Differential diagnosis of neonatal mild hypergalactosaemia detected by mass screening: clinical significance of portal vein imaging.

The aetiology of hypergalactosaemia in 100 neonates detected by screening using the Paigen method is discussed. Hypergalactosaemia was transient in 94 cases and persistent in 6. The aetiology among transient cases was unknown in 55, delayed closure of the ductus venosus in 19, heterozygous UDP-galactose 4-epimerase (GALE) deficiency in 16, and heterozygous galactose-1-phosphate uridyltransferase (GALT) deficiency in 6. The aetiology among persistent cases was hepatic haemangioendothelioma with portovenous shunting in 2, and patent ductus venosus with hypoplasia of the intrahepatic portal vein, citrin deficiency, homozygous GALE deficiency, and heterozygous GALE deficiency in one patient each. The abnormalities of the portal system were identified ultrasonographically at the initial consultation and measurements of the total bile acid and alpha-fetoprotein concentrations were helpful in resolving the differential diagnosis. The causes of hypergalactosaemia varied, but a major cause was portosystemic shunt. Evaluation of patients with hypergalactosaemia should not be limited to enzymatic analysis, but should also include hepatic imaging, especially ultrasonography. Additionally, determination of total bile acids and alpha-fetoprotein is helpful in identifying the aetiology of hypergalactosaemia in infants.

[A case of pulmonary alveolar proteinosis complicated with pneumoconiosis and myelodysplastic syndrome].

A 72-year-old man who had worked as a coal worker for 28 years and as a tunnel construction worker for 18 years was admitted because of fever, dyspnea, and appetite loss. Pneumoconiosis had been diagnosed when he was 64 years old and myelodysplastic syndrome at 71 years of age. After admission, the patient was treated with antibiotics and anti-fungal drugs but did not respond. Respiratory failure gradually worsened and he died. Autopsy specimens revealed that the cause of death was exacerbation of respiratory failure due to pulmonary proteinosis rather than pulmonary infection. This is a case of pulmonary proteinosis complicated with pneumoconiosis and myelodysplastic syndrome which, to our knowledge, is rare. We also considered the possibility that defective pulmonary macrophage function due to myelodysplastic syndrome and long-term silica inhalation played a part in the development of pulmonary alveolar proteinosis in this case.

[A case of lymphangioleiomyomatosis with carcinomatous lymphangiosis].

A 66-year-old woman had a history of partial gastrectomy and resection of the residual stomach because of early gastric cancer and its recurrence. She had been suffering from dyspnea on effort, hemosputum, and cough since the age of 52 years. Chronic pulmonary emphysema and bronchial asthma were diagnosed when she was 59. On January 31, 1996, she was admitted to UOEH hospital with a complaint of increased dyspnea. In spite of treatment with oxygen, steroid, and inhaled anti-cholinergic agent, her condition deteriorated. Subsequently, she had DIC, respiratory failure and reticulolinear opacities were seen on chest radiographs, and she died 2 weeks after admission. At autopsy, the lung specimen revealed numerous cystic spaces surrounded by a proliferation of smooth muscle cells. Immunohistological examination showed these cells to be positive for HMB-45. Signet cells were seen in the lymphatics and vessels, and hemosiderin-laden macrophages were found in the alveolar spaces. This was a rare case of lymphangioleiomyomatosis with carcinomatous lymphangiosis.

Bilateral massive pleural effusions caused by uremic pleuritis.

