Pentax Airway Scope® vs Macintosh laryngoscope for tracheal intubation in adult patients: a systematic review and meta-analysis.

The Pentax Airway Scope(®) is a single-use optical videolaryngoscope designed to assist with difficult tracheal intubation. We systematically reviewed the efficacy of the Pentax Airway Scope with that of a conventional laryngoscope for tracheal intubation in adults with 'normal' and 'difficult' airways. We included 17 randomised controlled trials with a total of 1801 participants. We used the DerSimonian and Laird random-effects model to calculate pooled relative risk or weighted mean differences. The relative risk (95% CI) of a Cormack-Lehane grade-1 laryngeal view was 2.40 (1.76-2.49) with the Pentax Airway Scope compared with the Macintosh laryngoscope, p < 0.00001. We found no other differences between the two laryngoscopes. Despite a superior laryngeal view, the Pentax Airway Scope provides little clinical benefit over the conventional laryngoscope.

Genetic and environmental factors affecting cryptic variations in gene regulatory networks.

BACKGROUND: Cryptic genetic variation (CGV) is considered to facilitate phenotypic evolution by producing visible variations in response to changes in the internal and/or external environment. Several mechanisms enabling the accumulation and release of CGVs have been proposed. In this study, we focused on gene regulatory networks (GRNs) as an important mechanism for producing CGVs, and examined how interactions between GRNs and the environment influence the number of CGVs by using individual-based simulations. RESULTS: Populations of GRNs were allowed to evolve under various stabilizing selections, and we then measured the number of genetic and phenotypic variations that had arisen. Our results showed that CGVs were not depleted irrespective of the strength of the stabilizing selection for each phenotype, whereas the visible fraction of genetic variation in a population decreased with increasing strength of selection. On the other hand, increasing the number of different environments that individuals encountered within their lifetime (i.e., entailing plastic responses to multiple environments) suppressed the accumulation of CGVs, whereas the GRNs with more genes and interactions were favored in such heterogeneous environments. CONCLUSIONS: Given the findings that the number of CGVs in a population was largely determined by the size (order) of GRNs, we propose that expansion of GRNs and adaptation to novel environments are mutually facilitating and sustainable sources of evolvability and hence the origins of biological diversity and complexity.

Evolution of gene regulatory networks by fluctuating selection and intrinsic constraints.

Various characteristics of complex gene regulatory networks (GRNs) have been discovered during the last decade, e.g., redundancy, exponential indegree distributions, scale-free outdegree distributions, mutational robustness, and evolvability. Although progress has been made in this field, it is not well understood whether these characteristics are the direct products of selection or those of other evolutionary forces such as mutational biases and biophysical constraints. To elucidate the causal factors that promoted the evolution of complex GRNs, we examined the effect of fluctuating environmental selection and some intrinsic constraining factors on GRN evolution by using an individual-based model. We found that the evolution of complex GRNs is remarkably promoted by fixation of beneficial gene duplications under unpredictably fluctuating environmental conditions and that some internal factors inherent in organisms, such as mutational bias, gene expression costs, and constraints on expression dynamics, are also important for the evolution of GRNs. The results indicate that various biological properties observed in GRNs could evolve as a result of not only adaptation to unpredictable environmental changes but also non-adaptive processes owing to the properties of the organisms themselves. Our study emphasizes that evolutionary models considering such intrinsic constraining factors should be used as null models to analyze the effect of selection on GRN evolution.

Postoperative pain status after intraoperative systemic dexmedetomidine and epidural neostigmine in patients undergoing lower abdominal surgery.

