Higher recovery of factor VIII (FVIII) with intermediate FVIII/von Willebrand factor concentrate than with recombinant FVIII in a haemophilia A patient with an inhibitor.
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Adolescent↗
Biomedical subjects
M Takeyama
Publications and source records attributed to M Takeyama.
The measurement of low levels of factor VIII or factor IX in hemophilia A and hemophilia B plasma by clot waveform analysis and thrombin generation assay.
BACKGROUND: Precise assessment of clotting function is essential for monitoring of hemostatic treatment for hemophilias A and B. MATERIALS AND METHODS: Clot waveform analysis and thrombin generation assays were performed on factor (F) VIII- and FIX-deficient plasmas, which had been reconstituted with known amounts of recombinant FVIII (rFVIII) and affinity-purified FIX respectively. Clot waveforms were assessed qualitatively and quantitatively by measuring the parameters clotting time, maximum coagulation velocity (Min1), and maximum coagulation acceleration (Min2). The thrombin generation assay was also assessed qualitatively and measurements made of time to peak and peak height. RESULTS: Overall results obtained with both assays showed good correlation for both clotting factors confirming that the changes in clotting waveform reflected changes in thrombin generation. Both assays demonstrated a predictable dose response to the addition of FVIII or IX. However, clot waveform analysis was more sensitive than the thrombin generation assay, particularly in detecting very low levels (0-0.1 IU dL(-1)) of both factors. CONCLUSIONS: These data suggest that the application of clot waveform analysis to the routine management of the hemophiliacs could increase our understanding of the clinical significance of low levels of FVIII and FIX that cannot be measured by assays in current use. This may be particularly useful in the management of hemophiliacs with inhibitors or undergoing gene therapy.
Biometry↗
Expression of inhibin alpha, glial cell line-derived neurotrophic factor and stem cell factor in Sertoli cell-only syndrome: relation to successful sperm retrieval by microdissection testicular sperm extraction.
BACKGROUND: Microdissection testicular sperm extraction (TESE) has provided new hope for successful sperm retrieval to patients with Sertoli cell-only syndrome (SCO). We determined expression of the inhibin alpha subunit, glial cell line-derived neurotrophic factor (GDNF) and stem cell factor (SCF) in Sertoli cells obtained from patients with SCO immunohistochemically and compared expression rates with rates of microdissection TESE sperm retrieval. METHODS: Testicular biopsy specimens were obtained from 52 men with non-obstructive azoospermia who underwent microdissection TESE and were diagnosed with SCO by histological analysis. RESULTS: All specimens showed intense staining for the inhibin alpha subunit. Moderate or intense staining for GDNF was observed in 65.8% of specimens. All but one showed moderate or intense staining for SCF. Among specimens negative for GDNF, the sperm retrieval rate was significantly higher (100%) for specimens with intense staining for SCF than for specimens with no or moderate staining (30.7%) (P<0.05) for SCF. CONCLUSION: GDNF expression differs among patients with SCO. The sperm retrieval rate was high in cases of no staining for GDNF and intense staining for SCF.
Adult↗
Conventional multiple or microdissection testicular sperm extraction: a comparative study.
BACKGROUND: Testicular sperm extraction (TESE) with ICSI is becoming the first-line treatment for non-obstructive azoospermia (NOA). Recently, the sperm retrieval rate (SRR) by microdissection TESE was reported to be higher than by conventional TESE. However, a comprehensive comparison between multiple and microdissection TESE patients including histological findings has not been reported. METHODS: Patients with NOA who underwent microdissection TESE (n = 56) or multiple TESE (n = 37) were compared. Pre-operative characteristics were similar between groups. In addition, microscopic findings during microdissection TESE also were investigated. RESULTS: Operative time was significantly longer for microdissection TESE than for multiple TESE. Histological examination suggested that spermatogenesis was relatively more impaired in the microdissection TESE group than in the multiple TESE group. Despite this, SRR by microdissection TESE (42.9%) appeared higher than by conventional TESE (35.1%) although this observation failed to reach statistical significance. Seventeen of 26 patients (65.4%) with heterogeneous tubule were successful for sperm retrieval. No severe operative complications occurred in any patient in either group, and no patient required post-operative hormone replacement to treat hypogonadism. CONCLUSIONS: Microsurgical technique is safe and may improve SRR for TESE in a variety of patients with NOA, especially patients with heterogeneous testicular tubules.
