A Case of Nemaline Myopathy With Sleep-Related Hypoventilation Diagnosed Using Polysomnography During Daytime Napping.

This is the case of a 49-year-old woman who was admitted to the hospital for a close examination of pulmonary hypertension; however, the next morning, she developed carbon dioxide (CO2) narcosis and was started on artificial ventilation. As pulmonary arterial hypertension was ruled out, the patient was extubated, and 24-hour transcutaneous partial pressure of carbon dioxide (PCO2)(transcutaneous carbon dioxide (TcPCO2)) monitoring was performed to diagnose sleep-related hypoventilation. Polysomnography (PSG) during daytime napping revealed markedly decreased chest motion and a "pseudo-central event," which was neither central nor obstructive hypopnea. Based on the PSG results and physical examination findings, a neuromuscular disorder was suspected, and a muscle biopsy was performed to diagnose nemaline myopathy. Neuromuscular diseases are widely recognized for their association with sleep-disordered breathing; thus, sleep-related hypoventilation should also be considered. Monitoring of TcPCO2 and PSG are useful tools in identifying the cause of hypoventilation; however, overnight PSG may cause CO2 narcosis in some diseases. In such cases, PSG may be beneficial during daytime napping.

Predictors of Morphine Efficacy for Dyspnea in Inpatients with Chronic Obstructive Pulmonary Disease: A Secondary Analysis of JORTC-PAL 07.

Objective: This study aimed to explore the predictors of morphine efficacy in the alleviation of dyspnea in COPD. Background: Dyspnea is prevalent in patients with chronic obstructive pulmonary disease (COPD) and often persists despite conventional treatment. Methods: A secondary analysis of a multi-institutional prospective before-after study was conducted focusing on morphine use for alleviating dyspnea in COPD patients. Subjects included COPD patients with dyspnea at seven hospitals in Japan. Patients received 12 mg/day of oral morphine (or 8 mg/day if they had low body weight or renal impairment). Univariate and multivariate logistic regression analyses were performed with numerical rating scale (NRS) score of the current dyspnea intensity in the evening of day 0, Eastern Cooperative Oncology Group Performance Status (ECOG PS; ≤2 or ≥3), age, and partial arterial pressure of carbon dioxide (PaCO2) as independent factors; an improvement of ≥1 in the evening NRS score of dyspnea from day 0 to 2 was the dependent factor. Results: Thirty-five patients were enrolled in this study between October 2014 and January 2018. Excluding one patient who did not receive the treatment, data from 34 patients were analyzed. In the multivariate analysis, lower PaCO2 was significantly associated with morphine efficacy for alleviating dyspnea (odds ratio [OR] 0.862, 95% confidence interval [CI] 0.747-0.994), whereas the NRS of dyspnea intensity on day 0 (OR 1.426, 95% CI 0.836-2.433), ECOG PS (OR 4.561, 95% CI 0.477-43.565), and patients' age (OR 0.986, 95% CI 0.874-1.114) were not. Discussion: Morphine can potentially alleviate dyspnea in COPD patients with lower PaCO2. Trial registration: UMIN000015288 (http://www.umin.ac.jp/ctr/index.htm).

Invasive Tracheobronchial Aspergillosis with Bronchial Ulcers Complicated by Nontuberculous Mycobacterial Disease.

Invasive tracheobronchial aspergillosis (ITBA) complicated by nontuberculous mycobacteria (NTM) is rare. An 88-year-old man was admitted for hemoptysis. Bronchoscopy revealed bronchial ulcers, and a tissue biopsy showed Aspergillus fumigatus. He was diagnosed with ITBA, which improved with voriconazole. During treatment, infiltrative shadows appeared in his lungs, and bronchoscopy was performed once again. A non-necrotic epithelioid granuloma and Mycobacterium intracellulare were detected in the biopsy specimen. He was diagnosed with NTM disease. It is important to note that tracheobronchial ulcers may cause hemoptysis and to identify the etiology and treat it appropriately when multiple bacteria are found.

Preparation of tiny biodegradable capsules using electrocapillary emulsification.

