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Y Kosaka

Publications and source records attributed to Y Kosaka.

At least 55 records · Page 3Linked to original sources
PubMed1999

Genetic polymorphism of CYP2D6 in the Japanese population.

The frequencies of CYP2D6 mutations in a Japanese population were investigated. Individuals were classified into three groups: control individuals, cancer patients and Parkinsonians. Genotyping for CYP2D6*3, CYP2D6*4 and CYP2D6*18 was carried out using the polymerase chain reaction, and that for CYP2D6*5 was also carried out using XbaI restriction fragment length polymorphism. The frequencies of the CYP2D6*3, CYP2D6*4, CYP2D6*5 and CYP2D6*18 mutant alleles were 0%, 0.77%, 4.10% and 0.53% in more than 256 Japanese control individuals, respectively. Based on these data, the population frequency of the CYP2D6 poor metabolizer phenotype was estimated to be 0.29%. The distribution of the four mutated alleles was not significantly different between control individuals and cancer patients or Parkinsonians.

Alleles↗
PubMed1999

Concentration of lidocaine affects intensity of sensory block during lumbar epidural anesthesia.

UNLABELLED: We investigated the effects of a twofold difference in concentration and volume of lidocaine on lumbar epidural block using a cutaneous current perception threshold (CPT) quantitative sensory testing device. Twenty ASA I patients scheduled for elective gynecological surgery were randomly divided into two equal groups to receive either 20 mL of 1% lidocaine or 10 mL of 2% lidocaine through an epidural catheter inserted at the L1-2 interspace. CPTs at 2000-, 250-, and 5-Hz stimulation and sensation to light touch, temperature, and pinprick at ipsilateral dermatomes V, T9, and L2 were measured before and every 5 min until 60 min after the epidural lidocaine. Epidural anesthesia with both solutions produced a significant increase in all CPTs at dermatomes T9 and L2. Alterations in CPTs were similar for both groups at T9 but were significantly greater in patients given 2% lidocaine than in those given 1% lidocaine at L2. There were no differences in the upper level of sensory block to cold, pinprick, and touch between the two groups. We conclude that lumbar epidural anesthesia with 10 mL of 2% lidocaine produces more intense blockade of both large- and small-diameter sensory nerve fibers than that with 20 mL of 1% lidocaine. IMPLICATIONS: The effects of local anesthetic concentration and volume on the quality of epidural anesthesia have not been adequately investigated. The results of the present study suggest that the concentration affects the intensity of sensory block during epidural anesthesia with lidocaine.

Adult↗
PubMed1998

Detection of nivalenol genotoxicity in cultured cells and multiple mouse organs by the alkaline single-cell gel electrophoresis assay.

We tested the genotoxicity of nivalenol (NIV), a potent toxic trichothecene from Fusarium nivale, in cultured CHO cells and in several mouse organs and tissues (liver, kidney, thymus, bone marrow and mucosa of stomach, jejunum, and colon) using the alkaline single-cell gel electrophoresis (SCG, or Comet) assay. NIV at 50 and 100 micrograms/ml damaged the nuclear DNA of CHO cells in the absence of S9 mix, showing that NIV was a direct mutagen. In an in vivo study, mice were sacrificed 2, 4, and 8 h after either oral (20 mg/kg) or intraperitoneal (3.7 mg/kg) administration of NIV. DNA damage was measured by the SCG assay as modified by us. After oral dosing, DNA damage appeared in the kidney and bone marrow at 2 h (returning to almost control level within the following 2 h), and in the stomach, jejunum, and colon at 2, 4, and 8 h, respectively. Liver and thymus DNA were not damaged. After intraperitoneal injection, no DNA damage appeared in any of the organs or tissues tested except for the colon, where extensive DNA damage was observed, as in the oral study, at 8 h. For histopathological examination, mice were sacrificed 2, 4, and 8 h after oral (20 mg/kg) administration of NIV. No necrotic changes were detected in any of the organs where NIV yielded statistically significant DNA damage. To measure the effect of NIV on transport activity in mice, 10 ml/kg (same volume as NIV treatments) of 1% brilliant blue FCF (BB) was administered orally. Thirty minutes later, the BB reached the colon, and simultaneous oral administration of NIV (20 mg/kg, dissolved in 10 ml BB solution) did not affect the dye transport rate. Thus, the strong yet delayed damage to colon DNA may follow from a systemic absorption rather than a topical effect. As a direct mutagen, NIV showed organ specific genotoxicity in mice in time and intensity.

