Development of Neonatal Airway Management Simulator for Evaluation of Tracheal Intubation.

The long-term goal of this study is a training system that can simulate medical cases and advise physicians based on quantitative evaluation of neonatal resuscitation. In this paper, we designed and manufactured a neonatal airway management simulator for quantitative evaluation of tracheal intubation. This robotic simulator is equipped with 25 sensors of 6 types, which detect motions that lead to complications, inside the manikin replicated a neonate. A performance experiment of the developed sensor and an evaluation experiment with physicians were conducted. We observed that an erroneous operation in the laryngoscopy can be detected by the sensors in our simulator.

In vivo eradication of MLL/ENL leukemia cells by NK cells in the absence of adaptive immunity.

It remains unclear how the immune system affects leukemia development. To clarify the significance of the presence of immune systems in leukemia development, we transferred MLL/ENL leukemia cells into immune-competent or immune-deficient mice without any preconditioning including irradiation. The wild-type mice did not develop leukemia, whereas all the Rag2(-/-)γc(-/-) mice lacking both adaptive immune cells and natural killer (NK) cells developed leukemia, indicating that leukemia cells were immunologically rejected. Interestingly, leukemia cells were also rejected in 60% of the Rag2(-/-) mice that lacked adaptive immune cells but possessed NK cells, suggesting that NK cells play a substantial role in the rejection of leukemia. Moreover, engraftment of leukemia cells was enhanced by NK cell depletion in Rag2(-/-) recipients and inhibited by transfer of NK cells into Rag2(-/-)γc(-/-) recipients. Upregulation of NKG2D (NK group 2, member D) ligands in MLL/ENL leukemia cells caused elimination of leukemia cells by NK cells. Finally, we found that leukemia cells resistant to elimination by NK cells had been selected during leukemia development in Rag2(-/-) recipients. These results demonstrate that NK cells can eradicate MLL/ENL leukemia cells in vivo in the absence of adaptive immunity, thus suggesting that NK cells can play a potent role in immunosurveillance against leukemia.

Helicobacter pylori-induced atrophic gastritis progressing to gastric cancer exhibits sonic hedgehog loss and aberrant CDX2 expression.

BACKGROUND: The loss of sonic hedgehog is an early change that occurs in the mucosa prior to neoplastic transformation and correlates with the type of intestinal metaplasia. Aberrant expression of CDX has also been shown to correlate with the development of intestinal metaplasia. AIM: To examine CDX2 expression in the non-cancerous mucosa of patients with gastric cancer and compared it to CDX2 expression in controls with intestinal metaplasia. METHODS: Sixty patients who had undergone endoscopic mucosal resection for early gastric cancer and 60 gender- and age-matched controls were studied. Two specimens each were obtained from the greater and lesser curves of the corpus and from the greater curve of the antrum. Expression of CDX2 and sonic hedgehog were evaluated by immunostaining. RESULTS: Gastric cancer was associated with a higher frequency of incomplete intestinal metaplasia (OR = 8.3; 95%CI, 3.7-18.9, P < 0.001). CDX2 negatively correlated with sonic hedgehog expression, however, multivariate analysis revealed that CDX2 correlated with the intestinal metaplasia scores. Sonic hedgehog indices were lower and CDX2 staining in the corpus lesser curve was higher in the cancer group than in the controls. Sonic hedgehog indices in the corpus decreased and CDX2 indices in both areas increased in patients in the ascending order of those without intestinal metaplasia, those with complete intestinal metaplasia and those with incomplete intestinal metaplasia (P < 0.001). CONCLUSIONS: Loss of sonic hedgehog expression and aberrant expression of CDX2 correlates with the type of intestinal metaplasia and may play a role in carcinogenesis.

Hypoacidity combined with high gastric juice nitrite induced by Helicobacter pylori infection is associated with gastric cancer.