Adult↗
Giant intrasacral cellular schwannoma treated with high sacral amputation.
STUDY DESIGN: A case report of a man with a gigantic cellular schwannoma in the sacrum treated with high sacral amputation accompanied by careful nerve root-sparing dissection. OBJECTIVES: To describe the atypical clinical course of an intrasacral cellular schwannoma and the surgical procedure of high sacral amputation performed in a way to prevent needless sacrifice of functionally essential nerve roots. SUMMARY OF BACKGROUND DATA: Fundamentally, a cellular schwannoma is a benign tumor, but the clinical course is atypical. The symptoms are mild and the clinicopathologic features often mislead us to make a diagnosis of malignancy. The occurrence rate of intraosseous cellular schwannoma was reported to be 0.2% of all bony tumors, and the main location was the retroperitoneal space in the pelvis. Forty-one cases of giant intrasacral schwannomas have been reported so far. Among them, large sacral schwannoma with anterior cortex erosion and associated intrapelvic extension was extremely rare. METHODS: The patient presented with a 5-year history of right leg and buttock pain, which did not disturb his daily activities. After a histopathologic diagnosis and a complete set of image studies, high sacral amputation with preservation of uninvolved nerve roots was performed at S1-S2 through a combined anterior and posterior approach. Both S1 nerve roots and the right S2-S3 nerve roots were saved using a threaded saw. The lumbar spine was stabilized to the pelvic girdle using spinal instrumentation with posterolateral fusion. RESULTS: Eighteen months after the tumor was resected the patient had a very good clinical outcome, and there were no radiologic signs of instability or recurrence of the tumor. Locomotor function of both lower extremities and bowel and urinary functions were well maintained. The patient returned to his previous work. CONCLUSIONS: High sacral amputation following a combined anteroposterior approach provided good results without causing any disability. A detailed preoperative planning and careful dissection of uninvolved nerve roots prevented unnecessary neurologic impairment in locomotion and the detrusor and anorectal function.
Dissection↗
[Emerging and re-emerging infections].
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Acquired Immunodeficiency Syndrome↗
Chromosomal variants among 1790 infertile men.
BACKGROUND: The largest cytogenetic survey involving infertile men was undertaken to clarify whether chromosomal abnormalities, including autosomal abnormalities, affect semen qualities. METHOD: All male patients who visited an infertility clinic from 1990 to 1998 underwent chromosomal and semen analysis. RESULTS: Chromosomal abnormalities were found in 225 of 1790 patients (12.6%). The most frequent anomaly was Klinefelter syndrome (64 cases). Autosomal anomalies accounted for 126 cases. 46,XY,1qh(+) was the most common autosomal anomaly (30 cases) and its incidence was significantly higher than those of normal controls. The seminograms of these patients varied widely, with nine patients having azoospermia and three patients achieving natural pregnancies. It is not yet clear if this karyotype affects spermatogenesis. CONCLUSION: Autosomal anomalies as well as sex chromosomal abnormalities might affect spermatogenesis. Cytogenetic study is important before intracytoplasmic sperm injection.
Chromosome Aberrations↗
Cisapride raises the bioavailability of paracetamol by inhibiting its glucuronidation in man.
