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Biomedical subjects

T Fujimoto

Publications and source records attributed to T Fujimoto.

At least 631 records · Page 35Linked to original sources

[Effect of S6472 and cefaclor on bacterial flora in adult human feces].

S6472 is a mixture of cefaclor (CCL) granules with gastric-soluble coating and those with enteric-soluble coating at the ratio (in potency) of 4 to 6. With administration of this formulation, a prolonged blood level of CCL is obtained. S6472 and CCL were administered orally to 19 healthy male volunteers between 20 and 27 years of age (mean: 23 years) weighing between 51 and 80 kg (mean: 64.7 kg). Four subjects were given 2 capsules and 5 subjects were given 4 capsules each containing 187.5 mg of S6472, 30 minutes after breakfast and supper for 5 days. Five subjects were given 1 capsule and 5 subjects were given 2 capsules each containing 250 mg of CCL 30 minutes after breakfast, lunch and supper for 5 days. The number of fecal bacteria was examined 5 days before the start of administration, the day of the start of administration, 3 and 5 days after the start of administration, and 3, 5 and 10 days after the end of administration. Concentration of CCL in feces and susceptibility of isolated fecal bacteria (at the inoculum size of 10(6) cells/ml) to CCL were examined. Adverse reactions and the effects on laboratory test values were also checked. In 4 subjects receiving 375 mg of S6472 twice a day, the mean population of E. coli was 10(7)-10(9) cells/g feces on all days of observation. There was no effect on the population of Klebsiella sp., Citrobacter sp. Enterobacter sp. and other Enterobacteriaceae. The mean population of all Enterobacteriaceae was 10(8)-10(9) cells/g feces on all days of observation. The population of other Gram-negative bacilli did not show a consistent change, either. There was no effect on the population of Gram-positive bacteria such as Staphylococcus sp., Enterococcus, sp., Micrococcus sp., and of Candida sp. Among anaerobic bacteria, Bacteroides sp. showed the mean population of 10(10) cells/g feces on all days of examination. C. difficile was isolated from 2 subjects out of 4 at the level of 10(2)-10(3) cells/g feces 5 days after the start of administration and 3 days after the end of administration. However, there was no production of toxin in either of the 2 subjects. In another subject, C. difficile was isolated at 10(2)-10(4) cells/g feces with a toxin titre of 10(-3)-10(-4) 3 and 5 days after the start of administration and 10 days after the end of administration. The total population of anaerobic bacteria was 10(10)-10(11) cells/g feces on all days of examination.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Effect of cefminox on bacterial flora in human adult feces].

Cefminox (CMNX), a new cephamycin, was administered by one shot intravenous injection twice daily with a dose of 1,000 mg each time for 5 days to seven healthy male volunteers whose ages ranged from 21 to 28 years (mean: 25 years) and body weights were from 60 to 92 kg mean: 72 kg). The effect of the drug on fecal bacterial flora was investigated and the concentrations of the drug in feces were measured on 5th day before the treatment, on 0, 3rd, and 5th day (the final day of the treatment) during the treatment, and on 3rd, 5th, and 10th day after the treatment. Antibiotic susceptibility tests of CMNX, cefmetazole (CMZ) and cefotaxime (CTX) against several strains of organisms isolated from feces of the seven volunteers were performed. Clinical adverse reactions and effect on laboratory examinations were also investigated. The results of the study are described as follows. Among Enterobacteriaceae, populations of E. coli, Klebsiella sp. and Citrobacter sp. temporarily disappeared during the treatment of CMNX. After 5-day-treatment, that of Citrobacter sp. transiently increased and the isolation of Enterobacter sp. increased during treatment and up to 5 days after treatment, while those of Proteus sp., H. alvei, or Serratia sp. did not show a definite change. The mean Enterobacteriaceae population in general was 10(8) to 10(9) cells/g feces, showing almost no variation, on all examination days except 5th day during treatment when these organisms were not isolated from only one subject. No remarkable change was not found in populations of other isolated organisms including Gram-negative bacilli; Aeromonas sp., Pseudomonas sp. and Acinetobacter sp., and Gram-positive bacteria; Staphylococcus sp., Enterococcus sp., Micrococcus sp. and Candida sp. Among anaerobes, the mean population of Bacteroides sp. was 10(10) to 10(11) cells/g feces, showing almost no variation, and C. difficile was not isolated from any subject, however the toxin was detected in samples from 5 of 7 subjects; one subject showed always positive for toxin on all examination days; 1 on 5th day during treatment to 10th day after treatment; 2 on 5th and 10th day after treatment, and 1 only on 10th day after treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗

