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Biomedical subjects

T Tajima

Publications and source records attributed to T Tajima.

At least 271 records · Page 15Linked to original sources

Sex differences in the anticoagulant effects of warfarin.

Sex differences in the anticoagulant effects of warfarin were studied in rats. Warfarin was administered to rats from 7 days of gestation until 14 weeks of age. In male rats, the normal prothrombin level in the plasma was reduced, and the blood coagulation time was prolonged by treatment with warfarin at 4, 9 and 14 weeks of age. However, in female rats, the effects of warfarin on the prothrombin level and blood coagulation time were observed at 4 weeks to the same degree as in male rats, but these effects were reduced with aging, and at 14 weeks, no effect of warfarin was observed. Rats ovariectomized at 12 weeks of age and subsequently treated with warfarin for 2 weeks showed prolongation of blood coagulation time to the same level as in warfarin-treated male rats, which was inhibited by administration of 17 beta-estradiol (100 micrograms/kg/day for 4 days, i.m.). In male rats, treatment with 17 beta-estradiol also inhibited the anticoagulant effects of warfarin without changing the warfarin level in plasma. These results suggest that there is a sex difference in the anticoagulant effects of warfarin, and that this difference may be related to the estradiol level in plasma.

Animals↗

Detection of the antibodies against porcine cytomegalovirus from whole blood collected on the blood sampling paper.

The usefulness of blood sampling paper for the detection of antibodies against porcine cytomegalovirus (PCMV) by enzyme-linked immunosorbent assay (ELISA) was examined. The PCMV antibody titer of whole blood collected on the paper agreed with that of serum and the absorbances of the corresponding samples were well correlated (r = 0.88). Blood was collected from 26 piglets in the field on the blood sampling paper and ELISA was performed. The maternal PCMV antibody of these piglets decreased during the 8 weeks after birth and IgM antibody against PCMV was detected in four piglets.

Aging↗

Serum c-erbB-2 in breast cancer patients.

The c-erbB-2 oncogene product in serum (serum c-erbB-2) was measured by an enzyme-immunoassay kit. The 12 U/ml cut-off level was estimated as the mean plus two standard deviations for 250 healthy women. With this cut-off level increased serum c-erbB-2 was found in 12.0% of primary breast cancer cases (n = 25), in 4.9% of non-recurrent breast cancer patients (n = 82), and in 31.4% of patients with recurrent breast cancer (n = 35). In patients with primary and recurrent breast cancer, whose sera were assayed concurrently for serum c-erbB-2, CEA and CA15-3, the positive rates of these markers were fairly similar. However, their combined use significantly increased the sensitivity as compared to the use of any one marker alone.

Adult↗

Inhibitory effect of simultaneous intraportal administration of 5-fluorouracil, uracil and degradable starch microspheres on experimental hepatic micrometastasis, is of colon cancer.

This study was designed to examine the optimal regimen of 5-fluorouracil (5-FU), uracil and degradable starch microspheres (DSM) to prevent the hepatic metastasis of colorectal cancer. BALB/C mice were used as a model of hepatic micrometastasis of mouse transplantable colorectal cancer, Colon 26. We intraportally administered to the mice 5-FU at a dose of 34.8 mg/kg body weight; uracil at the dose equal to, or 8 times higher than that of 5-FU in molar weight and DMS at a dose of 5 mg/kg body weight. We investigated the hepatic and serum concentrations of 5-FU and uracil and the inhibitory effect of various combinations of the three substances on hepatic metastasis. The study showed that concurrent use of 5-FU with uracil at a dose 8 times higher than that of 5-Fu could keep 5-FU concentration high in hepatic tissue and relatively low in serum. This tendency became more marked with the presence of DSM. These findings support the previous study results that uracil antagonizes breakdown of 5-FU in the liver and with the aid of DSM, retards excretion of 5-FU from the liver. Further investigations for clinical application of this method will lower the incidence of hepatic metastasis of colorectal cancer.