The effect of cisapride on plasma concentrations of paracetamol was investigated with respect to hepatic metabolism. Paracetamol (1 g) together with cisapride (7.5 mg) or placebo was orally administered to five healthy male volunteers. Venous blood samples were taken before and after administration. Plasma paracetamol and its glucuronide and sulfate conjugates were measured by HPLC. The pharmacokinetic variables were calculated from the plasma concentration-time curves of each volunteer. The area under the plasma paracetamol concentration-time curve from 0 to 180 min (mean +/- s.d.) increased from 1875.0 +/- 112.8 micrg min mL(-1) (placebo coadministration) to 2238.8 +/- 125.8 microg min mL(-1) (cisapride coadministration) (P < 0.01). The mean maximum plasma paracetamol concentration(18.2 microg mL(-1))with placebo was reached 30 min after administration, whereas mean maximum plasma paracetamol concentration (21.2 microg mL(-1)) with cisapride occurred 45 min after administration. The plasma paracetamol concentrations with cisapride were significantly greater at 45 to 120 min after administration compared with placebo. Plasma paracetamol glucuronide conjugate concentrations with cisapride were decreased at 15 to 60 min compared with placebo (P< 0.05), whereas plasma paracetamol sulfate conjugate concentrations did not change significantly. Hence the coadministration of paracetamol with cisapride reduced plasma paracetamol glucuronide concentrations and increased plasma paracetamol concentrations, presumably due to inhibition of paracetamol metabolism via paracetamol glucuronyltransferase. Thus, care is necessary when paracetamol and cisapride are coadministered.
Acetaminophen↗
Enhancement of salivary secretion and neuropeptide (substance P, alpha-calcitonin gene-related peptide) levels in saliva by chronic anethole trithione treatment.
Anethole trithione, a choleretic, has been reported to be effective in the treatment of dry mouth. We have examined the effects of chronic treatment with anethole trithione on salivary secretion, substance P immunoreactive substance (SP-IS) and alpha-calcitonin gene-related peptide immunoreactive substance (alpha-CGRP-IS) concentrations in human saliva. Anethole trithione caused significant increases of saliva SP-IS concentrations from the day 13 (25.3 +/- 1.6 pg mL(-1)) to day 14 (25.8 +/- 1.7 pg mL(-1)) compared with day 1 (19.9 +/- 1.9 pg mL(-1)). Anethole trithione caused significant increase in saliva alpha-CGRP-IS concentration on day 14 (39.9 +/- 4.7 pg mL(-1)) compared with day 1 (27.7 +/- 4.7 pg mL(-1)). Anethole trithione significantly increased the sialosis volumes from day 11 to day 14 (1.6 +/- 0.1-1.7 +/- 0.2 mL) compared with the day 1 (1.2 +/- 0.2 mL). Simple linear regression of the increase in sialosis volume with saliva SP-IS (r = 0.94) and alpha-CGRP-IS (r = 0.97) concentrations was found. These results demonstrated that chronic treatment with anethole trithione affected saliva SP-IS and alpha-CGRP-IS concentration in human saliva and sialosis volume.
Adult↗
Effects of mosapride citrate on human plasma levels of motilin, gastrin, somatostatin, and secretin.
The effect of mosapride citrate (mosapride) on plasma levels of gastrointestinal peptides (motilin, gastrin, somatostatin, and secretin) was studied in five healthy volunteers. After a single oral administration of mosapride (15 mg), the plasma mosapride level (85.0+/-13.7 ng/ml) was highest in the 60-min sample after the administration and then the plasma level fell. Peak plasma motilin levels (18.6+/-1.7 pg/ml) were achieved 60 min after administration of mosapride (p<0.01 vs. placebo), and returned to baseline levels within a further 120 min. Plasma gastrin levels (42.4+/-3.6 pg/ml) increased 60 min after administration of mosapride (p<0.01 vs. placebo). Plasma somatostatin and secretin levels did not change significantly. These results suggest that the pharmacological effects of mosapride on gastrointestinal functions are closely related to changes in motilin-immunoreactive substance levels in human plasma.