Conditions for preparing tiny biodegradable capsules were examined using electrocapillary emulsification that allows one to prepare monodisperse emulsions with ease by applying a DC potential between oil and water phases without mechanical agitation. The results obtained showed that a 1 : 4 mixture of polysorbate 80 (TO-10), a hydrophilic non-ionic surfactant, and sorbitan monooleate (SO-10), an oleophilic surfactant, is appropriate as the surfactant to be added to oil phase, cyclohexane is acceptable as the oil phase and 1000 V is optimum as the DC potential to be applied. The capsules prepared had sizes ranging from 100-300 nm and a surface roughness of approximately 10 nm and degraded in model intestinal juice more easily and rapidly than in model gastric juice. In addition, the capsules containing lactoferrin, an anti-carcinogenic protein, were found to keep 12.5% of the protein used in encapsulation without losing its activity.

Pulmonary coccidioidomycosis that formed a fungus ball with 8-years duration.

Coccidioidomycosis, caused by inhaling Coccidioides immitis, is a mycosis imported from endemic regions including the southwestern United States. C. immitis is so virulent that even a short-term stay in the endemic area can provide a chance for infection. Here, we report a 33-year-old Japanese man with formation of a fungus ball inside the pulmonary cavity secondary to coccidioidomycosis with a duration of 8 years, which is considered rare. He was infected with C. immitis in the United States in 1996. A nodule remained in the lung, which later cavitated with fungus ball formation. We identified Coccidioides immitis in the cultured specimen from the cavity and serum antibodies against it. We performed a lobectomy in 2003 since anti-fungal treatment was only temporarily effective. He is still free of disease 6 months later.

Percutaneous pneumatic and laser lithotripsy as a possible therapeutic strategy for bilateral large calculi in a horseshoe kidney.

This report concerns a case of bilateral large calculi in a horseshoe kidney. Three sessions of percutaneous nephrolithotripsy for the calculi successfully disintegrated and removed the fragments without any complications. For complete stone removal we used pneumatic and laser lithotriptors which were passed, respectively, through a rigid nephroscope and a flexible pyeloscope. It is emphasized that the selection of the most suitable lithotriptor by taking their various features into account is important in endoscopic surgery for calculi which are likely to recur such as stones accompanied by infection or for anatomically anomalous kidneys such as horseshoe kidneys.

Hepatoma-derived growth factor is involved in lung remodeling by stimulating epithelial growth.

Lung epithelial cells have an integral role in the maintenance of lung homeostasis; however, the regulatory mechanism thereof has not been fully clarified. Recently, hepatoma-derived growth factor (HDGF) was reported to be involved in organ development and remodeling through its mitogenic effect. We investigated the biological role of HDGF in lung remodeling. HDGF was more highly expressed in the lungs of idiopathic pulmonary fibrosis, chiefly in the epithelial cells, than in control nonfibrotic lungs. We also confirmed the expression of HDGF protein and mRNA in the lungs of bleomycin-instilled mice, mainly in the bronchial and alveolar epithelial cells, by immunohistochemical analysis and in situ hybridization. We found that recombinant HDGF promoted DNA synthesis in rat alveolar epithelial cells and A549 cells in vitro. Endogenous HDGF overexpressed by gene transfer was translocated into the nucleus and promoted the proliferation of A549 cells. In vivo intratracheal instillation of recombinant HDGF induced the proliferation of bronchial and alveolar epithelial cells without causing marked interstitial inflammation. These findings suggest that HDGF may be involved in lung remodeling after injury by promoting the proliferation of lung epithelial cells, probably in an autocrine manner.

Sustained interleukin-6 signalling leads to the development of lymphoid organ-like structures in the lung.

A variety of pathological changes are seen in lymphoproliferative disorders of the lung but the histogenesis of these abnormalities is not yet fully understood. We previously showed that adenovirus vector-mediated transient expression of both the human interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes, but not the IL-6 gene alone, in the rat lung induced lymphocytic alveolitis. In the present study, we explored the lung pathology of human IL-6 and IL-6R double transgenic mice to elucidate the effects of prolonged IL-6 signalling on the lung. The transgenic animals developed mononuclear cell accumulation in peribronchovascular regions, but little infiltration into alveolar spaces. Immunohistochemical analysis revealed that the cellular accumulations contained not only mixtures of inflammatory cells but also lymphoid tissue-like structures. As the expression of CXCL13/BLC, the indispensable chemokine for lymphoid organogenesis, was recognized in the B cell follicles of the pulmonary lesions, we speculate that this chemokine plays an inductive role in the development of the lymphoid tissue-like structures. These structures were distinguished from bronchus-associated lymphoid tissues (BALTs) by their location and by the lack of lymphoepithelium, which is a characteristic of BALT. These findings imply that IL-6 signalling may play a role in the pathogenesis of lymphoproliferative disorders of the lung.

