Biomedical subjects

R Fujii

Publications and source records attributed to R Fujii.

At least 109 records · Page 6Linked to original sources

PubMed1994

[Clinical studies on clarithromycin dry syrup in the pediatric field. Pediatric Study Group of TE-031 Dry Syrup].

Clarithromycin dry syrup, a new drug preparation, was clinically evaluated in the pediatric field and the following results were obtained: 1. Absorption and excretion In infants administered with single oral dose of 5 mg (potency)/kg and 10 mg/kg, the Cmax was 2.26 +/- 0.42 and 3.23 micrograms/ml; Tmax, 1.6 +/- 0.1 and 2.0 hours; T 1/2, 3.89 +/- 0.52 and 2.06 hours; AUC (0-infinity), 13.48 +/- 1.93 and 13.84 micrograms.hr/ml, respectively. Urinary concentrations peaked in 2-4 hours after administration at 5 mg/kg and 0-2 hours at 10 mg/kg. Urinary recovery rates in the first 6 hours were 25.8 +/- 3.9% at 5 mg/kg and 20.7% at 10 mg/kg. 2. Clinical results The clinical efficacy of the drug was evaluated in 150 patients with various infections. Clarithromycin dry syrup was administered to all the patients at daily doses of 10-15 mg/kg divided into 2-3 equal doses. The overall clinical efficacy rate was 98.0%, and this drug was effective in 98.9% of 90 patients for whom the causative pathogens were identified and in 96.7% of the other 60 patients for whom the causative pathogens were unknown. The bacteriological eradication rate was 88.5%. The efficacy and eradication rates for 19 patients who had not responded to previous chemotherapy that lasted for more than three days were 94.7% (18/19) and 75.0%, respectively. Side effects occurred in 4 (2.4%) of 169 patients subjected to safety analyses, but none was serious. As to abnormal laboratory test results, moderate increases of eosinophils and elevations of transaminases were observed in 5.9% of the cases. No particular and serious problems were associated with administration of this drug. Based on the above results, clarithromycin dry syrup is considered to be very useful and have a good compliance at a daily dose of 10-15 mg/kg divided into 2-3 doses.

Administration, Oral↗

PubMed1994

[Clinical evaluation of cefozopran in the pediatric field].

A new parenteral cephem, cefozopran (CZOP), was evaluated for its safety and efficacy in 21 children with acute infections. A mild side effect or an abnormality in laboratory tests was observed in one case each, but the safety of CZOP was otherwise observed. CZOP was effective in all of the 18 bacterial infections tested including pneumonia, cellulitis and urinary tract infections, and all the causative organisms were eradicated. Serum half-lives of CZOP were 1.5-1.8 hours and the urinary excretion rates were 63-96% in the first 5-8 hours after administration. These data suggest that CZOP is safe and effective in children with susceptible bacterial infections.

Acute Disease↗

PubMed1994

[Carbon-11 labeled diacylglycerol for signal transduction imaging: effect of the solubilizer on the distribution and radiation dosimetry].

Carbon-11 labeled diacylglycerol (11C-DAG) has been developed as a signal transduction imaging agent for the CNS, and it can visualize the second messenger. For clinical application by positron CT (PET), the 11C-DAG solution must be prepared for intravenous injection. However, the 11C-DAG does not dissolve in water because of its lipophilicity and requires a solubilizer such as human serum albumin (HSA) and Tween 80 (TW-80). We examined the influence of these solubilizers on the tissue distribution of 11C-DAG, and estimated the radiation dosimetry. In the brain, uptake of 11C-DAG dissolved with HSA was 1.3-1.8 times higher than that of dissolved with TW-80. On the other hand, the lung and spleen showed a higher uptake of 11C-DAG using TW-80 than when using HSA. Especially, the lungs showed 20-40 times higher uptake than when using HSA. Also, the washout of radioactivity from tissue was slower, and the dose of radiation exposure was estimated to be higher, with TW-80 than with HSA. Therefore, between TW-80 and HSA with different solubilizing mechanisms, the later was suggested to be a better solubilizer of 11C-DAG.

Animals↗

PubMed1994

Effect of newly synthesized indole derivatives on multidrug resistance in human cancer cells.

