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Biomedical subjects

Kevin K Brown

Publications and source records attributed to Kevin K Brown.

51 records · Page 3Linked to original sources
PubMed2003

Expression of human herpesvirus 8 in primary pulmonary hypertension.

BACKGROUND: Severe pulmonary hypertension constitutes a group of diseases characterized by complex, lumen-occluding vascular lesions that develop in genetically susceptible persons. The only viral infection associated with severe pulmonary hypertension has been that due to human immunodeficiency virus type 1, but neither the viral genome nor viral antigens have been demonstrated in pathologic lesions. METHODS: We examined lung-tissue samples from 16 patients with sporadic primary pulmonary hypertension and 14 patients with secondary pulmonary hypertension for evidence of infection with human herpesvirus 8 (HHV-8). HHV-8 infection was ascertained immunohistochemically with use of an antibody directed against latency-associated nuclear antigen 1 (LANA-1), and a polymerase-chain-reaction (PCR) assay was performed on lung DNA to detect the viral cyclin gene of HHV-8. Sequence analysis was also performed. RESULTS: In lung tissue from 10 of 16 patients with primary pulmonary hypertension (62 percent), cells within the plexiform lesions as well as cells outside the lesions were positive for LANA-1 on immunohistochemical analysis. Tissue from the same 10 patients contained viral cyclin on PCR analysis. No LANA-1 was detected in lung tissue from patients with secondary pulmonary hypertension, although one such patient had PCR evidence of viral cyclin. Plexiform lesions from patients with primary pulmonary hypertension had a histologic and immunohistochemical resemblance to cutaneous Kaposi's sarcoma lesions. CONCLUSIONS: The spectrum of trigger factors and molecular mechanisms leading to severe pulmonary hypertension and the formation of plexiform lesions is apparently wide, including both genetic and epigenetic factors. Our data suggest that infection with the vasculotropic virus HHV-8 may have a pathogenetic role in primary pulmonary hypertension.

Bone Morphogenetic Protein Receptors, Type II↗
PubMed2003

Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis.

There is significant heterogeneity in survival time among patients with idiopathic pulmonary fibrosis. Studies of baseline clinical and physiologic variables as predictors of survival time have reported inconsistent results. We evaluated the predictive value of changes in clinical and physiologic variables over time for survival time in 81 patients with biopsy-proven idiopathic pulmonary fibrosis. Six-month changes in dyspnea score, total lung capacity, thoracic gas volume, FVC, FEV1, diffusing capacity of carbon monoxide, partial pressure of arterial oxygen, oxygen saturation, and alveolar-arterial oxygen gradient were predictive of survival time even after adjustment for baseline values. Analyses were repeated on 51 patients with 12-month change data. Twelve-month changes in dyspnea score, total lung capacity, FVC, partial pressure of arterial oxygen, oxygen saturation, and alveolar-arterial oxygen gradient were predictive of survival time after adjustment for baseline values. Evaluation of changes in clinical and physiological variables over 6 and 12 months may provide clinicians with more accurate prognostic information than baseline values alone.

Aged↗
PubMed2003

Human pulmonary chimerism after hematopoietic stem cell transplantation.

Many of the body's tissues once thought to be only locally regenerative may, in fact, be actively replaced by circulating stem cells after hematopoietic stem cell transplantation. Localization of donor-derived cells ("chimerism") has recently been shown to occur in the lungs of mice after either hematopoietic stem cell transplantation or infusion of cultured marrow. To determine whether tissues of the human lung might be similarly derived from extrapulmonary sources, we examined lung specimens from a retrospective cohort of female allogeneic hematopoietic stem cell transplant recipients who received stem cells from male donors. Tissue samples from three such patients who had undergone diagnostic lung biopsy or autopsy were examined. Slides were stained by immunohistochemistry for cytokeratin (epithelium) and platelet endothelial cell adhesion molecule, CD31 (PECAM) (endothelium) and were imaged and then examined by fluorescent in situ hybridization analysis to identify male cells. The resulting overlapping in situ hybridization and immunohistochemistry images were examined for the presence and, if present, cell type of donor cells in the lung. We found significant rates of epithelial (2.5-8.0%) and endothelial (37.5-42.3%) chimerism. These results suggest that significant chimerism of the human lung may follow hematopoietic stem cell transplantation and that adult human stem cells could potentially play a therapeutic role in treatment of the damaged lung.