Alkalies↗
PubMed1998

Detection of pyrimethamine-induced DNA damage in mouse embryo and maternal organs by the modified alkaline single cell gel electrophoresis assay.

We studied the embryonic and maternal genotoxicity of pyrimethamine (PYR), a potent teratogen and folate antagonist, using alkaline single cell gel electrophoresis (SCG, or Comet) assay as modified by us (we used isolated nuclei instead of isolated cells). ICR mice were treated on the 13th day of pregnancy with a single oral dose of 50 mg PYR/kg. Six maternal organs (liver, kidney, lung, brain, spleen, bone marrow), maternal and fetal placentas, and two embryos were taken 6 and 16 h after treatment; the embryos were divided into head and body portions. Each sample was minced, homogenized gently, and centrifuged. The nuclei from the precipitates were used. PYR induced DNA damage in all maternal organs except spleen and bone marrow 6 h after administration. The DNA damage in all the affected organs was less at 16 h than at 6 h, and that of the kidney and brain returned to control level at 16 h. PYR also induced DNA damage in maternal and fetal placentas and embryos that was detected at 6 and 16 h, with greater damage at 6 h. Co-treatment of folinic acid calcium salt (FNA, 10 mg/kg ip), a reduced active folate form, prevented the PYR-induced DNA damage in all target tissues examined 6 h after treatment. These data indicate that the observed embryonic and maternal DNA damage caused by PYR may be related to folate deficiency, and that the modified alkaline SCG assay can be used to predict fetal/embryonic genotoxicity in vivo, in addition to the organ-specific maternal genotoxicity.

Animals↗
PubMed1998

Elevation of the serum Fas ligand in patients with hemophagocytic syndrome and Diamond-Blackfan anemia.

Fas ligand (FasL) is a membrane protein that is expressed in activated T cells and natural killer cells. FasL binds to Fas on target cells and induces apoptosis. There exists a soluble form of FasL (sFasL), and sFasL also induces apoptosis of Fas-bearing cells. The serum sFasL concentrations were reported to be elevated in patients with large granular lymphocytic leukemia and natural killer cell lymphoma. In this study, we have measured serum sFasL concentrations in other hematological disorders, including severe aplastic anemia (SAA), hemophagocytic lymphohistiocytosis (HLH), and Diamond-Blackfan anemia (DBA). The serum sFasL concentration of age-matched healthy controls was 0.16 +/- 0.11 ng/mL (mean +/- SD, n = 22). The serum sFasL levels in the patients with HLH and DBA were 3.75 +/- 3.82 (n = 19; P < .0001, HLH v control) and 2.76 +/- 2.43 ng/mL (n = 6; P = .012, DBA v control), respectively. Serum interferon-gamma concentration was elevated in the patients with HLH (1.61 +/- 2.62 ng/mL) but not in those with DBA (below the detectable level). These results suggest that the Fas-FasL system plays a role, at least in part, in the pathophysiology of HLH and DBA.

Adolescent↗
PubMed1998

Microparticle resins as a potential nasal drug delivery system for insulin.