Twenty indole derivatives were investigated for their ability to reverse multidrug resistance (MDR), for their ability to compete with [3H]azidopine in binding to P-glycoprotein (P-gp) and for their hydrophobicity. Six derivatives almost completely reversed the resistance to vincristine (VCR) in multidrug-resistant KB-C2 cells, and other derivatives partially overcame the resistance. The ability of the derivatives to enhance vincristine cytotoxicity did not significantly correlate with the inhibition of [3H]azidopine binding to P-gp or with their hydrophobicity. However, all the derivatives that inhibited > 50% of the photolabeling completely reversed VCR resistance. The 2-pyridyl group with a basic nitrogen atom attached at position 3 of indole in an appropriate spatial orientation seems to be an important feature for the interaction of the indole derivatives with P-gp. One of the derivatives, 1, which has low cytotoxicity and hydrophobicity, completely reversed the resistance of KB-C2 cells to Adriamycin, actinomycin D and VCR. Our data indicate that MDR-reversing indole derivatives with low cytotoxicity and hydrophobicity exist. These characteristics will surely be profitable for clinical use.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

[Clinical evaluation of a new carbapenem antibiotic, biapenem (L-627), in the pediatric field].

Biapenem (L-627) was evaluated for its safety and efficacy in 27 children with various bacterial infections. L-627 was effective in cases with osteomyelitis due to Staphylococcus aureus, pneumonia and purulent meningitis due to penicillin-resistant Streptococcus pneumoniae, and urinary tract infections due to Enterococcus faecalis, Escherichia coli, or Pseudomonas aeruginosa. However, L-627 failed to produce good responses in 2 of 7 cases of Haemophilus influenzae infections. Pharmacokinetic parameters of 30-minutes infusion of 12 mg/kg were as follows: Cmax 29-46 micrograms/ml, T 1/2 0.68-0.94 hr. Adverse reactions were minimal. These data suggest that L-627 is safe in children, and is valuable especially for treatment of infections in immunocompromised hosts and infections due to multiply resistant bacteria.

Adolescent↗

PubMed1994

[Pharmacokinetic and clinical studies with L-627 (biapenem) in the pediatric field. Pediatric study group of L-627].

To conduct pharmacokinetic and clinical studies on newly developed L-627 (biapenem) against various infections in pediatrics, a study group was organized and a joint research by 15 institutions and their related hospitals was undertaken. Informed consents of subjects were obtained prior to the study. The obtained results are as follows. 1. Plasma concentrations and urinary excretion Pharmacokinetics of L-627 in children was studied in 29 subjects using 30 minutes intravenous drip infusion of 6 mg/kg and 12 mg/kg. Maximum plasma levels of L-627 was observed at the completion of drip infusion and were 25.1 micrograms/ml with administration of 6 mg/kg and 39.2 micrograms/ml with administration of 12 mg/kg on average. Dose dependency was noted in Cmax and AUC with these doses. Maximum blood levels in all of the 5 participated sucklings under the age of one year were similar to the average. As for urinary excretion, L-627 was excreted 66.0% with administration of 5 mg/kg and 62.3% with 12 mg/kg. 2. Cerebrospinal fluid concentrations Cerebrospinal fluid concentrations ranged from 0.76 to 8.54 micrograms/ml in 30-240 minutes after the completion of drip infusion with dose of 20-40 mg/kg in 9 subjects with purulent meningitis, when they were measured within 3 days after the initiation of the treatment with L-627. 3. Clinical results Thirty-three cases of exclusion and drop-out were deducted from a total of 330 cases, hence 297 cases were evaluated as the subjects in the study for analysis of clinical effects. As for clinical effects in group A where pathogenic bacteria were detected, 166 out of 173 were rated as effective or above, hence the efficacy rate of 96.0% was obtained. In group B where pathogenic bacteria were not detected, 114 out of 124 cases were rated as effective or above, thus the efficacy rate was 91.9%, which is similar to that of the group A. The overall efficacy rate was 94.3% in the entire 297 cases. The rates of "excellent" responses out of the cases rated as effective or above were 62.7% (104/166) in the group A and 55.3% (63/114) in the group B, thus the rate was markedly high in the former group. Efficacy rate for each pathogenic strain was also high, and that in subjects infected by a single pathogenic strain was 96.7% (145/150) and that in subjects infected by two or more pathogenic strains was 91.3% (21/23).(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

PubMed1994

[Pharmacokinetic and clinical studies with cefozopran in the pediatric field. Pediatric Study Group of Cefozopran].

