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Biomedical subjects

M Takeyama

Publications and source records attributed to M Takeyama.

At least 55 records · Page 3Linked to original sources
PubMed1997

Pharmacokinetics of methotrexate in plasma and cerebrospinal fluid.

OBJECTIVE: To investigate the pharmacokinetics of methotrexate (MTX) in plasma and cerebrospinal fluid (CSF) during osmotic disruption of the blood-brain barrier and the intraarterial administration of combination chemotherapy postoperatively in a patient with glioblastoma. CASE SUMMARY: A 60-year-old Japanese woman with a glioblastoma received two courses of combination intraarterial chemotherapy. In the first course of treatment, 20 mL of mannitol 20%, peplomycin 10 mg, vindesine 2 mg, and MTX 500 mg were administered via the right internal carotid artery, and then via the right vertebral artery. In the second course of treatment, 20 mL of mannitol 20%, peplomycin 15 mg, vindesine 2.5 mg, and MTX 1000 mg were similarly administered. Blood samples and CSF samples from the ventricle and the space left by tumor removal were obtained; the MTX concentrations were measured from these sites by fluorescence polarization immunoassay. The pharmacokinetic parameters of MTX in plasma and CSF were estimated. DISCUSSION: The plasma concentration of MTX decreased in a biexponential decay pattern during each course of treatment. CSF concentrations of MTX in the ventricle and in the space left by tumor removal peaked at 2 and 6 hours, respectively, after drug administration and decreased monoexponentially. When the dose of MTX was doubled, the AUC for the plasma MTX concentration increased 2.4-fold and the AUCs for MTX in the ventricle and the space left by tumor removal increased 3.4- and 9.1-fold, respectively. The half-life of MTX in the CSF in the space left by tumor removal exceeded the half-lives of MTX in the plasma and in the ventricular CSF. CONCLUSIONS: The CSF AUCs of MTX in the ventricle and the space left by tumor removal increased markedly and in parallel with the MTX dosage increase during osmotic disruption of the blood-brain barrier and intraarterial combination chemotherapy. Such treatment improves the delivery of chemotherapy agents to the brain.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Study of trough type audiogram of sudden hearing loss].

We investigated 974 patients with sudden sensorineural hearing loss who consulted the otolaryngological service of Hamamatsu University Hospital and four affiliated hospitals from 1984 to 1992. Among them, we selected 569 new cases showing a pure tone average of 31 dB or more at 250 Hz, 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz on the affected side in the initial audiometry performed within 14 days after the onset of sudden sensorineural hearing loss. The 569 patients consisted of 13 with acoustic neuromas (SHLANs), 493 with idiopathic sudden sensorineural hearing loss (ISHLs) and 63 others. Ten of the 13 SHLANs and 40 of the 493 ISHLs showed the trough type audiogram on the initial examination. We defined the 10 cases as the Trough AN group and the 40 as the Trough ISHL group. Statistical analysis of the difference in pure tone averages at 5 frequencies between the 2 groups demonstrated that the mean hearing losses at 125, 250 and 500 Hz of Trough AN were significantly less than those of Trough ISHL. This study demonstrates that the trough type audiogram, especially a slight low tone loss, shown in patients with sudden sensorineural hearing loss was a significant finding suggesting the presence of acoustic neuroma.

Adult↗
PubMed1997

Elevated levels of substance P in tears of patients with allergic conjunctivitis and vernal keratoconjunctivitis.

BACKGROUND: Recent studies have suggested that the nervous system may participate in inflammatory processes. Substance P (SP) acts as a chemical mediator as well as a neurotransmitter. OBJECTIVE: In order to clarify the pathogenesis of ocular allergic diseases, we assessed the concentration of SP in tears. METHODS: Using a highly sensitive and specific double-antibody enzyme immunoassay (EIA), we determined the SP concentration in tears of 10 patients with seasonal allergic conjunctivitis, 10 with atopic dermatitis without keratoconjunctivitis (AD), 13 with vernal keratoconjunctivitis (VKC) and 65 normal controls. Giemsa's staining for brush cytology samples and histocytological study by immunocytochemical staining of giant papillary conjunctival cells from VKC and normal controls was conducted. RESULTS: The mean SP level was low in the normal controls and AD, whereas patients with seasonal allergic conjunctivitis and VKC showed significant elevation of SP (P < 0.01). Brush cytology samples showed conjunctival epithelial cells with lymphocytes, neutrophils and eosinophils that were not seen in normal subjects. Histocytological examination demonstrated SP positive cells in the conjunctiva of patients with VKC, but not in normal controls. CONCLUSION: This study suggests that the increased level of SP in tears may contribute to the pathogenesis and severity of ocular allergic diseases.

