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Biomedical subjects

A Shigematsu

Publications and source records attributed to A Shigematsu.

At least 37 records · Page 2Linked to original sources
PubMed2001

A possible relationship between abortions and placental embolism in pregnant rabbits given human granulocyte colony-stimulating factor.

Developmental toxicity studies were conducted in rats and rabbits with a human G-CSF derivative (NTG). As reported for G-CSF, increases in abortions and fetal mortality were observed in rabbits, but not in rats given NTG. Histopathological examination of the rabbit placenta revealed accumulation of neutrophils in vessels and necrosis of the tissues surrounding these vessels. To assess the mechanism of abortion and fetal death in rabbits given G-CSF, 125I-labeled NTG was given intravenously on Day 18 of pregnancy after repeated administration of cold NTG on Days 6 through 17 of pregnancy, and the feto-maternal distribution of radioactivity was examined. In a rabbit given 20 micrograms/kg, high radioactivity was observed in the endometrium, placenta, and some parts of the decidua at 6 hr when the concentration of radioactivity in maternal blood had already decreased. At 24 hr after administration of 200 micrograms/kg NTG, high radioactivity was still detected in parts of the maternal placenta. These patterns of distribution suggest that embolism occurred in parts of the uterus and placenta which might have caused congestion. Radioactivity in the TCA precipitates in the fetus was low, suggesting that NTG does not readily transfer to the fetus. These results strongly suggest that neutrophils accumulated in the vessels of placenta and induced embolism leading to abortions and fetal mortality in the rabbits given G-CSF.

Absorption↗
PubMed2001

[Anesthesia for patients with unexpected pulmonary embolisms due to a large abdominal tumor obstructing with inferior vena cava].

Several reports have highlighted the risk of pulmonary embolisms during the preoperative period in patients with large abdominal tumors obstructing the inferior vena cava. We describe a patient who developed pulmonary embolism just before surgery. A 68[correction of 64]-year-old female was scheduled to undergo elective resection of a large abdominal tumor under general anesthesia. She had no signs of deep venous thrombosis, but on the day of the operation, pulmonary embolism developed suddenly. Anticoagulant therapy was performed. Capnography and pulmonary artery pressure were monitored during the perioperative period to detect the recurrence of pulmonary embolism. The percutaneous cardio-pulmonary support (PCPS) was also prepared. The operation was performed successfully. In this patient, the pulmonary embolism occurred suddenly during the preoperative period, even though we had ruled out the existence of deep venous thrombosis. This case report emphasizes the risk of pulmonary embolism in any patient with a large abdominal tumor obstructing the inferior vena cava. This case of a large abdominal tumor suggests that capnography, monitoring of pulmonary artery pressure and preparation of a PCPS in case of pulmonary embolism during surgery are necessary even in patients without signs of deep venous thrombosis.

Abdominal Neoplasms↗
PubMed2001

[Anesthesia using propofol for a patient with arthrogryposis multiplex congenita].

Arthrogryposis multiplex congenita (AMC) is a syndrome with multiple persistent limb contractures, often accompanied by associated anomalies. Pediatric patients with AMC frequently require operations, necessitating general endotracheal anesthesia. We report on the anesthesia used for a 14-year-old male with AMC, who required the surgical removal of soft tissue from both hip joints. We used propofol and vecuronium bromide to induce anesthesia, and maintained anesthesia with 40% nitrous oxide, oxygen, and propofol at 6 mg.kg-1.1 hr-1. Both induction and maintenance were smooth, and no hyperthermia occurred perioperatively. Propofol can be safely used for anesthesia in AMC patients.

Adolescent↗
PubMed2001

[Difficult ventilation during induction of anesthesia in a patient with Arnold-Chiari malformation type II].

Arnold-Chiari malformation is a congenital disorder with caudal displacement of the cerebellar tonsils through the foramen magnum into the cervical canal. We report difficulty with ventilation during the induction of anesthesia due to apnea and laryngospasm in a 5-year-old female with Arnold-Chiari malformation type II diagnosed at birth. She had had short periods of apnea during infancy, but was asymptomatic recently. Slow induction of anesthesia was performed using sevoflurane, but just after induction, the patient developed apnea and we could not ventilate her due to laryngospasm. We woke her up, and induced anesthesia with barbiturates. The operation was performed without complications, but she had another apnea attack with laryngospasm at extubation. This case suggests that it is important to be aware of the possibility of apnea due to disorder of the respiratory center in patients with Arnold-Chiari deformity.

Anesthesia, Inhalation↗
PubMed2001

Inhibition by tramadol of muscarinic receptor-induced responses in cultured adrenal medullary cells and in Xenopus laevis oocytes expressing cloned M1 receptors.