[Effect of orally administered lenampicillin and ampicillin on bacterial flora in human adult feces].

Newly developed lenampicillin (LAPC) which is a prodrug of ampicillin (ABPC), and ampicillin (as the control) were each administered to 6 healthy male volunteers, aged from 21 to 25 years (mean 22.4 years) and weighing 57-78 kg (mean 67.0 kg) to study the effect of LAPC and ABPC on fecal bacterial flora. Each drug was given orally 3 times daily (after meals) with each dose of 250 mg for five days. Changes of the fecal bacterial flora caused by the antibiotic were investigated by determining fecal bacterial counts on the 3rd day before the treatment, 0 (the start of treatment), 3rd and 5th days (the final day of treatment) during treatment, and 3rd, 5th and 10th days after the treatment. Fecal concentrations of LAPC and the metabolites (ABPC, 2-aminobenzyl penicilloic acid (ABPA) and 5S-ABPA) for the LAPC group and ABPC for the ABPC group were assayed. A single dose of 500 mg of LAPC was administered orally after breakfast to additional 6 healthy male volunteers and concentrations of LAPC, metabolites (ABPC, ABPA and 5S-ABPA) in the entire stool were determined daily for 5 successive days after the administration. Clinical adverse reactions and abnormal laboratory-findings caused by either drug were studied in the 18 volunteers. The results obtained are summarized as follows. In the bacterial flora of the 6 volunteers to whom LAPC was administered (the LAPC group), the number of isolated E. coli showed no tend of decrease. Mean bacterial counts obtained 3 days before the treatment and at the day of the treatment were 10(9) and 10(8) cells/g, respectively. These values were compared to the counts obtained on the 3rd and the 5th days during the treatment and were found to be about 10(2)-folds as high as the latter. The decreased counts observed on the 3rd and the 5th days did not last and counts increased again to similar levels observed before the treatment. Klebsiella sp. was isolated from 1 or 2 samples before the treatment. It was isolated from as many as 5-6 cases with mean bacterial counts of 10(7)-10(11) cells/g during and up to 5 days after the treatment. The frequency of isolation then decreased to 4 cases on the 10th day after the treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

Distribution of fibronectin on the migratory pathway of primordial germ cells in mice.

The distribution and localization of fibronectin (FN) on the migratory pathway of primordial germ cells (PGCs) in mouse embryos were studied immunocytochemically at the light and electron microscopic levels. In embryos 9.5 to 11.0 days of gestation, the dorsal mesentery as the final region through which PGCs migrate was rich in FN. At this stage, migrating PGCs often showed amoeboid features with pseudopods in contact with neighboring mesentery (mesenchymal) cells. With the electron microscope, the reaction product to FN was visualized on the surfaces of somatic cells and of PGC pseudopods and at the site of contact between PGCs and somatic cells. Abundant extracellular FN was also found, probably binding with the extracellular matrices. By 11.5 to 12.0 days, when PGCs had arrived in the gonadal anlage, FN reaction had weakened or disappeared in the dorsal mesentery. Thus, the results suggest that FN plays a significant role in the migration of PGCs at least in the last portion of the migratory pathway.

Animals↗

Characteristics of growth and palatal shelf development in ICR mice after exposure to methylmercury.