Adolescent↗
PubMed1997

[A randomized study on intravesical pirarubicin (THP) chemoprophylaxis of recurrence after transurethral resection of superficial bladder cancer].

A prospective randomized study was conducted to evaluate the efficacy of prophylactic intravesical instillation of tetrahydropyranyladriamycin (THP) following complete transurethral resection (TUR) of superficial bladder cancer. A total of 80 patients were randomized into "THP" or "control" group. In the THP group, 20 mg of THP dissolved in 40 ml saline (or 5% dextrose) was administered intravesically once a week for 10 weeks, starting from about 7 days after TUR. In the control group, 40 ml saline was given with the same schedule. The patients were followed up by cystoscopy and urinary cytology every 3 months. The number of evaluable patients was 36 for the THP group and 37 for the control group. The non-recurrence rates in the THP group and control group were 79.4% versus 63.2% at 1 year and 69.8% versus 47.4% at 3 to 5 years, respectively. These figures were not statistically significant. However, THP instillation significantly reduced tumor recurrence rates for multiple tumors, and also tended to decrease recurrence rates for primary and pT1 tumors. Adverse effects were observed in 53.6% of the patients in the THP group, but they were tolerable. Our results suggest that intravesical THP instillation would not be effective for all patients with superficial bladder cancer. Further study is warranted in a selected group of patients.

Administration, Intravesical↗
PubMed1996

Substance P-like immunoreactive substance in bronchoalveolar lavage fluids from patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis.

In order to find out whether substance P (SP) participates in the inflammatory and fibrotic processes of interstitial lung diseases or not, SP-like immunoreactive substance (SP-IS) concentrations in bronchoalveolar lavage (BAL) fluids from patients with idiopathic pulmonary fibrosis (IPF) and pulmonary sarcoidosis were measured using enzyme immunoassay (EIA). The mean SP-IS concentrations in BAL fluids from healthy nonsmokers and healthy smokers were 0.87 +/- 0.19 and 0.98 +/- 0.23 pg/ml, respectively. The mean SP-IS concentration in BAL fluids from patients with IPF was 1.15 +/- 0.39 pg/ml. The value of patients with IPF was significantly higher than that of healthy nonsmokers (p < 0.01). The mean SP-IS concentrations in BAL fluids from pulmonary sarcoidosis patients in stage I, stage II and stage III were 0.91 +/- 0.19, 0.96 +/- 0.35 and 1.00 +/- 0.29 pg/ml, respectively. No correlation was found between SP-IS concentration and pulmonary functions in IPF and sarcoidosis patients. The present results indicate that SP may be involved in the inflammatory process in IPF.

Adult↗
PubMed1996

Effect of cysteamine on gastric nerve fibers containing gastrin-releasing peptide in the rat.

In rats, changes in gastric nerve fibers containing gastrin-releasing peptide (GRP) in cysteamine-induced duodenal ulcer were investigated in relation to the dynamics of gastrin-producing cells (G-cells). Marked increases in gastric acid secretion and serum gastrin level were observed from 2 h after the administration of cysteamine. The number of G-cells was significantly decreased from 2 h after the injection of cysteamine. Two and 4 h after the administration of cysteamine, the G-cells showed ultrastructural changes characterized by a markedly decreased number of secretory granules. Circulating GRP levels were significantly elevated from 2 h after the administration of cysteamine. In the control group given vehicle only, nerve fibers showing immunoreaction for GRP formed a fine network in the gastric wall and were densely distributed in the oxyntic mucosa, located close to capillaries and demonstrated varicosities that contained either small clear vesicles or GRP-immunopositive vesicles with large cores. Eight h after the administration of cysteamine, there was depleted GRP immunoreactivity, evidenced by a markedly decreased number of vesicles, with large electron-dense cores, in the oxyntic mucosa. These findings suggest that, in cysteamine-induced duodenal ulcer, alterations in gastric nerve fibers containing GRP may be related to hypergastrinemia.

Animals↗
PubMed1996

Evaluation of unbound serum carbamazepine and carbamazepine-10,11-epoxide concentration prediction methods in polytherapy adult patients with epilepsy.

