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We describe the clinical courses and outcomes of allogeneic hematopoietic stem cell transplantation-associated organizing pneumonia (HOP) observed in our institution over the past 20 years. Charts and chest radiographs of 603 allogeneic transplant recipients were retrospectively reviewed for HOP. In total, 12 cases of HOP were identified (2.0%) at a median interval of 148 days after transplantation (range, 53-475 days), presenting with low-grade fever, nonproductive cough and dyspnea at onset. Initial antibiotic treatment did not ameliorate symptoms, but most patients responded well to 0.5-1 mg/kg of prednisolone. HOP flare-up occurred after discontinuing treatment or while tapering doses in 9 of 12 patients, but responded to re-treatment with the initial dose of steroid. Although three patients died, no deaths were attributable to pulmonary failure. The remaining nine patients displayed no relapse of primary disease and 5-year survival rate was 74.1%. Clinical features of the 12 patients were similar in that all underwent irradiation-containing conditioning and most had a prior history of acute graft-versus-host disease (GVHD) and cytomegalovirus (CMV) infection. Furthermore, eight patients had active chronic GVHD at onset of HOP. These findings suggest that factors such as irradiation-containing regimens, previous CMV infection and allogeneic immune reaction may contribute to HOP occurrence.

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Gefitinib is a potent drug used in the treatment of nonsmall-cell lung cancer (NSCLC). Gefitinib acts by inhibition of the epidermal growth factor receptor tyrosine kinase. Clinical trials have confirmed the efficacy of gefitinib for NSCLC. Adverse drug reactions, although frequent, are mild, and include acne-like skin rash and diarrhoea. The present study describes the case of a 56-yr-old male with NSCLC who, 4 weeks after treatment with gefitinib, suffered from a severe alveolar haemorrhage diagnosed by bronchoalveolar lavage. This is the first case report of an acute life-threatening lung injury in a patient with nonsmall-cell lung cancer who had been given gefitinib.

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A 36-year-old woman admitted to our hospital because of numbness in the left limbs and weakness in the right arm, and was subsequently given a diagnosis of intramedullary spinal cord metastases from lung cancer. The patient had lung adenocarcinoma with metastases to the brain, spine and lymph nodes. Occipital craniotomy, radiation therapy and chemotherapy were performed on the lesions in the year following June 1994. In June 1995, however, she complained of numbness in the left limbs and weakness in the right arm. Compatible with her neurological manifestation, MRI demonstrated tumors in the right side of the cord at the spinal level of C3-4 and C7-Th1, both of which were of high density in T2-enhanced conditions with enhancement by gadolinium-diethylenetriamine pentaacetic acid. No invasion from spinal metastasis was detected by CT, scintigraphy or MRI. We therefore diagnosed her manifestation as Brown-Séquard syndrome caused by intramedullary spinal cord metastatic tumors of lung adenocarcinoma. In order to avoid paraplegia and dysfunction of the bladder and bowel, radiation therapy of the cord lesions with total dose of 44 Gy was performed. Her neurologic manifestation was improved, restoring her quality of life, as the tumor size estimated by MRI decreased. Four months later, however, she died of lung adenocarcinoma that developed accompanied with severe peritonitis carcinomatosa and multiple metastases.

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After allogeneic bone marrow transplantation (allo-BMT), recipient alveolar macrophages (AM) are gradually replaced by AM of the donor origin. An influx of mononuclear phagocytes of donor origin to the lung is responsible for the repopulation, but the detailed kinetics remain unclear. We therefore studied 24 BMT recipients who underwent bronchoalveolar lavage (BAL) from 24 to 83 days after BMT. AM cell number, size, morphology, proliferating ability, and genotype of AM were measured. Before day 50, the number and size of AM in BAL fluid were similar to those of normal nonsmokers. However, after day 50, the mean number of AM increased threefold and the mean cell size decreased due to the increase of small AM. These small cells are presumably of donor origin based on DNA fingerprinting analysis and based on fluorescence in situ hybridization for the Y chromosome in a sex-mismatched case. Immunohistochemistry and cell cycle analysis demonstrated that the increase in AM number coincided with a remarkable increase of AM expressing proliferating cell nuclear antigen, suggesting that small AM are proliferating. This is the first report representing that augmented proliferation of donor AM in situ may contribute to the reconstitution of AM population after BMT.

