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Biomedical subjects

T Tajima

Publications and source records attributed to T Tajima.

At least 361 records · Page 20Linked to original sources

[Pharmacokinetics and clinical studies on aztreonam in neonates and premature infants (the first report). Study on effectiveness and safety in mono-therapy with aztreonam. A study of aztreonam in the Perinatal Co-research Group].

Pharmacokinetics and clinical study of aztreonam (AZT) in neonates and premature infants were conducted with the following results: 1. Pharmacokinetics (1) Serum concentrations of AZT at 30 minutes after one-shot intravenous injection of 10 mg/kg and 20 mg/kg to neonates including premature infants were 20.6-26.6 micrograms/ml and 38.5-46.4 micrograms/ml, respectively, and decreased thereafter. A dose response was observed in the serum concentrations with administration of AZT 10 mg/kg and 20 mg/kg. (2) Serum half-lives (T1/2) tended to be shorter in both mature and premature infants as their day-ages increased and T1/2 tended to be prolonged in premature infants compared with mature infants. (3) Changes in serum concentration upon one-hour intravenous drip infusion of AZT 20 mg/kg were very similar to those upon one-shot intravenous injection. (4) Urinary excretions in the first 6 hours after one-shot intravenous injection of AZT 10 mg/kg or 20 mg/kg tended to increase in mature infants as they grew and showed excretion rate of 26.2-54.3% but those in premature infants did not show any specific tendency with rate of 17.5-45.1%. Urinary excretions upon intravenous drip-infusion showed a tendency very similar to those upon intravenous injection. 2. Clinical studies (1) Clinically evaluable cases of AZT treatment were 88 cases (91 diseases), in which pathogenic organisms were identified in 56 cases (Group A), i.e., sepsis 9, purulent meningitis 2, pneumonia 8, urinary tract infection (UTI) 33 and others. Total efficacy rate was 98.2% including "excellent" (39), "good" (16) and "fair" (1). Number of cases in which pathogenic organisms were unknown (Group B) was 11, i.e., suspected sepsis (4), pneumonia (3) and intrauterine infection (4) and the efficacy rate was 100% with "excellent" (4) and "good" (7). Thus, both group A and B showed excellent results. AZT was also given to 24 cases for prophylaxis and all the cases showed prophylactic effect of AZT.4+ Bacteriologically AZT was deemed effective in 53 cases out of 56 (Group A) with identified pathogens "eradicated" and "unchanged" (2), thus the bacterial eradication rate was 96.2%. (3) A minor degree of loose feces was observed in 1 (1.3%) of 80 cases as a side effect. Abnormal laboratory test values found were eosinophilia (3 cases), elevation of GOT and GPT (2), platelet-increase (1), elevation of GOT (1), and thrombocytopenia.elevation of GOT.GPT.LDH (1). Every one of these was of a minor degree and transient. From the above pharmacokinetics and clinical results, standard dosage of AZT to neonates and premature infants should be in a unit dose of 20 mg/kg, twice daily to those with ages between 0 and 3 days, and 2 to 3 times daily to those with ages 4 days and above, by intravenous injection or intravenous drip infusion.

Age Factors↗

[Pharmacokinetics and clinical studies on aztreonam in neonates and premature infants (the second report). Study on effectiveness and safety in combination therapy using aztreonam and ampicillin. A study of aztreonam in the Perinatal Co-research Group].

