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Biomedical subjects

Fumio Goto

Publications and source records attributed to Fumio Goto.

At least 37 records · Page 2Linked to original sources

Reduced expression of kinase-associated phosphatase in cortical dendrites of MAP2-deficient mice.

We previously demonstrated that cAMP-dependent protein kinase was reduced in the dendrites of MAP2-deficient mice. In this study, we compared the expression of various protein phosphatases (PPs) between wild-type and map2(-/-) dendrites. Kinase-associated phosphatase (KAP) was the only PP which showed difference between the two phenotypes: (1) the expression of KAP was reduced in map2(-/-) cortical dendrites, and (2) the amount of KAP bound to microtubules was reduced in map2(-/-) brains. We also demonstrated in cultured neuroblastoma cells that KAP is not only expressed in dividing cells, but also in the neurites of differentiated cells. Our findings propose that KAP, which has been reported to function in cell-cycle control, has an as yet uncovered role in regulating dendritic functions. We also propose MAP2-deficient mice as an ideal system for identifying protein phosphatases essential for dendritic functions.

Animals↗

The interaction of noradrenaline with sevoflurane on GABA(A) receptor-mediated inhibitory postsynaptic currents in the rat hippocampus.

Little is known about the interaction of noradrenaline with volatile anesthetics in inhibitory synaptic transmission. The purpose of the present study was to investigate the interactions of noradrenaline and sevoflurane on inhibitory synaptic transmission mediated by GABA(A) receptors in the rat hippocampus. Pharmacologically isolated GABA(A) receptor-mediated IPSCs were recorded with whole-cell patch-clamp techniques in pyramidal neurons of the CA1 region of rat hippocampal slices. The actions of noradrenaline, noradrenaline analog, sevoflurane, and the interactions of these agents on the frequency and kinetics of spontaneous GABA(A) receptor-mediated IPSCs were studied. Noradrenaline (10 microM) caused an increase in the frequency of action potential-dependent sIPSCs. These effects were completely reversed by the addition of tetrodotoxin (1 microM), suggesting that noradrenaline produces the discharge of GABAergic interneurons innervating on pyramidal cells via adrenoceptors. Although sevoflurane (0.40 mM, 20 min) slightly depressed the amplitude of sIPSCs, sevoflurane significantly prolonged the decay time constant to 451.1 +/- 89.0% of control (n = 9, P < 0.001) without affecting the rise time. In addition, sevoflurane increased the frequency of sIPSCs up to 3-fold. However, pretreatment of cadmium, multiple Ca channel blocker, abolished sevoflurane effects on the frequency whereas the effects on the decay were still observed. Application of both noradrenaline and sevoflurane produced a significant increase of the IPSC frequency than that of noradrenaline alone or sevoflurane alone with prolonged decays. These results provide evidence that both agents have additive effects on GABAergic synaptic transmission at the central nervous system via different mechanisms.

Action Potentials↗

A dopamine infusion decreases propofol concentration during epidural blockade under general anesthesia.

PURPOSE: It is common clinical practice to use dopamine to manage the reduction in blood pressure accompanying epidural blockade. As propofol is a high-clearance drug, propofol concentrations can be influenced by cardiac output (CO). The purpose of the present study was to investigate the effects of dopamine infusions on propofol concentrations administered by a target-controlled infusion system during epidural block under general anesthesia. METHODS: 12 patients undergoing abdominal surgery were enrolled in this study. Anesthesia was induced with propofol and vecuronium 0.1 mg.kg(-1), and maintained using 67% nitrous oxide, sevoflurane in oxygen and constant infusion of propofol. Propofol was administered to all subjects via target-controlled infusion to achieve a propofol concentration at 6.0 microg.mL(-1) at intubation and 2.0 microg.mL(-1) after intubation. Before and after the administration of 10 mL of 1.5% mepivacaine from the epidural catheter and dopamine infusion at 5 microg.kg(-1).min(-1), CO and effective liver blood flow (LBF) were measured using indocyanine green. Blood propofol concentration was also determined using high-performance liquid chromatography. RESULTS: At one hour after epidural block and dopamine infusion, CO was significantly increased from 4.30 +/- 1.07 L.min(-1) to 5.82 +/- 0.98 L.min(-1) (P < 0.0001), and effective LBF was increased 0.75 +/- 0.17 L.min(-1) to 0.96 +/- 0.18 L.min(-1) (P < 0.0001). Propofol concentration was significantly decreased from 2.13 +/- 0.24 microg.mL(-1) to 1.59 +/- 0.29 microg.mL(-1) (P < 0.0001). CONCLUSIONS: Propofol concentrations decrease with an increase in CO, suggesting the possibility of inadequate anesthetic depth following catecholamine infusion during propofol anesthesia.

