Successful closure of intractable tracheoesophageal fistula using a combination of a modified silicon stent and metallic stents.

Although surgery is the usual management strategy for acquired benign tracheoesophageal fistula, sometimes this approach is contraindicated or the patient declines surgical management. In this report, we describe a case of a patient with tracheoesophageal fistula at the level of the carina due to bronchial arterial infusion chemotherapy. Closure could not be achieved in response to multiple treatment strategies, including airway stenting, esophageal stenting, occlusion with microcoils, or cyanoacrylate glue. We subsequently achieved closure of this fistula through the combination of a modified silicon stent and metallic stents.

Percutaneous radiofrequency lung ablation combined with transbronchial saline injection: an experimental study in swine.

To evaluate the efficacy of radiofrequency lung ablation with transbronchial saline injection. The bilateral lungs of eight living swine were used. A 13-gauge bone biopsy needle was inserted percutaneously into the lung, and 1 ml of muscle paste was injected to create a tumor mimic. In total, 21 nodules were ablated. In the saline injection group (group A), radiofrequency ablation (RFA) was performed for 11 nodules after transbronchial saline injection under balloon occlusion with a 2-cm active single internally cooled electrode. In the control group (group B), conventional RFA was performed for 10 nodules as a control. The infused saline liquid showed a wedge-shaped and homogeneous distribution surrounding a tumor mimic. All 21 RFAs were successfully completed. The total ablation time was significantly longer (13.4 +/- 2.8 min vs. 8.9 +/- 3.5 min; P = 0.0061) and the tissue impedance was significantly lower in group A compared with group B (73.1 +/- 8.8 Omega vs. 100.6 +/- 16.6 Omega; P = 0.0002). The temperature of the ablated area was not significantly different (69.4 +/- 9.1 degrees C vs. 66.0 +/- 7.9 degrees C; P = 0.4038). There was no significant difference of tumor mimic volume (769 +/- 343 mm(3) vs. 625 +/- 191 mm(3); P = 0.2783). The volume of the coagulated area was significantly larger in group A than in group B (3886 +/- 1247 mm(3) vs. 2375 +/- 1395 mm(3); P = 0.0221). Percutaneous radiofrequency lung ablation combined with transbronchial saline injection can create an extended area of ablation.

Creation of a tumor-mimic model using a muscle paste for radiofrequency ablation of the lung.

The purpose of this study was to develop an easily created tumor-mimic model and evaluate its efficacy for radiofrequency ablation (RFA) of the lung. The bilateral lungs of eight living adult swine were used. A tumor-mimic model was made by percutaneous injection of 1.0 ml muscle paste through the bone biopsy needle into the lung. An RFA probe was then inserted into the tumor mimics immediately after tumor creation. Ablation time, tissue impedance, and temperature were recorded. The tumor mimics and their coagulated regions were evaluated microscopically and macroscopically. The muscle paste was easily injected into the lung parenchyma through the bone biopsy needle and well visualized under fluoroscopy. In 10 of 12 sites the tumor mimics were oval shaped, localized, and homogeneous on gross specimens. Ten tumor mimics were successfully ablated, and four locations were ablated in the normal lung parenchyma as controls. In the tumor and normal lung parenchyma, ablation times were 8.9 +/- 3.5 and 4.4 +/- 1.6 min, respectively; tissue impedances at the start of ablation were 100.6 +/- 16.6 and 145.8 +/- 26.8 Omega, respectively; and temperatures at the end of ablation were 66.0 +/- 7.9 and 57.5 +/- 7.6 degrees C, respectively. The mean size of tumor mimics was 13.9 x 8.2 mm, and their coagulated area was 18.8 x 13.1 mm. In the lung parenchyma, the coagulated area was 15.3 x 12.0 mm. In conclusion, our tumor-mimic model using muscle paste can be easily and safely created and can be ablated using the ablation algorithm in the clinical setting.

