The safety of a nitric oxide inhalation system using a conventional infant respirator

Attention is becoming increasingly focused on inhalation of nitric oxide (NO) as a selective pulmonary vasodilator. Its metabolite nitrogen dioxide (NO₂), however, is a toxic molecule. The purpose of the present study was to evaluate the safety of a NO inhalation system using a conventional infant respirator from the viewpoint of NO₂ production. The NO inhalation system consisted of a standard neonatal ventilator, a neonatal circuit and a test lung. The NO concentration was increased from 0 up to 19 ppm. At each level of NO, the oxygen (O₂) concentration was changed from 21 to 100%. The NO and NO₂ concentrations were measured with a chemiluminescence analyzer using a molybdenum converter. The NO₂ concentration was increased when either the O₂ or the NO concentration was increased. The maximum concentration of NO₂ was 0.10 ± 0.02 ppm when the concentrations of NO and O₂ were 19 ppm and 100% respectively. The NO inhalation system, using a conventional infant respirator, can be used safely when monitoring NO and NO₂ concentrations.     

Oral Tolerance Induced by Enterobacteria Altered the Process of Lymphocyte Recruitment to Intestinal Microvessels: Roles of Endothelial Cell Adhesion Molecules,TGF‐beta and Negative Regulators of TLR Signaling

Objective: Although enterobacteria are implicated in intestinal immune response, there has been no report on how intraluminal pathogens affect lymphocyte recruitment. The aim of this study was to determine how the presence of intestinal flora affects lymphocyte migration to intestine under physiological and lipopolysaccharide (LPS)‐induced inflammatory conditions. Methods: Interaction of T‐cells with ileal microvessels was monitored by using an intravital microscope in mice under germ‐free (GF) and specific pathogen‐free (SPF) conditions. LPS was administered into either the peritoneal cavity or duodenum before lymphocyte injection. Results: Adherence of T‐cells was greater in SPF than in GF mice, indicating that the presence of enterobacteria upregulated migration under physiological conditions. Intraperitoneally administered LPS significantly increased the adherence of T‐cells in both GF and SPF mice accompanied by the expression of adhesion molecules and proinflammatory cytokines. However, intraluminally administered LPS did not enhance the adherence of T‐cells in SPF mice. A significant induction of increase in mRNA expression of IRAK‐M, a negative regulator of TLR4 signaling, and transforming growth factor beta (TGF‐beta), a regulatory cytokine, was observed in SPF mice after luminal LPS treatment. Conclusions: Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK‐M and TGF‐beta.     

Solitary juvenile polyp developing adenocarcinoma with submucosal invasion

Solitary juvenile polyps are generally non‐neoplastic hamartomatous polyps. Inflammation is suggested as the cause of proliferation and progression of these polyps, and adenomatous and carcinomatous changes are rare. We report a rare case of a solitary juvenile polyp with malignant transformation that developed in the sigmoid colon of a 12‐year‐old boy. A 3 cm, pedunculated polyp was endoscopically resected, and histologic evaluation revealed the characteristic features of a juvenile polyp. However, mucous‐filled ectatic glandular spaces were lined by mucin‐secreting columnar epithelial cells with atypical change, and an admixture of adenocarcinoma invading the submucosa was confirmed. The histologic features may suggest the involvement of the adenoma–carcinoma sequence in the development of adenocarcinoma in the present case. Although rare, solitary juvenile polyps should develop adenocarcinoma and thorough histologic evaluation of the resected polyps is warranted to identify the adenomatous tissue.     

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) as a Direct-Acting Teratogen in Micromass in vitro Tests

3-Chloro-4-(dichloromethyl)-5-hydroxy-2( 5H )-furanone (MX) causes complete inhibition of rat embryonic midbrain (CNS) cell differentiation in the micromass in vitro test when applied at a concentration of 5 μ g/ml under conditions where MX is rapidly degraded in culture medium with a half-life of 56 min. This study investigated whether or not degradation products of MX have inhibitory effects on CNS cell differentiation following pre-incubation of MX in culture medium for 0.5, 1 or 2 hr. When MX was pre-incubated for 0.5 hr, the mean number of differentiated foci was 0.2 against 62.5 for the control. However, the number increased to 44.7 when pre-incubation time was extended to 2 hr. These results suggest that MX, but not its degradation products, is a teratogen in vitro. MX manifested almost complete inhibitory effects on CNS cell differentiation by 0.5 hr of exposure.     