We retrospectively evaluated the ability of equations with in vivo population binding parameters of our previous study (Method 1) or an average unbound fraction of 0.25 of Pynnönen (Method 2) to predict the unbound serum carbamazepine (CBZ) concentration in 35 serum samples from 18 adult patients with epilepsy receiving polytherapy. In 9 serum samples from 6 patients, the ability of equations for unbound serum carbamazepine-10,11-epoxide (CBZ-E) concentration prediction was also determined in predictive performance with in vivo population binding parameters of our previous study (Method A) or an average unbound fraction of 0.5 of Pynnönen (Method B). Mean prediction error, mean absolute prediction error (MAE), and root mean squared error (RMSE) were calculated for each method, and these values served as a measure of prediction bias and precision. Method 1 shows a bias to underpredict unbound serum CBZ. The MAE and RMSE were smaller in Method 2 (MAE = 0.454 &mgr;m/L, RMSE = 0.597 &mgr;m/L) than Method 1 (MAE = 0.597 &mgr;m/L, RMSE = 0.721 &mgr;m/L). Method 2 is superior to Method 1 in accuracy and precision. The effects of antiepileptic comedications on predictive performance of Methods 1 and 2 were determined in each group of serum samples with (n = 18, Group 1) or without (n = 17, Group 2) valproic acid (VPA) comedication. The results obtained by Method 1 show a bias to underprediction in Group 1 and no bias to over- or underprediction in Group 2. Results obtained by Method 2 show no bias to over- or underprediction in Groups 1 and 2. The effects of VPA comedication on predictive performance of unbound serum CBZ are relatively larger in Method 1 than Method 2. There was a weak but significant positive relationship between age and unbound serum CBZ fraction by simple regression analysis (n = 35, r = 0.368, p = 0.0297). The determined coefficient indicated that only about 14% of variations in unbound serum CBZ fraction can be explained by age, however. In each of Groups 1 and 2, no significant relationship was observed between age and unbound serum CBZ fraction. The effects of age on predictive performance of unbound serum CBZ are relatively small in patients receiving polytherapy. For unbound CBZ-E prediction, each of Methods A and B has no bias to over- or underprediction. The MAE was larger in Method B (MAE = 0.311 &mgr;m/L) than Method A (MAE = 0.233 &mgr;m/L). The differences in RMSE were small between Methods A (RMSE = 0.349 &mgr;m/L) and B (RMSE = 0.333 &mgr;m/L), however. Each of Methods A and B may have similar accuracy and precision.

Journal Article↗
PubMed1996

Clearance of phenytoin and valproic acid is affected by a small body weight reduction in an epileptic obese patient: a case study.

The interaction between clearance of phenytoin, valproic acid, phenobarbital and carbamazepine, and changes in body weight was determined in a 19-year-old obese woman with epilepsy (body weight 93 kg, BMI 36.3 kg/m2). The patient, who was given daily oral doses of 100 mg phenobarbital, 350 mg phenytoin, 800 mg valproic acid and 800 mg carbamazepine over 5 months was hospitalized for obesity treatment. The daily dosage of each drug was held constant during treatment of the obesity. Blood samples were taken five times. Weight reduction was 7 kg (7.5%) over 46 days. Estimation of the pharmacokinetic parameters in each drug was performed by Higuchi's Bayesian program, PEDA Pearson's correlation coefficient (r) between clearance and body weight was calculated for each drug. High positive correlations were found between clearance and body weight for phenytoin (r = 0.800) and valproic acid (r = 0.785), but not for phenobarbital (r = -0.227) and carbamazepine (r = 0.152). Clearance of phenytoin and valproic acid may be potentially affected by small changes in body weight.

Adult↗
PubMed1996

Comparison of two binding equations for prediction of the concentration of unbound valproic acid in the serum of adult epileptic polytherapy patients.

Because binding of valproic acid to plasma proteins affects the efficacy of the drug in the treatment of epilepsy (only the unbound fraction of the drug is effective) we have compared two methods which use different binding parameters to predict the in-vivo concentration of unbound valproic acid in serum. The study was performed on 46 serum samples from 29 polytherapy adult patients with epilepsy. Mean prediction error, mean absolute prediction error and root mean squared error were calculated for each method; these values served as a measure of prediction bias and precision. The mean absolute prediction errors and root mean squared errors for the two methods were similar in magnitude (Method 1, mean absolute prediction error = 10.0 microM, root mean squared error = 15.0 microM; Method 2, mean absolute prediction error = 10.3 microM, root mean squared error = 13.5 microM). Method 2 had a general tendency to over-predict unbound valproic acid; both methods had a tendency to over-prediction for total concentrations above 500 microM. Method 1 had a tendency to under-prediction at total concentrations below 250 microM. Within the total concentration range of valproic acid investigated, Method 1 was superior to Method 2 for prediction of unbound serum valproic acid. Our approach using Method 1 may be useful for prediction of unbound serum valproic acid concentration in patients with total valproic acid concentrations ranging from 250 to 500 microM; Method 2 may be useful for patients with total valproic acid below 500 microM. Our results suggest that there is wide and unpredictable variability in valproic acid binding to serum proteins among study populations.