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The utility of 111In-DTPA-IgG imaging for the detection of intrathoracic lesions was evaluated in 10 patients with the suspicion of inflammatory or infectious diseases. They were intravenously administered 40 or 80 MBq of 111In-DTPA-IgG, and scanned after 24 or 48 hours. Of these, 8 cases, consisted of 4 cases with pneumonia and 2 cases with lung abscess and one case of pulmonary tuberculosis and one of a tuberculous pleuritis, showed true positive results. Others were one false negative case of pneumonia and one true negative case of lung cancer. Overall sensitivity and specificity were 88.9% and 100%, respectively. There were no cases which showed side effects or abnormal laboratory findings caused by the radiopharmaceuticals administered. Thus, 111In-DTPA-IgG imaging is a useful tool for the detection of intrathoracic infectious lesions.

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A 53-year-old female was admitted to our hospital complaining of chest pain and gait disturbance. Examinations on admission showed that she was immunocompetent except the negative tuberculin test. The chest X-ray showed infiltrative shadows with old tuberculous lesions in the bilateral upper lung fields. In CT, a mass lesion was revealed in the lesion, which destructed the fifth thoracic vertebra and invaded into the epidural space. She died of meningitis on the 18th day after admission. On autopsy, it was made clear that the mass lesion was caused by Aspergillus fumigatus, and that the meningitis was the result of the invasion of the fungus into the epidural space.

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To detect cytomegalovirus-associated interstitial pneumonia (CMV-IP) in recipients of BMT in its earliest stage, five CMV methods were assessed for their usefulness using bronchoalveolar lavage fluid as the test specimen. Of the 43 cases enrolled in the study, PCR was positive in 12 cases, shell vial in eight, culture in eight and cytology in three. There were no positive cases in in situ hybridization. Based on this result, the 43 cases were classified into four groups: Group 1, three cases: positive in PCR, shell vial and cytology; Group 2, five cases: positive in PCR and shell vial; Group 3, four cases: positive only in PCR; and Group 4, 31 cases: negative in all CMV tests. Cases in Group 1 were judged as having the highest risk of overt CMV-IP. They were successfully treated with a combination of ganciclovir and immunoglobulin. Group 2 was diagnosed as having active CMV infection and ganciclovir monotherapy was effective for these patients. Groups 3 and 4 were not given anti-CMV therapy, but they were free from CMV-related manifestations throughout the study. The sensitivity and specificity of each survey method for the detection of Groups 1 and 2 were 1.0 and 0.89 in PCR, 1.0 and 1.0 in shell vial, 0.88 and 1.0 in culture, and 0.38 and 1.0 in cytology. Similarly, the positive and negative predictive values were 0.67 and 1.0 in PCR, 1.0 and 1.0 in shell vial, 1.0 and 0.97 in culture, and 1.0 and 0.88 in cytology. Thus, CMV survey on bronchoalveolar fluid was thought to be useful in detecting post BMT CMV-IP in its earliest stage.

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A 69-year-old male was admitted to our hospital on Jan. 10, 1995 complaining of bloody sputum, left back pain and fever of 39 degrees C. He had a history of pulmonary tuberculosis 45 years ago. His chest X-ray and CT showed the presence of air-fluid level in the left pleural cavity with thickening and calcification of the pleura. Salmonella Enteritidis was isolated from the sputum, bronchoalveolar lavage fluid and stool. He was diagnosed as suffering from Salmonella-empyema with an internal fistula. Based on the in vitro sensitivity test, sulfamethoxazole/trimethoprim was started. However, the efficacy of the antimicrobia was not sufficient. He then underwent left pleuropneumonectomy. Salmonella was cultured also from the specimen obtained at the operation. His course after operation was uneventful. Thus, although Salmonella Enteritidis is known as a common pathogen of food poisoning, it can cause empyema, especially in a case with an impaired host defence system.

