Change of valproic acid concentrations during cerebrospinal fluid perfusion chemotherapy.
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Biomedical subjects
Publications and source records attributed to M Takeyama.
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A case of male adenomatoid tumor of tunica albuginea of the testis is reported. A 45-year-old man referred to our hospital because of intrascrotal mass on the right side. The mass increased in size for eight months. Then we excised the tumor, and spared the right testis. The tumor was arising from the tunica albuginea of the testis with a pedicle. The histological diagnosis was adenomatoid tumor. Adenomatoid tumor is a rare benign tumor. A total of 97 cases of adenomatoid tumor of epididymis have been reported in males, but only 23 cases of adenomatoid tumor of the testis have been reported in Japan. Herein, 24 cases of adenomatoid tumor of testis including our case are discussed and reviewed.
We made an attempt to compare the complaints about sleep disturbance in the elderly based on the questionnaires using self-rating scales carried out in 1983 and 1996. It was noted that the score of awakening frequency from the course of sleep was the highest of all the items in men and women in both the 1983 and 1996 inquiries. The scores of insomnia nights per week and the difficulty in falling asleep were slightly higher in women than in men in both inquiries.
We have evaluated urine specimens of presumptive cases of legionnaires' disease (110 cases, 173 sample), collected in the past eight years (April, 1990-August, 1998) with the Binax EIA kit which detects the soluble antigen of Legionella pneumophila serogroup (SG) 1, and the Biotest EIA kit which detects Legionella species. Seven cases (19 specimens) were positive for the Binax EIA kit, and nine cases (22 specimens) were positive for the Biotest EIA kit. The sensitivity for culture, PCR, IFA method were 100%, 100%, and 50%, the specificity for these method were 93%, 97.1%, and 90% respectively. Overall agreements for these method were 93.5%, 97.4%, 86.8%, these results suggested that the urinary antigen detection test had high sensitivity and specificity. Our study indicated that concentrated urine samples increase sensitivity. We also evaluated the capabilities of both EIAs to detect soluble antigens were extracted from bacterial suspension of 18 strains of 5 Legionella species by heating. Both assays detected L. pneumophila serogroups 1 to 14, L. bozemanii. The Binax EIA proved to be useful as the Biotest EIA for diagnosis of legionellosis caused by Legionella species and serogroups other than L. pneumophila serogroup 1. Some cases have been shown to excrete antigen for prolonged period of times despite recovery from infection, so that the patient's history should be sought. The urine antigen detection EIA methods proved to be rapid and easy to use, detect antigen in the early stage of the disease with high sensitivity and specificity. Its use for the definition of legionellosis should be considered in Japan.
We examined the effect of Dai-kenchu-to (DKCT), a traditional Chinese (Kampo) medicine, on the levels of 3 brain-gut peptides (motilin, gastrin and somatostatin) in plasma from 24 healthy subjects. A single oral administration of DKCT, at a dose of 7.5 g, caused significant increases in plasma motilin levels (about 12 pg/ml) at 60 to 90 min, compared with a placebo-treated group. Transient elevations of gastrin levels were noted after administration of both DKCT (25.9+/-1.4 pg/ml) and placebo (23.5+/-1.3 pg/ml). DKCT did not alter the levels (about 5.7 pg/ml) of somatostatin. In conclusion, these results indicate that the action of DKCT closely relates to changes in motilin-immunoreactive substance levels in human plasma.
