Biomedical subjects

O Nagata

Publications and source records attributed to O Nagata.

At least 19 recordsLinked to original sources

PubMed2005

Comparison of the intubating laryngeal mask airway and laryngeal tube placement during manual in-line stabilisation of the neck.

We compared the placement of the laryngeal tube (LT) with the intubating laryngeal mask airway (ILMA) in 51 patients whose necks were stabilised by manual in-line traction. Following induction of anaesthesia and neuromuscular blockade, the LT and ILMA were inserted consecutively in a randomised, crossover design. Using pressure-controlled ventilation (20 cmH(2)O inspiratory pressure), we measured insertion attempts, time to establish positive-pressure ventilation, tidal volume, gastric insufflation, and minimum airway pressure at which gas leaked around the cuff. Data were compared using Wilcoxon signed-rank tests; p < 0.05 was considered significant. Insertion was found to be more difficult with the LT (successful at first attempt in 16 patients) than with the ILMA (successful at first attempt in 42 patients, p < 0.0001). Time required for insertion was longer for the LT (28 [23-35] s, median [interquartile range]) than for the ILMA (20 [15-25] s, p = 0.0009). Tidal volume was less for the LT (440 [290-670] ml) than for the ILMA (630 [440-750] ml, p = 0.013). Minimum airway pressure at which gas leak occurred and incidence of gastric insufflation were similar with two devices. In patients whose necks were stabilised with manual in-line traction, insertion of the ILMA was easier and quicker than insertion of the LT and tidal volume was greater with the ILMA than the LT.

Adult↗

PubMed2004

Intubating laryngeal mask airway allows tracheal intubation when the cervical spine is immobilized by a rigid collar.

BACKGROUND: An intubating laryngeal mask airway (ILMA) facilitates tracheal intubation with the neck in neutral position, which is similar to the neck position maintained by a rigid cervical collar. However, a cervical collar virtually obliterates neck movement, even small movements that normally facilitate airway insertion. We therefore tested the hypothesis that the ILMA will allow tracheal intubation even in patients wearing a rigid cervical collar. METHODS: We performed blind tracheal intubation via an ILMA under general anaesthesia in 50 patients with a rigid Philadelphia collar in place undergoing cervical spine surgery and 50 general surgical patients. Time required for intubation, intubation success rate, and numbers and type of adjusting manoeuvres used were recorded. RESULTS: Inter-incisor distance was significantly smaller (4.1 (0.8) vs 4.6 (0.7) cm, mean (sd), P<0.01) and Mallampati scores were significantly greater (P<0.001) in the patients with collars. ILMA insertion took longer (30 (25) vs 22 (6) s), more patients required two insertion attempts (15 vs 3; P<0.005), and ventilation adequacy with ILMA was worse (P<0.05) in collared patients. However, there were no significant differences between the collars and control patients in terms of total time required for intubation (60 (41) vs 50 (30) s), number of intubation attempts, overall intubation success rate (96 vs 98%), or the incidence of intubation complications. CONCLUSIONS: Blind intubation through an ILMA is thus a reasonable strategy for controlling the airway in patients who are immobilized with a rigid cervical collar.

Adolescent↗

PubMed2001

Accumulation of the 1-methyl-4-phenylpyridinium ion in suncus (Suncus murinus) brain: implication for flavin-containing monooxygenase activity in brain microvessels.

The metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was examined in an effort to evaluate the role of flavin-containing monooxygenase (FMO) expressed in the brain of suncus (Suncus murinus) and rats. MPTP was metabolized to generate both 1-methyl-4-phenylpyridinium ion (MPP(+)) and MPTP N-oxide by brain homogenates from rats. Although the level of MPP(+)-producing activity was similar in suncus and rats, a remarkable difference was found between the animal species in MPTP N-oxygenase activity, which was not detectable in brain homogenates from suncus. The concentrations of MPP(+) in suncus brain after a single ip administration of MPTP were markedly higher than that in rats, probably because of the lack of FMO activity in the suncus brain. The MPTP N-oxygenase activity of microvessel homogenates of rat brain was 21-fold greater than that of whole brain homogenates. These results suggest that FMO(s) plays a significant role in the detoxification of MPTP in cerebral endothelial cells.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2001

Racemization kinetics of meluadrine tartrate in aqueous solution.