Tramadol is a widely used, centrally acting analgesic, but its mechanisms of action are not completely understood. Muscarinic receptors are known to be involved in neuronal function in the brain and autonomic nervous system, and much attention has been paid to these receptors as targets of analgesic drugs in the central nervous system. This study investigated the effects of tramadol on muscarinic receptors by using two different systems, i.e., a Xenopus laevis oocyte expression system and cultured bovine adrenal medullary cells. Tramadol (10 nM-100 microM) inhibited acetylcholine-induced currents in oocytes expressing the M1 receptor. Although GF109203X, a protein kinase C inhibitor, increased the basal current, it had little effect on the inhibition of acetylcholine-induced currents by tramadol. On the other hand, tramadol did not inhibit the current induced by AlF4-, a direct activator of GTP-binding protein. In cultured bovine adrenal medullary cells, tramadol (100 nM-100 microM) suppressed muscarine-induced cyclic GMP accumulation. Moreover, tramadol inhibited the specific binding of [3H]quinuclidinyl benzilate (QNB). Scatchard analysis showed that tramadol increases the apparent dissociation constant (Kd) value without changing the maximal binding (Bmax), indicating competitive inhibition. These findings suggest that tramadol at clinically relevant concentrations inhibits muscarinic receptor function via QNB-binding sites. This may explain the neuronal function and anticholinergic effect of tramadol.

Acetylcholine↗
PubMed2000

Viability of liver slices exhibiting absorption, metabolism, and elimination of substrates in culture medium.

In an attempt to improve liver slice culture for in vitro tests of newly developed drugs, we found that a relatively thick 2-mm slice was much more viable, long-lived, and metabolically functional than the conventionally used 300-microm-thick slices. Results revealed that some ionic and nonionic compounds (Na(125)I, [(14)C]Ala, and [(14)C]Xyl) dissolved in culture medium were absorbed into the slices, reaching from the cut edges deep into the inner part, in only a short period. Moreover, the slices could be observed for 24 h after incubation so that a normal histological image could be obtained. Each semi-microautoradiographic image was also clearly positive not only at the margin but also in the inner part of each slice. Furthermore, we determined the specific functioning of each donated liver for each substrate added, in uptake, metabolism, and excretion.

Absorption↗
PubMed2000

Outcomes of out-of-hospital ventricular fibrillation: their association with time to defibrillation and related issues in the defibrillation program in Japan.

The aim of this study was to provide data on the outcomes of out-of-hospital cardiac arrest caused by ventricular fibrillation (VFOHCA) and analyze factors influencing patient outcomes in order to further improve EMS system performance in the resuscitation of VFOHCA patients in Japan. A datasheet was mailed to the fire defense headquarters throughout Japan, and returned data were analyzed for 614 cases of VFOHCA that occurred from January 1 through December 31, 1996. In relation to the time interval from receipt of emergency call to defibrillation, the subjects were stratified into five groups: 0-8 (n = 39), 9-12 (n = 87), 13-16 (n = 154), 17-20 (n = 118) and more than 21 min (n = 216). The discharge survival rates were 18*, 13.8*, 5.2, 4.2 and 4.2%, respectively (*P < 0.05). When defibrillation was delivered within 12 min after a call, 30.2% (38/126) converted to pulse-generating rhythm (PGR) after defibrillation and 43.6% (17/39) of patients with PGR on arrival at the hospital survived to discharge. In spite of these findings, a marked delay to defibrillation (more than 13 min) was observed in the majority (79.5%). The data shown in this study demonstrated that important issues that limit the benefits of an early defibrillation program reside in the EMS system.

Adult↗
PubMed2000

A new method of predicting pulmonary capillary wedge pressure: the arterial pressure ratio.

The response of arterial blood pressure to an increase in intrathoracic pressure has been shown to be predictive of pulmonary capillary wedge pressure. We devised a new method, which we termed the arterial pressure ratio. We defined arterial pressure ratio as the ratio of systolic blood pressure of the final beat during the strain phase of the Valsalva manoeuvre to that during apnoea before the manoeuvre, and tested the accuracy of arterial pressure ratio in predicting pulmonary capillary wedge pressure. In 30 patients scheduled for elective abdominal aortic reconstruction, following induction of general anaesthesia and tracheal intubation, a 20-G catheter and pulmonary artery catheter were inserted through the radial artery and right internal jugular vein, respectively. Pulmonary capillary wedge pressure was then measured during a brief period of apnoea and the Valsalva manoeuvre was performed by application of pressure to the reservoir bag. Airway pressure was maintained at 30 cmH2O for 10 s and then released. Radial arterial pressure and airway pressure were recorded simultaneously, and arterial pressure ratio was calculated. There was a close linear correlation between arterial pressure ratio and pulmonary capillary wedge pressure (r = 0.88, p < 0.0001).