Pharmacokinetics and clinical effects were studied in a combination therapy with aztreonam (AZT) and ampicillin (ABPC) in neonates and premature infants. The results obtained are summarized as follows. 1. Pharmacokinetics (1) Average serum concentrations at 30 minutes after one-shot intravenous injection of AZT 20 mg/kg and ABPC 25 mg/kg to a 4-7 days age-group of neonates were 41.3 (AZT) and 30.5 (ABPC) micrograms/ml, respectively. They gradually decreased to 14.7 and 2.7 micrograms/ml at 6 hours after the administration, but the concentration of AZT was always higher than that of ABPC. (2) Serum half-lives (T1/2) in the 4-7 days age-group were 3.61 hours for AZT and 1.42 hours for ABPC, thus T1/2 of AZT was longer. However, T1/2 of AZT was scarcely affected in the concomitant administration of ABPC. (3) Urinary excretion of AZT in the concomitant administration to the 4-7 days age-group was 52.7%, which was the same or a little higher comparing to that in AZT alone administration. 2. Clinical studies (1) AZT and ABPC were concomitantly administered to 160 cases and 133 cases were evaluated for efficacy. Pathogenic organisms were identified in 29 cases (Group A) and the efficacy rate was 86.2% (25/29). The number of cases in which pathogenic organisms were not identified (Group B) was 50 and in this group, the efficacy rate was excellent, 94.0% (47/50). AZT and ABPC were concomitantly administered to 54 cases for prophylaxis and in all the cases the administrations showed prophylactic effect. (2) Bacterial changes were confirmed in 21 of the 29 cases in which pathogenic organisms were identified initially and all of these 21 cases showed bacterial eradication, i.e., the bacterial eradication rate in the treatment was 100%. (3) There were 2 cases in which side-effects were observed among the analyzed 152 cases (1.3%). The side effects found were 1 case each of diarrhea and eruption. Abnormal laboratory values were found in 23 cases (15.9%), i.e., eosinophilia (9 cases), platelet-increase (4), elevation of GOT (4), elevation of GOT and GPT (3) and others (3). From the above pharmacokinetics and clinical results, the combination therapy of AZT and ABPC is considered to be one of the useful empiric antibiotic-therapies when pathogenic organisms are unknown in the infections of neonates and premature infants.

Ampicillin↗

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

Cefdinir (CFDN, FK482) was evaluated for its safety, efficacy and pharmacokinetics in 28 children. CFDN was effective in 100% of 22 evaluable cases with respiratory, middle ear, urinary or soft tissue infections. From the clinical response, adverse effects and the pharmacokinetic results, daily dose of 9-18 mg/kg, administered in 3 divided portions is suggested. Increase of dose will be associated with increase of gastrointestinal side effects. The data suggest that CFDN is safe and effective when used in children with infections caused by susceptible bacteria including Staphylococcus aureus.

Administration, Oral↗

[Clinical and pharmacokinetic studies on aztreonam in neonates].

Clinical and pharmacokinetic studies on aztreonam (AZT) were performed in neonates. The results are summarized as follows: A total of 6 cases consisting of 5 mature and 1 low-birth-weight infants was clinically evaluated. AZT 20 mg/kg was administered 2-3 times daily, via 1 hour intravenous drip infusion for 6-21 days. Concomitantly, vancomycin (VCM) 15 mg/kg was administered to 1 case 3 times daily, via 1 hour intravenous drip infusion for 3 days and ampicillin (ABPC) 20-50 mg/kg to 3 cases 3 time daily via 30 minutes intravenous drip infusion for 2-6 days. Of the 6 bacterial infection cases (1 with sepsis and purulent meningitis, 2 with sepsis, 2 with urinary tract infection and 1 with perirectal abscess), clinical effects of AZT were evaluated in 4 cases (2 each with sepsis and urinary tract infection) as "excellent" in all the cases. All of the causative organisms (Escherichia coli in 3 and Enterobacter cloacae in 1) were eradicated by the treatment with AZT. Neither clinical side effect nor abnormal laboratory test value caused by AZT was observed. MICs of AZT against 10 clinical isolates (Staphylococcus aureus 1, E. coli 4, Klebsiella pneumoniae 1, E. cloacae 1, Haemophilus influenzae 1 and Pseudomonas aeruginosa 2) from neonatal patients with bacterial infections were examined. As results, AZT showed very good antibacterial activity comparable or even superior to cefoperazone, cefotaxime, latamoxef; however, the activity against P. aeruginosa was inferior to imipenem.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampicillin↗

Hydrostatic pressure versus osmotic pressure in the development of vasogenic brain edema induced by cold injury.

