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Biomedical subjects

R Fujii

Publications and source records attributed to R Fujii.

At least 217 records · Page 12Linked to original sources

[Pharmacokinetic and clinical studies with imipenem/cilastatin sodium in the pediatric field. Pediatric Study Group for Imipenem/Cilastatin Sodium].

Pharmacokinetic and clinical studies of imipenem/cilastatin sodium (MK-0787/MK-0791), a new carbapenem antibiotic and a dehydropeptidase-I inhibitor, respectively, were carried out in a joint study in the pediatric field by a study group consisting of investigators at 16 institutions. The results were summarized below. Pharmacokinetic studies Peak plasma concentrations of MK-0787/MK-0791 were 27.7-190.0/28.3-216.4 micrograms/ml at doses of 10/10-50/50 mg/kg administered by a 30 or 60-minute drip infusion. The above findings proved that dose response was clearly observed. Over a period of 6 or 7 hours, the urinary excretion of MK-0787 and MK-0791 totaled 54.2-88.0% and 53.6-89.0% of the dose administered, respectively. Plasma half-lives of MK-0787 and MK-0791 in the beta-phase were 0.87-1.05 hours and 0.59-0.95 hour, respectively. The cerebrospinal fluid (CSF) levels of MK-0787 in patients with purulent meningitis were 2.0-14.4 micrograms/ml; however, the penetration rate of the drug into the CSF was relatively poor in patients with normal meninges. Clinical study Clinical efficacy was evaluated in 283 patients. In 112 patients the daily dosage ranged from 30/30 mg/kg to 59/59 mg/kg, and in 138 patients it ranged from 60/60 mg/kg to 99/99 mg/kg. The maximum dose administered was 222/222 mg/kg. The drug was administered either 3 or 4 times per day. The clinical efficacy rate was 92.5% among 187 patients with identified etiologic pathogens. The drug was effective in 3 out of 4 patients with purulent meningitis and in 7 out of 10 patients with septicemia. The clinical efficacy rate was 96.7% in 90 patients with respiratory tract infection (pneumonia, lung abscess, etc.), 96.5% in 57 patients with urinary tract infection, 90.9% in 11 patients with SSTI. The clinical efficacy rate in those with no identified etiologic pathogen was 97.0% among 101 patients. Bacteriologically, the eradication rate for S. aureus was 87.9% of 33 isolates. Comprehensively, the eradication rate for Gram-positive bacteria was 94.7% of 75 isolates. The eradication rate for P. aeruginosa was 87.5% of 8 isolates. Including these strains, the eradication rate for Gram-negative bacteria was 90.3% of 134 isolates. The MK-0787/MK-0791 exhibited an eradication rate of 91.9% among a total of 211 Gram-positive and Gram-negative bacteria including anaerobes.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗

[A comparative, well-controlled study of ceftizoxime suppository against ceftizoxime intravenous injection in infantile acute pneumonia].

We have attempted to clinically define the therapeutic usefulness of ceftizoxime suppository (CZX-S) in children with bacterial pneumonia, in a randomized trial. Intravenous injection of ceftizoxime (CZX) was used as the control. The results are summarized below. Subjects were inpatients with bacterial pneumonia, ranging in age from 9 months to 7 years and 10 months. As a rule, the daily dose was either four 250 mg (in potency) suppositories given at 6-hour intervals or 60 mg/kg body weight intravenous CZX (control) given in 4 injections at 6-hour intervals over a period of 7 days. The number of children in the study was 67. These children were divided into 2 dosage groups (suppository, 35; injection, 32) with matching pretreatment background factors. The severity of the target disease in the majority of the children was "moderate". The rate of therapeutic effectiveness was 97.1% for the suppository and 93.8% for the injection, and did not differ significantly between the 2 groups. Rates of efficacy by severity, presence or absence of underlying diseases, daily dose and/or complications were high without exception, and did not differ significantly between the 2 groups. Eradication rates for causative microorganisms, as studied in 16 children of each group, were both 93.8%. The 2 most frequently isolated causative organisms were Haemophilus influenzae and Streptococcus pneumoniae. Side effects were examined for 36 children of each group. The frequency of side effects did not differ significantly between the suppository group (2 with diarrhea and 1 with abdominal pain) and the injection group (1 with urticaria), and 8.3% and 2.8%, respectively. The frequency of abnormal laboratory test findings differed significantly (P less than 0.01) with respect to eosinophilia which occurred in 7 (20.6%) of the injected subjects but was not encountered in the subjects treated with suppositories. Other abnormal laboratory findings included thrombocytosis in 3 (14.3%) of the injection group and increased GOT in 1 (3.2%) of the suppository group. The suppository formulation of CZX appears to be a highly useful substitute for the injectable form, and should find a special use in children whose treatment with injections experiences some difficulty.

