[Pulmonary dirofilariasis with cavity formation and pleural effusion].

A 61-year-old man visited a community hospital because of hemosputum. A solitary nodule in the left lower lung field was pointed out on a chest roentgenogram. The patient was treated with antibiotics, but the solitary nodule increased in size. He was referred to our hospital because of high fever and observations of cavity formation and pleural effusion on a chest roentgenogram. The pleural effusion showed no cytologic evidence of malignancy, and cultures were also negative for bacteria. An increased percentage of lymphocytes was detected in the pleural effusion, but slight eosinophilia was found in blood samples. Dot enzyme-linked immunosorbent assay and Ouchterlony's double-diffusion test yielded a diagnosis of pulmonary dirofilariasis. After drainage of the pleural effusion by thoracentesis, spontaneous regression was observed. Cavity formation, pleural effusion, and spontaneous regression are in general rare in patients with pulmonary dirofilariasis.

[Bronchial atresia with atelectasis of the left upper lobe].

A 69-year-old woman visited her physician on October 1 complain of dry cough. However, the chest radiograph revealed no abnormalities. She was later admitted to our hospital because a radiograph taken by another physician on November 26 revealed a massive lesion in the right upper mediastinum. Computed tomographic findings showed a massive lesion containing a branching structure with a few calcifications, suggesting a case of atelectasis of the left upper lobe with mucus plug. Bronchoscopic examination revealed complete obstruction of the orifice of the left upper lobe bronchus, and so a diagnosis of bronchial atresia was made. However, since the patient had a history of tuberculous peritonitis and the mass lesion was somewhat calcified, the possibility that this was an acquired case could not be ruled out. After treatment with oral antibiotics, the size of the atelectasis was decreased. Therefore, we considered that the expansion of the atelectasis could have been due to superimposed bacterial infection.

[Eosinophilic pneumonia without eosinophilia in BALF or peripheral blood and diagnosed by open lung biopsy].

A 47-year-old woman was referred to our hospital because of cough and an abnormal shadow in the left lung field. The infiltrate reduced without therapy and another infiltrate appeared in the right lung field. Bronchiolitis obliterans organizing pneumonia was clinically suspected due to the absence of signs of eosinophilia in peripheral blood and bronchoalveolar lavage fluid (BALF). Open lung biopsy specimens disclosed alveolitis with mononuclear cell infiltration and organization within the air spaces of bronchioli and alveolar ducts. The observation of pronounced eosinophil infiltration in the alveolar spaces of some specimens yielded a diagnosis of eosinophilic pneumonia. After steroid therapy, the abnormal shadows disappeared. BALF lymphocyte surface marker analysis detected no decrease in the CD4/CD8 ratio; activated CD4 and CD8 lymphocytes were notably higher than the corresponding levels in peripheral blood. IL-5, IL-3, and GM-CSF values in BALF were not significantly elevated. This was a case of borderline eosinophilic pneumonia that was difficult to diagnose on the basis of clinical parameters alone.

[Thymic cyst with elevated SLX levels in serum and cystic fluid].

A 24-year-old man was admitted to our hospital in June 1996 with complaints of anterior chest discomfort. Chest X-ray films on admission showed an abnormal mediastinal shadow with well-defined margin. Chest X-ray examinations about 6 weeks earlier had not detected any abnormalities. Laboratory tests on admission showed a high serum concentration of Siaryl Lewis X-i antigen (SLX). A computed tomographic scan of the chest showed a large (6 x 6 x 12 cm) homogeneous mass in the right anterior mediastinum. The mass was removed completely and histologically diagnosed as a thymic cyst. Biochemical analysis of fluid from the cyst revealed remarkably high levels of SLX, CA 19-9, and CEA. In immunohistochemical studies, epithelial cells from the cystic walls stained positive for SLX, CA 19-9, and CEA. After the operation, the level of serum SLX returned almost to normal.

[Idiopathic interstitial pneumonia exacerbated by alveolar hemorrhage].