Aged↗

Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats.

PURPOSE: Systemic ketamine suppresses several types of chronic pain. Although ketamine is used as a general anesthetic agent, the analgesic effect of systemic ketamine for early-stage postoperative pain is not clear. We investigated the efficacy and mechanism of systemic ketamine in a rat model of postoperative pain. METHODS: An incision was made in the plantar aspect of the left hind paw in male Wistar rats. Mechanical hypersensitivity was measured using calibrated von Frey filaments. The anti-hypersensitivity effect of systemic or intrathecal administration of ketamine was determined every hour after making the incision. We examined the effects of intrathecal pretreatment with yohimbine, an alpha2-adrenoceptor antagonist, and methysergide, a serotonergic receptor antagonist, on the anti-hypersensitivity effect of ketamine. We also examined the effect of systemic ketamine on the c-fos immunoreactivity in the spinal cord. RESULTS: Systemic administration of ketamine at doses from 3 to 30 mg.kg(-1) produced anti-hypersensitivity effects in a dose-dependent manner. Intrathecal administration of ketamine had no effect. There was no significant difference between effects of pre- and post-incisional administration. Intrathecal pretreatment with yohimbine (10 microg) or methysergide (15 microg) completely reversed the anti-hypersensitivity effects of systemic ketamine. Systemic ketamine reduced fos expression in laminae I-II in the dorsal horn of the lumbar spinal cord ipsilateral to the paw incision. CONCLUSIONS: The results suggest that systemic administration of ketamine perioperatively suppresses early-stage postoperative pain via monoaminergic descending inhibitory pathways.

Analgesics↗

Landiolol and esmolol prevent tachycardia without altering cerebral blood flow.

PURPOSE: Several ss-adrenergic-blocking drugs have been used during electroconvulsive therapy (ECT) to stabilize the hemodynamic alterations following electrical stimulation. The effects of two ultra-short acting ss-adrenergic-blocking drugs, esmolol and landiolol, on systemic and cerebral circulation were studied during ECT. METHODS: In the first study (n = 15), dose-dependent hemodynamic changes were studied when landiolol was administered immediately after induction of anesthesia. In the second study (n = 12), effects of esmolol and landiolol on systemic and cerebral circulation were compared. Patients in Study 1 received three doses of landiolol, and patients in Study 2 received two types of ss-adrenergic-blocking drugs, in a randomized cross-over design in a series of ECT trials. RESULTS: In the first study, 0.25 to 0.5 mg.kg(-1) landiolol induced a lower heart rate after the electrical stimulation compared to vehicle (P < 0.01). Landiolol did not have significant effects on blood pressure. In the second study, heart rate was stabilized by 1.0 mg.kg(-1) esmolol iv or 0.5 mg.kg(-1) landiolol iv. Increase in mean blood pressure was ameliorated by esmolol (P < 0.01), but not by landiolol. Mean cerebral blood flow velocity in the middle cerebral artery increased at one to two minutes after the electrical stimulation regardless of the use of ss-adrenergic-blocking drugs (P < 0.01). Muscular and electroencephalographic seizure durations were not significantly altered by the ss-adrenergic-blocking drugs. CONCLUSION: Landiolol suppresses heart rate elevation during ECT without affecting blood pressure. Cerebral blood flow velocity in the middle cerebral artery is not affected by the use of either esmolol or landiolol.

Adrenergic beta-Antagonists↗

Plasma concentration for optimal sedation and total body clearance of propofol in patients after esophagectomy.

The present study investigated plasma propofol concentration for optimal sedation and total body clearance in patients who required sedation for mechanical ventilation after esophagectomy. Seven patients after esophagectomy were enrolled in this study. Plasma propofol concentrations were measured with high performance liquid chromatography. Total body clearance was calculated from the steady-state concentration. The infusion rate of propofol for achieving the sedation score of level 3 (drowsy, responds to verbal stimulation) was 1.74 +/- 0.82 mg kg(-1) h(-1) (mean +/- SD, n = 7) when the plasma propofol concentration and the total body clearance were 0.85 +/- 0.24 microg ml(-1) and 1.83 +/- 0.54 l min(-1) (mean +/- SD, n =7), respectively.

Adult↗

Percutaneous radiofrequency lumbar facet rhizotomy guided by computed tomography fluoroscopy.