Abdomen↗

[Bacteriological, pharmacokinetic and clinical evaluations of ceftriaxone in the pediatric field. Pediatric study group of ceftriaxone].

UNLABELLED: Ceftriaxone (CTRX), a new injectable cephem antibiotic agent, was evaluated bacteriologically and clinically for its efficacy and safety in the pediatric field by a study group organized with pediatricians from all over the country. The following are a summary of the results of the evaluation. Antibacterial effects: The inhibition of growth was attained for over 90% of strains of K. pneumoniae, H. influenzae and Salmonella spp. at the concentration of 0.10 micrograms/ml and of strains of S. pneumoniae and E. coli at the concentration of 2.0 micrograms/ml. The CTRX was proved to have excellent antibacterial effects. Absorption and excretion: Thirty minutes after one shot intravenous administration with 10, 20, 40 and 50 mg/kg of CTRX, its serum levels were 73, 124, 169 and 190 micrograms/ml, respectively, a clear tendency of dose-response relationship being noticed. The serum levels decreased only gradually and stayed as high as 10 to 20 micrograms/ml even after 12 hours. The half-lives of the drug were 5.5, 6.3, 6.0 and 4.7 hours for the 4 different dose levels, respectively. Following the intravenous injection with 10, 20 and 40 mg/kg, the urinary excretion rates were 55, 52 and 54%, respectively. Following the one shot intravenous administration or by the drip infusion for 30 minutes with about 50 mg/kg, CTRX levels in the cerebrospinal fluid ranged from 1 to 20.3 micrograms/ml in case of purulent meningitis (5 to 10 micrograms/ml in most cases). CLINICAL RESULTS: A total of 322 cases was enrolled. The efficacy of CTRX was evaluated in 295 cases out of the 322, excluding drop-outs and the cases which did not meet the protocols. The clinical efficacy rate was 94% of 191 cases where the causative bacteria were identified, CTRX being "excellent" in 108 cases and "effective" in 72. In the remaining 104 cases where the causative bacteria were not identified, the efficacy rate was 92%, CTRX being "excellent" in 42 cases and "effective" in 54. Furthermore, the efficacy rate was 89% of 18 cases infected with more than one kind of bacteria. The drug showed "excellent" or better effectiveness in 88% of 75 cases which had not responded to other antibiotics. Bacteriologically, 174 out of 216 strains (93%) which were judged to be causative bacteria disappeared with the use of CTRX. Eighty-five percent of 53 strains which had not responded to other antibiotics disappeared by the CTRX treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[A pharmacokinetic and clinical evaluation of ceftazidime in neonates and premature infants. A study of ceftazidime in the perinatal co-research group].

