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Biomedical subjects

S Minami

Publications and source records attributed to S Minami.

At least 37 records · Page 2Linked to original sources

Increased platelet aggregability in patients with vertigo, sudden deafness and facial palsy.

Many patients suffering from episodic vertigo have no cochlear symptoms. These patients have so far been diagnosed as having Meniere's disease of the vestibular type. However, the underlying mechanisms are still to be established. In the present study, we investigated platelet aggregability in patients with dizziness, Meniere's disease, sudden deafness and facial palsy, to examine whether abnormalities in platelet aggregation is one of the causes of episodic vertigo. In 36 patients with dizziness, in 13 with Meniere's disease, in 7 sudden deafness, and in 7 facial palsy, platelet aggregability to adenosine diphosphate (ADP) was assessed by optometric technique. It was found that platelet aggregability was increased in the patients with dizziness as well as with Meniere's disease, sudden deafness and facial palsy and only the two former patient groups showed a tendency of hyperlipidemia. The administration of antiplatelet and lipidemia drugs resulted in no recurrence of vertigo during at least 3 months' follow-up. Hence, the results of our study suggest that a possible initializing factor of vertigo without cochlear symptoms might be disturbed microcirculation due to platelet hyperaggregability.

Adolescent

[Clinicopathological evaluation of etoposide or estramustine phosphate in castrated patients with advanced prostatic cancer].

BACKGROUND: We conducted a multicentric randomized trial to compare bilateral orchiectomy versus bilateral orchiectomy plus etoposide or estramustine phosphate as first-line therapy for advanced prostatic cancer (stage D2). METHODS: From January 1991 to December 1992 a total of 46 newly diagnosed cases (registered cases) of advanced (stage D2) prostatic cancer was randomized into 3 groups as follows; Group A: bilateral orchiectomy and 25 mg/day of etoposide every 2 weeks for 6 months. Group B: bilateral orchiectomy and 560 mg/day of estramustine phosphate for 6 months. Group C: bilateral orchiectomy alone. One of group A and one of group B were ineligible cases, so 44 were eligible. In the eligible cases, ages were ranged from 54 to 90 (mean of 71.2) years old. No significant difference of patients' characteristics was found among 3 groups and median follow-up period was 25 months. Response was evaluated based on the response criteria according to Japanese urological association. Specifically, a central pathologist who blinded to the treatment was employed for evaluating pathological response at six months. RESULTS: Of the 44 eligible patients, 33 and 25 were evaluated for clinically and pathological analyses, respectively. Clinical response rates were 80% (12/15) of group A, 100% (4/4) of group B and 78.6% (11/14) of group C. No significant difference in the clinical response and survival rate was shown among the three groups. Significantly higher frequencies of side effects were noted in the grop B compared to the other two groups (p < 0.05) and cardiovascular complications were the most frequent in group B. Favorable pathological response was obtained in all of group B, but not statistically significant compared with 7/21 (33.3%) of response rate in group A and C. The pathological response was significantly correlated with the clinical one in all patients (p < 0.01). While 8 of 11 patients (73%) with pathological response grade 1, 2 and 3 achieved clinical PR (partial response) or CR (complete response), only 5 of 14 (36%) with grade 0 received PR or CR. CONCLUSIONS: We conclude that low dose administration of etoposide or estramustine phosphate dose not improve clinical response and survival in a short term in castrated patients, but increases the adverse effects due to the drugs in these patients. In addition, the pathological evaluation at 6 months after treatment appears to reflect the clinical response at that time in newly diagnosed patients with advanced prostatic cancer.

Administration, Oral

[Microbiological assay method for T-3761 concentration in body fluids].

A microbiological assay method for measurement of T-3761 and its stability in body fluids were investigated. The paper disc method proved suitable for this assay using Escherichia coli Kp as a test organism and commercially available heart infusion agar as a test medium. When using the paper disc method, lower detection limit of T-3761 was approximately 0.05 microgram/ml and 0.1 microgram/ml for 1/15M phosphate buffer (pH 7.0) and human serum, respectively. T-3761 in human serum and urine was stable under freezing -20 degrees C for at least 28 days.

Agar

[Absorption, distribution, metabolism and excretion of T-3761, a new quinolone derivative, in experimental animals].

