Intractable diffuse pulmonary diseases: Manual for diagnosis and treatment

This manual has been compiled by a joint production committee with the Diffuse Lung Disease Assembly of the Japanese Respiratory Society (JRS) to provide a practical manual for the epidemiology, diagnosis, and treatment of intractable diffuse pulmonary diseases. The contents are based upon the results of research into these diseases by the Diffuse Pulmonary Diseases Study Group (principal researcher: Sakae Homma) supported by the FY2014–FY2016 Health and Labor Sciences Research Grant on Intractable Diseases.This manual focuses on: 1) pulmonary alveolar microlithiasis, 2) bronchiolitis obliterans, and 3) Hermansky-Pudlak Syndrome with interstitial pneumonia. As these are rare/intractable diffuse lung diseases (2 and 3 were first recognized as specified intractable diseases in 2015), there have not been sufficient epidemiological studies made, and there has been little progress in formulating diagnostic criteria and severity scales; however, the results of Japan's first surveys and research into such details are presented herein. In addition, the manual provides treatment guidance and actual cases for each disease, aiming to assist in the establishment of future modalities.The manual was produced with the goal of enabling clinicians specialized in respiratory apparatus to handle these diseases in clinical settings and of further advancing future research and treatment.     

The utility of superb-microvascular imaging for evaluating the full length of carotid artery stents

Transoral carotid ultrasonography (TOCU) is a powerful tool for evaluating internal carotid artery (ICA) lesions located from the carotid bifurcation up to the level of the second cervical vertebra. Superb-microvascular imaging (SMI) is a new Doppler imaging technique whose algorithm analyze tissue movements to minimize motion artifacts by eliminating clutter signals. SMI significantly reduces motion artifacts and allows visualization of low-velocity blood flow even in minute vessels. TOCU with SMI produces clear intraluminal image of the distal extracranial ICA, which is not possible with conventional carotid artery ultrasonography (CUS). CUS with SMI and TOCU with SMI were performed in a patient with a history of carotid artery stenting for symptomatic left ICA stenosis, providing images of the full length of the stents with intimal hyperplasia.     

Monoclonal antibodies to herpes simplex viruses antigens--specificity and utility in rapid serotyping of clinical isolates]

Sixteen hybridomas secreting antibodies to HSV-1 and 22 hybridomas secreting antibodies to HSV-2 were derived from fusion of SP2/0 myeloma cells with spleen cells from BALB/c mice immunized with each respective virus. Four of the former 16 hybridomas and seven of the latter 22 hybridomas were subcloned and injected into pristane-primed mice to obtain high titers of monoclonal antibodies. Antigen specificity of these monoclonal antibodies were determined by the Western blotting (WB) assay. Two out of four monoclonal antibodies that showed selective reactivity for HSV-1 in IFA, reacted with HSV-1 specific proteins; #1 reacted with 100 KD and 70 KD proteins and #4 with a 150 KD protein, respectively, while the remaining two antibodies reacted only with a 50 KD protein that is type-common antigen. On the other hand, two out of seven antibodies which showed selective reactivity for HSV-2 in IFA, reacted with HSV-2 specific proteins: #5 with a 100 KD protein and #10 with three proteins of 30, 25, and 20 KD, and the other two antibodies reacted with a 50 KD protein that is a type-common antigen. The remaining three antibodies, two of which were found to be immunoglobulin type IgM, reacted with neither HSV-1 nor HSV-2 antigens in WB assay. In order to determine their utility in serotyping, 11 monoclonal antibodies were examined by IFA test for reactivity to cells that were infected with 20 HSV-1 or 16 HSV-2 isolates which had been typed by neutralization test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aerosolized administration of N-acetylcysteine attenuates lung fibrosis induced by bleomycin in mice

