Efficacy of steroid pulse therapy for miliary tuberculosis complicated by acute respiratory distress syndrome.

Introduction: Acute respiratory distress syndrome (ARDS) is considered a poor prognostic factor for miliary tuberculosis (MTB), but little is known about the effectiveness of steroid pulse therapy for MTB complicated by ARDS. Patients and methods: Medical records were used to retrospectively investigate the prognosis and clinical information of 13 patients diagnosed with MTB complicated by ARDS among 68 patients diagnosed with MTB at our hospital between January 1994 and October 2016. None of the patients had multidrug resistant tuberculosis (TB). MTB was diagnosed by 1 radiologist and 2 respiratory physicians based on the observation of randomly distributed, uniformly sized diffuse bilateral nodules on chest computed tomography and the detection of mycobacterium TB from clinical specimens. ARDS was diagnosed based on the Berlin definition of ARDS. The effect of steroid pulse therapy on death within 3 months of hospitalization was examined using Cox proportional hazards models. Variables were selected by the stepwise method (variable reduction method). Results: Six of 8 patients with MTB complicated by ARDS were alive 3 months after hospitalization in the steroid pulse therapy group, whereas only 1 of 5 patients was alive in the non-steroid pulse therapy group. Analysis of factors related to the survival of patients with MTB complicated by ARDS revealed that steroid pulse therapy was the strong prognostic factor (hazard ratio = 0.136 (95 % CI: 0.023-0.815)). Conclusion: Our findings suggest that steroid pulse therapy improves the short-term prognosis of patients with MTB complicated by ARDS.

Prognostic value of serial serum KL-6 measurements in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The prognostic significance of serial measurements of serum KL-6 levels in patients with idiopathic pulmonary fibrosis (IPF) is unclear; hence, it was assessed in this study. METHODS: Medical records of 66 patients with IPF, who were not treated with pirfenidone prior to enrollment, were retrospectively reviewed for information on clinical progress, forced vital capacity (FVC), survival, and serum KL-6 levels. We assessed initial serum levels of KL-6, serial changes in serum KL-6 levels, yearly decline in FVC (ΔFVC), and the rate of decline (%ΔFVC). RESULTS: Patients with increased serum KL-6 levels during follow-up had a significantly steeper decline in ΔFVC than those with no KL-6 increase (-201 vs. -50.7ml/year; p=0.0001). Patients with both initial serum KL-6 ≥1000U/ml and serial increases in serum KL-6 had the steepest decline, while those with both initial serum KL-6 <1000ml and no serial increases in KL-6 had the least decline in ΔFVC and %ΔFVC. Relative to the non-increased KL-6 group, survival in the increased KL-6 group tended to be poorer (p=0.0530). Patients with both initial serum KL-6 values <1000U/ml and no serial increase in KL-6 had more favorable prognoses than those with serial increases in KL-6 or initial serum KL-6 values ≥1000U/ml (p<0.0044). Prognosis was significantly poorer in patients with serial KL-6 changes >51.8U/ml/year than in those with serial KL-6 changes <51.8U/ml/year (p=0.0009). CONCLUSION: Thus, serial serum KL-6 measurements can be useful for assessing prognosis in patients with IPF.

[A case of myocarditis associated with polymyositis preceded by interstitial pneumonia].

A 33-year old man was admitted to our hospital because of an abnormal shadow on the chest radiograph, dry cough, and exertional dyspnea. Chest radiograph and high-resolution computed tomography (HRCT) on admission showed ground-glass opacities and bronchiectasis with volume loss in the bilateral dorsal areas. Thoracoscopic lung biopsy specimens showed mainly a pattern of NSIP (nonspecific interstitial pneumonia). We considered this case as hypersensitivity pneumonia or interstitial pneumonia (IP) associated with collagen disease. Oral prednisolone (PSL) was initiated at 55 mg/day (1 mg/kg). However he complained of proximal muscle weakness and pain and difficulty of breathing. He had heart failure due to the myocarditis. We established a diagnosis of IP associated with polymyositis and it was confirmed by his symptoms, muscle biopsy findings and elevation of serum CPK. We considered this case as the myocarditis due to polymyositis.

