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Background: Anesthetic management of pheochromocytoma and paraganglioma with Fontan circulation is challenging for physicians, with attention to cardiovascular physiology., Case Presentation: We performed anesthetic management for pheochromocytoma and paraganglioma in three patients with Fontan circulation. We maintained intraoperative central venous pressure at preoperative level under fluid infusion and administrating nitric oxide to decrease pulmonary arterial resistance. We administered noradrenaline or vasopressin if low blood pressure was present despite adequate central venous pressure. Although noradrenaline is prevalent for the case of noradrenaline-secreting tumor especially after resection, we could maintain blood pressure to administrate vasopressin without increasing central venous pressure. Retroperitoneal laparoscopic approach which could avoid intra-abdominal adhesions might be selectable as case 3., Conclusions: Sophisticated management is required for pheochromocytoma and paraganglioma with Fontan circulation., (© 2023. The Author(s).)

Background: Hepatectomy for patients with Fontan circulation consists of high central venous pressure and low pulmonary vascular resistance, and is challenging for physicians., Case Presentation: We performed anesthetic management for hepatectomy in three patients with Fontan circulation. Massive bleeding and transfusion as well as careful management were needed. Open abdominal surgery had to be conducted instead of laparoscopic surgery for controlling bleeding in one case. We successfully performed general anesthesia using nitric oxide and inotropes while monitoring arterial pressure and central venous pressure in all the cases., Conclusions: To maintain Fontan circulation during hepatectomy, it is important to manage central venous pressure and ensure appropriate circulatory volume., (© 2022. The Author(s).)

Background: Carbamoyl phosphate synthetase deficiency (CPS1D) is a urea-cycle disorder (UCD). We report successful perioperative management of pediatric living donor liver transplantation (LDLT) in a CPS1D patient., Case Presentation: A 10-year-old female patient with CPS1D underwent LDLT. Proper administration of dextrose 50% and 60 kcal/kg/day with L-arginine and L-carnitine resulted in the avoidance of intraoperative hyperammonemia induced by hypercatabolism. Serum ammonia level transiently increased to 61 mmol/L in the anhepatic phase and decreased to 44 mmol/L after reperfusion., Conclusions: We suggest anesthesia management with administration of dextrose to avoid hyperammonemia during LDLT in patients with CPS1D., (© 2022. The Author(s).)

Background: Postreperfusion syndrome (PRS) after portal vein reperfusion during liver transplantation (LT) has been reported to cause rapid hemodynamic changes and is associated with a prolonged postoperative hospital stay, renal failure, and increased mortality. Although there are some reports on risk factors for PRS in brain-dead donor LT, there are a few reports on those in living donor LT. Therefore, we retrospectively reviewed the factors associated with PRS to contribute to the anesthetic management so as to reduce PRS during living donor LT., Methods: After approval by the ethics committee of our institution, 250 patients aged ≥20 years who underwent living donor LT at our institution between January 2013 and September 2018 were included in the study. A decrease in mean arterial pressure of ≥30% within 5 minutes after portal vein reperfusion was defined as PRS, and estimates and odds ratio (OR) for PRS were calculated using logistic regression. The backward method was used for variable selection in the multivariable analysis., Results: Serum calcium ion concentration before reperfusion (per 0.1 mmol/L increase; OR, 0.74; 95% confidence interval (CI), 0.60-0.95; P < .001), preoperative echocardiographic left ventricular end-diastolic diameter (per 1-mm increase: OR, 0.90; 95% CI, 0.85-0.95; P < .001, men [versus women: OR, 2.45; 95% CI, 1.26-4.75; P = .008]), mean pulmonary artery pressure before reperfusion (restricted cubic spline, P = .003), anhepatic period (restricted cubic spline, P = .02), and graft volume to standard liver volume ratio (restricted cubic spline, P = .03) were significantly associated with PRS., Conclusions: In living donor LT, male sex and presence of small left ventricular end-diastolic diameter, large graft volume, and long anhepatic period are associated with PRS, and a high calcium ion concentration and low pulmonary artery pressure before reperfusion are negatively associated with PRS., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

In structural heart disease (SHD) interventions, the exposure of staff other than the first operator such as anesthesiologists and transesophageal echocardiography (TEE) operators to the radiation can also pose the risks of cancer and cataracts in the long term. This study was conducted to test our new radiation protective device (RPD) for anesthesiologists and TEE operators in SHD interventions. The RPD, which consists of a head side shield and a cradle shield, was mounted on a 0.25 mm Pb-equivalent unleaded radiation protection sheet on a self-made J-shaped acrylic table, and it was placed on the head side and cradle on the operating table. A CT human body phantom was placed on the operating table, and the C-arm was set in five directions: posteroanterior, right anterior oblique 30°, left anterior oblique 30°, caudal 30°, and cranial 30°. The ambient dose equivalent rate at the usual positions of the anesthesiologist and TEE operator were measured under a fluoroscopic sequence with and without the RPD, and the dose reduction rate was obtained. The height of each measurement point was set to 100, 130 or 160 cm. The reduction rates at the positions of the anesthesiologist and the TEE operator were 82.6-86.4% and 77.9-89.5% at the height of 100 cm, 48.5-68.4% and 83.3-91.0% at 130 cm, and 23.6-62.9% and 72.9-86.1% at 160 cm, respectively. The newly developed RPD can thus effectively reduce the radiation exposure of anesthesiologists and TEE operators during SHD interventions., (© 2020. Japanese Association of Cardiovascular Intervention and Therapeutics.)

Purpose: Ionized magnesium (iMg) is considered to be the biologically active fraction of circulating total serum Mg (tMg). However, only the relationship between tMg and postoperative shivering has been studied. To our knowledge, hitherto no clinical studies have investigated the association between serum ionized magnesium concentration ([iMg]) and postoperative shivering. Therefore, we aimed to retrospectively examine this association, focusing on hypomagnesemia and depletion of [iMg]., Methods: This retrospective study involved 421 patients who underwent pancreaticoduodenectomy under general anesthesia at our center from December 2012 to September 2019. Logistic regression analysis was performed to estimate the odds ratio (OR) for the incidence of postoperative shivering., Results: Postoperative shivering developed in 111 out of 421 patients. The post-surgical concentration of [iMg] was significantly associated with postoperative shivering in the non-adjusted model, but not in the multivariable-adjusted model. In multivariable-adjusted analysis, progressive decrease of [iMg] by 0.1 mmol/L significantly increased the risk of postoperative shivering (OR: 1.64, 95% CI 1.02-2.64, p = 0.04). The multivariable-adjusted OR for postoperative shivering was 3.65 (95% CI 1.25-13.55, p = 0.02) in subjects with post-surgical [iMg] less than 0.6 mmol/L and decrease in [iMg] during surgery compared with those with post-surgical [iMg] more than 0.6 mmol/L and constant or increased of [iMg] during surgery., Conclusion: A decrease in the [iMg] during surgery was significantly associated with postoperative shivering. Subjects who had an [iMg] lower than 0.6 mmol/L post-surgery and decreased [iMg] during surgery had a significantly higher risk of postoperative shivering. Intraoperative depletion of [iMg] was significantly associated with shivering.