The application of various resins for the nasal delivery of insulin was examined in rabbits. Intranasal administration of human insulin (28 U, 1 mg) mixed with fractionated sodium polystyrene sulfonate powder (an anionic resin with a particle size of 20-45 microns) caused a rapid increase of the plasma insulin level 413.0 +/- 71.7 microU/ml (mean +/- S.D.) after 15 min, while intranasal administration of insulin alone caused little increase. The blood glucose level decreased from 118.8 +/- 18.5 mg/dl to 65.8 +/- 13.8 mg/dl at 45 min after administration. These results were superior to those obtained with the unfractionated resin. Styrene-divinylbenzene copolymer (a nonionic resin; 20-45 microns fraction) showed similar enhancement of nasal insulin absorption. In contrast, polyacrylester (a nonionic resin; 20-45 microns fraction) and cholestyramine (a cationic resin) did not promote insulin absorption. These results suggest that some resins may be useful for nasal delivery of insulin.

Administration, Intranasal↗
PubMed1998

Anaesthetic management of caesarean section in a patient with myelodysplastic syndrome.

PURPOSE: This case report describes the anaesthetic management for Caesarean section in a patient with myelodysplastic syndrome. CLINICAL FEATURES: A woman with myelodysplastic syndrome underwent Caesarean section on two occasions. The first Caesarean section was performed at age 20 yr using general anaesthesia with nitrous oxide-oxygen and fentanyl. In her second pregnancy at 25 yr, there was severe pancytopenia at 28-wk gestation with a leukocyte count 3.6 x 10(9).L-1, erythrocyte count 1.2 x 10(12).L-1, haemoglobin 50 g.L-1, haematocrit 14.7% and platelet count 51 x 10(9).L-1. Following leukocyte poor red cells and platelet transfusion, general anaesthesia was maintained with nitrous oxide-oxygen-sevoflurane and fentanyl. Both operations were uneventful and healthy infants were delivered. CONCLUSION: It is important to have a team approach (anaesthetist, obstetrician and haematologist) for the perianaesthetic management of patients with myelodysplastic syndrome. An exact assessment of the haematological condition, the need for prophylactic treatment and anaesthetic management should be determined for each individual patient.

Adult↗
PubMed1998

Translocation (10;12)(q24;q15) in a T-cell lymphoblastic lymphoma with myeloid hyperplasia.

We present a case of childhood T-cell lymphoblastic lymphoma (T-LBL) with a translocation (10;12)(q24;q15) as a main clonal abnormality, which to our knowledge is the first reported karyotype of this malignancy. The patient's peripheral blood and bone marrow showed marked leukocytosis mostly myeloid lineage cells, at diagnosis. The enlarged lymph node consisted of two different cell populations: CD2+/CD7+ prothymic lymphoblasts and a cluster of peroxidase-positive myeloid cells around vessels. This case might represent a rare but distinct clinical entity of LBL.

Adolescent↗
PubMed1998

Quantitative and selective assessment of sensory block during lumbar epidural anaesthesia with 1% or 2% lidocaine.

We have examined sensory block during lumbar epidural anaesthesia using a cutaneous current perception threshold (CPT) sensory testing device in 20 patients who received 10 ml of either 1% or 2% lidocaine (lignocaine). CPT at 2000, 250 and 5 Hz stimulation at the trigeminal (V), ninth thoracic (T9) and second lumbar (L2) dermatomes, and dermatomal levels of block to light touch, temperature and pinprick discrimination were measured before and every 5 min until 60 min after epidural lidocaine. There were significant differences between 1% and 2% epidural lidocaine in all CPT at T9 and L2, in addition to maximal cephalad spread of the three sensory modalities. After 2% lidocaine, all CPT increased significantly at T9 and L2. In contrast, only at 250 and 5 Hz for L2 did epidural block with 1% lidocaine produce significant increases in CPT. Maximal level of loss of touch sensation after 1% lidocaine was significantly lower than that of cold and pinprick sensations. We conclude that the dose of lidocaine affected intensity of sensory block during lumbar epidural anaesthesia. In addition, differential neural block resulting from epidural anaesthesia appeared to be associated with a differential effect on nerve fibres of different sizes.

Adult↗
PubMed1998

Antinociceptive effects of intrathecal L-type calcium channel blockers on visceral and somatic stimuli in the rat.

