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.

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.

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 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.

[A case of mediastinitis and bilateral pyothorax, following acute epiglottitis with concurrent Aspergillus infection].

Life threatening mediastinitis as a complication of acute epiglottitis is very rare. A 38-year-old male in previously good health was admitted to our hospital in a state of unconsciousness. Seven days prior to admission he had complained of a sore throat, dysphagia, high fever and dyspnea. A chest X-ray on admission showed widening of the mediastinum, mediastinal emphysema, subcutaneous emphysema and left pleural effusion. Bronchoscopy showed the swelling of supraglottic structures. He was diagnosed as having acute mediastinitis and pyothorax as a complication of acute epiglottitis, but pathogens were not identified. The blood was hyperglycemic and insulin therapy was started. Though he gradually improved by massive antibiotic therapy, steroid therapy, tracheotomy and surgical drainage of both the left thoracic cavity and the mediastinum, he died suddenly of massive hemoptysis. Autopsy revealed that the acute mediastinitis had healed, but that the Aspergillus infection was present in both lungs and the pericardium. The Aspergillus infection was not lethal in the present case, and it seemed that death had resulted from arterial hemorrhage caused by erosion of the trachea. The present case suggests the need for antifungal therapy even in non-immunocompromised patients in particular when massive doses of antibiotics and steroids are administered.

[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.

[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 case of brain abscess associated with enterococcal endocarditis].

Enterococcal infections involving the central nervous system are uncommon clinical entities. A 74-year-old male was admitted to our hospital on November 3, 1991 for high fever. Nuchal rigidity was observed at neurological examination. All four blood cultures yielded E. faecalis. The MIC value of ABPC against the isolated E. faecalis was 0.25 microgram/ml. Vegetation on the mitral valve and mitral regurgitation were revealed by an echocardiogram. Enhanced CT scan showed low density area with ring enhancement in the right basal ganglia and a CSF examination suggested bacterial meningitis. He became better after ABPC 8 g/day was intravenously administered. Then the vegetation on the mitral valve and the brain abscess disappeared. He was discharged with no complications. We reported a rare case of brain abscess associated with enterococcal endocarditis.

[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.

[A comparison of pathohistological findings of transbronchial lung biopsy specimens between Mycobacterium tuberculosis and mycobacteria other than Mycobacterium tuberculosis infections].

The pathohistological findings of transbronchial lung biopsy (TBLB) were compared between Mycobacterium tuberculosis infection (group A) and Mycobacteria other than Mycobacterium tuberculosis (MOTT) infections (group B). The number of positive pathological findings in TBLB were 14 (70%) in group A and 2 (16%) in group B, respectively. Eleven cases (55%) in group A were positive for acid-fast bacilli in TBLB by Ziehl-Neelsen stain, and 3 cases of group A showed granulomatous lesion in TBLB. In pathohistological findings of group B, 2 cases (16%) were granulomatous lesion, 4 cases (33%) were fibrosis, and 3 cases (25%) were inflammatory changes. The pathohistological examination of TBLB was more useful for the diagnosis of pulmonary tuberculosis than for MOTT infection.

[The nature of immunohistochemically defined astrocytic cells in rat gliomas].

