Retraction notice to "Infusion of amino acid enriched solution hastens recovery from neuromuscular block caused by vecuronium" [Br J Anaesth 2001; 86: 814-821].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief of British Journal of Anaesthesia. The study is retracted for the following reasons: Statistical analysis suggests that the data may be fabricated. Y Saitoh provided a statement in a personal communication to a member of the editorial board of British Journal of Anaesthesia that the study was not approved by the Institutional Review Board and that no evidence exists to support the study findings.

Retraction notice to "Monitoring of neuromuscular block after administration of vecuronium in patients with diabetes mellitus" [Br J Anaesth 2003; 90: 480-486].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief of British Journal of Anaesthesia. The study is retracted for the following reasons: Statistical analysis suggests that the data may be fabricated. Y Saitoh provided a statement in a personal communication to a member of the editorial board of British Journal of Anaesthesia that the study was not approved by the Institutional Review Board and that no evidence exists to support the study findings. Additionally, the Japanese Society of Anesthesiologists has recommended retraction of this article: http://www.anesth.or.jp/english/pdf/news20170925.pdf.

Gabexate mesilate hastens recovery from vecuronium-induced neuromuscular blockade.

BACKGROUND AND OBJECTIVE: To test the hypothesis that gabexate mesilate, a protease inihibitor, hastens recovery from neuromuscular blockade, we examined the effect of gabexate mesilate on the recovery of vecuronium-induced neuromuscular blockade in anaesthetized patients in a double-blind, randomized fashion. METHODS: Thirty adult patients were divided into two groups of 15. In the gabexate mesilate group, immediately after administration of vecuronium 0.1 mg kg(-1), a continuous infusion of gabexate mesilate was started at a speed of 1.5 mg kg(-1) h(-1). In the control group, normal saline was administered instead of gabexate mesilate. Times to the return of T1, T2, T3 or T4 (first, second, third and fourth response of train-of-four (TOF)), times to the recovery of T1/control to 0.25 (T25) or 0.5 (T50), recovery of T1/control or TOF ratio (T4/T1) were compared between the two groups. RESULTS: Times to the returns of T1, T2, T3 and T4 in the gabexate mesilate group were significantly shorter than in the control group (19.4 +/- 6.8 vs. 25.7 +/- 7.2 min for T1; mean +/- SD, P = 0.020). Times to T25 and T50 were significantly shorter in the gabexate mesilate group than in the control group (34.0 +/- 9.9 vs. 51.3 +/- 10.2 min for T25, P < 0.001). T1/control and TOF ratio in the gabexate mesilate group were significantly higher than in the control group 40-80 min and 40-120 min after administration of vecuronium, respectively (P < 0.05). CONCLUSION: Gabexate mesilate hastens recovery from neuromuscular block in anaesthetized patients receiving vecuronium.

Reversal of vecuronium with neostigmine in patients with diabetes mellitus.

Reversal of vecuronium-induced neuromuscular blockade with neostigmine was compared in two groups of 16 subjects: patients with Type 2 diabetes mellitus and normal controls. When the first twitch of the train-of-four had returned to 25% of the control value, neostigmine 40 microg x kg(-1) and atropine 20 microg x kg(-1) were given to reverse the neuromuscular blockade. The train-of-four ratio was lower at 3 min, 6 min, 9 min, 12 min and 15 min after reversal in the diabetic group than in the control group but the differences did not reach statistical significance. Fifteen minutes after reversal, the number of patients in whom recovery from neuromuscular blockade was judged insufficient to guarantee good respiratory function (train-of-four ratio < 0.74) did not differ between the groups. However, 15 min after reversal, the number of patients with a train-of-four ratio < 0.9 was significantly higher in the Diabetic Group than in the Control Group (15 vs. 10, p = 0.033).

Effect of milrinone on vecuronium-induced neuromuscular block.