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The value of the measurement of (1-->3)-beta-D-glucan, a major and common cell wall constituent of fungi, for diagnosing pulmonary aspergillosis was assessed in comparison with that of conventional examinations. The concentrations of (1-->3)-beta-D-glucan in sera was elevated in 7 out of 8 patients with active aspergillosis, but not in cases without active diseases, except for one sample. Further, the concentrations well reflected the activity of the aspergillosis in each case. Regarding conventional examinations, with the immunodiffusion test it was difficult to detect the present activity of the disease. The radioallergosorbent test was useful for diagnosing bronchopulmonary aspergillosis, but not for other types of aspergillosis. The Aspergillus-specific component, galactomannan, was insensitive and the enzyme-linked immunosorbent assay gave highly variable results. Thus, although the assessment of the specificity of the assay is still necessary, compared with other tests, the assay of (1-->3)-beta-D-glucan has the advantage of diagnosing pulmonary aspergillosis and also of assessing the disease activity.

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A 70-year-old man was admitted for evaluation of an abnormal shadow on his chest X-ray film, consisting of a mass containing an air bronchogram. He was also found to have a monoclonal gammopathy (IgM kappa type) and Sjögren syndrome. Open lung biopsy was performed with the suspicion of primary pulmonary lymphoma or pseudolymphoma. Southern blot analysis of the tissue revealed clonal rearrangements of immunoglobulin gene, supporting the diagnosis of B-cell lymphoma. Using conventional immunoperoxidase staining (PAP) method, the monoclonality in the tissue specimen is sometimes quite difficult to prove. Southern blot analysis, however, gives more accurate and reliable results. The analysis of immunoglobulin gene rearrangements is quite useful in determining the presence or absence of monoclonality in a specimen in cases of suspected lymphoproliferative disease such as primary pulmonary lymphoma and pseudolymphoma. We strongly recommend the use of Southern blot analysis in making the diagnosis of lymphoproliferative disease.

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Lidocaine concentrations in 49 endotracheobronchial aspirates ranged from 12,580 to 23 micrograms/ml. The aspirates taken from the larger airway contained higher concentrations of lidocaine than those obtained from the smaller airway. Of the aspirates collected before 10 minutes after the final lidocaine administration, the lidocaine concentration of 7 (24.1%) of 29 specimens was greater than 3,000 micrograms/ml, however, in the aspirates collected after 10 minutes, only 1 (5%) of 20 specimens showed a concentration greater than 3,000 micrograms/ml. Using the dilution technique method (DTM) of lidocaine in the fiberscope (FS) suction channel, gradual injection of a 2 ml saline solution into the suction channel and removal of the saline solution in the suction channel were performed immediately with a suction machine; the statistically significant differences (p < 0.001) between lidocaine concentrations in the specimens before and after the DTM procedure were determined.

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Granulocyte colony formation by human bone marrow cells in serum-free cultures was studied using purified recombinant granulocyte colony-stimulating factor (rG-CSF). The cloning efficiency of the serum-free cultures was about 80% that of the serum-containing cultures. In addition to purified G-CSF, four ingredients were found to be essential to granulocyte colony formation: bovine serum albumin (BSA), iron-saturated human transferrin, cholesterol, and L-alpha-phosphatidylcholine. Their optimal concentrations were also investigated. Insulin was not indispensable for granulocyte colony formation, but its addition did increase the number of granulocyte colonies. Hydrocortisone was found to be inhibitory to granulocyte colony formation at high concentrations.

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A 44-year-old previously healthy male was diagnosed as anemic and treated at a nearby hospital. A year later, he was admitted to our hospital for precise examination of the progression of refractory anemia. Blood examination showed hemolytic anemia and more detailed examination of this hemolysis revealed pyruvate kinase deficiency. The activity was 15.1% of a normal control. Pyruvate kinase activities of his family members were normal or slightly decreased. Ten months after admission to our hospital, 2% of blast cells with Auer's body in the peripheral blood were noted which increased progressively. The bone marrow contained 17.3% of blast cells with a subsequent diagnosis of acute myelogenous leukemia being made. Although intensive chemotherapy was performed, the patient achieved a brief remission and died 2 years after admission to our hospital.

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Repeated subcutaneous (s.c.) injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to Pneumocystis carinii (P. carinii)-infected balb/c nude (nu/nu) mice had no effects on the number of the P. carinii cysts in the lungs, despite neutrophilic infiltration in the tissues and a marked increase in blood neutrophil count. This finding indicates that neutrophils in the absence of T cells do not play an important role in the killing of P. carinii. However, survival periods of the rhG-CSF treated mice seemed to extend to some extent compared with the controls presumably because of the prevention of mixed bacterial infections.

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