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This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief of British Journal of Anaesthesia.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This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief of British Journal of Anaesthesia.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.

Deficiency of coagulation factor XIII A subunit caused by the dinucleotide deletion at the 5' end of exon III.

A congenital deficiency of the coagulation Factor XIII A subunit (F XIII A) is a rare autosomal recessive disorder that is characterized by a life-long bleeding tendency complicated by a difficulty in healing. Thus far, no molecular genetic analysis of this disorder has been reported. In this study, we demonstrate the molecular abnormalities in a family with this disorder. We performed Northern blot analysis of peripheral blood monocytes obtained from the propositus and found a 4-kb single band of F XIII A mRNA whose size was identical with that of normal subjects. Exons II-XV, which encode all the amino acids, were individually amplified by a polymerase chain reaction (PCR). All PCR products from the propositus had lengths indistinguishable from those of the wild type on agarose gel, suggesting that this defect results from either a point mutation or a short deletion/insertion. The sequencing of F XIII A cDNA from the propositus revealed a deletion of the dinucleotide AG within the AGAG repeat at the position of 210 to 213. Concerning the genomic sequence, a deletion of dinucleotide AG was also demonstrated in the intron B-exon III boundary. This deletion appeared to cause a frameshift mutation making a new stop codon shortly thereafter, and leading to a deficiency of plasma F XIII A. The heterozygosity of the F XIII A deficiency in the patient's offspring was documented by the nucleotide sequences of their exon III.

Proteolytic activation of MST/Krs, STE20-related protein kinase, by caspase during apoptosis.

The Fas system has been extensively investigated as a model of apoptosis and the caspase cascade has been shown to be a characteristic mechanism of signaling of apoptosis. We have identified and purified a kinase that was activated after the stimulation of Fas on human thymoma-derived HPB-ALL cells. Partial amino acid sequencing of the purified kinase revealed it to be MST/Krs, member of the yeast STE20 family of protein kinases. MST/Krs was activated by proteolytic cleavage and proteolytic activation was blocked by the caspase inhibitor, Z-VAD-FK. A mutant MST with Asp-->Asn replacement at a putative caspase cleavage site was resistant to either the proteolytic cleavage or the activation of the kinase activity. These findings suggest that proteolytic activation is one activation mechanism of MST and plays a role in apoptosis.

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.

Factors associated with postoperative respiratory complications in pediatric liver transplantation from living-related donors.

Factors associated with respiratory complications (RCs) after pediatric living-related liver transplantation were statistically analyzed in the first 100 cases where surgery was performed at Kyoto University. The overall incidence of postoperative RCs was 45%, including atelectasis (23%), pleural effusion (23%), and pneumonia (12%). Univariate and multivariate analyses were performed with regard to the association between postoperative RCs and 13 pre- and intraoperative variables that were considered to represent the preoperative medical status of the patients and the severity of operative insult. The following four independent variables were found to have prognostic significance with regard to the postoperative RCs: (1) history of preoperative RCs, (2) height < or = -2 SD from the mean for the age, (3) United Network for Organ Sharing score = 1, and (4) intraoperative blood loss > or = 20% of body weight. Postoperative death was highly affected by postoperative RCs: 8 of 11 deaths during the study period were directly or closely related to postoperative RCs. We conclude that postoperative RCs are major contributing factors to operative morbidity and mortality in pediatric living-related liver transplantation, which may possibly be reduced by intensive respiratory management of patients with the above risk factors for postoperative RCs.

Diversity of primary structures of the carboxy-terminal regions of mammalian fibrinogen A alpha-chains. Characterization of the partial nucleotide and deduced amino acid sequences in five mammalian species; rhesus monkey, pig, dog, mouse and Syrian hamster.

