Removal methods of rigid stylets to minimise adverse force and tracheal tube movement: a mathematical and in-vitro analysis in manikins.

This study investigated displacement of the tracheal tube caused by different methods of intubating stylet removal, using in-vitro experiments and mathematical analysis. In the first in-vitro experiment, we measured the distance travelled by the tube tip during stylet extraction. Then, we investigated the ideal technique for stylet extraction using mathematical analysis, which would cause minimal tube displacement. Then, using a training manikin, we measured the force applied to the vocal cords and stylet extraction force during tracheal intubation. When the stylet was extracted along a straight path towards the stylet end, the distance travelled by the tube tip significantly increased as the bending angle increased. Mathematical analysis revealed that the stylet should be diagonally extracted (in the sagittal plane) at an appropriate angle, rather than along a straight path towards the direction of the stylet end. In simulated tracheal intubation, extraction force and force applied to the vocal cords both significantly increased as the bending angle increased. Compared with the 'hockey stick'-shaped stylet, the arcuate-shaped stylet resulted in reduced force. Our results indicate the potential risk for vocal cord injury when using hockey stick-shaped stylets with large bending angles.

The effects of Patent Blue dye on peripheral and cerebral oxyhaemoglobin saturations.

We measured the effect of Patent Blue dye on oxyhaemoglobin saturations after injection into breast tissue: 40 women had anaesthesia for breast surgery maintained with sevoflurane or propofol (20 randomly allocated to each). Saturations were recorded with a digital pulse oximeter, in arterial blood samples and with a cerebral tissue oximeter before dye injection and 10, 20, 30, 40, 50, 60, 75, 90, 105 and 120 min afterwards. Patent Blue did not decrease arterial blood oxyhaemoglobin saturation, but it did reduce mean (SD) digital and cerebral oxyhaemoglobin saturations by 1.1 (1.1) % and 6.8 (7.0) %, p < 0.0001 for both. The falsely reduced oximeter readings persisted for at least 2 h. The mean (SD) intra-operative digital pulse oxyhaemoglobin readings were lower with sevoflurane than propofol, 97.8 (1.2) % and 98.8 (1.0) %, respectively, p < 0.0001.

Large current MOSFET on photonic silicon-on-insulator wafers and its monolithic integration with a thermo-optic 2 × 2 Mach-Zehnder switch.

n-channel body-tied partially depleted metal-oxide-semiconductor field-effect transistors (MOSFETs) were fabricated for large current applications on a silicon-on-insulator wafer with photonics-oriented specifications. The MOSFET can drive an electrical current as large as 20 mA. We monolithically integrated this MOSFET with a 2 × 2 Mach-Zehnder interferometer optical switch having thermo-optic phase shifters. The static and dynamic performances of the integrated device are experimentally evaluated.

Sevoflurane suppresses tumour necrosis factor-α-induced inflammatory responses in small airway epithelial cells after anoxia/reoxygenation.

BACKGROUND: Lung ischaemia-reperfusion (I/R) injury is correlated with poor clinical outcome. The inflammatory cytokines interleukin (IL)-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) are produced by pulmonary epithelial cells during lung transplantation and are considered to be involved in I/R injury. The volatile anaesthetic sevoflurane has been shown to exert a protective effect on I/R injury in various organs. We investigated the effect of sevoflurane on the inflammatory functions of pulmonary epithelial cells in vitro. METHODS: Human normal small airway epithelial cells (SAEC) were incubated under anoxic conditions for 24 h with or without sevoflurane and then stimulated with tumour necrosis factor (TNF)-α under hyperoxic conditions for 5 h with or without sevoflurane. After incubation, IL-6, IL-8, and MCP-1 mRNA expression was analysed by quantitative real-time RT-PCR. The production of IL-6, IL-8, and MCP-1 was assayed by enzyme-linked immunosorbent assay, the effects of sevoflurane on inflammatory gene expression were examined by DNA microarray analysis, and the effects of sevoflurane on NF-κB-mediated inflammatory cytokine production were examined by immunoblotting. RESULTS: Sevoflurane suppressed TNF-α-induced IL-6, IL-8, and MCP-1 gene expression and the production of IL-6 and IL-8 in SAEC under anoxia/reoxygenation conditions. DNA microarray analysis indicated that sevoflurane modulated NF-κB-related gene expression. Sevoflurane significantly inhibited TNF-α-induced translocation of p65 NF-κB into the nucleus. Sevoflurane enhanced TNF-α-induced gene expression of inhibitor κB (IκB) but not of NF-κB. CONCLUSIONS: Sevoflurane suppressed the NF-κB-mediated production of pulmonary epithelial cell-derived inflammatory cytokines, including IL-6 and IL-8, which are capable of causing I/R injury.