UNLABELLED: L-type calcium channels can modulate neuronal transduction in the spinal cord. However, their role in noxious information processing in animals that are physiologically intact has not been elucidated. We evaluated the effects of L-type calcium channel blockers diltiazem and verapamil on somatic and visceral nociception at the level of the spinal cord. Intrathecal catheters were inserted at the L4-5 level in Sprague-Dawley rats. The tail flick (TF) test and colorectal distension (CD) test were used to assess somatic and visceral antinociceptive effects, respectively. Motor function was assessed by posture and muscle tone in the limbs. TF latency and CD threshold were measured before and for 180 min after the intrathecal administration of verapamil (50, 100, 300, and 500 microg), diltiazem (100, 300, 500, and 1000 microg), or isotonic sodium chloride solution. The percent maximal possible effect (%MPE) was calculated by transforming response threshold in TF and CD tests. Intrathecally administered diltiazem or verapamil increased both TF latency and CD threshold in a dose-dependent fashion. Isotonic sodium chloride solution, diltiazem 100 microg, and verapamil 50 microg did not increase %MPE in either test. Diltiazem 300 or 500 microg or verapamil 300 or 500 microg significantly (P < 0.05) increased %MPE, with the peak effects 5 min after administration and short-duration antinociception. %MPE was 100% until 15 min after the administration of diltiazem 1000 microg, and significant antinociception continued until 180 min in the TF test. Motor paralysis was observed after the administration of the larger dose of each drug. We demonstrated that intrathecally administered L-type calcium channel blockers diltiazem or verapamil produced both somatic and visceral antinociception and motor block dose-dependently. IMPLICATIONS: We examined the effects of intrathecally administered L-type calcium channel blockers diltiazem and verapamil on somatic and visceral nociception in rats. L-type calcium channel blockers produced antinociceptive effects, suggesting a possible clinical application to control pain.

Analgesics↗
PubMed1998

Interaction of intrathecally infused morphine and lidocaine in rats (part I): synergistic antinociceptive effects.

BACKGROUND: Synergistic antinociception of opioids and local anesthetics has been established in bolus injections but not in long-term use. The somatic and visceral antinociceptive effects of intrathecally infused morphine or lidocaine were characterized, and the nature of the interaction of those agents in rats was evaluated. METHODS: Intrathecal catheters were implanted in rats. Morphine (0.3 to 10 microg x kg(-1) x h(-1)), lidocaine (30-1,000 microg x kg(-1) x h(-1)), a combination of those, or saline was infused intrathecally at a constant rate of 1 microl/h for 6 days. The tail flick and colorectal distension tests were used to measure the somatic and visceral antinociceptive effects, respectively. Nociceptive tests and motor function tests were repeated on days 1, 2, 3, 4, and 6. Isobolographic analysis was performed on the results of the tail flick test to determine the magnitude of the interaction. RESULTS: Intrathecally infused morphine produced dose-dependent antinociceptive effects in both the tail flick and the colorectal distension tests. Morphine showed a lower peak percentage maximum possible effect (%MPE) in the colorectal distension test than in the tail flick test. Intrathecal lidocaine also produced dose-dependent antinociceptive effects. Lidocaine infusion at 1,000 microg x kg(-1) x h(-1) caused motor impairment. Coinfusion of morphine 0.3 microg x kg(-1) x h(-1) and lidocaine 200 microg x kg(-1) x h(-1), which had no effects by themselves, significantly increased the percentage maximum possible effects (P < 0.01). Coinfused lidocaine potentiated the duration and the magnitude of morphine antinociception. Isobolographic analysis of the tail flick test on day 1 showed a synergistic interaction between morphine and lidocaine. CONCLUSIONS: Morphine and lidocaine intrathecally coadministered synergistically potentiated the antinociceptive effects of each other. That coinfusion dramatically potentiated visceral antinociception, whereas the infusion of morphine alone showed little visceral antinociception.