A 60-year-old man, in who idiopathic interstitial pneumonia (IIP) was diagnosed in 1990, was admitted to our hospital in March 1995 with exertional dyspnea, hemosputum and fever. On chest X ray, new infiltrates in the bilateral middle lung fields were seen, in addition to reticulonodular shadows in the bilateral lower lung fields, which had been noted in 1990. Intubation was reformed because of hypoxemia, and bronchoalveolar lavage (BAL) was performed in right B6. The BAL fluid was bloody, and a diagnosis of alveolar hemorrhage was made based on the presence of many hemosiderin-laden macrophages in the fluid. After pulse therapy with methylprednisolone, the hypoxemia and chest X ray findings improved, and he was extubated. Alveolar hemorrhage may be one possible complication leading to an exacerbation of IIP.

[Severe bronchorrhea accompanying alveolar cell carcinoma: treatment with clarithromycin and inhaled beclomethasone].

We report the efficacy of oral clarithromycin and inhaled beclomethasone against severe bronchorrhea in a patient with alveolar cell carcinoma. A 54-year-old man produced about 500 to 900 ml of clear and egg-white-like sputum each day. Anti-cancer chemotherapy and erythromycin therapy did not reduce the volume of sputum. After administration of clarithromycin and inhaled beclomethasone, sputum volume decreased to about 300 nl each day and the patient's ability to perform daily activities improved. Two months later, clarithromycin was stopped and the patient was treated with inhaled beclomethasone alone. Sputum volume did not increase for 6 months, although the chestroentgenographic findings gradually worsened. Then the sputum volume gradually increased. Five months after the sputum volume began to increase, he was producing about 2 liters of sputum each day and died of respiratory failure. Although the levels of CA 19-9, SLX, and CEA in serum were all within the normal range, the sputum contained high levels of CA 19-9 (1,133,620 U/ml), SLX (3,000 U/ml), and CEA (283 ng/ml). In patients with bronchorrhea, measurement of tumor markers in sputum may be useful for the diagnosis of alveolar cell carcinoma.

Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis.

Human neutrophils contain three isoforms of antimicrobial and cytotoxic peptides in the azurophil granules, which belong to a family of mammalian neutrophil peptides named defensins. Here we investigate the role of these peptides in diffuse panbronchiolitis (DPB). Defensins (human neutrophil peptide-1, -2 and -3) were measured by radioimmunoassay in bronchoalveolar lavage fluid (BALF) of 30 patients with DPB, 16 patients with idiopathic pulmonary fibrosis (IPF) and 15 healthy adults. The concentration of defensins was higher in BALF of patients with DPB than in patients with IPF and healthy subjects. DPB and IPF patients also had significantly higher plasma concentrations of defensins than controls. In patients with DPB, BALF concentration of defensins correlated significantly with neutrophil count or BALF concentration of interleukin (IL)-8. Immunohistochemistry of open-lung biopsy specimens from four DPB patients showed localization of defensins in neutrophils and mucinous exudate in the airways, and on the surface of bronchiolar epithelial cells. In vitro studies showed an enhanced extracellular release of defensins following stimulation of neutrophils with phorbol myristate acetate, N-formyl-methionyl-leucyl-phenyalamine, and human recombinant IL-8. Treatment of DPB with macrolides for 6 months significantly reduced neutrophil count and concentrations of defensins and IL-8 in BALF. Our results indicate accumulation of neutrophil-derived defensins in the airway in diffuse panbronchiolitis, and suggest that defensins may be a marker of neutrophil activity in this disease.

Elevated levels of soluble adhesion molecules in serum of patients with diffuse panbronchiolitis.