Aged↗
PubMed2000

Preferential potentiation by nitric oxide of spontaneous inhibitory postsynaptic currents in rat supraoptic neurones.

Magnocellular neurones in the supraoptic nucleus and paraventricular nucleus express mRNA for nitric oxide synthase (NOS) and the expression becomes more prominent when the release of vasopressin or oxytocin is stimulated. It has also been reported that NO donors inhibit the electrical activity of supraoptic nucleus neurones, but the mechanism involved in the inhibition remains unclear. In the present study, to know whether modulation of synaptic inputs into supraoptic neurones is involved in the inhibitory effect of NO, we measured spontaneous excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) from rat supraoptic nucleus neurones in slice preparations identified under a microscope using the whole-cell mode of the slice-patch-clamp technique. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP), reversibly increased the frequency of spontaneous IPSCs mediated by GABAA receptors, without affecting the amplitude, indicating that NO potentiated IPSCs via a presynaptic mechanism. The NO scavenger, haemoglobin, suppressed the potentiation of IPSCs by SNAP. On the other hand, SNAP did not cause significant effects on EPSCs mediated by non-NMDA glutamate receptors. The membrane permeable analogue of cGMP, 8-bromo cGMP, caused a significant reduction in the frequency and amplitude of both IPSCs and EPSCs. The results suggest that NO preferentially potentiates the inhibitory synaptic inputs into supraoptic nucleus neurones by acting on GABA terminals in the supraoptic nucleus, possibly via a cGMP-independent mechanism. The potentiation may, at least in part, account for the inhibitory action of NO on the neural activity of supraoptic neurones.

Animals↗
PubMed2000

Inhibition by neuromuscular blocking drugs of norepinephrine transporter in cultured bovine adrenal medullary cells.

UNLABELLED: Pancuronium stimulates the cardiovascular system, whereas vecuronium, a derivative of pancuronium, has far fewer effects. The inhibition of norepinephrine transporter (NET) in the sympathetic nervous system may partly account for the stimulatory actions of pancuronium. To investigate the mechanism of action of pancuronium on NET, we examined the effects of pancuronium on NET activity by using cultured bovine adrenal medullary cells and compared pancuronium with other neuromuscular blocking drugs. Pancuronium (1-300 microM) inhibited desipramine-sensitive [(3)H]norepinephrine (NE) uptake in a concentration-dependent manner. Vecuronium (100-300 microM) and d-tubocurarine (300 microM) also decreased [(3)H]NE uptake but were less potent than pancuronium at clinical concentrations. Succinylcholine had little effect on [(3)H]NE uptake. Saturation analysis showed that pancuronium and vecuronium reduced an apparent maximum velocity (V(max)) of [(3)H]NE uptake without altering Michaelis-Menten constant, indicating noncompetitive inhibition. Pancuronium did not inhibit the specific binding of [(3)H]desipramine to plasma membranes isolated from bovine adrenal medulla. A protein kinase C inhibitor, GF109203X, did not affect the inhibition of [(3)H]NE uptake by pancuronium. Pancuronium enhanced the inhibition of NET induced by ketamine. These results suggest that pancuronium, with clinically relevant concentrations, inhibits NET activity by interacting with a site distinct from the recognition site for NE and the desipramine binding site on the transporter. IMPLICATIONS: In this study, pancuronium inhibited norepinephrine uptake and was the most potent of the neuromuscular blocking drugs we tested, including pancuronium, vecuronium, d-tubocurarine, and succinylcholine. Pancuronium may affect the sympathetic nervous system by inhibiting the activity of the presynaptic norepinephrine transporter at clinically relevant concentrations.

Adrenal Medulla↗
PubMed2000

Dual effects of intravenous anesthetics on the function of norepinephrine transporters.