The present paper investigates the pharmacokinetics of etoposide (VP-16) and carboplatin (CBDCA) in plasma and the cerebrospinal fluid (CSF), in the space left by tumor removal, of patients with glioma. Eight Japanese patients with glioma received a course of hyperosmotic disruption of the blood-brain barrier (HODBBB) and intraarterial combination chemotherapy with 60 mg/m2 of VP-16 and 300 mg/m2 of CBDCA. All patients were initially administered mannitol, followed by infusion of the anticancer drugs into the right internal carotid artery. Blood samples and samples of CSF in the space left by tumor removal were obtained. VP-16 and CBDCA concentration were measured by HPLC, and the pharmacokinetic parameters of these drugs estimated in CSF and plasma. The plasma concentrations of VP-16 and CBDCA peaked at the end of infusion, then decreased in a bi-exponential decay pattern during the remainder of the treatment period. Both VP-16 and CBDCA were detectable in CSF beginning 0.5 h after the initiation of each infusion, and were then slowly eliminated from the space left by tumor removal. The mean maximum CSF concentration of VP-16 and CBDCA was 0.17 and 15.25% of that in plasma, respectively. The mean area under the time-CSF concentration curve from 0 to 24 h after VP-16 and CBDCA infusion was 1.91 and 113.6% of plasma, respectively. In two of the eight patients, the clinical response to treatment was a partial response and other patients showed no change. HODBBB and intraarterial combination chemotherapy with VP-16 and CBDCA may be useful in patients with brain tumors for maintenance chemotherapy.
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OBJECTIVE: To investigate the postoperative pharmacokinetics of methotrexate in the plasma and cerebrospinal fluid (CSF) in the space created by tumor removal of a patient with glioblastoma during hyperosmotic disruption of the blood-brain barrier (BBB) and intraarterial chemotherapy with a stepwise increase in the methotrexate dosage. CASE SUMMARY: A 30-year-old Japanese woman with glioblastoma received four courses of hyperosmotic disruption of the BBB and intraarterial chemotherapy with a combination of peplomycin, vindesine, nimustine, pirarubicin, and methotrexate. The patient was initially administered mannitol; anticancer drugs were then infused into the left internal carotid artery. Following the first, second, third, and fourth courses of treatment, methotrexate 350, 700, 1000, and 1500 mg, respectively, were administered for 30 minutes. Samples of blood and CSF from the space created by tumor removal were obtained. Methotrexate concentrations were measured by fluorescence polarization immunoassay and the pharmacokinetic parameters of methotrexate in plasma and CSF were estimated. RESULTS: The plasma concentration of methotrexate peaked at the end of drug infusion, then decreased in a biexponential decay manner during the remainder of the treatment period. The CSF concentration of methotrexate in the space created by tumor removal peaked two hours after drug administration, then monoexponentially decreased. Although the maximal CSF concentration of methotrexate in the space created by tumor removal was lower than that in the plasma, the CSF concentration of methotrexate in the space created by tumor removal exceeded that in the plasma six hours after drug infusion. The half-life of methotrexate in the CSF exceeded that in the plasma. The AUC for the plasma and CSF methotrexate concentration increased parallel with the methotrexate dosage. The mean CSF AUC of methotrexate was 59.4% of that found in plasma. CONCLUSIONS: The CSF AUC of methotrexate in the space created by tumor removal increased parallel with the methotrexate dosage during hyperosmotic disruption of the BBB and intraarterial chemotherapy.
A case of azoospermia due to genitourinary tuberculosis is reported with discussion on the treatment of infertility in such a case. A 38-year-old man visited us complaining of 4-year sterility. We suspected obstructive azoospermia due to previous genitourinary tuberculosis because of his treatment history, calcifications in the seminal vesicles and nodules in the right epididymis. After microsurgical epididymal sperm aspiration (MESA) was performed twice without success, we extracted sperm from his testis (testicular sperm extraction, TESE) and fertilized his wife's egg by intracytoplasmic sperm injection.