A 61-year-old man was started on hemodialysis in June 1998. Just after the commencement of dialysis, a chest X-ray film revealed bilateral pleural effusions. The effusions were hemorrhagic and exudative, and did not respond to dialysis. He was transferred to our university hospital on October 8,1998. Repeated thoracentesis demonstrated hemorrhagic and exudative characteristics without any diagnostic evidence. Pleural biopsies showed fibrosis and lymphocyte infiltration. The effusions were massive and did not respond to treatments including hemodialysis, repeatedly performed pleurodesis and the administration of antituberculous drugs. He died of respiratory failure on December 30, 1998. The autopsy confirmed bilateral fibrinous pleuritis without any underlying infections or malignancy. We diagnosed this case as uremic pleuritis from this clinical course and the autopsy findings. The clinical entity of uremic pleuritis was recognized as a complication of patients with hemodialysis in 1969. Uremic pleuritis generally responds to continued hemodialysis and the prognosis is usually good. However, some case reports demonstrated that surgical decortication is only indicated in cases with a severe clinical course. The clinical course of the present case was progressive and fatal. Uremic pleuritis is a serious complication of hemodialysis, which may lead to death.

[A case of Pneumocystis carinii pneumonia with pulmonary cysts and increased level of serum KL-6].

In August, 1999, a 46-year-old man with fever, cough, and dyspnea was admitted to a hospital. On the basis of the clinical and radiographic findings, bacterial pneumonia was suspected. Antibiotics were not effective, because of atypical lymphocytes in the peripheral blood and positive anti-human T-cell leukemia virus antibody, and he was transferred to our hospital. A chest radiograph and a CT scan revealed bilateral ground-glass opacities with huge multiple cysts. Intensive treatment of Pneumocystis carinii pneumonia associated with human T-cell leukemia was unsuccessful. Pneumocystis carinii was found in the bronchoalveolar lavage fluid. Human T-cell leukemia and Pneumocystis carinii pneumonia were diagnosed. In this case, numerous pulmonary cysts were progressing rapidly, the largest cyst being 8.7 cm in diameter, and the largest cyst in our experience either in clinical practice or in reading of the literature in Pneumocystis carinii pneumonia. The maximum serum KL-6 was markedly increased to 15,200 U/ml, which is the highest level reported for Pneumocystis carinii pneumonia.

[Pulmonary involvement in acute febrile neutrophilic dermatosis (Sweet's syndrome)].

We encountered a 55-year-old man with pulmonary involvement in acute febrile neutrophilic dermatosis (Sweet's syndrome). He had been treated with steroids for Sweet's syndrome for 2 years, and on September 17, 1998 presented with a cough and a fever of 38.9 degrees C. Physical examination revealed fine crackles at the bases of both lungs. Chest radiography and computed tomography demonstrated reticular and nodular infiltrates in both lungs. Treatment with a variety of antibiotic agents and an antifungal agent was not effective. Sputum culture was sterile and bronchial washings were negative for infectious pathogens. Transbronchial biopsy revealed a mild chronic interstitial infiltrate and an inflammatory exudate in bronchiolo-alveolar tissue. The pulmonary lesions and cutaneous lesions were resolved by intradermal injections of triamcinolone acetonide in addition to oral prednisolone. Although the apparent neutrophilic infiltrates cited by earlier reports were not observed in transbronchial biopsy specimens, the clinical course in this case suggested that our patient had Sweet's syndrome with pulmonary involvement.

A case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) together with total atelectasis of a lung caused by lymphadenopathy and pleural effusion.

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a clinicopathologic entity established by Frizzera in 1974. Reported cases of AILD with pleuropulmonary involvement have been increasing recently. At Nogata Central Hospital, an 82-year-old male inpatient with brain infarctions and chronic bronchitis showed a rapid growth of systemic lymphadenopathy and various other symptoms. We diagnosed the case as AILD by histopathologic examination of a lymph node. Chest radiography and computed tomography demonstrated a loss of volume of the right lung caused by intrathoracic lymphadenopathy and a pleural effusion. Although cases of AILD with pleuropulmonary involvement have been increasing, no cases with almost total atelectasis of a lung have been reported as yet. AILD should be taken into account as a disease which may cause atelectasis of a lung.

[A case of pulmonary fibrosis with many asbestos bodies in bronchoalveolar lavage fluid after exposure to asbestos and man-made mineral fibers].