Ceftazidime (CAZ) was evaluated for its pharmacokinetics and clinical usefulness in neonates and premature infants. The results obtained were summarized below. Following intravenous injection of CAZ 10 or 20 mg/kg to neonates and premature infants, dose response was observed in serum concentrations ranging from 5.1 to 21.9 micrograms/ml at 6 hours after the injection. The serum half-life tended to be longer in premature infants than in neonates; the half-life being longer for an infant with lower day-age. Urinary recovery rates during the first 6 hours after single administrations of 10 mg/kg of CAZ tended to be higher in neonates than in premature infants, and higher rates were observed in older infants. However, no noticeable difference was observed after the administration of CAZ 20 mg/kg. Clinical efficacy was evaluated in 99 neonates and 55 premature infants (156 infections), daily doses ranging from 21.1 to 246.4 mg/kg. Out of 105 cases of common infections, mainly 44 cases with causative organisms identified (including 17 of sepsis, 7 of pneumonia, 4 of purulent meningitis, 11 of urinary tract infections) were examined for the clinical efficacy. The efficacy of CAZ was excellent in 21, good in 18, fair in 1 and poor in 4, with the efficacy rate of 88.6%. In the remaining 61 cases, i.e., 37 with causative organisms unknown and 24 with signs of intrauterine infections, the efficacy rate was 95.1%. Other than these cases, additional 51 cases were given CAZ solely for prophylaxis of infections, and the results were found satisfactory. On the whole, clinical efficacy rate of CAZ was 94.9% in 156 cases. Out of the 44 cases examined for bacteriological responses, 38 were evaluated as 'eradicated', 3 'persisted' and 3 'unknown' with eradication rate of 92.7%. Replacement of organisms (superinfection) was observed in 3 cases. Out of 179 cases in which adverse effects were assessable, adverse effects were observed in a total of 4 cases (2.2%), i.e., 3 cases of diarrhea (1.7%) and 1 case of rash (0.6%), and abnormal laboratory findings were observed in a total of 14 cases (7.8%), i.e., increase in eosinophiles count in 8 (4.5%), elevation of GOT in 3 (1.7%), increase in platelet, elevation of GOT . GPT, and elevation of GOT . GPT . BUN in 1 case each (0.6%). None of them were severe and they were transient. Elevations of bilirubin and cases of positive PIVKA II associated with CAZ were not observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗

[Clinical evaluation of ceftazidime in the treatment of neonatal infections].

Ceftazidime (CAZ) was evaluated for its safety and efficacy in 27 newborns. Four confirmed cases of bacterial infections were cured by the CAZ therapy (efficacy rate 100%). The CAZ was assessed as effective in sepsis (2) and urinary tract infections (2). Main pathogens which responded to CAZ were Escherichia coli, Enterobacter cloacae and Acinetobacter anitratum. As adverse effects, elevations of GOT and GPT (1 case) were found to be associated with the CAZ therapy. Half-lives of the serum levels in mature infants were 1.93-3.52 hours, and those in low birth weight infants were 2.92-4.17 hours. Penetration into the cerebrospinal fluid in 1 case of viral meningitis was satisfactory. The data suggest that CAZ is a safe and effective injectable antibiotic when used in newborn with infection caused by CAZ-susceptible bacteria.

Bacterial Infections↗

[Clinical evaluation of cefixime in children].

A new beta-lactamase-stable oral cephem antibiotic, cefixime (CFIX), was evaluated for safety, efficacy and pharmacokinetics in children. CFIX was effective in 19 of 20 cases (95%) with bacterial infections. The drug was especially effective against the cases of pneumonia due to beta-lactamase-producing H. influenzae or B. catarrhalis. Pharmacokinetic parameters of CFIX (3 mg/kg) with premeal administration were as follows: Kel 0.328 +/- 0.066 hr-1, T 1/2 2.14 +/- 0.36 hrs, AUC 10.9 +/- 8.7 micrograms X hr/ml, and Vd/F 1.64 +/- 1.42 L/kg. In most of the cases tested, the urinary excretion rate in 12 hours was 5 to 17%. A dose of 3 mg/kg twice daily seems to be adequate for a regular treatment.

Bacterial Infections↗

[Septicemia of children in Japan (1980-1984). Part 3. Antibiotic therapy and prognosis].

Seven hundred and thirteen cases of proved bacteremia experienced at 48 pediatric institutions throughout Japan during 1980-1984 were analyzed with respect to their chemotherapeutic treatment and prognosis. Case fatality rate was the lowest in cases of monotherapy and the highest in those treated with 3 different antibiotics. Those treated with 2 different antibiotics showed significantly higher fatality rate than in cases treated with single antibiotic. Cephalosporins showed a trend to be administered singly more often than penicillins. Of all penicillin prescriptions ampicillin (ABPC) was chosen in 61.1% and in 62.3% of any combination therapies of penicillins. Among combination therapies gentamicin (GM) was most frequently combined with ABPC, i.e., in 58.9%. In 135 cases treated with combination of ABPC and GM or similar combination like ABPC and antipseudomonas aminoglycosides, deaths resulted in 42 cases compared with 108 deaths out of 578 cases treated with other chemotherapy revealing a statistically significant difference (P less than 0.005). The utilization of new cephem antibiotics found in this study clearly paralleled to the trend of the consumption of new injectable cephalosporins in Japan since the appearance of new cephem antibiotics in 1980. The clinical effect of new cephem antibiotics in pediatric bacteremia seems fairly good but will need further observations, particularly when combined with aminoglycosides. A very large difference exists in the choice of chemotherapy for bacteremia in children among different hospitals. In general, those institutions that prefer monotherapy with some combination therapies of other antibiotics than penicillins and aminoglycoside demonstrated better therapeutic results than those that prefer therapies with the orthodox ABPC and GM combination. Further analysis is necessary concerning backgrounds of these cases examined in our study.