Introduction: Supplementation of fresh frozen plasma immediately after cardiopulmonary bypass is an effective method to enhance clotting ability as coagulation factors are consumed in the extracorporeal circuit during cardiopulmonary bypass. On the other hand, the anticoagulation factors in fresh frozen plasma can also deter the clotting ability. This study investigated the effect of fresh frozen plasma administration on the comprehensive clotting ability following cardiopulmonary bypass., Methods: This prospective observational study included 22 patients scheduled for cardiac surgery. Clotting times and maximum clot firmness were evaluated using the types of rotational thromboelastometry, intrinsic rotational thromboelastometry, and heparinase thromboelastography preoperatively, immediately after cardiopulmonary bypass, and 1 hour after cardiopulmonary bypass. Activated clotting time, antithrombin activity, and heparin concentration were also measured at these time-points., Results: Antithrombin activity (62.9 ± 7.2% vs. 51.1 ± 7.4%, p < 0.0001) and activated clotting time (132.6 ± 9.6% vs. 120.0 ± 9.0%, p < 0.001) were significantly higher 1 hour after cardiopulmonary bypass compared to measurements taken immediately after cardiopulmonary bypass. Heparin concentration 1 hour after cardiopulmonary bypass was significantly decreased compared to that immediately after cardiopulmonary bypass. On the other hand, maximum clot firmness determined via intrinsic rotational thromboelastometry was significantly greater 1 hour after cardiopulmonary bypass (53.8 ± 4.8 mm) than that immediately after cardiopulmonary bypass (49.5 ± 4.8 mm). Clotting time determined via intrinsic rotational thromboelastometry and heparinase thromboelastography was also significantly shorter 1 hour after cardiopulmonary bypass than that immediately after cardiopulmonary bypass., Conclusion: Fresh frozen plasma administration increased antithrombin activity and caused activated clotting time prolongation, but then increased clotting ability. Thus, testing by rotational thromboelastometry after cardiopulmonary bypass could be valuable in the detection of comprehensive clotting ability.

Background: The central focus of anesthesia management in kidney transplantation is to avoid hypotensive episodes and maintain adequate perfusion pressure to the graft. However, it is not clear whether there is an optimal systolic blood pressure (SBP) level after reperfusion for living-donor transplant outcomes. The aim of this study is to investigate the effect of SBP after reperfusion on early graft function in living-donor kidney transplantation., Methods: We retrospectively analyzed 315 patients who underwent living-donor kidney transplantation from January 2013 to December 2017. We divided the patients into 4 groups according to SBP after reperfusion and compared the postoperative estimated glomerular filtration rate and creatinine., Results: There were no differences in the postoperative recovery of kidney graft function in the first 7 postoperative days among the 4 SBP groups after reperfusion. However, the urine output after reperfusion was significantly less in the group with SBP < 140 mm Hg after reperfusion compared with the remaining 3 groups in a multivariate analysis (P = .04)., Conclusions: No significant differences in early graft function were observed among the 4 SBP groups. SBP ≥ 140 mm Hg after reperfusion, which is linked to greater urine output, can be beneficial in terms of long-term graft survival and mortality., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The G protein-gated inwardly rectifying K+ (GIRK) channels play important signaling roles in the central and peripheral nervous systems. However, the role of GIRK channel activation in pain signaling remains unknown mainly due to the lack of potent and selective GIRK channel activators until recently. The present study was designed to determine the effects and mechanisms of ML297, a selective GIRK1/2 activator, on nociception in the spinal cord by using behavioral studies and whole-cell patch-clamp recordings from substantia gelatinosa (SG) neurons. Rats were prepared for chronic lumber catheterization and intrathecal administration of ML297. The nociceptive flexion reflex was tested using an analgesy-meter, and the influence on motor performance was assessed using an accelerating rotarod. We also investigated pre- and post-synaptic actions of ML297 in spinal cord preparations by whole-cell patch-clamp recordings. Intrathecal administration of ML297 increased the mechanical nociceptive threshold without impairing motor function. In voltage-clamp mode of patch-clamp recordings, bath application of ML297 induced outward currents in a dose-dependent manner. The ML297-induced currents demonstrated specific equilibrium potential like other families of potassium channels. At high concentration, ML297 depressed miniature excitatory postsynaptic currents (mEPSCs) but not their amplitude. The ML297-induced outward currents and suppression of mEPSCs were not inhibited by naloxone, a μ-opioid receptor antagonist. These results demonstrated that intrathecal ML297 showed the antinociceptive effect, which was mediated through direct activation of pre- and post-synaptic GIRK channels. Selective GIRK channel activation is a promising strategy for the development of new agents against chronic pain and opioid tolerance., Competing Interests: The authors have declared that no competing interests exist.

Background: Cardiac sarcoidosis (CS) causes severe conduction abnormalities and arrhythmias. CS patients are increasingly being treated with cardiac resynchronization therapy-defibrillators (CRT-Ds). For the first time, we report the anesthetic management of a CS patient with a CRT-D., Case Presentation: A 65-year-old male with an implanted CRT-D due to CS was scheduled for a laparoscopy-assisted total proctocolectomy for his transverse colon cancer. His left ventricular ejection fraction was 32.0%, and his physical status was a New York Heart Association class III. General and epidural anesthesia were performed while using standard monitors and a FloTrac TM system. The dual-chamber pacing (DDD) modality of the CRT-D was unchanged, and its defibrillation function was deactivated before surgery. The surgery was successfully performed, and the patient was discharged without worsening of his cardiac condition., Conclusions: A detailed understanding of this patient's condition, as well as sarcoidosis, helped to facilitate successful anesthetic management of this patient.

Background: Bleeding and carbon dioxide (CO 2 ) gas embolism have been reported as serious complications associated with laparoscopic surgery. We present a case of cerebral infarction presumably caused by CO 2 gas embolism during laparoscopic hepatectomy., Case Presentation: During liver resection, the end-tidal CO 2 suddenly dropped from 40 to 21 mmHg. Simultaneously, ST elevation in lead II and ST depression in lead V5 of the electrocardiogram were observed. After improvement of these electrocardiographic changes, surgery was continued. Postoperatively, incomplete paralysis was present in the right arm and leg. Magnetic resonance imaging revealed cerebral infarction in the broad area of the left cerebral cortex. These complications might have been caused by paradoxical embolism., Conclusion: We should always keep in mind the risk of cerebral infarction with neurological deficits in the case of laparoscopic surgery. Careful monitoring and appropriate treatment for gas embolism are necessary during laparoscopic surgery.