Analgesics↗
PubMed1998

Interaction of intrathecally infused morphine and lidocaine in rats (part II): effects on the development of tolerance to morphine.

BACKGROUND: There has been little information regarding the effects of local anesthetics on tolerance to opioids, although chronic use of combination of opioids and local anesthetics is popular for pain control. This study was designed to examine the effects of lidocaine on morphine tolerance to somatic and visceral antinociception. METHODS: Rats received a continuous intrathecal infusion of morphine (0.3-10 microg x kg(-1) x h(-1)), lidocaine (30-1000 microg x kg(-1). h(-1)), a combination of those, or saline. After 6- day infusion, intrathecal morphine challenge test (5 microg/10 microl) was performed, and time-response curve was constructed to assess the magnitude of tolerance. The tail flick (TF) test and colorectal distension (CD) test were used to measure somatic and visceral antinociceptive effects, respectively. RESULTS: Antinociceptive effects in the TF and CD tests caused by morphine challenge were reduced (P < 0.01) in the morphine infused groups. The magnitude of the tolerance was inversely associated with the amount of morphine infused. Lidocaine infusion induced no different change in the morphine challenge test from that seen in the saline infusion group. Development of tolerance was greater in morphine 3 microg x kg(-1) h(-1) than in morphine 0.75 microg x kg(-1) x h(-1) + lidocaine 150 microg x kg(-1) x h(-1) despite their similar antinociceptive effects during intrathecal infusion. The infusion of a low dose of morphine (0.3 microg kg(-1) x h(-1)) did not reduce the antinociceptive effects in the challenge test. CONCLUSION: Lidocaine in combination with morphine does not reduce tolerance to morphine nor develop cross-tolerance. The intrathecal infusion of morphine induced tolerance to somatic and visceral antinociception in a dose-dependent fashion.

Analgesics↗
PubMed1998

[Measurement of functional residual capacity by nitrogen washout during mechanical ventilation].

A medical gas analyzer AMIS 2000 SP, which is a mass spectrometer, incorporating a fractional residual capacity (FRC) measuring program based on a nitrogen washout method, has been introduced recently. The purpose of this study was to assess the reliability and the reproductivity of the FRC measuring system in a clinical situation. FRC was measured by this system connected to a ventilator (Bennet 7200ae). Our study examined; 1) the accuracy of the measurement using a syringe. 2) the difference in two consecutive measurements in the same subject during mechanical ventilation, and 3) the correlation between the measured and the predicted value calculated with Gorldman's formula in 18 subjects during ventilation. The first study has showed an excellent correlation (y = 0.953x + 0.092, r = 0.996, P < 0.001) or y = 0.909x + 0.132 (r = 0.999, P < 0.001) with a tidal volume of 400 ml or 500 ml, respectively) between the measured value and the syringe capacity. Reproductivity was proved by the linear regression (y = 0.977x + 0.024, r = 0.998, P < 0.001) between the two consecutive measurements. A good correlation was shown between the measured values and the predicted values (y = 0.656x - 0.415, r = 0.849, P < 0.0001). These results showed good reliability and reproductivity of our FRC measuring system. It is concluded that the FRC measurements using AMIS2000SP system can be used in clinical respiratory managements in ICU.

Functional Residual Capacity↗
PubMed1998

Analysis of serum cytokine levels in primary biliary cirrhosis patients and healthy adults.

By using commercially available ELISA kits, serum IL-6 and TNF-alpha levels in healthy adults, and the levels of various cytokines in patients with primary biliary cirrhosis or chronic viral liver diseases, were investigated. IL-6 levels of healthy subjects were distributed in a wide range, and the distribution pattern was similar to those of the patients. TNF-alpha levels tended to be low in females in their 30s, but there were no abnormalities in the patients. Characteristic findings, in the primary biliary cirrhosis patients, were an increase of IFN-gamma and IL-2 levels, and a decrease of GM-CSF levels (P < 0.05). IL-8 levels were higher in the patients than in the healthy subjects (P < 0.05), and the increase was remarkable in chronic viral liver disease patients. We believe that measurement of serum cytokine levels as a clinical immunological test is highly useful. Further development of simpler, more rapid, and more sensitive analysis methods is desired.