Reactive oxygen species (ROS) play an important role in the pathogenesis of pulmonary fibrosis. We previously demonstrated that N-acetylcysteine (NAC), an antioxidant, inhibited adhesion molecule expression and cytokine production in lung cells. When NAC is inhaled into the alveolar space, it is expected to directly interact with inflammatory cells and to elevate glutathione levels in the epithelial lining fluids. We therefore examined whether inhaled NAC inhibits lung fibrosis induced by bleomycin (BLM). Male ICR mice were given a single intravenous injection of BLM (150 mg/ kg). Thirty milliliters of NAC (70 mg/ml) or saline were inhaled twice a day for 28 d using an ultrasonic nebulizer. In the inflammatory phase (Day 7), NAC administration attenuated the cellular infiltration in both bronchoalveolar lavage fluid (BALF) and alveolar tissues. At Day 28, the fibrotic changes estimated by Aschroft's criteria and hydroxyproline content in the NAC inhalation group were significantly decreased compared with the BLM-only group (p < 0.05). CXC chemokines, macrophage inflammatory protein-2 (MIP-2), cytokine-induced neutrophil chemoattractant (KC), and CC chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha), in BALF were mostly elevated on Day 7 in the BLM-only group; however, these elevations were significantly repressed by NAC inhalation (p < 0.05). Lipid hydroperoxide (LPO) was also quantified in BALF. LPO was markedly increased on Day 3 in the BLM-only group, and this increase was significantly decreased by NAC inhalation (p < 0.05). These results revealed that aerosolized NAC ameliorated acute pulmonary inflammation induced by BLM injection via the repression of chemokines and LPO production, resulting in the attenuation of subsequent lung fibrosis. These findings are limited to the BLM-induced lung fibrosis animal model. However, NAC inhalation will be expected to be a potential therapy for patients with other interstitial pneumonias because ROS are involved in the pathogenesis of lung injury in most interstitial pneumonia.     

Clinical characteristics and early outcomes of patients newly diagnosed with pulmonary Mycobacterium avium complex disease

Background

The incidence of asymptomatic pulmonary Mycobacterium avium complex (MAC) disease appears to be increasing. This study aimed to determine the clinical characteristics and examine early outcomes of patients newly diagnosed with MAC disease.

Efficacy of prophylactic extended lymphadenectomy with gastrectomy for patients with node-negative advanced gastric carcinoma

BACKGROUND/AIMS: Extended lymphadenectomy with gastrectomy is widely performed for patients with advanced gastric carcinoma. However, the therapeutic value of prophylactic extensive lymphadenectomy in patients with node-negative advanced gastric cancer is controversial. METHODOLOGY: We retrospectively analyzed 221 patients who underwent curative gastrectomy for advanced gastric carcinoma without lymph node metastasis to evaluate the effect of prophylactic extended lymphadenectomy on postoperative survival. The postoperative survival rate of patients who underwent extended lymphadenectomy was compared with that of patients who underwent limited lymphadenectomy. Predictive risk factors for tumor recurrence and recurrent patterns also were analyzed. RESULTS: Extended lymphadenectomy improved the postoperative survival rate of patients with advanced tumors even when lymph node spread was absent. Whether or not prophylactic extended lymphadenectomy was performed significantly affected tumor recurrence in patients with node-negative advanced gastric carcinoma. CONCLUSIONS: Extensive lymphadenectomy with gastrectomy prolongs survival of patients with node-negative advanced tumors.     

Risk stratification of patients with non-ST-elevation acute coronary syndromes by assessing global longitudinal strain

Noninvasive detection of left main/three-vessel diseases (LM/3VD) among patients with non-ST-elevation acute coronary syndromes (NSTEACS) has been difficult using echocardiography. However, two-dimensional (2D) strain/strain-rate analysis is more sensitive in quantitatively assessing contractile abnormality. Accordingly, we aimed to clarify the usefulness of 2D strain/strain-rate analysis for risk stratification of NSTEACS. A total of 50 patients with NSTEACS underwent echocardiography and coronary angiography. We evaluated global longitudinal peak strain (global PS), peak systolic strain rate (global SSR), early diastolic global peak strain rate (global ESR), time from aortic valve closure to peak strain (TAVC-global PS), and global ESR (TAVC-global ESR) in apical four-, two-, and three-chamber views. Patients were divided into two groups according to coronary angiographic findings, the high-risk group (n = 15) with either of left main or three-vessel disease, and the low-risk group (n = 35). There were no significant differences in global SSR and global ESR between the two groups. The amplitude of global PS was significantly reduced in high-risk patients with LM/3VD in comparison with low-risk patients (?17.5 ± 2.4 % vs ?19.8 ± 2.7 %, P = 0.007, respectively). TAVC-global PS and TAVC-global ESR were significantly prolonged in high-risk patients with LM/3VD in comparison with low-risk patients (15.3 ± 25.7 ms vs ?36.8 ± 32.7 ms, P < 0.0001 and 162.8 ± 32.7 ms vs 135.7 ± 41.5 ms, P < 0.03, respectively). Receiver-operating characteristic analysis demonstrated that TAVC-global PS most strongly detected high-risk patients with sensitivity of 100 % and specificity of 74.3 % (area under the curve = 0.938, 95 % confidence interval 0.832–0.986, P = 0.0001). Temporal analysis of 2D strain appeared to be useful in detecting high-risk patients with LM/3VD among patients with NSTEACS.