Search PubMed⌕ Search

Biomedical subjects

T Fujimoto

Publications and source records attributed to T Fujimoto.

At least 505 records · Page 28Linked to original sources

[Pharmacokinetic and clinical studies on cefmenoxime in neonates and premature infants].

Cefmenoxime (CMX) was administered by intravenous bolus injection to a total of 23 neonates and premature babies with aged 1 to 26 days at a dose of 10 or 20 mg/kg and their plasma and urine concentrations and urinary recovery rates were determined up to 6 hours after administration. In addition, for the treatment of bacterial infections, diagnosed or suspected, or for the prophylaxis of bacterial infections, the drug was administered to a total of 27 neonates, premature babies and infants, with ages of 0 day to 3 months. It was possible to evaluate therapeutic efficacy and prophylactic efficacy in 15 cases and 7 cases, respectively. In these cases, side effects and bacteriological effects and, in some of them, changes in laboratory test values were also investigated. The obtained results are summarized below. 1. At a dose level of 10 mg/kg (n = 7), peak plasma concentrations at 5 minutes after administration, were 42.6 microns/ml in neonates with ages of 15 to 21 days and 45.9 microns/ml in those with ages of 22 to 28 days in a group of less than 2,500 g b.w. (birth weight), and 36.9 microns/ml in neonates with ages of 4-7 days and 38.9 microns/ml in those of 8-14 days in the other group of greater than of equal to 2,500 g b.w., indicating no large differences among the 4 subgroups (each of the above concentration values is either the value for an individual when only one neonates was involved or a mean value when 2 or more neonates were involved. The same applies hereinafter). Though 1 exceptional case showed a biphasic change, its cause is unknown. Half-lives in the above-mentioned 4 subgroups were 1.5, 1.6, 2.4 and 1.9 hours, respectively. The half-life of 2.4 hours in 1 patient with an age of 5 days of the greater than or equal to 2,500 g b.w. group was longer than in any of the other 3 subgroups. 2. At 20 mg/kg (n = 16) dosage level, mean peak plasma concentrations were 63.8 microns/ml in the infants of 0-3 days, 68.1 microns/ml in those of 8-14 days and 59.4 microns/ml in those of 15-21 days in the group of less than 2,500 g b.w., and 109.9 microns/ml in the neonates aged 8-14 days and 79.7 microns/ml in those of 15-21 days in the group greater than or equal to 2,500 g b.w.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗

[Fundamental and clinical studies of cefsulodin in the neonates and premature infants].

Fourteen neonates and premature infants with ages ranging 1 to 28 days were intravenously given one shot injection of 20 mg/kg of cefsulodin (CFS). Plasma and urine levels and recovery rates of CFS were determined in the first 6 hours after administration. For prophylaxis of infection, a daily average dose of 52.8 mg/kg of CFS was injected intravenously to 3 neonates with ages ranging 2 to 16 days in 2 to 3 divided doses during an average period of 7 days. Along with observations of prophylactic effects on infection, side effects and abnormalities in laboratory test values were examined. The results obtained are summarized below: 1. Of the 9 patients with birth weight of 2,500 g or above, the plasma levels peaked in 6 patients at 5 minutes, in 2 patients at 15 minutes and in the other at 1 hour after administration, with peak levels ranging between 35.8 and 60.6 micrograms/ml. Subsequently, gradual decreases or bimodal tapering changes were noted in the plasma levels. The cause of the delay in the occurrence of maximum peak observed in the 3 patients at 15 minutes or 1 hour after administration and the cause of the appearance of bimodal tapering changes in 3 subjects are not known. A tendency was observed that the younger the age of subject was, the larger the AUC and the longer the half-life became. Half-lives in all 9 neonates were longer than those in average infants who were given intravenous injection at the same dose. 2. Of 5 patients with birth weight of less than 2,500 g, the determination of peak plasma levels was not performed in those within 7 days after birth. Plasma levels, however, were observed to reach their peaks in 4 patients at 5 minutes and in another at 15 minutes after administration, the levels ranging between 41.5 and 56.0 micrograms/ml. Subsequently to this, gradual decreases and bimodal tapering changes of plasma levels were noted. The cause of the delay in plasma levels to reach their maximum peaks values in the 1 patient to 15 minutes after administration and the cause of occurrence of bimodal tapering changes in the 2 patients are not known. A tendency was observed that the younger the age of subjects was, the larger the AUC and the longer the half-life became. This tendency was similar to that observed in the group with birth weight of 2,500 g or above.(ABSTRACT TRUNCATED AT 400 WORDS)

Cefsulodin↗

[A case of the thyroidea ima artery arising from the aortic arch].