We report a case of severe pulmonary fibrosis in a patient exposed to asbestos and other natural and man-made mineral fibers (MMMF) over a period of time. A 63-year-old man was admitted to our hospital because of progressive dyspnea and severe hypoxemia with hypercapnea. Mineral fibers recovered by bronchoalveolar lavage were analyzed by scanning electron microscope (SEM) and energy-dispersive x-ray spectroscopy (SEM-EDS). The bronchoalveolar lavage fluid (BALF) included a large number of asbestos bodies (116,000/ml). The cores of the asbestos fibers were crocidolite, and no vitreous fibers nor other kinds of man-made mineral fibers (MMMFs) were identified. To our knowledge, the number of asbestos bodies per ml of this patient's BALF is the greatest ever reported. Insufficient personal protection of the airways, high concentrations of inhaled fibers, co-exposure to cigarette smoke, and prolonged biopersistence of crocidolite asbestos fibers are presumed to be the causes of such severe asbestosis.

[Imipenem/cilastatin sodium and other beta-lactams for respiratory tract infections: clinical benefit and treatment days for cure].

Therapeutic efficacy and the treatment days for cure of imipenem/cilastatin sodium (IPM/CS) in treatment of pulmonary infections were prospectively determined in comparison with those of beta-lactams other than carbapenems mainly ceftazidime (CAZ) or sulbactam/cefoperazone (SBT/CPZ). The overall response rate was 84.9% (62/73) in the IPM/CS group and 74.7% (56/75) in the beta-lactam group, the difference not being significant. In the subjects having underlying respiratory diseases, the response rate was 91.1% (41/45) and 73.9% (34/46) in the IPM/CS and beta-lactam groups, respectively. In patients with infections secondary to chronic respiratory disease, the rate was 91.2% (31/34) in the former group and 66.7% (24/36) in the latter group, respectively. The differences were significant for both stratified analyses. The treatment days for cure judged by the attending physician were 12.9 +/- 0.6 days in the IPM/CS group, and 14.5 +/- 0.7 days in the beta-lactam group. The difference was not, however, significant. In patients with mild to moderate infections, the treatment days for cure was 12.0 +/- 0.6 days (n = 64) in the IPM/CS group and 14.3 +/- 0.7 days (n = 70) in the beta-lactam group. In patients with underlying respiratory disease, the treatment days for cure were 11.8 +/- 0.7 days (n = 45) and 14.7 +/- 0.9 days (n = 46) in the IPM/CS and beta-lactam groups, respectively. In patients with infections secondary to chronic respiratory disease, the days were 11.1 +/- 0.7 days (n = 34) and 14.7 +/- 1.1 days (n = 36), respectively. Thus, IPM/CS therapy significantly reduced the number of treatment days until cure. There was, however, no significant difference between the two therapy groups in treatment of the patients with severe infections, those without underlying respiratory disease, or those with pneumonia and/or lung abscess. The treatment days for cure were also assessed by the members of review committee taking into consideration of body temperature, leukocyte count, and C-reactive protein. As the result, it was 6.9 +/- 0.5 days in the IPM/ CS and 10.3 +/- 0.7 days in the beta-lactam groups; respectively, and the difference was significant. Time (days) until cure was also compared between the two groups using survival time analysis, confirming a more rapid response in the IPM/CS group. Although IPM/CS therapy was associated with a shorter response time as assessed by both the attending physicians and the review committee, there were considerable differences between the results of these judgements. Thus, the duration of treatment with injectable antibiotics requires reevaluation in the future. No significant differences were observed between the groups with respect to parameters indicating side effects and laboratory abnormalities. There were no severe symptoms or laboratory findings, and symptoms and changes in laboratory values, if any resolved during the course of therapy or after the withdrawal of treatment. In conclusion, IPM/CS seems to be very useful as first-line therapy for respiratory tract infections and for shortening the duration of treatment.