Adolescent↗
PubMed1996

Elcatonin raises levels of vasoactive intestinal peptide in human plasma.

Elcatonin, used for treatment of hypercalcaemia, Paget's disease and osteoporosis, causes flushing of the face and hands. To determine whether this was because of increased levels of vasoactive intestinal peptide, which is known to induce vasodilation, the effect of elcatonin on the plasma levels of vasoactive intestinal peptide was studied in five healthy volunteers. After a single intramuscular administration of elcatonin (20 int units), peak plasma elcatonin levels (approx. 30 pg mL-1) were achieved 30 min after injection. Plasma vasoactive intestinal peptide concentrations rose similarly with peak levels of about 17 pg mL-1 after 30 min. Side-effects such as cutaneous flushing (most obvious in the face and hands) occurred to an extent dependent on the amount of elcatonin administered, and declined over 45 min in parallel with the fate of plasma vasoactive intestinal peptide. The side-effects of elcatonin, especially cutaneous flushing, seem to be closely connected with vasoactive intestinal peptide.

Adult↗
PubMed1995

Comparison of equations for predicting bound serum concentrations of carbamazepine and carbamazepine-10, 11-epoxide after polytherapy in patients with epilepsy.

In a previous study, an equation with in vivo population binding parameters of carbamazepine and carbamazepine-10, 11-epoxide (CBZ-E) to serum proteins for the relation between unbound and bound serum concentrations was defined. A review by Pynnönen indicates that the average bound/unbound plasma fraction ratio is 3.0 for carbamazepine and 1.0 for CBZ-E. In this study, the ability of equations with in vivo population binding parameters of the previous study (method 1) or with the average bound/unbound plasma fraction ratio of 3.0 of Pynnönen (method 2) to predict the bound serum carbamazepine concentration was retrospectively evaluated using 85 serum samples from 46 patients with epilepsy taking carbamazepine polytherapy. In 21 serum samples from 16 patients, the ability of these equations to predict bound serum CBZ-E concentration was also determined with in vivo population binding parameters from the previous study (method A) or with the average bound/unbound plasma fraction ratio of 1.0 of Pynnönen (method B). Mean prediction error, mean absolute prediction error (MAE), and root mean squared error (RMSE) were calculated for each method, and these values served as a measure of prediction bias and precision. Method 1 showed a bias to overpredict bound serum carbamazepine. The MAE and RMSE were significantly smaller with method 2 (MAE = 2.4 mumol/L; RMSE = 3.2 mumol/L) than with method 1 (MAE = 4.1 mumol/L; RMSE = 4.8 mumol/L). Method 2 was superior to method 1 in terms of accuracy and precision. For bound CBZ-E prediction, method B had a bias to underprediction. The MAE and RMSE were smaller with method A (MAE = 0.581 mumol/L; RMSE = 0.796 mumol/L) than with method B (MAE = 0.724 mumol/L; RMSE = 0.905 mumol/L). Method A was superior to method B in terms of accuracy and precision.

Adolescent↗
PubMed1995

Evaluation of equations for unbound serum concentration prediction of carbamazepine and carbamazepine-10,11-epoxide in polytherapy pediatric patients with epilepsy.

We retrospectively evaluated the ability of equations with in vivo population binding parameters of our previous study (Method 1) or an average unbound fraction of 0.25 of Pynnönen (Method 2) to predict the unbound serum carbamazepine (CBZ) concentration in 50 serum samples from 28 polytherapy pediatric patients with epilepsy. In 12 serum samples from 10 patients, the ability of equations for unbound serum carbamazepine-10,11-epoxide (CBZ-E) concentration prediction was also determined in predictive performance with in vivo population binding parameters of our previous study (Method A) or an average unbound fraction of 0.5 of Pynnönen (Method B). Mean prediction error, mean absolute prediction error (MAE), and root mean squared error (RMSE) were calculated for each method, and these values served as a measure of prediction bias and precision. Method 1 shows a bias to underpredict unbound serum CBZ. The MAE and RMSE were lower in Method 2 (MAE = 0.696 microM, RMSE = 0.912 microM) than in Method 1 (MAE = 0.946 microM, RMSE = 1.138 microM). Method 2 is superior to Method 1 in accuracy and precision. The effects of antiepileptic co-medications on predictive performance of Method 1 are relatively larger in a co-medicated group of serum samples with valproic acid (n = 33, MAE = 0.994 microM, RMSE = 1.211 microM) than in a group of serum samples without valproic acid co-medication (n = 17, MAE = 0.853 microM, RMSE = 0.979 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Alteration in gastric nerve fibers containing gastrin-releasing peptide in relation to the gastrin-producing cell population after truncal vagotomy in a rat model.