We investigated pharmacokinetics and clinical effectiveness of a newly developed cephem antibiotic cefozopran (SCE-2787, CZOP) against various pediatric infections in 18 institutions and their affiliates. We obtained the following results. 1. Serum concentration and urinary excretion rates Pharmacokinetics of CZOP in children was examined after intravenous injection and 30-minute drip infusion of 10, 20 and 40 mg/kg of CZOP. Peak serum concentrations of CZOP in 30 minutes after intravenous injection were 21.7, 51.5 and 77.8 micrograms/ml, respectively, showing a clear dose response. Half-lives were 1.99, 1.85 and 1.67 hours, respectively. In the first 6 hours after administration, urinary excretion rates of CZOP were 87.3, 67.4 and 84.1%, respectively. In the cases of 10, 20 and 40 mg/kg administration of CZOP 30-minute drip infusion, peak serum concentration of CZOP in 30 minutes, when the infusion was completed, were 38.1, 72.8 and 95.6 micrograms/ml, respectively. Again, there was a clear dose response. Half-lives were 1.67, 1.69 and 1.43 hours, respectively. In the first 6 hours after administration, urinary excretion rates of CZOP were 53.9, 59.7 and 77.3%, respectively. Cerebrospinal fluid concentrations of CZOP administered by intravenous injection of 50 mg/kg to patients with purulent meningitis were 1.6 to 43.4 micrograms/ml in 1 to 1.5 hours after administration. 2. Clinical study Clinical efficacy was evaluated in 337 cases. The largest number of cases, 138 cases, were found in 2 to < 6-year olds. The majority of the patients were under age 9, and 70 cases were of less than 1-year old infants. 183 cases were males and 154 cases were females. In terms of illness, a majority, or 185 cases, suffered from pneumonia, followed by 39 cases of UTI and 23 infections of the skin and soft tissue. There were 7 cases of purulent meningitis. In 218 cases, CZOP was administered at a daily dose of 60- < 80 mg/kg. The drug was administered for 6-10 days, the most frequent duration, in 188 cases. In the cases where causative organisms were identified (group A), the efficacy rates ("excellent" and "good") obtained were 100% (5/5) against purulent meningitis, 100% (2/2) against sepsis, 98.3% (119/121) against pneumonia, 100% (13/13) against acute bronchitis, 100% (11/11) against upper respiratory tract infection, 96.3% (26/27) against UTI. Overall, "excellent" and "good" responses were observed in 97.5% (197/202) of cases with known causative organisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1994

[Clinical studies of arbekacin sulfate in the pediatric field].

UNLABELLED: A clinical investigation was carried out to evaluate arbekacin, an aminoglycoside, in the treatment of MRSA infections (pneumonia, septicemia, etc.) of pediatric patients. The obtained results are summarized as follows. 1. CLINICAL RESULTS: Excluding those patients who met the present exclusion criteria and withdrawal cases from a total of 18 patients, 10 patients (3, 6, and 1 cases of septicemia, pneumonia, and urinary tract infection, respectively) were subjected to clinical evaluation. These were composed of 1, 1, 6, and 2 cases of neonate, infants, pre- and school age children, respectively. Excellent, good and fair results were obtained in 5, 2, and 3 patients, respectively; thus, the efficacy rate was 70.0%. The efficacy rate by disease was 100%, 50.0% and 100% in septicemia, pneumonia, and urinary tract infection, respectively. The bacteriological eradication were obtained in 70.0% of the total patients; by disease, these rates were 100% and 50.0% in septicemia/urinary tract infection and in pneumonia, respectively. The MIC50 as well as the MIC80 against MRSA strains isolated from 9 patients were 0.39 microgram/ml and 1.56 micrograms/ml, respectively. No adverse reactions were observed in the 15 patients, while in laboratory test values, one case each out of 12 patients examined showed gamma-GTP elevation, proteinuria, and hematuria. 2. Pharmacokinetics: The pharmacokinetics of the agent was investigated in a total of 9 patients, which included 1 neonate and 4 cases each of pre- and school age children. The Cmax, 4.85-8.83 micrograms/ml, was observed immediately after the termination of the instillation. The T1/2's were 4.96 hours, 1.24-2.54 hours, and 1.78-1.88 hours in the neonate, the pre- and the school age children, respectively; in the neonate the half-life was longer. When 1.92-2.7 mg/kg were administered to 3 each of the pre- and school age children, urinary excretion rates in the first 6-8 hours were 40.1-56.5% of the dosages administered. In all cases, the urinary concentrations were highest in the first 2 hours, after the administration, and then gradually decreased. These results suggest that arbekacin is a useful antibiotic for treating MRSA infections in the pediatric field.