BACKGROUND AND OBJECTIVES: To determine whether intraoperative systemic dexmedetomidine improves postoperative pain and interacts with epidural neostigmine to produce analgesic effects. METHODS: Sixty patients undergoing gynaecological surgery were randomly divided into four groups to receive epidural neostigmine and/or systemic dexmedetomidine: control (Group C), epidural neostigmine (Group N), systemic dexmedetomidine (Group D) and co-administered neostigmine and dexmedetomidine (Group ND). Epidural neostigmine (0.3 mg) was administered with 10 mL of 0.75% ropivacaine before the induction of general anaesthesia. Systemic dexmedetomidine (loading dose of 1 mug kg-1 over 10 min followed by 0.4 mug kg-1 h-1) was infused after the induction of general anaesthesia and continued until the end of surgery. The pain status of patients was assessed using the visual analogue scale at 2, 4, 6, 24 and 72 h postoperatively. RESULTS: Intraoperative systemic dexmedetomidine alone did not reduce postoperative pain scores. However, co-administered neostigmine and dexmedetomidine significantly decreased scores at 24 and 72 h (Group C: 3.0 [1.0-5.8] and 2.0 [0.3-3.0]; Group N: 1.5 [0.3-3.4] and 0 [0-1.3]; Group D: 3.5 [0-5.0] and 0 [0-1.4]; and Group ND: 0 [0-1.0]* and 0 [0-0]; median [interquartile range] *P = 0.0031, P = 0.0045 compared with Group C). CONCLUSIONS: The intraoperative systemic infusion of dexmedetomidine alone at doses causing sedation does not result in postoperative analgesic effects. However, the co-administration of systemic dexmedetomidine and epidural neostigmine at higher doses may be a useful method to improve postoperative pain although side-effects have to be evaluated.

[3H]alpha,beta-methylene ATP binding to P2X purinoceptor is unaffected by volatile anaesthetics.

BACKGROUND AND OBJECTIVE: The P2X receptor is responsible for fast excitatory neurotransmission in the central nervous system. This receptor is suggested as one of the targets of volatile anaesthetics. The study was undertaken to examine the site of action of volatile anaesthetics, especially for P2X purinoceptor-mediated neurotransmission. METHODS: The effect of sevoflurane and isoflurane on [3H]alpha,beta-methylene ATP binding was investigated in rat crude synaptic membranes. The crude synaptic membranes were prepared from Sprague-Dawley rat brains by centrifugation and then incubated with volatile anaesthetics or P2 receptor antagonists. RESULTS: [3H]alpha,beta-methylene ATP binding was unchanged by either sevoflurane or isoflurane at clinically relevant concentrations. Suramin, a P2 antagonist, significantly (P < 0.05) decreased the binding of [3H]alpha,beta-methylene ATP in a dose-dependent manner (68.7 +/- 14.7% at 10 micromol, 49.5 +/- 6.4% at 50 micromol, 24.3 +/- 5.7% at 100 micromol, n = 10, mean +/- SD), whereas pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), another P2 antagonist, did not affect the binding. CONCLUSIONS: The suppressive effect of volatile anaesthetics on ATP-mediated excitatory synaptic transmission could be one site of action. However, the blockade of ATP binding to P2X receptors is not a mechanism of action of volatile anaesthetics.

Reduction by sevoflurane of adenosine 5'-triphosphate-activated inward current of locus coeruleus neurons in pontine slices of rats.

Increasing evidence indicates that volatile general anesthetics exert their effects by affecting various types of membrane conductance expressed in the central nervous system (CNS), such as ligand-gated receptor-channels. The most recently identified family of the receptor-channels in the CNS are the extracellular ATP-gated channels (P2X purinoceptors). In the present study, we tested whether volatile anesthetics can affect P2X receptor function in the CNS network. We recorded whole-cell currents of locus coeruleus (LC) neurons in pontine slices from young rats. Adenosine 5'-triphosphate (ATP) sodium (0.03-3 mM) evoked a rapidly rising and moderately desensitizing inward current (50-200 pA) in a dose-dependent manner in LC neurons at a holding potential of -80 mV. Perfusion with clinically relevant concentration of sevoflurane (0.1-0.5 mM) reduced the ATP-induced inward current in a dose-dependent manner (to 56.8+/-5.9% of control with 0.5 mM sevoflurane; mean+/-S.E.M., n=13). Estimated IC(50) of sevoflurane was 0.59 mM. We conclude that the attenuation of extracellular ATP-mediated signaling in the central nervous system might be one of the multiple actions of volatile anesthetics.

Extracellular ATP potentiates steroidogenic effect of adrenocorticotropic hormone in bovine adrenocortical fasciculata cells.