Adult↗
Effects of Ninjin-to on levels of brain-gut peptides (motilin, vasoactive intestinal peptide, gastrin, and somatostatin) in human plasma.
We examined the effects of Ninjin-to, a traditional Chinese (Kampo) medicine, on the levels of brain-gut peptides (motilin, vasoactive intestinal peptide (VIP), gastrin, and somatostatin) in plasma from healthy subjects. A single oral administration of Ninjin-to, at a dose of 6.0 g, caused significant increases in plasma motilin levels at 40 to 90 min and somatostatin levels at 20 to 90 min, compared with a placebo treated group. Transient elevations of gastrin levels in the placebo group were inhibited by administration of Ninjin-to, but the medicine did not alter the levels of VIP. In conclusion, these results suggest that pharmacological effects of Ninjin-to on gastrointestinal functions closely relate to changes of motilin, gastrin, and somatostatin-immunoreactive substance levels in human plasma.
Drugs, Chinese Herbal↗
Pharmacokinetics of nimustine, cytosine arabinoside, and methotrexate in cerebrospinal fluid during cerebrospinal fluid perfusion chemotherapy.
This report investigates the pharmacokinetics of nimustine (ACNU), cytosine arabinoside (Ara-C), and methotrexate (MTX) in cerebrospinal fluid (CSF) during CSF perfusion chemotherapy. A 47-year-old Japanese man with spinal cord, cerebellum and brain stem dissemination of oligo-astrocytoma received nine courses of CSF perfusion chemotherapy with ACNU, Ara-C, and MTX. A CSF perfusion chemotherapy solution was perfused via an Ommaya reservoir in the ventricle, and was discharged by drainage though another Ommaya reservoir in the lumbar spinal canal. CSF samples via Ommaya reservoirs in the lumbar spinal canal were obtained during the fifth and eighth courses of treatment. The concentrations of ACNU and Ara-C in CSF were measured by HPLC, and the MTX concentrations by fluorescence polarization immunoassay. In the fifth course of treatment, a CSF injection chemotherapy solution, consisting of 5 mg of ACNU dissolved in 20 ml of artificial CSF, was injected over a few minutes using the Ommaya reservoir. Next, a CSF perfusion chemotherapy solution, consisting of 10 mg of Ara-C and 5 mg of MTX dissolved in 100 ml of artificial CSF, was perfused over 2 h. In the eighth course of treatment, a CSF perfusion chemotherapy solution, consisting of 5 mg of ACNU, 10 mg of Ara-C and 5 mg of MTX dissolved in 100 ml of artificial CSF, was perfused over 2 h. In both treatments, the highest concentrations of Ara-C and MTX in CSF were observed 1 or 2 h after the end of perfusion, with the values of each drug being similar. The CSF AUCs of Ara-C and MTX in each treatment were of similar values. Although the highest concentration of ACNU in CSF was observed in the fifth treatment 1 h after injection (an injection chemotherapy of ACNU plus a perfusion chemotherapy of Ara-C and MTX), the concentration of ACNU in CSF was undetectable in the eighth treatment (a perfusion chemotherapy of ACNU, Ara-C and MTX). We were successful in administering all anticancer drugs, and reaching a level of over 1.0 microg/ml concentration in CSF of the lumbar spinal canal, using an injection chemotherapy of ACNU plus a perfusion chemotherapy of Ara-C and MTX; this was done even though the drugs, in particular ACNU, underwent some perfusion-period dependent decomposition.
Adult↗
Rikkunshi-to raises levels of somatostatin and gastrin in human plasma.
Rikkunshi-to, a traditional Chinese (Kampo) medicine, has been used to treat chronic hypofunctions of the gastrointestinal tract. The effects of Rikkunshi-to on the plasma levels of gut-regulated peptide (somatostatin, motilin, gastrin, and vasoactive intestinal peptide (VIP)) levels were studied in healthy subjects. A single oral administration of Rikkunshi-to caused significant increases in plasma somatostatin and gastrin levels at 60 to 240 min compared with a placebo group. On the other hand, this medicine showed no effects on motilin and VIP levels. In conclusion, these results might indicate that the pharmacological action of Rikkunshi-to is closely related to changes in somatostatin- and gastrin-immunoreactive substance levels.