Adult↗
PubMed2002

Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: calreticulin and CD91 as a common collectin receptor complex.

Removal of cells dying by apoptosis is essential to normal development, maintenance of tissue homeostasis, and resolution of inflammation. Surfactant protein A (SP-A) and surfactant protein D (SP-D) are high abundance pulmonary collectins recently implicated in apoptotic cell clearance in vitro. Other collectins, such as mannose-binding lectin and the collectin-like C1q, have been shown to bind to apoptotic cells and drive ingestion through interaction with calreticulin and CD91 on the phagocyte in vitro. However, only C1q has been shown to enhance apoptotic cell uptake in vivo. We sought to determine the relative importance of SP-A, SP-D, and C1q in pulmonary clearance of apoptotic cells using knockout and overexpressing mice, and to determine the role of calreticulin and CD91 in this process. SP-A, SP-D, and C1q all enhanced apoptotic cell ingestion by resident murine and human alveolar macrophages in vitro. However, only SP-D altered apoptotic cell clearance from the naive murine lung, suggesting that SP-D plays a particularly important role in vivo. Similar to C1q and mannose-binding lectin, SP-A and SP-D bound to apoptotic cells in a localized, patchy pattern and drove apoptotic cell ingestion by phagocytes through a mechanism dependent on calreticulin and CD91. These results suggest that the entire collectin family of innate immune proteins (including C1q) works through a common receptor complex to enhance removal of apoptotic cells, and that collectins are integral, organ-specific components of the clearance machinery.

Animals↗
PubMed2002

Vasculitis: Wegener granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, polyarteritis nodosa, and Takayasu arteritis.

Identification, diagnosis, and management of the primary vasculitides and their attendant complications is a challenging task for the critical care physician. However, with appropriate therapy, the morbidity and mortality of these diseases can be markedly improved and allow the individual patient to return to their previous functional state.

Churg-Strauss Syndrome↗
PubMed2002

Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis.

Cystic fibrosis is characterized by an early and sustained influx of inflammatory cells into the airways and by release of proteases. Resolution of inflammation is normally associated with the orderly removal of dying apoptotic inflammatory cells through cell recognition receptors, such as the phosphatidylserine receptor, CD36, and alpha v integrins. Accordingly, removal of apoptotic inflammatory cells may be impaired in persistent inflammatory responses such as that seen in cystic fibrosis airways. Examination of sputa from cystic fibrosis and non-cystic fibrosis bronchiectasis patients demonstrated an abundance of apoptotic cells, in excess of that seen in patients with chronic bronchitis. In vitro, cystic fibrosis and bronchiectasis airway fluid directly inhibited apoptotic cell removal by alveolar macrophages in a neutrophil elastase-dependent manner, suggesting that elastase may impair apoptotic cell clearance in vivo. Flow cytometry demonstrated that neutrophil elastase cleaved the phosphatidylserine receptor, but not CD36 or CD32 (Fc gamma RII). Cleavage of the phosphatidylserine receptor by neutrophil elastase specifically disrupted phagocytosis of apoptotic cells, implying a potential mechanism for delayed apoptotic cell clearance in vivo. Therefore, defective airway clearance of apoptotic cells in cystic fibrosis and bronchiectasis may be due to elastase-mediated cleavage of phosphatidylserine receptor on phagocytes and may contribute to ongoing airway inflammation.

Adolescent↗
PubMedDate not supplied

Respiratory bronchiolitis-associated interstitial lung disease: radiologic features with clinical and pathologic correlation.

