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Biomedical subjects

R Fujii

Publications and source records attributed to R Fujii.

At least 163 records · Page 9Linked to original sources

[Pharmacokinetic and clinical evaluation of imipenem/cilastatin sodium in neonates and premature infants. A study of imipenem/cilastatin sodium by a perinatal co-research group].

Pharmacokinetics and clinical studies of imipenem/cilastatin sodium (IPM/CS), a combined preparation of a new carbapenem antibiotic and a dehydropeptidase-I inhibitor, respectively, were carried out in neonates and premature infants in a joint study by a co-research group. 1. Peak blood levels of IPM/CS when administered at 10 mg/10 mg/kg or 20 mg/20 mg/kg by 30- or 60-minute intravenous drip infusion were achieved at the end of infusion. A dose response was clearly observed between the doses and the peak levels achieved. 2. The areas under the blood concentration time curve (AUC) of CS were greater than those of IPM in most patients. Blood half-lives of IPM and CS tended to be longer in younger neonates and premature infants than in older subjects. The blood half-life of CS tended to be longer than that of IPM. 3. Cumulative urinary recovery rates of CS were greater than those of IPM, cumulative urinary recovery rates tended to be greater in older neonates and premature infants than younger subjects. 4. One hundred and thirteen patients were treated for bacterial infections with IPM/CS and 32 patients were treated prophylactically. Daily doses of IPM/CS ranged from 9 mg/9 mg/kg to 150 mg/150 mg/kg. 5. Clinical efficacies of IPM/CS were evaluated in a total of 56 patients with identified etiologic pathogens. The efficacy rate was 98.2% with 33 patients rated as excellent, 22 patients as good and 1 patient as fairly good. (Diagnoses were sepsis in 10 patients and meningitis in 2 patients, etc.) Fifty-seven patients with no identified etiologic pathogens were rated as excellent for 22 patients, good for 34 patients and fairly good for 1. The efficacy rate in these patients was 98.2%. Thirty-two patients were treated prophylactically and the results obtained were satisfactory. 6. Bacteriologically, the eradication rate was 94.5% in 56 patients; i.e., 52 were eradicated, 2 were decreased, 1 persisted and 1 was unknown. 7. Adverse effects were observed in 7 (4.4%) of 160 patients, i.e., 2 patients had diarrhea and 2 patients had rash, etc. Abnormal laboratory data considered related to the therapy occurred in 28 (17.6%) of 159 patients, with 10 patients with eosinophilia (6.3%) and elevation of GOT and/or GPT, etc. All these were non serious, and all values returned to normal after discontinuance of therapy. An abnormal prothrombin (PIVKA II) was observed in 1 of 10 patients tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

[Overall clinical evaluation of cefpodoxime proxetil against infections in pediatric fields].

Dry syrup and tablet of newly developed cefpodoxime proxetil (CS-807, CPDX-PR) was investigated in the departments of pediatrics of 17 institutes and their related hospitals. 1. Pharmacokinetics of CPDX-PR in pediatrics were investigated. Peak blood levels of CPDX at dose levels of 3 mg/kg and 6 mg/kg were 2.24 +/- 0.21 and 4.68 +/- 0.54 micrograms/ml, respectively, in fasting and 1.65 +/- 0.07 and 3.71 +/- 0.41 micrograms/ml, respectively, after meal. Urinary recovery rates in 6 hours were 31.2 +/- 2.2% of dose in average. 2. Clinical efficacies of CPDX-PR on various infectious diseases were studied in 748 cases. Clinical efficacy rate in 499 cases with causative bacteria isolated was 94.6%: efficacy rates for individual infections were 96.8% (120/124) for tonsillitis, 96.0% (96/100) for urinary tract infection, 93.5% (58/62) for pneumonia, 92.4% (61/66) for impetigo, 100% (32/32) for scarler fever and 93.2% for pharyngitis or laryngitis. Bacteriological eradication rate for Gram-positive organisms was 91.0% (244/268); and for Gram-negative organisms, 89.7% (210/234). The clinical efficacy rate for cases which were non-responsive to previous antibiotic therapy was 88.1% (74/84). 3. Side effects and clinical laboratory findings were investigated in 779 cases. Two each of vomiting, loose stool and rash, 10 of diarrhea and 1 of diarrhea associated with candidiasis were reported, but no serious side effects were noted. There was no serious laboratory test abnormality except slight elevations of eosinophile, platelet, transaminase or prolongation of prothrombin time, totalling 34 occurrences.