[A case of pulmonary tuberculous initially diagnosed as sarcoidosis because of necrotizing granuloma].

A 75-year-old man with diabetes mellitus visited our hospital because of a chest radiograph abnormality. He was asymptomatic, and no abnormality was detected by blood tests including QuantiFERON-TB Gold (QFT-2 G); hence we conducted a follow-up examination. In 8 months, his chest radiography and CT findings worsened despite remaining asymptomatic. He was admitted for further tests. Analysis of bronchoalveolar lavage fluid (BALF) showed normal results for total cell counts and lymphocytes, but the CD4/8 ratio increased, and bacterial examination yielded negative results. Surgical lung biopsy showed an epithelioid cell granuloma with fibrinoid necrosis and Langhans giant cells, and some bacilli were positive for acid-fast stain. At this point, we suspected sarcoidosis, necrotizing granulomatosis, and mycobacterosis. However, the mycobacterial culture from the lung tissue was positive, and it was identified as Mycobacterium tuberculosis. We diagnosed pulmonary tuberculosis. Even if QuantiFERON-TB Gold In-Tube (QFT-3 G) for active tuberculosis is negative, it may yield false negative results in individuals in an immunosuppressed state and low CD4 count. When we suspect pulmonary tuberculosis from radiographic and pathological findings, we should consider the results of QFT-2 G and QFT-3 G carefully as an adjunct to the diagnosis of tuberculosis.

[A case of pulmonary toxocariasis successfully treated with ivermectin].

A 36-year-old man who often ate raw chicken meat had abnormal chest radiograph findings on a health check-up in July 2009, and visited our department. A chest computed tomographic scan revealed 6 nodular shadows in both lungs, and a hematologic examination revealed eosinophilia and elevation of IgE. Because of his history of eating raw chicken meat, antiparasite antibody testing was performed which revealed antibodies to Toxocara canis, leading to the diagnosis of pulmonary toxocariasis due to Toxocara canis. Although treatment with albendazole was performed, it was discontinued because of hepatic impairment. However, hematological examination showed that his eosinophil count and IgE increased again, and chest image findings were exacerbated. Therefore, ivermectin, reported as effective in cases outside Japan, was administered, resulting in decreased peripheral eosinophils, normalized IgE level, and disappearance of the shadows on chest images. In Japan, no cases of pulmonary toxocariasis responding well to ivermectin have previously been reported. Administration of ivermectin should be considered when albendazol cannot be used due to hepatic impairment or related problems.

[Anesthetic management of caesarean section following the Fontan procedure by using TaskForce Monitor].

The Fontan procedure is performed for patients with a corrected transposition of great arteries, and pregnancies following this surgery are likely to increase in number. We present a parturient with the Fontan physiology. In this case, we used thoracic bio-impedance cardiac output monitoring system "TaskForce Monitor". It was shown that the cardiovascular management by using TaskForce Monitor was useful because of the non-invasive beat-to-beat cardiac output monitoring.

[Two cases of Mycobacterium szulgai pulmonary disease in the elderly].

The rate of pulmonary nontuberculous mycobacteriosis (NTM) in the total pulmonary mycobacteriosis has been continuously increasing. While M. avium complex is the most common cause of NTM, there are a few case reports of pulmonary infection due to M. szulgai. We described two cases of pulmonary NTM caused by M. szulgai. A 75-year-old male was admitted to our hospital because of dyspnea on effort, and productive cough. A chest X-ray showed an infiltrative shadow with cavity in the right upper lobe. A sputum smear for mycobacteria was positive, and a culture grew M. szulgai which was identified by DNA-DNA hybridization. He was treated with isoniazid, rifampicin, and ethambutol. His symptoms and CT and X-ray findings improved, and his sputum smear and culture converted to negative for mycobacteria. Second case was a 73-year-old male who had previously been diagnosed as MAC and pulmonary aspergillosis, and had been treated with antituberculous and antifungal drugs. He was readmitted to our hospital, because of general fatigue and hemoptysis. A chest X-ray revealed a consolidation with bronchiectasis and cavity in the both upper lung fields. A sptum smear for mycobacteria was positive, and a grown culture was identified as M. szulgai. He was treated with rifampicin, ethambutol and kanamycin based on the results of susceptibility testing. After 3 months of this treatment his sputum smear and culture converted to negative for mycobacteria, and his symptoms, and CT and X-ray findings improved.