Adolescent↗

PubMed1994

[Pharmacokinetic and clinical studies of SY5555 in the pediatric field. Pediatric Study Group of SY5555].

SY5555, a new oral penem, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained: 1. Pharmacokinetics Pharmacokinetics of SY5555 dry syrup (powder which is dissolved before use) was investigated in 64 children. At a dose level of 3 mg (potency)/kg, Cmax and T1/2 were 0.33 micrograms/ml and 0.95 hours (n = 1), respectively, in the non-fasting state. At a dose level of 5 mg/kg Cmax and T1/2 were 2.09 +/- 1.25 micrograms/ml and 1.20 +/- 1.07 hours, respectively, in the fasting state, and were 1.21 +/- 0.70 micrograms/ml and 1.33 +/- 0.90 hours, respectively, in the non-fasting state. At a dose level of 10 mg/kg, Cmax and T1/2 were 2.96 +/- 1.89 micrograms/ml and 0.89 +/- 0.43 hours, respectively, in the fasting state, and were 2.45 +/- 1.37 micrograms/ml and 1.17 +/- 0.53 hours, respectively, in the non-fasting state. At a dose level of 15 mg/kg, Cmax and T1/2 were 4.30 +/- 2.15 micrograms/ml and 0.82 +/- 0.09 hours, respectively, in the non-fasting state. Data of Cmax and AUC showed that plasma concentration of the drug depended on dose levels. Urinary recovery rates in the first 6 hours were 1.71% (n = 1) in the non-fasting state at a dose level of 3 mg/kg, 4.13 +/- 1.40% in the fasting state and 4.17 +/- 3.29% in the fasting and the non-fasting state, respectively at a dose level of 5 mg/kg, and 6.02% (n = 1) and 4.64 +/- 2.81%, respectively, at a dose level of 10 mg/kg. At a dose level of 15 mg/kg, urinary recovery rate in the first 6 hours was 7.97% (n = 2) in the non-fasting state. 2. Clinical results 1) Dry syrup The clinical efficacy of the SY5555 dry syrup was evaluated in 506 cases. SY5555 was administered at daily doses of 15-30 mg/kg divided into 3 equal doses to most patients. Daily doses of 12- < 18 mg/kg were given to 46.6% of the patients. The overall clinical efficacy rate was 92.9%, and this drug was effective in 93.0% of the 301 patients for whom the causative pathogens were identified, and in 92.7% of the 205 patients with infections for whom the causative pathogens were unknown. The efficacy rate at daily doses of 12 - < 18 mg/kg was 94.5% similar to those obtained at daily doses of 18- < 27 mg/kg (91.7%) or 27- < 33 mg/kg (91.3%). The bacteriological eradication rate was 82.3%.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

PubMed1993

Circadian motile activity of erythrophores in the red abdominal skin of tetra fishes and its possible significance in chromatic adaptation.

