Bioavailability of PCBs to male laboratory rats maintained on litters of contaminated soils: PCB burden and induction of alkoxyresorufin O-dealkylase activities in liver and lung

We examined the incidence and clinical outcome of late-onset noninfectious pulmonary complications (LONIPC) in a series of 234 patients who underwent allogeneic bone marrow transplantation at our institution between April 1982 and October 1996. The 179 patients who survived 3 months or more were evaluated. Clinical, radiologic, pulmonary function, and pathologic tests were reviewed to identify 18 patients (10%) who fulfilled the diagnostic criteria of LONIPC. Accordingly, the pulmonary processes included bronchiolitis obliterans (BO, five patients), bronchiolitis obliterans with organizing pneumonia (BOOP, three patients), diffuse alveolar damage (DAD, one patient), lymphocytic interstitial pneumonia (LIP, one patient), and nonclassifiable interstitial pneumonia (NCIP, eight patients). Various methods of enhanced immunosuppressive therapy resulted in marked durable remission in nine patients (50%) (3/3 with BOOP, 3/8 with NCIP, 1/1 with DAD, 1/1 with LIP, 1/5 with BO). The presence of chronic graft-versus-host disease (cGVHD) and prophylaxis for GVHD with cyclosporine and prednisone were the only variables significantly associated with the development of LONIPC (P = 0.0001 and 0.008, respectively). Regardless of histology, a reduction in the forced expiratory volume to < 45% of the predicted range was associated with poor response to treatment. These findings suggest a strong association between cGVHD and LONIPC and that the risk of LONIPC development may be influenced by the particular method of GVHD prophylaxis. Most patients with BOOP or mild airflow limitation at diagnosis achieved durable remissions.     

Interstitial pneumonia in patients receiving granulocyte colony-stimulating factor during chemotherapy: survey in Japan 1991-96

Twenty cases of interstitial pneumonia secondary to treatment with granulocyte colony-stimulating factor (G-CSF) were reviewed. Their interstitial pneumonia had the following features: (a) it occurred predominantly in patients aged 60 years or older; (b) it was prevalent among patients with haematological malignancies, particularly non-Hodgkin's lymphoma; (c) in all patients G-CSF was given after anti-cancer agents with potential to affect the lungs; (d) at the onset, many patients had symptoms such as dyspnoea and fever; and (e) the leucocyte (neutrophil) count as well as lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels were usually higher than normal at the onset. These findings indicate that, when G-CSF is used in combination with pneumotoxic anti-cancer agents, respiratory function should be monitored before and during treatment. If the leucocyte (or neutrophil) count and/or LDH and CRP increase suddenly in association with dyspnoea and fever during administration of G-CSF, interstitial pneumonia should be suspected. Accordingly, a chest radiograph and pulmonary functional tests should be performed promptly. If a diagnosis of interstitial pneumonia is made, steroid pulse therapy should be commenced immediately.     

A case of interstitial pneumonia of polymyositis-dermatomyositis with various pathological findings in open lung biopsy

A 60-year-old woman was admitted to our hospital with a two month history of dry cough and dyspnea on exertion. A chest roentgenogram revealed diffuse interstitial shadows with a reduction of lower lung volume. Laboratory examinations revealed an increase in CPK and aldolase. There was decreased proximal muscle power, and the findings of a biopsy of the right deltoid were compatible with polymyositis. Myositic symptoms were stable, but the respiratory symptoms worsened, and an open lung biopsy was performed for diagnosis and to determine the best treatment. The histological findings of biopsy materials demonstrated active interstitial pneumonia complicated by cellular interstitial pneumonia, bronchiolitis obliterans organizing pneumonia, usual interstitial pneumonia and lymphoid hyperplasia. The patient responded well to adrenocorticosteroid and immunosuppressive therapy, and is now attending as an out patient. It is well known that PM-DM can be associated with interstitial pneumonia, and this complication is an important prognostic factor clinically. The pathological patterns of interstitial pneumonia in PM-DM may be divided into usual interstitial pneumonia and bronchiolitis obliterans organizing pneumonia. Furthermore, it is well documented that these patterns are concurrent with the response to adrenocorticosteroid and prognostic factors. However, our case of PM-DM, in which various patterns such as rheumatoid arthritis (RA) were pathologically revealed, cannot be considered as having uniform pathological pattern. We consider that pulmonary pathological patterns of PM-DM are very varied, as with RA. It is a very important to evaluate the nature of these patterns and the subsequent clinical course in PM-DM with interstitial pneumonia.     