BACKGROUND: In patients with Helicobacter pylori infection, the concentration of nitrite in gastric juice is elevated. The degree of elevation correlates with that of inflammation and H. pylori density. AIM: The aim of this study was to examine hypoacidity and high nitrite levels related to H. pylori infection in patients with gastric cancer. METHODS: We studied 88 patients with more than one history of endoscopic mucosal resection (EMR) for early gastric cancer and 88 age-matched controls. Concentration of nitrite in gastric juice was measured by Griess reaction, and serum pepsinogen levels were measured by RIA. RESULTS: Multiple malignant lesions were found in 20 of the 88 patients. Serum gastrin, gastric juice pH and nitrite levels in patients with gastric cancer were significantly higher and pepsinogen I and pepsinogen I/II significantly lower than in control subjects. Pepsinogen I level and I/II ratio were lower and gastric juice pH was higher in the protruded-type group than in the depressed-type group. Pepsinogen I and pepsinogen I/II were lower and gastric juice pH was higher in multiple than in single cases. CONCLUSIONS: Hypoacidity combined with high gastric juice nitrite induced by H. pylori infection is associated with the intestinal type of gastric cancer, especially protruded lesions.

Helicobacter pylori infection and increased nitrite synthesis in the stomach. Inflammation and atrophy connections.

BACKGROUND: We have previously shown that the nitrite content in the gastric juice of Helicobacter pylori-positive patients is significantly higher than that of H. pylori-negative patients and it decreases after eradication of H. pylori. AIM: To examine the relationship between the nitric oxide synthesis in the gastric lumen and histological findings. METHODS: Eighty-five middle aged Japanese patients were studied. Four specimens, each obtained from the greater and lesser curvature of antrum and gastric body were processed for the determination of histopathological scores using the updated Sydney System. Gastric juice was collected endoscopically to determine the concentration of nitrite using a modified Griess reaction. RESULTS: There was a significant positive correlation between the nitrite and the pH levels (r = 0.81, P < 0.001) and between the pH levels and the histopathological scores in the corpus. The gastric juice pH and concentration of the nitrite increased in patients with histological diagnosis of normal, antral-predominant gastritis, pangastritis and corpus-predominant gastritis in due order. CONCLUSIONS: H. pylori infection effects nitric oxide synthesis in the gastric lumen which is mainly connected with hypoacidity. The gastric juice pH is one of the useful markers for corpus dominant gastritis and probably for high-risk group of gastric cancer.

Anesthetic effects on mitochondrial ATP-sensitive K channel.

BACKGROUND: Volatile anesthetics show an ischemic preconditioning-like cardioprotective effect, whereas intravenous anesthetics have cardioprotective effects for ischemic-reperfusion injury. Although recent evidence suggests that mitochondrial adenosine triphosphate-regulated potassium (mitoK(ATP)) channels are important in cardiac preconditioning, the effect of anesthetics on mitoK(ATP) is unexplored. Therefore, the authors tested the hypothesis that anesthetics act on the mitoK(ATP) channel and mitochondrial flavoprotein oxidation. METHODS: Myocardial cells were isolated from adult guinea pigs. Endogenous mitochondrial flavoprotein fluorescence, an indicator of mitochondrial flavoprotein oxidation, was monitored with fluorescence microscopy while myocytes were exposed individually for 15 min to isoflurane, sevoflurane, propofol, and pentobarbital. The authors further investigated the effect of 5-hydroxydeanoate, a specific mitoK(ATP) channel antagonist, on isoflurane- and sevoflurane-induced flavoprotein oxidation. Additionally, the effects of propofol and pentobarbital on isoflurane-induced flavoprotein oxidation were measured. RESULTS: Isoflurane and sevoflurane induced dose-dependent increases in flavoprotein oxidation (isoflurane: R2 = 0.71, n = 50; sevoflurane: R2 = 0.86, n = 20). The fluorescence increase produced by both isoflurane and sevoflurane was eliminated by 5-hydroxydeanoate. Although propofol and pentobarbital showed no significant effects on flavoprotein oxidation, they both dose-dependently inhibited isoflurane-induced flavoprotein oxidation. CONCLUSIONS: Inhalational anesthetics induce flavoprotein oxidation through opening of the mitoK(ATP) channel. This may be an important mechanism contributing to anesthetic-induced preconditioning. Cardioprotective effects of intravenous anesthetics may not be dependent on flavoprotein oxidation, but the administration of propofol or pentobarbital may potentially inhibit the cardioprotective effect of inhalational anesthetics.