The partial amino acid sequences of fibrinogen A alpha-chains from five mammalian species have been inferred by means of the polymerase chain reaction (PCR). From the genomic DNA of the rhesus monkey, pig, dog, mouse and Syrian hamster, the DNA fragments coding for alpha-C domains in the A alpha-chains were amplified and sequenced. In all species examined, four cysteine residues were always conserved at the homologous positions. The carboxy- and amino-terminal portions of the alpha-C domains showed a considerable homology among the species. However, the sizes of the middle portions, which corresponded to the internal repeat structures, showed an apparent variability because of several insertions and/or deletions. In the rhesus monkey, pig, mouse and Syrian hamster, 13 amino acid tandem repeats fundamentally similar to those in humans and the rat were identified. In the dog, however, tandem repeats were found to consist of 18 amino acids, suggesting an independent multiplication of the canine repeats. The sites of the alpha-chain cross-linking acceptor and alpha 2-plasmin inhibitor cross-linking donor were not always evolutionally conserved. The arginyl-glycyl-aspartic acid (RGD) sequence was not found in the amplified region of either the rhesus monkey or the pig. In the canine alpha-C domain, two RGD sequences were identified at the homologous positions to both rat and human RGDS. In the Syrian hamster, a single RGD sequence was found at the same position to that of the rat. Triplication of the RGD sequences was seen in the murine fibrinogen alpha-C domain around the homologous site to the rat RGDS sequence. These findings are of some interest from the point of view of structure-function and evolutionary relationships in the mammalian fibrinogen A alpha-chains.

A randomized phase II trial of low-dose aclarubicin vs very low-dose cytosine arabinoside for treatment of myelodysplastic syndromes.

We performed a randomized phase II trial comparing low-dose aclarubicin (LC-ACR) with very low-dose cytosine arabinoside (VLD-AC) in 39 consecutive untreated patients with myelodysplastic syndromes (MDS), including refractory anemia (RA), RA with excess of blasts (RAEB) and RAEB in transformation (RAEB-t). Nineteen patients received the VLD-AC therapy; 2 good responses (GR) and 2 partial responses (PR) were obtained in 11 patients with RAEB and RAEB-t, while 2 PR were obtained in 8 RA patients. Eighteen patients received the LD-ACR therapy; 2 GR and 4 PR were obtained in 11 RAEB/RAEB-t patients while 2 PR in 7 RA patients. There was no significant difference in the therapeutic effects and survival between these two groups of patients. These observations suggest that the LD-ACR therapy is effective in some patients with MDS and can be used as an alternative to the low-dose Ara-C therapy.

Development of an ultrathin fiberscope with a built-in channel for bronchoscopy in infants.

Flexible fiberoptic bronchoscopy (FFB) is of great importance for diagnostic and therapeutic purposes in pediatric respiratory management. However, lack of a built-in channel in commercially available ultrathin fiberscopes has limited its usefulness in neonates and infants. Bronchoscopic procedures, including suctioning, BAL, bronchography, and selective drug injection have instead been performed by temporary extubation followed by mask ventilation. However, such techniques are not suitable for repeated FFB and are open to considerable risks, especially in critically ill patients. In this context, we developed a directable ultrathin fiberscope with an external diameter of 2.7 mm and a 0.8-mm internal diameter built-in channel. This prototype fiberscope, the XPF27, is useful during spontaneous ventilation and can be inserted through a 3.5-mm or larger endotracheal tube. The XPF27 was utilized for 55 FFB procedures and allowed suctioning, BAL, bronchial toileting, and bronchography in 16 critically ill children without complications. We conclude that XPF27 is useful for pediatric FFB despite its limited flexibility, visual field, and resolution.

Serum concentration of the soluble interleukin-2 receptor for monitoring acute graft-versus-host disease.

Soluble interleukin-2 receptors (sIL-2R) are elevated in various disorders involving the activation of T cells. We measured serial serum concentrations of sIL-2R in 30 patients receiving allogeneic BMT to evaluate the usefulness of sIL-2R as a parameter for acute GVHD. In the 17 patients who developed acute GVHD, the sIL-2R concentration rose significantly on day 3 following transplantation, preceding the occurrence of acute GVHD. This change was not seen in the 13 patients without acute GVHD. The serum concentration of sIL-2R decreased as the acute GVHD subsided. The peak concentration of serum sIL-2R correlated with the severity of the acute GVHD. Simultaneous measurement of tumor necrosis factor alpha (TNF alpha) showed a significant rise in patients with acute GVHD, that became evident earlier than the sIL-2R elevation. TNF alpha concentrations also decreased following treatment of the acute GVHD. However, significant rise in TNF alpha were also seen in the early phase of allogeneic BMT in patients who did not develop acute GVHD. Our data suggest that the serum concentrations of sIL-2R as well as TNF alpha might reflect the severity of acute GVHD, and that the serum sIL-2R concentration might be a sensitive and practical indicator for acute GVHD.

Autologous peripheral blood stem cell transplantation for acute myelogenous leukemia.