Administration, Oral↗

[Multiple myeloma in a patient with primary hyperparathyroidism].

A 50-year-old man presented with knee pain and general fatigue and was found to have severe hypercalcemia and renal failure. Hyperparathyroidism was suspected by hypercalcemia and a nodular lesion of the thyroid gland with CT-scan of the patient's neck. Exploration of the neck disclosed two slightly enlarged parathyroid glands. After surgery, the patient's serum calcium levels remained normal for two weeks, but after that his serum calcium levels rose again and renal failure continued. So needle biopsy of the kidney was enforced, and myeloma of the kidney was suspected. Multiple myeloma was diagnosed by bone marrow puncture.

Humans↗

[Clinical evaluation of sulbactam/ampicillin in the pediatric infections].

Sulbactam/ampicillin (SBT/ABPC) was administered to 33 pediatric inpatients with 34 bacterial infections. Clinical efficacies were judged to be good in 33 cases (97.1%) out of 34 which included 13 cases of 14 with infections caused by beta-lactamase-producing strains of organisms, and successfully cured by this drug. There were no particular side effects to comment except some cases of diarrhea and loose stool. These results indicated that SBT/ABPC would be useful in the treatment of pediatric infections as a first choice of drug. Serum half-lives of ABPC and SBT were 0.79 hour and 1.02 hours, respectively, hence, q.i.d. dosage regimen would be appropriate.

Age Factors↗

[Pharmacokinetic, bacteriological and clinical studies on imipenem/cilastatin sodium in neonates].

Pharmacokinetic, bacteriological and clinical studies on imipenem/cilastatin sodium (IPM/CS) were performed in neonates. The results were as follow: 1. A total of 27 patients consisting of 17 mature and 10 immature infants were treated with IPM/CS. Each dose was 20 mg/20 mg/kg, and it was administered 2 approximately 3 times daily, in a 1-hour intravenous drip infusion for 3 approximately 12 days. The clinical efficacy of IPM/CS in 10 patients with bacterial infections (2 with sepsis, 3 with suspected sepsis, 2 with pneumonia, 2 with urinary tract infection and 1 with acute omphalitis) was evaluated as excellent in all patients, with an efficacy rate of 100%. All 5 causative organisms found in 5 patients (Staphylococcus aureus in 1, Staphylococcus epidermidis in 1, Escherichia coli in 2 and Flavobacterium meningosepticum in 1) were eradicated. Among 27 patients administered IPM/CS, adverse reactions were observed in 2 patients. These were rash and diarrhea. As for abnormal laboratory test values, elevations of GOT and GPT were observed. 2. MICs of IPM against 14 clinical isolates (S. epidermidis 1, S. aureus 6, Streptococcus agalactiae 4, E. coli 1, Enterobacter cloacae 1 and F. meningosepticum 1) from neonatal patients with bacterial infections were examined. IPM showed good antibacterial activity comparable to that of cefotaxime against S. agalactiae; however, the activity against methicillin-resistant S. aureus was poor. 3. Serum levels of IPM and CS were investigated in a total of 22 patients consisting of 15 mature and 7 immature infants after 20 mg/20 mg/kg of IPM/CS was administered. IPM and CS produced peak serum levels at the end of the drip infusion. In mature infants, peak serum levels of IPM and CS were 31.8 micrograms/ml (17.1 approximately 59.0 micrograms/ml) and 59.9 micrograms/ml (35.6 approximately 99.0 micrograms/ml), respectively. In low birth weight infants, these were 25.0 micrograms/ml (16.8 approximately 41.8 micrograms/ml) and 55.2 micrograms/ml (33.8 approximately 82.4 micrograms/ml), respectively. Half-lives of IPM and CS were 1.0 approximately 2.7 hrs. and 0.9 approximately 7.4 hrs. in mature infants, and 1.6 approximately 3.0 hrs. and 1.3 approximately 9.7 hrs. in immature infants, respectively. Generally the longer half-lives were observed in the younger neonates. Serum levels of CS remained higher and half-lives of CS were longer than those of IPM. The pharmacokinetics in neonates were different from those in adults or children.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

[Clinical evaluation of a new oral cephem, cefpodoxime proxetil in children].