Adult↗
PubMed1998

Flow cytometric analysis of IL-6 receptors on peripheral lymphocytes in patients with primary biliary cirrhosis.

Interleukin-6 receptors (IL-6R) and interleukin-1 receptors (IL-1R) on lymphocyte surfaces were analyzed, using flow cytometry and dye-labeled IL-6 and IL-1 beta, to examine the clinical and immunological significance of these receptors. Incubation of peripheral blood mononuclear cells in the presence of mitogen resulted in a remarkable increase of lymphocytes expressing the IL-6 and IL-1 beta receptors on the cell surface. The increase in lymphocytes bearing these cytokine receptors may reflect an increase in stimulated lymphocytes. When peripheral blood from patients with primary biliary cirrhosis (PBC) was examined for these receptors, the percentage of IL-6R positive cells was significantly higher in the patients than in healthy controls (P < 0.01). The increase in IL-6R positive cells was only significant for the T lymphocyte fraction (P < 0.01). No significant change in IL-1R was observed. There was a significant positive correlation between the percentage of IL-6R positive T lymphocytes and the titer of antimitochondrial antibody in patients with PBC. These findings concerning IL-6R may be noteworthy elucidating autoimmune etiological features of PBC.

Adult↗
PubMed1998

[Circulatory collapse during laparoscopic cholecystectomy].

A 52 year-old female without any cardiac disease underwent laparoscopic cholecystectomy. Anesthesia was induced with thiamylal and maintained with nitrous oxide and isoflurane. Epidural anesthesia was also used during surgery. When the intraabdominal insufflation was performed in reverse-trendelenburg position 15 minutes after the start of incision, the heart rate suddenly decreased from 75 to 49 bmp with a fall in blood pressure. Her hemodynamic state recovered immediately after the release of intraabdominal pressure and the administration of ephedrine with a rapid infusion of Hespander. The circulatory collapse did not occur when the second insufflation was tried carefully. The circulatory collapse was probably due to the vagal reflex. The decrease in cardiac preload during the reverse trendelenburg position and the epidural administration of local anesthetics may have caused or worsened the circulatory collapse. In anesthetic managements of laparoscopic cholecystectomy using general anesthesia with epidural anesthesia, prophylactic hydrogenation and prevention of parasympathetic domination are important to minimize the vagal reflex.

Anesthesia, Epidural↗
PubMed1998

[Quantitative assessment of differential nerve block during lumbar epidural anesthesia].

The study was performed to evaluate differential neural blockade during lumbar epidural anesthesia with a cutaneous current perception threshold (CPT) sensory testing device. Fourteen patients undergoing elective gynecological surgery received 10 ml of 2% lidocaine through an epidural catheter inserted at the L 1/2 interspace. CPTs at 2000, 250, and 5 Hz stimulation and sensation to light touch, temperature, and pinprick at ipsilateral dermatomes V, Th 9, and L 2 were measured before and every 5 min, until 60 min after the epidural lidocaine. The epidural block caused a significant increase in all CPTs at dermatome L 2 and in CPTs at 250 and 5 Hz at Th 9. Touch sensation at Th 9 was intact during the study period in 12 patients, most of whom lost sensation to the other stimulus: 12 patients did not respond to the cold stimulus and 10 patients to the pinprick. At L 2, sensory block to light touch, temperature, and pinprick was found in 11, 14, and 14 patients, respectively. There was no effect on any measurements made at V. In conclusion, epidural lidocaine results in a differential neural blockade as measured with CPT testing. Since the 2000-Hz stimulus detect abnormalities that correlate with large fiber functioning, it is suggested that loss of touch sensation is associated with effects of epidural lidocaine on large fibers.

Adult↗