A single dose of 25 mg/kg methylmercuric chloride (MeHg) was given orally to gravid ICR mice. Cleft palate was induced in 100% of the offspring, with the critical treatment period ranging from day 10/8 hours (10/8) to 12/16 of gestation. Dose-dependent body weight reduction was observed in day 18 fetuses from both the day 10/8 and 12/16 groups. However, fetal weight reduction was greater in the day 12/16 group for all the MeHg treatments investigated. The relative potency of the induction of cleft palate by MeHg was slightly but significantly higher in the fetuses of the day 12/16 group (1.044-1.197-fold in 95% limits) than in the day 10/8 group. The results showed that when 25 mg/kg of MeHg was given to the fetuses in the day 10/8 group, palatal shelf growth was delayed at a more primitive stage than in the day 12/16 fetuses. Moreover, disharmony of development between the overall fetus and palatal shelf was noticed. Furthermore, in the day 12/16 fetuses, a delay of palatal shelf growth occurred just prior to shelf elevation. Prior to shelf elevation, coordination was probably lost in the development between the fetus and the palatal shelves. Normal palatal closure in ICR fetuses occurs about 1 day and 10 hours earlier (P less than 0.05) than in the A/J fetuses (Biddle, '80). Normal palatal shelves in ICR fetuses moved rapidly, with 3.0 to 5.7 hours (in 95% limits) required for all fetuses to achieve elevation, while, in MeHg-treated groups, palatal shelf elevation did not occur. The results suggest that the cause of the failure in palatal shelf elevation may be understood by examining the disharmonious development of the fetus after exposure to MeHg.

Animals↗

Coronary aneurysms in Kawasaki disease: follow-up observation by two-dimensional echocardiography.

The development and regression of the coronary aneurysms in Kawasaki disease was studied with serial two-dimensional echocardiographic (2D echo) examinations. The diameter of the aneurysms at the proximal portions of the left coronary artery was measured on the 2D echo images in ten patients with Kawasaki disease, in whom left coronary aneurysms were found at the acute stage of the illness, and followed by 2D echo for longer than eight months. It was found that coronary aneurysms usually developed during the second week of the illness, reached maximal size at 3-8 weeks, and regressed gradually thereafter. Small aneurysms disappeared in several months, and those of intermediate size regressed in one to two years. Large aneurysms may remain for many years. Mural thrombi within the aneurysms were detected with 2D echo in three patients. They decreased in echodensity and eventually disappeared echographically.

Angiocardiography↗

Reduced citrovorum factor rescue for high-dose methotrexate therapy in childhood malignancies.

Clinical toxicities and pharmacokinetics of methotrexate (MTX), associated with reduced citrovorum factor (CF) neutralization, were studied on 279 infusions in 25 children with various malignancies. MTX, at 1000-8400 mg/m2, was infused during six to 24 hours with multiple schedules of reduced CF rescue. Plasma MTX levels ranged from 7.0 X 10(-5) to 7.0 X 10(-4) M during MTX infusion. The levels declined rapidly with a two-phase elimination pattern (t1/2 = 1.2-2.5 hours, t1/2 = 18-32 hours). The folate level in the plasma ranged from 5 X 10(-7) M to 1.4 X 10(-6) M when CF was administered every six hours or every three hours, respectively. Limited bone marrow suppression was seen in only seven percent of infusions, with moderate elevation of GOT and GPT in 20% of infusions, and stomatitis in only 2.6% of infusions, despite reduction in the total dose of CF from 225 mg to 105 mg and despite delaying CF initiation from nine hours to thirty-six hours after the start of MTX infusion.

Adolescent↗

[Fundamental and clinical studies of cefminox in children].

