Clinical application of arterial spin-labeling MR imaging in patients with carotid stenosis: quantitative comparative study with single-photon emission CT.

BACKGROUND AND PURPOSE: Arterial spin-labeling is an emerging technique for noninvasive measurement of cerebral perfusion, but concerns remain regarding the reliability of CBF quantification and clinical applications. Recently, an ASL implementation called QUASAR was proposed, and it was shown to have good reproducibility of CBF assessment in healthy volunteers. This study aimed to determine the utility of QUASAR for CBF assessment in patients with cerebrovascular diseases. MATERIALS AND METHODS: Twenty patients with carotid stenosis underwent CBF quantification by ASL (QUASAR) within 3 days of performance of (123)I-iodoamphetamine-SPECT. CVR to acetazolamide also was assessed by ASL and SPECT. In surgically treated patients, the respective scans before and after the procedures were compared. RESULTS: Regional CBF and CVR values measured by ASL were significantly correlated and agreed with those measured by SPECT (r(s) = 0.92 and 0.88, respectively). A Bland-Altman plot demonstrated good agreement between 2 methods in terms of CBF quantification. Furthermore, ASL could detect pathologic states such as hypoperfusion, impaired vasoreactivity, and postoperative hyperperfusion, equivalent to SPECT. However, ASL tended to overestimate CBF values especially in high-perfusion regions. CONCLUSIONS: ASL perfusion MR imaging is clinically applicable and can be an alternative method for CBF assessment in patients with cerebrovascular diseases.

Side population cells have the characteristics of cancer stem-like cells/cancer-initiating cells in bone sarcomas.

BACKGROUND: Several human cancers have been found to contain cancer stem-like cells (CSCs) having cancer-initiating ability. However, only a few reports have shown the existence of CSCs in bone and soft tissue sarcomas. In this study, we identified and characterised side population (SP) cells that showed drug-resistant features in human bone sarcoma cell lines. METHODS: In seven osteosarcoma cell lines (OS2000, KIKU, NY, Huo9, HOS, U2OS and Saos2) and in one bone malignant fibrous histiocytoma (MFH) cell line (MFH2003), the frequency of SP cells was analysed. Tumourigenicity of SP cells was assessed in vitro and in vivo. Gene profiles of SP cells and other populations (main population; MP) of cells were characterised using cDNA microarrays. RESULTS: SP cells were found in NY (0.31%) and MFH2003 (5.28%). SP cells of MFH2003 formed spherical colonies and re-populated into SP and MP cells. In an NOD/SCID mice xenograft model, 1 x 10(3) sorted SP cell-induced tumourigenesis. cDNA microarray analysis showed that 23 genes were upregulated in SP cells. CONCLUSIONS: We showed that SP cells existed in bone sarcoma cell lines. SP cells of MFH2003 had cancer-initiating ability in vitro and in vivo. The gene profiles of SP cells could serve as candidate markers for CSCs in bone sarcomas.

[Hemodynamic changes during slow induction of anesthesia using propofol and the effect of cardiac output on the propofol concentration].

This investigation assessed the hemodynamic changes during the slow induction of anesthesia using propofol, and evaluated the effects of cardiac output (CO) and other factors on the hypnotic dose of propofol, the time for hypnosis and the plasma propofol concentration. We studied 26 scheduled surgical patients and induced anesthesia with continuous infusion of propofol at the rate of 15 mg.kg-1.hr-1. The required dose of propofol and time for hypnosis were determined and the plasma concentration of propofol was measured after the administration of propofol 2 mg.kg-1. Cardiac output was determined by dye densitometry using indocyanine green 4 times during induction and CO did not show any significant changes during induction of anesthesia. Multiple linear regression analysis demonstrated that in addition to the age and total body weight, CO determined at achieving hypnosis was significantly related to the plasma concentration of propofol. Cardiac output might affect the pharmacokinetics of propofol during induction of anesthesia.

[Cuff failure in tracheal tubes sprayed with lidocaine].