The kinetics of racemization of meluadrine tartrate in aqueous solution was investigated by HPLC, over the pH range of 1.2 to 12 at 40, 60 and 80 degrees C. The racemization was followed by measuring both the residual (R)-enantiomer and formed (S)-enantiomer of meluadrine. The pH-racemization rate profile of meluadrine showed a minimum racemization rate constant between pH 4 and 6, and the rate constant increased rapidly with decreasing pH below pH 3. In the basic region, the racemization rate constant showed a maximum at around pH 9. Four pathways of racemization of meluadrine are proposed, depending on the dissociation state of the phenolic and amino groups. The calculated racemization rate-pH profile agreed well with the observations. The values of activation energy (95-115 kJ/mol) suggest that a similar quinoid intermediate is involved throughout the pH range examined. The objective of this study is to clarify the racemization mechanism of benzylalcohol derivative with phenoric group. This study offers fundamental knowledge for the other benzylalcohol derivatives, which have similar moiety structure.

Adrenergic beta-2 Receptor Agonists↗

PubMed2001

Structure-activity relationship (SAR) studies on oxazolidinone antibacterial agents. 1. Conversion of 5-substituent on oxazolidinone.

A structure-activity relationship (SAR) study on 5-substituted oxazolidinones as an antibacterial agent is described. The oxazolidinones, of which 5-acetylaminomethyl moiety was converted into other functions, were prepared and evaluated for antibacterial activity. Elongation of the methylene chain (8) and conversion of the acetamido moiety into guanidino moiety (12) decreased the antibacterial activity. The replacement of carbonyl oxygen (=O) by thiocarbonyl sulfur (=S) enhanced in vitro antibacterial activity. Especially, compound 16, which had the 5-thiourea group, showed 4-8 stronger in vitro activity than linezolid. Our SAR study revealed that the antibacterial activity was greatly affected by the conversion of 5-substituent.

Anti-Bacterial Agents↗

PubMed2001

Structure-activity relationship (SAR) studies on oxazolidinone antibacterial agents. 2. Relationship between lipophilicity and antibacterial activity in 5-thiocarbonyl oxazolidinones.

5-Thiourea and 5-dithiocarbamate oxazolidinones were synthesized as a continuation of research on 5-thiocarbonyl oxazolidinone antibacterial agents considering the hydrophobic parameters of the molecule. The structure-activity relationship (SAR) study revealed that the antibacterial activity on 5-thiocarbonyl oxazolidinones was significantly affected by the lipophilicity, especially the calculated log P value and the balance between 5-hydrophilic (or hydrophobic) substituent and hydrophobic (or hydrophilic) substituents on the benzene ring. Some of 5-thiocarbonyl oxazolidinones were found to have good in vitro antibacterial activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

Anti-Bacterial Agents↗

PubMed2001

Structure-activity relationship (SAR) studies on oxazolidinone antibacterial agents. 3. Synthesis and evaluation of 5-thiocarbamate oxazolidinones.

A series of 5-thiocarbamate oxazolidinones was prepared and tested for in vitro and in vivo antibacterial activities. The results of in vitro antibacterial activity indicated that the 5-thiocarbamate group was a suitable substituent for the activity by the 5-moderate hydrophilicity. The compounds within a favorable logP value range were found to have potent in vitro antibacterial activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Compounds 3a and 4h were superior to linezolid in both in vitro and in vivo potency and were considered to be hopeful compounds. We also discuss the pharmacokinetic properties of several compounds in mice.

Anti-Bacterial Agents↗

PubMed2001

An improved synthesis of butyl 4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetate (AU-224).

A new and facile route for the synthesis of the novel gastrointestinal prokinetic butyl 4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetate (1b), which exhibited potent gastro- and colon-prokinetic activities by oral administration without significant side effects, was established. The key intermediate, butyl 4-amino-1-piperidineacetate (16), was prepared from commercially available 4-amino-1-benzylpiperidine (2) in a high yield with four steps. Compound 1b was prepared by condensation of commercially available 4-amino-5-choloro-2-methoxybenzoic acid (7) with 16 in 84% yield. This improved synthetic route was appropriate for large-scale synthesis of 1b.