Assessment of the potential for pathogen dispersal during high-flow nasal therapy.

High-flow nasal therapy is increasingly used in hospitals because of its effectiveness and patient comfort. However, pathogens in the patient's nasal and oral cavities may be dispersed by forced air. This study aimed to investigate the risk of pathogen dispersal during high-flow nasal therapy. Liquid and bacterial dispersal were assessed via in-vitro experimental set-ups using a manikin. Thickened water or fresh yeast solution mimicked saliva and nasal mucus secretions. Dispersal was limited to the proximal area of the face and nasal cannula, suggesting that high-flow nasal therapy does not increase the risk of droplet and contact infection.

Isovolaemic haemodilution decreases the shivering threshold in rabbits.

BACKGROUND AND OBJECTIVE: The inhibition of thermoregulatory control by anaesthesia is manifested by reduced vasoconstriction and shivering thresholds. As intraoperative bleeding can result in haemodynamic changes, including vasoconstriction, we investigated the effect of experimental bleeding on the shivering threshold in rabbits. METHODS: Twenty-four rabbits were randomly assigned to one of three treatment strategies: (1) no blood removal (control), (2) 5 mL kg(-1) isovolaemic blood removal and (3) 10 mL kg(-1) isovolaemic blood removal. After tracheal intubation under isoflurane anaesthesia, anaesthesia was maintained with 50% nitrous oxide in oxygen. The removed blood volume was replaced with the same volume of warm hydroxyethyl starch colloid solution. Oesophageal temperature was measured as a core temperature at 1-min intervals. After blood removal, the animal's body was cooled at a rate of 2-3 degrees C h(-1) by perfusing water at 10 degrees C through a U-shaped thermode positioned in the colon. Hypothermic shivering was evaluated by visual inspection, and the core temperature at which shivering was triggered was identified as the thermoregulatory threshold for this response. RESULTS: Just before the cooling, the body temperature of the animals was around 38.6 degrees C in all of the three groups. The shivering threshold in the control group was 37.2 +/- 0.2 degrees C (mean +/- SD). The shivering thresholds in the 5 mL kg(-1) (36.9 degrees +/- 0.3 degrees C) and 10 mL kg(-1) (36.5 degrees +/- 0.5 degrees C) blood removal groups were significantly lower and in proportion with the volume of blood removed than that in the control group. CONCLUSION: Isovolaemic haemodilution decreased the shivering threshold in rabbits in proportion with the volume of blood removed.

Urinary bladder and oesophageal temperatures correlate better in patients with high rather than low urinary flow rates during non-cardiac surgery.

BACKGROUND AND OBJECTIVE: To investigate the effect of urinary flow rate on the urinary bladder temperature, we compared the accuracy and precision of urinary bladder temperature with oesophageal temperature at both high and low urine flow rates. METHODS: Twenty-four patients ASA physical status I or II who were undergoing tympanoplasty were randomly assigned to two groups with different intravenous fluid volumes: high (10 mL kg(-1) h(-1), n = 12) and low (3 mL kg(-1) h(-1), n = 12). General anaesthesia was induced with propofol and maintained with sevoflurane (1.5-2.5%) in nitrous oxide and oxygen. Urinary bladder temperature was measured using a Foley urinary catheter; distal oesophageal temperature was measured using a stethoscope thermocouple. These temperatures were measured every 5 min during surgery and the accuracy and precision of urinary bladder temperature with oesophageal temperature were determined using regression and Bland and Altman analyses. RESULTS: The correlation coefficient for oesophageal and urinary bladder temperature was 0.90 in the high urinary volume group and 0.75 in the low urinary volume group. The offset (oesophageal-urinary bladder) was -0.13 +/- 0.32 degrees C and -0.46 +/- 0.45 degrees C, respectively. CONCLUSION: Urinary bladder temperature appears to be more accurate at high urinary flow rates than at low urinary flow rates for clinical use.