Lidocaine jelly or spray is usually applied to tracheal tube cuffs as lubricants, and we encountered some cuff troubles in using the spray. Damages on polyvinyl chloride (PVC) tracheal tube cuffs by applying lidocaine spray have been reported. We studied cuff injury with 5 kinds of tracheal tubes (PVC and non-PVC cuffs) with three different substances (normal saline, lidocaine jelly and lidocaine spray). No tracheal tube cuffs were damaged by normal saline and lidocaine jelly, while lidocaine spray changed the shape of some tracheal tube cuffs (PVC and non-PVC). Therefore, we recommend to apply lidocaine jelly on tube cuffs rather than lidocaine spray, even on non-PVC cuffs.

[Preliminary report: the effect of flumazenil on the hypnotic dose of propofol in ddY mice].

The present investigation dealt with the effect of simultaneous administration of flumazenil on the hypnotic activity of propofol using a behavioral model of ddY mice. The mixed solution of propofol and flumazenil was administered intravenously into the mice tail vein and the achievement of hypnosis was defined as the loss of the righting reflex. Flumazenil 0.2 mg.kg-1 significantly decreased the required dose of propofol for hypnosis (8.43 +/- 0.46 mg.kg-1) compared to the control group (10.55 +/- 0.55 mg.kg-1). The mixture with a pH-3.9 acetate buffer solution did not change the hypnotic dose of propofol (10.88 +/- 0.62 mg.kg-1). The results suggest that flumazenil might potentiate the hypnotic activity of propofol in ddY mice.

Effect of dexmedetomidine on the release of [3H]-noradrenaline from rat kidney cortex slices: characterization of alpha2-adrenoceptor.

The presynaptic modulation of [3H]-noradrenaline (NA) release from rat kidney cortex slices, a method used for the first time, was investigated. Rat kidney cortex slices were loaded with [3H]-NA and the release of radioactivity at rest and in response to field stimulation was determined. The alpha(2)-adrenoceptor agonist, dexmedetomidine inhibited the stimulation-evoked release of NA from kidney slices in a concentration-dependent manner, whereas alpha(2)-adrenoceptor antagonist CH-38083 (7,8-methyenedioxy-14-alpha-hydroxyalloberbane HCl), an alpha(2)-adrenoceptor antagonists, enhanced it. When dexmedetomidine and BRL-44408, a selective alpha(2A) antagonist, were added together, the effect of dexmedetomidine was significantly antagonized. In contrast, ARC-239 (2-(2,4-(o-piperazine-1-yl)-ethyl-4,4-dimethyl-1,3-(2H, 4H)disoguinolinedione chloride), a selective alpha(2B)-antagonist, had no effect on the release and failed to prevent the effect of dexmedetomidine. Prazosin, an alpha(1)- and alpha(2B/C)-adrenoceptor antagonist enhanced the release evoked by field stimulation. It is therefore suggested that there is a negative feedback modulation of NA release at the sympathetic innervation of kidney cortex, and dexmedetomidine, a clinically used anesthetic adjunct inhibits the release via activation of alpha(2C)-adrenoceptors.

[The effect of propofol anesthesia on striatal dopamine of awake freely moving and anesthetized rats examined by in vivo microdialysis study].

We investigated the effect of propofol anesthesia on the level of interstitial dopamine in vivo awake free moving and anesthetized rats brain striatum using microdialysis techniques. Rats were implanted a microdialysis probe to right striatum of the brain and administered intravenously 20 mg.kg-1 of propofol for induction and followed by continuous infusion at 12.5, 25 and 50 mg.kg-1.hr-1 up to 1 hour. The microdialysis probe was perfused with artificial cerebrospinal fluid and dialysates from the probe were determined every 20 minutes by high performance liquid chromatography and electrochemical detection. Propofol anesthesia reduced the amount of dopamine derived from dialysate, but no prolonged increases of dopamine metabolites were observed, as we demonstrated in previous investigation for halothane, isoflurane or sevoflurane anesthesia. We hypothesize that the characteristics of propofol anesthesia for dopamine and its metabolites might contribute to low incidence of postoperative nausea and vomiting in its clinical use.

[The effect of acetate ringer solution, 6% hydroxyethyl starch saline and 20% mannitol solution on the serum concentration of propofol continuously infused].