The role of hydrostatic pressure and osmotic pressure gradient in the development of vasogenic brain edema induced by cold lesion made in the parietal cortex was studied in cats under ketamine anesthesia and blood pressure monitoring. The animals were divided into a hypertensive group and a normotensive group and were kept alive for 6 hr. The brain was removed and cut coronally at the lesion for tissue sampling from various areas of edematous white matter to measure both the SG and the amount of extravasated serum albumin in the same samples. Our result showed that the edema confined in the area containing extravasated serum albumin and the increase of water content correlated linearly with the amount of extravasated serum albumin both in the normotensive group and hypertensive group. However, the slope of the regression line indicated albumin content in the edema fluid was significantly different between the two groups. The slope became lower as the MABP during the experiment became higher, indicating that protein concentration in the edema fluid became lower when hypertension sustained. Thus, both hydrostatic and osmotic pressure gradient regulate the extravascular accumulation of edema fluid in the cold lesion edema.

Albumins↗

NAD and NADH values in rapidly sampled dog heart tissues by two different extraction methods.

To clarify the most quantitative extraction method for the determination of NAD and NADH in dog heart tissues, both pyridine dinucleotides were extracted from normal and ischemic heart tissues by the Klingenberg method and the Karp method and determined by bacterial luciferase. Tissues from normal beating hearts were sampled by a specially developed freeze-clamping device in 120 ms to minimize ischemic NADH production during sampling. Samples were obtained from both the subendocardium and the subepicardium of the frozen heart tissues. In the Klingenberg method, NAD and NADH were separately extracted with 0.6 M HClO4 and 0.5 M KOH in 50% ethanol, respectively. Both pyridine dinucleotides were simultaneously extracted with 70% ethanol in 0.01 M phosphate buffer in the Karp method. The mean values of NAD and NADH in the normal tissues were 5.08 +/- 0.84 and 0.18 +/- 0.10 nmol/mg protein, respectively, with a NAD/NADH ratio of 25-30 by the Klingenberg method. While the values by the Karp method were 4.37 +/- 0.68 and 0.09 +/- 0.04 nmol/mg protein, with a NAD/NADH ratio of 55-65. The efficiency of extraction of both pyridine dinucleotides by the Karp method was lower than that by the Klingenberg method in all tested samples and states of the tissues. These results suggest that the Klingenberg method is preferable for the extraction of both pyridine dinucleotides from dog heart tissues and that the mean NAD/NADH ratio in normal dog heart tissues is 25-30.

Animals↗

A new compact and cell dense continuous culture system.

A new compact and cell dense continuous culture system was developed. The system consisted of a culture bag, which had two compartments separated by a semipermeable membrane, and an external rotator. Cells were cultured in the inner compartment with medium containing serum or the necessary growth factors. The outer compartment was filled with medium without serum or growth factors. The concentration of cells in culture was normally in the order of 10(7). Due to the large number of cells, sufficient carbon dioxide was produced so that use of a CO2 incubator was unnecessary. The medium in the outer part was frequently changed, but no medium changes were necessary in the inner bag. Using this system, a concentrated yield of antibody as well as a large number of cells could be obtained.

Animals↗

[Hematopoietic recovery after autologous bone marrow transplantation in high-dose chemotherapy of cancer patients].

In order to evaluate the possible utility of autologous bone marrow transplantation (ABMT), eighteen cancer patients were treated with high-dose combination chemotherapy supported by ABMT. We investigated CFU-GM/kg infused as well as bone marrow nucleated cells/kg to predict for hematopoietic recovery. Although hematopoietic recovery was not related to the nucleated cell number of the transfused bone marrow, CFU-GM infused related significantly to neutrophil recovery to 500/mm3 (correlation coefficient, r = -0.73, p less than 0.001) and platelet recovery to 50,000/mm3 (r = -0.69, p less than 0.001). Furthermore, a significant relationship of CFU-GM infused to the period of neutropenia below 500/mm3 was observed (r = -0.67, p less than 0.001). Taken together, CFU-GM dose can predict for neutrophil and platelet recovery, suggesting that ABMT can shorten the period of bone marrow suppression following high-dose chemotherapy.

Adult↗

Interpretation of cutaneous pressure threshold (Semmes-Weinstein monofilament measurement) following median nerve repair and sensory reeducation in the adult.