We studied the absorption, distribution, metabolism and excretion of T-3761, a new quinolone derivative, in experimental animals. The following results were obtained. 1. The peak serum levels of T-3761 after a single oral administration to various fasting animals at a dose of 5 mg/kg were high in the order of rats, dogs, mice and rabbits, showing favorable absorption in all animals except for rabbits. In mice and rats, T-3761 showed higher peak serum levels than ofloxacin and ciprofloxacin but T-3761 were more rapidly eliminated from serum than ofloxacin and ciprofloxacin. 2. Tissue concentrations of T-3761 in rats were similar to those of ofloxacin but its ratio of tissue to serum levels were lower than those of ofloxacin. 3. Urinary excretion of T-3761 as active form until 24 hours after oral administration was 27.3%, 63.1%, 41.0% and 63.3% in mice, rats, rabbits and dogs, respectively. Only unchanged T-3761 was detected as active form in urine of all animals tested. In rats, urinary concentrations until 2 hours after administration were higher than those of ofloxacin. 4. Biliary excretion of T-3761 in mice and rats were 2.9% and 1.4% as active form. 5. The absorption of T-3761 was not different in male and female rats or 8 and 14 weeks old rats. The meal lowered absorption of T-3761 in rats. There was no significant difference in serum levels, urinary excretion and distribution to tissues after multiple administration of T-3761 comparing with its single administration. 6. In rats with liver dysfunction induced by D-galactosamine, the serum levels and urinary excretion were slightly higher than in normal rats. On the other hands, in rats with kidney dysfunction induced by HgCl2, the serum levels were significantly higher and urinary excretion of T-3761 was significantly lower than in normal rats. Above results show that T-3761 has unique characteristics in absorption, excretion and distribution after oral administration to animals among new quinolones, i.e., T-3761 was eliminated rapidly and poorly distributed to tissues but showed superior absorption and high peak serum levels.

Administration, Oral

[Serum protein binding of T-3761].

We investigated the extent of the binding of T-3761 to serum protein and obtained the following results. 1. The binding rates of T-3761 to serum protein from various animals and human were 16.9-27.7%, and a little higher than those of ciprofloxacin and ofloxacin. 2. The binding rates of T-3761 to human serum protein were 19.1-23.8% at concentrations of 0.25-20 micrograms/ml. 3. The binding rates of T-3761 lowered as the decrease of protein concentration. 4. The binding rates of T-3761 (2 micrograms/ml) to human serum protein were 12.4, 21.3 and 32.1% at pH 7.0, 7.4 and 8.0, respectively, showing the effect of the pH. 5. The binding of T-3761 to human serum protein was reversible. 6. In vivo binding rates of T-3761 in rabbits after a single oral administration of 20 mg/kg were 26.1-33.2%, which were similar to those obtained in vitro.

Animals

[Clinical value of rapid clearance in resting sestamibi cardiac SPECT in patients with acute myocardial infarction].

Resting 99mTc sestamibi (MIBI) SPECT and exercise-reinjection thallium-201 (T1) SPECT were performed in fourteen patients with acute myocardial infarction (AMI). MIBI SPECT were obtained 90 min (MIBI-90) and 300 min (MIBI-300) after injection of 370 MBq of MIBI at rest. MIBI-90 and MIBI-300 were compared with exercise T1 imaging (T1-EX) and T1 reinjection imaging (REINJ). Each SPECT image was divided into 22 segments and myocardial uptake was scored visually. Abnormal perfusion defects were observed in 94 myocardial regions. Worsening of the score was observed in 79 segments (84%) on MIBI-300 compared with MIBI-90. Total MIBI-300 uptake score per person was significantly greater than that at MIBI-90 (14.8 +/- 8.6 vs. 7.7 +/- 7.9, p = 0.001). The concordance rate of defect score between MIBI-90 and REINJ was significantly higher than that between MIBI-300 and REINJ (55% vs. 17%, p = 0.001). In nine patients without recanalization of an infarct-related artery, perfusion defects were seen in 74 segments. The concordance rate of defect scores between MIBI-300 and T1-EX was significantly higher than that between MIBI-90 and T1-EX (45% vs. 16%, p = 0.001). In conclusion, rapid clearance of MIBI was observed frequently in patients with AMI. MIBI-90 and MIBI-300 may reflect myocardial viability and areas at risk for AMI, respectively.

Contrast Media

Effect of D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2 (KP-102) on GH secretion in urethan-anesthetized rats.