Background: Intestinal pseudo-obstruction, which is a rare complication of pheochromocytoma, can be caused by hypersecreted catecholamines., Case Presentation: A 45-year-old woman was admitted for local recurrence of pheochromocytoma complicated by intestinal pseudo-obstruction. The intestinal pseudo-obstruction showed poor response to α-adrenergic receptor blocker and she was scheduled for surgical resection of pheochromocytoma. The surgery was uneventfully accomplished with general anesthesia combined with epidural anesthesia. The latter was performed with the aim of not only perioperative pain management but also of promoting intestinal peristalsis. The anticipated effect for intestinal peristalsis was not apparent in the early postoperative phase. The abdominal symptoms were gradually relieved over the course of about 1 month., Conclusions: For intestinal pseudo-obstruction induced by pheochromocytoma, although inhibition of the sympathetic system by epidural infusion of local anesthetics may be promising, short-term usage of epidural local anesthetics infusion did not provide a quick recovery after pheochromocytoma removal surgery.

Objectives: Seizure duration and morphology, postictal suppression, and sympathetic nervous system activation are all recommended as assessments of adequate seizure in electroconvulsive therapy (ECT). However, blood pressure and heart rate are not typically assessed as part of sympathetic nervous system activation because of the administration of anesthetic or cardiovascular agents during ECT. Although the pupils are known to reflect to the activity of autonomic nervous system and the degree of brain damage, previous studies have not examined the relationship between seizure of electroconvulsive therapy and pupillary response., Methods: We conducted 98 sessions of ECT with 13 patients, divided into two groups according to seizure quality: (1) adequate or (2) inadequate. Pupillary light reflex [% constriction = (maximum resting pupil size {MAX} - minimum pupil size after light stimulation)/MAX × 100] was measured using a portable infrared quantitative pupilometer before anesthesia induction and immediately after electrical stimulation., Results: The number regarded as adequate was 67 times and as inadequate was 31 times. Maximum pupil size at the control and immediately after electrical stimulation was similar between the adequate and inadequate groups. Pupillary light reflex was similar at the control between both groups, but significantly smaller immediately after stimulation in the adequate group (2.5 ± 3.6%) compared with the inadequate group (10.6 ± 11.5%). Receiver operating characteristic curve analysis revealed that pupillary light reflex (> 5.5%) predicted adequate seizure., Conclusions: The current findings suggest that pupillary constriction immediately after ECT could provide a helpful method for assessing the efficacy of ECT.

Background: ABO-incompatible living-donor kidney transplantation (LDKT) requires immunotherapy and plasma exchange therapy (PEX). PEX with albumin replacement fluid reportedly decreases fibrinogen levels. However, no reports have described the effects of PEX with albumin replacement fluid on blood coagulation parameters and blood loss during the perioperative period. Therefore, we investigated the effects of preoperative PEX on blood coagulation parameters and blood loss during the perioperative period in patients undergoing ABO-incompatible LDKT as measured by rotational thromboelastometry (ROTEM®)., Methods: Twenty-eight patients undergoing LDKT were divided into the PEX group (ABO incompatible with PEX, n = 13) and non-PEX group (ABO compatible without PEX, n = 15). ROTEM® parameters, standard laboratory test parameters, bleeding volume, and transfusion volume were compared between PEX and non-PEX group. MCE platelet , which represents platelet contribution to clot strength and where "MCE" stands for maximum clot elasticity, was calculated from the difference in MCE between EXTEM and FIBTEM., Results: The bleeding volume during surgery and the intensive care unit (ICU) stay was significantly higher in the PEX than non-PEX group (p < 0.01). Maximum clot firmness (MCF) of EXTEM (MCF EXTEM ), MCF FIBTEM , and MCE platelet was significantly lower in the PEX than non-PEX group (p < 0.01). In the PEX group, the bleeding volume during surgery was very strongly correlated with the baseline MCF EXTEM and MCE platelet , and the bleeding volume during the ICU stay was strongly correlated with the postoperative MCF EXTEM and MCE platelet ., Conclusions: These results suggest that the increased blood loss in the PEX group during surgery and the ICU stay was associated with decreased platelet contribution to clot strength as measured by ROTEM®., Trial Registration: UMIN-Clinical Trial Registry UMIN000018355 . Registered 21 July 2015.

We herein present a case of intramuscular hematoma that developed after transversus abdominis plane block in a patient undergoing cesarean delivery. The patient had HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) preoperatively. Ultrasonography-guided transversus abdominis plane block was performed at the end of surgery. Postoperatively, the platelet count and antithrombin III level decreased, and computed tomography revealed intramuscular hematomas that possibly were related to vascular injury and potential disseminated intravascular coagulation. We should be mindful of the possibility of intramuscular hematoma formation in patients with HELLP syndrome, even when using ultrasound guidance.

Pupil reactivity can be used to evaluate central nervous system function and can be measured using a quantitative pupillometer. However, whether anesthetic agents affect the accuracy of the technique remains unclear. We examined the effects of anesthetic agents on pupillary reactivity. Thirty-five patients scheduled for breast or thyroid surgery were enrolled in the study. Patients were divided into four groups based on the technique used to maintain anesthesia: a sevoflurane-remifentanil (SEV/REM) group, a sevoflurane (SEV) group, a desflurane-remifentanil (DES/REM) group, and a propofol-remifentanil (PRO/REM) group. We measured maximum resting pupil size (MAX), reduction pupil size ratio (%CH), latency duration (LAT) and neurological pupil index (NPi). A marked reduction in MAX and %CH compared with baseline was observed in all groups, but LAT was unchanged during surgery. NPi reduced within the first hour of surgery in the SEV/REM, SEV, and DES/REM groups, but was not significantly different in the PRO/REM group. Compared with the PRO/REM group, mean %CH and NPi in patients anesthetized with SEV/REM, SEV or DES/REM were markedly lower at 1 h after surgery had commenced. There was no correlation between NPi and bispectral index. Fentanyl given alone decreased pupil size and %CH in light reflex, but did not change the NPi. NPi was decreased by inhalational anesthesia not but intravenous anesthesia. The difference in pupil reactivity between inhalational anesthetic and propofol may indicate differences in the alteration of midbrain reflexs in patients under inhalational or intravenous anesthesia.