U-46619-induced Ischaemic Electrocardiographic Changes in Rats: Preventive Effects of Prostacyclin and Nitroglycerin

Abstract— The anti-anginal effect of nitroglycerin and prostacyclin was examined using, as an index, the ischaemic electrocardiogram (ECG) change (ST elevation) induced by intracoronary arterial injection of 9,11-dideoxy-11α,9α-epoxymethano-PGF_2α (U-46619), a stable thromboxane A₂ agonist, in anaesthetized rats. The ST elevation induced by U-46619 (5–20 μg kg^?1, i.c.a.) was dose-dependent and reproducible. U-46619-induced ST elevation was markedly prevented by the pretreatment of intravenous administration of prostacyclin (0·01 μg kg^?1), and to a lesser extent by nitroglycerin (0·3 mg kg^?1). Simultaneously, platelet count decreased significantly in the coronary arterial blood which indicated that platelet aggregation was enhanced by U-46619. The decrease of platelet count in coronary arterial blood at the time of ST elevation was significantly suppressed by prostacyclin (0·1 μg kg^?1, i.v.), but not by nitroglycerin (0·3 mg kg^?1, i.v.). These results suggest that the ST elevation induced by intracoronary arterial injection of U-46619 may be derived from spasm of coronary artery and platelet aggregation in the intracoronary artery in rats.     

Epidural air associated with spontaneous pneumomediastinum in children: Uncommon complication?

BACKGROUND: The purpose of the present study was to evaluate the incidence of epidural air associated with spontaneous pneumomediastinum in children. METHODS: The subjects consisted of 25 boys and 17 girls with an age range of 3-14 years (mean age: 8.5 years) who underwent chest computed tomography (CT) for evaluation of spontaneous pneumomediastinum. The CT scans and medical records were reviewed retrospectively. RESULTS: Of the 42 patients, four (9.5%) had intraspinal air on CT. The air was interpreted as epidural in every patient. The small number of patients with epidural air meant that there was no significant difference in age, gender, or clinical manifestations between groups with and without epidural air. Subcutaneous emphysema was identified in all four patients with epidural air versus 18 out of 38 patients (47%) without epidural air. The patients with epidural air did not have any neurologic symptoms. Irrespective of the presence or absence of epidural air, every patient had a favorable outcome without any serious complications. CONCLUSION: In patients with spontaneous pneumomediastinum, epidural air may be more common than was previously realized. It is suggested that an air leak may spread from the mediastinum into the epidural space via the cervical fascial planes and neural foramina.     

Comprehensive treatment of advanced neuroblastoma involving autologous bone marrow transplant

Encouraging results are reported with high-dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation in the treatment of advanced neuroblastoma. However, relapse remains a significant problem. We used high-dose chemotherapy, surgery, intraoperative radiation and an autologous bone marrow transplant treated in vitro to remove tumor cells followed by 13-cis-retinoic acid to treat 36 children with advanced neuroblastoma. This comprehensive treatment appears to improve the survival rate of patients with advanced neuroblastoma, including those with N-myc amplification and bony involvement. The disease-free survival rate was 66% (95% confidence interval, 49–84%) at 3 years. All patients who received 13-cis-retinoic acid developed cheilitis, but no bone marrow depression occurred in these patients. Five patients developed hemolytic uremic syndrome (HUS) post-transplant. This may have been related to the procedure used for total body irradiation. Patients who had their kidneys shielded during this procedure did not develop this syndrome. Patients who received local irradiation at the primary site showed no evidence of relapse in this region, indicating that such therapy may help to prevent a relapse. These data suggest a high rate of 3 year disease-free survival with this treatment strategy. The nonrandomized nature of the study and use of multiple modalities precludes analysis of the specific contribution of each.     

The safety of a nitric oxide inhalation system with high frequency oscillatory ventilation

Nitric oxide (NO) inhalation and high frequency oscillatory ventilation (HFOV) has been indicated in infants with severe respiratory failure. The purpose of the present study was to evaluate the safety of an NO inhalation system with HFOV in terms of nitrogen dioxide (NO₂) production. The NO inhalation system consisted of a high frequency oscillatory ventilator, a neonatal circuit and a test lung. The NO concentration was changed from 0 to 19 p.p.m. At each level of NO, the oxygen (O₂) concentration was changed from 21 to 100%. The NO and NO₂ concentrations were measured with a chemiluminescence analyzer using a molybdenum converter. The NO₂ concentration was increased when either the O₂ or the NO concentration was increased. The interposition of the endotracheal tubes increased NO₂ concentrations at 4 p.p.m. NO. The high stroke volume and high mean airway pressure produced a significant increase in NO₂ production at 4 p.p.m. NO. The increase in NO₂ production was prevented by placing a one-way valve at the joint of the NO gas line to the inspired limb. It was concluded that the NO inhalation system with HFOV can be safely used when a one-way valve is placed at the joint of the NO gas line to the inspired limb and when inhaled NO is at a relatively low concentration.