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.

Early diffusion MR imaging findings and short-term outcome in comatose patients with hypoglycemia.

BACKGROUND AND PURPOSE: The relationship between the MR imaging features and clinical outcomes in patients with hypoglycemic encephalopathy has always been evaluated retrospectively. The aim of this study was to prospectively evaluate whether MR imaging features of patients presenting with hypoglycemic coma are predictive of short-term (1-week) outcomes. MATERIALS AND METHODS: Subjects were 36 consecutive patients with hypoglycemia who were in a comatose state on arrival at our hospital from April 2006 to March 2010. MR imaging findings on arrival in relation to the patients' clinical course after glucose infusion were evaluated. RESULTS: Thirteen of the 36 patients showed no MR imaging abnormalities on arrival. DWI revealed focal lesions involving the internal capsule in 13 patients and lesions involving bilateral hemispheric white matter in 10 patients. After glucose administration, the patients without lesions and patients with focal internal capsule lesions recovered completely within 1 day. However, patients with diffuse white matter lesions did not recover even within 1 week despite glucose administration. There was no statistical difference in the initial blood glucose levels among patients with the various types of MR imaging findings. CONCLUSIONS: On early MR imaging, hypoglycemic brain injury may first appear in the internal capsule and then spread into the hemispheric white matter. The absence of a lesion or the presence of a focal internal capsule lesion may suggest a good outcome. However, diffuse hemispheric white matter lesions may indicate a poor 1-week outcome.

Novel transdermal photodynamic therapy using ATX-S10.Na(II) induces apoptosis of synovial fibroblasts and ameliorates collagen antibody-induced arthritis in mice.

We aimed to test the effect of transdermal photodynamic therapy (PDT) on synovial proliferation in vitro and in vivo, using a novel photosensitizer, ATX-S10.Na(II). Synovial fibroblasts were obtained from patients with RA (RASF). Cell viability with or without PDT was determined by MTT assay. Cell morphology was examined by light and transmission electron microscopy. DNA fragmentation was labeled by TUNEL stain. Collagen antibody-induced arthritis (CAIA) was induced in DBA/1 mice, and the effects of transdermal PDT were evaluated by clinical and histological examination. PDT showed drug concentration-dependent and laser dose-dependent cytotoxicity on RASF. TUNEL stain and TEM study revealed the induction of apoptotic cell death of RASF. Transdermal PDT significantly reduced clinical arthritis and synovial inflammation in this model of arthritis. These results suggest that transdermal PDT using ATX-S10.Na(II) might be a novel less invasive treatment strategy for small joint arthritis and tenosynovitis.

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.

Idiopathic severe pulmonary hypertension in an infant with pulmonary infection.

We report a 5-month-old infant who showed typical echocardiographic findings of primary pulmonary hypertension without the typical histopathological findings and who recovered from severe pulmonary hypertension. Histopathological findings revealed mild thickening of small pulmonary arteries and activated macrophages in the lung. Some cases with idiopathic severe pulmonary hypertension in infants are associated with pulmonary infection.

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.

[Investigation to sequelae of acute encephalopathy].

We investigated 22 children with sequelae of acute encephalopathy. The patients were divided into 4 groups; group I with almost complete recovery (2 cases), group II with mild mental deterioration (4 cases), group III with severe mental deterioration (8 cases) and group IV with severe mental deterioration and severe physical disabilities (8 cases). There was no difference between 4 groups with regard to the past history, and status at the onset. The period of rehabilitation in hospital was different, being 0.4 month in group I, 2.6 months in group II, 3.0 months in group III and 3.6 months in group IV. The rehabilitation approach consisted mainly of medical therapy and range of motion exercise in the early stage followed trainings for walking and cognition. Family support was essential during the entire course. Evaluation with the functional independence measure was very useful for the rehabilitation.

[Development of gait in childhood: a systematic gait analysis].