The red abdominal skin of the neon tetra Paracheirodon innesi and the cardinal tetra P. axelrodi was found to blanch at night or in the dark. Melatonin added to the bathing medium caused blanching of the red skin. Microscopic observations of the erythrophores indicated that the erythrosomes aggregated in response to norepinephrine, melanin-concentrating hormone (MCH), and melatonin. Of these compounds, melatonin was the most effective. By contrast, many erythrophores were refractory to MCH. Alpha-melanophore-stimulating hormone, isoproterenol, adenosine, and ATP each caused dispersal of the pigment to some extent. Isoproterenol dispersed the pigment only when an alpha-adrenergic blocker, tolazoline, was present. It appears that the change in color of the abdominal skin is primarily due to increased secretion during the night of the pineal hormone melatonin, while other hormonal and nervous factors may modify the distribution of the pigment in the erythrophores.

Adaptation, Physiological↗

PubMed1993

Muscarinic cholinoceptors that mediate pigment aggregation are present in the melanophores of cyprinids (Zacco spp.).

Like melanophores of many teleosts, those of the dark chub, Zacco temmincki, and the common minnow, Z. platypus (Cyprinidae, Cypriniformes) responded to norepinephrine (NE) by the aggregation of pigment. It was further found that some melanophores were responsive to acetylcholine (ACh) in the same way. The response to NE was blocked by an alpha-adrenergic blocker, phentolamine, whereas the response to ACh was not. By contrast, two muscarinic cholinoceptor antagonists, namely, atropine and scopolamine, effectively blocked the action of ACh. The pigment aggregation due to the liberated sympathetic neurotransmitter was blocked by phentolamine but not by cholinergic blockers. These results suggest that, although the melanophores of these species are controlled in an orthodox manner by the sympathetic nervous system, some of them possess extra muscarinic cholinoceptors that also mediate the aggregation of pigment. The present report is the first to describe the presence of cholinoceptors on the chromatophores in species of fish other than those that belong to the order Siluriformes. The evolutionary implications of these findings are discussed.

Acetylcholine↗

PubMed1993

Molecular cloning and sequence analysis of the crtB gene of Thermus thermophilus HB27, an extreme thermophile producing carotenoid pigments.

We have cloned and sequenced a 1.5-kb chromosomal fragment of Thermus thermophilus which promoted the overproduction of carotenoids in T. thermophilus. An open reading frame (ORF-A) coding for a polypeptide with 289 amino acids was responsible for carotenoid overproduction. The putative ORF-A protein showed significant homology with the amino acid sequences of crtB gene products (phytoene syntheses) of other microorganisms. The clone containing the ORF-A on a multicopy plasmid produced about three times as much carotenoid as that produced by the host strain, suggesting that the crtB gene product is a rate-limiting enzyme for carotenoid biosynthesis in T. thermophilus.

Amino Acid Sequence↗

PubMed1993

Rapid detection of human group C rotaviruses by reverse passive hemagglutination and latex agglutination tests using monoclonal antibodies.

Reverse passive hemagglutination (RPHA) tests and a latex agglutination test with monoclonal antibodies (MAbs) were developed for the rapid detection of noncultivatable human group C rotaviruses. For RPHA tests, two MAbs, MAb 5A12 recognizing the outer capsid and MAb 13A3 recognizing the inner capsid, were separately used for the coating of sheep erythrocytes (SRBCs). Forty-six fecal samples were examined to confirm the practicality of the tests. As a result, there was concordance between the RPHA test with SRBCs coated with MAb 5A12 and polyacrylamide gel electrophoresis of viral RNA (RNA-PAGE) in 44 (95.6%) of 46 samples, while the diagnoses by the RPHA test with SRBCs coated with MAb 13A3 were in complete agreement with those by RNA-PAGE. Furthermore, a latex agglutination test with MAb 13A3 was also developed, and this test was fast enough and sensitive enough to successfully detect the viruses from most fecal samples within 2 min. The present procedures would be useful for the diagnosis of human group C rotavirus infections in clinical laboratories which are not well equipped.

Antibodies, Monoclonal↗

PubMed1993

[Nonfunctioning pituitary tumor--subunit, inactive hormone producing tumor].

Approximately 25-30% of the patients with pituitary adenomas were clinically non-functioning adenoma. Recent studies, using molecular biology techniques combined with culture of removed tumors, have revealed that most of these tumors synthesize glycoprotein hormones and/or their subunits. Recent progress and current diagnostic issues are discussed.