BACKGROUND: Norepinephrine transporters (NETs) terminate the neuronal transmission of norepinephrine, which is released from noradrenergic neurons. To investigate the interaction with NET, the authors examined the effects of short- and long-term treatment with anesthetics on the activity and mRNA level of NET. METHODS: To assay [3H]norepinephrine uptake, bovine adrenal medullary cells in culture were incubated with [3H]norepinephrine in the presence of intravenous anesthetics, including propofol, thiamylal, and diazepam. To study the direct interaction between the anesthetics and NET, the effect of propofol on the binding of [3H]desipramine to the plasma membrane was examined. To study the long-term effect of anesthetics, [3H]norepinephrine uptake by cells pretreated with propofol for 6-24 h and [3H]desipramine binding after pretreatment for 12 h were measured. Simultaneously, we examined the effect of anesthetics on the expression of NET mRNA using the reverse transcriptase-polymerase chain reaction. RESULTS: All of the intravenous anesthetics inhibited [3H]norepinephrine uptake in a concentration-dependent manner. The active concentrations of propofol (1-3 microm) and thiamylal (< or = 30 microm) were similar to those encountered clinically. The kinetic analysis revealed that all the anesthetics noncompetitively inhibited [3H]norepinephrine uptake. Propofol inhibited [3H]desipramine binding with a potency similar to that observed in [3H]norepinephrine uptake. Scatchard analysis showed that propofol competitively inhibited [3H]desipramine binding. On the other hand, long-term treatment of cells with propofol (10 microm) enhanced the NET functional activity and [3H]desipramine binding, and also increased the level of NET mRNA. CONCLUSIONS: These results suggest that intravenous anesthetics have a dual effect on NET; short-term treatment causes inhibition, whereas long-term treatment leads to up-regulation. The interaction of intravenous anesthetics with NET may modulate the neuronal transmission of norepinephrine during anesthesia.

Adrenal Medulla↗
PubMed2000

Role of interleukin-10 on hyporesponsiveness of endotoxin during surgery.

OBJECTIVE: To examine whether surgical stress causes blood cells to lose their responsiveness to endotoxin during surgery. DESIGN: Prospective case series. SETTING: A university hospital. PATIENTS: Sixteen volunteers classified as American Society of Anesthesiologists physical status I-II who were scheduled for elective distal partial gastrectomy. INTERVENTIONS: We studied nine patients who underwent elective distal partial gastrectomy. Blood samples for tumor necrosis factor (TNF) and interleukin (IL)-10 assay were obtained before anesthesia, preincision, 2 hrs and 4 hrs postincision, postextubation, and 24 hrs postincision. The rest of each blood sample was diluted with 5 volumes of endotoxin-free saline, incubated for 4 hrs in the presence of lipopolysaccharide (LPS), centrifuged to remove cells, and assayed for TNF. In another seven patients, antihuman IL-10 antibody was added into the diluted whole blood sample before LPS stimulation. MEASUREMENTS AND MAIN RESULTS: TNF activity was not detected in the blood of any patient throughout the study. In contrast, plasma cortisol and IL-10 levels increased rapidly during surgery (p < .01, p < .05, respectively). LPS-induced TNF activity in whole blood decreased significantly during surgery (p < .01) and recovered to control levels by 24 hrs postincision. The peak suppression of LPS-induced TNF and the peak value of plasma IL-10 levels occurred postextubation. Treatment with anti-IL-10 antibody partially restored the ability of LPS to induce TNF activity postextubation (p < .05). CONCLUSIONS: Surgical trauma rapidly induces a transient hyporesponsiveness of blood cells to endotoxin. Plasma IL-10, which increases during surgery, participates in this hyporesponsiveness.

Adult↗
PubMed1999

Proposition for assessment of quantitative whole-body autoradiography.

To assess recent improvements in quantitative whole-body autoradioluminography (QWBA), the entire QWBA procedure was divided into five processes. Each process was then investigated carefully to determine whether there were any problems in defining a clear standard operating procedure. Results show that use of two instruments, Macro-Cut, Leica, Germany, and the Bioimaging Analyzer with IP, Fuji Photo Film, was essential to produce macroautoradiographs for QWBA data. The remaining problems include the process for freezing the animal carcass and the process for freeze-drying or lyophilizing the frozen sections of the biomaterials. In addition, a desirable standard operating procedure (SOP) must be developed for assessing QWBA. This article proposes satisfactory SOPs with sufficient clarification and experimental proofs to ensure regulatory compliance for the QWBA technique.

Animals↗
PubMed1999

Fibreoptic assessment of laryngeal aperture in patients with difficult laryngoscopy.