PURPOSE: The purpose of this work was to describe the radiographic and CT findings in patients with respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) and to correlate them with clinical, physiologic, and pathologic features. METHOD: RB-ILD was proved pathologically in all 21 patients. Sixteen (76%) patients were current smokers, and five (24%) patients were ex-smokers. The mean cigarette consumption was 38.7 pack-years. Chest radiographs and CT scans were semiquantitatively analyzed and correlated with clinical findings, physiologic measures, and a pathologic score of disease extent. RESULTS: The major radiographic findings were bronchial wall thickening in 16 patients (76%) and ground-glass opacity in 12 patients (57%). The predominant initial CT findings were central bronchial wall thickening (proximal to subsegmental bronchi) in 19 patients (90%), peripheral bronchial wall thickening (distal to subsegmental bronchi) in 18 patients (86%), centrilobular nodules in 15 patients (71%), and ground-glass opacity in 14 patients (67%), None of these CT findings had a significant zonal predominance. Other findings were upper lung predominant centrilobular emphysema (57%) and patchy areas of hypoattenuation (38%) with a lower lung predominance. Radiologic findings were similar in both current and ex-smokers. The amount of ground-glass opacity correlated inversely with arterial oxygen saturation ( r = -0.67, p = 0.04), and the areas of hypoattenuation correlated with alveolar-arterial oxygen gradient ( r = 0.56, p = 0.04). The extent of centrilobular nodules correlated with the extent of macrophages in respiratory bronchioles ( r = 0.53, p = 0.03) and with chronic inflammation of respiratory bronchioles ( r = 0.57, p = 0.02). The extent of ground-glass opacity correlated with the amount of macrophage accumulation in the alveoli and alveolar ducts ( r = 0.56, p < 0.01 and r = 0.54, p = 0.04, respectively). At follow-up CT after steroid treatment and smoking cessation, in nine patients, the extent of bronchial wall thickening, centrilobular nodules, and ground-glass opacity had decreased, but the areas of hypoattenuation had increased (p < 0.05). CONCLUSION: The CT findings of RB-ILD are centrilobular nodules, ground-glass opacity, and air trapping. These radiologic features, in patients with a history of heavy cigarette smoking, may differentiate RB-ILD from other interstitial lung diseases.

Adult↗
PubMedDate not supplied

Diffuse pulmonary neuroendocrine cell hyperplasia: radiologic and clinical features.

PURPOSE: The purpose of this study was to define the radiologic features of pulmonary neuroendocrine cell hyperplasia and correlate them with clinical findings. METHOD: Five women, ranging in age from 45 to 63 years, were diagnosed with pulmonary neuroendocrine cell hyperplasia. Two radiologists assessed the presence and extent of airway wall thickening, mosaic pattern, air trapping, ground-glass opacity, nodular opacity, and centrilobular opacity on high resolution CT. The CT findings were compared with physiologic data and histologic features. RESULTS: On CT scans, mosaic pattern was the predominant finding in all patients. The extent of mosaic pattern was correlated with the forced expiratory volume in 1 s/forced vital capacity ratio (r = 0.8508, p = 0.0317). Nodular lesions were noted in three patients. Airway walls were thickened in four patients. In one patient, ground-glass opacity and centrilobular opacity were also noted on high resolution CT. CONCLUSION: Pulmonary neuroendocrine cell hyperplasia is characterized by mosaic perfusion due to air trapping, airway wall thickening, and occasional small nodules on high resolution CT scans. The extent of mosaic perfusion correlates with physiologic evidence of airway obstruction.

Female↗
PubMedDate not supplied

Organizing pneumonia: prognostic implication of high-resolution computed tomography features.

PURPOSE: Most patients with biopsy-proven organizing pneumonia (OP) show complete resolution of radiographic lesions with treatment, but some patients do not respond to treatment and progress to pulmonary fibrosis. The authors investigated the prognostic implication of high-resolution computed tomography (CT) features in this condition. METHOD: We reviewed the high-resolution CT findings of 26 patients diagnosed with OP by histopathology, who had radiographic follow-up for a median of 44 weeks after treatment. We scored the presence and extent of each pretreatment high-resolution CT finding (ground-glass opacity, consolidation, nodules, reticular opacity, and honeycombing). The predominant pattern and distribution of the lesions were recorded. Follow-up radiographs were used to determine whether the parenchymal abnormalities had regressed or progressed in response to treatment. RESULTS: Of the 26 patients, 9 had persistent or progressive parenchymal abnormalities at follow-up (group 1), whereas 17 had complete or partial resolution of abnormalities (group 2). Consolidation was present on the initial CT scan in 14 (82%) of the 17 patients in group 2, but in only 2 of the 9 patients in group 1 (P = 0.009). None of the 6 patients who had reticular abnormality as the predominant pattern on initial CT showed complete resolution on follow-up imaging (P = 0.02). CONCLUSION: In patients with OP, the CT finding of consolidation is associated with partial or complete resolution, whereas reticular opacity is associated with persistent or progressive disease.