Changes in serum concentrations of propofol after administration of three different fluids were investigated in 42 scheduled surgical patients. Anesthesia was induced with propofol 2 mg.kg-1 and maintained with constant rate infusion of propofol 6 mg.kg-1.hr-1. After achieving a stable depth of anesthesia, 5 ml.kg-1 of acetate Ringer's solution, 6% hydroxyethyl starch saline solution or 20% mannitol solution was infused in 15 minutes. Blood samples each 2 ml were taken before and 0, 5, 15, 30 and 60 minutes after fluid treatment. We measured hemoglobin and hematocrit of the samples for calculating the dilution rate of the plasma with infusion treatment, and determined the serum concentration of propofol by HPLC-spectrofluorometry. After administration of each fluid, the serum concentrations of propofol decreased significantly to 17 +/- 15, 25 +/- 10 and 35 +/- 8%, respectively (mean +/- SEM). The dilution rate of the plasma from the fractional change in blood hemoglobin increased to 0.08 +/- 0.02, 0.24 +/- 0.03, and 0.36 +/- 0.03, respectively. Administration of mannitol might markedly increase distribution volume of propofol, and this can be attributed to osmotic action of mannitol and resultant expansion of extracellular fluid volume. The results of the present investigation suggest that this pharmacokinetic change decreased the concentration of propofol more significantly in mannitol treatment patients than in Ringer's solution or 6% hydroxyethyl starch saline treatment patients.

Effects of alpha adrenoreceptor antagonists, prazosin and. yohimbine, on intrathecal lidocaine-induced antinociception in mice.

BACKGROUND: The precise mechanisms involved in the spinal analgesic effect of lidocaine are not yet clear. We previously found that lidocaine releases noradrenaline, a modulator of nociception, in rat spinal cord. Here, we attempted to clarify whether or not the noradrenaline release contributes to spinal analgesia by lidocaine. METHODS: The effects of intrathecal injections of the alpha adrenoreceptor antagonists, prazosin (0.01-0.3 nmol) and yohimbine (0.1-3 nmol), on intrathecal 2% lidocaine were assessed using the tail-flick (TF) test in mice. RESULTS: Lidocaine significantly increased the TF latency for 15 min. Prazosin (0.03, 0.1 or 0.3 nmol) and yohimbine (0.3, 1.0 or 3.0 nmol) significantly reduced the lidocaine-induced increase of the TF latency 10 min after injection, although both drugs showed a ceiling effect. CONCLUSION: These results suggest that stimulation of the noradrenergic systems plays an important role in spinal analgesia by lidocaine.

The effect on intracuff pressure of various nitrous oxide concentrations used for inflating an endotracheal tube cuff.

UNLABELLED: We sought to determine the optimal concentration of nitrous oxide (N(2)O) for inflating endotracheal tube cuffs, to avoid overinflation and air leaks. Female patients undergoing endotracheal intubation (inner diameter 7.5 mm) during anesthesia with 67% N(2)O were randomly assigned to five groups of 25 subjects each, in which cuffs were inflated with 0% (Air), 30% (N30), 40% (N40), 50% (N50), or 67% (N67) N(2)O. The cuff pressure and the N(2)O concentration in the cuff were measured. In an additional 15 patients (N40-a group), pilot balloons were replaced with metal tubes, and the mouths and noses of the patients were wrapped with tape, to minimize N(2)O efflux into the air. Postoperative sore throats were evaluated in double-blinded interviews. Cuff pressures increased significantly in the Air and N30 groups but decreased in the N67 group. Cuff pressures were <22 mm Hg in the N40 and N50 groups, but the N50 group had air leaks. The N(2)O concentration in the cuff in the N40 group was significantly smaller than that in the N40-a group, suggesting N(2)O rediffusion. The incidence of sore throats (40% in the Air group) was reduced significantly in the N40 and N50 groups. Therefore, 40% N(2)O is optimal for filling the cuff during anesthesia with 67% N(2)O. IMPLICATIONS: Nitrous oxide (N(2)O) diffuses into the cuff, equilibrating at a smaller concentration than the gas mixture with which patients are ventilated. Our data indicate that inflation of the cuff with 40% N(2)O is recommended to prevent both excessive endotracheal cuff pressure and air leaks during anesthesia with 67% N(2)O, reducing postoperative sore throats.