Anti-Bacterial Agents↗

[Septicemia of children in Japan (1980-1984). Part 4. Antibiotic treatment and prognosis according to causative agents].

Seven hundred and thirteen cases of septicemia whose causative organisms were detected from peripheral blood at 48 pediatric institutions throughout Japan during 1980-1984 were analyzed with respect to their chemotherapeutic outcome relative to causative microorganisms. Against Gram-positive cocci including S. pyogenes, S. agalactiae, S. viridans, S. pneumoniae, E. faecalis, penicillins (PCs) demonstrated excellent results, and cephalosporin antibiotics (CEPs) also showed good results except against E. faecalis. Combinations of PCs and aminoglycosides (AGs) resulted in a significantly high fatality rate in streptococcal infections, and very significantly high fatality rate of 38.7% in infections due to S. aureus. Combinations of CEPs and AGs showed a little lower rate than the above combinations, but monotherapy gave the best result. Infections due to S. epidermidis revealed better prognosis than those due to S. aureus. We recommend that PC II (PCase resistant) and CEP I or II should be combined with fosfomycin (FOM), if necessary, for the treatment of staphylococcal septicemia. For the treatment of septicemia due to H. influenzae, ampicillin (ABPC) is the best drug against sensitive strains and CEP IV or V may also be the drug of choice even against ABPC resistant strains. Against septicemia due to E. coli, although its prognosis is not good in general, monotherapy gave the lowest mortality. Among combined therapies, "CEPs + AGs" resulted in a significantly lower death rate of 13.3% than "PCs + AGs" which showed a death rate of 38.3%. Pseudomonas septicemia is very difficult to treat with by a monotherapy using even PC IV, CEP V or AGs any of which is effective against P. aeruginosa. However, even then, the combination of "beta-lactam + AGs" gave higher mortality than monotherapies.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglycosides↗

[Pharmacokinetic and clinical studies on cefuzonam in the pediatric field].

A multi-center open study was conducted to investigate cefuzonam (L-105, CZON), a newly developed cephalosporin from pharmacokinetic, bacteriological and clinical aspects, in the pediatric field with the participation of 17 institutions and their related facilities. The results are summarized as follows. Serum concentrations and urinary excretion. The pharmacokinetics in pediatric patients was investigated with a dose of 20 mg/kg, via one shot intravenous injection or intravenous drip infusion over 1 hour. The results were nearly the same as those in adult patients. Mean serum concentrations 5 minutes after one shot intravenous injections were: 52.8 micrograms/ml with the dosage of 10 mg/kg, 135 micrograms/ml with 20 mg/kg, and 317 micrograms/ml with 40 mg/kg, and T1/2 beta's for the 3 dosages were 1.07 hours, 0.91 hour, and 1.01 hours, respectively. With 1-hour intravenous drip infusion, mean serum concentrations at the end of infusion were: 22.4 micrograms/ml with 10 mg/kg, 46.3 micrograms/ml with 20 mg/kg, 72.5 micrograms/ml with 40 mg/kg, and 69.2 micrograms/ml with 50 mg/kg, and T1/2 beta's for these dosages were 1.31 hours, 1.45 hours, 0.84 hour, and 0.66 hour, respectively. In 6 hours after administration of CZON, urinary excretion rates were 43.5-51.4% for one shot intravenous injections of 10-40 mg/kg, and 42.7-58.6% for 10-50 mg/kg drip infusions. Concentrations in cerebrospinal fluid Penetrations into cerebrospinal fluids in patients with purulent meningitis achieved levels of 2.80-6.40 micrograms/ml with the administration of CZON at 100 mg/kg in acute cases of within 6 days after onset. When the administration of the drug was done at the earlier stage, the greater penetration occurred. However, rates of penetration were 3.10% to 5.03% within 4 days after a drug administration, thus, the penetration was not thought to be as good as other beta-lactam agents which achieve higher penetration rates. Clinical results Of 407 cases treated with CZON, 18 cases were excluded from the statistical analysis. The remaining 389 cases plus 8 cases each of which had 2 complicated diseases, with a total of 397, were statistically analyzed for the clinical effectiveness of this drug against various infections. The efficacy was evaluated as "good" or "excellent" in 248 out of 266 cases from which pathogens were isolated, for an efficacy rate of 93.2%. The efficacy rate was 88.5% for 131 cases for which pathogens were unidentified, thus no statistically significant difference was noted between the 2 groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Ceftizoxime↗

