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H Sakata

Publications and source records attributed to H Sakata.

At least 145 records · Page 8Linked to original sources

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

Pharmacokinetic and clinical evaluations in pediatrics were made on meropenem (SM-7338, MEPM), a new parenteral dehydropeptidase-1 stable carbapenem used without any inhibitors, at 33 medical institutions. The results are summarized as follows. 1. Pharmacokinetic studies. MEPM at a dose of 10, 20, or 40 mg/kg was administered to 53 children by 30-minute drip infusion. Peak plasma concentrations (Cmax's) and plasma half-lives (T1/2's) of these doses were 28.5, 47.2 and 130.0 micrograms/ml, and 0.80, 0.93 and 0.94 hours, respectively. A clear dose response was observed in Cmax's and T1/2 values were quite similar to those observed in adults. In the first 6 hours after administration, 54.4 to 68.1% of the administered drug was recovered in urine. The cerebrospinal fluid (CSF) levels of MEPM in patients with purulent meningitis were 0.13 microgram/ml at a dose of 6 mg/kg, and 0.64 to 4.22 micrograms/ml at a dose of 29 to 44 mg/kg within day 4 of onset. The penetration rate of MEPM showed an intermediate value among those for other cephalosporin antibiotics. 2. Clinical study. Clinical efficacies of MEPM were evaluated in 389 cases. The most common doses used were 10 to 20 mg/kg/once, 2 to 3 times a day. The maximum dose was 173 mg/kg/day q.i.d. MEPM gave "excellent" or "good" responses in 242 (97.6%) out of 248 cases in which causative organisms were documented and in 134 (95.0%) out of 141 cases in which causative organisms were not identified. Clinical efficacy rates were 100% in 11 patients with purulent meningitis, 85.7% in 7 with septicemia, 98.8% in 173 with pneumonia, and 100% in 65 with UTI. Bacteriologically, 260 strains (96.7%) out of 269 strains were eradicated by MEPM treatment. Eradication rates were 89.2% for Staphylococcus aureus (37 strains) and 100% for Streptococcus pneumoniae (35 strains). The overall eradication rate for Gram-positive bacteria was 94.6%. Among Gram-negative bacteria, 98.3% out of 172 strains were eradicated. The eradication rate of Haemophilus influenzae (73 strains) was 98.6% and Pseudomonas aeruginosa (11 strains) was 90.9%, and all of Branhamella catarrhalis (15 strains), Escherichia coli (42 strains), and Klebsiella pneumoniae (6 strains) were eradicated. Out of 84 cases for which previous antibiotic therapies of 3 days or longer were not successful, MEPM gave "excellent" or "good" responses in 77 cases (91.7%) and excellent bacteriological responses (95.7%).(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗

[Clinical and pharmacokinetic evaluation of meropenem and its effect on fecal flora in children].

Forty-five children were treated with meropenem (MEPM) and the clinical efficacy and side effects were evaluated. The ages of the patients ranged from 1 month to 9 years and their body weights from 5.2 to 25 kg. Doses given were 17.2-45.5 mg/kg every 6 to 8 hours for 2 to 24.5 days. Those patients who responded to the MEPM treatment included 15 children with pneumonia, 7 with pharyngitis, 3 with cervical lymphadenitis, 3 with cellulitis, 10 with urinary tract infections and 4 with other infections. Among 42 children, the results were excellent in 29, good in 12 and fair in 1. The drug was well tolerated, although slightly elevated serum concentrations of transaminases occurred in 5 patients, eosinophilia in 2 patients, and neutropenia in 1 patient among 45 patients examined. The pharmacokinetic studies on MEPM were done in 6 patients. Their ages ranged from 2 to 9 years and body weights from 14.5 to 23.2 kg. In 4 patients, plasma concentrations at the end of 30 minutes drip infusion of 20 mg/kg were 29.28 +/- 10.29 micrograms/ml and those 3 hours later were 0.49 +/- 0.26 micrograms/ml. Serum elimination half-lives of the drug were 0.66 +/- 0.12 hours in these patients. Excretion rates of this drug into urine in the first 6 hours after initiation of drug administration were 53 and 40% in 2 of these patients. In 2 patients with 35 and 44 mg/kg of drug administration, plasma concentrations were higher than those given 20 mg/kg of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

[Charge distribution of serum IgA in IgA nephropathy with episodes of macrohematuria].