We examined the effect of extracellular adenosine 5'-triphosphate (ATP) on adrenocorticotropic hormone (ACTH)- and angiotensin II-induced steroidogenesis in bovine adrenocortical fasciculata cells. The low concentration of ATP (5 microM) potentiated ACTH-induced steroidogenesis synergistically. However, the purine derivative did not affect angiotensin II-induced steroidogenesis. Although adenosine (100 microM) (a metabolite of ATP) showed a weak steroidogenic effect, it did not potentiate ACTH-induced steroidogenesis. ATP also enhanced the steroidogenesis by NaF synergistically in bovine adrenocortical cells, but did not potentiate forskolin- and dibutyryl cyclic AMP-induced steroidogenesis. The stimulating effect of ACTH on cyclic AMP production was synergistically accelerated by ATP (5 microM), which has no effect by itself on cyclic AMP formation. These results suggest that extracellular ATP affected the ACTH receptor-adenylyl cyclase coupling processes, and potentiation of steroidogenesis by ACTH ensued in bovine adrenocortical fasciculata cells.

The anesthetic interaction between adenosine triphosphate and N-methyl-D-aspartate receptor antagonists in the rat.

Modulation of synaptic neurotransmission through the ligand-gated ion channel is probably involved in the mechanisms of analgesic and anesthetic actions. In the central nervous system, adenosine triphosphate and glutamate are fast excitatory neurotransmitters through their effects on P2X and N-methyl-D-aspartate (NMDA) receptors respectively. To examine the anesthetic interaction between adenosine triphosphate and NMDA receptor antagonists, we studied the effect of intracerebroventricular administration of P2 and/or NMDA antagonists on the minimum alveolar concentration (MAC) of sevoflurane in rats. Intracerebro- ventricular administration of phosphonopentanoic acid azophenyl-2',4'-disulfonate and D (-)-2-anino-5-phophonopentanoic acid, P2 and NMDA antagonists, significantly reduced the MAC of sevoflurane. The reduction of the MAC by both phosphonopentanoic acid azophenyl-2',4'-disulfonate and D (-)-2-anino-5-phophonopentanoic acid was dose-dependent. The effect of coadministration of both antagonists was additive in the reduction of sevoflurane minimum alveolar concentration. These results suggest that P2 and NMDA receptors mediate nociceptive/anesthetic processing as inhibition of these receptors resulted in analgesic and anesthetic effects. However the pathway mediated through each receptor may be different postsynaptically and/or one of these presynaptic receptors may modulate the neurotransmitter release of the other.

Capacitative calcium entry is involved in steroidogenesis in bovine adrenocortical fasciculata cells.

Capacitative Ca(2+) entry into bovine adrenocortical fasciculata cells was investigated by using the mobilization of intracellular Ca(2+) concentration ([Ca(2+)](i)) and Ca(2+)-induced steroidogenesis as the indicators. Bovine adrenocortical fasciculata cells on a glass coverslip were loaded with fura-2. The [Ca(2+)](i) mobilization was detected by a change of fura-2 fluorescence intensity. In the intracellular Ca(2+) store depleted cells, the addition of Ca(2+) to the incubation medium elicited a marked and sustained increase in [Ca(2+)](i). In the intracellular Ca(2+) store non-depleted cells, the addition of thapsigargin, an endoplasmic reticulum Ca(2+)-ATPase inhibitor, in the absence of extracellular Ca(2+), induced a slight and transient increase in [Ca(2+)](i), but an extensive and sustained increase in [Ca(2+)](i) was obtained by adding Ca(2+) to the incubation medium after the thapsigargin treatment. The sustained increase induced by thapsigargin was not inhibited by nifedipine, but was inhibited by Zn(2+) and Cd(2+) in a concentration-dependent manner. The effect of Zn(2+) was more potent than that of Cd(2+). Thapsigargin stimulated steroidogenesis in the presence of extracellular Ca(2+). The steroidogenic effect of thapsigargin was inhibited by Zn(2+) and Cd(2+) but not by nifedipine. These results suggest that there is, in bovine adrenocortical fasciculata cells, a steroidogenesis-linked Ca(2+) entry process other than that involving voltage-operated Ca(2+) channels and that the process might be capacitative Ca(2+) entry.