Adult↗
[Prophylactic effect of pirarubicin (THP) on postoperative recurrence of superficial bladder cancer in terms of intravesical retention time].
In order to determine the modality of prophylactic intravesical instillation of pirarubicin (THP = tetrahydropyranyladriamycin) following transurethral resection (TUR) of superficial bladder cancer, a prospective randomized study was performed. A total of 79 patients were randomized into "2-hour instillation" (A), "5-min instillation" (B) and "control" (C) groups. Prophylactic efficacy and side effects were analyzed in each group. In groups A and B, 20 mg of THP was first dissolved in 10 ml of distilled water, adjusted to 40 ml with saline and was administered intravesically once a week for 10 weeks, starting from 1 week after TUR. The recurrence-free rate was calculated in 65 evaluable patients. The one-year recurrence-free rate was 70.2% in group A, 62.8% in group B and 52.1% in group C. The one-year recurrence-free rate was significantly higher in group A than in group C. Adverse effects were observed in 21.4% of the patients in group A and 40.7% in group B. There was no significant difference in the occurrence rate of side effects between these two groups. Taking the prophylactic efficacy and side effects into consideration, "2-hour instillation" seemed to be better than "5-min instillation".
Administration, Intravesical↗
Nitric oxide-mediated antitumor activity induced by the extract from Grifola frondosa (Maitake mushroom) in a macrophage cell line, RAW264.7.
We have investigated D-fraction (MDF) extracted from Grifola frondosa (Maitake mushroom) on the inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) production in RAW264.7 (RAW) cells, a murine monocyte/macrophage cell line, with special reference to antitumor activity of MDF against human hepatoma-derived huH-1 cells. MDF could induce iNOS mRNA expression in RAW cells in a dose range of more than 30 microg/ml, but the effect of 10 microg/ml of MDF was negligible. The iNOS mRNA expression induced by 100 microg/ml of MDF was 6 hrs later, but lasted for a longer time than that of lipopolysaccharide (LPS), a representative iNOS inducer. Although iNOS mRNA levels in MDF-stimulated cells were almost equal to LPS-stimulated cells at the peak time, the cumulative amount of nitrite was only about 50% compared with that of LPS-treated cells. When huH-I cells were cultured in MDF containing media in a 24-well plate with inserted porous bottom in the presence or absence of RAW cells, the viability of huH-1 cells decreased significantly only in the presence of RAW cells in MDF dose-dependent manner. This antitumor activity of RAW cells in the presence of MDF was abolished or attenuated by the addition of L-NAME, a NOS inhibitor, confirming that this phenomenon is due to iNOS-mediated NO production by RAW cells, but not direct cytotoxic activity of MDF against huH-1 cells. These data suggest that MDF is a novel inducer for iNOS which contributes at least in part to antitumor activity of MDF.
Agaricales↗
Effects of Dai-kenchu-to on levels of 5-hydroxytryptamine (serotonin) and vasoactive intestinal peptides in human plasma.
We examined the effects of Dai-kenchu-to (DKCT) on the levels of vasoactive intestinal peptide (VIP) and 5-hydroxytryptamine (serotonin; 5-HT) in plasma taken from 6 healthy subjects. A single oral administration of 7.5 g DKCT caused significant increases in plasma VIP at 30, 60 to 90 and 120 min (3.5-5.5 pg/ml), compared with the response in a placebo group (about 1.0 pg/ml). DKCT also caused significant increases in plasma 5-HT at 30 (121.8+/-7.3 ng/ml) and 60 (156.5+/-8.0 ng/ml) min, compared with the response in the placebo group (about 101 ng/ml). These results indicate that the stimulatory effect of DKCT on VIP-immunoreactive substance (VIP-IS) secretion is due, at least in part, to increased 5-HT levels in the abdomen. As a consequence, increased VIP-IS may improve feelings of coldness in the abdomen.