A 27-year-old woman with Crohn's disease, who had sustained clinical remission for two years following treatment with mesalazine and nutrition therapy, was admitted to our hospital complaining of dry cough, mild dysphagia, and slight fever. A computed tomography of the chest demonstrated an increase in the thickness of the tracheal wall. Bronchoscopy showed a diffusely erythematous and edematous mucosa with whitish granular lesions in the trachea and main carina. Bronchial biopsy specimens showed epithelioid cell granuloma. We diagnosed tracheobronchitis as an extraintestinal manifestation of Crohn's disease. She was treated with 40mg/day prednisolone. Her symptoms improved immediately. However, dry cough recurred two months after prednisolone treatment, and further treatment with inhaled steroids was prescribed. Tracheobronchial involvement in Crohn's disease is rare, with only 13 cases having been reported. Tracheal involvement should be considered in Crohn's disease patients with respiratory symptoms.

Dominant mutations in the Serca2 gene, which encodes sarco(endo)plasmic reticulum calcium-ATPase, predispose mice to gastrointestinal epithelial carcinoma [1-4] and humans to Darier disease (DD) [14-17]. In this study, we generated mice harboring N-ethyl-N-nitrosourea (ENU)-induced allelic mutations in Serca2: three missense mutations and one nonsense mutation. Mice harboring these Serca2 mutations developed tumors that were categorized as either early onset squamous cell tumors (SCT), with development similar to null-type knockout mice [2,4] (aggressive form; M682, M814), or late onset tumors (mild form; M1049, M1162). Molecular analysis showed no aberration in Serca2 mRNA or protein expression levels in normal esophageal cells of any of the four mutant heterozygotes. There was no loss of heterozygosity at the Serca2 locus in the squamous cell carcinomas in any of the four lines. The effect of each mutation on Ca(2+)-ATPase activity was predicted using atomic-structure models and accumulated mutated protein studies, suggesting that putative complete loss of Serca2 enzymatic activity may lead to early tumor onset, whereas mutations in which Serca2 retains residual enzymatic activity result in late onset. We propose that impaired Serca2 gene product activity has a long-term effect on squamous cell carcinogenesis from onset to the final carcinoma stage through an as-yet unrecognized but common regulatory pathway., (Copyright © 2016. Published by Elsevier Inc.)

Cannulation of the internal jugular vein (IJV) under ultrasound guidance can reduce complications, such as common carotid artery (CCA) puncture, accidental vertebral artery (VA) puncture. However, these complications still occur, especially in pediatric patients probably due to anatomical predisposition of VA. This study compared differences in anatomical location of VA and IJV between pediatric and adult patients. Children with body weight <20 kg (n = 16) and adults who required central venous or pulmonary arterial pressure monitoring (n = 21) were enrolled. After induction of general anesthesia and tracheal intubation, patients were positioned for IJV cannulation. Images of the right CCA, IJV and VA were recorded by ultrasonography. The size of each vessel, anatomical relationship of other vessels, distance between vessels and between each vessel and skin were measured. The size of VA relative to IJV was significantly larger in children than in adults (14 vs 7 %, P < 0.001). The absolute and relative distance between IJV and VA were significantly shorter in children than those in adults (P < 0.01). The anatomical relationships between IJV and CCA and that between IJV and VA were not different between children and adults. In children, VA was relatively larger and located closer to IJV than adults. The results call for careful attention to the position of VA during ultrasound-guided IJV cannulation especially in children.

Background: Ultiva® is commonly administered intravenously for analgesia during general anaesthesia and its main constituent remifentanil is an ultra-short-acting μ-opioid receptor agonist. Ultiva® is not approved for epidural or intrathecal use in clinical practice. Previous studies have reported that Ultiva® provokes opioid-induced hyperalgesia by interacting with spinal dorsal horn neurons. Ultiva® contains glycine, an inhibitory neurotransmitter but also an N-methyl-D-aspartate receptor co-activator. The presence of glycine in the formulation of Ultiva® potentially complicates its effects. We examined how Ultiva® directly affects nociceptive transmission in the spinal cord., Methods: We made patch-clamp recordings from substantia gelatinosa (SG) neurons in the adult rat spinal dorsal horn in vivo and in spinal cord slices. We perfused Ultiva® onto the SG neurons and analysed its effects on the membrane potentials and synaptic responses activated by noxious mechanical stimuli., Results: Bath application of Ultiva® hyperpolarized membrane potentials under current-clamp conditions and produced an outward current under voltage-clamp conditions. A barrage of excitatory postsynaptic currents (EPSCs) evoked by the stimuli was suppressed by Ultiva®. Miniature EPSCs (mEPSCs) were depressed in frequency but not amplitude. Ultiva®-induced outward currents and suppression of mEPSCs were not inhibited by the μ-opioid receptor antagonist naloxone, but were inhibited by the glycine receptor antagonist strychnine. The Ultiva®-induced currents demonstrated a specific equilibrium potential similar to glycine., Conclusions: We found that intrathecal administration of Ultiva® to SG neurons hyperpolarized membrane potentials and depressed presynaptic glutamate release predominantly through the activation of glycine receptors. No Ultiva®-induced excitatory effects were observed in SG neurons. Our results suggest different analgesic mechanisms of Ultiva® between intrathecal and intravenous administrations.

Mutant mouse models are indispensable tools for clarifying the functions of genes and elucidating the underlying pathogenic mechanisms of human diseases. We carried out large-scale mutagenesis using the chemical mutagen N-ethyl-N-nitrosourea. One specific aim of our mutagenesis project was to generate novel cancer models. We screened 7012 animals for dominant traits using a necropsy test and thereby established 17 mutant lines predisposed to cancer. Here, we report on a novel cancer model line that developed osteoma, trichogenic tumor, and breast cancer. Using fine mapping and genomic sequencing, we identified a point mutation in the adenomatous polyposis coli (Apc) gene. The Apc1576 mutants bear a nonsense mutation at codon 1576 in the Apc gene. Although most Apc mutant mice established thus far have multifocal intestinal tumors, mice that are heterozygous for the Apc1576 mutation do not develop intestinal tumors; instead, they develop multifocal breast cancers and trichogenic tumors. Notably, the osteomas that develop in the Apc1576 mutant mice recapitulate the lesion observed in Gardner syndrome, a clinical variant of familial adenomatous polyposis. Our Apc1576 mutant mice will be valuable not only for understanding the function of the Apc gene in detail but also as models of human Gardner syndrome., (© 2013 Japanese Cancer Association.)