In order to examine further the role of the electrical change of IgA in the pathogenesis of IgAN, we studied the charge distribution of serum IgA in IgAN with episodes of macrohematuria. Blood samples were taken from 20 IgAN patients during bouts of macrohematuria and again more than 3 months later. Twenty healthy adults were used as controls. All samples were focused by Multiphor II flatbet electrofocusing unit apparatus (LKB) on an agarose gel (0.8% isogel agarose-EF, 2.5% pharmalyte 4.0-6.5). The focused gels were incubated with polyclonal goat anti-human IgA and were washed in several changes of saline for 48 hours. Immunofixed materials remaining in the gels after washing were fixed and stained with coomassie brilliant blue R250. The stained gels were analysed by densitometry. The relative areas of the individual peaks and their proportional contributions to the total IgA spectrotype were determined by computer. The results were as follows: 1. The percentage of proportional contribution of IgA peaks (pI 4.7-5.15) in IgAN were higher in patients than in controls (p less than 0.01). 2. The percentage of proportional contribution of IgA peaks (pI 4.9-5.05) in IgAN at bouts of macrohematuria was higher than in the same patients when not undergoing episodes of macrohematuria (p less than 0.01). These results suggest that the excess amount of anionic IgA may contribute to the pathogenesis of IgAN.

Adult↗

B95a, a marmoset lymphoblastoid cell line, as a sensitive host for rinderpest virus.

We reported earlier that B95a, an Epstein-Barr virus-transformed marmoset B lymphoblastoid cell line, is more susceptible to infection with measles virus than other cells. The cell line also was found to be susceptible to infection with the lapinized Nakamura III (L) strain of rinderpest virus and various strains derived from it. The B95a cell line was therefore the only host cell system available for the propagation and quantification of the L strain. In contrast to the adaptation of the L strain to Vero cells which results in a diminution of virulence in rabbits, the propagation of the virus in B95a cells preserved the virulence and some other properties in rabbits. Furthermore, when Vero cell-adapted variants of the L strain with diminished virulence were serially passaged in B95a cells, virulence in rabbits was gradually regained.

Animals↗

Primary osteosarcoma of the ovary. A case report.

A case of primary osteosarcoma arising in the left ovary of a 75-year-old female is described. The chief complaint was a sensation of lower abdominal mass. An abdominal plain film showed a large calcified mass in pelvic region, and a preoperative diagnosis of "ovarian fibroma" was made. The excised tumor was divided into 4 pieces, resembling an oyster shell. Microscopically, the tumor fragments were composed of compact bone or woven bone with surrounding atypical osteoblasts and osteoclasts. The tumor was partly composed of numerous spindle cells with malignant osteoid or atypical chondroid formation, and diagnosed as "osteosarcoma". The cystic part of the lesion was lined with a single layer of columnar cells, but the tumor contained no other germ elements or stem cells, or malignant epithelium. Therefore, it is doubtful that this tumor originated from teratoma or malignant mixed mesodermal tumor, and we conclude that this ovarian osteosarcoma arose through a neoplastic change in ovarian stromal cells. The patient died 4 months after surgery due to intra-abdominal and intrathoracic dissemination of the tumor.

Aged↗

[Effects of cefixime and cefaclor on pharyngeal flora in children].