[A case of cervical and mediastinal lymph nodes tuberculosis, tuberculous pleurisy, spinal caries and cold abscess in the anterior chest wall].

A 61-year-old woman with schizophrenia that had been treated in a psychiatric hospital was admitted to our hospital because of subileus and back pain. Though subileus was improved, she had a sudden attack of fever 7 days later and developed right pleural effusion, a cold abscess in the anterior chest wall and swelling of a thumb-sized right cervical lymph node which broke through the skin. We made a diagnosis of cervical and mediastinal lymph nodes tuberculosis, tuberculous pleurisy, spinal caries and cold abscess in the anterior chest wall due to the biopsy findings of the specimen taken from the cervical lymph node, examination of pleural effusion, chest CT, bacteriological examination of the cold abscess and spinal MRI. We started chemotherapy with the antituberculous drugs (HRSZ) and symptoms except back pain improved. She complained of paresis of the both lower extremities, which completely paralyzed 8 months later in spite of continued chemotherapy. Thereafter her paralysis was gradually improved and she was able to walk by herself after 12 months chemotherapy.

Erythromycin suppresses the expression of cyclooxygenase-2 in rheumatoid synovial cells.

OBJECTIVE: To investigate whether erythromycin (EM) can suppress the expression of cyclooxygenase-2 (COX-2) in rheumatoid synovial cells, and determine the mechanisms involved. Methods. Synovial tissues were obtained from 25 patients with rheumatoid arthritis (RA). Rheumatoid synovial cells were cultured with or without EM (0.1-1000 nM) in the presence of interleukin 1beta (IL-1beta) for various times. Protein expression of COX-2, and phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) were detected by Western blot. COX-2 messenger RNA (mRNA) was detected by RT-PCR. DNA binding activity of nuclear factor kappa B (NF-kB) was detected by ELISA. Results. IL-1beta-stimulated synovial cells expressed COX-2 protein. EM suppressed the IL-1beta-induced COX-2 protein expression in a dose-dependent manner and inhibited IL-1beta-induced p38 MAPK phosphorylation, which was correlated with COX-2 expression in synovial cells. In contrast, EM had no effect on DNA binding activity of NF-kB and ERK1/2 expression. CONCLUSION: Our results indicated that EM downregulated COX-2 expression by inhibiting the p38 MAPK cascade, but had no effect on NF-kB or ERK1/2, in rheumatoid synovial cells.

Fosfomycin inhibits neutrophil function via a protein kinase C-dependent signaling pathway.

We investigated effects of fosfomycin (FOM) on neutrophil function, specifically the oxidative burst and adhesion molecule expression (CD11b/CD18, or MAC-1) using flow cytometry assay. Preincubation of polymorphonuclear leukocytes (PMNL) with FOM from 1 to 100 microg/ml prior to stimulation by phorbol 12-myristate 13-acetate (PMA, 2 ng/ml) significantly suppressed the oxidative burst in a concentration-dependent manner. However, FOM did not affect the oxidative burst of PMNL stimulated by a chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP). Stimulation with PMA (2 ng/ml) caused a rapid up-regulation of CD11b surface expression on PMNL, followed by time-dependent loss of this receptor. FOM also suppressed loss of CD11b in PMNL stimulated by PMA. FOM then inhibits the PMA-induced oxidative burst and CD11b epitope loss in PMNL. The suppressive effect appears to be mediated by the protein kinase C-dependent signaling pathway.