Gastrointestinal Agents↗

PubMed2001

[Efficiency of bispectral index in anesthetic management of a patient with hypothyroidism].

A 72-year-old, female patient with severe hypothyroidism underwent tracheostomy using deltopectral flap. During the anesthetic management, we assessed the hypnotic level using the bispectral index and regulated the dose of general anesthetics to maintain the bispectral index at about 50. The general anesthetics caused a marked cardiovascular depression, but the condition was treatable with the intravenous administration of dopamine. Using these methods, we could anesthetize this patient safely without a prolonged awakening time from general anesthesia. Although the anesthetic requirement for patients with hypothyroidism is generally thought to be decreased, there is no practical index by which we can estimate the optimal dose of anesthetic agents for these patients. This case report shows that the assessment of the hypnotic level by the bispectral index can be utilized as an efficient index to determine the optimal dose of general anesthetics for patients with hypothyroidism.

Aged↗

PubMed2001

[Evaluation of emergence from total intravenous anesthesia with propofol for long neurosurgery].

In six neurosurgical patients we examined their emergence from more than six hours of total intravenous anesthesia with propofol and fentanyl. The anesthesia was maintained properly with total intravenous anesthesia with propofol and fentanyl without nitrous oxide. We calculated the estimated blood concentration of propofol from the anesthesia record using a three-compartment pharmacokinetic model. The patients were extubated after they had shown good awareness. The average time for extubation was 18 minutes after discontinuation of propofol infusion. The mean estimated concentration of propofol at the extubation was 1.36 micrograms.ml-1 (range: 1.1-1.5 micrograms.ml-1). The estimated emergence times in these cases, also calculated with the pharmacokinetic model, correlated significantly with the time from discontinuation of propofol infusion to the patients' awakening. It was concluded, first, that the estimated concentration of propofol at extubation after long anesthesia was similar to that measured in common cases, and second, that we could reduce the emergence time at the tail end of long-sustained neurosurgery by avoiding the delay in emergence.

Adolescent↗

PubMed2001

[Anesthetic management of a hyper-obese patient by target-controlled infusion (TCI) of propofol and fentanyl].

We gave total intravenous anesthesia to an over-100% hyper-obese patient using target-controlled infusion (TCI) of propofol and fentanyl. To keep him asleep, we maintained his BIS in a range of 40 to 60 by adjusting the target concentration of propofol. For the target concentration of fentanyl, we chose 2 ng.ml-1 at incision and 1.6 ng.ml-1 during the operation. At the patient's emergence from anesthesia, his estimated blood concentration of propofol was 1.51 micrograms.ml-1 and his BIS was 80. The relationship between BIS value and effect-site concentration of propofol was almost the same as that assessed in ordinary adults of a normal weight. We conclude that the estimated concentration of propofol is a good indicator of the effect of propofol and that TCI is a useful technique in obese patients as well as in ordinary adults.

Adult↗

PubMed2001

[Anesthetic management for gastrojejunostomy in a patient with hemiplegia and recurrent laryngeal nerve palsy].

A 70-year-old man who had undergone a low anterior resection for primary rectal cancer 9 years before complained of anorexia, hemiplegia, and recurrent laryngeal nerve palsy. The anorexia was caused by duodenal stenosis due to swollen lymph nodes, the hemiplegia was caused by a metastatic brain tumor, and the recurrent laryngeal nerve palsy was caused by metastases of the cancer to the mediastinal space. Metastases were also found in the bilateral lungs, liver, ureter, and cervical vertebra. In choosing the anesthesia for the gastrojejunostomy to improve the malnutrition of this patient, we decided, on the basis of the patient's full stomach, malnutrition, hypovolemia, hemiplegia, cerebral compression, recurrent laryngeal nerve palsy, renal dysfunction, and respiratory dysfunction, to use thoracic epidural anesthesia rather than spinal anesthesia or general anesthesia. Thoracic epidural anesthesia could provide sufficient analgesia, and the operation was uneventful. In anesthetic management of an end-stage patient undergoing a palliative operation like this, we should consider the purpose of the operation, its complications, and further complications which may be induced by anesthesia in order to plan out an anesthetic regimen unlikely to lead to harmful events in perioperative period.

Aged↗

PubMed2001

[The effects of the fat component of propofol solution of ketogenesis during propofol anesthesia].