Cefpodoxime proxetil (CPDX-PR, CS-807) was evaluated for its efficacy, safety and pharmacokinetics in children. CPDX-PR was effective in 93.6% of 47 cases with respiratory tract, middle ear, skin or urinary tract infections. Twice or 3 times daily administration of 3 mg/kg each was sufficient to treat streptococcal pharyngitis and Haemophilus influenzae infections. No severe adverse reaction was encountered in 52 cases treated with CPDX-PR. The serum half-life was approximately 2.17 +/- 0.24 hours after oral administration.

Administration, Oral↗

Identification of a polypeptide secreted by human breast cancer cells (MCF-7) as the human estrogen-responsive gene (pS2) product.

Human epidermal growth factor-like immunoreactive factor (designated as EGF-LI) synthesized and secreted by human breast cancer cells, strain MCF-7, was isolated in pure form. Thirty-seven micrograms of EGF-LI was purified by anion-exchange, gel permeation, and reverse-phase high-performance liquid chromatography from 2 liters of serum-free medium conditioned by the cells. The sequence of the first 36 amino acids from the N-terminus was determined with a gas-phase protein sequencer. Computer-assisted screening revealed, quite unexpectedly, this sequence to be completely identical to that of the translational product encoded by pS2, the human estrogen-responsive gene, over the region extending from residue 25 to 60 (Jakowlew, S. B. et al. (1984) Nucleic Acids Res., 12, 2861-2878).

Amino Acid Sequence↗

Quantitative measurement of renal function using Ga-68-EDTA.

We studied renal function using a positron emission tomography with C15O gas and 68Ga-EDTA in 6 normal subjects (male, 21-77 years old). The blood volume (ml/100 g (kidney] was 19.2 +/- 1.8 for the one 21 years old subject and 11.8 +/- 2.0 for the rest (65-77 years old). The glomerular filtration rate (ml/min/100 g (kidney] was 57.8 +/- 1.1 for the 21 years old subject and 30.4 +/- 2.8 for the rest.

Aged↗

[Studies on susceptibility of isolated organisms from pediatric infections against various antimicrobial agents].

Twelve oral antimicrobial agents were tested for their antimicrobial activities against causative organisms isolated from pediatric infections. Activities of these antimicrobial agents against Streptococcus pyogenes were also examined in relation to T-antigen typing of the species. The results of the investigation are summarized as follows. 1. Against Staphylococcus aureus, rokitamycin (RKM), josamycin, ofloxacin, minocycline exhibited strong antimicrobial activities, and few strains of S. aureus showed resistance to these antimicrobial agents. More strains exhibited resistance to erythromycin (EM) than to other macrolide antibiotics (MLs) examined. Amoxicillin (AMPC)-resistance was often observed also. 2. Against S. pyogenes, beta-lactam antibiotics (beta-lactams) and RKM had MIC80 of 0.20 microgram/ml or below, and no resistant strains of this organism were observed against these antibiotics. Only 2 resistant strains (2.0%) of S. pyogenes to MLs were detected, but resistance to tetracyclines (TCs) was observed at a high frequency, with 71.4% or more strains among T-4, T-6, T-12 and T-28 antigen types exhibited resistance to TCs. Among the 21 strains of T-12 antigen type examined, only one strain (4.8%) was found resistant to MLs. These observations suggested that the reduction in the frequency of ML-resistant strains was not due to the reduction in the number of T-12 antigen type strains but due to losses of resistance factors against MLs of plasmids. 3. Antibacterial activities of beta-lactams and MLs against Streptococcus pneumoniae strains were good, similarly to activities against S. pyogenes. But many strains of S. pneumoniae were resistant to TCs. 4. New quinolone antimicrobial agents (quinolones) showed excellent activities against Branhamella catarrhalis strains with EM and RKM showing the next best activities. The number of resistant strains against quinolones, however, seemed to be on an increase. 5. Quinolones had strong antimicrobial activities against Haemophilus influenzae, few strains of which showed resistance to quinolones. AMPC had the next best activity, but approximately 10% of H. influenzae exhibited resistance to this antibiotic. 6. Against Campylobacter spp., quinolones and MLs showed the best activities with MIC80 values at or below 0.25 microgram/ml, and no resistant strains of the species against these antimicrobial agents were observed. Fosfomycin and TCs showed somewhat inferior activities to quinolones and MLs, with beta-lactams showing still lower activities. 7. Only few strains of Mycoplasma pneumoniae and Chlamydia trachomatis were examined, but MLs and TCs appeared to be effective against these organisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