Activation of mu-opioid pathway is associated with the canceling effect of footshock stimulus on the restraint stress-induced inhibition of small intestinal motility in rats.

We previously reported that small intestinal motility was significantly inhibited by restraint stress, but not by footshock stress. In the present study, we found that plasma beta-endorphin levels were more significantly elevated by footshock stress than restraint stress, and that preloading of footshock stimulus canceled the inhibition of small intestinal motility by restraint stress. Pretreatment with the mu-opioid receptor antagonist naltrexone significantly attenuated this canceling effect of footshock stimulus. These results suggest that footshock stimulus may cancel the inhibition of small intestinal motility by restraint stress via activation of mu-opioid receptors.

Beta3-adrenoceptor is involved in the inhibition of small intestinal motility due to restraint stress in rats.

We have reported that acute restraint stress inhibits small intestinal motility in rats. In order to clarify this inhibitory mechanism, we examined the effects of alpha- and beta-adrenergic antagonists on the inhibition of small intestinal motility induced by restraint stress. This inhibition underwent recovery by propranolol (beta1/beta2-antagonist) or SR59230A (beta3-antagonist), but not by atenolol (beta1-antagonist), ICI-118,551 (beta2-antagonist), prazosin (alpha1-antagonist) or yohimbine (alpha2-antagonist). These results suggest that beta3-adrenoceptors play an important role in the inhibition of small intestinal motility caused by restraint stress.

Synthesis and evaluation of novel 2-oxo-1,2-dihydro-3-quinolinecarboxamide derivatives as potent and selective serotonin 5-HT4 receptor agonists.

A series of 8'-substituted N-(endo-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamides were synthesized. The 5-HT4 receptor agonistic activity was evaluated using the isolated guinea pig ileum preparation. Of the compounds synthesized, N-(endo-8-(3-hydroxypropyl)-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (15a, TS-951) exhibited the most potent serotonin 5-HT4 receptor agonistic activity. This compound had a high affinity for the serotonin 5-HT4 receptor although it had no affinities for other broad spectrum receptors. Furthermore, it remarkably enhanced gastrointestinal motility in conscious fed dogs without unfavorable effects that non-selective serotonin 5-HT4 receptor agonist has. TS-951 may be useful in improving gastrointestinal dysfunction.

The design of cyclic AMP--recognizing oligopeptides and evaluation of its capability for cyclic AMP recognition using an electrochemical system.

A novel 17-mer peptide ligand for cyclic AMP was designed using the amino acid sequences of essential subsites in various cyclic AMP-dependent protein kinase (protein kinase A) families. The Au disk electrode, which was modified with the designed 17-mer oligopeptide, responded to cyclic AMP but virtually did not respond to any other cyclic nucleotides using the ion channel sensor mechanism. On the other hand, a scrambled peptide, which had the same amino acid composition as and had an amino acid sequence different from the 17-mer oligopeptide, did not respond to any nucleotides. This indicates that the designed 17-mer peptide actually acted as a selective ligand for cyclic AMP. This ligand-designing strategy using peptide sequences in target-binding proteins may possibly be extended to the design of peptide ligands for other second messengers.

Intraosseous pneumatocyst of the scapula.

Intraosseous pneumatocyst is a gas-containing cyst-like lesion that occurs most frequently in the ilium, sacrum or vertebrae. We present a case involving the left scapula that was found incidentally on CT. To our knowledge, intraosseous pneumatocyst of the scapula has not been previously reported.

Clinical significance of anticentromere antibodies in patients with systemic lupus erythematosus.