Idiopathic nonspecific interstitial pneumonia/fibrosis: comparison with idiopathic pulmonary fibrosis and BOOP

Based on past difficulties in clinically differentiating patients with idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans-organizing pneumonia (BOOP), and nonspecific interstitial pneumonia/fibrosis (NSIP), which all manifest clinically as interstitial lung disease, experience with pathologically confirmed examples of the three diseases was reviewed to compare clinical profiles and prognosis and to define NSIP more clearly. Thirty-one patients (15 males and 16 females) were pathologically identified as NSIP and subclassified into either the cellular (n=16) or fibrotic group (n=15). All 31 patients were clinically considered to be idiopathic NSIP cases. Patients with idiopathic BOOP (n=16) and IPF (n=64) were compared with the NSIP patients. Subacute presentation of interstitial lung disease characterized both idiopathic NSIP and idiopathic BOOP. NSIP patients showed volume loss on a chest radiograph (29.0%) and honeycombing on a computed tomography scan (25.8%); these features were not found in BOOP patients. Bronchoalveolar lavage lymphocytosis was characteristic of both BOOP and NSIP. Two subgroups of NSIP can be recognized histologically: patients in the fibrotic group had a less favourable outcome than those in the cellular group. BOOP and NSIP had a more favourable outcome than IPF. In conclusion, idiopathic nonspecific interstitial pneumonia can be differentiated from other types of idiopathic interstitial pneumonia, both pathologically and clinically.     

Implant-supported prostheses after maxillary cancer resection: preliminary report

Interstitial pneumonia and aseptic neutrophilic infiltration in the lung are rare pulmonary manifestations of myelodysplastic syndrome (MDS). We report a patient with progressive interstitial pneumonia associated with MDS. Histological examination of the lung revealed infiltration of atypical haematopoietic cells associated with MDS and diffuse alveolitis with honeycombing. Neutrophils obtained from the patient showed superoxide hyperproduction after stimulation with phagocytosis and phorbol myristate acetate, which might be attributed to the pathogenesis of interstitial pneumonia.     

Scintigraphy with gallium-67 citrate in patients with AIDS: pathologic extrapulmonary uptake

67Gallium citrate can accumulate in different inflammatory and neoplastic lesions. The mechanisms of 67Gallium uptake in abnormal tissue are still partially unknown and the tracer is considered a nonspecific indicator of disease. In AIDS patients, 67Gallium citrate is used in the diagnosis and characterization of opportunistic pulmonary infections and especially of Pneumocystis carinii pneumonia. From June 1989 through December 1992 in our Department 140 67Gallium scans were performed on 103 AIDS patients, referred for evaluation of pulmonary symptoms. All studies were carried out 72 hours after i.v. administration of 185 MBq 67Gallium citrate, with anterior and posterior views of head, chest and abdomen. The images were evaluated with conventional diagnostic criteria and site, number and intensity of abnormal foci of extrapulmonary uptake were recorded. Abnormal extrapulmonary uptake was found in 17 patients (12%): gastric (3, two of which also exhibited abnormal intestinal uptake), esophageal (1) hepatic (1), intestinal (2) renal (4), nodal (3), ocular (1), cutaneous (1), sinusal (1) localizations. In all cases clinical, endoscopic, bioptic or microbiological demonstration of the possible cause of 67Gallium uptake was obtained. An intriguing finding in our series was the lower incidence of gastric uptake (two patients with miliary tuberculosis and one patient with gastric candidiasis) than in the literature. This finding could be explained by clinical and epidemiologic differences between different patient populations. However, the scan interval after tracer administration should be also taken into account, since in our study scans were always performed at 72 hours, while in other series the interval ranged 24-48 hours. The relatively high incidence of abnormal extrapulmonary uptake confirms the opportunity of whole body exploration after 67Gallium administration in the patients with such multisystemic disease as AIDS, even when the patients are referred mainly for respiratory problems.     

