Uniportal video-assisted thoracic surgery and perioperative pirfenidone for lung cancer and idiopathic pulmonary fibrosis: a case report.

Patients with idiopathic pulmonary fibrosis (IPF) occasionally experience acute exacerbations after surgery for lung cancer. Several recent studies have revealed a prophylactic effect of perioperative pirfenidone treatment on postoperative acute exacerbations of IPF in patients with lung cancer. A 75-year-old woman consulted with her pulmonologist because of an IPF shadow detected by follow-up chest computed tomography 2 months after surgical treatment of biliary cancer. Another 7 months later, chest computed tomography showed a 23- × 14-mm nodule located in the right lower lobe with high accumulation of fluorodeoxyglucose detected by positron emission tomography, resulting in a radiological diagnosis of primary lung cancer with IPF. We administered perioperative pirfenidone treatment followed by right lower lobectomy using uniportal video-assisted thoracoscopic surgery after attaining a pathological diagnosis of adenocarcinoma. The patient developed no acute exacerbations of IPF during the postoperative period, and she had no recurrence of lung cancer for 15 months after surgery. We successfully used a combination of perioperative antifibrotic medication and minimally invasive surgery after lung cancer surgery in a patient with IPF.

A Case of Candidemia after Long-term Presence of Urethral Foreign Bodies.

A 52-year-old man presented to our hospital complaining of general malaise, cough, and fever. Total body computed tomography revealed scattered pneumonia and urethral foreign bodies that had been inserted during adolescence. Candida glabrata was detected in blood and urine cultures. Based on these findings, the patient was diagnosed with candidemia that developed due to Candida urinary tract infection, complicated by septic pulmonary embolism and severe diabetes mellitus. Candidemia likely persisted despite the initiation of intravenous antifungal therapy and control of blood sugar level. Therefore, surgical removal of the urethral foreign bodies was performed, which resulted in resolution of the patient's symptoms. Herein, we report a rare case of candidemia complicated by Candida urinary tract infection that developed due to the long-term presence of urethral foreign bodies. A multidisciplinary therapeutic approach, including surgical removal of the infected foreign bodies, is effective in such cases. This case indicates that long-term presence of foreign bodies and acquired immune dysfunction can be risk factors for candidemia. Therefore, detailed history should be obtained and systemic examination should be performed to identify the complicating risk factors on diagnosis of candidemia.

CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema.

Excessive apoptosis and prolonged inflammation of alveolar cells are associated with the pathogenesis of pulmonary emphysema. We aimed to determine whether CD40 affects alveolar epithelial cells and endothelial cells, with regard to evoking apoptosis and inflammation. Mice were repeatedly treated with agonistic-anti CD40 antibody (Ab), with or without agonistic-anti Fas Ab, and evaluated for apoptosis and inflammation in lungs. Human pulmonary microvascular endothelial cells and alveolar epithelial cells were treated with agonistic anti-CD40 Ab and/or anti-Fas Ab to see their direct effect on apoptosis and secretion of proinflammatory molecules in vitro. Furthermore, plasma soluble CD40 ligand (sCD40L) level was evaluated in patients with chronic obstructive pulmonary disease (COPD). In mice, inhaling agonistic anti-CD40 Ab induced moderate alveolar enlargement. CD40 stimulation, in combination with anti-Fas Ab, induced significant emphysematous changes and increased alveolar cell apoptosis. CD40 stimulation also enhanced IFN-γ-mediated emphysematous changes, not via apoptosis induction, but via inflammation with lymphocyte accumulation. In vitro, Fas-mediated apoptosis was enhanced by CD40 stimulation and IFN-γ in endothelial cells and by CD40 stimulation in epithelial cells. CD40 stimulation induced secretion of CCR5 ligands in endothelial cells, enhanced with IFN-γ. Plasma sCD40L levels were significantly increased in patients with COPD, inversely correlating to the percentage of forced expiratory volume in 1 s and positively correlating to low attenuation area score by CT scan, regardless of smoking history. Collectively CD40 plays a contributing role in the development of pulmonary emphysema by sensitizing Fas-mediated apoptosis in alveolar cells and increasing the secretion of proinflammatory chemokines.

Role of CD69 in acute lung injury.

AIMS: CD69 is an early activation marker in lymphocytes and an important signal transmitter in inflammatory processes. However, its role in acute lung injury (ALI) is still unknown. We used a lipopolysaccharide (LPS)-induced mouse model of ALI to study the role of macrophage-surface CD69 in this condition. MAIN METHODS: We investigated bronchoalveolar lavage fluid (BALF) cell subpopulations, myeloperoxidase levels in lung homogenates, lung pathology, and lung oedema in CD69-deficient (CD69(-/-)) mice 24h after LPS instillation. We also determined cytokine/chemokine expression levels in BALF and macrophage culture supernatant from CD69(-/-) and wild type (WT) mice. Also, we investigated CD69, keratinocyte-derived chemokine (KC) and macrophage inflammatory protein (MIP)-2 localization in the lungs after LPS administration. Furthermore, we examined the effect of anti-CD69 antibody on LPS-induced cytokine/chemokine release from cultured macrophages. KEY FINDINGS: Our study shows that intratracheal instillation of LPS-induced neutrophilic infiltration, histopathological changes, myeloperoxidase positivity, and oedema in the lung to a lower degree in CD69(-/-) mice than in WT mice. The immunoreactivities for CD69, KC and MIP2 were induced in the lung of WT mice instilled with LPS and were predominantly localized to the macrophages. Moreover, the cytokine/chemokine expression profile between the two genotypes of cultured macrophages in response to LPS was similar to that observed in the BALF. In addition, anti-CD69 antibody inhibited the LPS-induced cytokine/chemokine expression. SIGNIFICANCE: These results suggest that CD69 on macrophages plays a crucial role in the progression of LPS-induced ALI and may be a potentially useful target in the therapy for ALI.