OBJECTIVE: To clarify the clinical significance of anticentromere antibodies (ACA) in patients with systemic lupus erythematosus (SLE). METHODS: Two hundred sixteen patients with SLE who were treated in our department were surveyed cross sectionally for the presence of ACA using indirect immunofluorescence on HEp-2 cell lines. ACA were identified by their discrete speckled pattern. Antibodies to the major centromere protein, CENP-B, were also studied with ELISA. Serial determinations of anti-CENP-B were carried out using stored serum samples, if available. RESULTS: ACA were recognized in 12 (5.6%) patients with SLE. All patients were receiving steroid therapy, with a mean dose of prednisolone of 14.4 mg/day. These patients also tested positive for anti-CENP-B with high titers despite the low serological disease activity in most. Three or more CREST features were observed in 2 patients and 2 others had no such features. Both patients without CREST features had a relatively short disease duration. The age at onset of SLE was significantly higher and Raynaud's phenomenon was more frequent in patients with ACA than in patients without ACA. In 8 of 10 patients tested, retrospective analysis using stored sera revealed no consistent change in anti-CENP-B titers over time. CONCLUSION: The presence of ACA in patients with SLE is apparently more frequent than previously believed. Patients with SLE with ACA may be a distinct subgroup. A longterm followup is warranted to fully determine the clinical significance of ACA in patients with SLE.

Synthesis and evaluation of novel 2-oxo-1,2-dihydro-3-quinolinecarboxamide derivatives as serotonin 5-HT4 receptor agonists.

A series of N-azabicycloalkyl-1-alkyl-2-oxo-1,2-dihydro-3-quinolinecarboxamides were synthesized and tested for serotonin 5-HT4 receptor-stimulating effects in the regulation of electrically-evoked contraction in guinea pig muscle. Among them, N-azabicycloalkyl-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (8c, 9c, 10c, 11c, 12c) exhibited potent serotonin 5-HT4 receptor-stimulating activity. The most potent compound, N-(endo-8-methyl-8-azabicyclo[3.2.1 oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (8c, ED50 = 36.3 nMi), was seven times as active as cisapride, while 8c had no affinity for 5-HT1A, 5-HT1D, D2, muscarinic M2 or muscarinic M3 receptors even at 10 microM. Compound 8c stimulated digestive tract motility in conscious fed dogs (1.0 mg/kg p.o.).

A fluorescent-labeled oligopeptide for monitoring PKA-mediated phosphorylation.

A fluorescent-labeled oligopeptide (DACM-CLRRASLK-fluorescein), containing a consensus amino acid sequence (RRXSL) of cyclic AMP (cAMP) dependent protein kinase A (PKA) substrate-proteins, was designed. The fluorescent peptide was a good substrate of PKA, and the phosphorylation of its serin residue caused an intensive change in fluorescent intensity. We expect that the peptide will be useful as a fluorescent indicator for monitoring PKA activity in living cells.

Discordant uptake of Tc-99m PMT and Tc-99m GSA by two hepatocellular carcinoma lesions.

Tc-99m PMT and Tc-99m GSA can be taken up by hepatocellular carcinoma (HCC), but there has been no report concerning HCC showing accumulation of both of Tc-99m PMT and Tc-99m GSA. In this paper we describe a case of two simultaneously developed HCCs, one of which took up both tracers but the other took up neither of them.

Prevalence of hypoxemia in 102 Japanese patients with alcoholic and nonalcoholic cirrhosis.

