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Biomedical subjects

L J Wesselius

Publications and source records attributed to L J Wesselius.

35 records · Page 2Linked to original sources

Release of interleukin-1 by human alveolar macrophages after in vitro irradiation.

Therapeutic thoracic irradiation may induce two late pulmonary injury syndromes: radiation pneumonitis and subsequent pulmonary fibrosis. The alveolar macrophage has been considered a radioresistant cell and not a target cell involved in the pathogenesis of either type of radiation-induced lung injury. Alveolar macrophage-derived cytokines, including interleukin-1 (IL-1) and tumor necrosis factor (TNF), have been demonstrated to participate in inflammatory and fibrotic responses in the lung after various other types of lung injury. To evaluate whether the release of cytokines by alveolar macrophages is induced by radiation doses used clinically, alveolar macrophages recovered from nonsmoking volunteers were exposed in vitro to a single dose of 2 Gy and then maintained in culture for 18 h. Culture supernatants and cell lysates were then recovered and analyzed for IL-1 alpha and IL-1 beta by radioimmunoassay. Supernatants of irradiated alveolar macrophages contained significantly increased amounts of IL-1 alpha (P < 0.04) and IL-1 beta (P < 0.02) as well as total IL-1 (IL-1 alpha and IL-1 beta) (P < 0.02) compared to nonirradiated alveolar macrophages. Cell lysates of irradiated alveolar macrophages also contained increased amounts of IL-1 alpha and IL-1 beta, although differences from controls were not significant. The finding of increased release of IL-1 by alveolar macrophages after exposure to a single, clinically relevant dose of radiation suggests that the function of human alveolar macrophages is likely altered during therapeutic use of thoracic irradiation. Whether this release of IL-1 by alveolar macrophages contributes to early lung inflammation induced by thoracic irradiation is unclear.

Adult↗

Pulmonary mucinous cystic tumor. Case report with review of the literature.

Mucinous cystic tumors of the lung are exceedingly rare. We describe the case of a 59-year-old white man with a left upper lobe mass documented on chest radiographs 11 years before thoracotomy. Grossly, the lobectomy specimen contained a 4.5 x 4.5 x 4.0 cm cystic gelatinous mass with complete occlusion of the anterior segmental bronchus by mucinous material. Although microscopically this pulmonary mucinous cystic tumor contained a focus of marked glandular atypia consistent with adenocarcinoma, the patient has remained free of recurrence or metastasis during 5 years of close postoperative follow-up. Pulmonary mucinous cystic tumors appear to have a remarkably favorable prognosis and should be distinguished from other common lung neoplasms.

Cysts↗

Alveolar macrophage content of isoferritins and transferrin. Comparison of nonsmokers and smokers with and without chronic airflow obstruction.

Alveolar macrophages (AM) contain iron and ferritin, and concentrations of both are increased in AM of smokers compared with nonsmokers. Ferritin stores iron in a nontoxic form but can release iron in the presence of reducing agents and thereby catalyze the generation of toxic hydroxyl radicals via the Haber-Weiss reaction. Two distinct isoferritins are found in peripheral monocytes, L ferritin and H ferritin. H ferritin is the predominant isoferritin in human monocytes and is more effective than L ferritin in detoxifying iron in vitro. In this study we quantitated content of H and L ferritins, transferrin, and iron in AM recovered by bronchoalveolar lavage (BAL) of 24 subjects, including eight nonsmokers, eight smokers with normal spirometry, and eight smokers with chronic airflow obstruction (CAO). Of total AM ferritin in nonsmokers 95% was composed of L ferritin. Smokers without CAO demonstrated a 6.5-fold increase in the AM content of L ferritin (1,886 +/- 266 versus 290 +/- 51 ng, mean +/- SEM; p less than 0.0001) and a 3.8-fold increase in H ferritin (61 +/- 18 versus 16 +/- 2 ng per 1 x 10(6) AM, p less than 0.01) compared with nonsmokers. Compared with smokers without CAO, AM recovered from smokers with CAO demonstrated a greater increase in L ferritin (5,059 +/- 493 versus 1,886 +/- 266 ng per 1 x 10(6) AM, p less than 0.002) but a similar increase in H ferritin (64 +/- 8 versus 61 +/- 18 per 1 x 10(6) AM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pulmonary complications of cancer therapy.

Significant improvements in the result of cancer treatment have resulted in longer survival for many of these patients and increasing numbers of patients who are cured. Unfortunately, the toxic effect of cancer therapy on other organs, and particularly the lung, has become an increasingly recognized problem in these patients. There are no specific tests that are diagnostic for chemotherapy or radiation-induced lung injury so the clinician must keep this diagnosis in mind and attempt to evaluate other possibilities. If treatment induced lung injury is considered likely, whether radiation pneumonitis or drug-induced pneumonitis, corticosteroid therapy may be of benefit. Therapy should be initiated at high doses and then tapered slowly following the clinical response. Most of these patients will do well, however, pulmonary toxicity may lead to respiratory impairment or mortality in some patients. Hopefully, as we gain more understanding of the risk factors and mechanisms of treatment-induced lung toxicity, new methods will be developed to decrease lung impairment due to cancer treatment.

Antineoplastic Agents↗

Airway carcinoembryonic antigen concentrations in patients with central lung cancer or chronic bronchitis.