Aged↗
PubMedDate not supplied

Collagen vascular disease-related lung disease: high-resolution computed tomography findings based on the pathologic classification.

Collagen vascular disease (CVD) can cause a variety of lung abnormalities, including usual interstitial pneumonia, nonspecific interstitial pneumonia, organizing pneumonia, diffuse alveolar damage, lymphoid interstitial pneumonia, bronchiectasis, constrictive bronchiolitis, follicular bronchiolitis, alveolar hemorrhage, pulmonary hypertension, and drug-induced lung disease. The frequency of each lung disease is different among underlying CVDs. Although high-resolution computed tomography (HRCT) findings of lung disease are often nonspecific, there are some characteristic HRCT findings for some lung diseases based on pathologic findings.

Adult↗
PubMedDate not supplied

High-resolution computed tomography features of nonspecific interstitial pneumonia and usual interstitial pneumonia.

OBJECTIVE: To assess the accuracy of high-resolution computed tomography (HRCT) in the diagnosis of nonspecific interstitial pneumonia (NSIP). We hypothesized that the computed tomography (CT) features of NSIP could be distinguished from those of usual interstitial pneumonia (UIP). METHODS: The HRCT images of 47 patients with surgical lung biopsy-proven NSIP (n = 25) and UIP (n = 22) were independently reviewed by 2 thoracic radiologists. Predominant imaging patterns, most likely diagnosis, and diagnostic level of confidence were recorded. A confident HRCT diagnosis of NSIP was based on the presence of spatially uniform, bilateral, basal-predominant ground-glass and/or reticular opacities with little if any honeycombing, whereas UIP was confidently diagnosed if a spatially inhomogeneous, bilateral, peripheral, basal-predominant pattern of reticular opacities and honeycombing with little if any ground-glass attenuation was identified. RESULTS: A predominant pattern of ground-glass and/or reticular opacity with minimal to no honeycombing was demonstrated in 48 (96%) of 50 readings in patients with NSIP. Conversely, the presence of honeycombing as a predominant feature had a predictive value of 90% for UIP (P < 0.001). Usual interstitial pneumonia was more likely than NSIP to be subpleural and patchy (P < 0.001). A confident CT diagnosis of NSIP and UIP was correct in 73% and 88% of cases, respectively. The correctness of a CT diagnosis made at intermediate or high confidence was 68% and 88%, respectively. The kappa value for distinction of NSIP from UIP was 0.72. CONCLUSION: In contrast to previous reports, NSIP can be separated from UIP in most cases. The presence of honeycombing as a predominant imaging finding is highly specific for UIP and can be used to differentiate it from NSIP, particularly when the distribution is patchy and subpleural predominant. The presence of predominant ground-glass and reticular opacity is highly characteristic of NSIP, but there is a subset of patients with UIP who have this pattern and may require biopsy for differentiation from NSIP.

Adult↗
PubMedDate not supplied

Lung diseases in patients with common variable immunodeficiency: chest radiographic, and computed tomographic findings.

OBJECTIVE: To evaluate chest radiographic and computed tomographic (CT) findings of lung disease related to common variable immunodeficiency. METHODS: Thirty-five chest radiographs and 30 CT scans of 46 patients were assessed. Lung parenchymal abnormalities that were evaluated included airspace consolidation, ground-glass attenuation, nodules, bronchiectasis, and air trapping. RESULTS: On CT, ground-glass attenuation and nodules were the most frequent findings, observed in 60% (n = 18/30) and 83% (n = 25/30), respectively. Three major CT patterns were identified: airway disease (n = 13), nodules (n = 8), and parenchymal opacification (n = 6). All 13 patients with airway disease showed centrilobular opacities. One patient with peribronchial nodules showed lymphoid interstitial pneumonia, and 1 with randomly distributed nodules showed noncaseating granulomas. Patients with a CT pattern of parenchymal opacification showed lower lung predominance; surgical biopsies showed organizing pneumonia in 1 patient and lymphoid interstitial pneumonia with nonnecrotizing granulomas in another. CONCLUSIONS: Common variable immunodeficiency is associated with 3 major CT patterns: airway disease, nodules, and parenchymal opacification.

Adolescent↗