P2-purinergic receptor antagonists reduce the minimum alveolar concentration of inhaled volatile anesthetics.

In the central nervous system (CNS), adenosine triphosphate (ATP) is reported to serve as a fast excitatory neurotransmitter via P2X receptor. To examine possible involvement of inhibition of ATP signal-transmission in anesthetic mechanism, the effect of intracerebroventricular (ICV) administration of P2 receptor antagonists on the minimum alveolar concentration (MAC) of sevoflurane and isoflurane was studied in rat. ICV administration of P2 receptor antagonists, suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), significantly reduced MAC of both anesthetics. The reduction of the MAC by both suramin and PPADS was dose-dependent and reached plateau at 150 microgram/rat. These results suggest that the inhibition of ATP-signal transmission may be involved in analgesic or anesthetic effect in brain.

Halogenated volatile anesthetics inhibit carbon monoxide-stimulated soluble guanylyl cyclase activity in rat brain.

BACKGROUND: Because of halogen contents, halogenated volatile anesthetics (HVA) have a similarity to nitric oxide (NO) in terms of great affinity for the ferrous ion. Interactions between HVA and NO at the ferrous ion of soluble guanylyl cyclase (sGC) have been reported in different tissues. Carbon monoxide (CO), a more stable gas than NO, activates sGC by the same mechanism as NO. This study was undertaken to examine the effect of HVA on CO-stimulated sGC activity in rat brain. METHODS: Sprague-Dawley rat brain was homogenized and ultracentrifuged. The resulting supernatant was used as sGC fraction. The fraction was incubated with CO and HVA, and the activity of sGC was determined by measuring cyclic guanosine monophosphate (cGMP) production using an enzyme immunoassay in aliquots of the supernatant. RESULTS: CO clearly increased cGMP production in a dose-dependent manner. Sevoflurane and isoflurane produced significant and dose-dependent inhibition of CO-stimulated sGC activity. There was no difference in the inhibitory effect between the two anesthetics. GTP dose-dependently increased CO-stimulated cGMP production. Both anesthetics decreased GTP production, but the inhibition by the anesthetics was not significant at higher GTP concentrations. CONCLUSIONS: These results suggest that HVA can compete with CO at the ferrous ion of sGC and inhibit the activity of this enzyme.

Anesthetic management of high-risk cardiac patients undergoing noncardiac surgery under the support of intraaortic balloon pump.

Patients with severely impaired left ventricular function, an uncorrectable coronary artery disease, and a recent myocardial infarction are at high risk of cardiac complications after major noncardiac surgery. We present two patients with extensive three-vessel coronary artery disease who underwent intraperitoneal surgery under the support of intraaortic balloon pump (IABP). In one patient, the IABP was inserted urgently because of the development of chest pain with significant ST depression on arrival in the operating room, and the other patient was managed with prophylactic IABP. There were no intraoperative or postoperative cardiac events in either patient. Thus, IABP should be considered in the perioperative management of patients with severe cardiac diseases.

Methylene blue, a soluble guanylyl cyclase inhibitor, reduces the sevoflurane minimum alveolar anesthetic concentration and decreases the brain cyclic guanosine monophosphate content in rats.

UNLABELLED: The nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signal pathway plays an important role in anesthetic and analgesic effects. We sought to determine the involvement of inhibition of soluble guanylyl cyclase (sGC) in the anesthetic mechanism and site of action of volatile anesthetics. We examined the effect of intracerebroventricular (ICV) administration of methylene blue (MB), a sGC inhibitor, on the minimum alveolar anesthetic concentration (MAC) of sevoflurane and the brain cGMP content in rats in vivo. We also investigated the effect of sevoflurane on NO-stimulated sGC activity in vitro. The rats were divided into three groups. After the ICV administration of MB, sevoflurane MAC and brain cGMP contents were measured in the first group and the second group, respectively. In the third group, brain cGMP contents were determined after sevoflurane anesthesia without the ICV administration of MB to examine the direct effect of sevoflurane on brain cGMP contents. MB significantly decreased sevoflurane MAC and brain cGMP content in a dose-dependent manner. Sevoflurane itself also dose-dependently decreased cGMP contents in brain in vivo and inhibited the NO-stimulated sGC activity in vitro. These results suggest that the inhibition of the NO-cGMP signal pathway at the sGC level could be involved in anesthetic or analgesic effects, and the inhibitory effect of sevoflurane on sGC would be one of the sites of action of this anesthetic. IMPLICATIONS: Because the nitric oxide-cyclic guanosine monophosphate signal pathway mediates nociception and the site of action of halogenated volatile anesthetics in uncertain, we examined the possible involvement of inhibition of soluble guanylyl cyclase in the anesthetic mechanism. The inhibitory effect of sevoflurane on soluble guanylyl cyclase could be one of sites of this anesthetic.