[Successful fiberoptic intubation for a patient with lingual tonsillar hyperplasia].

Hypertrophied lingual tonsils are rare, but may cause difficulty or inability in tracheal intubation during induction of general anesthesia. A 39-yr-old woman was scheduled for resection of symptomatic hypertrophied lingual tonsils. In this patient, we examined two methods of oro-tracheal intubation either with rigid laryngoscopy or flexible fiberoscopy using trans-nasal fiberopic monitoring. Direct laryngoscopy failed to expose the trachea because of large hypertrophied tissue, and fiberoscopic intubation was also difficult since a large mass hindered acquiring a suitable view. However, transnasal fiberoscopic monitoring could guide the orotracheal fiber into the trachea for intubation. When an anesthesiologist can predict the abnormality of lingual tonsils, this combination might be recommended for difficult airway and intubation.

[Investigations on the position and safety of Swan-Ganz catheters].

Swan-Ganz catheters (S-G catheter) may cause many complications. We measured floating distance (FD) of catheter tip with balloon inflation or deflation, and distal movement (DM) before and after the operation. FD and DM were significantly altered with 7 Fr. S-G catheters. These results suggest that careful observation is required in order to prevent unpredictable pulmonary artery perforation and infarction during the use of 7 Fr. S-G catheters.

Small dose midazolam or droperidol reduces the hypnotic dose of propofol at the induction of anaesthesia.

We investigated the effect of a small dose of midazolam, ketamine, droperidol or lidocaine on the propofol dose required for hypnosis during induction of general anaesthesia. These drugs were randomly administered to 100 patients about to undergo scheduled surgery. Propofol was then infused at a rate of 250 microg kg-1 min-1 and the hypnotic dose to produce hypnosis was evaluated. Midazolam (20 microg kg-1) and droperidol (20 microg kg-1) significantly reduced the mean hypnotic dose of propofol (mean) S.D.) compared with the placebo (43.7 +/- 17.8 mg, 61.9 +/- 10.6 mg and 72.5 +/- 27.7 mg after pretreatment with midazolam, droperidol and placebo, respectively), whereas ketamine (0.1 mg kg-1) and lidocaine (1 mg kg-1) did not significantly affect the hypnotic dose of propofol (63. 1 +/- 25.6 mg and 65.1 +/- 24.8 mg, respectively). Only midazolam when compared with saline administration, (176 +/- 66 s and 298 +/- 126 s, respectively), shortened the time to achieve hypnosis. The changes in blood pressure (non-invasive) and heart rate were not significantly different in all groups during the induction of anaesthesia and oro-tracheal intubation. These results raise the possibility that new combinations of central nervous system drugs, such as droperidol and propofol, have a potential to reduce the dose of intravenous anaesthetics, including propofol, that produce hypnosis without significant adverse effects.

[Decrease in serum propofol concentrations after acute autologous blood letting].

A change in serum propofol concentrations associated with acute autologous blood letting during anesthesia was investigated in seven scheduled surgical patients. Anesthesia was induced with propofol 2 mg.kg-1 and maintained with infusion of propofol 6 mg.kg-1.hr-1 at a constant rate. After achieving a stable anesthesia, about 10 g.kg-1 of autologous blood was withdrawn in about 15 minutes and 20 ml.kg-1 of acetated Ringer's solution was infused to manage the hypotension caused by withdrawal. A blood sample each 4 ml was taken before and 0, 5, 15, 30 minutes after blood withdrawing. Another 7 patients were anesthetized with the same procedure without blood letting to distinguishing the effect of blood letting from rapid infusion therapy of crystalloid. Assay of serum concentration of propofol was performed with HPLC-spectrofluorometry. Concentrations of propofol were significantly decreased from 2.8 micrograms.ml-1 to 2.3 micrograms.ml-1 just after blood letting, and remained at 2.3 micrograms.ml-1 after 30 minutes from letting. Rapid infusion therapy also decreased the concentrations of propofol from 2.4 micrograms.ml-1 to 1.7 micrograms.ml-1. Continuous infusions of propofol may become a major method of general anesthesia with target controlled infusion techniques (TCI) in clinical settings for the accuracy and reliability of prediction of blood concentrations. However, this study demonstrated unexpected decreases of concentration of propofol during acute autologous blood letting similar to surgical mass bleeding, which might be mainly caused by rapid infusion therapy. The rate of infusion of anesthetic should be readjusted to counteract the effect of acute blood loss or volume replacement.