"Spoon bowl" deformity of proximal femoral bypass vein graft: a cause of late graft failure on four occasions

Six patients with specific pulmonary diseases had pulmonary tissue surgically resected for diagnostic purposes. All six cases were characterized by space-occupying lesions surrounded by a peculiar reaction of the pulmonary parenchyma indistinguishable from desquamative interstitial pneumonia. If small biopsies from these areas had been taken, a diagnosis of desquamative interstitial pneumonia would have been made, and the underlying process would have gone undetected. These cases corroborate even further the concept that desquamative interstitial pneumonia is a pattern of pulmonary reaction, rather than a well-defined disease entity. Furthermore, it seems advisable to make the dianosis of desquamative interstitial pneumonia only when other conditions have been carefully ruled out by thorough clinical and pathologic investigations.     

Two patients with idiopathic pulmonary fibrosis and monoclonal gammopathy

A 67-year-old man and a 70-year-old man were admitted to our hospital because of dyspnea and dry coughing. Chest X-ray films showed bilateral reticulonodular shadows in the middle and lower lung fields. Specimens were obtained by open lung biopsies and the findings were compatible with those of usual interstitial pneumonia. Immunoelectrophoresis revealed monoclonal gammopathy in both patients. The levels of interleukin 6 in bronchoalveolar lavage fluid were high. In these two patients, idiopathic pulmonary fibrosis was associated with multiple myeloma and monoclonal gammopathy, and the levels of interleukin-6 in bronchoalveolar lavage fluid were high. These findings may help to elucidate the pathogenesis and development of idiopathic pulmonary fibrosis.     

Discrepancy of clinical, radiographic and histopathologic findings in two children with chronic pulmonary graft-versus-host disease after HLA-identical sibling stem cell transplantation

We report two children who presented with cough and shortness of breath 7-8 months after a matched sibling stem cell transplant (SCT) for chronic myelogenous leukemia and myelodysplastic syndrome, respectively. Pulmonary function tests (PFTs) revealed severe airways obstruction (AO). However, radiographic investigations showed no serious abnormalities in the early phase and open lung biopsy revealed only mild lymphocytic bronchiolitis and bronchiolitis obliterans consistent with pulmonary graft-versus-host disease (GVHD). Despite administration of bronchodilators and various immunosuppressive agents obstructive lung disease progressed to pulmonary failure in patient 1, whereas stabilization of the clinical course was observed in patient 2. Serial PFTs were the best predictor of the clinical course in contrast to radiographic and histologic findings. It is concluded that PFTs should be performed repeatedly in pediatric patients after allogeneic SCT with the aim of diagnosing GVHD-associated AO in the subclinical phase. Progressive post-transplant AO necessitates prompt initiation of intensive immunosuppressive therapy in order to stop the underlying immunopathologic process even in the absence of severe radiographic and histologic findings.     

Fulminant hepatic failure related to immunosuppressive therapy in an asymptomatic HBsAg carrier with idiopathic interstitial pneumonia

A 72-year-old woman who was an asymptomatic HBsAg carrier was admitted because of productive cough and dyspnea on exertion. After close examination, she was given a diagnosis of idiopathic interstitial pneumonia (IIP), and treated with glucocorticoids and cyclophosphamide. However, fulminant hepatitis type B developed and the patient died of respiratory complications stemming from the acute exacerbation of IIP. To avoid such outcomes, extra caution should be taken when planning immunosuppressive therapy for HBsAg carriers.     