X-ray fluoroscopy-guided percutaneous radiofrequency facet rhizotomy is used to treat chronic low back pain. The traditional fluoroscopic approach to the medial branch of the posterior rami, however, is associated with a small incidence of complications. We describe a new method for radiofrequency lumbar facet rhizotomy in which computed tomography (CT) fluoroscopy is used to guide needle placement. Three patients with chronic intractable low back pain underwent CT fluoroscopy-guided percutaneous facet rhizotomy. After the safest and shortest route to the target site was determined on the CT image, the needle was advanced along the predetermined route under real-time CT fluoroscopy. When the needle tip was located at the target site, electrical stimulation was applied to verify proper electrode placement. After confirming the clinical effect and lack of complications under test block with a local anesthetic, denervation was performed using radiofrequency current. Pain scores of all patients were reduced after the procedure without any complications such as paralysis or neuritic pain. None of the patients complained of severe discomfort during the procedure. CT fluoroscopy-guided percutaneous lumbar facet rhizotomy appears to be safe, fast, and effective for patients with lumbar facet pain.

Aged↗

Thermogangliolysis of the Gasserian ganglion under computed tomography fluoroscopy.

Gasserian ganglion block is an established treatment for trigeminal neuralgia. A landmark approach assisted by X-ray fluoroscopy is the most common method; however, visualization of the foramen ovale is difficult in some cases. Here we report two cases in which a novel technique using modern computed tomography (CT) fluoroscopy was employed. A 63-year-old woman suffering pain in the maxillary nerve area was treated by thermogangliolysis under CT fluoroscopy. The patient was positioned on a CT stage with the head in an overhanging position. The CT gantry was set at an oblique angle to obtain a coronal view of the foramen ovale. The safest and shortest route to the foramen was designed using the CT image and a 22-gauge insulated needle was advanced following the designed route under CT fluoroscopy. The effect of the nerve block was estimated by injection of a test dose of mepivacaine, after which the ganglion was thermally coagulated at 90 degrees C. Satisfactory analgesia was obtained in this case without any complications. Another patient (65 years old) was also treated by the same technique, and satisfactory pain relief was obtained. In conclusion, CT fluoroscopy-guided Gasserian ganglion thermolysis is considered a safe, quick, and effective treatment for trigeminal neuralgia.

Aged↗

Postoperative myasthenic crisis successfully treated with immunoadsorption therapy.

Myasthenia gravis (MG) is an autoimmune disorder characterized by loss of acetylcholine receptors (AChR) due primarily to the production of anti-AChR autoantibodies. We report a case of MG associated with elevated anti-acetylcholine receptor antibody (anti-AChR Ab) and refractory crisis after thymectomy, in which immunoadsorption therapy was used successfully to stabilize myasthenic symptoms and decrease the anti-AChR Ab titer. A 79-year-old woman underwent extended thymectomy under the diagnosis of MG. One day after surgery she suddenly underwent a myasthenic crisis and was successfully resuscitated. Immunoadsorption therapy with a tryptophan-linked polyvinyl alcohol adsorber was performed three times for the purpose of decreasing the anti-AChR antibodies. The anti-AChR Ab titer was reduced by immunoadsorption during each therapy session; however, the level of anti-AChR Ab before immunoadsorption was higher than that of the previous treatment. This case suggests that the absolute serum level of anti-AChR Ab does not always correlate with the severity of the disease. Removal of pathogenic factors, not only anti-AChR Ab but other antibodies with specificities to skeletal muscles or certain components of the complement system, may contribute to effective treatment of myasthenic crisis.

Aged↗

Analysis of the factors related to a decrease in jugular venous oxygen saturation in patients with diabetes mellitus during normothermic cardiopulmonary bypass.

PURPOSE: We sought to examine what factors, including cerebrovascular carbon dioxide (CO(2)) reactivity, are related to a decrease in internal jugular venous oxygen saturation (SjvO(2)) during normothermic cardiopulmonary bypass (CPB) in patients with diabetes mellitus. METHODS: Twenty-three diabetic patients scheduled to undergo elective coronary artery bypass grafting were studied. As a control, 27 age-matched control patients without diabetes mellitus were also examined. After the induction of anesthesia, a fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor SjvO(2). Arterial and jugular venous blood gases were measured during CPB. The cerebrovascular CO(2) reactivity was measured after the induction of anesthesia and before the start of surgery using a 2.5-MHz pulsed transcranial Doppler probe. RESULTS: The SjvO(2) values in the diabetic group were lower than those in the control group at the initiation of CPB and at 20, 40, and 60 min after the start of CPB. The values for pre- and post-CO(2) reactivity in the control group did not significantly differ (pre-CPB: 4.8% +/- 2.3% mmHg(-1); post-CPB: 5.9% +/- 4.4% mmHg(-1)). In contrast, the values for CO(2) reactivity were lower post CPB than pre-CPB in the diabetic group (Pre-CPB: 6.3% +/- 2.9% mmHg(-1); post-CPB: 4.7% +/- 2.6% mmHg(-1); P < 0.05). In the diabetic group, glycosylated hemoglobin A1c (HbA1c) is considered to be a factor related to a decrease in SjvO(2) during CPB. CONCLUSIONS: Cerebrovascular CO(2) reactivity in diabetic patients decreased after the cessation of CPB but not in the control patients. In addition, HbA1c is also thought to be a factor related to a decrease in SjvO(2) in diabetic patients.