Animals↗

[Pharmacokinetic, bacteriological and clinical studies on cefozopran in children].

Pharmacokinetic, bacteriological and clinical studies on cefozopran (CZOP) were performed in children. The results were as followed: 1. A total of 13 patients were treated with CZOP. The tested dose was 20 mg/kg (50 mg/kg in maxillary sinusitis), and the drug administered via intravenous bolus injection or 30-minute intravenous drip infusion 3 times daily, for 3-11 days. Clinical efficacies of CZOP in 13 patients with bacterial infections (11 with pneumonia, 1 with otitis media and 1 with maxillary sinusitis) were evaluated as excellent in 13 with an efficacy rate of 100%. Any adverse reactions or abnormal laboratory test results were not observed in any patients. Fourteen causative strains were found in 10 patients. Streptococcus pneumoniae in 4 cases out of 4, Streptococcus pyogenes in 1/1, Moraxella (Branhamella) catarrhalis in 3/3, Haemophilus influenzae in 4/6 were eradicated. 2. Pharmacokinetic studies. The mean serum concentration immediately after intravenous drip infusion over 30-minute of 20 mg/kg was 39.1 micrograms/ml (range: 25.6-52.5 micrograms/ml). The mean urinary recovery rate over 8 hours after administration was 49.0% (range: 45.2-51.8%). Based on the above results and the broad spectrum and great antibacterial activity of CZOP, it is considered that CZOP is a promising antibiotic usable as a single agent for the primary therapy of acute bacterial infections ranging from mild to severe in children.

Bacteria↗

[Chemotherapy with autologous stem cell support for breast cancer].

The importance of dose intensity in breast cancer chemotherapy has been stressed in recent years with clear correlations demonstrated between dose intensity and clinical outcome of the patients in both therapeutic and adjuvant settings. In addition to various and intense supportive care, autologous stem cell support (ASCS) has been used over the past 15 years in order to overcome myelotoxicity of cancer chemotherapy. ASCS was initially practiced in the form of bone marrow transplantation, and more recently peripheral stem cell transplantation has been combined in addition to administration of G-CSF. Our pilot study in patients with recurrent/advanced breast cancer showed a higher response rate and a higher survival rate as compared to conventional chemotherapy, and there have been some long-term disease-free survivors with probable cures among complete responders with ASCS-supported chemotherapy. In adjuvant settings for patients with a high risk for recurrence who had been given a high-dose, the ASCS-supported regimen showed a higher disease-free survival rate as compared to those who were treated with conventional adjuvant therapy. Whether these apparently better results in our pilot studies hold true generally remains to be seen with well-scheduled randomized clinical trials.

Antineoplastic Agents↗

[Pharmacokinetic, bacteriological and clinical studies on biapenem (L-627) in children].

The results are summarized as follows: 1. A total of 10 patients were treated with biapenem (L-627). We received informed consent from all of their parents. Each dose was 6 mg/kg, and it was administered 3 times daily (40 mg/kg, 4 times daily in meningitis), in a 30-minute intravenous drip infusion for 5-17 days. The clinical efficacies of L-627 in 10 patients with bacterial infections (1 with purulent meningitis, 1 with sepsis, 5 with pneumonia, 2 with urinary tract infection and 1 with purulent tonsillitis) were evaluated as excellent in 8 patients, as good in 2 patients with an efficacy rate of 100%. Seven causative organisms found in 5 patients (Streptococcus pneumoniae in 2, Moraxella (Branhamella) catarrhalis in 2, Haemophilus influenzae in 2 and Pseudomonas aeruginosa in 1) were eradicated. No adverse reaction was observed in any of the 10 patients. 2. Pharmacokinetic studies Peak plasma concentrations of L-627 were 12.5-13.7 micrograms/ml at the dose of 6 mg/kg administered by 30-minute drip infusion. Plasma half-lives of L-627 in the beta-phase averaged 0.72 hour (0.63-0.80 hour). CSF concentration/plasma concentration ratios of L-627 were 1.12/8.16 micrograms/ml (Day 2, 1.17 hours after at dose of 20 mg/kg), 0.88/3.44 micrograms/ml (Day 3, 4.0 hours after at dose of 30 mg/kg) and 0.68/5.12 micrograms/ml (Day 13, 3.0 hours after at dose of 40 mg/kg) administered by 30-minute drip infusion in the child with purulent meningitis (case 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗

[Occult CSF flow disturbance of patients with Alzheimer type dementia and vascular dementia--results from iotrolan CT-cisternography].

We report results of Iotrolan CT-cisternography on 41 demented patients (13 males and 28 females) to find "occult normal pressure hydrocephalus". These patients were suspected to have CSF flow disturbance from clinical symptoms and simple brain CT scan findings. Their average age, duration of dementia, and score of Hasegawa's dementia scale (HDS) were 76.2 years, 5.9 years, 9.5/32.5, respectively. Before performing CT-cisternography, clinical diagnosis for their dementia were vascular dementia in 18 patients, Alzheimer type dementia in 12, suspect of NPH in 5, and other diagnoses in 6. From the results of cisternography, we found 13 patients with CSF flow disturbance (contrast material remained in the ventricle more than 48 hours after injection), and 17 patients with normal CSF flow. The former showed lower scores of HDS, higher urinary incontinence scores and smaller areas of the interhemispheric fissure on CT scan than the latter. But the former showed no significant difference from the latter in the average age, duration of dementia and width of the ventricles.

Aged↗

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

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

Adolescent↗

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

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

Adolescent↗

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

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

Absorption↗

Study on dermatomes by means of selective lumbar spinal nerve block.

Regions of sensory impairment of 71 patients in 86 lumbar spinal nerve blocks (L4 19 cases, L5 41 cases, S1 26 cases) were determined by the writing brush method. Distinctive regions included the medial side of the lower leg, the side of the first dorsal digit, and the side of the fifth digit respectively of the L4 (88%), L5 (82%) and S1 (83%) spinal nerves without 100% matching because of displacement of one spinal segment by the furcal nerve. A band-like impaired zone from the proximal to the periphery appeared in 42%, 44%, and 92%, respectively, of the L4, L5, and S1 blocks. The marked difference between L4, L5, and S1 may be caused by the diversity of the dorsal rami of the spinal nerves and double control by the lateral cutaneous nerve of the thigh.

Afferent Pathways↗

Menatetrenone inhibits bone resorption partly through inhibition of PGE2 synthesis in vitro.

We studied the effect of menatetrenone, a vitamin K2 homolog, on bone resorption stimulated by interleukin-1 alpha (IL-1 alpha), prostaglandin E2 (PGE2), parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Bone-resorbing activity was assessed by measurement of calcium and hydroxyproline in the media and calvariae. IL-1 alpha (0.1-100 U/ml), 1,25-(OH)2D3 (10(-10)-10(-7) M), PGE2 (10(-9)-10(-6) M), and PTH (3 x 10(-8)-3 x 10(-7) M) dose dependently increased the levels of calcium and hydroxyproline in the medium. Indomethacin (10(-6) M) completely inhibited bone resorption induced by IL-1 alpha and partially inhibited bone resorption induced by 1,25-(OH)2D3. However, indomethacin did not affect the action of PGE2 or PTH. Menatetrenone (3 x 10(-6)-3 x 10(-5) M) inhibited the bone resorption induced by IL-1 alpha (2 U/ml), PGE2 (10(-7) M), PTH (3 x 10(-7) M), and 1,25-(OH)2D3 (3 x 10(-10) M) in a dose-dependent manner. Menatetrenone also inhibited the PGE2 production stimulated by IL-1 alpha. These results indicate that menatetrenone may inhibit bone resorption through at least two different mechanisms; one possibly is an inhibitory effect on prostaglandin production.

Animals↗