Cefminox (CMNX, MT-141), a newly developed injectable cephem antibiotic, was administered intravenously as one shot injection at 3 different dosages of 10, 20 and 40 mg/kg to 9 children; for each dose level 3 children were used. In these children serum and urinary concentrations as well as recovery rates were determined. In addition, in order to determine clinical and bacteriological efficacies of CMNX, it was used in the treatment of 37 cases of various infections consisting of 2 cases of acute tonsillitis, 1 case of acute tonsillitis associated with otitis media, 1 case of acute bronchitis, 1 case of chronic bronchitis, 20 cases of pneumonia, 1 case of pneumonia associated with otitis media, 8 cases of urinary tract infections, 2 cases of purulent lymphadenitis and 1 case of gluteal abscess. The drug was administered intravenously as one shot injection at a mean daily dosage of 76.6 mg/kg, in 4 divided doses in most cases, for a mean period of 6 days. Finally, in 43 cases added of 6 drop out cases which were included in analysis of efficacy side effects and abnormal laboratory findings were examined. The following results were obtained. In 9 cases, which received CMNX at 3 different dosages of 10, 20 and 40 mg/kg for 3 cases each intravenously as one shot injection, mean serum concentrations reached the peaks of 109.4, 218.1 and 357.1 mcg/ml at 5 minutes after injection, respectively, showing dose response relation. The mean half-lives were 1.74, 1.62 and 1.84 hours, respectively. The mean concentrations of CMNX in urine in the same cases as used for determinations of serum concentrations were highest during the 0 approximately 2 hours period, reaching 1,582, 3,304 and 4,618 mcg/ml at the respective doses. The mean recoveries within the first 6 hours were 82.8, 69.8 and 81.3%, the rate for 20 mg/kg group being lower than those obtained for the other groups. This is possibly due to 1 case which showed unusually low recovery rate of 44.4%. When this case is excluded, the recovery rates became similar for all groups. As to clinical results, responses rated as good or higher were obtained for 91.9% of the cases (34 cases/37 cases), with high efficacy rate. No side effects were seen in 43 cases included of drop out cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Effect of BRL 25000 (clavulanic acid-amoxicillin) on bacterial flora in human feces].

BRL 25000 (187.5 and 375 mg tablets), a formulation of CVA-K and AMPC in the ratio of 1:2, and AMPC (as control drug) were administered to healthy volunteers, aged 20 approximately 28 years and weighing 60 approximately 85 kg (68.8 kg, on average). Each drug was administered 3 times a day (after meals) for 5 days and the volunteers were separated into 3 groups of 4 subjects each. The effect on the fecal flora was studied before dosage, during administration (day 3 and 5) and day 3 and 5 after the administration course was completed. Studies were undertaken to isolate C. difficile on the last day of administration and 3 and 5 days after administration had ceased. Fecal concentrations and the susceptibility of the isolates to AMPC, CVA-K and BRL 25000 were measured. Side effects and laboratory findings were studied. The results obtained were as follows: 1. In BRL 25000 (187.5 mg X 3/day) group, the population of E. coli was on average, 1 X 10(6) approximately 9 X 10(6) cells/g feces before initiation of administration and it increased by 2 logarithms 3 and 5 days after initiation of administration. By 3 and 5 days after end of administration, the E. coli population was similar to the initial population. The population of Klebsiella sp. was 1 X 10(6) approximately 9 X 10(6) cells/g feces on average before commencement of dosage and it increased by 2 logarithms 3 days after initiation of administration but there was no consistent change in the Klebsiella sp. population thereafter. The Enterobacter sp., population was not consistent neither was the population of other Enterobacteriaceae. In total, the mean Enterobacteriaceae population was 1 X 10(7) approximately 9 X 10(7) cells/g feces before initiation of administration and increased by 2 logarithms 3 days after initiation of administration, and then returned to the initial level 5 days after end of administration. No consistent changes in population were noted for the other Gram-negative bacilli. The Staphylococcus sp. population was 1 X 10(6) approximately 9 X 10(6) cells/g feces on average before initiation of administration. This organism was detected in only 1 case 3 days after initiation of administration and in another 5 days after initiation of administration, thereafter, the population was similar to the initial population.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