Elevated sympathetic nerve activity in patients with accelerated essential hypertension.

To determine if an abnormality exists in the sympathetic nervous system of patients with accelerated hypertension, we recorded muscle sympathetic nerve activity (MSNA) from the tibial nerve by microneurography in eight benign essential hypertensives and seven accelerated essential hypertensives. Basal MSNA, plasma renin activity, and plasma angiotensin II levels were significantly higher in accelerated hypertensives than in benign hypertensives (P < 0.05). To clarify the relationship between the renin-angiotensin axis and sympathetic nervous system in the accelerated hypertensives, we measured the MSNA after 7 d of oral administration of captopril (75 mg/d) for antihypertensive treatment in the benign hypertensives and accelerated hypertensives. After administering captopril, the arterial pressure decreased significantly in the benign hypertensives and accelerated hypertensives with decreases in plasma angiotensin II levels, and the decreases in arterial pressure were greater in the accelerated hypertensive than in the benign hypertensives. After captopril administration, the MSNA decreased significantly in the accelerated hypertensives but did not change in the benign hypertensives. Thus, in accelerated hypertensives, sympathetic tone is elevated, and the elevated sympathetic tone is closely related to the activated renin-angiotensin axis tone.

The use of patient-controlled epidural fentanyl in elderly patients.

We studied whether delivering postoperative analgesia, using a patient-controlled epidural analgesia (PCEA) device was effective and safe in elderly patients. We enrolled 40 patients aged > 65 years (elderly group) and 40 patients aged 20-64 years (young group) scheduled for elective major abdominal surgery. PCEA infusion was started following completion of surgery. Mean (SD) fentanyl consumption (10.7 (3.7) compared with 10.5 (2.7) microg.kg(-1), p = 0.76) and number of times patients pressed the bolus switch (32 (36) compared with 44 (38), p = 0.16) during the first 24 h postoperatively were similar in the two groups. Pain scores, which were similar in both groups at rest, were significantly lower in the elderly on coughing (at 24 h, p < 0.05). In addition, average pain scores were similar at the time of PCEA bolus demands in the two groups. Elderly and young adult patients therefore required similar amounts of patient-controlled epidural fentanyl to produce satisfactory pain relief.

Upregulation of retinal transglutaminase during the axonal elongation stage of goldfish optic nerve regeneration.

Fish CNS neurons can repair their axons following nerve injury, whereas mammalian CNS neurons cannot regenerate, and become apoptotic within 1-2 weeks after the nerve lesion. One explanation for these differences is that one, or several molecules are upregulated in fish CNS neurons during nerve regeneration, and this same molecule is downregulated in mammalian CNS neurons before the development of apoptosis caused by nerve injury. A molecule satisfying these criteria might successfully rescue and repair the mammalian CNS neurons. In this study, we looked for such a candidate molecule from goldfish retinas. Transglutaminase derived from goldfish retina (TG(R)) was characterized as a regenerating molecule after optic nerve injury. A full-length cDNA for TG(R) was isolated from the goldfish retinal cDNA library prepared from axotomized retinas. Levels of TG(R) mRNA and protein increased only in the retinal ganglion cells (RGCs) between 10 and 40 days after optic nerve transection. Recombinant TG(R) protein enhanced neurite outgrowth from adult fish RGCs in culture. Specific interference RNA and antibodies for TG(R) inhibited neurite outgrowth both in vitro and in vivo. In contrast, the level of TG(R) protein decreased in rat RGCs within 1-3 days after nerve injury. Furthermore, the addition of recombinant TG(R) to retinal cultures induced striking neurite outgrowth from adult rat RGCs. These molecular and cellular data strongly suggest that TG(R) promotes axonal elongation at the surface of injured RGCs after optic nerve injury.