STUDY OBJECTIVE: Adhesion molecules have been implicated in the pathogenesis of inflammatory diseases. This study was designed to determine whether soluble adhesion molecules in serum reflect the disease activity in diffuse panbronchiolitis (DPB). PATIENTS AND METHODS: Using an enzyme-linked immunosorbent assay, we measured the serum levels of soluble L-, E-, and P-selectin (sL-, sE-, and sP-selectin), intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in 27 patients with DPB, 13 with bronchiectasis, and 15 normal adults. BAL was also performed, and the levels of interleukin (IL)-8 and IL-1 beta in BAL fluid (BALF) were measured. RESULTS: The serum levels of these molecules were significantly elevated in DPB patients compared with the control subjects. DPB patients also had significant high levels of circulating sE- and sP-selectin compared with patients with bronchiectasis. There was a significant correlation between serum sE-selectin and the percentage of neutrophils in BALF in all patients. There was a significant inverse correlation between serum sE-selectin and percent vital capacity in DPB patients. In the same patients, the relationships between serum sE-selectin and BALF concentrations of IL-1 beta as well as between serum sL-selectin and BALF IL-8 were also significant. Treatment of DPB patients with macrolides significantly reduced the serum levels of these soluble adhesion molecules and BALF concentrations of IL-1 beta and IL-8. CONCLUSIONS: Our results suggest that these soluble adhesion molecules, particularly selectins, may reflect the disease activity of DPB, and that their levels may be regulated by cytokines produced in the lungs.

[Serum-soluble adhesion molecules in patients with idiopathic pulmonary fibrosis and acute respiratory distress syndrome].

We measured the concentrations of soluble adhesion molecules in serum obtained from healthy volunteers and from patients with idiopathic pulmonary fibrosis (IPF) and the acute respiratory distress syndrome (ARDS). The concentrations of soluble intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and P-selectin were significantly higher in serum from the patients than in serum from the healthy volunteers. In patients with IPF, the concentration of soluble ICAM-1 in serum was inversely related to the vital capacity (expressed as a percent of the predicted value). The concentrations of L-selectin in serum from patients with ARDS were significantly lower than those in serum from healthy volunteers and from patients with IPF. These data suggest that serum-soluble adhesion molecules may be useful as markers of disease activity, severity, and prognosis in ARDS and IPF.

[Pulmonary sequestration associated with high levels of tumor markers in serum].

A 20-year-old woman was admitted to our hospital because of an abnormal shadow on a chest X-ray film. Laboratory tests done on admission showed high levels of tumor markers in serum. A computed-tomographic scan of the chest showed a multilocular cystic mass in the S10 of the right lung. Angiography revealed an abnormal artery that branched from the abdominal aorta, and therefore pulmonary sequestration was diagnosed. A right lower lobectomy was done. Analysis of fluid from the cyst revealed very high levels of CA19-9, CEA, and SLX. In an immunohistochemical study, epithelial cells of the cyst's walls were stained for CA19-9, CEA, and SLX. After the operation the levels of these tumor markers in serum were almost normal.

[Kartagener's syndrome with aspergilloma].

A 47-year-old man was referred to our hospital because of hemoplysis. He had a history of chronic sinusitis and surgical treatment of a spinal arteriovenous malformation. A chest X-ray film and computed tomographic scan showed dextrocardia, diffuse bronchiectasis, and an aspergilloma in the right upper lung field. The source of the bleeding could not be detected by fiberoptic bronchoscopy. Transbronchial mocosal biopsy was done and examination of a specimen by transmission electron microscopy revealed the lack of inner and outer dynein arms. A chest X-ray film and computed tomographic scan of his nephew, who had a long history of productive cough showed dextrocardia and right lower-lobe bronchiectasis. These findings indicate that hemoptysis in patients with Kartagener's Syndrome can be caused not only by bronchiectasis but also by aspergilloma.

[Defensin in plasma and in bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome].

We measured the levels of defensins, antimicrobial peptides, and cytotoxic peptides in azurophil granules of neutrophils in plasma, and in bronchoalveolar lavage fluid (BALF) from patients with the acute respiratory distress syndrome (ARDS). High levels of plasma defensins were observed in samples from patients with ARDS. Samples of BALF from patients with ARDS also had more neutrophils and higher concentrations of defensins than did samples from healthy volunteers and from patients with idiopathic pulmonary fibrosis or diffuse panbronchiolitis. In addition, the concentration of interleukin (IL)-8 in BALF was higher in patients with ARDS than in other subjects. A significant correlation was found between the concentration of defensins and that of IL-8 in BALF from patients with ARDS. These findings suggest that the lung injury in ARDS is caused by defensins released by neutrophils that accumulate in the lungs.