[A case of chronic thromboembolic pulmonary hypertension based on essential thrombocythemia].

We report a case of chronic thromboembolic pulmonary hypertension based on essential thrombocythemia. A 72-year-old woman was admitted to our hospital with dyspnea. The hematologic workup revealed a platelet count of 99.2 x 10(4)/microliter. Chest radiographic examination revealed cardiomegaly with bilateral pulmonary artery enlargement. A perfusion lung scan suggested and pulmonary angiography confirmed--multiple pulmonary embolism. Pulmonary artery pressure was 90/30 (51) mmHg. Thrombolytic therapy was performed successfully, and a diagnosis of essential thrombocythemia was made on the basis of the criteria proposed by the Polycythemia Vera Study Group. The therapy of essential thrombocythemia including ranimustine was effective, and one year later, the essential thrombocythemia and chronic respiratory failure had improved. To our knowledge, this case of chronic thromboembolic pulmonary hypertension based on essential thrombocythemia is a very rare one.

A p38 MAPK inhibitor, FR-167653, ameliorates murine bleomycin-induced pulmonary fibrosis.

To elucidate the pathophysiology of pulmonary fibrosis, we investigated the involvement of p38 mitogen-activated protein kinase (MAPK), which is one of the major signal transduction pathways of proinflammatory cytokines, in a murine model of bleomycin-induced lung fibrosis. p38 MAPK and its substrate, activating transcription factor (ATF)-2, in bronchoalveolar lavage fluid cells were phosphorylated by intratracheal exposure of bleomycin, and the phosphorylation of ATF-2 was inhibited by subcutaneous administration of a specific inhibitor of p38 MAPK, FR-167653. FR-167653 also inhibited augmented expression of tumor necrosis factor -alpha, connective tissue growth factor, and apoptosis of lung cells induced by bleomycin administration. Moreover, daily subcutaneous administration of FR-167653 (from 1 day before to 14 days after bleomycin administration) ameliorated pulmonary fibrosis and pulmonary cachexia induced by bleomycin. These findings demonstrated that p38 MAPK is involved in bleomycin-induced pulmonary fibrosis, and its inhibitor, FR-167653, may be a feasible therapeutic agent.

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer.

BACKGROUND: The aim of this study was to investigate the efficacy and safety of high-dose chemotherapy (HDCT) for the treatment of patients with advanced testicular cancer. METHODS: Fourteen patients were treated with high-dose carboplatin, etoposide and cyclophosphamide (with or without THP-adriamycin) followed by peripheral blood stem cell transplantation. The treatment was used for two refractory cases, a second relapse, and for consolidation after the first relapse in one case each. It was also used for nine cases as part of the first-line treatment following primary conventional-dose chemotherapy, and for one case as the first salvage for a late recurrent tumor of teratoma with malignant transformation. RESULTS: The first two patients who received intensive pretreatment with cisplatin-based chemotherapy did not respond to HDCT. The two patients who were treated with HDCT as the first or second salvage therapy achieved successful outcomes. The results for the subsequent nine patients (consisting of two with stage IIIC, five with IIIB2, one with IIB, and one extragonadal seminoma) were two progressive disease, three no change and four partial remission. Only three are alive with NED following salvage surgery. Finally, a case of teratoma with malignant transformation did not respond well to two cycles of HDCT. There were no marked adverse reactions except one episode of severe neutropenic colitis. CONCLUSIONS: The results demonstrated the limited efficacy of HDCT even in cases with a good to intermediate risk rating according to classification by the International Germ Cell Cancer Collaborative Group. Because treatment for relapse after HDCT is extremely difficult, new HDCT regimens consisting of drugs that are not used in induction chemotherapy need to be established.