The present report describes a case of the thyroidea ima artery observed in a 65-year-old Japanese male on dissection in 1988. The thyroidea ima artery arose from the aortic arch between the branchiocephalic trunk and the left common carotid artery. The thyroidea ima passed to the left lobe and isthmus of the thyroid gland for the supply of these. The inferior thyroid artery on the right side was of common type in its origin and course, though that on the left side was absent. Either of the superior thyroid arteries arose from the common carotid artery.

Aged↗

Flow cytometric determination with bromodeoxyuridine/DNA assay of sensitivity of S-phase cells to cytosine arabinoside in childhood acute lymphoblastic leukemia.

The percentages of S-phase cells in leukemic and normal bone marrow cells and their sensitivity to cytosine arabinoside (Ara-C) were determined by in-vitro bromodeoxyuridine (BrdUrd)/DNA analysis in children with acute lymphoblastic leukemia. The lymphoblasts during relapse showed a higher proliferating activity than at the time of the diagnosis. The sensitivity of S-phase cells to Ara-C was measured by the percentages of the residual S-phase cells capable of incorporating BrdUrd after incubation with various concentration of Ara-C (1 ng-10 micrograms/ml). A constant dose response was found in the normal bone marrow cells of disease-free children who were in complete remission with a marked reduction of the S-phase population at a concentration of 100 ng/ml. In the leukemic bone marrow cells, in contrast, there was a wide variation in sensitivity to Ara-C. The sensitivity did not correlate with the proliferating activity of leukemic cells. In two patients, there was a good correlation between in-vitro sensitivity and clinical response to Ara-C.

Adolescent↗

Abnormalities of calcium ion movement in platelets of patients with myeloproliferative disorders.

We investigated abnormalities in calcium ion influx in platelets of patients with myeloproliferative disorders (MPD). 45Ca2+ influx into the cytosol of MPD platelets was lower than that of normal controls. To determine whether the low Ca2+ influx is caused by a functional abnormality of membrane glycoprotein (GP) IIb-IIIa complex for Ca2+ channel or not, we investigated the Ca2+ influx through GP IIb-IIIa complex, which was reconstituted into liposomes. The purified GP IIb-IIIa complex from platelets of 5 patients was reconstituted into phospholipid liposomes. Ca2+ influx into the liposomes measured by fluorescence of intravesicular Fura-2 was lower in 2 of these patients. These findings corresponded with the results of intracellular calcium concentration after stimulation in these platelets. We concluded that functional abnormalities of GP IIb-IIIa is involved in the mechanism of impaired Ca2+ influx in MPD platelets.

Blood Platelets↗

[Salivary calculus of the parotid gland: report of a case].

We reported a case of parotid sialolithiasis. A man, aged 72, complained of swelling of the left buccal region accompanied by a sensation of inflammation. On diagnosis of sialolithiasis of the parotid gland, a surgical operation was performed with a small incision in the left cheek region. About one month after the operation, a salivary calculus was discharged spontaneously from the left buccal region. He recovered satisfactory without the formation of a parotid salivary fistula. Morphological observation on the salivary calculus was carried out using the scanning electron microscope (SEM).

Aged↗

[Autologous bone marrow transplantation as a measure against myelosuppression in cancer chemotherapy].

One hundred seventy-three patients were treated 256 times with chemotherapy supported by autologous bone marrow transplantation during the past 9 years. The two most commonly used protocols were (cyclophosphamide 1,600-2,400 mg/m2 + adriamycin 80 mg/m2 + ACNU 3 mg/kg) and (cyclophosphamide 1,600-2,400 mg/m2 + adriamycin 100 mg/m2 + CDDP 100-150 mg/m2). Among 115 patients in the therapeutic setting in which two courses were usually given, 75 were evaluable and the overall response rate was 42.7% with 12.0% CR rate. Breast and pediatric groups responded well; the response rate in breast cancer was 67.9% with 21.4% CR rate. Two patients with breast cancer who had multiple distant metastases and 2 pediatric patients are now alive with NED after 5 years of the treatment and seem to have been cured. The results in adjuvant settings have also been quite promising, e.g., 79.4% 5-year survival probability among breast patients mainly in stage III. Although drops of blood cell counts to the nadirs (WBC counts: less than 100-300) could not be prevented, the periods of myelosuppression appeared to have been effectively shortened so that the patients could be safely managed with intensified general supportive measures. Platelet counts are usually less affected, but the recovery is slower than for WBC counts. There were 13 patients who died within 10 weeks of the initiation of the treatment. Two of them succumbed to sepsis, and progressive disease was the cause of death in 8 patients whose terminal phases were undoubtedly affected by some infectious problems. We have shown that there are inverse relationships between infused numbers of CFU-GM and marrow recovery judged by the duration of neutropenia and the time required for neutrophils to recover over 500. Our recent laboratory experiments testing CFU-E, BFU-E and CFU-Mk in addition to MNC counts and CFU-GM showed that vulnerabilities of marrow progenitors seem to differ from cell lineage to cell lineage. This must therefore be taken into careful consideration in pursuing marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗

[Pharmacokinetic, bacteriological and clinical studies of sulbactam/ampicillin in pediatric patients].

Plasma and urine concentrations of sulbactam (SBT) and ampicillin (ABPC) were determined following bolus administration of injectable SBT/ABPC combined in a fixed ratio of 1:2 to 6 pediatric patients, 3 at a dose of 30 mg/kg and the other 3 at 60 mg/kg. Clinical and bacteriological efficacies of SBT/ABPC were evaluated in a total of 65 patients composed of 45 cases with pneumonia, 3 cases each with bronchitis, urinary tract infections, staphylococcal scalded skin syndrome, purulent lymphadenitis, 2 cases each with tonsillitis, pleuropneumonia, phlegmon and 1 case each with pyothorax, submaxillitis. The dosage used was 101.2 mg/kg daily given in 3 or 4 divided doses (t.i.d. in 24 patients and q.i.d. in 41 patients) by bolus intravenous injection for 7 days on an average. Side effects and effects on clinical laboratory parameters were monitored in the 65 patients. The results of these evaluations are summarized as follows. 1. Mean serum concentrations of SBT and ABPC in 3 children each given an intravenous bolus injection of 30 mg/kg and other 3 each given 60 mg/kg reached peak levels at 5 minutes after administration with values of 49.8 and 90.3 micrograms/ml, respectively, for SBT and 99.8 and 189.7 micrograms/ml, respectively, for ABPC. The latter values were about twice as high as SBT, and both were dose-related. Mean half-lives were 0.889 hour for SBT and 0.857 hour for ABPC in the 30 mg/kg group and 0.882 hour for SBT and 0.834 hour of ABPC in the 60 mg/kg group, showing similarities between the 2 dosage groups as well as between SBT and ABPC. 2. Mean urine concentrations in the 2 groups mentioned above were the highest for both SBT and ABPC during the first 2 hours after administration, with values of 1,677 micrograms/ml for SBT and 2,730 micrograms/ml for ABPC in the 30 mg/kg group and 2,693 micrograms/ml and 3,623 micrograms/ml, respectively, in the 60 mg/kg group. Mean recovery rates in urine in the first 6 hours were 72.4% for SBT and 56.8% for ABPC in the low dosage group and 72.7% and 52.0%, respectively, in the high dosage group. In the 2 groups, the amounts of ABPC recovered were less than those of SBT. 3. Clinical efficacies of SBT/ABPC in 65 patients with various bacterial infections were excellent or good in 62 (95.4%) patients. 4. The bacteriological efficacy was evaluable with 10 patients. The pathogenic bacteria were eradicated in 9 patients and the efficacy rate was 90%.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

[Pharmacokinetic and clinical evaluations of imipenem/cilastatin sodium in neonates and premature infants].

Pharmacokinetic and clinical studies on imipenem/cilastatin sodium (IPM/CS), a beta-lactam antibiotic of the carbapenem class and its renal dehydropeptidase-I inhibitor in a 1:1 ratio, were performed in neonates, premature infants and an infant. IPM/CS was administered intravenously to 4 neonates and 5 premature infants at a dose level of 10 mg/kg. Plasma levels and urinary excretion of IPM and CS were determined in 2 neonates and 2 premature infants after 30-minute infusion, and in 2 neonates and 3 premature infants after 1-hour infusion. Plasma and cerebrospinal fluid (CSF) concentrations of IPM and CS were determined in 2 cases with purulent meningitis with ages of 2 and 26 days and 1 with purulent meningitis/bacteremia with an age of 4 days. The drug was administered to a total of 31 patients with ages between 0 and 30 days, consisting of neonates, premature infants and an infant (24 suffering with various bacterial infections, 5 treated for prophylaxis of infections and 2 treated for aseptic meningitis diagnosed at the completion of therapy) by intravenous drip infusion in a mean daily dose level of 50.1 mg/kg in 2 to 4 divided doses for 9 days on the average. Clinical efficacy, prophylactic effectiveness and bacteriological response of IPM/CS were evaluated in 29 cases. Adverse effects and abnormal laboratory test results were examined in 31 cases including 2 drop-out cases. The results obtained are summarized as follows. 1. Plasma concentrations of IPM and CS after 30-minute infusion of the drug reached their peaks at the end of administration, and obtained values were 22.4 to 29.0 micrograms/ml for IPM and 26.3 to 34.6 micrograms/ml for CS, thus peak plasma levels of CS were a little higher than IPM. Plasma half-lives of IPM were 1.05 to 2.43 hours, and those of CS were 1.24 to 4.76 hours, and the half-life of CS tended to be longer than that of IPM. Drug concentrations in plasma after 1-hour infusion of IPM/CS reached their peaks at the end of administration and the levels of CS (25.7 to 32.0 micrograms/ml) were a little higher than those of IPM (20.8 to 23.9 micrograms/ml). Plasma half-lives of IPM were 1.40 to 1.63 hours, whereas those of CS were 1.51 to 2.90 hours. The half-life of CS tended to be longer than IPM. 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