Aged↗

Differential effects of propofol on cerebrovascular carbon dioxide reactivity in elderly versus young subjects.

STUDY OBJECTIVE: To examine the age-related difference between elderly and young patients in the effect of propofol on cerebrovascular carbon dioxide (CO(2)) reactivity. DESIGN: Prospective controlled study. SETTING: University hospital. PATIENTS: Elderly (older than 70 years, n = 13) and young patients (younger than 25 years, n = 13) scheduled for elective orthopedic surgery. INTERVENTIONS: After induction of anesthesia, a 2.5-MHz pulsed transcranial Doppler probe was attached to the patient's head at the right temporal window, from which mean blood flow velocity of the middle cerebral artery was measured continuously. MEASUREMENTS: After obtaining baseline values of velocity of the middle cerebral artery, arterial blood gases, and cardiovascular hemodynamics, end-tidal CO(2) was decreased by increasing the ventilatory frequency by 2 to 5 breaths per minute. Measurements were repeated when end-tidal CO(2) decreased and remained stable for 5 to 10 minutes. Cerebrovascular CO(2) reactivity, at propofol doses of 5 and 10 mg/kg/h, was measured. MAIN RESULTS: No significant differences were observed between the 2 groups in baseline absolute and relative CO(2) reactivity. However, there were significant differences between the 2 groups in absolute or relative CO(2) reactivity at a propofol dosage of 5 mg/kg/h. (Absolute CO(2) reactivity in young patients: 2.1 +/- 0.8 cm/s/mm Hg; elderly: 1.6 +/- 0.4* cm/s/mm Hg. Relative CO(2) reactivity in young patients: 7.4% +/- 1.6%/mm Hg; in the elderly: 6.5% +/- 0.9%*/mm Hg; unpaired t test, *P < .05). In contrast, there were no significant differences between the 2 groups in terms of absolute or relative CO(2) reactivity at a propofol dosage of 10 mg/kg/h. CONCLUSIONS: Cerebrovascular CO(2) reactivity in elderly patients was lower than that in young patients at a propofol dosage of 5 mg/kg/h.

Adolescent↗

Fentanyl-induced hemodynamic changes after esophagectomy or cardiac surgery.

STUDY OBJECTIVE: The goal of this study was to characterize the hemodynamic response to propofol vs propofol with fentanyl when used for sedation after esophagectomy or cardiac surgery. DESIGN: Prospective, randomized, controlled study. SETTING: University Hospital, Intensive Care Unit. PATIENTS: Thirty patients undergoing elective cardiac surgery and 26 patients undergoing esophagectomy were examined. INTERVENTION: Patients were randomized to receive propofol (0.5 mg/kg bolus over 10 minutes, followed by continuous infusion at 1 mg/kg per hour) with or without fentanyl (2.0 microg/kg per hour) to achieve sedation overnight while in the intensive care unit. Randomization was performed in a double-blind manner. MEASUREMENT: Mean arterial pressure (MAP) was monitored throughout the treatment period, and sedation level was measured. Sedation level was targeted to achieve a Ramsay score of 4. MAIN RESULTS: The number of patients experiencing a greater than 20% drop in baseline MAP was higher in cardiac patients receiving propofol alone (11 of 15 patients, 73%) than in cardiac patients receiving propofol with fentanyl (4 of 15 patients, 27%). Furthermore, the time of optimal sedation was lower in the cardiac patients who received propofol than in cardiac patients who received propofol with fentanyl group (propofol alone, 79%; propofol with fentanyl, 88%). In contrast, there was no difference in the number of esophagectomy patients experiencing a greater than 20% drop in baseline MAP or in the mean time of optimal sedation when comparing the 2 treatment regimens. CONCLUSIONS: Propofol has a differential effect on hemodynamics and sedation when comparing patients after cardiac surgery and esophagectomy.

Analgesics, Opioid↗

Risk factors for cognitive dysfunction after coronary artery bypass graft surgery in patients with type 2 diabetes.