The effect of a newly developed growth hormone (GH)-releasing hexapeptide (KP-102) on GH secretion was studied in urethan-anesthetized adult male rats. Although KP-102 alone exerted a small influence on GH secretion, it produced a large plasma GH response in the presence of exogenous GH-releasing factor (GRF). During the continuous infusion of GRF, the somatotropes became refractory to a large bolus dose of GRF, but KP-102 induced a marked increase of plasma GH. The GH response to KP-102 alone or KP-102 with GRF was significantly augmented when antiserum to somatostatin (ASS) was previously administered. Although KP-102 and GRF acted synergistically on GH secretion in control animals, they acted additively in ASS-administered rats. The KP-102 effect on plasma GH was significantly attenuated in control animals and ASS-administered rats by prior i.v. injection of antiserum to GRF. Taken together, KP-102 stimulates GH secretion dependent on GRF and appears to act synergistically with GRF by antagonizing the SS effect.

Animals

A double-blind controlled study of granulocyte colony-stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. Kohseisho Leukemia Study Group.

We conducted a prospective, double-blind controlled study to determine the efficacy of a recombinant granulocyte colony-stimulating factor (G-CSF, 200 microgram/m2) starting daily from 2 days before an induction therapy until neutrophils recovered to above 1,500/microL or until 35 days after the therapy in 58 patients with relapsed or refractory acute myeloid leukemia (AML). Twenty-eight patients in the G-CSF group showed significantly faster recovery of neutrophils (P < .001) than 30 patients in the placebo group. The incidence of febrile episodes and of documented infections was almost the same in both groups. However, among 39 patients who did not show any infectious episodes during the 2-week period after the start of chemotherapy, the incidence of documented infections after the third week tended to be lower in the G-CSF group, but not statistically significantly. There was no evidence that G-CSF stimulated the growth of AML cells in the bone marrow during the 2-day period before the chemotherapy, nor that G-CSF accelerated the regrowth of AML cells during the 5-week period after the therapy. Fifty percent of patients in the G-CSF group and 37% in the placebo group had complete remission (CR). Although the rate was higher in the G-CSF group, the difference was not statistically significant (P = .306). There was no difference between the two groups in event-free survival of all patients and in disease-free survival of patients who had achieved CR.

Adolescent

Clinical significance of serum iron and ferritin in patients with colorectal cancer.

To clarify the significance of serum iron and ferritin as indicators of iron loss caused by continuous bleeding, and, thus, to determine their value as markers of colorectal cancer, values for the two were compared in male patients with early and advanced colorectal cancer and age-matched male controls. The mean value of serum iron levels in patients with advanced colorectal cancer was significantly decreased compared with values in patients with early colorectal cancer and controls, 50.5 +/- 38.6 micrograms/dl vs 93.0 +/- 32.1 micrograms/dl and 107.1 +/- 32.9 micrograms/dl, respectively (p < 0.001). The mean value of serum ferritin levels in patients with early and advanced colorectal cancer was also significantly decreased compared with controls, 80.5 +/- 35.0 ng/ml (p < 0.01) and 48.8 +/- 72.8 ng/ml (p < 0.001), respectively, vs 117.1 +/- 46.8 ng/ml. However, there was no significant difference between mean serum iron levels in patients with early colorectal cancer and controls. Eighteen (78.3%) of the 23 patients with advanced colorectal cancer and 3 (16.7%) of the 18 patients with early colorectal cancer had serum iron levels below 85 micrograms/dl and serum ferritin levels below 60 ng/ml. Levels of both serum iron and ferritin, without clinically evident anemia, are useful indicators of advanced colorectal cancer.

Aged

Postantibiotic effects and postantibiotic sub-MIC effects of benzylpenicillin on viridans streptococci isolated from patients with infective endocarditis.

We investigated the postantibiotic effects (PAEs) and the postantibiotic sub-MIC effects of benzylpenicillin on three strains of viridans streptococci isolated from infective endocarditis patients. The PAEs of benzylpenicillin on penicillin tolerant Streptococcus sanguis TW-70 (0.4-3.9 h), penicillin tolerant S. sanguis TW-80 (0.3-6.3 h) and nontolerant Streptococcus oralis TW-186 (0.5-3.1 h) were dependent on exposure time. The PAEs were not concentration dependent for S. sanguis TW-70 and S. sanguis TW-80 above the MIC, and for S. oralis TW-186 above 16 x MIC. The antimicrobial effects of benzylpenicillin at sub-MIC concentrations were examined in bacteria pretreated with benzylpenicillin (8 x MIC) for 2 h and compared with untreated bacteria. At the sub-MICs tested, the regrowth of pretreated S. oralis TW-186 cells was more prolonged than that of untreated cells and bactericidal action was seen only in pretreated cells. These effects (so-called 'postantibiotic' sub-MIC effects') were not observed in penicillin tolerant S. sanguis TW-70. The presence of the postantibiotic sub-MIC effect may be an important factor in determining the dosing regimen for infective endocarditis.