[Pharmacokinetic and clinical studies on cefpodoxime proxetil dry syrup in the field of pediatrics].

Cefpodoxime proxetil (CPDX-PR, CS-807) is a new oral cephem derivative drug in which carboxylic acid was esterified to the 4-position of CPDX (oxime type cephem antibiotic). CPDX-PR is hydrolyzed mainly with esterase in intestinal wall and CPDX exists as an active form in body fluid. While there are numerous study reports using CPDX-PR in tablet forms in Japan, the dry syrup formula for pediatric use was newly developed. The dry syrup of CPDX-PR was orally administered 20 minutes after meal to the 6 boys of ages from 8 years and 1 month to 10 years and 10 months, with doses of 3 and 6 mg/kg, respectively, for 3 cases each. Serum concentrations and urinary concentrations and recovery rate of the drug were investigated. In addition to the above, the clinical and bacteriological studies were performed in a total of 105 cases consisting of children with ages ranging from 2 months to 11 years and 8 months, upon administering an average dose of 3.4 mg/kg, 3 to 4 times per day (96 cases of 3 times and 9 cases of 4 times). The 105 cases included 13 cases of pharyngitis, 21 cases of tonsillitis, 4 cases of acute bronchitis, 6 cases of pneumonia, 1 case of pleurisy, 13 cases of scarlet fever, 41 cases of urinary tract infection, 3 cases of posthitis and 3 cases of bacillary dysentery. Drug sensitivity test was performed for the following strains: (i) Strains retained by our department; 52 strains of Streptococcus pyogenes, 18 strains of Streptococcus agalactiae, and 11 strains of Bordetella pertussis, and (ii) strains isolated from cases to which CPDX-PR was administered; 2 strains of Staphylococcus aureus, 8 strains of S. pyogenes, 2 strains of Haemophilus influenzae, 10 strains of Escherichia coli, and 1 strain of Proteus mirabilis. Drug sensitivities of the strains retained by our department were tested with the inoculum sizes of 10(8) and 10(6) cfu/ml for R-3746 (Na-salt of CPDX), cefaclor (CCL), cephalexin (CEX), amoxicillin (AMPC), and methicillin (DMPPC), and those against strains separated from the cases to which CPDX-PR was administered were tested with the same inoculum sizes for R-3746, CCL, CEX, cefadroxil, ampicillin (ABPC), DMPPC and cloxacillin (MCIPC). Adverse reactions and abnormal clinical laboratory test results were also examined.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

[Clinical study of cefpodoxime proxetil dry syrup for skin and soft tissue infections in the field of pediatrics].