[Pharmacokinetic and clinical studies on the use of ceftizoxime in premature and newborn infants. The Chemotherapy Research Group for Mother and Child].

A pharmacokinetic and clinical study of ceftizoxime (CZX), a newly developed cephem antibiotic intended for parenteral use, was conducted in premature and newborn infants, and resulted in the following findings. 1. Pharmacokinetics (1) Average serum half-lives (T 1/2) following a one shot intravenous dose of 20 mg/kg of CZX to mature and premature newborn infants in age groups of 0-3, 4-7, 8-14, and 15-30 days were: 4.14, 3.01, 2.57, and 1.98 hours (for mature infants) and 5.26, 4.59, 3.71, and 2.64 hours (for premature infants), respectively, decreasing with ages in days of the infants. (2) Average T 1/2's after a one shot 10 mg/kg dose was similar to that after a 20 mg/kg dose. Serum concentrations of CZX were dose-dependent. (3) T 1/2 after 1-hour intravenous drip infusion revealed a same trend after one shot injection. (4) Urinary in the first approximately 6 hours recoveries following a 20 mg/kg one shot dose to mature and premature newborn infants were as follows: 35% (0-3 days old) and 45-55% (4 days old and older) in mature infants and 30% (0-3 days old) and 45% (4 days old and older) in premature infants. 2. Therapeutic effectiveness (1) The subjects examined were 112 newborn infants consisting of 83 with infections and 29 who received CZX for prophylaxis. The 83 infants had 86 cases of infections, which were classified as A, when the causative organisms were identified and as B, when the causative organisms were not identified. Rates of therapeutic effectiveness were 95.0% for group A and 95.7% for group B. Bacteriological effectiveness were studied on 41 strains isolated from group A, and were as high as 89.5% for Gram-positive organisms and 95.5% for Gram-negative organisms. The rate of successful prophylaxis for the 29 infants was 96.6%. (2) Side effects did not occur among the 120 newborn infants. Laboratory tests with abnormalities included leukopenia, neutropenia, eosinophilia, thrombocytosis and increased GOT or GPT. These pharmacodynamic and clinical findings have fully substantiated the satisfactory therapeutic usefulness of CZX in both the treatment and prevention of neonatal infections in the usual dose of 20 mg/kg, which is to be given b.i.d. for infants up to 3 days old; b.i.d. or t.i.d. for infants 4 to 7 days old, and t.i.d. or q.i.d. for infants 8 days old and older. The drug can be given in a daily dose as high as 120 mg/kg when infection is severe.

Bacterial Infections↗

[Pharmacokinetic and clinical studies of ceftizoxime in the perinatal period. The Chemotherapy Research Group for Mothers and Children].

Pharmacokinetic and clinical studies of ceftizoxime (CZX) in the perinatal period gave the following results: 1. Peak concentrations of CZX in the maternal serum, umbilical cord serum and amniotic fluid in mothers after one intravenous injection of 1 g were, respectively, 70.2 micrograms/ml at 0 hour; 15.7 micrograms/ml at 0.5 hour; and 10-30 micrograms/ml at 3-6 hours. Concentrations of CZX in the neonatal serum were 0.87-13.5 micrograms/ml during 6-14 hours after parturition. The mean concentration of CZX in the milk in 1-8 hours after injection was less than 0.32-0.52 microgram/ml. 2. Good or excellent clinical efficacy was obtained in 28 of the 29 patients with perinatal infections, with an efficacy rate of 96.6%. Prophylactic effectiveness was obtained in 14 of the 15 patients, with an efficacy rate of 93.3%. 3. No side effects were observed in 44 cases. GOT and GPT values increased slightly in 1 patient. No abnormal values in total serum bilirubin or other parameters were found in any neonates after parturition. 4. The above results suggest that CZX is safe and effective for the treatment and prophylaxis of infection in the perinatal period.