Endocarditis, Bacterial

Restoration of growth hormone secretion in prolonged food-deprived rats depends on the level of nutritional intake and dietary protein.

Prolonged food deprivation inhibits GH secretion in rats. To learn more about the nutritional regulation of GH secretion, we observed whether the recovery of GH secretion from prolonged food deprivation depends on the level of nutritional intake or a specific macronutrient in the refeed meal. Adult male Wistar rats were deprived of food for 72 h. Serial blood specimens were withdrawn via an indwelling right atrial cannula every 10 min using an automatic blood-sampling device. In the 72-hour food-deprived rats, the amplitude of the GH pulse progressively decreased but the pulse frequency did not differ compared to that of the fed control rats. When adult male rats were fed 5, 10 or 40 kcal of mixed meal consisting of carbohydrate 60%, protein 25% and fat 15% after 72 h of food deprivation, both the pulse amplitude and the pulse frequency immediately increased compared to those of the fasted control rats. Following these changes, the pulsatility of GH secretion was restored to normal, while the pulse amplitude was recovered in a meal-size-dependent manner. The GH secretory pattern no longer differed from that of the fed control rats in the rats fed 40 kcal of mixed meal. In the second study, the 72-hour food-deprived rats were fed 10 or 40 kcal of a protein meal consisting only of casein powder or 40 kcal of a protein-deficient meal consisting of carbohydrate 85% and fat 15%. The GH secretory pattern was restored to normal among the food-deprived rats fed 40 kcal of a protein meal.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity Cycles

Growth hormone induces expression of the c-fos gene on hypothalamic neuropeptide-Y and somatostatin neurons in hypophysectomized rats.

The neuronal expression of the protooncogene c-fos may serve as a marker of neural activity. We previously examined brain sites upon which GH exerts an immediate early influence in rats and determined that the c-fos gene was transiently expressed in the hypothalamic periventricular nucleus (PeV) and arcuate nucleus (ARC) after recombinant human GH (rhGH) administration. As the distribution of c-fos messenger RNA (mRNA)-containing cells appeared to overlap with that of somatostatin (SS) neurons in both the PeV and ARC, we hypothesized that GH exerts a feedback effect on hypothalamic SS neurons. To extend this hypothesis, we characterized the neurons expressing the c-fos gene in response to rhGH administration in hypophysectomized rats. Adult male Wistar rats were hypophysectomized 10 days before use. After hypophysectomy, rats received daily sc injections of cortisone acetate (0.5 mg/kg BW) and L-T4 (20 micrograms/kg BW). Four international units (1.33 mg) of rhGH were given iv through an indwelling right atrial cannula. The vehicle was given to the control animals. Coronal sections of the hypothalamus were processed for in situ hybridization after rhGH or vehicle administration. To estimate the localization of neurons expressing the c-fos gene, the adjacent hypothalamic sections, 30 microns in thickness, were processed for hybridization histochemistry for SS, neuropeptide-Y (NPY), or GRF mRNA. In the ARC, the distribution of c-fos mRNA-containing cells appeared to overlap with that of NPY and partially with that of SS mRNA-containing cells, but it clearly differed from the distribution of GRF mRNA-containing cells. In the PeV, distribution of the cells expressing the c-fos gene was comparable to that of SS mRNA-containing cells. To further ascertain the distribution, hypothalamic sections, 6 microns in thickness, were processed by double label in situ hybridization using a 35S-labeled c-fos cRNA probe and a digoxigenin-labeled NPY or SS cRNA probe. In the ARC, 65% of the c-fos gene-expressing cells were NPY neurons. In the PeV, 60% of the c-fos gene-expressing cells were SS neurons. NPY is known to act within the hypothalamus and inhibit GH secretion via SS in rats, and the NPY neurons in the ARC have been shown to project to SS neurons in the PeV. Our findings suggest that the feedback effect of GH on the hypothalamus is mediated not only by SS neurons in the PeV, but also by NPY neurons in the ARC.

Animals

Migration of canine neutrophils to chitin and chitosan.

Suspension of chitin and chitosan particles (mean size of 1 micron) were found to attract canine neutrophils chemotactically as determined by a checkerboard assay through polycarbonate filter with 5 microns pore size in Blind well chamber. Suspension of chitin induced chemokinetic migrations of the neutrophils. These evidences might reflect accumulation of neutrophils to chitin- and chitosan-implanted regions in dogs.