[Halothane anesthesia decreases the level of interstitial striatal dopamine of awake freely moving rats in an in vivo microdialysis study].

We investigated the effect of halothane on the level of interstitial dopamine of in vivo awake, free moving rats brain striatum using microdialysis techniques. Rats were implanted a microdialysis probe to right striatum of the brain and administered 1.5% of halothane (approximately 1.2 MAC) for 1 or 2 hours, and dialysates from the probe were determined every 20 minutes. Halothane anesthesia reduced the amount of dopamine derived from dialysate, and after discontinuation of halothane and at emergence from anesthesia, the level of dopamine was increased. The levels of metabolites of dopamine during anesthesia were increased lineally in a time dependent manner. We hypothesized that halothane might increase the rate of re-uptake of dopamine at nerve endings and decreased level of interstitial dopamine is compensated by dopamine releases during anesthesia.

Long-term clomipramine treatment upregulates forebrain acetylcholine muscarinic receptors, and reduces behavioural sensitivity to scopolamine in mice.

We have investigated the effects of long-term treatment with clomipramine, a tricyclic antidepressant, on central muscarinic acetylcholine receptors (mAChR) in mice. Repeated clomipramine administration resulted in an increase in the forebrain receptor density value (Bmax) for [3H]quinuclidinyl benzilate, a muscarinic ligand (P < 0.05), that was dependent on dose per administration (saline or 5, 10, or 20 mg kg(-1) once a day for 7 days) and number of days treated (20 mg kg(-1) for 1, 3, 5, or 7 days). No change in apparent affinity (defined as the reciprocal of the dissociation constant) (KD) occurred. Seven daily treatments with clomipramine (saline or 5, 10, or 20 mg kg(-1)) reduced hyperlocomotion induced by scopolamine (0.5 mg kg(-1), s.c.) dose-dependently, and the effect of 20 mg kg(-1) clomipramine was significant (P < 0.05). These results suggest that an upregulation of mAChR is produced by repeated clomipramine administration, and such a change is responsible for the decreased sensitivity to the muscarinic antagonist scopolamine.

Evaluation of the cardiovascular responses to fiberoptic orotracheal intubation with television monitoring: comparison with conventional direct laryngoscopy.

STUDY OBJECTIVE: To evaluate and compare cardiovascular responses to a new method of orotracheal intubation incorporating TV monitoring, with conventional orotracheal intubation via rigid blade laryngoscopy. DESIGN: Prospective single-blind study. SETTING: Operating room of a medical college hospital. PATIENTS: 90 ASA physical status I and II surgical patients requiring general anesthesia and orotracheal intubation. INTERVENTIONS: Patients were randomly allocated to two groups, one for the new intubation method and the other for conventional intubation using a rigid laryngoscope. In the new method, an anesthesiologist inserted an endotracheal tube alone into the trachea via TV monitoring through the bronchoscope, which was inserted by an assistant through the mouth to the middle larynx. The patient's trachea was intubated without extreme stretching of laryngeal tissues or deep insertion of the tip of the bronchoscope. In the conventional method, orotracheal intubation was performed with rigid direct laryngoscopy. MEASUREMENTS: Noninvasive blood pressure (BP) and heart rate (HR) were measured before arrival at the operating room, and before and after orotracheal intubation. MAIN RESULTS: Although this method was expected to be a minimally invasive fiberoptic intubation technique, the patients showed significant increases in BP and HR. No significant differences between the two groups were observed in cardiovascular responses immediately after intubation: the systolic BP, 169.5 +/- 28.3 versus 167.0 +/- 23.1 mmHg, and HR, 100.2 +/- 18.2 versus 98.8 +/- 16.6 bpm. CONCLUSIONS: Insertion of an endotracheal tube may itself be the most invasive stimulus during intubation procedures.

