solution were added 3alpha-hydroxysteroid : oxidoreductase (EC 1.1.1.50; 3alpha-HSD), NAD, diaphorase (EC 1.6.4.3) and resazurin. The mixture was incubated at 20 degrees C for 1 h. The resultant fluorescence of resorfin was measured at 580 nm with the excitation at 560 nm. The blank value was obtained after the same treatment of another 0.1 ml of the same serum without 3alpha-HSD. A linear relationship was obtained between the amount of bile acids and the fluorescence intensities in the range of 1 to 150 mumol/1. The recovery of bile acids added to the serum was 81.4 +/- 2.5 (S.D.)% for cholate, chenodeoxycholate and deoxycholate. The bile acid content in the serum was 48.8 mumol/1 with a standard deviation of +/- 0.42 and a coefficient of variation of +/- 0.87% in 10 replicate determinations. The mean bile acid content of normal fasting male sera was 8.0 mumol/1 (3.6-12.6 mumol/1, n = 12) and of female sera 6.8 mumol/1 (3.2-12.7 mumol/1, n = 13).

Bile Acids and Salts↗

Gas chromatography of bile acids as their hexafluoroisopropyl ester-trifluoroacetyl derivatives.

Bile acids, such as cholic, chenodeoxycholic, deoxycholic, lithocholic and ursodeoxycholic acids, were allowed to react with hexafluoroisopropanol and tri-fluoracetic anhydride at 37 for 30 min. The resulting derivatives were gas chromatographed on QF-1, with flame ionization detection, and were identified by gas chromatography-mass spectrometry. Separation was good. By using this method, these acids were detected in samples of human duodenal fluid; the ratios of each were 24.4, 41.5, 24.9, 2.3 and 6.9%, respectively.

Bile Acids and Salts↗

Effect of type of dietary fat, cholesterol and chenodeoxycholic acid on gallstone formation, bile acid kinetics and plasma lipids in squirrel monkeys.

To explore the effect of type of dietary fat, cholesterol and chenodeoxycholic acid on gallstone formation, bile formation, bile composition, bile acid kinetics and plasma lipids in squirrel monkeys, 39 monkeys were studied using seven different diets. Safflower oil, a highly unsaturated fat, added to a diet with cholesterol resulted in at least as high an incidence of cholesterol gallstones as butter added to the same diet. On the other hand, diets with high levels of saturated or unsaturated fat without cholesterol did not result in gallstone formation. Dietary chenodeoxycholic acid (0.1%) did not reduce the incidence of cholesterol gallstones, although the proportion of bile acids as chenodeoxycholic acid increased. Gallbladder biles from monkeys fed semipurified diets with cholesterol had a significantly higher lithogenic index than the comparable groups without cholesterol. Pool sizes of bile acids in all semipurified diet groups were reduced and the lithogenic indices were increased compared with the group fed a commercial feed. Dietary chenodeoxycholic acid caused a decrease in plasma cholesterol in butter groups and an increase in triglyceride concentrations in safflower groups. Diet infuences bile composition and bile acid kinetics, as well as the incidence of gallstones, in squirrel monkeys.

Animals↗