Inhibitory effect of nitric oxide on the metabolism of halogenated volatile anesthetics by cytochrome P-450.

PURPOSE: This study was undertaken to examine the effect of nitric oxide (NO) on the metabolism of halogenated volatile anesthetics (HVA) by cytochrome P-450 (CYP) under both aerobic and anaerobic conditions using rat hepatic microsomes. METHODS: A microsomal fraction was prepared by centrifugation from normal and phenobarbital-treated male SD rats. The anaerobic metabolism of HVA by CYP was followed by measuring the formation of a halothane CYP complex spectrophotometrically. Aerobic CYP activity was determined using either the defluorination of sevoflurane or the demethylation of aminopyrine. RESULTS: The formation of the halothane-CYP complex was dose-dependently inhibited by NO. NO also decreased CYP defluorination of halothane in a dose-dependent manner. In phenobarbital-induced microsomes, the inhibition rates of both complex formation and the defluorination of halothane were the same as those seen in normal microsomes. Although the defluorination of sevoflurane and the demethylation of aminopyrine were inhibited by NO aerobically, the inhibition was much less than that of the metabolism of halothane under anaerobic conditions. CONCLUSION: These results suggest that NO binds the heme of CYP and inhibits the metabolism of HVA, with the effect lasting for a prolonged period of time. Furthermore, the balance between NO and O(2) is important for NO to inhibit CYP.

Trends of survival in neuroblastoma and independent risk factors for survival at a single institution.

To assess the progress of survival in neuroblastoma which varies with many risk factors and to evaluate the influence of these factors on survival as independent risk factors. The study subjects were 159 neuroblastoma patients seen from 1965-1994 at the oldest and largest children's hospital in Japan. Trends of survival in three treatment eras-1965-81, 1982-86, 1987-94-were assessed by the Kaplan-Meier method for different sex, age at diagnosis, the clinical stage, the site of onset, and the histological type. Then the influence on survival of these factors as independent prognostic variables was evaluated by the Cox proportional hazards regression analysis. Age at diagnosis, the clinical stage, the site of onset, the histological type, and the treatment era were independent risk factors in the order of their influence on survival. Unfavorable survival outcomes were obtained for patients with age at diagnosis above 1 year, the clinical stage of VI by the Evans classification, adrenal onset, and neuroblastoma rather than ganglioneuroblastoma. Survival improved from the first to the second and from the second to the third treatment era. Improvement of survival in neuroblastoma took place during the past 3 decades. Age at diagnosis, the clinical stage, and the histological type have still remained overwhelming prognostic factors over the progress in treatment.

Vascular effects of halothane and isoflurane: cGMP dependent and independent actions.