ATP, thapsigargin and cAMP increase Ca2+ in rat hepatocytes by activating three different Ca2+ influx pathways

OBJECTIVE: To evaluate the risk and efficacy of pulmonary lobectomy in dogs with pneumonia. DESIGN: Retrospective study. ANIMALS: 59 dogs with pneumonia. PROCEDURE: Review of medical records and telephone conversations. RESULTS: 54.2% of dogs had resolution of pneumonia after lobectomy, 20.3% died in the perioperative period, and 25.4% survived the perioperative period but pneumonia did not resolve. Pneumonia was caused by bacteria (25 dogs), fungi (12), foreign bodies (8), parasites (1), viruses (1), and allergies (1). In 11 dogs, the etiologic agent was not isolated. Bacterial or fungal pneumonias were significantly less likely to resolve compared with foreign body pneumonia or when an etiologic agent was not isolated. Perioperative mortality rate increased significantly with an increase in number of pulmonary lobes removed. Complications during surgery significantly increased perioperative mortality rate. Surgical era (1972 to 1983 vs 1984 to 1994) was a significant predictor of mortality, with the odds of dying in the perioperative period being 11 times greater between 1972 to 1983. The odds of failure to resolve pneumonia was 3 times greater during 1972 to 1983. CLINICAL IMPLICATIONS: Number of pulmonary lobes removed and complications during surgery significantly affect perioperative mortality rate. Identification of etiologic agents may help in predicting dogs likely to resolve pneumonia after surgery.     

Pneumomediastinum and subcutaneous emphysema associated with fatal interstitial pneumonia in dermatomyositis

We described a 65-year-old woman who died of acute interstitial pneumonia associated with dermatomyositis. Subcutaneous emphysema and pneumomediastinum simultaneously developed. The association of the pulmonary rupture with vasculitis has been assumed as the common cause in interstitial pneumonia. Diffuse alveolar damage, however, might have led to the pneumomediastinum and subcutaneous emphysema in our patient, who had no signs of cutaneous vasculitis.     

Deposition and retention of radiolabeled serum constituents in hair after systemic administration

We investigated the relationship between the changes in the pulmonary blood flow and histology during acute rejection following single lung transplantation. In single lung transplantation using adult mongrel dogs, immunosuppression with cyclosporine and azathioprine was discontinued after postoperative day 14 to induce rejection. Doppler flow probes were placed adjacent to the ascending aorta and the left pulmonary artery to measure the blood flow on a daily basis. In addition, chest roentgenograms were also examined daily. The pulmonary pressure was measured using a Swan-Ganz catheter prior to and following the induction of rejection. Open lung biopsies were performed when the left pulmonary artery flow decreased to half of the prerejection value. The pulmonary artery flow decreased to 14.3% of the aortic flow 5 days after the discontinuation of immunosuppression. The graft pulmonary vascular resistance increased significantly compared to the prerejection values (P < 0.001). This was not accompanied by any abnormalities on chest roentgenography. The histology was consistent, with marked perivascular lymphocytic infiltration with little alveolar or interstitial changes. During rejection, the increased pulmonary vascular resistance in the graft was probably the result of perivascular inflammatory cell infiltration, which was seen prior to changes on chest roentgenography. Changes in the left pulmonary artery flow and histology thus appear to be closely correlated in the early stages of acute rejection.     

Low-dose methotrexate may cause air trapping in patients with rheumatoid arthritis

Both rheumatoid arthritis (RA) and methotrexate (MTX) are reported to be associated with the development of pulmonary disease. To determine whether MTX enhanced the risk of developing abnormalities in pulmonary function in patients with RA, we prospectively studied 31 subjects (12 male, 19 female) with the diagnosis of classic RA for an average period of 4.4 yr (range, 1 to 5 yr). Each subject was placed on low-dose weekly MTX (mean 17 mg, range 2.5 to 40) for control of RA symptoms. Other medications included non-steroidal anti-inflammatory agents and prednisone if required for control of arthritis symptoms. No other immunosuppressive therapy was used. Each subject was evaluated by pulmonary function tests (PFT) and chest X-ray initially, and at 1, 2, 3.5, and 5 yr. Chest X-rays obtained initially and at the end of the study period were found to be normal. The percent predicted values for initial PFTs in the study group were within the normal range. From the beginning to the end of the observation period, the following mean changes in lung function were observed: 1.9% increase in TLC, 5.1% increase in residual volume (RV), 1.8% increase in FVC, 0.71% decrease in FEV1, 14.7% improvement in alveolar-arterial oxygen (A-aO2) difference, and a 12.7% increase in single-breath diffusing capacity (DLCO). To determine whether MTX (average dose, weekly dose, or cumulative dose) was significantly related to changes in pulmonary function, we used multivariate techniques to control for the initial measure of lung function while assessing the relationship between MTX and the subsequent measures of lung function.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of multiple muscular abscesses of the lower limbs by Staphylococcus aureus after chemotherapy for lung cancer