[Acute bronchiolitis due to Mycoplasma pneumoniae and successfully treated with steroids].

A high fever, coughing, stridor, and dyspnea developed in a 52-year-old woman on October 19, 1995. She went to a local clinic and was treated with oral penicillin and intravenous cefpirome. The symptoms worsened, and she was admitted to our hospital on October 26. Coarse crackles and wheezing were heard in both lung fields. The white blood cell count was 9000/mm3 and arterial blood gas analysis revealed a PaO2 of 49.8 Torr on room air. A chest roentgenogram obtained on admission showed a few small bibasilar nodular infiltrates, and a chest CT scan showed thickened bronchial walls along with small nodules having a centrilobular distribution. Of the cells in bronchoalveolar lavage fluid, 88% were neutrophils, but tests for bacteria and mycobacteria were negative. The cold-agglutinin titer was 1:512. The Mycoplasma pneumoniae antibody titer (IIIA) was 1:640 and viral serology tests were negative. Acute bronchiolitis due to M. pneumoniae was diagnosed and treatment with intravenous minocycline was started. The symptoms (coughing, fever, and stridor) resolved and the small nodules on chest CT scan disappeared, but hypoxemia remained. At the same time, an obstructive ventilatory defect (FEV1% 62.8%) and abnormal ventilation/perfusion lung scans were noted. Development into bronchiolitis obliterans was suspected, so administration of methyl prednisolone (1 g/day for 3 days) and prednisolone was started. The response to steroids was good. Pulmonary function improved and the arterial PaO2 at the time of discharge was 86 Torr (room air). Use of steroid therapy in the early phase of bronchiolitis obliterans seemed to be effective.

Neutrophil-related cytokines and neutrophil products in bronchoalveolar lavage fluid of a patient with ANCA negative Wegener's granulomatosis.

We report a case of Wegener's granulomatosis (WG), with neutrophil accumulation in bronchoalveolar lavage fluid (BALF). Peripheral blood neutrophilia was present but the anti-neutrophil cytoplasmic antibody (ANCA) was negative. The serum and BALF levels of neutrophil-related cytokines, including interleukin (IL)-8, granulocyte colony-stimulating factor (G-CSF) and IL-1 beta, were increased, particularly in BALF. Plasma and BALF levels of neutrophil elastase and defensins, which are released by neutrophils and are potentially toxic to cells, were also elevated. Our findings suggest that neutrophils and neutrophil-related cytokines may play an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody negative as well as anti-neutrophil cytoplasmic antibody positive Wegener's granulomatosis.

[Clinical evaluation of sulbactam/cefoperazone for lower respiratory tract infections. Correlation between the efficacy of sulbactam/cefoperazone and beta-lactamase].

The efficacy and safety of sulbactam/cefoperazone (SBT/CPZ) were evaluated in 42 patients with respiratory tract infections, including pneumonia (29 patients) and lower respiratory tract infections (5 patients). Overall clinical efficacy rates (excellent + good) were 79% in pneumonia and 80% in respiratory tract infections in 34 patients evaluated for clinical efficacy. It was excellent that the clinical efficacy rate was 92% in mild and moderate pneumonia. Pathogens isolated from sputa were 31 strains, including 8 strains of Pseudomonas aeruginosa, 7 of Streptococcus pneumoniae, 3 of Staphylococcus aureus and 3 of Haemophilus influenzae. Since the isolates were eradicated in 18 strains, replaced in 3, unchanged in 2 and unknown in 8, the overall eradication rate was 91%. The eradication rates were 89% in beta-lactamase producing strains and 100% in beta-lactamase positive sputum, and excellent or good in 19 (83%) of 23 patients with beta-lactamase negative sputum. The eradication rate was 88% in 5 patients with beta-lactamase positive sputum. One patient experienced a moderate rash. Abnormal laboratory test values were observed in 10 patients (26.3%), but these abnormalities were mild and transient. These results suggested that SBT/CPZ was effective and safe for the treatment of respiratory tract infections caused by beta-lactamase producing as well as beta-lactamase non-producing bacteria.