This study investigated the effects of halothane and isoflurane on cGMP-dependent and independent regulation of vascular contraction of the isolated rat aorta and on NO-stimulated soluble guanylate cyclase (sGC) isolated from the perfused rat liver. For the studies of the aorta, isometric tension of isolated rings, with and without, endothelium was recorded and cGMP content measured. ACh was used to initiate endothelial-dependent relaxation of norepinephrine (NE)-contracted rings while NO was used to directly stimulate isolated aortic ring sGC which catalyzes the isolated aortic ring formation of cGMP. Both halothane and isoflurane interfered with ACh and NO relaxations and with NO-stimulated increases in cGMP. Halothane was more potent, having significant attenuating effects at 0.34 mM (1 MAC) and 0.72 mM (2 MAC) while isoflurane had effects only at 0.53 mM (2 MAC). For the isolated sGC studies, a soluble liver fraction was prepared from perfused rat livers. In the absence of NO stimulation, neither halothane nor isoflurane modified the activity of the sGC. However, during NO-stimulation halothane produced significant, concentration-dependent, inhibition of sGC activity over a wide range of NO concentrations. Isoflurane also inhibited sGC activity, but to a lesser extent than halothane. The mechanism whereby the anesthetics could interfere with sGC from liver and blood vessels is unknown. It could result from anesthetic interaction at hydrophobic sites that may exist in GC. However, the results of both the aorta and liver sGC enzyme studies support the suggestion that these anesthetics can compete with NO for its binding site on the ferrous heme of sGC, with chemical structural differences accounting for the potency variations. Both anesthetics also had cGMP independent effects, causing concentration dependent relaxations of NE-contracted vessels without endothelium. Isoflurane was about 5 times more effective at 1 MAC than halothane. Therefore, the net effects of these anesthetics involve the sum of two opposite effects on tension of vessels with intact endothelium: 1) interference with NO-stimulated cGMP relaxation and 2) direct stimulation of relaxation (not dependent on changes in cGMP).

[Diagnosis of sinusitis in children with allergic diseases--comparison of waters projection radiographs and CT scans].

Sinusitis is common in children with allergic diseases, and the relationship between sinusitis and reactive airway diseases involving asthma has been reported. Most pediatricians and physicians base their diagnosis of sinusitis on findings from plain radiographs of the sinuses, especially Waters projection radiographs. We compared the diagnoses made by 11 pediatric allergists using 56 Waters projection radiographs with transverse CT findings. The ratio for the two diagnosis being consistent (normal plain radiographic findings and normal CT findings, or abnormal plain radiographic findings and abnormal CT findings) was approximately 60%. Sinusitis in children is often misdiagnosed on the basis of findings from Waters projection radiographs alone. Therefore, the use of CT findings for the diagnosis of sinusitis together with Waters projection radiographs is recommended.

Serum fluoride concentration after sevoflurane anesthesia in ethanol treated rats: special reference to cytochrome P-450 in the liver.

The relationship between serum concentration of inorganic fluoride (F(-)) and cytochrome P-450 content after sevoflurane anesthesia was investigated in ethanol treated rats. Twenty male Wistar rats were randomly divided into 2 isocaloric diet groups of 10 rats each: one group receiving a standard diet and the other an ethanol diet. After 28 days on the diets the animals were administered 2.5% sevoflurane for 2 hr with 30% oxygen and 70% nitrous oxide. Cytochrome P-450 and cytochrome b(5) were induced by the ethanol diet. In the ethanol diet group serum concentration of F(-) was significantly higher than that of the standard diet group after sevoflurane anesthesia. These results suggest that cytochrome P-450 and b(5), which were induced by ethanol, enhanced sevoflurane defluorination.

Effect of halothane and enflurane on hepatic blood flow and oxygen consumption in dogs.

We investigated the relative effects of 0.5, 1.0, 1.5, 2.0 MAC halothane and enflurane, and concurrent noxious stimulus on hepatic blood flow and oxygen consumption in 14 mongrel dogs randomly divided into groups of seven each. Hepatic arterial and portal venous blood flow (HABF and PVBF, respectively) were measured continuously using ultrasonic transit time flow meter. Mean arterial blood pressure (MAP), cardiac index (CI), hepatic oxygen supply, and hepatic oxygen consumption (HVO2) were measured. Halothane significantly deceased HABF, but not PVBF in a dose dependent manner. Enflurane did not affect HABF and PVBF significantly. MAP and CI decreased in both groups, with halothane producing more marked decreases than enflurane. HVO2 did not change with enflurane, but did with halothane, producing significant differences, with halothane being greater at 1.5, 2.0 MAC. A noxious stimulus only caused minor change in blood flow. The results suggest that liver blood flow and oxygen consumption are affected differently by halothane and enflurane and that halothane has a stronger tendency to cause an imbalance between liver oxygen supply and consumption than dose enflurane.