Adult↗

[Pharmacokinetics and clinical evaluation of ceftriaxone in neonates].

A parenteral cephem antibiotic ceftriaxone (CTRX) was studied for its pharmacokinetic features and clinical efficacy and safety in various infections in neonates including premature infants at 11 institutions associated with Japan Perinatal Infection Research Group. The following results obtained are summarized as follows. 1. Following single intravenous bolus injections with 10 and 20 mg/kg of CTRX, serum levels of the drug at 30 minutes post-dose 36-42 micrograms/ml and 46-76 micrograms/ml, respectively, and those at 12 hours post-dose were 10-14 micrograms/ml and 13-21 micrograms/ml, respectively, in a total of 105 neonates. Serum levels detected were on very gentle descending curves. 2. Half-lives (T 1/2) of the drug in serum were significantly prolonged in 0-3 day age groups of both mature and premature infants: it was especially long in premature infants with age of 0-3 days; i.e., 17.1 hours. There was no difference in T 1/2 between the 4-7 day and 8-28 day age groups. 3. Urinary excretion rates were 20-30% in the first 6 hours post-dose and 30-40% in 12 hours post-dose, in 80 neonates examined. 4. Clinical efficacy: Clinical efficacies were evaluated in 112 of 168 enrolled excluding infants with 90 days of age or older, who were treated for prophylaxis and unevaluable cases. The safety was evaluated in 161 of the 168. (1) Demographic background of the 112 cases: The 112 cases were composed of 89 neonates with ages of 28 days or younger, 21 premature infants, 57 males and 55 females. The drug was given to 102 of the cases by intravenous bolus injection, with 81 cases administered twice a day and 97 cases receiving 10-50 mg/kg a day. (2) Efficacy rate in the 112 cases: In 60 cases for whom causative pathogens were identified the efficacy rate was 90.0% in total (excellent: 31/60; good: 23/60); efficacy rates of 87.5% were obtained in 8 cases with purulent meningitis and 90.9% in 11 with septicemia. In 52 with causative pathogen not identified, the efficacy rate was 96.2% in total (excellent: 21/52; good: 29/52). (3) Adverse reaction: Adverse reactions were noted in 14 of the 161 cases where the safety was evaluated (8.7%). These reactions included diarrhea in 11, vomiting in 2 and exanthema in 1. Abnormalities in laboratory test values were observed in 25 of the 152 cases (16.4%). They included eosinophilia in 14, elevated GOT in 4 and thrombocytosis in 3 etc.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

[Clinical evaluation of aztreonam against pediatric purulent meningitis].

A monotherapy of aztreonam (AZT) was applied to 9 male and 3 female pediatric patients of ages ranging from 2 months to 8 years and 11 months with serious purulent meningitis. The results are summarized as follows: 1. Daily dosages of 134 to 400 mg/kg were given 3 to 4 times a day for 10 to 28 days. 2. The isolated pathogens were Neisseria meningitidis in 2 cases, Escherichia coli in 3 cases, Haemophilus influenzae in 6 cases, but the pathogen of the last case was unknown. In this case, the patient had myelomeningocele and suffered from recurrent purulent meningitis. 3. Clinical effect was "excellent" in 5 of 12 cases, "good" in 7 cases and efficacy rate was 100%. Microbiological tests were performed on 9 cases during the course of treatment and bacterial elimination rate was 100%. All the pathogens were eliminated in 72 hours. 4. One case of diarrhea was observed, but the diarrhea started before the administration of AZT and was stopped after the AZT treatment. A slight elevation of GOT value was observed in 1 case but the value returned to the initial level promptly after the treatment was completed. It is considered that AZT is highly useful for purulent meningitis caused by Gram-negative pathogens such as H. influenzae, E. coli and N. meningitidis.

Age Factors↗

[Appraisal of rokitamycin in the pediatric field].