[Negative-pressure pulmonary edema associated with transurethral resection syndrome].

We described a patient who had developed negative-pressure pulmonary edema associated with severe transurethral resection syndrome. A relatively healthy, 67-yr-old man (171 cm and 77 kg) with hypertrophic prostate was scheduled for transurethral resection of the prostate under spinal anesthesia. The patient was sedated with continuous propofol infusion because of his anxiety and wish of being asleep. Fifty minutes after starting the operation, electrolyte analysis revealed a decrease in serum Na+ concentration (116 mEq.l-1), and 10 mg of furosemide and hypertonic saline were administered. Thirty minutes later, the arterial oxygen saturation dropped suddenly and arterial blood gas analysis suggested marked pulmonary insufficiency (PaO2: 64 mmHg and PaCO2: 59.4 mmHg). The patient's trachea was intubated and endotracheal release of pinkish foamy sputum was observed. Chest X-ray showed severe lung edema. Massive absorption of the irrigation fluid might have decreased the electrolyte concentration (Na+: 101.0 mEq.l-1) and colloid oncotic pressure. No evidence of cardiac failure was observed immediately after the incidence of pulmonary edema with pulmonary catheter monitoring. The patient's airway was almost intact under spontaneous breathing, but augmented negative-pressure derived from intermittent snoring was considered to be sufficient to break hydrostatic balance of pulmonary capillary vessels and lead to severe pulmonary edema.

Halothane anesthesia decreases the extracellular level of dopamine in rat striatum: a microdialysis study in vivo.

PURPOSE: In our previous microdialysis study, sevoflurane or isoflurane anesthesia significantly decreased the extracellular level of dopamine in rat striatum in vivo. On the other hand, other investigators demonstrated that halothane anesthesia either increased or did not affect the extracellular dopamine level. To explore the differences among these volatile anesthetics, the effects of halothane and nitrous oxide on the striatal dopamine level were reinvestigated. METHODS: Halothane alone, nitrous oxide with or without halothane, or drugs known to affect the dopaminergic pathway were administered to rats. Microdialysates were collected every 20 min and directly applied to an on-line high-performance liquid chromatograph without any pretreatment. The effects of halothane on respiratory and cardiovascular variables were monitored. RESULTS: General anesthesia with halothane alone decreased the dialysate (extracellular) concentration of dopamine but increased that of dopamine metabolites. Nitrous oxide alone slightly increased dopamine metabolites in dialysates but did not affect the halothane-induced decrease in extracellular dopamine. Apomorphine and haloperidol reproduced reported results, confirming the adequacy of our methodology. Nomifensine- or methamphetamine-induced increase in extracellular dopamine was augmented by halothane. CONCLUSION: These results suggest that halothane potently enhances striatal dopamine release and activates the reuptake or metabolic process, which is consistent with our previous results for sevoflurane or isoflurane. Volatile anesthetics interfere with dopamine regulation, at least in the rat striatum.

[The effect of sevoflurane and isoflurane on striatal dopamine of awake freely moving rats observed in an in vivo microdialysis study].

We investigated the effect of sevoflurane and isoflurane on the level of interstitial dopamine of in vivo awake, free moving rats brain striatum using microdialysis techniques. Rats were implanted with a microdialysis probe to the right striatum of the brain and administered with 1.2 MAC of each volatile anesthetics for 1 hour, and dialysates from the probe were determined every 20 minutes. Both anesthetics reduced the amount of dopamine derived from dialysate, and increased the efflux of dopamine with pretreatment of nomifensine 10mg. kg-1 i.p. The change of metabolites of dopamine during anesthesia was increased. No significant difference was found between sevoflurane and isoflurane. We hypothesized that these anesthetics might have special actions on interactions between metabolism and re-uptake of dopamine in rats striatum during anesthesia.