Augmentation of postconfluence growth arrest of 10T1/2 fibroblasts by endogenous cyclic adenosine 3':5'-monophosphate.

We have previously demonstrated that, by elevating intracellular adenosine 3':5'-cyclic monophosphate (cAMP) levels by inhibition of cAMP phosphodiesterase with Ro 20-1724 or by forskolin stimulation of adenylcyclase, the growth of neoplastically transformed 10T1/2 fibroblasts could be inhibited when these cells were in contact with growth-inhibited nontransformed 10T1/2 cells (J. S. Bertram and M. B. Faletto, Cancer Res., 45: 1946-1952, 1985) and furthermore that the extent of this growth inhibition correlated strongly with the degree of junctional communication between the two cell types (P.P. Mehta et al., Cell, 44: 187-196, 1986). To determine if these treatments enhance the degree of growth control of the nontransformed 10T1/2 cells, cultures were exposed to varying concentrations of Ro 20-1724 and/or forskolin. Drug treatment caused no significant effects on growth rate or cell spreading when cells were treated during logarithmic growth phase; however, major reductions of up to 70% in confluent saturation density and concomitant increases in cell spreading occurred in cultures making extensive cell/cell contacts. Decreases in saturation density correlated strongly with induced elevations of both intra- and extracellular cAMP concentrations. These effects could not be duplicated by the addition of exogenous cAMP agonists 8-bromo-cAMP and/or dibutyryl-cAMP. Two-dimensional electrophoresis of phosphate-labeled proteins revealed that forskolin treatment induced a quantitatively and qualitatively different phosphorylation profile than did 8-bromo-cAMP. Both basal and drug-induced intracellular cAMP levels fell as cells progressed from logarithmic to confluent growth state, implying that cells become sensitized to cAMP by the attainment of extensive cell/cell contacts. It is suggested that the drug-induced elevations of endogenously synthesized cAMP are accentuating a physiological role of cAMP on the postconfluent growth arrest of murine fibroblasts. The requirements for cell/cell contact and the known increased junctional communication induced by cAMP furthermore suggest that cAMP is enhancing the junctional transfer of a growth-inhibiting regulatory molecule. A likely candidate is cAMP itself.

Predisposing factors for the development of malignant essential hypertension.

To clarify predisposing factors for malignant hypertension, we retrospectively investigated the histories of 39 patients with malignant hypertension and 39 patients with benign hypertension. Between the malignant and benign groups, there was a statistically significant difference in blood pressure but not in age when hypertension was first noticed. The number of patients who had discontinued drug treatment was significantly greater in the malignant group (19; 49%) than in the benign group (11; 28%). Insufficient sleep, overwork, and/or mental burden of long duration were factors noticed within one year before the occurrence of the malignant phase in 11 (37%) of the 30 patients in that group in whom this information was available. Patients in the malignant group tended to belong to a lower social class. These results suggest that severe hypertension from an early phase, interruption of drug treatment, and physical and/or mental burden may predispose to the development of malignant hypertension, and that these predisposing factors are likely to be associated with social class.

Up-regulation of upstream stimulatory factors by protein malnutrition and its possible role in regulation of the IGF-binding protein-1 gene.

Protein malnutrition drastically induces the expression of the IGF-binding protein-1 (IGFBP-1) gene. We have previously shown that the region between -77 and -112 bp upstream of the rat IGFBP-1 gene contributes to the response of this gene to amino acid limitation. In an attempt to elucidate the basis of the responsiveness of this putative amino acid response unit (AARU), we searched the nucleus of the rat liver for a trans-acting factor whose binding to AARU was dependent on protein nutrition. Liver nuclear extracts of rats fed a protein-free diet and of those fed a control diet were compared by EMSA using the AARU as probe. One of the protein-probe complexes underwent a drastic increase after dietary protein deprivation. Assays using specific antibodies and several competitor oligonucleotides led to identification of the protein composing the complex as upstream stimulatory factor-1 (USF) and USF-2. The binding site of the USF proteins in the AARU turned out to be a CACGGG sequence that was homologous to the consensus USF-binding sequence (E box; CANNTG). Further, Western blot analyses showed that a protein-free diet caused significant increases in USF-1 and USF-2 levels. Thus, elevated expression of the IGFBP-1 gene under protein malnutrition can be attributable to increased binding of USF to its promoter, which results from increased USF levels. The data suggest that the changes in these ubiquitously distributed transcription factors play an important role in the nutritional regulation of expression of mammalian genes.