In a study of rokitamycin (RKM) dry syrup for its usefulness in pediatric infections, the following results were obtained: 1. Frequencies of RKM-resistant strains among fresh isolates from sick children were very low, and 4.4% of 68 isolates of Staphylococcus aureus, 4.2% of 48 isolates of Streptococcus pneumoniae, and none of 96 isolates of Streptococcus pyogenes were found to be RKM-resistant. 2. Hypo- to achlorhydria was found in 2 (3.77%) of 53 children. 3. When children were administered once orally with 5, 10 and 15 mg/kg of RKM dry syrup at fasting, mean peak values of plasma concentration were 0.25, 0.55 and 0.74 micrograms/ml with a T1/2 (beta) of 2.18, 1.97 and 2.00 hours, respectively. Urinary recovery rates during the first 0-6 hours were quite low, and values were 1.21, 1.38 and 2.23%, respectively. 4. The clinical efficacy of RKM dry syrup was studied on children chiefly with acute pneumonia, mycoplasmal pneumonia and tonsillitis. Among 379 children from whom pathogens had been determined, responses to the treatment were excellent in 186, good in 144, fair in 24, poor in 20 and unknown in 5 patients, the overall efficacy rate being 88.2%. Among all 598 treated patients, including those with undetermined pathogens, responses were excellent in 247, good in 269, fair in 42, poor in 35 and unknown in 5 patients, the efficacy rate being 87.0%. 5. The clinical efficacy of the drug in treating Chlamydia infection in 12 patients including a Chlamydia carrier and the clinical efficacy in treating Campylobacter enteritis in 36 patients were studied. All the cases showed "good" responses. Among 66 patients with mycoplasmal pneumonia, responses were excellent in 33 and good in 27 patients, with an efficacy rate of 90.9%. 6. The optimal dose of RKM dry syrup seemed to be in the range between 20 and 40 mg/kg. It appeared, however, that a dose of about 40 mg/kg would be required to eradicate the pathogen from the pharynx in S. pyogenes infection. 7. Adverse reactions to RKM dry syrup were found in 9 (1.45%) of 622 patients. The reactions were gastrointestinal symptoms except eruption occurred in 1 patient, but they were all mild. Laboratory examinations revealed eosinophilia in 19 and abnormal hepatic enzyme activities in 8 of 455 patients studied, but such abnormalities were all transient and mild.

Bacterial Infections↗

[Clinical and pharmacokinetic studies of rokitamycin in children].

Rokitamycin dry syrup (RKM), a new macrolide antibiotic preparation, was evaluated for its safety, efficacy and pharmacokinetics in 19 children. RKM was effective in mycoplasmal pneumonia, Chlamydia trachomatis pneumonitis and Campylobacter gastroenteritis. Efficacies of RKM in streptococcal pharyngitis and Haemophilus influenzae pneumonia, however, were insufficient. Pharmacokinetic observations seemed to indicate that RKM achieved higher blood concentrations than older macrolides, but a large individual variation was observed. Diarrhea which was the only type of side effect observed in our cases, was encountered in 2 of 17 evaluable cases. From these data, RKM seems to have a place in the treatment of pediatric infectious diseases.

Campylobacter Infections↗

[Clinical evaluation of sultamicillin fine granules in pediatric infections].

Sultamicillin fine granules (SBTPC), a mutual prodrug of sulbactam (SBT) and ampicillin (ABPC), were administered to 16 pediatric patients with bacterial infections. The efficacy rate was 93.3%. MICs (10(6) cells/ml) of SBTPC against beta-lactamase non-producing strains were not significantly different from those of ABPC, and ranged from less than or equal to 0.05 to 1.56 micrograms/ml. MICs of SBTPC, however, were 2-4 fold smaller than MICs of ABPC against beta-lactamase producing strains. Diarrhea and loose stool as side effects were observed in 4 (25%) of 16 patients, but none of them were severe. After oral administration of SBTPC (10 mg/kg), serum levels of ABPC and SBT peaked at 3.41 micrograms/ml and 2.43 micrograms/ml after 0.6 hour, and declined with half-lives of 1.79 and 1.00 hours, respectively.

Age Factors↗