Cervicoisthmic pregnancy is a rare obstetric condition that is potentially dangerous for the pregnant woman due to a high risk of abortion or preterm delivery. We here present a 29-year-old woman with cervicoisthmic pregnancy undergoing cesarean section at full-term. Under combined epidural and spinal anesthesia, an infant was delivered alive, and the placenta was preserved without any forces to detach from the uterus. The surgery was completed without massive bleeding. The retained placenta was treated with methotrexate infusion into the uterus from the 6th day as well as uterine artery embolization at the 51th day postpartum. She subsequently required manual removal of the retained placenta under combined epidural and spinal anesthesia with only small bleeding. She was discharged from our hospital uneventfully. Meticulous preparation for massive bleeding and long-term treatment of the retained placenta are important in the perioperative management for cesarean section of a full-term patient with cervicoisthmic pregnancy.

Background: Posterolateral or standard axillar incisions for the pediatric thoracic surgery are occasionally associated with poor motor as well as cosmetic results, including chest deformities and large surgical scars. A muscle sparing axillar skin crease incision (MSASCI) was initially proposed by Bianchi et al. (in J Pediatr Surg 33:1798-1800, 1998) followed by Kalman and Verebely (in Eur J Pediatr Surg 12:226-229, 2002) resulting in satisfactory cosmetics. However, they performed operations through the third or fourth intercostals space (ICS), therefore the target organs were restricted in the upper two-thirds of the thoracic cavity., Patients and Methods: Thoracic surgeries were performed using MSASCI in 27 patients (1-day to 9-year old). There were ten patients with esophageal atresia, seven with congenital cystic adenomatoid malformation, five with pulmonary sequestration, two with mediastinal neuroblastoma, two with right diaphragmatic hernia, and one with pulmonary hypertension. A thoracotomy was performed through the appropriate ICS (from third to eighth)., Results: In all patients, the expected procedures, including pulmonary lower lobectomy, were successfully performed by MSASCI throughout the thoracic cavity. A good operational field was easily obtained in neonates and infants. Most of the patients achieved excellent motor and aesthetic outcomes., Conclusions: MSASCI may become the standard approach for the thoracic surgery for small children.

We experienced a case of coil embolization for unexpected massive bleeding due to the injury of the internal carotid artery during surgery. A 78-year-old woman underwent right maxillectomy for a malignant tumor in the maxilla. Three hours after the start of the operation, uncontrollable bleeding occurred suddenly, with the blood loss reaching 4,600 ml in 10 minutes. Blood pressure decreased precipitously, but systolic blood pressure recovered to 90 mmHg after rapid infusion and transfusion. The bleeding point could not be identified, and hemostasis by gauze compression was tried in vain. After a large amount of fluid replacement in a short period, the hemoglobin concentration decreased to 2.5 g x dl(-1) temporarily. Angiography revealed the injury of the right internal carotid artery. Coil embolization in the internal carotid artery was performed unilaterally for hemostasis. The total blood loss amounted to 28 liters, and the patient received 2,000 ml of albumin solution, 68 units of red cell concentrates and 50 units of fresh frozen plasma in addition to 18,420 ml of lactated Ringer solution. Operation time was 17 hours and 48 minutes. Despite unexpected massive bleeding and hemodilution, maxillectomy was completed and the patient recovered without any postoperative sequelae.

Background and Aim: Capsule endoscopy (CE) is effective in the detection of small bowel lesions. Many studies have been conducted on the effectiveness of preparations in improving diagnostic yield, but an effective method has yet to be confirmed. We used magnesium citrate as preparation for CE and evaluated its effectiveness., Methods: 50 patients who underwent CE were randomly allocated to two groups - group A (preparation provided) and group B (no preparation). Group A were administered 34 g of magnesium citrate at 8 p.m. the night before the examination. Group B were not administered a laxative., Results: The cleansing efficacy score was 24.4 ± 4.4 points for group A and 22.9 ± 4.4 points for group B, with no significant difference between groups. No significant difference was seen in the large bowel arrival rate between groups: 14 cases (63.6%) for group A and 16 cases (72.7%) for group B., Conclusion: In this study, superiority was not seen for cleansing efficacy, large bowel arrival rate for the preparation method involving administration of hypertonic MC solution 12 h prior to the procedure., (Copyright © 2012 S. Karger AG, Basel.)

Background: Although rare, duodenal lesions have been reported in association with ulcerative colitis (UC); however, there have been very few reports on small bowel lesions, and many aspects of their pathology and frequency remain unknown. This study determined whether small bowel lesions are present in UC by using wireless capsule endoscopy (WCE)., Patients and Methods: WCE was performed on 20 patients with active UC and 10 who had undergone proctocolectomy., Results: Small bowel lesions (e.g. edema or ulcers) were observed in 11 of the 30 patients (36.6%): in eight (40%) of the 20 patients with active UC and in three (33.3%) of the 10 post-proctocolectomy patients. Ulcers that extended over a long segment or whole tertile of the small bowel were observed in five patients, and the disease type was extensive colitis in three of these and pouchitis in the other two. Age at onset was significantly lower in the 20 active UC patients that had small bowel lesions., Conclusion: WCE revealed the presence of ulcers that extended over a long segment or a whole tertile in the small bowel in active extensive colitis and pouchitis. In future, it will be necessary to assess the clinical significance of small bowel lesions in UC in detail., (© 2011 The Authors. Digestive Endoscopy © 2011 Japan Gastroenterological Endoscopy Society.)

The Ca(2+)-permeable cation channel TRPA1 acts as an ionotropic receptor for various pungent compounds and as a noxious cold sensor in sensory neurons. It is unclear what proportion of the TRPA1-mediated current is carried by Ca(2+) ions and how the permeation pathway changes during stimulation. Here, based on the relative permeability of the nonstimulated channel to cations of different size, we estimated a pore diameter of approximately 11 A. Combined patch-clamp and Fura-2 fluorescence recordings revealed that with 2 mM extracellular Ca(2+), and at a membrane potential of -80 mV, approximately 17% of the inward TRPA1 current is carried by Ca(2+). Stimulation with mustard oil evoked an apparent dilatation of the pore of 3 A and an increase in divalent cation selectivity and fractional Ca(2+) current. Mutations in the putative pore that reduced the divalent permeability and fractional Ca(2+) current also prevented mustard-oil-induced increases in Ca(2+) permeation. It is interesting that fractional Ca(2+) currents for wild-type and mutant TRPA1 were consistently higher than values predicted based on biionic reversal potentials using the Goldman-Hodgkin-Katz equation, suggesting that binding of Ca(2+) in the pore hinders monovalent cation permeation. We conclude that the pore of TRPA1 is dynamic and supports a surprisingly large Ca(2+) influx., (2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Topical application of nicotine, as used in nicotine replacement therapies, causes irritation of the mucosa and skin. This reaction has been attributed to activation of nicotinic acetylcholine receptors (nAChRs) in chemosensory neurons. In contrast with this view, we found that the chemosensory cation channel transient receptor potential A1 (TRPA1) is crucially involved in nicotine-induced irritation. We found that micromolar concentrations of nicotine activated heterologously expressed mouse and human TRPA1. Nicotine acted in a membrane-delimited manner, stabilizing the open state(s) and destabilizing the closed state(s) of the channel. In the presence of the general nAChR blocker hexamethonium, nociceptive neurons showed nicotine-induced responses that were strongly reduced in TRPA1-deficient mice. Finally, TRPA1 mediated the mouse airway constriction reflex to nasal instillation of nicotine. The identification of TRPA1 as a nicotine target suggests that existing models of nicotine-induced irritation should be revised and may facilitate the development of smoking cessation therapies with less adverse effects.