Age-related changes in muscle sympathetic nerve activity in essential hypertension.

To investigate the pathophysiological role of the sympathetic nervous system in essential hypertension, this study recorded the muscle sympathetic nerve activity (MSNA) of the tibial nerve and examined the age-related changes in patients with essential hypertension and in normotensive persons. There were 43 normotensive subjects (16-69 years old) and 63 patients with essential hypertension (18-67 years old) in the study. The MSNA at rest, recorded by microneurography, was evaluated by burst rate (bursts/min), burst incidence (bursts/100 heart beats), and spike frequency (spikes/min). The MSNA recording showed a high reproducibility with a correlation coefficient of 0.86 (p less than 0.01) in repeated studies. The MSNA was significantly greater in the hypertensive patients than in the normotensive subjects, irrespective of activity units (p less than 0.01), and this finding was consistent in the young (30 years old or less), middle-aged (31-50 years old), and old groups (51 years old or more). Furthermore, MSNA showed a significant positive correlation with age both in the normotensive subjects (r = 0.43, p less than 0.01 for burst rate; r = 0.49, p less than 0.01 for burst incidence; and r = 0.50, p less than 0.01 for spike frequency) and in the hypertensive patients (r = 0.40, p less than 0.01 for burst rate; r = 0.44, p less than 0.01 for burst incidence; and r = 0.40, p less than 0.01 for spike frequency).(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle sympathetic nerve activity in renovascular hypertension and primary aldosteronism.

Previous studies, including our own, have demonstrated that muscle sympathetic nerve activity (MSNA) is increased in patients with essential hypertension compared with normotensive subjects. However, the features of sympathetic nerve activity are still unknown in secondary hypertension. We examined MSNA in eight patients with renovascular hypertension and in 11 patients with primary aldosteronism. Twenty patients with essential hypertension and 20 normotensive subjects who were age-matched to the patients with renovascular hypertension and those with primary aldosteronism were also studied. The MSNA of a bundle of the tibial nerve was recorded by microneurography in supine subjects and expressed as both burst rate (bursts/min) and burst incidence (bursts/100 heart beats). Plasma renin activity and the plasma concentration of angiotensin II and aldosterone were also measured. MSNA was increased in the patients with renovascular hypertension compared with the patients with primary aldosteronism and those with essential hypertension and the normotensive subjects (p less than 0.01 for each). MSNA was decreased in the patients with primary aldosteronism compared with those with essential hypertension (p less than 0.01), and it was smaller than in the normotensive subjects (p less than 0.1). Furthermore, MSNA, plasma renin activity, and the plasma concentration of angiotensin II decreased significantly in five patients with renovascular hypertension 4-10 days after successful percutaneous renal angioplasty. Thus, the changes in MSNA seem to characterize the pathophysiology of renovascular hypertension and primary aldosteronism. Activation of the renin-angiotensin system may be involved in the increase in the central outflow of sympathetic nerve activity, thus exacerbating hypertension in patients with renovascular hypertension.

A simple estimation of peroxisomal degradation with green fluorescent protein - an application for cell cycle analysis.

When nutrients are depleted from the environment, mammalian cells begin to degrade their own cytosol and organelles. This bulk protein degradation is mediated by autophagy. In this study, peroxisomes in living CHO-K1 cells were visualized by targeting the green fluorescent protein (GFP) tagged with a type 1 peroxisomal targeting signal. The nutrient-starved condition induced a decay of GFP fluorescence in the peroxisomes and autophagic inhibitors such as 3-methyladenine suppressed the decay of GFP fluorescence (13-60% of starvation). By double labeling the nuclear DNA and peroxisomal GFP, the autophagy specifically occurred at the G1 phase of the cell cycle and the autophagic inhibitors suppressed the G1 arrest. The vital stain technique with GFP is a very simple and useful marker to quantitatively estimate or to further study peroxisomal degradation.