Influences of cefixime and cefaclor, oral antibiotics, were studied in 50 children (age range, 11 months to 13 years) with pharyngitis. Daily doses of cefixime were 6 to 10 mg/kg in 25 children and those of cefaclor were 40 to 50 mg/kg in 25 children. Pharyngeal swabs were taken before and after 3 to 7 days of the antibiotic treatment. Pathogenic organisms, such as Streptococcus pyogenes, Haemophilus influenzae and Streptococcus pneumoniae, were isolated in 14 children before and in 1 child after cefixime use. But these bacteria were isolated in 15 children before and in 9 children, and 3 strains of H. influenzae and 3 strains of S. pneumoniae were newly isolated after cefaclor use. An isolation rate of Gram-negative bacilli, such as Acinetobacter spp., were increased after use of cefixime. In both antibiotics, isolation rates of yeasts were slightly increased. An isolation rate of alpha-hemolytic streptococci was increased from 16% to 48% by cefixime treatment and from 24% to 52% by cefaclor treatment. The MIC50 of cefixime and cefaclor against alpha-hemolytic streptococci isolated after treatment was higher than that isolated before. Effects of cefixime and cefaclor was less extensive than that of ampicillin in previous reports.

Adolescent↗

[Mechanochemical solid state reactions of natural products for medicinal use containing hydroxyanthraquinone derivatives].

In commercial powdered natural products for medicinal use containing various combined forms of hydroxyanthraquinone derivatives such as Sennae Folium, Cassiae Semen, Rhei Rhizoma and Aloe a considerable amount of stable free radicals (ca. 10(17)-10(18) spin/g) was found to be contained by use of electron spin resonance (ESR) spectral measurements. It was also found that the vibratory milling of such powders in a metallic vessel enhanced the ESR spectral intensities, demonstrating the occurrence of mechanoradical formation. Separate experiments also demonstrated that the vibratory milling of various kinds of powdered hydroxyanthraquinone derivatives mixed with calcium oxalate has produced the mechanoradicals effectively, but they decayed gradually on standing at room temperature. It was suggested, therefore, that the mechanoradicals formed in the above natural products are metal complexes of the corresponding semiquinone anion radicals induced by solid state one electron transfer mechanism from the active metal surface, part of which is further immobilized in polymeric fibers or the like in the plant tissues.

Anthraquinones↗

[A clinical evaluation of fetal wellbeing--based on fetal behavior with emphasis on conditions contributing to the dissociation of behavior].

The recent developments in Medical Electronics (M.E) have led to the possibility of noninvasive methods of evaluating conditions which previously were considered to be a "Black Box". Among the conditions now evaluable are fetal and placental morphology and functional aspects including fetal movements and behavioral studies. This has led to the discovery that the progressive development of the fetal Central Nervous System (CNS) is concurrent with the progression of fetal maturity and attainment of synchronicity of various fetal activities. This has led to the clinical application of ME for the evaluation of various fetal parameters in an attempt to assess fetal wellbeing. However in the presence of increase in frequency and strength of the various fetal activities with the advance of pregnancy, there is in fetuses of less than 28 weeks of development no synchronicity of the fetal activities, and in IUGR and fetuses under various forms of stress, the relationships between CNS development and fetal activity may become misaligned, or dissociated leading to the pitfall of misdiagnoses. Thus, in order to better understand the effects of chronic stress on the fetus we ran long term studies on pregnant ewes using physiologic and biochemical evaluations as our parameters for assessment. We observed a convergence of the various fetal behavior parameters with advancement of fetal age which we termed as the achievement of association of fetal behavior. However, when fetal hypoxemia is induced as a chronic condition, the phenomenon of convergence of the various behavioral parameters is inhibited, leading to a so called dissociation of those functions. Further, the greater the severity of the hypoxemia (stress), the greater the inhibitory effect on the convergence of the various activities, thus the greater the dissociation. A possible reason for this effect is the inhibition of respiratory activity. In order to clarify the hypothesis stated above, we induced hypoxemia in fetal lambs, as well injecting them with various materials. We found that AVP which increases in hypoxemia has no effect on pulse rate, but does inhibit respiratory activity, a clear representation of dissociation of fetal behavior. In conclusion, if fetal behavior is to be used as a method for evaluating wellbeing, it is necessary to also assess the convergence or association of the various behavioral parameters in order for it to be utilized as a clinical tool.

