Dean Chamberlain

Lymphocytic airway infiltration as a precursor to fibrous obliteration in a rat model of bronchiolitis obliterans.

BACKGROUND Bronchiolitis obliterans is the most significant complication adversely affecting prolonged survival of lung allograft recipients. The evolution from the initial insult to the final pathologic entity is largely unknown. The aim of this study was to characterize the evolution of transplant-induced fibrous airway obliteration in a rat tracheal transplant model of bronchiolitis obliterans. METHODS Tracheal segments were transplanted from Brown Norway rats to Brown Norway rats (isografts) or to Lewis rats (allografts). Grafts were implanted into a subcutaneous pouch and an abdominal omental wrap. They were harvested at 14 different time points (from 1 day to 1 year after transplantation) and assessed histologically. RESULTS The fibrous airway obliteration developed only in allografts showing a triphasic time course: an initial ischemic phase (observed in both isografts and allografts) was followed by a marked lymphocytic infiltrative phase with complete epithelial loss (observed only in allografts, P<0.01), and finally by an obliterative phase with fibrous obliteration of the allograft airway lumen (P<0.01). CONCLUSIONS This animal model shows a distinct and reproducible triphasic time course in the development of obliterative airway lesions in allografts. It confirms that the mechanism leading to airway obliteration is immune mediated as only allografts showed this lesion and that lymphocytic infiltration is a precursor of the lesion in this model. The insights into the different phases demonstrated may lead to novel approaches regarding the type and timing of therapeutic interventions.

Isoxsuprine-induced release of pulmonary surfactant in the rabbit fetus☆

Rabbit fetuses were injected intramuscularly with 0.5 mg. of isoxsuprine on the twenty-eighth day of gestation. They were killed in utero four hours after the injection, and fetal pulmonary fluid (FPF) was collected through a tracheal catheter. The quantity of FPF and the lung weight/body weight ratio were both significantly less in the isoxsuprine-treated fetuses than in control fetuses. Surface activity, evaluated with pulsating bubble, and the lecithin/sphingomyelin (L/S) ratio were greater in FPF from isoxsuprine-treated animals than in control samples. We concluded that isoxsuprine is able to dehydrate the fetal lung and cause a release of surfactant stored in type II pneumocytes. This latter conclusion was supported by a significant decrease in the number of lamellar inclusions observed in these cells.

Role of basic fibroblast growth factor in revascularization of rabbit tracheal autografts

Despite omentopexy of the bronchial anastomosis, donor airway ischemia remains a problem after lung transplantation. This study examined the hypothesis that surface abrasion and topical application of basic fibroblast growth factor (bFGF) would enhance omental revascularization of trachea in a rabbit heterotopic autograft model. Tracheal segments were excised, primary tracheal anastomoses performed, and the segments placed in the peritoneal cavity wrapped in omentum. Animals were randomized to one of six groups according to tracheal segment treatment: control, surgical abrasion, Surgicel wrap with topical bFGF, Surgicel wrap with bFGF vehicle, Gelfoam wrap with bFGF, and topical bFGF alone. One week later, animals were heparinized, perfused with Aquablak dye, and killed. Tracheal segments were excised and sectioned for light microscopic quantitative assessment of viability and dye perfusion. There was no significant improvement in viability or perfusion between abraded tracheal segments or segments treated with bFGF/Gelfoam or bFGF alone when compared with control segments. Airways wrapped in Surgicel had significantly greater ischemic injury compared with the control group, regardless of bFGF application. Neither surgical abrasion nor topical bFGF increased omental revascularization of transplanted tracheal segments after 7 days.

Mediastinal Parathyroid Cysts

BACKGROUND Mediastinal parathyroid cysts are a relatively rare clinical entity. The clinical presentation can be quite varied, although most are found incidentally during investigations for esophageal or respiratory symptoms. METHODS We present a review of the literature and describe two instructive cases showing specific clinical findings. The clinical presentation, radiologic and pathologic findings, and treatment of mediastinal parathyroid cysts are discussed. RESULTS In the first patient, the presenting symptom was increasing hoarseness resulting from paresis of the right recurrent laryngeal nerve. This case illustrates the rare association of a benign mediastinal parathyroid cyst with unilateral vocal cord palsy. The second patient presented with the more classic findings of progressive dyspnea and stridor related to tracheal compression. CONCLUSIONS Although mediastinal parathyroid cysts are rare and can have varied presentations, thorough investigation can reveal the underlying cyst. Surgical excision is the treatment of choice and can be expected to produce excellent results.