Isoproterenol enhances myofilament Ca(2+) sensitivity during hypothermia in isolated guinea pig beating hearts.

UNLABELLED: Isoproterenol is often required to treat acute left ventricular dysfunction during separation from cardiopulmonary bypass for cardiac surgery. We hypothesized that heart rate and intracellular Ca(2+) concentration ([Ca(2+)]i) homeostasis may be important factors when isoproterenol improves the cardiac function during hypothermia. Accordingly, we investigated the effect of isoproterenol on the cardiac functional variables, [Ca(2+)]i, and myofilament Ca(2+) sensitivity under spontaneous beating during hypothermia. Intact guinea pig hearts were perfused with a modified Krebs-Ringer solution (baseline) and Krebs-Ringer solution containing isoproterenol (1 nM) at 37 degrees C, 32 degrees C, and 27 degrees C while all cardiac variables and [Ca(2+)]i were recorded. Isoproterenol increased developed left ventricular pressure (LVP), maximum rate of increase in LVP, and coronary inflow at 27 degrees C, and it also increased heart rate and maximum rate of decrease in LVP at each temperature (P < 0.05). Isoproterenol produced a leftward shift of the curve of developed LVP as a function of available [Ca(2+)]i at 32 degrees C and 27 degrees C (P < 0.05), without changing available [Ca(2+)]i. Isoproterenol improves the cardiac function, especially systolic ventricular function, by enhancement of myofilament Ca(2+) sensitivity under spontaneous beating during hypothermia in intact guinea pig hearts. IMPLICATIONS: Enhancement of myofilament Ca(2+) sensitivity is involved in the improvement of cardiac function by isoproterenol under spontaneous beating during hypothermia.

Association of fasting breath nitrous oxide concentration with gastric juice nitrate and nitrite concentrations and Helicobacter pylori infection.

Fasting breath nitrous oxide (N2O) concentration was determined in relation to pH, nitrate (NO3-) and nitrite (NO2-) concentrations in gastric juice, and Helicobacter pylori infection in 86 successive patients. N2O was measured with an infrared-photoacoustic analyzer. NO3- and NO2- were measured using the Griess reaction. Fasting breath N2O concentration in controls (87 +/- 21 ppb) was not significantly different from that in patients with gastric ulcer or other gastric lesions. Breath N2O was significantly correlated with gastric NO3- (P < 0.01) and was higher in patients with elevated gastric NO2- (246 +/- 87 ppb) than in patients without NO2- (75 +/- 13 ppb). Breath N2O did not differ significantly between subjects who were positive or negative for H. pylori. In conclusion, fasting breath N2O concentration is in some manner related to intragastric NO3- and NO2- concentrations. The possible use of measuring breath N2O as predictors of cancer needs further research.

[Two sibling patients with non-Fukuyama type congenital muscular dystrophy with low serum selenium levels--therapeutic effects of oral selenium administration].

We report a pair of siblings with non-Fukuyama type, merosin-positive congenital muscular dystrophy, born to unrelated parents. Patient 1 was a 16-year-old girl with myopathy, cardiomyopathy, severe mental retardation and epilepsy. Patient 2 was a younger brother of patient 1, a 10-year-old boy with myopathy, severe mental retardation and epilepsy. Their serum selenium levels were decreased to 25 micrograms/l and 55 micrograms/l, respectively (normal 97-147 micrograms/l). Their muscle biopsy findings were similar to those seen in selenium deficient myopathy, showing abnormal mitochondrial distribution and giant mitochondria. After oral administration of selenium for 3 months, their gait disturbance apparently improved, which was confirmed by a gait analysis system. Why their gait improved remain unclear, but a defect in selenium metabolism may play a role in the development of congenital muscular dystrophy and mental retardation.