The nature of astrocytic cells in rat gliomas induced by ethylnitrosourea (ENU) was studied by means of immunohistochemically demonstrating glial fibrillary acidic protein (GFAP), vimentin and beta-subunit of S 100 protein (S 100 beta) on paraffin sections. A special attention was paid to elucidating whether astrocytic cells would be neoplastic or not. The astrocytic cells in tumors were compared with astrocytes in normal rat brains and reactive astrocytes around a stab wound for their morphology, distribution and immunohistochemical characteristics. GFAP positive astrocytic cells in tumors were roughly divided into astrocytic cells and hypertrophic cells that showed morphologically similar appearance to fibrous astrocytes and hypertrophic reactive astrocytes around a stab wound respectively. A few multi-nucleated pleomorphic cells regarded as a kind of hypertrophic cells were also noted in gross tumors. GFAP positive cells were diffusely distributed in early neoplastic proliferations and microtumors, while in gross tumors they tended to be localized at the periphery. The GFAP positive cells were scattered among negative cells of tumors, forming no tumor mass. These findings suggest that the GFAP positive cells show no neoplastic growth, even though histopathologically they exhibit atypism or pleomorphism. The quantitative analysis of GFAP positive cells in tumors indicated more than 8% in most tumors in the white matter, whereas less than 8% in tumors in the gray matter and approximately 5% in gross tumors. The predominance of GFAP positive cells in the white matter was also observed in lesions induced by a stab wound.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

[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.

[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.

[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.

A sequential ultrastructural and histoautoradiographic study of early neoplastic lesions in ethylnitrosourea-induced rat glioma.

A sequential study of the early stage of development of ethylnitrosourea (ENU)-induced glioma in the rat was performed by electron microscopy and [3H]thymidine histoautoradiography. Hyperplasia, the earliest neoplastic change that was detectable morphologically, consisted of a few or several immature oligodendroglia-like cells which were connected with one another or with preexisting neural tissue by junctional apparatus, and showed no reactive changes in the astrocytes or microglia. The labelling index of hyperplastic cells was 2.6%. Foci of early neoplastic proliferation (ENP) showed mild destructive changes in the neighboring neural tissue, and their major constituent cells had characteristics of immature oligodendroglias. The labelling index of cells showing ENP was 3.3%. The intercellular spaces exhibited slight enlargement with accumulation of extracellular matrix and a decrease in the number of junctional apparatus on the neoplastic cells. Microtumors showed apparent destruction of the preexisting neural tissue to form a tumor mass with an increase in the extracellular matrix. Constituent cells of the microtumors were similar to those of the ENP, although reactive astrocytes and microglias occurred more frequently. The labelling index was 9.6% in the central area of microtumors and 5.3% in the peripheral area. These findings suggest that in the initial or very early stages of glial cell neoplastic proliferation, it is necessary for the neoplastic cells to maintain contact with the neurons for metabolic purposes, and that after losing contact, these cells can proliferate autonomously with the accumulation of extracellular matrix.

[A case of interstitial pneumonitis with hemoptysis, BOOP (bronchiolitis obliterans organizing pneumonia) pattern, granulomas and foreign body giant cells in lung biopsy].

A 66-year-old male presented to our hospital in January 1990 with chief complaints of hemoptysis and cough. These symptoms had developed 10 months previously and had gradually increased. Fine crepitations were audible over the right lower lung field. There were no results suggesting an inflammatory process such as leucocytosis, elevation of ESR or positive CRP reaction. Chest X-ray film on the first visit showed fine nodular shadows in the right lower lung field, and chest CT revealed fine nodular shadows and mild dilatation of the right lower lobe bronchus. Transbronchial lung biopsy specimens showed granulomas with multinucleated giant cells, alveolitis and Masson bodies. The open lung biopsy specimens showed numerous macrophages and foreign body giant cells, and extensive organizing exudates in the bronchioles and alveolar spaces. Proliferation of smooth muscle and fibrosis around the dilated bronchioles were also seen. Thus, this patient demonstrated BOOP pattern, with granulomas and foreign body giant cells. His hemoptysis appeared to have resulted from inflammation of dilated bronchioles. His symptoms and abnormal shadows on chest X-ray improved without any therapy after admission. After treatment with corticosteroid, the diffuse fine nodular shadows disappeared. There has been no recurrence of symptoms to date, although this patient has continued living in the same environment as prior to admission. BAL findings during his prolonged follow-up revealed decrease in lymphocytes and elevation of CD4/CD8 ratio. Although the presence of granulomas suggests the possibility of an allergic reaction, no antigenic material could be identified in this case.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.