Mechanical stresses regulate physiological and pathological functions of vascular endothelial cells. We examined, in this study, the effects of hypergravity on endothelial functions. Hypergravity (3 G) applied by low speed centrifuge immediately induced a membrane translocation of small G-protein RhoA and tyrosine phosphorylation of 125 kDa FAK in bovine aortic endothelial cells (BAECs). Hypergravity also induced a transient reorganization of actin fibers in 3 min, which was inhibited by Rho-kinase inhibitor (Y27632) and tyrosine kinase inhibitors (herbimycin A and tyrphostin 46). Furthermore, the extracellular ATP concentration ([ATP]o) was increased by 2 G and 3 G hypergravity in 5 min, and the inhibitors of Rho-kinase, tyrosine kinase, and volume-regulated anion channels (VRAC; verapamil, tamoxifen and fluoxetine) significantly suppressed [ATP]o elevation. Application of 3 G hypergravity for 1 h increased the nuclear uptake of BrdU, which was inhibited by Rho-kinase inhibitor and VARC inhibitors. Furthermore, intermittent application of 3 G hypergravity for 1 or 2 h/day stimulated endothelial migration in 5 days, and this was inhibited by suramin, a P2 antagonist. Collectively, these results indicate that hypergravity induces ATP release and actin reorganization via RhoA activation and FAK phosphorylation, thereby activating cell proliferation and migration in BAECs. These also suggest that gravity can be regarded as an extracorporeal signal that could significantly affect endothelial functions.

TRPA1 functions as an excitatory ionotropic receptor in sensory neurons. It was originally described as a noxious cold-activated channel, but its cold sensitivity has been disputed in later studies, and the contribution of TRPA1 to thermosensing is currently a matter of strong debate. Here, we provide several lines of evidence to establish that TRPA1 acts as a cold sensor in vitro and in vivo. First, we demonstrate that heterologously expressed TRPA1 is activated by cold in a Ca(2+)-independent and Ca(2+) store-independent manner; temperature-dependent gating of TRPA1 is mechanistically analogous to that of other temperature-sensitive TRP channels, and it is preserved after treatment with the TRPA1 agonist mustard oil. Second, we identify and characterize a specific subset of cold-sensitive trigeminal ganglion neurons that is absent in TRPA1-deficient mice. Finally, cold plate and tail-flick experiments reveal TRPA1-dependent, cold-induced nociceptive behavior in mice. We conclude that TRPA1 acts as a major sensor for noxious cold.

The transient receptor potential channel of the ankyrin-binding repeat subfamily, TRPA1, is a Ca(2+)-permeable non-selective cation channel that depolarizes the plasma membrane and causes Ca(2+) influx. A typical feature of TRPA1 is its rapid desensitization following activation by agonists such as mustard oil (MO), cinnamaldehyde, and a high intracellular Ca(2+) concentration. In whole-cell recordings on Chinese hamster ovary (CHO) cells expressing TRPA1, desensitization was delayed when phosphatidylinositol 4,5-biphosphate (PIP(2)) was supplemented via the patch pipette, whereas the PIP(2) scavenger neomycin accelerated desensitization. Preincubation with the PI-4 kinase inhibitor wortmannin reduced both constitutive TRPA1 channels activity and the response to MO. Run down was also accelerated by high intracellular Mg(2+) concentrations, whereas chelating intracellular Mg(2+) with 10 mM ethylenedinitrilotetraacetic acid (EDTA) increased the basal channel activity. In inside-out patches, we observed a rapid run down of TRPA1 activity, which could be prevented by application of diC8-PIP(2) or 2 mM Mg-ATP but not Na(2)-ATP to the cytosolic side of the excised patches. In isolated trigeminal ganglion neurons, preincubation with wortmannin resulted in inhibition of endogenous TRPA1 activation by MO. Taken together, our data indicate that PIP(2) modulates TRPA1, albeit to a lesser extent than other known PIP(2)-dependent TRP channels, and that tools modifying the plasma membrane PIP(2) content often have direct effects on this channel.

Calcium signaling controls multiple cellular functions and is regulated by the release from internal stores and entry from extracellular fluid. In bone, osteoclast differentiation is induced by RANKL (receptor activator of NF-kappaB ligand)-evoked intracellular Ca(2+) oscillations, which trigger nuclear factor-activated T cells (NFAT) c1-responsive gene transcription. However, the Ca(2+) channels involved remain largely unidentified. Here we show that genetic ablation in mice of Trpv4, a Ca(2+)-permeable channel of the transient receptor potential (TRP) family, increases bone mass by impairing bone resorption. TRPV4 mediates basolateral Ca(2+) influx specifically in large osteoclasts when Ca(2+) oscillations decline. TRPV4-mediated Ca(2+) influx hereby secures intracellular Ca(2+) concentrations, ensures NFATc1-regulated gene transcription, and regulates the terminal differentiation and activity of osteoclasts. In conclusion, our data indicate that Ca(2+) oscillations and TRPV4-mediated Ca(2+) influx are sequentially required to sustain NFATc1-dependent gene expression throughout osteoclast differentiation, and we propose TRPV4 as a therapeutic target for bone diseases.