Cystic change (Pseudocavitation) associated with bronchioloalveolar carcinoma : a report of four patients

Cavitation in bronchioloalveolar carcinoma is uncommon, but apparent radiologic cavitation may be produced by other causes of abnormal air collections in and around the tumor. We report four patients whose plain films and computed tomography scans were interpreted as showing cavitary masses. Paracicatricial emphysema, fibrosis with honeycombing, and localized bronchiectasis were present pathologically to explain the abnormal air collections.

Isoxsuprine Infusion to the Pregnant Rabbit and Its Effect on Fetal Lung Surfactant

Rabbit does, pregnant on the 28th day, were infused with isoxsuprine 2.5 mg/kg body weight/h in 50 ml 5% glucose, or with glucose only. The isoxsuprine caused maternal heart rate to increase and blood pressure, mean and diastolic, to decrease. The volume of fetal pulmonary fluid (FPF) and the wet lung weight/body weight ratio were significantly lowered by isoxsuprine. Lecithin/sphingomyelin ratio of FPF in isoxsuprine-infused animals was higher, compared with controls, not infused. Minimal surface tension of FPF, evaluated with pulsating bubble, was significantly lower in treated fetuses. Histologic examination of the fetal lungs after fixation with potassium dichromate and mercuric chloride showed that in isoxsuprine-treated litters FPF contained more granular and sudanophilic material. The results offer further evidence that isoxsuprine causes dehydration of fetal lungs and a release of pulmonary surfactant.

Role of open lung biopsy for diagnosis in lung transplant recipients: ten-year experience.

Between November 1983 and August 1993, The Toronto Lung Transplant Program performed 153 transplantations in 144 recipients: 53 single-lung transplantations (SLT) and 100 double-lung transplantations (DLT). Thirty-eight open lung biopsies (OLBs) were done in 32 (22% of all recipients): 19 in SLT (36% of SLT) 12 in DLT (12% of DLT), and 1 in a patient who had a SLT and then a double retransplantation. Six recipients underwent OLB twice: 1 DLT, 3 SLT, and 2 who had OLB both before and after retransplantation. Indication for 11 early OLBs (< or = 45 days postoperative) was persistent parenchymal infiltrates. Indications for 27 late OLBs (> 45 days postoperative) included progressive radiologic disease with clinical findings or progressive loss of pulmonary function (18), persistent poor graft function (3), mass or nodules (3), persistent infiltrates without functional loss (2), and persistent lymphocytosis in bronchoalveolar lavage (1). Open lung biopsy confirmed a previous clinical or pathologic diagnosis in 11, suggested a diagnosis in 2, yielded nonspecific information in 16, and provided different diagnosis in 9. New diagnosis that changed therapy was made in 1 of 11 early OLBs and in 8 of 27 late OLBs. These 9 diagnoses included in SLTs: bronchiolitis obliterans (2), bronchiolitis obliterans organizing pneumonia (1), malignant lymphoma (1), and chronic vascular rejection (1) in SLT, and bronchiolitis obliterans organizing pneumonia (3) and Burkholderia cepacia infection (1) in DLT. We conclude that OLB is of little value in the perioperative period but yields useful information in approximately 30% of patients when performed late.

Precocious emphysema in intravenous drug abusers

It is becoming increasingly clear that obstructive airway disease and early emphysema occur in some drug addicts who intravenously abuse drugs intended for oral use. We report four patients with such a history who had clinical, pathophysiologic, and radiologic evidence of severe obstructive airway disease with hyperinflation. Three patients had bullae. All had radio-logic changes of intravenous talc granulomatosis. One patient had moderately severe emphysema at autopsy. The pathogenesis of this disease is uncertain but may involve synergism with cigarette smoke, direct toxic effects of the drug, or induced intravascular leukocyte sequestration causing proteolytic pulmonary injury.

Bronchioloalveolar carcinoma and the air bronchogram sign: a new pathologic explanation.

Bronchioloalveolar carcinoma (BAG) is one of the few lung tumors known to demonstrate the air bronchogram sign. Production of this valuable radiologic sign by this tumor has been ascribed to an “alveolar” filling process in which tumor grows along alveolar walls with preservation of the architecture and secretes copious amounts of mucus. Thus, aerated bronchi are surrounded by alveoli that are filled with mucus and tumor. We present a case in which the air bronchogram sign and pulmonary consolidation are associated with a non-secretory BAG. Alternative mechanisms that may produce the air bronchogram sign in BAG are offered.

Wegener Granulomatosis Presenting on CT with Atypical Bronchovasocentric Distribution

AbstractWe report a patient with Wegener granulomatosis who presented with nonspecific pulmonary infiltrates on routine chest radiographs, but who showed a “bronchovasocentric” distribution on CT.