We examined the effect of milrinone, a phosphodiesterase III inhibitor, on neuromuscular block induced by vecuronium. Thirty adult patients were randomly assigned to one of two equal groups: the milrinone group and the control group. Subjects in the milrinone group received an intravenous loading dose of milrinone 5 microg x kg-1x min-1 for 10 min, followed by an infusion at a rate of 0.5 microg x kg-1x min-1. Subjects in the control group received normal saline at a rate of 0.1 ml x kg-1 x h-1. Thirty minutes after the beginning of the infusion of milrinone, anaesthesia was induced with intravenous thiopental 4 mg x kg-1 and fentanyl 2 microg x kg-1, and was maintained with isoflurane in oxygen and nitrous oxide. Neuromuscular blockade was monitored electromyographically at the adductor pollicis muscle. The times from the administration of vecuronium 0.1 mg.kg-1 to the onset of neuromuscular block and the return of the first, second, third, and fourth response of the train-of-four were compared between the two groups. Times to the recovery of the ratio of the first twitch to the control twitch to 25%, 50% and 75%, and times to the recovery of train-of-four ratio to 25%, 50% and 75% were also compared between the two groups. The onset of neuromuscular block in the milrinone group was significantly slower than in the control group. The times to the returns of the four twitches of the train-of-four, times to recovery of the ratio of the first twitch to the control twitch to 25% and 50%, and the times to the recovery of the train-of-four ratio to 25% and 50% were significantly shorter in the milrinone group than in the control group. We conclude that milrinone delays the onset of neuromuscular blockade but hastens its recovery in anaesthetised patients receiving vecuronium.

Monitoring of neuromuscular block after administration of vecuronium in patients with diabetes mellitus.

BACKGROUND: We studied the supramaximal current for ulnar nerve stimulation during electromyographic monitoring of onset and recovery of neuromuscular block using a neuromuscular transmission module (M-NMT Module, Datex-Ohmeda) in patients with Type 2 diabetes undergoing anaesthesia with nitrous oxide, oxygen, isoflurane and fentanyl. METHODS: Thirty-six diabetic patients were randomly assigned to a post-tetanic count (PTC) group (n=17) or train-of-four (TOF) group (n=19). In addition, 30 non-diabetic patients were divided into control PTC (n=15) and TOF groups (n=15). RESULTS: In the diabetic patients (diabetes PTC and diabetes TOF groups), the mean supramaximal stimulating current was significantly higher than in the non-diabetic patients (control PTC and TOF groups) (50.5 (SD 14.1) vs 33.4 (6.1) mA, P<0.01). Onset of neuromuscular block (time to disappearance of T1) after vecuronium 0.1 mg kg(-1) in the diabetic patients did not differ significantly from that in the non-diabetic patients (276 (77) vs 244 (44) s, P=0.055). Time to return of PTC1 did not differ significantly between the diabetes and control PTC groups (21.0 (12.1) vs 15.7 (5.0) min, P=0.126). Times to return of T1 and T4 in the diabetes TOF group were significantly longer than in the control TOF group (T1: 37.5 (15.2) vs 25.7 (7.6) min, P=0.01; T4: 61.4 (23.7) vs 43.5 (11.4) min, P=0.01). During recovery, PTC and T4/T1 in the diabetes PTC and TOF groups were similar to those in the control PTC and TOF groups, respectively. T1/T0 in the diabetes TOF group was significantly less than in the control TOF group, 80-120 min after vecuronium (P<0.05). CONCLUSIONS: In diabetic patients, supramaximal current is higher than in non-diabetic patients. After vecuronium, onset of neuromuscular block and recovery of PTC or T4/T1 are not altered, but time to return of T1 or T4, and recovery of T1/T0 are delayed in diabetic patients.

Effects of xenon on acetylcholine release in the rat cerebral cortex in vivo.

BACKGROUND: We have reported previously the effects of several anaesthetics on cholinergic activity in the central nervous system (CNS). In this study, we report the effects of xenon on cholinergic cell activity. METHODS: Using in vivo brain microdialysis, we measured acetylcholine (ACh) release in the rat cerebral cortex in vivo during xenon anaesthesia. RESULTS: Xenon induced an initial increase in ACh release, followed by a gradual decrease. The level of Ach release at 40 min of xenon administration was significantly higher than the control. CONCLUSIONS: Xenon activates CNS cholinergic cell activity followed by development of acute tolerance.

Comparison of the expression patterns of two LIM-homeodomain genes, Lhx6 and L3/Lhx8, in the developing palate.