Do plasma and urine trypsinogen activation peptides (TAP) really increase in trypsin-taurocholate-induced pancreatitis?

Plasma and urine levels of trypsinogen activation peptides (TAP) reflect the severity of acute pancreatitis in experimental and clinical acute pancreatitis. In trypsin-taurocholate-induced pancreatitis in rats, the extrinsic bovine trypsin used for the induction of pancreatitis might influence on the TAP levels after induction of pancreatitis. The aim of the present study was to elucidate whether infused trypsin itself affects TAP levels in trypsin-taurocholate-induced pancreatitis. Rats were divided into three groups. In the pancreatitis group, acute pancreatitis was induced by a retrograde infusion of bovine trypsin and sodium taurocholate into the pancreatic duct. In the duct infusion group and peritoneal injection group, a mixture of bovine trypsin and trypsin inhibitor, ONO-3403, was infused into the pancreatic duct or the peritoneal cavity. Plasma and urine TAP concentration significantly increased in trypsin-taurocholate-induced pancreatitis but not in the duct infusion and peritoneal injection groups for 6 hours after the infusion of trypsin. Serum rat immunoreactive trypsin (IRT) and amylase significantly increased in the pancreatitis and duct infusion groups but not in the peritoneal injection group. Serum levels of bovine IRT in the pancreatitis group was significantly lower than those in duct infusion and peritoneal injection groups. In conclusion, an intraductal infusion of bovine trypsin itself into pancreatic duct does not influence the levels of plasma and urine TAP in trypsin-taurocholate-induced pancreatitis.

Hemopexin as a carrier protein of tumor-localizing Ga-metalloporphyrin-ATN-2.

During size exclusion HPLC, ATN-2 binding protein separated from human and mouse sera, SCCVII and colon 26 tumor tissues were found in fraction 13 (A: estimated molecular weight 70,000). Fraction 13(A) of human sera was exclusively reactive to the human hemopexin antibody. During two-dimensional electrophoresis and amino acid sequence analysis, Fraction 13(A) of C3H/He mouse sera was found to have partial homology with the mouse hemopexin precursor. Glycoprotein with the same domain structure of hemopexin has been proposed to be an important carrier protein that forms the tumor-localizing activity of water-soluble porphyrin.

Preoperative anxiety and volume and acidity of gastric fluid in children.

Forty-three patients aged 3-6 years, undergoing minor surgery were studied. Parents staying with their children were asked to evaluate the anxiety of their children and themselves by a visual-analogue scale the night before surgery (VAS-N) and just before premedication in the morning (VAS-M). After induction, gastric fluid was collected and the volume and pH were measured. Patients with a VAS-M lower than 5 were considered the low-anxiety group (L-group; n=24) and the remainder comprised the high-anxiety group (H-group; n=19). The gastric volume of the H-group was significantly lower than that of the L-group. No difference was found in pH. A significant overall correlation of VAS-N was found between patients and their parents. These results suggest that the low level anxiety of children and their parents could not reduce the volume and acidity of gastric fluid and consequently the risk of aspiration pneumonia.

Islet cell tumor in von Hippel-Lindau disease.

We describe a 42-year-old man with von Hippel-Lindau disease and islet cell tumor of the pancreas. He had retinal and cerebellar hemangioblastomas. His sister had pheochromocytoma. A pancreatic tumor was detected by ultrasonography at his periodical medical checkup. Contrast enhanced computed tomography and abdominal angiography revealed a hypervascular tumor in the pancreatic head. Histological examination of the resected tumor revealed characteristics of islet cell tumor of the pancreas, which was positive for chromogranin-A, S-100 protein, and pancreatic polypeptide, but was negative for insulin, gastrin, glucagon, somatostatin, vasoactive intestinal peptide, serotonin, and adrenocorticotropic hormone.