To study the normal gait development in childhood, we performed a systematic gait analysis on 37 normal children (20 boys and 17 girls) aged between two and six years. The gait cycle, single support phase, ratio of stride length to body height, plantiflexor angles of the feet and propelling force increased with age, whereas the ratio of gait width to stride length and dorsiflexor angles of the feet decreased. The knee-flexion waves, heel-strikes were found in all subjects. From two to six years of age, balance-holding ability and feet plantiflexor forces developed, resulting in more efficient locomotion. The pattern of the lower limb movements on gait is considered to mature during the first three years of life.

A valid quantitative histochemical technique for assaying cytochrome c oxidase in single cells.

A quantitative histochemical method for assaying cytochrome c oxidase (COX) has been validated with two new findings concerning the optimal tissue thickness and a suitable substrate. The kinetics of a COX-catalysed reaction coupled to the oxidation of diaminobenzidine (DAB) were followed at 37 degrees C in single muscle fibres in unfixed sections of mouse gastrocnemius using a real-time image analysis system. The optimum composition of the substrate medium for the reaction was 0.1 mM reduced cytochrome c, 4 mM DAB, 2% dimethylsulphoxide, 2% polyvinyl alcohol and 0.1 mM HEPES buffer, final pH 7.5. The absorbances at 451 nm of the final reaction products, DAB polymer oxides, deposited in the intermyofibrillar mitochondria increased linearly as a function of incubation time for at least 80 s after the start of incubation. The initial velocities (v(i)) of the COX reaction calculated from the gradients of the linear regression best fits for times between 40 and 60 s were reproducible. The v(i) determined in single muscle fibres at a saturated concentration of cytochrome c (0.1 mM) were proportional to section thickness for thicknesses less than 3 microns, but they decreased exponentially when the thickness was greater than 4 microns. Thus, for the quantitative assay, unfixed sections 3 microns thick must be used. The Michaelis constants (Km) determined for commercial cytochrome c in the range of 20-26 microM for COX in three types of skeletal muscle fibres of mouse gastrocnemius were higher than the corresponding in situ Km (12-13 microM) for reduced cytochrome c. However, the Km values for commercial cytochrome c were in good agreement with the value previously determined with homogenates of rat hind limb muscle. Therefore, reduced cytochrome c is a more suitable substrate for the kinetic study and assay of COX in situ.

[Latex allergy in patients with severe motor and intellectual disabilities syndrome].

Our experience of an anaphylactic reaction to latex in a severely disabled patient led us to investigate latex allergy in 58 cases with severe motor and intellectual disabilities syndrome. Latex specific IgE, total serum IgE, and eosinophil counts in peripheral blood were evaluated, as well as past history of treatment with medical latex materials, operation and allergic disorders. Only one case who had been operated three times, had anaphylactic reaction and mild atopic dermatitis. Fifteen cases (25.9%) had latex specific IgE of class 2 or more. In this latex positive group, past history of allergic disorders, such as bronchilal asthma, atopic dermatitis and drug eruptions, were the most prominent factor. Those without such a history were characterized by frequent use of medical latex materials and multiple operations. In conclusion, the danger of an anaphylactic reaction to latex should be recognized, particularly in the medical care for disabled patients.

Most apoptotic cells in mdx diaphragm muscle contain accumulated lipofuscin.

An age-related pigment, lipofuscin (LF), which accumulates in postmitotic, long-lived cells, is formed by the oxidative degradation of cellular macromolecules by oxygen-derived free radicals. In the present study we show that LF is accumulated in some myofibres, myosatellite cells and interstitial cells in the diaphragm muscles of the X chromosome-linked muscular dystrophic (mdx) mice at the age of 10 weeks when repetitive cycles of de- and regeneration of myofibres occur. In contrast, LF is virtually absent in diaphragm muscles of age-matched C57BL/10 (C57) normal control mice. Therefore, mdx muscle is more susceptible to oxidative stress than normal muscle. We hypothesise that gene-regulated cell death (apoptosis) occurs in dystrophic muscle cells that accumulate LF as a consequence of either oxidative stress or injury. We found that 74-79% of apoptotic myosatellite cells, interstitial cells and myofibres in mdx diaphragm contain accumulated or dotted LF granules, but only 12-20% of non-apoptotic cells contain LF. Apoptotic cells are very rare in the diaphragm of age-matched C57 control mice. This suggests that the regeneration of mdx diaphragm muscle initiated from myosatellite cells is impaired by their apoptosis as the result of either oxidative stress or a product of oxidative injury.