OBJECTIVES: The mechanisms of postoperative cognitive dysfunction in patients with diabetes after coronary artery bypass grafting are not fully understood. We sought to determine which type 2 diabetes-related factors contributed to postoperative cognitive dysfunction at 7 days and 6 months after coronary artery bypass grafting. METHODS: One hundred eighty patients with type 2 diabetes who were scheduled for elective coronary artery bypass grafting were studied. As a control group, 100 patients without diabetes mellitus matched for age, sex, and educational level were examined. Hemodynamic parameters (arterial and jugular venous blood gas values) were measured during cardiopulmonary bypass. All patients underwent a battery of neurologic and neuropsychologic tests the day before surgery, 7 days after surgery, and 6 months after surgery. RESULTS: Age (odds ratio 1.5, 95% confidence interval 1.3-1.8, P = .03), presence of hypertension (odds ratio 1.8, 95% confidence interval 1.3-2.0, P = .01), jugular venous oxygen saturation less than 50% time (odds ratio 1.5, 95% confidence interval 1.1-2.0, P = .045), presence of ascending aorta atherosclerosis (odds ratio 1.5, 95% confidence interval 1.1-2.6, P = .01), diabetic retinopathy (odds ratio 2.0, 95% confidence interval 1.3-3.0, P = .01), and insulin therapy (odds ratio 2.0, 95% confidence interval 1.3-3.0, P = .05), were associated with cognitive impairment at 7 days. Insulin therapy (odds ratio 2.0, 95% confidence interval 1.3-3.8, P = .01), diabetic retinopathy (odds ratio 1.3, 95% confidence interval 1.2-2.9, P < .01), and hemoglobin A 1c (odds ratio 1.9, 95% confidence interval 1.3-3.1, P = .047) were associated with cognitive impairment at 6 postoperative months. CONCLUSIONS: Insulin therapy, diabetic retinopathy, and hemoglobin A 1c were factors in cognitive impairment at 7 days and 6 months after coronary artery bypass grafting in patients with type 2 diabetes.

Aged↗

Human kidneys play an important role in the elimination of propofol.

BACKGROUND: Extrahepatic clearance of propofol has been suggested because its total body clearance exceeds hepatic blood flow. However, it remains uncertain which organs are involved in the extrahepatic clearance of propofol. In vitro studies suggest that the kidneys contribute to the clearance of this drug. The purpose of this study was to confirm whether human kidneys participate in propofol disposition in vivo. METHODS: Ten patients scheduled to undergo nephrectomy were enrolled in this study. Renal blood flow was measured using para-aminohippurate. Anesthesia was induced with vecuronium (0.1 mg/kg) and propofol (2 mg/kg) and then maintained with nitrous oxide (60%), sevoflurane (1 approximately 2%) in oxygen, and an infusion of propofol (2 mg . kg . h). Radial arterial blood for propofol and para-aminohippurate analysis was collected from a cannula inserted in the radial artery. The renal venous sample and the radial arterial sample were obtained at the same time after the steady state of propofol was established. RESULTS: The renal extraction ratio of propofol was 0.58 +/- 0.15 (mean +/- SD). The renal clearance of propofol was 0.41 +/- 0.15 l/min (mean +/- SD), or 27 +/- 9.9% (mean +/- SD) of total body clearance. CONCLUSION: Human kidneys play an important role in the elimination of propofol.

Aged↗

Somatotopy in human primary somatosensory cortex in pain system.

BACKGROUND: Compared with somatotopical organization (somatotopy) in the postcentral gyrus in the tactile system, somatotopy in the pain system is not well understood. The aim of this study is to elucidate whether there is somatotopy in the human pain system. METHODS: To elucidate the somatotopy of nociceptive neurons in the postcentral gyrus, the authors recorded pain-evoked cortical responses to noxious intraepidermal electrical stimulation applied to the left hand and left foot in 11 male subjects, using magnetoencephalography. RESULTS: Brief painful stimuli evoked sustained cortical activity in the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulated side and in the secondary somatosensory cortex in both hemispheres. In SI, representations of the hand and foot were distinctly separated, with a more medial and posterior location for the foot, whereas no significant difference was found in the locations for the secondary somatosensory cortex dipole. The SI arrangement along the central sulcus was compatible with the homunculus revealed by Penfield using direct cortical stimulation during surgery. CONCLUSIONS: The human pain system contains a somatotopical representation in SI but with less somatotopical organization in the secondary somatosensory cortex. The current results provide supporting evidence of SI involvement in human pain perception and suggest that human SI subserves the localization of the stimulated site in nociceptive processing.

Adult↗