Relationship between inflammatory cells in bronchoalveolar lavage fluid and pathologic changes in the lung interstitium.

Bronchoalveolar lavage (BAL) is recognized as an important research tool for various lung diseases, but it is still uncertain whether inflammatory cells in BAL fluid (BALF) accurately reflect pathologic changes in the lung interstitium. We used a morphometric method to quantify the density of inflammatory cells in the lung interstitium by utilizing a computer-aided graphic analyzer and compared those findings with BALF results. Two types of animal models were studied, i.e., endotoxemia (Escherichia coli endotoxin) and hypersensitivity pneumonitis (inhaled ovalbumin). Male Wistar rats were used; the right lungs were lavaged and the left lungs were prepared for morphometric study. In the endotoxemia model, the neutrophil fraction in BALF and the neutrophil density in the lung interstitium correlated significantly at 18 h (r = 0.81, p < 0.05) and 24 h (r = 0.81, p < 0.05) but not at any other time points after injection. In the hypersensitivity pneumonitis model, the neutrophil fraction in BALF and the neutrophil density in the lung interstitium correlated significantly (r = 0.80, p < 0.05) only at 3 h after inhalation. The lymphocyte fraction in BALF and the lymphocyte density in the lung interstitium were correlated positively at 3 h (r = 0.83, p < 0.05), 1 day (r = 0.82, p < 0.05), 2 days (r = 0.67, p = NS), and 4 days (r = 0.87, p < 0.05), but not at 6 days after inhalation. Our data suggest that neutrophil fraction in BALF does not reflect neutrophil populations in the lung interstitium except at the time of maximal neutrophil count in lung lavage. For lymphocytes in the hypersensitivity pneumonitis model, those in BALF and in the lung interstitium roughly correlate in the majority of measurements.

Characterization of amiodarone pneumonitis as related to inflammatory cells and surfactant apoprotein.

STUDY OBJECTIVE: To characterize the inflammation observed in amiodarone-induced pneumonitis. DESIGN: The density of inflammatory cells in BAL fluid (BALF) and lung interstitium was quantified in a rat model of amiodarone pneumonitis. Immunoperoxidase staining for surfactant apoprotein was evaluated in lung tissue. ANIMALS AND INTERVENTIONS: Male Fischer 344 rats weighing 170 to 180 g received amiodarone, 150 mg/kg/d, suspended in 0.5% methylcellulose by gavage 5 d/wk. Control animals were given only methylcellulose. Rats were killed after 3, 5, 7, 9, and 12 weeks. Histologic sections were prepared for hematoxylin-eosin staining and the immunoperoxidase method. MEASUREMENTS AND RESULTS: Significant positive correlations between the density of neutrophils in BALF and the interstitium were seen at 5 weeks (r=0.90, p<0.05) and 7 weeks (r=0.90, p<0.05). Significant positive correlations were observed between the density of lymphocytes in BALF and the interstitium at 9 weeks (r=0.90, p<0.05) and 12 weeks (r=0.90, p<0.05). The density of type II pneumocytes was significantly increased in the amiodarone-fed rats. Extracellular surfactant apoprotein was found in the alveolar space and the cytoplasm of type II pneumocytes, Clara cells, and large, foamy macrophages throughout drug treatment. Extracellular surfactant apoprotein filled some alveoli at 9 weeks. CONCLUSIONS: The density of lymphocytes and neutrophils increased significantly in the BALF and the lung interstitium throughout amiodarone administration. The relationship between the density of lymphocytes in BALF and in the interstitium differed from that of neutrophils. In addition, amiodarone caused hyperplasia of type II pneumocytes and deposition of conglomerated, extracellular surfactant apoprotein in the alveolar space.

Features of idiopathic pulmonary fibrosis with organizing pneumonia.