PURPOSE: To determine the relationship between the area of the laryngeal aperture (LA) seen fibreoptically during laryngoscopy and the difficulty of tracheal intubation in patients with difficult laryngoscopy METHODS: In 587 adult patients after induction of general anesthesia and muscle relaxation, the best laryngoscopic view of the larynx using a Macintosh 3 blade was classified according to Cormack. When the LA could not be seen, with laryngoscope blade in place, the LA view provided by a fibreoptic bronchoscope (FOB)-camera passed nasally was photographed. Then, the laryngoscopist attempted to intubate the trachea using the Macintosh blade. Tracheal intubation requiring more than three attempts was defined as difficult. After the third attempt, the trachea was intubated orally aided by FOB. The LA view after jaw thrust during FOB-aided intubation was photographed. RESULTS: Laryngoscopy was difficult in 17 of 587 patients. In four, intubation was difficult. In the remaining 13 patients the trachea was easy to intubate. The LA area obtained by the FOB in the difficult group (median, 0.19; intra-quartile range, 0.14 to 0.39 cm2) was smaller than that in the easy group (2.43; 1.84 to 2.93 cm2)(P = 0.003). In contrast, the LA area provided by jaw thrust during the FOB-aided intubation in the difficult group (2.28; 1.99 to 2.73 cm2) was similar to that during laryngoscopy in the easy group. CONCLUSION: Inability of the laryngoscope to provide an adequate LA view is one cause of difficult intubation with the Macintosh laryngoscope in patients with difficult laryngoscopy.

Adult↗
PubMed1999

Pharmacokinetic analysis and antitumor efficacy of MKT-077, a novel antitumor agent.

MKT-077 (1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4- oxothiazolidin-2-ylidenemethyl] pyridinium chloride), a novel rhodacyanine dye in phase I/II clinical trials, may provide a new approach to cancer therapy based on the accumulation in the mitochondria of the cells of certain carcinomas, for example, those of the colon, breast and pancreas. To support the development of MKT-077 for clinical application as an intravenous (i.v.) therapy, we investigated the metabolic fate of [14C]MKT-077 in BDF1 mice as well as the distribution of MKT-077 in experimental LS174T tumor-bearing mice using a high-performance liquid chromatography (HPLC) method. The plasma levels of 14C after i.v. administration of [14C]MKT-077 declined in a triphasic manner. In the first distribution phase, the levels of 14C decreased with a T1/2 of approximately 5 min. In the second and terminal phase, the T1/2 of 14C was 2.8-4.6 h and 16.2 h, respectively. Cmax (1 min after injection) increased from 0.3 to 1.5 microg/ml linearly, but less than proportionately between the doses. The AUC(0-infinity) at 0.3, 1 and 3 mg/kg were 0.030 +/- 0.002, 0.60 +/- 0.12 and 1.73 +/- 0.25 microg x h/ml, respectively. Plasma clearance was approximately 1.8 l/h per kg (at doses of 1 and 3 mg/kg). The steady state volume of distribution (6.8 and 25.1 l/kg) indicated that MKT-077 distributed as a lipid-soluble molecule. The mean residence time (MRT) was 4.1 (at a dose of 1 mg/kg) and 14.1 h (at a dose of 3 mg/kg). In the first rapid phase (5 min after dosing), 14C radioactivity was detected in most of the tissues and organs, most strongly in the kidney cortex, and not in the central nervous system and testes. In the terminal phase (24 h after dosing), 14C contents increased in the intestinal tract, and in the kidney and liver were nearly to the background level. After i.v. bolus administration at a dose of 3 mg/kg of [14C]MKT-077, the predominant route of elimination of the radioactivity was via the feces, and recoveries of total radioactivity in urine and feces corresponded to 33.5% and 61.1%, respectively. More than 60% was recovered within 24 h and 95% within 1 week. MKT-077 was primarily excreted in unmetabolized form with five unidentified metabolites found in the urine and plasma. Intact MKT-077 was retained in the tumor tissue longer than in plasma and kidney in LS174T tumor-bearing mice receiving MKT-077 at an i.v. therapeutic dose (10 mg/kg). This accumulation decreased very slowly, suggesting that the high membrane potentials of tumor cell mitochondria may help retain the drug in tumors.

Animals↗
PubMed1999

Anesthetic management of a patient with laryngeal amyloidosis.

A 73-year-old woman who suffered from progressive hoarseness for 6 years and dysphagia without pain for 1 year presented with a soft tissue deposition on the posterior region of the vocal cords and narrowing in the subglottic area. Biopsy of this soft tissue and histological examination revealed laryngeal amyloidosis. A tracheostomy and partial removal of the amyloid were performed with general anesthesia. The airway was secured with a smaller diameter endotracheal tube, which was inserted atraumatically with Magill's forceps. The larynx is a rare site for amyloidosis. Laryngeal amyloidosis is fragile and hemorrhagic. Therefore, massive bleeding may occur during intubation. Anesthetists should take care in intubating the tracheas of these patients and be aware of other systemic diseases in laryngeal amyloidosis.

Aged↗