OBJECTIVE: Liver cirrhosis is often accompanied by arterial hypoxemia in the absence of cardiopulmonary disease. The aim of this study was to investigate the relationship between various clinicopathological conditions and the hypoxemia seen in Japanese patients with liver cirrhosis. METHODS: In 102 consecutive patients with alcoholic (N = 45) and nonalcoholic (N = 57) cirrhosis not associated with cardiopulmonary disease, we performed lung perfusion scintigraphy, contrast echocardiography, and arterial blood gas analysis and measured oxygen consumption. RESULTS: No abnormality was seen in pulmonary blood flow in cirrhotic patients, but 38 (38%) of them had a decreased partial pressure of oxygen (PaO2). The hypoxemic patients did not show any pulmonary signs or symptoms. The hypoxemia was not associated with the Child-Pugh grade, and was observed in 32 (71%) of the 45 alcoholic patients but in only six (11%) of the 57 nonalcoholic patients (p < 0.001). Oxygen consumption was significantly higher in the alcoholic group than in the nonalcoholic group (p < 0.0001), and a high incidence of oxygen consumption was seen in all 45 (100%) of the alcoholic patients and in 34 (60%) of the nonalcoholic subjects, the difference being significant (p < 0.01). The relationship between oxygen consumption and PaO2 in the 102 cirrhotic patients showed an inverse correlation (r = -0.85, p < 0.0001). Among the alcoholic patients, the incidence of hypoxemia did not differ between the 33 smokers and the 12 nonsmokers. After 1 wk of abstinence from alcohol a significant increase (p < 0.0001) in the PaO2 was seen in 14 of 19 patients with alcoholic cirrhosis. CONCLUSIONS: We conclude that the hypoxemia in Japanese patients with liver cirrhosis occurs mainly in drinking alcoholic patients, presumably due to an increased oxygen consumption by alcohol.

Role of peroxynitrite in airway microvascular hyperpermeability during late allergic phase in guinea pigs.

We investigated the role of peroxynitrite, which is formed by a rapid reaction between nitric oxide (NO) and superoxide anion (O(2)(-)), in the airway microvascular hyperpermeability during the late allergic response (LAR) in sensitized guinea pigs in vivo. The occurrence of LAR was assessed as a 100% increase in the transpulmonary pressure, which was monitored by the esophageal catheter technique. Airway microvascular permeability was assessed by Monastral blue dye trapping between the endothelium using an image analyzer. In the LAR phase (4 to 6 h after antigen inhalation), microvascular hyperpermeability and eosinophil infiltration within the airway wall were observed. NO production and xanthine oxidase (XO)/xanthine dehydrogenase activity, which are responsible for O(2)(-) production, were enhanced during the LAR. Peroxynitrite formation assessed by nitrotyrosine immunostaining was also exaggerated at that time. The microvascular hyperpermeability during the LAR was largely reduced by NO synthase inhibitor (L-NAME, 72.7% inhibition; p < 0.05), XO inhibitor (AHPP, 60.8% inhibition; p < 0. 05) and peroxynitrite scavenger (ebselen, 81.0% inhibition; p < 0. 05). L-NAME had a small but significant inhibitory effect on airway eosinophil accumulation, but AHPP and ebselen had no effect. These results suggest that excessive production of O(2)(-) and NO occurs in the LAR. These two molecules appear to cause airway microvascular hyperpermeability via peroxynitrite formation.

Possible neural mechanisms involved in footshock stress-induced enhancement of exploratory behavior in mice.

The effect of inescapable footshock stress on open-field activity, as measured by the number of ambulations, was studied in male mice. Ambulations significantly increased after footshock stress, the most significant effect appeared after 20 min-stimulation and the effect decreased as footshock time lengthened. The footshock stress-induced enhancement of ambulation was inhibited by haloperidol (0.2, 0.5 and 1 mg/kg), phentolamine (5 and 10 mg/kg), mianserin (20 mg/kg), atropine (0.5, 1 and 2 mg/kg), naltrexone (10 mg/kg) and MK-801 (0.05, 0.1 and 0.2 mg/kg), but was not influenced by propranolol (5, 10 and 20 mg/kg) or diazepam (1, 2 and 5 mg/kg). Haloperidol (0.5 and 1 mg/kg) and mianserin (5, 10 and 20 mg/kg) also exerted an inhibitory effect on non-stressed normal mice. These results suggest that dopaminergic, alpha-adrenergic, cholinergic, opioidergic and N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission systems are involved in the footshock stress-induced ambulatory activation.

Histamine-induced calcium mobilization in single cultured cells expressing histamine H1 receptors: a relationship between its sensitivity and the density of H1 receptors.