To characterize the clinical features of patients with idiopathic pulmonary fibrosis (IPF) having organizing pneumonia (OP), we retrospectively reviewed the clinical charts, chest X-rays, CT scans, and transbronchial lung biopsy (TBLB) specimens of patients with IPF. Patients with IPF and OP had a subacute onset of symptoms (within 2 months) (87.5%), leukocytosis (> 10,000/mm3) (62.5%), and a strong C-reactive protein (CRP) reaction (> 3+) (75%). Some of these features were distinctly different from those of IPF patients without OP (subacute onset of symptoms 0%, leukocytosis 0%, strong CRP reaction 16.7%). In the patients with IPF with OP, A-aDo2 and semiquantitative scores of chest X-ray abnormalities improved significantly after prednisolone treatment. Those abnormalities improved only slightly in the patients with IPF without OP. Diffusing capacity remained decreased and abnormal interstitial infiltration persisted, even after prednisolone treatment in the patients with IPF with or without OP. Clinical features of IPF patients with OP differed from those of patients with IPF without OP. IPF patients with OP showed good clinical response to corticosteroid therapy. These findings warrant further study of the presence of OP in TBLB specimens in predicting corticosteroid responsiveness and prognosis of patients with IPF.

[A case of sarcoidosis with advanced cystic and fibrotic changes in a young patient].

A 29-year-old man was referred to our hospital because of exertional dyspnea and progressive eruption on the buttocks and the lower extremities. Chest roentgenograms and computed tomograms taken at that time revealed diffuse fibrotic changes accompanied by multiple cavities and bullae in the lungs. There were no signs of mediastinal or hilar lymphadenopathy. A chest roentgenogram taken 7 years before admission showed no abnormalities. Serum ACE and lysozyme levels were high: 29.9 IU/l and 14.1 micrograms/ml, respectively. 67Ga scintigraphy showed diffuse uptake in both lung fields. The PPD skin test was negative, and repeated sputum smears and cultures were negative for pyogenic bacteria and acid-fast bacilli. Examination of transbronchial lung biopsy and skin biopsy specimens confirmed the diagnosis--they showed noncaseating epithelioid granulomas with giant cells and a negative reaction of the stain to acid-fast bacilli, which are compatible with sarcoidosis. The patient was given 30 mg/d of prednisone orally. The dyspnea and eruption were clearly alleviated, although there was little roentgenographic regression of cystic or fibrotic changes. There have been only a few reports of cystic and fibrotic changes early in the course of sarcoidosis. The cystic lesions in this case were probably secondary pulmonary cavities caused by the contracting and obstructive changes related to pulmonary fibrosis.

[A case of limited Wegener's granulomatosis with hemophilia A, complicated by empyema, bronchopleural fistula and herpes zoster during therapy].

A 36-year-old man with hemophilia A was admitted to hospital because of otalgia, hearing loss, nasal obstruction, nonproductive cough, and high fever. His laboratory data showed high-grade acute inflammatory reactions. His chest X-ray and CT films showed multiple cavitary masses in the right lower lung field. Bronchoscopy performed at our institution revealed bronchial nodules in the intermediate truncus, and BAL revealed increases in the neutrophils and an IgG index (BAL IgG/albumin divided by serum IgG/albumin). Biopsy specimens obtained from nasal mucosa showed epithelioid granulomas with Langerhans' giant cells and necrotizing vasculitis. Antineutrophil cytoplasmic antibodies were also positive, but no evidence of glomerulonephritis was observed. The diagnosis of limited Wegener's granulomatosis was thus made. He was treated with standard therapy (daily cyclophosphamide and glucocorticoids), but within 1 month he had complications of empyema with herpes zoster, and bronchopleural fistula. The complications resolved with appropriate treatment.

[A case of bronchiolitis obliterans organizing pneumonia: diagnostic utility of bronchoalveolar lavage and CT scan].