Clotrimazole (CLT) is a widely used drug for the topical treatment of yeast infections of skin, vagina, and mouth. Common side effects of topical CLT application include irritation and burning pain of the skin and mucous membranes. Here, we provide evidence that transient receptor potential (TRP) channels in primary sensory neurons underlie these unwanted effects of CLT. We found that clinically relevant CLT concentrations activate heterologously expressed TRPV1 and TRPA1, two TRP channels that act as receptors of irritant chemical and/or thermal stimuli in nociceptive neurons. In line herewith, CLT stimulated a subset of capsaicin-sensitive and mustard oil-sensitive trigeminal neurons, and evoked nocifensive behavior and thermal hypersensitivity with intraplantar injection in mice. Notably, CLT-induced pain behavior was suppressed by the TRPV1-antagonist BCTC [(N-(-4-tertiarybutylphenyl)-4-(3-cholorpyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide)] and absent in TRPV1-deficient mice. In addition, CLT inhibited the cold and menthol receptor TRPM8, and blocked menthol-induced responses in capsaicin- and mustard oil-insensitive trigeminal neurons. The concentration for 50% inhibition (IC50) of inward TRPM8 current was approximately 200 nM, making CLT the most potent known TRPM8 antagonist and a useful tool to discriminate between TRPM8- and TRPA1-mediated responses. Together, our results identify TRP channels in sensory neurons as molecular targets of CLT, and offer means to develop novel CLT preparations with fewer unwanted sensory side effects.

TRPA1 is a calcium-permeable nonselective cation transient receptor potential (TRP) channel that functions as an excitatory ionotropic receptor in nociceptive neurons. TRPA1 is robustly activated by pungent substances in mustard oil, cinnamon, and garlic and mediates the inflammatory actions of environmental irritants and proalgesic agents. Here, we demonstrate a bimodal sensitivity of TRPA1 to menthol, a widely used cooling agent and known activator of the related cold receptor TRPM8. In whole-cell and single-channel recordings of heterologously expressed TRPA1, submicromolar to low-micromolar concentrations of menthol cause channel activation, whereas higher concentrations lead to a reversible channel block. In addition, we provide evidence for TRPA1-mediated menthol responses in mustard oil-sensitive trigeminal ganglion neurons. Our data indicate that TRPA1 is a highly sensitive menthol receptor that very likely contributes to the diverse psychophysical sensations after topical application of menthol to the skin or mucous membranes of the oral and nasal cavities.

Lysophosphatidic acid (LPA) is a bioactive phospholipid that is released from activated platelets and affects contractile properties of airway smooth muscle cells. However, possible roles of LPA on cell migration, one of the initial events of airway remodeling, are not clarified. This study aimed to examine the effects of LPA on migration and actin fiber formation in bovine tracheal smooth muscle cells (BTSMCs). Random and oriented cell migrations were examined with wound assay and Boyden chamber assay, respectively. Cytosolic actin fibers were stained with rhodamine-phalloidin. Membrane translocation of RhoA, a hallmark of RhoA activation, was assessed by Western blotting. LPA augmented the migration of BTSMCs from wounded confluent monolayer but did not accelerate the chemotactic migration toward LPA. LPA also induced a transient actin reorganization and RhoA activation. Dense actin fibers were observed mainly in the wound edge but not in migrated cells, thereby suggesting the role of actin reorganization in the initiation of cell migration. LPA-induced actin fiber formation was blocked by Y27632 [R-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexane carboxamide], an inhibitor of Rho kinase. Effects of LPA on migration and actin fiber formation were also inhibited by cAMP-elevating agents, i.e., dibutyryl cAMP, forskolin, isoproterenol, and theophylline. KT5720 (9S,10S,12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid hexyl ester], a protein kinase A (PKA) inhibitor, reversed the inhibitory actins of cAMP on LPA-induced responses. These results indicate that LPA induces cAMP/PKA-sensitive, RhoA-mediated random migration of BTSMCs. Regulation of this mechanism would be beneficial for the control of airway remodeling.

We have previously reported that both hypotonic stress (HTS) and lysophosphatidic acid (LPA) induce ATP release and a transient reorganization of actin through sequential activation of RhoA/Rho-kinase and focal adhesion kinase F-actin (FAK)/paxillin in human umbilical cord vein endothelial cells (HUVECs). LPA is known to induce the activation of RhoA via its specific receptors, but the mechanisms by which HTS initiates these intracellular signals are not known. The present study aimed to identify the molecule(s) that are unique to the sensing and/or transducing the mechanical stress. Reverse transcriptase-polymerase chain reaction revealed the expression of several integrin subunits in HUVECs. Anti-integrin alpha5beta1 antibody (Ab), but not anti-integrin alpha2, alpha6, alpha v, or beta4 antibodies, inhibited HTS-induced RhoA translocation, tyrosine phosphorylation of FAK and paxillin, ATP release, and actin reorganization. However, the LPA-induced ATP release and actin reorganization were not inhibited by any of these anti-integrin antibodies, indicating that integrin alpha5beta1 plays a pivotal role in the HTS-induced but not in the LPA-induced responses. It is therefore reasonable to assume that this particular subtype of integrin is involved in the initiation of the responses induced by mechanical stimuli in HUVECs.

The large-scale mouse mutagenesis with ENU has provided forward-genetic resources for functional genomics. The frozen sperm archive of ENU-mutagenized generation-1 (G1) mice could also provide a "mutant mouse library" that allows us to conduct reverse genetics in any particular target genes. We have archived frozen sperm as well as genomic DNA from 9224 G1 mice. By genome-wide screening of 63 target loci covering a sum of 197 Mbp of the mouse genome, a total of 148 ENU-induced mutations have been directly identified. The sites of mutations were primarily identified by temperature gradient capillary electrophoresis method followed by direct sequencing. The molecular characterization revealed that all the identified mutations were point mutations and mostly independent events except a few cases of redundant mutations. The base-substitution spectra in this study were different from those of the phenotype-based mutagenesis. The ENU-based gene-driven mutagenesis in the mouse now becomes feasible and practical.

We have investigated the cellular mechanisms of mechanical stress-induced immediate responses in human umbilical vein endothelial cells (HUVECs). Hypotonic stress (HTS) induced ATP release, which evoked a Ca(2+) transient, followed by actin reorganization within a few minutes, in HUVECs. Disruption of the actin cytoskeleton did not suppress HTS-induced ATP release, and inhibition of the ATP-mediated Ca(2+) response did not affect actin reorganization, thereby indicating that these two responses are not interrelated. ATP release and actin reorganization were also induced by lysophosphatidic acid (LPA). HTS and LPA induced membrane translocation of RhoA, which occurs when RhoA is activated, and tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin. Tyrosine kinase inhibitors (herbimycin A or tyrphostin 46) inhibited both HTS- and LPA-induced ATP release and actin reorganization, but did not affect RhoA activation. In contrast, Rho-kinase inhibitor (Y27632) inhibited all of the HTS- and LPA-induced responses. These results indicate that the activation of the RhoA/Rho-kinase pathway followed by tyrosine phosphorylation of FAK and paxillin leads to ATP release and actin reorganization in HUVECs. Furthermore, the fact that HTS and LPA evoke exactly the same intracellular signals and responses suggests that even these immediate mechanosensitive responses are in fact not mechanical stress-specific.