A 67-year-old male was admitted to our hospital because of lung cancer and interstitial pneumonia. Cisplatin, vindesie and mitomycin C were administered for treatment of lung cancer. The leucocyte-counts declined to 1700/microliter on the eighth day after the chemotherapy. Though granulocyte colony-stimulating factor was administered, pain in the right thigh and high grade fever developed. Because Staphylococcus aureus was isolated from the blood specimen, piperacillin was administered. But the high grade fever continued and the pain was expanded to the right hip, left hip, thigh and leg. Because a computed tomograph of the lower limbs showed low density areas in bilateral gluteus maximus muscle right adductor magnus muscle, left biceps femoris muscle and left soleus muscle and the culture of an aspirate from abscess of right leg detected S. aureus, multiple muscular abscesses of the lower limbs was confirmed. We changed the antibiotics from PIPC to imipenem/cilastatin and minocycline on nineteenth day after the chemotherapy. His symptoms improved after the change of antibacterial agents. But he died of acute exacerbation of interstitial pneumonia, after about two months of the chemotherapy. Muscular abscesses of the limbs are very rare in Japan. Only four cases with muscular abscess of the limbs were reported in Japan, since 1988. This case suggests that a muscular abscess must be considered in the differential diagnosis of fever in patients with neutropenia.     

Gastroenterological surgery for patients with chronic respiratory insufficiency

BACKGROUND/AIMS: The aim of this study was to clarify the surgical indications for patients with chronic respiratory insufficiency. METHODOLOGY: Fourteen patients with chronic respiratory insufficiency who underwent abdominal surgical procedures, were retrospectively studied. The surgical indications were carefully determined based primarily on the performance status (PS) of each patient and cardiopulmonary function tests. A PS of equal to or less than 3, which meant the patient's status required bed rest > 50% of the time, and the need for assistance in performing normal activities were all factors considered for surgical indications. RESULTS: During the period studied, two patients were excluded from the surgical indications due to the fact that one was at a terminal stage of pulmonary disease and was completely bedridden (PS = 4), while the other demonstrated active pneumonia with a considerable amount of purulent sputa. Regarding the pulmonary function tests for patients who underwent surgery, the lowest limits of those examinations were as follows: 810 ml of vital capacity (VC), 23.8% of predicted VC, 610 ml of forced expiratory volume in one second (FEV1.0), 38.6% of predicted FEV1.0, 50.5 mmHg of PaO2 while inhaling 4 liters of oxygen and 73.8 mmHg of PaCO2. No surgery related mortality or hospital death within 30 days after operation was observed. Only two patients had cardiopulmonary complications (consisting of pulmonary edema with atrial fibrillation in one patient, and acute myocardial infarction in another patient). However, neither pneumonia, prolonged ventilatory support for more than 2 days, nor the need for a tracheostomy after surgery was observed. CONCLUSIONS: Gastroenterological surgery is thus considered to be indicated even for patients with chronic respiratory insufficiency, as long as the PS can be maintained (PS of equal to or less than 3) and no active pneumonia with a considerable amount of purulent sputa is present.     