OBJECTIVES: To compare and contrast the gene expression of two LIM-homeobox type transcription factors, Lhx6 and L3/Lhx8, in secondary palate formation. METHODS: In situ hybridization histochemistry with digoxygenin (DIG) labelled cRNA probes specific for Lhx6 and L3/Lhx8. MATERIALS: Serial cryo-sections of embryonic day (E)13.5, 14.5, and 15.5 mice (C57BL/6). OUTCOME MEASURE: Comparison of the signal intensities of NBT/BCIP precipitate by alkaline phosphatase conjugated anti-DIG antibody. RESULTS: From E13.5 to E15.5, Lhx6 and L3/Lhx8 signals are detected in palatal mesenchyme, but the L3/Lhx8 signal is much more intense than the Lhx6 signal. In palatal epithelium, covering the mesenchyme, Lhx6 mRNA is transiently expressed at E14.5, while L3/Lhx8 mRNA expression is never detected throughout the development. CONCLUSION: Lhx6 and L3/Lhx8 functions may be partially redundant in the mesenchyme of the secondary palate, but not in the palatal epithelium.

The effect of ulinastatin pre-treatment on vecuronium-induced neuromuscular block in patients with hepatic cirrhosis.

The aim of this study was to investigate the effect of ulinastatin, a protease inhibitor, on the neuromuscular block produced by vecuronium in patients with hepatic cirrhosis. Thirty adult patients with hepatic cirrhosis were randomly allocated to receive ulinastatin (cirrhosis/ulinastatin group, n = 15) or saline (cirrhosis/saline group, n = 15). Fifteen healthy adult patients without hepatic cirrhosis comprised a control group. Patients were given a standardised anaesthetic that included nitrous oxide and isoflurane in oxygen, and fentanyl. A bolus dose of ulinastatin 5000 unit x kg(-1) was given to members of the cirrhosis/ulinastatin group. The same volume of normal saline was given to the other two groups. Two minutes later, vecuronium 0.1 mg x kg(-1) was given. The onset of neuromuscular block was significantly slower in the cirrhosis/ulinastatin group than in the cirrhosis/saline and control groups (p < 0.05). Spontaneous recovery of neuromuscular function was significantly quicker in the cirrhosis/ulinastatin and control groups than in the cirrhosis/saline group (p < 0.05). The time course of recovery in the cirrhosis/ulinastatin and control groups was similar. We conclude that in cirrhotic patients, ulinastatin delays the onset of neuromuscular block produced by vecuronium. After pretreatment with ulinastatin, the speed of recovery from neuromuscular block in patients with cirrhosis becomes similar to that seen in healthy patients.

Precordial compression without airway management induces lung injury in the rodent cardiac arrest model with central apnea.

To investigate whether the lung injury induced by precordial compression without ventilation or not, in the cardiac-arrest animal model with central apnea. Thirty male Sprague-Dawley rats were anesthetized with halothane. The cardiac arrest was induced by 100 mg/kg ketamine (IV) and accompanied with central apnea. They were allocated to four groups by means of resuscitation. Group A was treated with only precordial compression without the other treatments. In group B with tracheotomy and precordial compression. In group C was performed tracheotomy, oxygenation, and precordial compression. The animals in group D were treated with tracheotomy, oxygen administration, artificial ventilation, and precordial compression. Four minutes after cardiac arrest, the resuscitation was started and continued for 20 min. PaCO(2) in the group without mechanical ventilation increased significantly after the start of the resuscitation. All animals were sacrificed after resuscitation procedure. The wet/dry weight ratio of lung in group A (6.9+/-0.8) was significantly higher than that of the other groups B, C and D (5.9+/-0.6, 5.7+/-0.4 and 5.6+/-0.4, P<0.05 in each). The pathological findings also demonstrated the lung injuries, such as edema, migration, and destruction of structure in group A. The precordial compression alone did not improve CO(2) elimination in the gasping-less cardiac arrest model, as well as maybe inducing more severe lung injury than that with the protective management. This experimental model raises the possibility that chest compressions without airway management might result in lung injury.

Infusion of amino acid enriched solution hastens recovery from neuromuscular block caused by vecuronium.