To examine the effects of the fat component in propofol solution on the fat metabolism during propofol anesthesia, we measured the urine ketone body (UKB) and blood concentrations of 3-hydroxybutyrate (3-OHBA) and glucose. The anesthesia was maintained with propofol, fentanyl, and vecuronium. Infusion fluid without glucose was used while we measured the concentration of 3-OHBA. UKB was detected only when the concentration of 3-OHBA was more than 400 mumol.ml-1. The blood concentration of 3-OHBA increased in proportion to the total amount of propofol solution, while UKB did not show any such relationship. Furthermore, the rate of increase of 3-OHBA was larger in the group whose concentration of 3-OHBA was higher than the normal range. The blood concentration of glucose ranged within the normal fasting level. There were no cases who needed special treatment for hyperketonemia in this study. We concluded that 3-OHBA was a more sensitive indicator of ketogenesis than UKB, and that ketogenesis was accelerated both by propofol anesthesia with the lipidemic solution of propofol and by fasting before surgery. The acceleration of ketogenesis was especially marked in the patients with hyperketonemia.

3-Hydroxybutyric Acid↗

PubMed2001

[Anesthetic management using propofol and fentanyl for transrectal ultrasound-guided prostatic biopsy].

We prospectively evaluated the efficiency of the anesthetic management using propofol and fentanyl for the transrectal, ultrasound-guided, prostatic biopsy. In the anesthetic management for the transrectal, ultrasound-guided, prostatic biopsy, it is required to obtain enough muscle relaxation of the anal sphincter for placing the transrectal ultrasound probe and to secure immobilization of the patient during the prostatic biopsy. Eight patients undergoing the transrectal, ultrasound-guided, prostatic biopsy participated in this study. Without premedication, anesthesia was induced using fentanyl (100 micrograms) and target-controlled infusion of propofol with an estimated blood concentration of 3 micrograms.ml-1. We obtained both sufficient muscle relaxation of the anal sphincter and complete immobilization of the patient during the prostatic biopsy in all patients. Moreover, this anesthetic management assured short awakening time from anesthesia and low incidence of adverse effects. From these results, we conclude that the anesthetic management using propofol and fentanyl for the transrectal, ultrasound-guided, prostatic biopsy is efficient and practical.

Aged↗

PubMed2000

A high-level expression of CYP2A in the lung of the suncus (Suncus murinus) and its role in the activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

Northern blot analysis of mRNA prepared from the lung of Suncus murinus (suncus), which was classified as an ancestor of primates, revealed that the expression level of cytochrome P450 2A (CYP2A) mRNA was about 100-fold higher than in the lung from rats and mice. To confirm that the pulmonary CYP2A of the suncus had a catalytic activity, the metabolism of a specific substrate for CYP2A6, (+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502), was determined. The intrinsic clearance for SM-12502 S-oxidation by the suncus lung microsomes was calculated to be 99-fold higher than that by rat liver microsomes. The mutagen-producing activity of a 9,000 g supernatant fraction prepared from suncus lung was examined using 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as a promutagen. The results showed that the suncus lung possessed 82-fold higher mutagen-producing activity than the rat lung, indicating that NNK was efficiently activated by the CYP2A isoform expressed in the suncus lung and that the suncus was a sensitive animal species to the genotoxicity of NNK contained in tobacco smoke.

Animals↗

PubMed2000

The suncus (Suncus murinus) shows poor metabolic phenotype for trimethylamine N-oxygenation.

In vitro and in vivo N-oxygenation of trimethylamine (TMA) in the suncus (Suncus murinus) was investigated. The N-oxygenation of TMA has been thought to be catalyzed by flavin-containing monooxygenase (FMO). In a previous study, we found that the levels of mRNAs for FMOs were extremely low in the suncus. Thus, we intended to evaluate the capacity of the suncus to N-oxygenate TMA compared to the rat. Eadie-Hofstee plots of the TMA N-oxygenation by suncus liver microsomes showed a biphasic pattern, suggesting that more than two enzymes were involved in this reaction. The low K(m) component in the suncus showed a twofold higher K(m) (55 vs. 31 microM) and a fourfold lower V(max) (0.61 vs 2.5 nmol/min/mg protein) values than those obtained using rat liver microsomes, resulting in a sevenfold lower V(max)/K(m) (11 vs 82 microl/min/mg protein) value. After an intraperitoneal administration of TMA (10 mg/kg body wt), the suncus excreted 39.6% of the dose in 24-h urine as TMA, whereas the rats excreted 6.3%. Metabolic ratio in the TMA N-oxygenation was 1.42 and 0.11 in the suncus and the rat, respectively. These results indicate that the suncus can be an animal model for a poor metabolizer phenotype in TMA metabolism.