Exercise-induced nausea is exaggerated by eating.

This study was conducted to determine whether and under what circumstances exercise causes nausea. Twelve healthy volunteers (20-37 years), including six athletes, participated in the study. Subjects were studied on seven occasions. Each subject performed low and high-intensity exercise without eating, immediately after eating a beef patty and 60 min after eating. Besides these exercise experiments, effect of meal on nausea was studied in each subject for 180 min without exercise. Exercise was done on a bicycle ergometer for 60 min at 40-50% maximal heart rate reserve and 20 min at 70-80% maximal heart rate reserve. Subjects were tested for nausea by visual analogue scales. Both low and high-intensity exercise caused nausea. Scores for nausea were greater during exercise at fasting state and immediately after eating than those without exercise (p<0.05 during low-intensity exercise, and p<0.01 during high-intensity exercise). Immediately after eating, scores for nausea were greater during high-intensity exercise than during low-intensity exercise (p<0.05). During high-intensity exercise, scores for nausea were greater immediately after eating than without eating (p<0.05). There were no differences in ratings for nausea between the sexes in any of the experimental conditions. Training did not decrease exercise-induced nausea. In conclusion, exercise causes nausea, the severity of which is related to exercise intensity and food intake, but not sex differences nor physical training.

[Effect of diazepam on apnea attacks in a 6-year-old girl with Rett syndrome: a polysomnographic study].

We reported a 6-year-old girl with Rett syndrome with severe apnea attacks following hyperventilation during wakefulness for which oral diazepam, 1.5 mg per day, showed marked effect. We evaluated the efficacy of diazepam by polysomnography. Polygraphical examinations revealed decrease of apnea attacks from 15.7/hour to 0.6/hour and of the duration of the longest apnea attack from 40 seconds to 18 seconds. These results support the previous reports which suggests involvement of the cerebral cortex and the reticular formation for respiratory disturbance in Rett syndrome.

Morphine enhances myofilament CA(2+) sensitivity in intact guinea pig beating hearts.

UNLABELLED: We investigated whether morphine alters intracellular Ca(2+) concentration ([Ca(2+)](i)), left ventricular pressure (LVP), and myofilament Ca(2+) sensitivity under physiologic conditions in intact guinea pig beating hearts and whether delta(1), delta(2), and kappa opioid stimulations are related to the direct cardiac effects of morphine. Transmural LV phasic [Ca(2+)](i) was measured from fluorescence signals at 385 nm and 456 nm. The Ca(2+) transients during each contraction were defined as available [Ca(2+)](i). The hearts were perfused with modified Krebs-Ringer solution containing morphine in the absence and presence of delta(1) (BNTX), delta(2) (NTB), and kappa (nor-BNI) antagonists, while developed LVP and available [Ca(2+)](i) were recorded. Morphine (1 microM) decreased available [Ca(2+)](i) by 44 +/- 12 nM without decreasing developed LVP at 2.5 mM of [CaCl(2)](e) (P < 0.05). Morphine (1 microM) caused a leftward shift in the curve of developed LVP as a function of available [Ca(2+)](i) (P < 0.05). BNTX (1 microM), but not nor-BNI (1 microM) or NTB (0.1 microM) blocked morphine (1 microM) effects to decrease available [Ca(2+)](i). Morphine decreases available [Ca(2+)](i) but not LVP, and it enhances myofilament Ca(2+) sensitivity under physiologic conditions at clinical concentrations in intact isolated beating guinea pig hearts. The delta(1) opioid stimulation modifies the effects of morphine on Ca(2+) transients and myofilament Ca(2+) sensitivity. IMPLICATIONS: Morphine modifies myofilament Ca(2+) sensitivity and Ca(2+) transients in guinea pig hearts at concentrations that are clinically relevant.