Concurrently with administering a newly developed cephem derivative antibiotic (CEP), cefpodoxime proxetil (CPDX-PR, CS-807) dry syrup, to children with skin and soft tissue infections, activities of 7 drugs against a group of microorganisms were tested. The drugs tested included 4 drugs of the cephem group, R-3746, a Na-salt form of CPDX, cefaclor (CCL), cephalexin (CEX) and cefadroxil (CDX), and 3 drugs of the penicillin group, ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC). The bacterial strains tested were 71 strains of Staphylococcus aureus and 1 strain of Streptococcus pyogenes, all isolated from the above cases of pediatric infections. Inoculum sizes used in these tests were 10(6) and 10(8) cfu/ml. Ages of children in those cases to which the drug was administered ranged from 2 months to 15 years. A total of 66 cases were treated, including 60 cases of impetigo, 5 cases of subcutaneous abscess and 1 case of phlegmon. The drug was administered for an average of 6 days with a daily average dose level of 9.4 mg/kg divided into 3 doses except 1 case where a twice daily dose regimen was used. Clinical and bacteriological effects were examined, and the occurrence of adverse reactions and abnormal laboratory test results were recorded. The results of these tests are summarized below. 1. The activity test for R-3746 (Na-salt of CPDX) against 71 strains of S. aureus performed at an inoculum level of 10(8) cfu/ml showed 2 peaks of MIC values, one in a range of 1.56 to 6.25 micrograms/ml and the other higher than 100 micrograms/ml. The most prevalent MIC value was 3.13 micrograms/ml with MIC against 51 strains or 71.8% of the strains tested showing this value, and MIC values of 25 micrograms/ml or higher were obtained for 13 strains or 18.3% of the strains tested. The MIC80 was 6.25 micrograms/ml. Thus, R-3746 showed an antibacterial activity slightly weaker than MCIPC and DMPPC but similar to CCL, CEX and CDX. MIC values obtained at an inoculum level of 10(6) cfu/ml also had 2 peaks, one in a range of 1.56 to 3.13 micrograms/ml and the other higher than 25 micrograms/ml. Strains against which R-3746 had the MIC value of 3.13 micrograms/ml were the most numerous with 47 strains or 66.2%, and strains against which the MIC value of higher than 25 micrograms/ml was obtained were next with 13 strains or 18.3%.(ABSTRACT TRUNCATED AT 400 WORDS)

Abscess↗

Fluorescence polarization immunoassay of gentamicin or netilmicin in blood spotted on filter paper.

In this improved simple method for determination of aminoglycoside antibiotics in dried-blood spots on filter paper, gentamicin or netilmicin is recovered from the blood spot most effectively by incubation for 60 min in an ultrafiltration tube containing 500 microL of 0.5 mol/L Na2HPO4 buffer. The eluates from the paper are centrifuged, then transferred to an Abbott TDx cartridge for measurement of gentamicin or netilmicin by fluorescence polarization immunoassay. The dried sample on paper is stable for about eight days at ambient temperature. Intra-assay CVs for gentamicin and netilmicin are less than 8.5% and less than 6.1%, respectively. Analytical recovery of gentamicin and netilmicin from the paper exceeded 90%. This method permits simple blood collection and monitoring of the therapeutic concentration of gentamicin or netilmicin in serum, particularly that of newborn infants and small children.

Blood Stains↗

Low intracellular calcium concentration in the platelets after stimulation in patients with myeloproliferative disorders.

Intracellular calcium levels in the platelets of patients with myeloproliferative disorders (MPD) were measured by the Aequorin method. In the patients with MPD, the maximum intracellular calcium level [Ca2+]i was significantly lower and the time required to reach the peak calcium level was significantly longer than in normal controls after thrombin (0.5 U/ml) and collagen (2.5 micrograms/ml) stimulation. The rate of increase in intracellular calcium levels after thrombin (0.5 U/ml) stimulation in the presence of various concentrations of extracellular calcium was lower than in the normal controls, which suggests that the low level of intracellular [Ca2+]i after stimulation is caused mainly by a low Ca2+ influx. These results suggest the relationship between abnormalities of membrane glycoprotein and the impaired calcium influx of MPD platelets.

Blood Platelets↗

[The 5q-syndrome--report of two cases].

Case 1. A 67-year-old man was admitted to our hospital because of fever, diarrhea and abdominal pain. Hemoglobin was 10.7 g/dl, white cell count 6,900/microliters and platelet count 36.7 x 10(4)/microliters. Bone marrow biopsy showed non-lobulated megakaryocytes. The karyotype was 47, XY, +8, -16, 5q-, + mar. We have followed up this case without any special treatment except for red blood cell transfusions. The platelet count has increased to 70.9 x 10(4)/microliters. Case 2. An 84-year-old man was admitted to our hospital because of tinnitus and headache. Hemoglobin was 7.9 g/dl, white cell count 1,200/microliters and platelet count 22.5 x 10(4)/microliters. Bone marrow biopsy showed hypocellular marrow and non-lobulated megakaryocytes. The karyotype was 46, XY, 5q-. We have followed up this case only with red blood cell transfusions. The platelet count has increased to 68.9 x 10(4)/microliters. The hematological findings and clinical courses of the two cases were similar to those in the 5q-syndrome first described by Van den Berghe et al. in 1974. And these cases are important in relation to c-fms oncogene and hematopoietic abnormalities.

Aged↗