Animals↗

PubMed2000

The house musk shrew (Suncus murinus): a unique animal with extremely low level of expression of mRNAs for CYP3A and flavin-containing monooxygenase.

Expression of drug-metabolizing enzymes including cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) in various tissues of Suncus murinus (Suncus) were examined. Northern blot analysis showed that mRNAs hybridizable with cDNAs for rat CYP1A2, human CYP2A6, rat CYP2B1, human CYP2C8, human CYP2D6, rat CYP2E1, human CYP3A4 and rat CYP4A1 were expressed in various tissues from Suncus. The mRNA level of CYP2A in the Suncus lung was very high. Furthermore, it was found that the level of CYP2A mRNA in the Suncus lung was higher compared to the Suncus liver. The expression level of mRNA hybridizable with cDNA for human CYP3A4 was very low. The presence of CYP3A gene in Suncus was proven by the induction of the CYP with dexamethasone. Very low expression levels of mRNAs hybridizable with cDNAs for rat FMO1, rat FMO2, rat FMO3 and rat FMO5 were also seen in Suncus liver. No apparent hybridization band appeared when human FMO4 cDNA was used as a probe. The hepatic expression of mRNAs hybridizable with cDNAs for UDP-glucuronosyltransferase 1*6, aryl sulfotransferase, glutathione S-transferase 1, carboxyesterase and microsomal epoxide hydrolase in the Suncus were observed. These results indicate that the Suncus is a unique animal species in that mRNAs for CYP3A and FMO are expressed at very low levels.

Animals↗

PubMed2000

Modifying effects of ethinylestradiol but not methoxychlor on N-ethyl-N-nitrosourea-induced uterine carcinogenesis in heterozygous p53-deficient CBA mice.

It is unknown whether endocrine-disrupting chemicals (EDCs) with estrogenic activities have any modifying effects on uterine carcinogenesis. In our previous study, we established a uterine-carcinogenesis model that is useful for detecting tumor-modifying effects of EDCs by the administration of N-ethyl-N-nitrosourea (ENU) to female heterozygous p53-deficient CBA mice [p53 (+/-) mice]. To investigate the effects of ethinylestradiol (EE) and methoxychlor (MXC) on development of ENU-induced uterine tumors, female p53 (+/-) mice and their wild-type littermates [p53 (+/+) mice] received an intraperitoneal injection of 120 mg/kg body weight (bw) of ENU, followed, in Group 1, by no further treatment; in Group 2, by a diet containing 1 ppm EE; in Group 3, by a diet containing 5 ppm EE for 4 weeks and 2.5 ppm EE thereafter; and in Group 4, by a diet containing 2000 ppm MXC for 26 weeks. Uterine proliferative lesions that were induced were composed of both endometrial-stromal and epithelial-cell types. Endometrial stromal sarcomas were induced in p53 (+/-) mice of Groups 1 to 4, and the incidence (87%) in Group 3 was significantly increased compared to Group 1 (47%). Atypical hyperplasias (clear-cell type) of the endometrial gland in p53 (+/-) mice were seen at incidences of 0, 14, 60, and 0% in Groups 1, 2, 3, and 4, respectively, while their incidence in p53 (+/+) mice was 0, 7, 53, and 0%, respectively, with a significant difference between Groups 1 and 3 in both cases. One p53 (+/-) mouse in Group 3 also had an adenocarcinoma consisting of clear cells, and the PCNA labeling indices of the clear-cell atypical hyperplasias, and this endometrial adenocarcinoma, were higher than those of glandular hyperplasias. The present study suggests that 2.5 ppm EE, but not MXC, exerts tumor-promoting effects on stromal and epithelial proliferative lesions of the uteri in p53 (+/-) mice initiated with ENU.

Adenocarcinoma, Clear Cell↗