Animals

Serum biochemical changes and chemiluminescent responses of whole blood in Holstein cattle with leukocyte adhesion deficiency.

Serum biochemical profile and whole blood chemiluminescent (CL) responses in 8 Holstein cattle affected with leukocyte adhesion deficiency (LAD) were evaluated. Concentrations of sodium, chloride and calcium in serum from cattle affected with LAD were significantly (p < 0.05) decreased as compared with controls. The characteristic changes in serum proteins were hypoalbuminemia and hyperglobulinemia, and the concentrations of albumin and gammaglobulin in serum from normal cattle and cattle affected with LAD were significantly (p < 0.01) different. Significantly (p < 0.01) diminished CL indices and prolonged peak time of CL responses in whole blood were detected in cattle affected with LAD. These findings indicate that the CL response associated with iC3b receptor mediated phagocytic activity is impaired in cattle affected with LAD. The whole blood CL assay appeared to be practical and useful for routine evaluation of blood samples from cattle affected with LAD.

Animals

[Bone marrow transplantation from donors other than HLA matched siblings for hematological malignancies. Nagoya Bone Marrow Transplantation Group and Tokai Marrow Donor Bank].

One hundred and fourteen patients with hematological malignancies received bone marrow transplantation from donors other than HLA-identical siblings. Sixty-three patients received transplantations from related donors; 20 were phenotypically identical for HLA-A, B, D/DR (RM0). 32 differed at one locus (RM1) and 11 differed at more than one loci (RM2). Fifty-one transplantations were from unrelated donors; 37 were phenotypically identical and mixed lymphocyte culture (MLC) negative (UR0) and 14 were MLC positive (UR1). One hundred and four patients had durable engraftment. Four (RM1(1), RM2(2), UR0(1)) failed to achieve engraftment. In terms of the probability of > or = Grade II acute graft-versus-host disease (GVHD), there was no significant difference among the groups according to HLA disparity (RM0:25%, UR0:33%, UR1:39%, RM1:47%, and RM2:50%). The probability of chronic GVHD was significantly higher in UR0 and UR1 than RM0 (71%, 75% vs 28%, p < 0.05). The disease-free survival at 3 years was 45% (RM0), 50% (RM1) and 42% (UR0). More than 50% of patients other than RM0 died of fatal complications including GVHD within 60 days after grafting. In conclusion, unrelated donor and related donor mismatched at one locus could be selected for marrow graft in the case of the absence of an HLA-matched related donor. However, more advances in post-transplant management and in histocompatibility testing should be required.

Adolescent

[Effect of nicardipine cardioplegia on A-V conduction system in coronary bypass surgery].

The effect of diltiazem and nicardipine cardioplegia on A-V conduction system was analyzed in 75 patients undergoing coronary bypass operation. The dose of these drugs into the crystalloid cardioplegia was 10 micrograms/kg in nicardipine group (n = 29) and 100 micrograms/kg in diltiazem group (n = 46). Among these patients, there was no operative death and no patient required IABP after surgery and there was no difference on the post operative CK-MB level, on the cardiac index and on the pulmonary pressure between two groups. The number of patients who had complete A-V block after release of aortic cross clamping was significantly smaller in nicardipine group than in diltiazem group: 45.7% in diltiazem group vs. 6.9% in nicardipine group at 30 minutes and 21.7% vs. 6.9% at 60 minutes. We conclude that the suppressive effect on A-V conduction system was significantly lower in nicardipine cardioplegia than in diltiazem cardioplegia in the patients undergoing coronary bypass operation.

Angina Pectoris

[Secondary leukemia after etoposide treatment involved MLL gene rearrangement].

The 11q23 chromosomal abnormality is frequently observed in infantile leukemia and secondary leukemia, and the translocation associated gene in infantile leukemia is called mixed-lineage leukemia (MLL) gene. A 50-year-old man was admitted because of left axillary lymphadenopathy and IBL like T cell lymphoma was diagnosed by lymph node biopsy. The patient responded to the LSG-9 protocol with complete remission. After 10 months he was readmitted because of fever and was diagnosed acute myeloblastic leukemia by bone marrow aspiration. Chromosome analysis revealed 11q23 abnormality, suggesting that the leukemia was induced by etoposide treatment. Southern blot analysis demonstrated DNA rearrangement in the MLL gene at 11q23. It was suggested that the breakpoint region of the MLL gene in secondary leukemia is the same as that of infantile leukemia.

Chromosomes, Human, Pair 11