Plasma alpha 2-macroglobulin-trypsin complexlike substance (MTLS) in pancreatic disease.

alpha 2-macroglobulin-trypsin complexlike substance (MTLS) was determined in plasma of pancreatic and nonpancreatic diseases using a two-step enzyme immunoassay to study the diagnostic and pathophysiological significance of MTLS. Plasma levels of MTLS in acute pancreatitis (mean +/- SD = 265.6 +/- 346.2 ng/ ml, n = 9), calcified chronic pancreatitis (128.6 +/- 257.4, n = 13), and noncalcified chronic pancreatitis (13.5 +/- 12.5, n = 10) were significantly higher than that in controls (3.6 +/- 1.8, n = 81). In other diseases such as gastric cancer, hepatoma, diabetes mellitus, and gallstones, MTLS values were not different from those of control. Plasma MTLS values showed low correlation with serum trypsin, elastase 1, pancreatic amylase, lipase, and pancreatic secretory trypsin inhibitor (PSTI). The elevation of plasma MTLS values in acute pancreatitis suggests that plasma MTLS levels reflect that protease is inappropriately activated in pancreatic acinar cell and released into the circulation and that the determination of MTLS can be useful for diagnosis and pathophysiology of acute pancreatitis and chronic pancreatitis.

[Effect of preoperative treatment with recombinant human erythropoietin in patients undergoing hemodilutional autologous transfusion].

This study evaluated whether a combination of recombinant human erythropoietin (rHuEPO) and hemodilutional autologous transfusion could reduce homologous blood transfusion in 37 patients who underwent elective urological surgery. A single dose of 6000 IU rHuEPO was administered 2 weeks before operation to patients whose preoperative hemoglobin was less than 12.0 g.dl-1 (8.5-12.0 g.dl-1) (EPO group, n = 15) and compared these with control subjects whose preoperative hemoglobin was more than 12.0 g.dl-1 (non-EPO group, n = 22). Both hemoglobin and hematocrit levels after administration of rHuEPO in the EPO group increased significantly to the same levels as in those in the non-EPO group and remained at these levels. The mean volume of donated autologous blood was 980 g in the EPO group and 110 g in the non-EPO group. The mean surgical blood loss was 1330 g in the EPO group and 1120 g in the non-EPO group. No homologous blood transfusion was required in 80 percent of the cases in both groups: however, homologous transfusions were added to 3 cases in the EPO group and 4 cases in the non-EPO group whose surgical blood loss was over 2500 g. We conclude that the combination of preoperative rHuEPO treatment and hemodilutional autologous transfusion can reduce homologous transfusion during surgery in anemic patients.

Blood coagulation and fibrinolytic activity during femoral neck prosthetic replacement using bone cement.

To assess the blood coagulative and fibrinolytic responses during cemented femoral neck replacement, we measured these parameters in 9 patients, including anti-thrombin III (AT-III), prothrombin time (PT) and activated partial thromboplastin time (APTT) before surgery, just before packing bone cement and after the insertion of the prosthesis. We also measured thrombin-anti-thrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC), and D-dimer. A significant increase in APTT, and decrease in AT-III and PT were observed before the insertion of bone cement and prosthesis. The value of TAT and D-dimer increased significantly after the insertion of the prosthesis, but there were no significant changes in PIC. The data suggest that blood coagulation is activated after the insertion of bone cement and prosthesis into the femoral shaft, and in addition, the fibrinolysis is also accelerated secondary to the activation of the coagulation. Further investigations are needed to establish whether the activation of the coagulation induced by the cemented replacement exerts a great influence on the appearance of pulmonary thrombosis or circulatory depression.