Immunomodulatory Effects of Ambroxol on Airway Hyperresponsiveness and Inflammation

Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.

Rapid on-site evaluation with BIOEVALUATOR during endobronchial ultrasound-guided transbronchial needle aspiration for diagnosing pulmonary and mediastinal diseases

Rapid on-site evaluation [ROSE] is used widely during endobronchial ultrasound-guided transbronchial needle aspiration [EBUS-TBNA]. BIOEVALUATOR is a device used for determining whether the tissues obtained by EBUS-TBNA are appropriate for a pathological diagnosis. This study describes our experience with ROSE using BIOEVALUATOR during EBUS-TBNA for diagnosing pulmonary and mediastinal diseases. We retrospectively evaluated the results of 35 patients who underwent EBUS-TBNA with BIOEVALUATOR between December 2011 and February 2013. For the diagnosis, the tissue areas were appearing white and red through BIOEVALUATOR are considered to be appropriate and inappropriate, respectively. We examined their medical records to obtain information concerning the examination of BIOEVALUATOR results of the patient's materials [white/red], the diagnosis yield, site and size of lymph nodes and number of needle passes. The median longest diameter of 40 lymph nodes [21 #7,13 #4R, 4 #4L and 2 #11] from 35 patients was 27.9 [range 12.4-50.6] mm and the median number of needle passes was 2 [range 1-5]. The definitive diagnosis was made by EBUS-TBNA in 28 of 35 patients, by thoracotomy in one patient and BIOEVALUATOR results were white and lymphocytes were seen in the rest six patients. The BIOEVALUATOR results of other patients without accurate diagnosis were left indefinitive. Finally, the six patients were judged as having benign lymphadenopathy because the lymph node size on computed tomography decreased or remained stable after for at least 8 months. Checking aspirated samples using BIOEVALUATOR appears useful for determining their adequacy for pathological diagnosis

The Necessity of Simulation Specialist / 医学教育

　Simulation specialist who masters simulators is important for a management of simulation center. Okayama university medical school started to train simulation specialists. Now simulation training are familiar in our university through the simulation specialists helps course directors.

Antagonizing with Flumazenil after Sedation with Midazolam in Upper Gastrointestinal Endoscopy / 日本農村医学会雑誌

We investigated the usefulness of the method of producing sedation with midazolam and reversing with antagonist flumazenil in upper gastrointestinal endoscopy. Twenty-five adult outpatients underwent diagnostic upper gastrointestinal endoscopy 3 min after having an intravenous injection of 5 mg of midazolam for sedation, and received 0.25 mg of flumazenil intravenously 5 min after the removal of the endoscope. Blood pressure, heart rate, and percutaneous arterial oxygen saturation (SpO2) were measured, recorded, and compared at nine points : 1 min before midazolam injection, 2 min after midazolam injection, 1, 3, and 5 min after the insertion of the endoscope, 1 and 3 min after the removal of the endoscope, 1 min after flumazenil injection, and their awakening time at which they are easily able to respond to verbal commands. Fifteen minntes after their awakening, we asked those patients about their memory during the endoscopy and evaluated their pain with the Visual Analogue Scale (VAS). A significant decrease in systolic blood pressure was noted 2 min after midazolam injection. But the systolic blood pressure measured 1 min after the insertion of the endoscope significantly increased when compared with the level 2 min after midazolam injection. Then it gradually started decreasing. Although the systolic blood pressures 1 min after flumazenil injection and at their awakening time increased slightly, the levels were significantly lower than those 1 min before midazolam injection. The heart rate increased to the maximum 1 min after the insertion of the endoscope. Then it gradually started decreasing. The heart rates 1 min after flumazenil injection and at their awakening time decreased significantly when compared with those 1 min after the insertion of the endoscope. SpO2 significantly decreased from 97.6±1.6% 1 min before midazolam injection to 95.7±2.5% 2 min after midazolam injection and remained depressing around 95% during the endoscopy. However, SpO2 recovered 96.6±2.0% at their awakening time. Two patients had a vague memory but all the rest had no memory recollection at all of what happened during the examination. VAS was 20 mm for one patient and 0 mm for another patient. We showed the clinical usefulness of the method of antagonizing with flumazenil after upper gastrointestinal endoscopy performed on patients given an i.v. injection of midazolam, because this method might provide a minimal circulatory change due to some protection against hemodynamics stress in response to manipulation of the endoscope, anterograde amnesia, and disappearance of pain. However, we should take care of respiratory depression of the patient during endoscopy.