Animals↗

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

We studied pharmacokinetics and clinical effects of 5% and 10% fine granules of cefdinir (FK 482, CFDN), a new oral cephalosporin, in the pediatric field and the following results were obtained. 1. Pharmacokinetics (blood concentration and urinary excretion) Pharmacokinetics of CFDN in 163 children was investigated. Cmax and T 1/2 were 0.92 +/- 0.45 micrograms/ml and 1.95 +/- 1.06 hours, respectively, in the fasting state, and were 0.63 +/- 0.29 micrograms/ml and 2.26 +/- 0.65 hours, respectively, in the non-fasting state, at a dose level of 3 mg (potency)/kg. At a dose level of 6 mg (potency)/kg, Cmax and T 1/2 were 1.29 +/- 0.49 micrograms/ml and 2.11 +/- 1.85 hours, respectively, in the fasting state and were 1.28 +/- 0.48 micrograms/ml and 2.01 +/- 0.84 hours, respectively, in the non-fasting state. Data of Cmax and AUC showed that blood concentration of the drug depended on dose levels. Urinary recovery rates in the first 8 hours were 20.5 +/- 8.8% in the fasting state and 14.8 +/- 5.9% in the non-fasting at a dose level of 3 mg (potency)/kg and 16.5 +/- 6.7% and 17.8 +/- 2.4%, respectively, at 6 mg (potency)/kg. 2. Clinical effects Clinical effects of CFDN on various infections were studied in 612 children who were treated with 5% fine granules of CFDN (5% granule group) and in 208 with 10% fine granules of CFDN (10% granule group). CFDN granules were administered mainly at daily doses of 9.0-18.0 mg (potency)/kg in 3 divided portions. Clinical efficacy rates in 428 children of the 5% granule group and in 159 of the 10% granule group from whom causative bacteria were isolated, were 94.9% and 96.2%, respectively. The clinical efficacy rates for patients who were responsive to previous antibiotic therapy were 91.2% in the 5% granule group and 100% in the 10% granule group. Bacteriological eradication rate was 82.1% for 491 strains in the 5% granule group, and was 84.0% for 175 strains in the 10% granule group. The incidences of side effects were 3.9% (24/608) in the 5% fine granule group and 5.8% (12/206) in the 10% granule group. All of the side effects were slight gastrointestinal disorders, and no serious side effects were found. As for clinical laboratory test results, slight elevations of eosinophile, platelet or transaminase were observed. Based on the above results, it is considered that the appropriate dose levels of CFDN for pediatric infections ranged from 9.0 to 18.0 mg (potency)/kg a day, divided into 3 portions.

Administration, Oral↗

[Flomoxef in neonates and young infants; clinical efficacy, pharmacokinetic evaluation and effect on the intestinal bacterial flora].

Forty-three newborn and young infants including 13 low-birth-weight (LBW) infants were treated with flomoxef (FMOX) and the clinical efficacy and side effect were evaluated. The ages of the patients ranged from 0 to 99 days, and their body weights from 797 to 9,000 g. Dose levels were 10.5 to 48.5 mg/kg every 6 to 8 hours for 3 to 12 days. Those patients who responded to the FMOX treatment included 8 infants with sepsis, 14 with suspected sepsis, 6 with intrauterine infection, 2 with meningitis, 7 with pneumonia, 1 with staphylococcal scalded skin syndrome, 1 with epididymitis and 4 with urinary tract infections. The results were excellent in 17 and good in 22 patients. The drug was well tolerated, although diarrhea occurred in 2, slightly elevated serum concentrations of transaminases in 2, and eosinophilia and thrombocytosis in 1 patient each. Pharmacokinetic studies on FMOX with 20 mg/kg dose were done in 19 patients including 8 LBW infants. Serum concentrations at 15 minutes after intravenous bolus injection in five 1- to 6-day-old LBW, five 1- to 6-day-old and four 8- to 19-day-old mature infants were 52.6, 52.7 and 58.0 micrograms/ml, respectively, and those at 4 hours were 22.1, 13.3 and 5.2 micrograms/ml, respectively. Serum half-lives of the drug were 3.93, 2.29 and 1.62 hours, respectively, and excretion rates of this drug into urine in the first 6 hours after administration were 30.4, 45.1 and 58.7%, respectively. Mean serum concentrations just after intravenous 1-hour drip infusion in three 8- to 54-day-old LBW and two 8- and 10-day-old mature infants, were 31.5 and 18.9 micrograms/ml, respectively, and those at 4 hours were 15.3 and 4.3 micrograms/ml, respectively. Serum half-lives of the drug were 2.88 and 1.75 hours, respectively, and excretion rates of the drug into urine in the first 6 hours were 22.6 and 47.5%, respectively. The cerebrospinal fluid level at 3 hours after a dose was 7.09 micrograms/ml on the second day of treatment in a patient with Staphylococcus aureus meningitis receiving 50 mg/kg of the drug every 6 hours per day. Its level at 1 hour after a dose was 3.52 micrograms/ml on the 8th day of treatment in the same patient. The influence of FMOX on the fecal flora was studied in 7 patients. The characteristic pattern observed during the drug administration was the disappearance of Bifidobacterium, the decrease or disappearance of Enterobacteriaceae and the preservation of Streptococcus.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Parietal cortex neurons of the monkey related to the visual guidance of hand movement.