Adenoma↗

PubMed1993

[A clinical study of fluconazole-granules and -injectable in pediatric patients with deep-seated mycoses].

Fluconazole (FLCZ) is an antifungal agent of triazole class developed by Pfizer, Inc. Its oral and injectable forms have been available on the market since June 1989 in Japan. FLCZ exhibits potent antifungal activities against Candida spp., Aspergillus spp. and Cryptococcus spp. and, as orally or intravenously administered, is widely distributed into organs and tissues. For its low protein binding rate of about 10 per cent and long serum half life of about thirty hours in adults, FLCZ has been proved highly effective and useful in the treatment of deep-seated mycosis in adult patients. In the present study, we have investigated the clinical effectiveness and antifungal activities of FLCZ granules, a new dosage form of the drug, and of intravenous form in pediatric patients with deep mycosis. A total of 72 patients were treated either with granules orally or with intravenous injection and 47 patients among them were evaluable on the clinical efficacy of the drug. Also, a study on the pharmacokinetics of pediatric patients including premature/new born babies was conducted employing multiple dose regimens in a total of 27 patients. The clinical efficacy rates were 79.5% (35 patients out of 44) in candidiasis and 100.0% (3 of 3) in aspergillosis. The safety of the drug was assessed in 63 patients. No side effects were observed. Clinical laboratory test abnormalities were observed in some patients with an incidence of 9.7% (6 patients out of 62) but most of the abnormalities were only mild and transient. The pharmacokinetics at repeated doses indicated that a steady-state is reached in 4 days after the initial administration of either granules or intravenous form. From these results, it may be concluded that FLCZ is a very useful medication in the treatment of deep mycosis in pediatric patients.

Administration, Oral↗

PubMed1993

[Criteria for clinical evaluation of antibiotics in pediatrics. The purpose and process for establishing the criteria].

This paper describes the purpose and process for establishing "Criteria for Clinical Evaluation of Antibiotics in the Pediatric Field", which was reported in the Japanese Journal of Antibiotics Vol. 46, May, 1993. The Criteria Committee was organized in November 1991. Four meetings were held to establish the draft criteria. The criteria were applied to the evaluation of oral cephem S-1108 and parenteral cephem SCE-2787. When the criteria were compared with the conventional criteria, the results indicated that no difference was obtained in the efficacy rate as a whole, the sum of "Good" and "Excellent" cases, but there was a difference in the cases judged to be "Excellent". Partial alteration was made to the draft criteria and the Committee produced the final version of the criteria. However, the criteria are far from complete, so it will be subjected to further revision it accordance with future advance in chemotherapy.

Bacterial Infections↗

PubMed1993

[Effect of cefditoren pivoxil on carnitine metabolism in pediatric patients].

Carnitine metabolism was studied in 16 pediatric patients with various infections under the treatment with cefditoren pivoxil (CDTR-PI) in granular form. Pivalic acid released from pivaloyloxymethyl ester of the drug was metabolized to pivaloylcarnitine. As results, an increase in urinary carnitine excretion (predominantly as pivaloylcarnitine) and, a decrease in free carnitine concentration and a high acyl/free carnitine ratio in serum (plasma) were observed during the treatment. When the dosing was terminated, pivaloylcarnitine in plasma and then in urine disappeared, and the concentration of free carnitine, acyl/free carnitine ratio returned to the normal range. No carnitine-related side effects were observed throughout the study.

Bacterial Infections↗

PubMed1993

[Clinical evaluation of S-1108 in children].

A new oral cephem antibiotic, S-1108, was evaluated for its clinical efficacy and safety in children. S-1108 was effective in 95% of the 59 examined cases of respiratory, middle ear, skin and urinary tract infections. S-1108 was highly effective in infections of Streptococcus pyogenes, Haemophilus influenzae and Escherichia coli, but was less effective in penicillin-resistant Streptococcus pneumoniae and Staphylococcus aureus infections. The serum half-life was 1.26 +/- 0.36 hours upon after meal administration of 4 mg/kg. No severe adverse reaction was encountered. From these data, S-1108 appears to be safe and effective in children with susceptible bacterial infections.

Bacterial Infections↗