We investigated the effect of an amino acid infusion on neuromuscular block produced by vecuronium, and on rectal temperature and surface temperature over the adductor pollicis muscle. Sixty adult patients undergoing general anaesthesia were randomly divided into four groups of 15 patients each: amino acid (AA)-post-tetanic count (PTC); AA-train-of-four (TOF); control (C)-PTC; or C-TOF group. In the AA-PTC and AA-TOF groups, after a bolus of vecuronium 0.1 mg kg(-1), a continuous infusion of an 18 amino acid enriched solution (AMIPAREN) was started at a rate of 166 kJ h(-1). In the C-PTC and C-TOF groups, normal saline was administered. Time from vecuronium to the return of the PTC in the AA-PTC group was significantly shorter than in the C-PTC group (mean (SD), 13.3 (4.5) versus 18.0 (5.6) min, P<0.05). Times to return of T1, T2, T3, and T4 (first, second, third, and fourth twitch of TOF) in the AA-TOF group were significantly shorter than in the C-TOF group (21.1 (4.5) versus 28.0 (8.2) min for T1, P<0.05). PTC in the AA-PTC group was significantly greater than in the C-PTC group; 25-35 min after administration of vecuronium (P<0.05). T1/T0 and T4/T1 in the AA-TOF group were significantly higher than in the C-TOF group, 40-120 and 50-120 min after vecuronium respectively (P<0.05). Rectal temperature and surface temperature over the adductor pollicis muscle in the AA-PTC and AA-TOF groups were significantly higher than in the control groups 50-120 and 100-120 min after vecuronium respectively (P<0.05). Infusion of amino acid enriched solution hastens recovery from neuromuscular block.

Apoptosis-inducing protein, AIP, from parasite-infected fish induces apoptosis in mammalian cells by two different molecular mechanisms.

AIP (apoptosis-inducing protein) is a protein purified and cloned from Chub mackerel infected with the larval nematode, Anisakis simplex, which induces apoptosis in various mammalian cells including human tumor cell lines. AIP has shown structural and functional homology to L-amino acid oxidase (LAO) which oxidizes several L-amino acids including L-lysine and AIP-induced apoptosis has been suggested to be mediated by H2O2 generated by LAO activity of AIP. In this study, we confirmed that recombinant AIP generated enough H2O2 in culture medium to induce rapid apoptosis in cells and this apoptosis was clearly inhibited by co-cultivation with antioxidants such as catalase and N-acetyl-cysteine. Surprisingly, however, we found that AIP still could induce H2O2-independent apoptosis more slowly than H2O2-dependent one in HL-60 cells even in the presence of antioxidants. In addition, the HL-60-derived cell line HP100-1, which is a H2O2-resistant variant, underwent apoptosis on treatment with AIP with a similar delayed time course. The latter apoptosis was completely blocked by addition of L-lysine to the culture medium, which is the best substrate of AIP as LAO, indicating that decreased concentration of L-lysine in the culture medium by AIP-treatment induced apoptosis. We also showed that the both apoptosis by AIP were associated with the release of cytochrome c from mitochondria and activation of caspase-9, and overexpressed Bcl-2 could inhibit both of the AIP-induced apoptosis. These results indicate that AIP induces apoptosis in cells by two distinct mechanisms; one rapid and mediated by H2O2, the other delayed and mediated by deprivation of L-lysine, both of which utilize caspase-9/cytochrome c system.

Episomal segregation of the adenovirus enhancer sequence by conditional genome rearrangement abrogates late viral gene expression.

We have constructed a recombinant adenovirus gene delivery system that is capable of undergoing growth phase-dependent site-specific recombination. When propagated in 293 producer cells, the vector retains its linear double-stranded form and can be propagated to high titer and purified by conventional procedures. Upon introduction into target cells, the viral chromosome undergoes cyclization to generate an autonomously replicating circular episome and a detached linear fragment. The viral enhancer and reporter gene segregate with the circular episome, which contains no adenovirus open reading frames. The effect of rearrangement of adenovirus gene expression was assessed by quantitative reverse transcription-PCR measurement of the abundance of transcripts encoding the tripartite leader sequence (TPL) of the major late promoter. Whereas nonrearranging viruses produced approximately 10(4) TPL transcripts per 10(6) infecting genomes in the HepG2 liver cell line, no transcripts were detectable in the same cells infected with comparable levels of circularizing vector. Because no helper virus is required to propagate these vectors, the problems of recombination with and contamination by helper virus are eliminated. We also present an efficient and reliable method for generating recombinant adenoviruses.

[Influence of impaired renal function and Helicobacter pylori infection on serum pepsinogen concentrations].