OBJECTIVE: This study was conducted to evaluate the pharmacokinetics of anticancer drugs in cerebrospinal fluid (CSF) perfusion chemotherapy. METHODS: We administered CSF perfusion chemotherapy with nimustine (ACNU), methotrexate (MTX), and cytosine arabinoside (Ara-C) to three patients with disseminated malignant brain disease. The drugs were infused via Ommaya's reservoirs to the lateral ventricle and removed by drainage from the temporal lobe or lumbar spine. CSF and plasma concentrations of the anticancer drugs were determined by high-performance liquid chromatography and fluorescence polarization immunoassay. RESULTS: The concentrations of anticancer drugs in the discharged CSF peaked about 40 min after the start of a 1-h CSF perfusion. After the perfusion, the drug level in CSF decreased exponentially in a monophasic manner. ACNU and Ara-C were not detectable in the discharged CSF in the temporal lobe at 6 h and 48 h after perfusion, respectively, but MTX was detectable at 48 h. The maximum concentration ratio of anticancer drugs and the duration of perfusion were inversely correlated. The plasma concentrations of anticancer drugs were much lower than those in CSF. The half-life of ACNU was very short (0.2-1.1 h), whereas the half-lives of MTX and Ara-C were relatively long (2.81-13.5 h and 1.84 6.25 h, respectively). The half-lives of the anticancer drugs in CSF tended to decrease with repeated CSF perfusion chemotherapy. CONCLUSION: Results suggest that CSF perfusion chemotherapy enables a high concentration of anticancer drug to be administered for dissemination in the spinal cord within a short period of time, with minimal adverse effects.
PURPOSE: Approximately 15 to 20% of infertile men have azoospermia. In the Y chromosome a deletion, termed the azoospermic factor, has been found in some cases of idiopathic azoospermia. We investigate the relationship of factors in autosomal chromosomes (HLA class I antigens) to spermatogenesis failure in idiopathic azoospermia. MATERIALS AND METHODS: We evaluated 65 infertile Japanese men with idiopathic azoospermia. The frequency of the HLA allele reported in 1,216 healthy Japanese men was used as a control. HLA class I typing was performed by the National Institutes of Health standard serological method or polymerase chain reaction-sequence specific primer analysis. Allele frequencies were calculated. We determined statistical significance in the frequency of each allele in patients and controls using the chi-square test. The relationship of HLA antigens to idiopathic azoospermia was expressed as relative risk. RESULTS: In Japanese men with idiopathic azoospermia the frequency of HLA-A33, B13 and B44 was significantly increased compared with controls. The relative risk of HLA-B44 was 8.4, an extremely high value compared with that of other diseases and HLA antigens. CONCLUSIONS: We suggest that HLA class I antigens are important genetic markers that represent a risk factor for idiopathic azoospermia.
In order to know the possible effects of gastrin releasing peptide (GRP) on nevus cells and melanocytes, we studied the effect of GRP on the proliferation of cultured human nevus cells and normal melanocytes. MTS assay showed that GRP stimulated the growth of viable melanocytes at 1000 ng/ml. GRP also stimulated the growth of nevus cells in a dose dependent manner and maximum stimulation was obtained at 100 ng/ml of GRP. GRP was less effective for growth stimulation of normal melanocytes than nevus cells. The cytoplasm of nevus cells were positively stained by polyclonal anti-GRP antibody. We also detected the expression of GRP and GRP receptor mRNAs in these cells by RT-PCR. These results suggest that GRP acts as an autocrine growth factor for nevus cells and normal melanocytes.
We made an attempt to express a complaint of sleep disturbance by a self-rating scale of radar chart mode. The questionnaire for sleep disturbance is made up of eight items. Each item was scored from grade 1 to 4. The score of each item was projected to the MY radar chart, designed by us. It is noted that this method is useful in following the effect of hypnotics on sleep disturbance.
The present paper investigates the pharmacokinetics of pirarubicin (THP) in the plasma and cerebrospinal fluid (CSF) of two patients with glioma during hyperosmotic disruption of the blood-brain barrier (HODBBB) and intra-arterial combination chemotherapy. A 42-year-old Japanese man (patient A) with glioblastoma and a 21-year-old Japanese woman (patient B) with astrocytoma received a course of HODBBB and intra-arterial combination chemotherapy with THP, methotrexate, peplomycin, and vindesine. Patient A was initially administered mannitol, followed by the infusion of anticancer drugs into the right internal carotid artery. Patient B was initially administered mannitol, followed by the infusion of anticancer drugs into the right internal carotid artery and, immediately thereafter, into the right vertebral artery. Samples of blood and of CSF in the brain ventricle were obtained. THP concentration was measured by HPLC, and the pharmacokinetic parameters of this drug were estimated in plasma and CSF. In both patients, the plasma concentration of THP peaked at the end of infusion, then decreased in a bi-exponential decay pattern during the remainder of the treatment period. THP was detectable in CSF beginning 1.0 h after the initiation of infusion, then was slowly eliminated from the ventricle. The maximum CSF concentration of THP was 0.97% of plasma in patient A and 0.89% in patient B. The CSF AUC of THP was 28.4% of plasma in patient A and 13.1% in patient B.