tclw5 is a t-complex recessive lethal mutation of the tw5-haplotype. Since tw5/tw5 embryos die soon after implantation, the tclw5 gene is thought to play an important role in early embryogenesis. Previous histological studies have demonstrated that tw5 homozygotes do not survive past the gastrulation stage due to extensive death of the embryonic ectoderm, whereas the extraembryonic tissues were less affected. In the present study, we demonstrate that tw5/tw5 embryos may be distinguished from wildtype littermates at embryonic (E) day 5.5. At this stage, the visceral endoderm of tw5/tw5 embryos appeared to be different, possessing smaller and fewer vacuoles compared to normal littermates. This led us to hypothesize that the visceral endoderm may be affected by tclw5. Confirmation was provided by the rescue of tw5/tw5 embryos following aggregation with tetraploid embryos. However, rescued embryos did not survive past E9.0 and displayed an underdeveloped posterior region. This would indicate that the actions of tclw5 extend beyond the midgestation stage., (Copyright 2003 Wiley-Liss, Inc.)

Surgical operations often induce acute hyperglycemia, which is known to affect endothelial functions. In this study, we examined the effects of propofol, a commonly used general anaesthetic, on bovine aortic endothelial cell (BAEC) dysfunction induced by glucose overload. 2 D-glucose overload (23 mM) induced an accumulation of superoxide anion (O2-), assessed by MCLA chemiluminescence, to a similar extent as that generated by 233 microU ml(-1) xanthine oxidase (XO) and 100 micro M xanthine. Propofol inhibited this accumulation with an IC50 of 0.21 micro M, whereas much higher concentrations of propofol were required to scavenge O2- generated by 250 microU ml(-1) XO and 100 microM xanthine (IC50: 13.5 micro M). 3 D-glucose overload attenuated ATP-induced NO production which was detected using diaminofluorescence-2 (DAF-2). The inhibition was reversed by propofol with an EC50 of 0.60 microM. In contrast, inhibitions caused by xanthine/XO were not altered by propofol (1 microM). 4 D-glucose overload suppressed ATP-induced Ca2+ oscillations and capacitative Ca2+ entry (CCE), which were both restored by superoxide dismutase, indicating that O2- was responsible. Propofol restored these attenuated Ca2+ oscillations and CCE with EC50 of 0.31 and 1.0 microM, respectively. 5 D-glucose overload (23 mM) increased the intracellular glucose concentration 4 fold, compared with cells exposed to 5.75 mM glucose, and 1 micro M propofol reduced this increase to 2.8 fold. 6 We conclude from these results that anaesthetic concentrations of propofol prevent the impairment of Ca2+-dependent NO production in BAEC induced by glucose overload. This effect is mainly due to the reduction of O2- accumulation, and involves, at least in part, the inhibition of cellular glucose uptake.

We examined the effects of superoxide anion (O) generated by xanthine plus xanthine oxidase (X/XO) on the intracellular Ca(2+) concentration ([Ca(2+)](i)) and muscle contractility in cultured bovine aortic smooth muscle cells (BASMC). Cells were grown on collagen-coated dish for the measurement of [Ca(2+)](i). Pretreatment with X/XO inhibited ATP-induced Ca(2+) transient and Ca(2+) release-activated Ca(2+) entry (CRAC) after thapsigargin-induced store depletion, both of which were reversed by superoxide dismutase (SOD). In contrast, Ca(2+) transients induced by high-K(+) solution and Ca(2+) ionophore A-23187 were not affected by X/XO. BASMC-embedded collagen gel lattice, which was pretreated with xanthine alone, showed contraction in response to ATP, thapsigargin, high-K(+) solution, and A-23187. Pretreatment of the gel with X/XO impaired gel contraction not only by ATP and thapsigargin, but also by high-K(+) solution and A-23187. The X/XO-treated gel showed normal contraction; however, when SOD was present during the pretreatment period. These results indicate that O(2)(-) attenuates smooth muscle contraction by impairing CRAC, ATP-induced Ca(2+) transient, and Ca(2+) sensitivity in BASMC.

A 36-year-old woman underwent MIDCAB surgery. During the exposure of LAD, the right ventricular wall was injured. The bleeding was controlled by compression. After that, she developed hypotension followed by cardiac arrest. At the same time, TEE showed bubbles in all of the right ventricle. The open chest massage and epinephrine 1 mg restored the heart beat. It was thought that bubbles were brought to the right ventricle via the injured wall by the blower. A few minutes after the cardiac arrest, bubbles were detected in the left atrium by TEE. This phenomenon was suspected as transpulmonary paradoxical embolism because no cardiac shunt could be detected by TEE.

The authors evaluated the memory of tracheal extubation during emergence from general anesthesia. We screened 3,039 consecutive patients undergoing elective surgery from November 1, 1998 to December 31, 1999. Of 3,039 patients, 1,993 were interviewed postoperatively at the anesthesia clinic and 202 had the memory of tracheal extubation. The incidence was higher in the groups of female, younger and propofol anesthesia compared to male, elder and inhalational anesthesia, respectively. The patients who were dissatisfied with anesthesia were more in the patients with the memory of tracheal extubation compared to the patients without the memory. We consider that the memory of tracheal extubation contributes to the dissatisfaction with anesthesia.

The King-Denborough syndrome (KDS) is a congenital myopathy with musculoskeletal abnormalities, and definitely associated with susceptibility to malignant hyperthermia (MH). We present the first report in Japan concerning the management of a KDS patient. A 2-year-old boy was scheduled for cryptorchidopexy. He had some physical signs of KDS, e.g. pectus excavatum, low-set ears, malar hypoplasia, micrognathia, ptosis and down-slanting palpebral fissures. Moreover, his mother and maternal grand-uncle had medical history of MH. Therefore, he was diagnosed as KDS by pediatricians. All of the preoperative examinations, including serum creatine phosphokinase level, are normal. Previous 15 case-reports suggest that in KDS patients MH might be triggered by volatile anesthetics. To avoid the trigger, we maintained the general anesthesia with propofol, fentanyl and vecuronium. During perioperative period, his body temperature was 36.3-38.1 degrees C, and no symptom of MH was observed. It is rare that a diagnosis of KDS is made preoperatively since the MH-induction is involved in the criteria of this syndrome. In the anesthesia of patients who are suspected of KDS from their characteristic features or familial histories, an anesthesiologist should pay attention to prevent MH. The total intravenous anesthesia method appears useful for the management of KDS.