Adult↗
Methotrexate concentration in cerebrospinal fluid of the space created by tumor removal.
This paper investigates the post-surgical pharmacokinetics of methotrexate (MTX) in the plasma, the cerebrospinal fluids (CSF), and the spaces created by tumor removal (STR) in patients with glioblastoma, during hyperosmotic disruption of the blood brain barrier (HODBBB) and intra-arterial chemotherapy with MTX. Eight Japanese patients with glioblastoma, three with open STRs and five with closed STRs, received a total of thirteen courses of HODBBB and intra-arterial combination chemotherapy with MTX. The patients were initially administered mannitol, then the anticancer drugs were infused into the carotid artery. Samples of blood and CSF from the STRs were obtained. MTX concentrations were measured by fluorescence polarization immunoassay and the pharmacokinetic parameters of MTX in plasma and CSF were estimated. The plasma concentrations of MTX peaked at the end of drug infusion, and then decayed bi-exponentially during the remainder of the treatment period. The CSF concentration of MTX in the STR peaked 2 h after drug administration, then mono-exponentially decreased. The area under the concentration-time curve (AUC) for plasma and CSF MTX concentrations increased in parallel with the MTX dose. In patients with open STRs, the mean AUC of MTX in CSF was 4.44% of that found in plasma, while in patients with closed STRs, the mean was 61.2% of that found in plasma. In the latter group, the MTX administered using HODBBB and intra-arterial chemotherapy was maintained in the STRs for long periods.
Area Under Curve↗
Pharmacokinetics of cytosine arabinoside, methotrexate, nimustine and valproic acid in cerebrospinal fluid during cerebrospinal fluid perfusion chemotherapy.
This report investigates the pharmacokinetics of cytosine arabinoside (Ara-C), methotrexate (MTX), nimustine (ACNU) and valproic acid (VPA) in cerebrospinal fluid (CSF) during CSF perfusion chemotherapy. A 28-year-old Japanese woman with disseminated glioblastoma was, on admission, on a stable oral regimen of prolonged-release VPA tablets (Depakene-R), 400 mg twice a day, for seizure control. Twelve courses of CSF perfusion chemotherapy with Ara-C, MTX, and ACNU were administered. Plasma samples and CSF samples via Ommaya reservoirs were obtained during the eleventh course of treatment. The Ara-C and ACNU concentrations were measured by HPLC. The MTX and VPA concentrations were measured by fluorescence polarization immunoassay. During CSF perfusion chemotherapy, the highest CSF concentrations of Ara-C, MTX, and ACNU were observed at the end of the perfusion and decreased in a monoexponential pattern. The half-lives of Ara-C, MTX, and ACNU were 2.65, 3.52, and 0.71 h, respectively. No anticancer drugs were detectable in plasma during CSF perfusion chemotherapy. Before CSF perfusion chemotherapy, the free VPA concentration in plasma was 14.4% of the total VPA concentration. The mean total and free VPA concentrations in plasma were 78.0+/-0.8 and 10.9-0.3 microg/ml, respectively. The free VPA concentrations in plasma and in CSF were of similar values. At the end of perfusion, the lowest free VPA concentration in CSF was 30.3% of that at the initiation of perfusion. The free VPA concentrations in CSF at 3, 7, 23, and 47 h after the end of perfusion were 79.8, 94.5, 100.9, and 100.9% respectively of that at the initiation of perfusion. During CSF perfusion chemotherapy, the ratio of free VPA concentrations to the total VPA in CSF was 86.3+/-6.9%. The VPA concentrations in CSF rapidly decreased during the CSF perfusion but recovered to pre-treatment levels within 7 h.
Adult↗