Stimulation of histamine H1 receptors initiates the hydrolysis of phosphatidylinositides and results in the production of inositol (1, 4,5)-triphosphate and intracellular Ca2+ mobilization. Although the mechanism for signal transduction via the H1 recptor has been extensively investigated, little is known about the correlation between the sensitivity of histamine-induced Ca2+ mobilization and the density of H1 receptors in cultured cells. Cytosolic free Ca2+ concentration ([Ca2+]i) after stimulation by histamine was monitored in single CHO and rat C6-glioma cells stably expressed with H1 receptors and astrocytoma 1321N1 cells using the Ca2+-sensitive dye Indo-1 and dynamic single cell imaging techniques (ACAS 570 laser cytometer). Both of the H1 receptor-expressed CHO cells and C6-glioma cells were over 10 times more sensitive to histamine than astrocytoma 1321N1 cells in which H1 receptors were naturally present. The density of H1 receptors in the transfected cells was also more than 10-fold that of 1321N1 cells. In addition, inhibition of intracellular Ca2+-ATPase by thapsigargin elicited an increase in [Ca2+]i in H1 receptor-overexpessed cells and astrocytoma 1321N1 cells with similar sensitivity. These data suggest that the sensitivity of Ca2+ mobilization by histamine in these cells was correlatively augmented with the increase in the density of H1 receptors.

Induction of nitric oxide synthase by lipopolysaccharide inhalation enhances substance P-induced microvascular leakage in guinea-pigs.

Inducible nitric oxide (NO) synthase (iNOS)-mediated hyperproduction of NO in airways has been reported in asthmatic patients. However, the role of NO in the pathogenesis of asthma has not yet been fully elucidated. The aim of this study was to examine whether the iNOS-derived NO affects airway microvascular leakage, one of the characteristic features of asthmatic airway inflammation. Guinea-pigs were exposed to lipopolysaccharide (LPS) (1 mg x mL(-1)) by inhalation in order to induce iNOS in the airways, and the histochemical staining of reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase activity was determined 5 h after the inhalation to confirm the iNOS induction. Airway microvascular leakage to subthreshold doses of substance P (0.3 microg x kg(-1), i.v.) was also examined in the absence and presence of an iNOS inhibitor (aminoguanidine) in LPS- or saline-exposed (control) animals using Evans blue dye and Monastral blue dye. In the LPS-exposed animals, increased NADPH-diaphorase activity was observed in the airway microvasculature compared with the control animals. Substance P caused significant airway microvascular leakage assessed by Evans blue dye in all airway levels in the LPS-exposed animals but not in the control group. This was also confirmed by Monastral blue dye extravasation. Aminoguanidine abolished this LPS-induced enhancement of plasma leakage to substance P without changing the systemic blood pressure. These results may suggest that inducible nitric oxide synthase-derived nitric oxide is capable of potentiating neurogenic plasma leakage in airways.

Protective effects of interleukin-10 on diaphragm muscle in a septic animal model.

The effects of Interleukin (IL)-10 intravenous injection after endotoxin administration on diaphragm muscle were studied using Wistar rats. The animals were divided into two treatment groups: A saline + endotoxin group as control and an IL-10 + endotoxin group. E. coli endotoxin (10 mg/kg) was injected intraperitoneally 5 minutes after saline or IL-10 (1250 U, 0.25 mg) injection. The force-frequency curves, twitch kinetics and fatigability were measured at 0 and 4 hours after endotoxin injection. In the saline + endotoxin group, the force-frequency curves and half relaxation time were significantly decreased at 4 hours (p < 0.001 and p < 0.05, respectively) compared to those at 0 hour. In the IL-10 + endotoxin group, the decrement in the force-frequency curves by endotoxin was prevented at 4 hours compared to that at 0 hour. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry showed positive staining in the saline + endotoxin at 4 hours, but there was no significant staining at 0 or 4 hours in the IL-10 + endotoxin group. These data suggest that IL-10 prevents the deterioration of contraction induced by endotoxin by inhibiting nitric oxide production in the diaphragm muscle.