A 54-year-old female was admitted to our hospital because of abnormal shadows on chest X-ray at annual checkup. She complained of dyspnea on exertion. Chest X-ray findings showed an increase in density at the bilateral lower lung fields and unclearness of the silhouette of the heart and the diaphragm. CT scan findings revealed irregular opacities of various density with many small cystic changes and air bronchograms and air bronchiolograms. The pulmonary function test showed restrictive ventilatory disturbance and reduced diffusing capacity. BALF findings revealed an increase in the total cell count, an increase in the percentage of lymphocytes and a decrease in the OKT4+/OKT8+ ratio. TBLB specimen showed infiltration of mononuclear cells in alveolar septa and organizing exudate in alveolar ducts. These findings suggested a diagnosis of BOOP rather than IPF, and an open lung biopsy was performed. Open lung biopsy specimen showed obstructive bronchiolitis with polypoid granulation tissue and thickening of alveolar septa with infiltration of mononuclear cells, and she was diagnosed as having BOOP. She responded well to corticosteroid and is free from any abnormalities on chest X-ray, CT scan and pulmonary function test at present. Analysis of BALF and CT scan findings are useful for the differential diagnosis of BOOP and IPF.

[Two cases of pulmonary lymphangioleiomyomatosis].

We report two cases of pulmonary lymphangioleiomyomatosis with recurrent spontaneous pneumothorax. The cases were diagnosed by open lung biopsy. Case 1 was a 38-year-old woman, whose chest X-ray showed linear and reticular shadows. Lung tissue was negative for hormone receptors. She was treated with tamoxifen, but developed allergic symptoms. Her condition gradually deteriorated despite oxygen and progesterone therapy. Case 2 was a 41-year-old woman, whose chest X-ray showed a reticular shadows and slight overinflation. Hormone receptors were not examined, but the disease did not progress with oxygen, progesterone and GnRH agonist (Sprecur) therapy.

[Clinical studies in three cases of pulmonary cryptococcosis].

We report three cases of pulmonary cryptococcosis in which one community acquired and two nosocomial infections were suspected. Clinical studies were focused on histological and immunological diagnosis and antifungal chemotherapy. The first case was initially suspected of having primary cryptococcosis. The second case was first suspected to have BOOP on the basis of clinical and radiological findings. The third was initially suspected of having lung cancer because of an enlarging mass lesion in fibrotic lung and elevated tumor markers. All cases were treated with antifungal agents. Two cases were treated with fluconazole alone, the other case with fluconazole and 5-fluorocytosine. In all cases, the abnormal shadows on chest X-ray demonstrated 50 to 90 percent improvement within 6 months, and cryptococcal antigen in the serum decreased. There were no side effects from the drugs.

[A case of intrapulmonary lymph node with silicotic nodules in a patient with idiopathic interstitial pneumonia].

A 61-year-old man was admitted to our hospital on October 8, 1991 because of abnormal shadows on chest X-ray at annual checkup at his company. Chest X-ray and CT on admission showed diffuse reticular shadows in bilateral lower lung fields and a nodular opacity approximately 10 mm in diameter in the right lower lung. Since transbronchial lung biopsy was not diagnostic, an open lung biopsy was performed on October 28, 1991. The lung specimens showed diffuse pulmonary fibrosis compatible with usual interstitial pneumonia and an intrapulmonary lymph node containing silicotic nodules. Only 29 cases (including the present case) of intrapulmonary lymph nodes have been reported. Although the causes of intrapulmonary lymph nodes are not clear, smoking is considered to play an important role in the development of pulmonary lymphoid tissue. In our case, the intrapulmonary lymph node contained silicotic nodules. Only several case have been reported to have silicotic nodules in the lymph nodes. As suggested by Kradin, they may be induced by relatively low levels of exposure to dust. Our case also had pulmonary fibrosis (IIP), and is the first reported case of intrapulmonary lymph node associated with IIP. Although it is difficult to determine these two diseases occurred coincidently or not, it is possible that a low level of dust exposure may have contributed to both silicotic nodules in the lymph node and IIP.