Melanin concentrating hormone (MCH) effects on teleost (Chrysiptera cyanea) melanophores.

The in vitro biological actions of synthetic chum salmon melanin concentrating hormone (MCH) on melanophores of the blue damselfish (a teleost), Chrysiptera cyanea, were studied. This cyclic heptadecapeptide stimulated melanosome (melanin granule) aggregation (centripetal migration) within melanophores at a threshold concentration of about 10(-10) M. The action of this putative hormone was not blocked by alpha- or beta-adrenoceptor antagonists. It was concluded that the effects of MCH were direct and were not mediated indirectly through the actions of adrenergic neurotransmitters released from nerve terminals. Further evidence for this view comes from the observation that, unlike the case of neurotransmitter release, melanosome aggregation in response to MCH proceeded in the absence of calcium. The possible role of MCH in the control of color change of teleost fishes is discussed.

Animals↗

Experience with cefotaxime in infections caused by gram-positive pathogens, especially Staphylococcus aureus.

Cefotaxime (CTX) was the first third-generation cephalosporin to be launched. According to my classification of cephalosporins for practitioners, in contrast to old beta-lactamase-labile cephalosporins (Group I-III), CTX is beta-lactamase-stable and belongs to Group V with anti-pseudomonas activity. A critical review of about 90 patients with Staphylococcus aureus infections, found among analyzable subjects treated with CTX for gram-positive infections, demonstrates that CTX can be expected to be bacteriologically and clinically effective against this pathogen. Moreover, CTX had excellent efficacy against gram-positive organisms compared with other so-called third-generation cephalosporins. CTX is comparable to or more effective than conventional antibiotics in the treatment of respiratory tract infections, soft tissue infections, and neonatal and pediatric infections caused by gram-positive organisms, S. aureus included, if used after taking the susceptibility of the pathogen into account.

Bacterial Infections↗

Receptor mechanisms in fish chromatophores--VII. Muscarinic cholinoceptors and alpha adrenoceptors, both mediating pigment aggregation, strangely coexist in Corydoras melanophores.

Both acetylcholine and catecholamines showed melanin-aggregating action within melanophores on an isolated bony plate of the mailed catfish Corydoras paleatus. Chromatic nervous stimulation either by an electrical field or by an elevation of [K+]0 brought about melanosome aggregation. Alpha adrenolytic agents antagonized the melanin-aggregating effects either of catecholamines or of nervous stimuli. Muscarinic cholinolytics interfered with the action of acetylcholine, but did not have any effect on the responses to nervous stimuli. In addition to the alpha adrenoceptors which participate in sympathetic-melanophore transmission, muscarinic cholinoceptors of unknown functional significance, which also mediate melanosome aggregation in the cell, exist in Corydoras melanophores.

Acetylcholine↗

Detection of Clostridium difficile enterotoxin in neonates by latex agglutination.

Clostridium difficile enterotoxin (D-1) was detected in 13 symptomatic and nine asymptomatic neonates in the neonatal intensive care unit by latex agglutination test but was not found in 18 healthy neonates in two other newborn nurseries. Environmental contamination in the intensive care unit may have been the cause. An association between the presence of enterotoxin and clinical symptoms is discussed.

Clostridium↗