A class of neurons specifically related to hand movements was studied in the posterior parietal cortex while the monkeys manipulated different types of objects. We examined the neuronal activity during manipulation of objects by the hand in the light and in the dark. Fifty-five neurons were active during manipulation in the dark and were classified as "hand-movement-related" neurons. Of these, 38/55 (69%) cells were also influenced by the visual stimulus. Most of the hand-movement-related neurons were selective in the type of objects manipulated. Moreover, some of these cells were selective in the axis of orientation of the object. These results suggest that the hand-movement-related neurons of the parietal cortex are concerned with the visual guidance of the hand movement, especially in matching the pattern of movement with the spatial characteristics of the object to be manipulated.

Animals↗

Antibiotic susceptibility of type b Haemophilus influenzae and Streptococcus pneumoniae, and antibiotic concentration in cerebrospinal fluid.

Antibiotic susceptibilities of 38 type b Haemophilus influenzae and 28 Streptococcus pneumoniae strains isolated from cerebrospinal fluid, blood and other specimens between 1973 and 1988 were studied. Minimal inhibitory concentrations (MICs) of ampicillin against 10 beta-lactamase positive and 28 negative H. influenzae isolates were 32-64 and 0.25 micrograms/ml, respectively. The MIC of chloramphenicol against one of the beta-lactamase positive H. influenzae strains was 8 but MICs against the rest of the organisms were 0.5-1 micrograms/ml. MICs of cefotaxime, ceftriaxone and cefuroxime against all H. influenzae strains were 0.016, 0.008 and 0.5 micrograms/ml, respectively. No S. pneumoniae isolates were resistant to penicillin G and MICs of this drug were 0.016-0.032 micrograms/ml. MICs of cefotaxime, cefriaxone and cefuroxime against all S. pneumoniae strains were 0.016-0.032, 0.016-0.032 and 0.032-0.063 micrograms/ml, respectively. MICs of chloramphenicol against 15, 4 and 9 of S. pneumoniae isolates were 2, 8 and 16 micrograms/ml, respectively. Antibiotic concentrations in the cerebrospinal fluid of patients with bacterial meningitis after intravenous administration of ampicillin (50-70 mg/kg x 4/day), penicillin G (31-63 mg/kg x 4/day), cefotaxime (50 mg/kg x 4/day) and chloramphenicol (25 mg/kg x 4/day) were 4.70 +/- 1.83 (n = 11), 0.57 +/- 0.32 (n = 7), 4.97 +/- 2.60 (n = 9) and 8.52 +/- 3.54 micrograms/ml (n = 3), respectively. The initial choice of antibiotics in older children with bacterial meningitis is a combination of ampicillin (75 mg/kg x 4/day) and cefotaxime (50 mg/kg x 4/day) to cover ampicillin-resistant H. influenzae, S. pneumoniae, and Listeria monocytogenes in Japan. These antibiotics should be changed according to the causative organisms and their antibiotic susceptibilities.

Cephalosporins↗

K1 antigen, serotype and antibiotic susceptibility of Escherichia coli isolated from cerebrospinal fluid, blood and other specimens from Japanese infants.