The safety and efficacy of myeloablative therapy followed by autologous peripheral blood stem cell transplantation (ABSCT) for acute myelogenous leukemia (AML) were evaluated in 60 patients. Peripheral blood stem cells (PBSC) were collected during recovery after consolidation chemotherapy. High-dose chemotherapy consisting of busulfan (16 mg/kg), etoposide (40 mg/kg), and cytosine arabinoside (3 g/m2 x 4) (BEA regimen) was used for pretransplant conditioning in 13 patients. For the remaining 47 patients, granulocyte colony-stimulating factor (G-CSF) was administered concurrently with the BEA regimen during conditioning. Unpurged, cryopreserved PBSC containing a median number of 5.4 x 10(8) MNC/kg or 12 x 10(4) CFU-GM/kg were reinfused at transplantation. The median number of days to granulocytes exceeding 500/microl and last platelet transfusion were 15 (8-44) and 24 (0->180), respectively. The 3-year probabilities of disease-free survival (DFS) and relapse were 78.6 and 21.4% for patients transplanted in first remission, 29.6 and 64.4% for those in second or third remission, and 11.1 and 77.8% for those in relapse, respectively. There were no transplant-related deaths within 100 days of transplantation. Age, disease status at transplantation, and number of induction chemotherapies to first complete remission were risk factors affecting the outcome of ABSCT. These results of ABSCT for AML in first remission warrant a prospective study of ABSCT as post-remission therapy.

Perioperative respiratory management with fiberoptic bronchoscopy in pediatric living-related liver transplantation.

BACKGROUND: Perioperative respiratory complications have been one of the largest obstacles to pediatric management of pediatric liver METHODS: The roles of fiberoptic bronchoscopy in perioperative respiratory management of pediatric liver transplantation were studied retrospectively. RESULTS: In a group of 162 children who underwent pediatric living-related liver transplantation, 44 underwent 222 bronchoscopic procedures for diagnostic and therapeutic purposes during the perioperative period. Major indications for bronchoscopy were atelectasis/retention of airway secretion (n = 27), pneumonia (n = 19), pulmonary edema (n = 8), airway stenosis (n = 7), and airway bleeding (n = 6). Visualization of the airway was helpful in diagnosing respiratory complications; in seven infants, bronchoscopy revealed tracheobronchial stenosis that other diagnostic modalities failed to detect. In 16 of 19 patients with pneumonia, specimens taken by bronchoscopy were positive for specific pathogens. Bronchoscopy also proved to have significant therapeutic value, especially in airway cleaning; bronchial suctioning resulted in immediate reexpansion of the collapsed lung in 16 of 20 cases of atelectasis. No complications were noted other than severe hypoxia and bradycardia in one infant. CONCLUSIONS: Fiberoptic bronchoscopy is a safe and useful modality for perioperative respiratory management in pediatric liver transplantation.

A sequence analysis of von Willebrand factor mRNA, gene, and pseudogene in two patients with von Willebrand disease type 2B, and an investigation of gene conversion in its gene.

We identified the point mutations in two unrelated patients with von Willebrand disease (vWD) type 2B using sequence analyses of the gene, pseudogene and messenger RNA of vWF. Both patients were determined to be heterozygotes with amino acid transitions of 1308 Arg-->Cys in Case 1 and 1316 Val-->Met in Case 2. Moreover, we also found single base transitions 7541 A-->G in intron 27 of the active gene, and 7642 A-->G, which thus destroyed the Kpn 1 site, in its pseudogene in both cases. Since these mutations represented changes in the base between the gene and its pseudogene, we studied the presence of gene conversion in exon 28 of vWF gene to clarify its pathological role. Using RT-PCR and an allele-specific restriction enzyme analysis, we identified no gene conversions in this region in four other patients with vWD, 25 normal subjects and one cell line, MEG01. Based on these findings, gene conversion in the vWF gene is not considered to be a frequent phenomenon in either vWD patients or normal subjects.

Pericentric inversion of chromosome 16 and eosinophilia in chronic myelomonocytic leukemia.

We report a case of myelodysplastic syndrome with bone marrow eosinophilia and the chromosomal abnormality, inv(16)(p13q22). Hematologic findings including monocytosis and trilineage myelodysplasia were consistent with chronic myelomonocytic leukemia, and numerous abnormal eosinophils were present in the bone marrow. Chromosomal analysis of all metaphase cells from peripheral blood and bone marrow revealed in(16)(p13q22), which is well known characteristic of acute myelomonocytic leukemia with eosinophilia (M4Eo). Both monocytes and eosinophils in this case may be derived from common leukemic progenitors affected by inv(16)(p13q22).

