A new method for measurement of blood flow,pH, and transmucosal potential difference in rat gastroduodenal mucosa by endoscopy

A method was developed to measure the mucosal blood flow (BF), mucosal pH (pH), and transmucosal potential difference (PD) in various sites from the oral cavity to the duodenum without surgical operation or damage to the subject rats. These measurements were carried out by using three indicator electrodes, which were attached to the various sites through the suction channel of an endoscope. The hydrogen gas clearance method was used for the measurement of BF. BF values obtained at the fundic, pyloric, and duodenal regions were 119±17, 69.9±8.8, and 114±18 ml/min/100 g (mean±se), respectively. The pH values were lowest at the cardiac portion and the forestomach and highest at the duodenum. PD showed higher values at the stomach and lower values at the pharynx and duodenum. Using this technique, it was possible to measure the BF, pH, and PD repeatedly and safely at various sites in the same rat. Therefore, it was suggested that this method is useful in studying the physiological functions of the stomach and duodenum and the pathogenesis of gastroduodenal ulceration and that this method is applicable to measure the change of the above parameters in the healing process of gastric ulcer in rats.     

Effect of hypertonic saline treatment on the inflammatory response after hydrochloric acid-induced lung injury in pigs

OBJECTIVES:

Hypertonic saline has been proposed to modulate the inflammatory cascade in certain experimental conditions, including pulmonary inflammation caused by inhaled gastric contents. The present study aimed to assess the potential anti-inflammatory effects of administering a single intravenous dose of 7.5% hypertonic saline in an experimental model of acute lung injury induced by hydrochloric acid.

METHODS:

Thirty-two pigs were anesthetized and randomly allocated into the following four groups: Sham, which received anesthesia and were observed; HS, which received intravenous 7.5% hypertonic saline solution (4 ml/kg); acute lung injury, which were subjected to acute lung injury with intratracheal hydrochloric acid; and acute lung injury + hypertonic saline, which were subjected to acute lung injury with hydrochloric acid and treated with hypertonic saline. Hemodynamic and ventilatory parameters were recorded over four hours. Subsequently, bronchoalveolar lavage samples were collected at the end of the observation period to measure cytokine levels using an oxidative burst analysis, and lung tissue was collected for a histological analysis.

RESULTS:

Hydrochloric acid instillation caused marked changes in respiratory mechanics as well as blood gas and lung parenchyma parameters. Despite the absence of a significant difference between the acute lung injury and acute lung injury + hypertonic saline groups, the acute lung injury animals presented higher neutrophil and tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-8 levels in the bronchoalveolar lavage analysis. The histopathological analysis revealed pulmonary edema, congestion and alveolar collapse in both groups; however, the differences between groups were not significant. Despite the lower cytokine and neutrophil levels observed in the acute lung injury + hypertonic saline group, significant differences were not observed among the treated and non-treated groups.

CONCLUSIONS:

Hypertonic saline infusion after intratracheal hydrochloric acid instillation does not have an effect on inflammatory biomarkers or respiratory gas exchange.     

A case of invasive Langerhans cell histiocytosis localizing only in the lung and diagnosed as pneumothorax in an adolescent female

In infants, Langerhans cell histiocytosis (LCH) is associated with poor clinical outcomes as Langerhans cells invade and damage multiple organs, a presentation that is different from that in adults. Here, we present a case of a 15-year-old female who visited ourclinic complaining of right chest pain and dyspnea. She was diagnosed with right pneumothorax by chest X-ray. Chest computed tomography showed multiple cystic changes in the bilateral lung. Additionally, bullous lesions occupying the upper lobe and multiple white tiny nodules on the surface of the lung were observed by thoracoscopy. These nodules comprised proliferating atypical CD1a/S-100-positive cells invading the pulmonary parenchyma, leading to the diagnosis of LCH. Because of the extensive invasion into the pulmonary parenchyma, chemotherapy was administered. This case of LCH was unique in that the age of onset was atypical and the tumor cells occupied a single organ, despite their malignant behavior.     

Histone deacetylase 6 inhibition enhances oncolytic viral replication in glioma

Oncolytic viral (OV) therapy, which uses genetically engineered tumor-targeting viruses, is being increasingly used in cancer clinical trials due to the direct cytolytic effects of this treatment that appear to provoke a robust immune response against the tumor. As OVs enter tumor cells, intrinsic host defenses have the potential to hinder viral replication and spread within the tumor mass. In this report, we show that histone deacetylase 6 (HDAC6) in tumor cells appears to alter the trafficking of post-entry OVs from the nucleus toward lysosomes. In glioma cell lines and glioma-stem–like cells, HDAC6 inhibition (HDAC6i) by either pharmacologic or genetic means substantially increased replication of oncolytic herpes simplex virus type 1 (oHSV). Moreover, HDAC6i increased shuttling of post-entry oHSV to the nucleus. In addition, electron microscopic analysis revealed that post-entry oHSVs are preferentially taken up into glioma cells through the endosomal pathway rather than via fusion at the cell surface. Together, these findings illustrate a mechanism of glioma cell defense against an incoming infection by oHSV and identify possible approaches to enhance oHSV replication and subsequent lysis of tumor cells.     

Pulmonary metastasectomy for pulmonary metastasis of breast cancer has a limited prognostic impact: a multi-institutional retrospective analysis

BackgroundPulmonary metastasectomy (PM) for breast cancer-derived pulmonary metastasis is controversial. This study aimed to assess the prognostic factors and implication of PM for metastatic breast cancer using a multi-institutional database.MethodsClinical data of 253 females with pulmonary metastasis of breast cancer who underwent PM between 1982 and 2017 were analyzed retrospectively.ResultsThe median patient age was 56 years. The median follow-up period was 5.4 years, and the median disease-free interval (DFI) was 4.8 years. The 5- and 10-year survival rates after PM were 64.9% and 50.4%, respectively, and the median overall survival was 10.1 years. Univariate analysis revealed that the period of PM before 2000, a DFI <36 months, lobectomy/pneumonectomy, large tumor size, and lymph node metastasis were predictive of a worse overall survival. In the multivariate analysis, a DFI <36 months, large tumor size, and lymph node metastasis remained significantly related to overall survival. The 5- and 10-year cancer-specific survival rates after PM were 66.9% and 54.7%, respectively, and the median cancer-specific survival was 13.1 years. Univariate analyses revealed that the period of PM before 2000, DFI <36 months, lobectomy/pneumonectomy, large tumor size, lymph node metastasis, and incomplete resection were predictive of a worse cancer-specific survival. Multivariate analysis confirmed that a DFI <36 months, large tumor size and incomplete resection were significantly related to cancer-specific survival.ConclusionsAs PM has limited efficacy in breast cancer, it should be considered an optional treatment for pulmonary metastasis of breast cancer.     

Bloodstream infection by multidrug‐resistant Streptococcus oralis in a leukemic patient with febrile neutropenia after hematopoietic stem cell transplantation

We reported the case of a patient with leukemia who developed febrile neutropenia after hematopoietic stem cell transplantation. Blood culture results revealed the presence of Streptococcus oralis, while antimicrobial susceptibility testing showed the resistance to penicillin and cephem. Furthermore, isolates were not susceptible to either meropenem or daptomycin but not to vancomycin. S oralis is known to belong to Streptococcus mitis group and be a causative agent of bacteremia in the neutropenic patients, but multidrug resistance of S oralis is rare. Our findings suggest that we might pay attention to the emergence of the microorganisms acquiring multidrug resistance in neutropenic patients.