Release of opioid peptides, gluten exorphins by the action of pancreatic elastase.

The release of opioid peptides, gluten exorphins A, which have been isolated from the pepsin-thermolysin digest of wheat gluten, with gastrointestinal proteases was examined. High levels of gluten exorphin A5 (Gly-Tyr-Tyr-Pro-Thr) immunoreactive materials were detected in the pepsin-pancreatic elastase digest by a competitive ELISA. From this digest, gluten exorphin A5, B5 and B4 were isolated. This means that these peptides are released in the gastrointestinal tracts after ingestion of wheat gluten. The yield of gluten exorphin A5 in the pepsin-elastase digest was larger than that in the pepsin-thermolysin digest. The gluten exorphin A5 sequence is found 15 times in the primary structure of the high molecular weight glutenin. The region from which gluten exorphin A5 was released by the action of pancreatic elastase was identified using synthetic fragment peptides.

Reduced baroreflex changes in muscle sympathetic nerve activity during blood pressure elevation in essential hypertension.

To determine whether the baroreflex control of sympathetic nerve activity is altered in patients with essential hypertension, muscle sympathetic nerve activity (MSNA) was recorded microneurographically from the tibial nerves of 23 normotensive subjects and 23 patients with essential hypertension. When phenylephrine (2 micrograms/kg) was injected intravenously, although the pressor response of mean arterial blood pressure (MAP) was significantly enhanced in the hypertensives as compared with the normotensives, the reflex decrease in MSNA was significantly smaller in the hypertensives. Furthermore, the baroreflex slope for MSNA, used as an index of baroreflex sensitivity and calculated by relating the change in MSNA to the change in MAP, was significantly less in the hypertensives. Following the injection of nitroglycerin (2 micrograms/kg), there were no significant differences between the normotensives and hypertensives in the depressor response, the reflex increase in MSNA or the baroreflex slope for MSNA. These observations suggest that the baroreflex change in sympathetic nerve activity is reduced during phenylephrine-induced blood pressure elevation but not during nitroglycerin-induced hypotension in the hypertensives, and that the blunted response of sympathetic nerve activity occurring during hypertension in these hypertensive patients may underlie the maintenance of high blood pressure in essential hypertension.

Gliotoxic effects of alpha-aminoadipic acid isomers on the carp retina: a long term observation.

The glutamate analogue, alpha-aminoadipic acid was intravitreally administered in the D-, DL- and L-forms to carp (Cyprinus carpio) retina in vivo. To make a quantitative assessment of its gliotoxic action, the activity of glutamine synthetase, whose localization was confirmed in glial Müller cells by an immunohistochemical technique, was examined at various intervals over one month. Intravitreal injection of 8 mumol alpha-aminoadipic acids reduced the glutamine synthetase activity within 4 h and maximally by 24 h. The maximum reduction evoked by L-, DL- and D-forms was about 65, 45 and 28% in reduction, and their minimum effective dose was 0.8, 1.5 and 2.0 mumol, respectively. At three to four days after alpha-aminoadipic acids injection, sodium dodecyl sulphate gel electrophoresis suggested that some retinal proteins including glutamine synthetase were significantly reduced, whilst others were increased. These biochemical changes were fully reversed one to two weeks after administration of the D- or DL-forms, but not until one month with the L-form. The electroretinographic b-wave, reflecting glial activity, was completely blocked by 8 mumol alpha-aminoadipic acids within 4 h. The electroretinographic b-wave was recovered first in the case of D- and then of DL-form at two to three weeks after injection, but only 50% recovery was seen in the case of L-form even two months later. A high dose of DL-alpha-aminoadipic acid (16 mumol) induced as long lasting a suppression in the glutamine synthetase and electroretinographic b-wave activities as 8 mumol L-alpha-aminoadipic acid. Therefore, the gliotoxic efficacy of L-alpha-aminoadipic acid at micromol orders was two-fold higher than that of DL-alpha-aminoadipic acid. Differences in the time-course of recovery of the suppression of glutamate synthetase and electroretinographic b-wave activities induced by alpha-aminoadipic acids are discussed in terms of its gliotoxicity.