Adult respiratory distress syndrome with increased serum and bronchoalveolar lavage fluid levels of squamous cell carcinoma-related antigen.

We report a case with adult respiratory distress syndrome (ARDS) associated with increased levels of squamous cell carcinoma-related antigen (SCC) in the serum and bronchoalveolar lavage fluid (BALF). ARDS was likely induced by ibuprofen, based on the presence of pancytopenia and a weakly positive drug lymphocyte stimulating test (DLST). High serum and BALF levels of interleukin (IL)-8, neutrophil elastase as well as SCC were detected. Corticosteroid therapy resulted in clinical improvement, resolution of pulmonary infiltrates on chest roentgenogram and normalization of serum and BALF levels of IL-8, neutrophil elastase and SCC.

[A case of fulminant psittacosis necessitating mechanical ventilation diagnosed by chlamydial isolation form BALF].

A 51-year-old female was admitted with complaints of fever and general fatigue. Chest X-ray showed diffuse bilateral fine nodular shadows and infiltrates. Complication of hepatic and muscular injury was suspected from increased levels of GOT, GPT and CPK in the serum. Arterial blood gas analysis revealed hypoxemia. Because hypoxemia aggravated despite treatment with intravenous minocycline (200 mg/day), corticosteroids and mechanical ventilation were started, and the administration of minocycline (400 mg/day) and sparfloxacin was added. Consequent, chest X-rays and several laboratory data improved gradually. The final diagnosis was established with a significant rise of both IgG and IgM antibody against Chlamydia psittaci with MIF and identification of Chlamydia with the cell culture method. Chlamydia was successfully isolated from BALF of this patient obtained 5 days after commencement of minocycline treatment. Psittacosis should be considered as a possible cause of severe respiratory failure necessitating emergency care including mechanical ventilation.

[A study of defensins in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis].

We estimated defensins, antimicrobial and cytotoxic peptides localized in azurophil granules of neutrophils, in bronchoalveolar lavage fluid (BALF) in patients with diffuse panbronchiolitis (DPB). BALF from DPB patients contained a higher concentration of defensins than those from patients with idiopathic pulmonary fibrosis and healthy volunteers. A significant correlation was observed between the concentration of defensins and the number of neutrophils, the concentration of interleukin-8 or neutrophil elastase in BALF of DPB patients. An immunohistochemical defensins in neutrophils and mucinous exudates in the airways and in the surface of bronchiolar epithelial cells. After treatment with macrolide antibiotics, significant reductions in the concentrations of defensins, IL-8 and neutrophil numbers in BALF of DPB patients were observed. These findings suggest that the lung injury in DPB could be caused by defensins released by neutrophils accumulated in the airways.

Detection of Cryptococcus neoformans in bronchial lavage cytology: report of four cases.

Four cases of pulmonary cryptococcosis were diagnosed by cytological detection of Cryptococcus neoformans in bronchial lavage. Three patients had underlying diseases, but not HIV infection. The chest X-rays showed 2 patients with nodular lesions and 2 with cavitary lesions. The cryptococcal antigen in the serum was positive in all four patients. In the cytology of bronchial lavage, Cryptococcus neoformans was detected after period-acid-Schiff (PAS) staining and was cultured in Sabouraud-dextrose agar. The cytology of bronchial lavage is useful for the rapid diagnosis of pulmonary cryptococcosis.

[A case of MRSA sepsis treated by the sequential combination therapy netilmycin and minocycline].

A sixteen year old female was feverish from June 12, 1993. Methicillin-resistant Staphylococcus aureus was isolated from the blood, the diagnosis of MRSA sepsis was established. Vancomycin (2 g/day) was administered for eighteen days, but MRSA was not eradicated in the blood culture. Then she was administered a combination therapy of arbekacin (200 mg/day) and imipenem/cilastain (1 g/day) for seven days, but MRSA in the blood was cultured continuously. The sequential combination therapy of netilmycin (200 mg/day) and minocycline (200 mg/day) was started, MRSA was eradicated from the blood culture after four days. The sequential combination therapy netilmycin and minocycline was seemed to be effective for MRSA infection.