The effects of halothane on the contents of putative transmitter amino acids in whole rat brain.

The effects of halothane on brain amino acid contents were investigated in rat by using a gas chromatography-mass spectrometry system. The contents of glycine and glutamate did not show any consistent changes in 1% or 2% halothane, but increased in 3% or 4% halothane. The levels of gamma-aminobutyric acid were not altered in any concentrations of halothane. The levels of aspartate increased in a dose-dependent manner up to 3% halothane, but returned to the control level in 4% halothane. These findings suggest that halothane brings the alteration of brain amino acid contents by affecting their synthesis and catabolism.

Nitrous oxide depresses somatocardiac sympathetic A- and C-reflexes in anesthetized rats.

Effect of nitrous oxide (N2O) on the somatosympathetic A- and C-reflexes was investigated using artificially ventilated rats anesthetized with alpha-chloralose and urethane. Somatocardiac sympathetic A- and C-reflexes were elicited in the inferior cardiac nerve by electrical stimulation of A and C afferent fibers of the tibial nerve, respectively. Both reflexes were depressed by inhalation of N2O for 20 min. The depression was greater in the C-reflex than in the A-reflex. The depressive effects of N2O on both reflexes were unchanged after pretreatment with intravenous naloxone (0.2 or 2.0 mg/kg) or by prolongation of the inhalation of N2O for 2 h. These results suggest that the opioid receptor is not involved and that acute tolerance is not developed in the depressive action of N2O on the somatosympathetic A- and C-reflexes.

Effects of neopterin on ischemic neuronal damage in gerbils.

The effects of neopterin on ischemic neuronal damage were examined. Cerebral ischemia was produced in the gerbil by bilateral common carotid occlusion for 8 min or unilateral occlusion for 30 min, which resulted in delayed neuronal death in the CA1 region of the hippocampus. However, preischemic treatment with neopterin (3 mg/kg i.p.) markedly reduced hippocampal neuronal damages in both cases. Since neopterin serves both as an antioxidant and as an oxidant depending on its redox state, these findings indicate that neopterin attenuates the ischemic neuronal injury by scavenging oxygen free radicals and/or by inhibiting their generation.

Blood clotting factor IX Nagoya 3: the molecular defect of zymogen activation caused by an arginine-145 to histidine substitution.

Factor IX Nagoya 3 (IX Nagoya 3) is a natural mutant of factor IX recognized in a patient with moderately severe hemophilia B. The patient had 0.60 units/ml of factor IX antigen and 2-5% of clotting activity. IX Nagoya 3 was purified from the patient's plasma by immunoaffinity chromatography with an anti-factor IX monoclonal antibody column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that the treatment of IX Nagoya 3 with factor XIa/calcium ions resulted in cleavage only at the Arg180-Val181 bond. The amino acid sequence analysis of one of the lysyl endopeptidase peptides derived from IX Nagoya 3 revealed that Arg-145 is replaced by His. This substitution impairs the cleavage between the light chain and the activation peptide by factor XIa/calcium ions.

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.

Anemia and neutropenia due to copper deficiency in enteral nutrition.

Copper deficiency has been regarded a rare complication of total parenteral nutrition. This report describes the first known case of anemia and neutropenia caused by copper deficiency in a patient receiving long-term enteral nutrition. A 34-year-old man presented with bulbar palsy and tetraplegia after an operation for cerebellar hemorrhage on June 7, 1989. Nasopharyngeal tube feeding with a defined-formula diet (Besvion) was instituted on June 19, 1989. He developed normocytic anemia and neutropenia approximately 19 months after the initiation of the tube feeding. Serum copper and ceruloplasmin levels were markedly below normal. There were anisocytosis and erythrocyte deformities in the peripheral blood smear. Bone marrow aspirates revealed a hypocellular marrow with numerous myeloid and erythroid cells with cytoplasmic vacuoles. Because the amount of copper administered was estimated to be 2.6 to 5.1 mumol/d during the tube feeding, copper deficiency was suspected to be the cause of the hematologic disorders. The patient's daily oral copper intake was increased to 34 mumol/d. His serum copper and ceruloplasmin concentrations reached a normal level after 16 days and 23 days of copper supplementation, respectively. A marked reticulocytosis occurred after 10 days of copper supplementation, and his anemia gradually improved over the next 3 months. His blood neutrophil count also returned to normal within 2 weeks.