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OBJECTIVE: To examine the pharmacokinetics of anticancer drugs in the cerebrospinal fluid (CSF) during chemotherapy by the lumbar-ventricular (LV) and ventricular-lumbar (VL) routes. CASE SUMMARY: A 69-year-old Japanese woman with disseminated glioblastoma received two LV and four VL courses of CSF perfusion chemotherapy with methotrexate, nimustine, and cytarabine hydrochloride. Samples of CSF from the ventricles and lumbar spinal canal were obtained via Ommaya reservoirs during one LV and one VL course. Drug concentrations in the CSF were measured by fluorescence polarization immunoassay or HPLC. RESULTS: During LV CSF perfusion, the highest CSF drug concentrations in both the ventricles and the lumbar spinal canal were observed at the end of perfusion. During treatment, the concentrations of all three drugs in the lumbar spinal canal were higher than those in the ventricles. The CSF AUC of methotrexate in the ventricles was 16.1% of that in the lumbar spinal canal. During VL CSF perfusion, the highest drug concentrations were also observed at the end of perfusion. The drug concentrations in the lumbar spinal canal were initially lower than those in the ventricles. However, the concentrations of methotrexate and cytarabine in the lumbar spinal canal exceeded those in the ventricles 3 hours after perfusion. The AUC of methotrexate in the lumbar spinal canal was 174.9% of that in the ventricles. CONCLUSIONS: The pharmacokinetics of anticancer drugs in ventricular CSF differ from those in lumbar CSF during LV and VL perfusion chemotherapy.
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Alanyl aminopeptidase (AAP) was purified to homogeneity from human seminal plasma. The calculated molecular weight of the purified enzyme was approximately 137,000+/-5,000 from light scattering, 140,000 (main) and 137,000 (minor) from non-denatured PAGE and 153,000 from SDS-PAGE in the absence or presence of 2-mercaptoethanol (2-ME). These findings suggest that the enzyme is monomeric in form in human seminal plasma. The enzyme hydrolyzed several amino acid 4-methyl-coumaryl-7-amide (MCA) substrates. The order of Kcat/Km values of AAP at optimal pH (pH 7.5) was Ala- > Lys-Ala- > or = Met- > Leu- > Phe- > Arg- > or = Arg-Arg- > Lys- > Gly-MCAs. AAP was potently inhibited by bestatin, leuhistin, actinonin, amastatin, and 1,10-phenanthroline. These findings suggest that AAP is an aminopeptidase. We determined that the amino acid sequence of the first 22 residues of the enzyme was Ser1-Thr-Thr-Pro-Ser5-Ala-Ser-Ala-Thr-Thr10-Asn-Pro-Al a-Ser-Ala15-Thr-Thr-Leu-Asp-Gln20-Ser-Lys-. This sequence was completely coincident with that downstream of the transmembrane site of human intestinal alanyl aminopeptidase N (CD13). We also isolated cDNA encoding AAP from human prostate cDNA library, sequenced its structure, and confirmed human seminal plasma AAP to be identical with alanyl aminopeptidase N. We postulated that native human seminal plasma alanyl aminopeptidase is released into the seminal plasma after the specific site is cleaved by elastase or an elastase-like enzyme. The enzyme level in human seminal plasma determined by single radial immunodiffusion was 5.2+/-3.2 mg/100 ml (mean+/-SD, n=20) in individuals 20-47 years of age. AAP was immunohistochemically stained in the luminal site-cell membrane of epithelial cells in the prostatic gland and ductuli efferentes of the testis.