Semmes-Weinstein nylon monofilaments are used to evaluate recovery of cutaneous pressure threshold in adults recovering from median nerve repair at the wrist level. Of the 46 patients studied, 22 received a program of sensory reeducation. The nylon monofilament measurements accurately described the improvement in recovered sensation following nerve repair. There was a statistically significant better recovery (lower threshold) in patients receiving sensory reeducation, which was present in those less than 30 years old (P less than .003) as well as those greater than 30 years old (P less than .05). However, normal thresholds were not recovered in these patient populations.

Adult↗

Results of median nerve repair in children.

Seven children ranging in age from 1 to 13 years (mean 8 years) were evaluated at a range of 8 months to 15 years (mean 4.7 years) following group fascicular repair of the median nerve at the wrist following a sharp transection of the nerve. At the follow-up evaluation, they were measured with Semmes-Weinstein nylon monofilaments, moving and static two-point discrimination, and were judged for the presence or absence of paresthesias in their hands. The children did not receive sensory reeducation in the postoperative period. All children recovered to normal levels of moving and static two-point discrimination and were free from disabling paresthesias. These results are contrasted with a group of similar nerve injuries in adult patients treated in the same way and over the same period of time. It is concluded that the capacity for peripheral neural regeneration and cerebral plasticity in children is such that excellent recovery of functional sensation in the hand can occur without the need for sensory reeducation.

Adolescent↗

Immunohistochemical studies on oncogene products (c-erbB-2, EGFR, c-myc) and estrogen receptor in benign and malignant breast lesions. With special reference to their prognostic significance in carcinoma.

It is a matter of debate whether the amplification of c-erbB-2 oncogene or production of the oncoprotein in breast cancers correlate with the presence of lymph node metastasis and with a poor prognosis. This study was aimed at elucidating the immunohistochemical localization of oncogene products which are related to cell growth, c-erbB-2 product, epidermal growth factor receptor (EGFR), c-myc protein and estrogen receptor (ER), in benign and malignant lesions of the breast. Fresh frozen sections of 25 breast cancers and 11 fibroadenomas from Japanese women were studied by indirect immunoperoxidase method with proper fixation. C-erbB-2 product and EGFR were localized on the cell membrane whereas c-myc protein and ER were observed in the nuclei. Immunohistochemical expression of oncogene products and ER were not only observed in the mammary carcinomas but also in the fibroadenomas. However immunoreactivities of EGFR and ER were more frequently seen in the fibroadenomas (p less than 0.05). In breast cancers, the incidence of immunoreactivity for c-erbB-2 was higher in the cases with lymph node metastasis than cases without nodal metastasis (p less than 0.05) and there was reciprocal correlation between the expressions of EGFR and ER (p less than 0.05). Regarding the size of the primary tumour, there was no statistically significant correlation with the expressions of c-erbB-2, EGFR, c-myc or ER. Histological grade correlated only with the expression of ER (p less than 0.05).

Adenofibroma↗

A new high-yield continuous cell-culture system for lymphokine-activated killer cells.

We performed basic studies on a new high-yield culture system (concentrate rotary tissue-culture system) for application to adoptive immunotherapy with lymphokine-activated killer (LAK) cells. Using this system, we demonstrated that up to 2 x 10(7) peripheral blood mononuclear cells/ml could be cultured in interleukin-2 with a sufficient recovery rate and cytotoxicity in short-term cultures (6 days). This system can also be used to proliferate LAK cells to four times the initial cell number with sufficient cytotoxicity for 14 days of culture. Thus, this system allows activation of sufficient numbers of cells to conduct clinical trials on humans.

Culture Techniques↗

Osteocompatibility of platinum-plated titanium assessed in vitro.

Suppression of dissolution is important to increase the biocompatibility of titanium implants. Therefore, the possibility of application of platinum-coated titanium as a biomaterial was explored in in vitro experiments using the MC3T3-E1 osteogenic cell line. The data obtained from long-term cultures indicated that pure platinum or titanium thickly coated with platinum inhibited calcification significantly, suggesting that the platinum ion fails to improve the osteocompatibility of titanium implants.

Alkaline Phosphatase↗