K1 antigens, serotypes and antibiotic susceptibilities of Escherichia coli isolates from neonates and infants were investigated. The presence of K1 antigen was tested by the K1-specific phage method. The number of K1 positive strains was 27 (84%) of 32 isolates from cerebrospinal fluid, 11 (25%) of 44 from blood and 4 (22%) of 18 from other specimens. Fourteen (33%) of the K1 positive strains were serotyped as O16:H6, and 8, 7 and 5 were serotyped as O18ac:H7, O1:H7 and O7:H-, respectively. One of 5 of the K1 negative strains were distributed into 30 different combinations of O and H antigens. The ampicillin resistance rates were 19% in K1 positive strains and 45% in K1 negative ones. The incidence of chloramphenicol resistance was the same in K1 positive and negative strains (21%). Ampicillin resistance was not noted in O16:H6 strains, but the incidence of antibiotic resistance was high (65% to ampicillin and 53% to chloramphenicol) in the rough-type strains.

Antigens, Bacterial↗

Septicemia in immunocompromised children and their intestinal flora.

Quantitative fecal bacteriology was performed in eight immunocompromised children with septicemia. The most marked change observed was suppression of the anaerobic bacteria. In seven patients, the predominant organisms were aerobic gram-negative bacilli (GNB), and in six of these were the same as the causative organism of the septicemia. Thus, overgrowth of GNB in the gastrointestinal tract may result in invasion of the blood stream and septicemia in immunocompromised patients. To prevent this complication it is necessary to allow the normal intestinal flora to be maintained in these patients as long as possible. Antibiotics should therefore be prescribed with caution. For the same reason, use of immunosuppressive drugs should be kept to a minimum. Bacteriological examination of the stool and pharynx is useful in the management of immunocompromised patients.

Bacteria↗

Effects of aztreonam on fecal flora and on vitamin K metabolism.

The effects of aztreonam on fecal flora and on descarboxy prothrombin (PIVKA-II) in plasma and gamma-carboxyglutamic acid (Gla) in urine as an index of vitamin K metabolism were studied in seven children (age range, 2 months to 2 years) with urinary tract infections. Daily doses of aztreonam were 60 to 80 mg/kg. Stool specimens were obtained before the treatment, on days 3 to 5 of aztreonam use, and from 3 to 5 days after the cessation of treatment. The counts of enterobacteria decreased (P less than 0.01) and those of streptococci increased (P less than 0.05) during aztreonam treatment. The anaerobic organisms, especially bifidobacteria and bacteroides, showed no marked change. PIVKA-II and Gla were investigated before and during the treatment with aztreonam. PIVKA-II was not detected in seven patients before or during aztreonam use. There were no significant differences in the levels of Gla in urine before or during the treatment.

1-Carboxyglutamic Acid↗

Marmoset lymphoblastoid cells as a sensitive host for isolation of measles virus.

B95-8, an Epstein-Barr virus-transformed marmoset B-lymphoblastoid cell line, and its derivative B95a, capable of attachment to a substrate surface, were 10,000-fold more sensitive to measles virus present in clinical specimens than were Vero cells. B95-8 and B95a cells were thus thought to be useful host cells for the isolation of measles virus. Quantitation of measles virus present in clinical specimens showed that a large quantity of virus, exceeding 10(6) 50% tissue culture infective doses per ml of a nasal-swab eluate, is shed into secretions by patients with acute measles, consistent with the contagiousness of the disease. Measles viruses isolated in B95a cells differed in some biological properties from those adapted to Vero cells. First, the viruses isolated in B95a cells did replicate in Vero cells, but release into the fluid phase was less efficient than that of Vero cell-adapted viruses. Second, minor antigenic differences were found between virus strains isolated in B95a cells and those isolated in Vero cells from the same clinical specimens. Third, the viruses isolated and propagated in B95a cells caused clinical signs in experimentally infected monkeys resembling those of human measles. It was suspected that measles virus is subject to host cell-mediated selection and that the viruses grown in B95a cells are more representative of measles virus circulating among humans than are the viruses selected in Vero cells.

Animals↗