Cigarette smoke-induced pulmonary inflammation is attenuated in CD69-deficient mice.

Cluster of differentiation 69 (CD69) has been identified as a lymphocyte early activation marker, and recent studies have indicated that CD69 mediates intracellular signals and plays an important role in various inflammatory diseases. Cigarette smoke (CS) is a strong proinflammatory stimulus that induces the release of proinflammatory mediators by recruiting macrophages and neutrophils into the lung tissue, and is one of the main risk factors for a number of chronic diseases. However, the potential role of CD69 in CS-induced pulmonary inflammation has not been determined. To address to this question, CD69-deficient (KO) and wild-type (WT) mice were subjected to CS-induced acute pulmonary inflammation. After the exposure with CS, the expression of CD69 in the lung of WT mice was significantly induced, it was predominantly observed in macrophages. In conjunction with this phenomenon, neutrophil and macrophage cell counts, and expression of several cytokines were significantly higher in the bronchoalveolar lavage fluid (BALF) of CS-exposed WT mice compared with air-exposed WT mice. Likewise, the CS-induced accumulation of inflammatory cells and cytokines expression were significantly lower in CD69-KO mice than in WT mice. These results suggest that CD69 on macrophages is involved in CS-induced acute pulmonary inflammation.

Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin.

BACKGROUND: Cluster of differentiation 69 (CD69), an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases. To determine the effect of CD69 deficiency on bleomycin(BLM)-induced lung injury, we evaluated the inflammatory response following intratracheal BLM administration and the subsequent fibrotic changes in wild type (WT) and CD69-deficient (CD69-/-) mice. METHODS: The mice received a single dose of 3 mg/kg body weight of BLM and were sacrificed at 7 or 14 days post-instillation (dpi). Lung inflammation in the acute phase (7 dpi) was investigated by differential cell counts and cytokine array analyses of bronchoalveolar lavage fluid. In addition, lung fibrotic changes were evaluated at 14 dpi by histopathology and collagen assays. We also used reverse transcription polymerase chain reaction to measure the mRNA expression level of transforming growth factor ß1 (TGF-ß1) in the lungs of BLM-treated mice. RESULTS: CD69-/- mice exhibited less lung damage than WT mice, as shown by reductions in the following indices: (1) loss of body weight, (2) wet/dry ratio of lung, (3) cytokine levels in BALF, (4) histological evidence of lung injury, (5) lung collagen deposition, and (6) TGF-ß1 mRNA expression in the lung. CONCLUSION: The present study clearly demonstrates that CD69 plays an important role in the progression of lung injury induced by BLM.

[Case of disseminated tuberculosis complicated with tuberculous meningitis while investigating an abdominal lymphadenopathy].

In February 2005, a 33-year-old man visited A hospital complaining of fever. The blood screening test revealed the liver dysfunction, then computed tomography showed swelling of abdominal lymph nodes. In April, headache and disorientation appeared. He was diagnosed as disseminated tuberculosis and tuberculous meningitis based on chest X-ray and computed tomography findings and examination of cerebrospinal fluid. After admission to our hospital, anti-tuberculous drugs were prescribed, but the cerebral infarction happened. The disturbance of consciousness and the left half of his body paralysis appeared. They did not improve and hydrocephalus was complicated in August, though he was treated by steroids. He needed all helps because of the left half of his body paralysis and an advanced sequelae was left. It was thought that the abdominal lymph adenopathy preceded as one of symptoms of the disseminated tuberculosis in this case. It is said to be rare that abdominal lymph node swelling is seen in the early stage of disseminated tuberculosis. But, we think that it is necessary to keep in mind that the possibility of disseminated tuberculosis as one of the diseases in differential diagnosis, when we examine enlargement of abdominal lymph nodes with symptoms suggesting the presence of infection such as fever.

[Clinical review of patients with pulmonary tuberculosis who were detected by the screening of homeless persons admitted in the shelter facilities].

PURPOSE AND METHODS: There has been a recent increase in the number of non-profit facilities that provide shelter for the homeless. These social service facilities aim to assist the social rehabilitation of homeless persons. The Public Health Center of Chiba City screened 1,054 residents of these homeless shelters between November 2002 and August 2004 and found 17 individuals (1.6%) with active pulmonary tuberculosis. We clinically reviewed these cases. RESULTS: All 17 individuals were male, and their ages ranged from 44 to 70 years (mean 54.9 years). Four cases were smear positive and three cases were smear negative but culture positive by sputum examination for acid-fast bacilli. Nine cases had cavitary lesions on chest X-ray. There were three cases complicated with hepatitis C, two cases with diabetes mellitus and two cases with past history of gastrectomy. Of the 17 individuals, 13 were treated as inpatients, and four as outpatients. The mean hospitalization duration was 146.7 days excluding two patients who were discharged by themselves. Of the 11 inpatients, four remained hospitalized until the completion of treatment. Final outcome of the treatment was the following; 12 patients were cured, while five patients dropped out or discontinued treatment. CONCLUSION: The screening performed by the Public Health Center of Chiba City revealed a very high prevalence of tuberculosis among shelter residents. Thus, in the future, public health centers and medical institutions must work in collaboration to actively screen and provide treatment for residents of homeless shelters. This study also revealed that in spite of recommended hospitalization or long-term treatment, patients often self-discharged or discontinued regular outpatient treatment. Health centers and other public agencies must therefore work in close cooperation to help the homeless to continue hospitalization and subsequent medication and treatment even after their discharge from hospital.