It has been known that patients with chronic renal failure have elevated concentrations of serum pepsinogens, which are raised by Helicobacter pylori (H. pylori) infection of the stomach. This study was conducted to examine how renal dysfunction and H. pylori infection affect serum pepsinogen (PG) concentrations. The subjects consisted of 93 patients with renal disease (60 males and 33 females with a mean age of 55 +/- 1.3 years). Dialysis patients were not included. Twenty-four-hour urinary collection was performed, and creatinine clearance (Ccr) was calculated for all the subjects. Status of H. pylori infection was assessed by serum IgG antibody against H. pylori. Fasting serum PG I and PG II were measured by RIA. The subjects were divided into 4 groups based on Ccr: group A: Ccr > or = 71 ml/min; group B: 30-70 ml/min; group C: 11-30 ml/min; group D: Ccr < or = 10 ml/min. Regardless of the H. pylori status, serum PG I concentrations were elevated as the renal function declined; serum PG I levels of groups C and D (177.5 +/- 15.2 ng/ml and 234.0 +/- 32.2 ng/ml, respectively) were significantly higher than those of group A (66.1 +/- 9.6 ng/ml, p < 0.01); Group D also had a significantly higher concentration of PG I than group B (106.0 +/- 17.2 ng/ml, p < 0.01). The same tendency was found in serum PG II concentrations. However, the differences among the 4 groups were not statistically significant (16.2 +/- 2.3, 24.2 +/- 4.0, 28.3 +/- 3.5, 34.3 +/- 5.6 ng/ml for group A, B, C, and D, respectively). There was a negative correlation between Ccr and serum PG I concentrations (r = -0.45, p < 0.01). In comparison between H. pylori-infected patients and uninfected patients, serum levels of PG II were higher in the former patients than in the latter. This difference was significant in groups A and C. Serum PG I concentrations were the same between H. pylori-infected patients and their uninfected counterparts for the 4 groups. The present study has shown that serum PG I concentrations are raised by a loss of renal function, while PG II levels are elevated mainly by H. pylori infection of the stomach. It is concluded that renal function and H. pylori infection should be taken into account when serum PG concentrations are evaluated in patients with renal diseases.

Influences of Helicobacter pylori on serum pepsinogen concentrations in dialysis patients.

BACKGROUND: Patients with impaired renal function have been known to have elevated concentrations of serum pepsinogens, which are raised by Helicobacter pylori infection of the stomach. The present study was performed to examine the effect of H. pylori infection on serum pepsinogen concentrations in dialysis patients. METHODS: Forty nine patients on dialysis and 48 subjects with no known kidney disease were examined for upper gastroduodenal endoscopy, H. pylori infection and serum concentrations of pepsinogen I and II. The status of H. pylori infection was evaluated from results of a urease test, histology and culture of biopsy specimens of the gastric mucosa. Serum pepsinogen levels were measured by radioimmunoassay. RESULTS: Serum concentrations of pepsinogen I and II were elevated in the dialysis patients in comparison with those in the controls (277.4+/-24.2 vs 52.6+/-4.0 pg/ml, P<0.01 for pepsinogen I, and 30.2+/-2.9 vs 14.9+/-1.3 pg/ml, P<0.01 for pepsinogen II). In both the dialysis patients and controls, those with H. pylori infection had significantly higher concentrations of serum pepsinogen I and II and a lower ratio of pepsinogen I to pepsinogen II than those without infection. Among the controls, 15 of 25 subjects with atrophic gastritis had a pepsinogen I/pepsinogen II ratio < or = 3.0, while only two out of 17 patients on dialysis fell into this range. CONCLUSIONS: We conclude that H. pylori status should be taken into account when serum pepsinogen concentrations are evaluated in dialysis patients.

Living related donor liver transplantation in a patient with severe aortic stenosis.

We report the successful anaesthetic management of a young girl with Alagille's syndrome and severe aortic stenosis (resting pressure gradient 88 mm Hg) undergoing living related donor liver transplantation (LRDLT). The patient had end-stage liver disease and LRDLT was performed before replacement of the aortic valve. Anaesthesia was conducted uneventfully with the aid of a pulmonary artery catheter. Intra-aortic balloon pumping was used in the perioperative period for protection against myocardial ischaemia. Total clamping of the inferior vena cava was avoided during surgery and volume administration was guided by the pulmonary artery pressure. A stable circulation was maintained in the reperfusion period. The patient was discharged from hospital on day 54 after operation with normal liver function. Two years later her aortic valve was replaced successfully.