The fine structural alteration in the gastric nerve fibers containing gastrin-releasing peptide (GRP) was studied in relation to the dynamics of gastrin-producing cells (G-cells) after truncal vagotomy in a rat model. The circulating gastrin levels were markedly elevated from the 1st day after vagotomy and the number of G-cells with positive immunoreaction for G17 and G34(1-15) was significantly increased in the vagotomized group. On the 3rd day after vagotomy, the G-cells showed conspicuous ultrastructural changes characterized by hypertrophy of the Golgi complexes and increased numbers of secretory granules. The GRP-positive nerve fibers formed a fine network in the gastric wall and were densely distributed in the oxyntic mucosa close to the blood vessels and showing varicosities composed of either small clear or GRP-positive large vesicles containing an electron-dense core. In the oxyntic mucosa of the vagotomized rats, axonal swelling of the nerves occurred on the 3rd day, and a depletion of GRP immunoreactivity was evidenced by a markedly decreased number of large-cored vesicles on the 7th day, when the serum GRP levels were also found to be markedly elevated. These findings indicate that the alteration in gastric nerve fibers containing GRP after truncal vagotomy may be related to hypergastrinemia and antral G-cell hyperplasia in the rat gastric mucosa.

Animals↗
PubMed1995

Enzyme immunoassay of elcatonin in human plasma.

A sensitive and specific double-antibody enzyme immunoassay (EIA) for detecting an elcatonin-like immunoreactive substance (ECT-IS) in human plasma has been developed. In competitive reactions, the ECT antibody was incubated with a plasma sample (or ECT standard) and beta-D-galactosidase-linked synthetic ECT. Free and antibody-bound enzymes were separated using an anti-rabbit IgG-coated immunoplate. Enzyme activity on the plate was determined by fluorescence analysis. This immunoassay allows the detection of 20 to 300 fmol/ml (67 to 1000 pg/ml) of ECT. The EIA was applied to determine the pharmacokinetic behavior of ECT after a single intramuscular administration (20 IU). The maximum level was achieved 30 min after administration, at approximately 30 pg ECT/ml of plasma.

Adult↗
PubMed1995

Evaluation of binding equation method for prediction of unbound serum valproic acid concentration in pediatric patients with epilepsy.

We retrospectively evaluated the ability of Scatchard binding equation method to predict the unbound serum valproic acid (VPA) concentration in 37 pediatric patients with epilepsy receiving VPA monotherapy. The correlation between predicted and observed unbound serum concentrations was high and significant (r = 0.873, p < 0.001). Mean prediction error (ME), mean absolute prediction error (MAE), and root mean squared error (RMSE) were calculated, and served as a measure of prediction bias and precision. The 95% confidence intervals of ME did not include 0, showing a bias to overpredict unbound concentration. The MAE and RMSE were not small in magnitude (MAE 17.4 mumol/l, RMSE 22.8 mumol/l). The current method using the in vivo population mean binding parameters from healthy young adults may be limited in the predictive performance of unbound serum VPA concentration.

Adolescent↗
PubMed1994

Effect of terfenadine on substance P and vasoactive intestinal polypeptide concentrations in nasal secretions from patients with nasal allergy.

Before terfenadine treatment, the mean substance P and vasoactive intestinal polypeptide (VIP) concentrations in nasal secretions from nasal allergy patients tended to be higher than the values of healthy subjects. During terfenadine treatment, the mean substance P concentrations in nasal secretions from patients allergic to house dust or pollen were significantly decreased to 62 and 39% of the initial values, respectively. The mean VIP concentrations in nasal secretions from the house dust allergy patients and the pollen allergy patients were significantly decreased to 52 and 18% of the initial values, respectively. Plasma substance P and VIP concentrations were not affected by nasal allergic symptom and terfenadine treatment.

Adolescent↗