The amyloid beta protein induces oxidative damage of mitochondrial DNA

A 55-year-old man was admitted to our hospital with of hemoptysis, progression of anemia and renal failure in February, 1996. Idiopathic interstitial pneumonia had been diagnosed and he had been followed at a regional hospital since 1988. On the third day after admission, he suffered from sudden and massive hemoptysis. Goodpasture's syndrome was diagnosed because anti-GBM antibody was detected in serum. A high titer of MPO-ANCA was also recognized simultaneously. Steroid pulse therapy, immunosuppressive therapy, and plasmapheresis were begun, but he died on the 28th hospital day because of severe hypoxemia and multi-organ failure. Histological examination after autopsy revealed crescentic glomerulonephritis with linear deposition of IgG in the glomerular capillary wall, and interstitial pneumonia accompanied by massive alveolar hemorrhage. It was suggested that in this patient, not only anti-GBM antibody but also circulating MPO-ANCA might have participated in the progression of the crescentic glomerulonephritis and alveolar hemorrhage observed in Goodpasture's syndrome.     

Idiopathic pulmonary fibrosis: current concepts

Idiopathic pulmonary fibrosis (IPF) is generally defined as a progressive, fibrosing inflammatory disease of the lung parenchyma of unknown cause. It is characterized by slowly increasing dyspnea, diffuse interstitial lung infiltrates, restrictive lung dysfunction, and impaired gas exchange. Ultimately, it is fatal in most patients, and treatment options remain unsatisfactory. The advent of high-resolution computed tomography of the chest and modifications in the histopathologic classification of interstitial pneumonias have reshaped the concept of IPF. Although initially thought to be a relatively specific clinicopathologic entity, it seems likely that IPF as previously defined is a heterogeneous disorder consisting of several clinicopathologic entities with differing histopathologic patterns, clinical course, response to therapy, and prognosis. The most common histologic pattern in cases previously defined as IPF is usual interstitial pneumonia, which is associated with a median survival of less than 3 years. For accurate prognosis and optimal management of patients, the clinician should attempt to be as precise as possible in distinguishing various clinicopathologic entities that have been included under the clinical heading of IPF. In the future, we recommend that the use of the term "idiopathic pulmonary fibrosis" be restricted to patients with usual interstitial pneumonia and that clinicians recognize the fact that other idiopathic interstitial pneumonias do not have the same prognostic effect traditionally ascribed to IPF.     

Delayed resolution of pneumonia. When is slow healing too slow?

Slowly resolving or nonresolving pneumonia is a clinical challenge, but we believe it can be dealt with in a rational and decisive manner. The following risk factors have been established for delayed radiographic resolution of pneumonia and should be considered in patient evaluation: Coexisting medical conditions History of smoking, Advanced age, Multilobar involvement, Persistent fever or leukocytosis. Diabetes, chronic obstructive pulmonary disease, renal failure, and alcohol abuse can impair immune function, which slows normal clearing of infiltrates. Common and uncommon infectious agents, conditions that mimic pneumonia (eg, a neoplasm, congestive heart failure), and pulmonary complications (eg, abscess) can also result in delayed resolution.     

Establishment of an animal model for pulmonary fibrosis in mice using monocrotaline

A preliminary attempt at experimental induction of pulmonary fibrosis in which male ICR mice received 15 weekly sc injections of 200 or 100 mg/kg monocrotaline (MC) revealed that most animals treated with the larger dose died of severe interstitial pneumonia, whereas those given 100 mg/kg exhibited only relatively slight lung injury. Based on these results, male mice were administered sc injections of 200 and 100 mg/kg MC once a week for 9 and 18 times, respectively, and then maintained without any further treatment until week 28 after the start. Mice treated with 200 mg/kg MC showed severe pulmonary damage and died by week 25. Mortalities also occurred in the 100-mg group from week 16, with 11 of 40 animals surviving at the termination of the experiment. Histologically, both dose groups demonstrated severe interstitial pneumonia and/or pulmonary fibrosis. Ultrastructurally, inflammatory edema possibly attributable to injuries of alveolar capillary endothelial cells was observed in the high-dose group at week 8, and there was a remarkable increase in collagen fibers in alveolar septa in this group thereafter. The present study results suggest that lung injuries induced by MC treatment progress to irreversible lung fibrosis and that this animal model may have advantage for studying the pathogenesis of lung cancers in patients with pulmonary fibrosis.