To determine the clinical utility of airway carcinoembryonic antigen (CEA) concentrations to distinguish malignant from inflammatory airway disease in patients undergoing bronchoscopy, we determined CEA concentrations by enzyme immunoassay in bronchial washings recovered in 48 subjects, including 20 patients with central lung cancer, 18 patients with chronic bronchitis, and ten nonsmoking patients with a diagnosis of pneumonia or peripheral granuloma. Concentrations of CEA in bronchial washings were standardized by using the total protein concentration in recovered fluid (CEA/TP). Concentrations of CEA were significantly increased in bronchial washings recovered from both patients with chronic bronchitis and lung cancer compared with patients with pneumonia or granuloma (252 +/- 47 ng/mg and 199 +/- 64 ng/ml vs 62 +/- 11 ng/mg, SEM, p less than 0.005). Airway CEA concentrations in patients with chronic bronchitis were somewhat increased compared with concentrations recovered from a cancer-involved airway (252 +/- 47 ng/ml vs 199 +/- 64 ng/mg, SEM, p less than 0.05). Measurement of airway CEA concentrations is not useful in distinguishing malignant from inflammatory airway disease as airway concentrations of CEA may be markedly increased in patients with both conditions.

Bronchitis↗

Arterial oxygen desaturation during gastrointestinal endoscopy.

This prospective study evaluated the incidence and severity of arterial oxygen desaturation during gastrointestinal endoscopy. Following pulmonary function testing, 115 male patients underwent esophagogastroduodenoscopy (EGD), colonoscopy, or colonoscopy followed by EGD, with continuous recording of arterial oxygen saturation (SaO2). Most patients (80/115, 70%) showed arterial oxygen desaturation (greater than 4% decrease from baseline SaO2); severe arterial oxygen desaturation (SaO2 less than or equal to 85%) reflecting hypoxemia (PaO2 less than or equal to 50 mm Hg) was noted in one-third of patients overall (37/115, 32%). Severe arterial oxygen desaturation occurred in 9/62 EGD patients (15%), 23/46 colonoscopy patients (50%), and 4/7 patients having colonoscopy followed by EGD (57%). Arterial oxygen desaturation occurs frequently during gastrointestinal endoscopy and is often severe. These data support the concept that continuous monitoring of SaO2 should be standard procedure during all gastrointestinal endoscopic procedures.

Age Factors↗

Alveolar macrophage proliferation in situ after thoracic irradiation of rats.

Saline lavage was performed on rat lungs at weekly intervals for as long as 6 wk after thoracic irradiation (24 Gy). The number of alveolar macrophages recovered by lavage was significantly increased compared with that in control animals beginning at 4 wk after irradiation (p less than 0.05). Autoradiographic analysis of macrophages recovered demonstrated an increased labeling index compared with that in control animals beginning 3 wk after irradiation (p less than 0.05). Macrophage proliferation in vivo was also assessed by injecting rats with vincristine and evaluating macrophages recovered by lung lavage for arrested mitoses. The number of arrested mitoses noted was significantly increased in rats at 4 wk after irradiation compared with that in control animals (p less than 0.05). These data indicate that after high dose thoracic irradiation there is an expansion of the alveolar macrophage population that is due at least in part to increased local proliferation of alveolar macrophages.

Animals↗

Airway secretory IgA concentrations in patients with lung cancer. Evaluation of the uninvolved lung.

To determine whether concentrations of the primary airway immunoglobulins (SIgA, IgG) are altered in the uninvolved lung of patients with lung cancer, we determined concentrations of SIgA and IgG in bronchial washings recovered from a proximal airway of the uninvolved lung in 24 patients with lung cancer and in ten patients with benign lung disease. When standardized for the amount of total protein recovered (SIgA/TP, IgG/TP), bronchial washings recovered from the uninvolved lung of lung cancer patients demonstrated a significantly decreased SIgA/TP ratio compared to control subjects (.14 +/- .02 vs .31 +/- .05, SEM, p less than 0.05). There were no differences in the IgG/TP ratios. Lung cancer patients with a decreased serum albumin (less than 3.2 g/dl) had a significantly decreased SIgA/TP ratio in bronchial washings compared to patients with a higher serum albumin (.08 +/- .03 vs .18 +/- .04, SEM, p less than 0.05). The decreased relative concentration of airway SIgA in lung cancer patients may adversely affect airway defenses against bacterial colonization.

Bronchi↗

Effect of corticosteroid treatment on cell recovery by lung lavage in acute radiation-induced lung injury.

The purpose of this study was to quantitate cell populations recovered by lung lavage up to 6 weeks following thoracic irradiation (24 Gy) as an index of the acute inflammatory response within lung structures. Additionally, rats were treated five times weekly with intraperitoneal saline (0.3 cc) or methylprednisolone (7.5 mg/kg/week). Lung lavage of irradiated rats recovered increased numbers of total cells compared to controls beginning 3 weeks after irradiation (P less than 0.05). The initial increase in number of cells recovered was attributable to an influx of neutrophils (P less than 0.05), and further increases at 4 and 6 weeks were associated with increased numbers of recovered macrophages (P less than 0.05). Lung lavage of steroid-treated rats at 6 weeks after irradiation recovered increased numbers of all cell populations compared to controls (P less than 0.05); however, numbers of recovered total cells, macrophages, neutrophils, and lymphocytes were all significantly decreased compared to saline-treated rats (P less than 0.05). The number of inflammatory cells recovered by lung lavage during acute radiation-induced lung injury is significantly diminished by corticosteroid treatment. Changes in cells recovered by lung lavage can also be correlated with alteration in body weight and respiration rate subsequent to treatment with thoracic irradiation and/or corticosteroids.

Animals↗

Effect of bronchial brush size on cell recovery.

The effect of bronchial brush size on cell recovery during fiberoptic bronchoscopy was investigated. In 20 patients undergoing diagnostic bronchoscopy, 3 additional brushings in normal peripheral airways were performed using sheathed brushes of 1.0, 1.73, and 3.0 mm in diameter. Mean cell recovery was 5.7, 8.1, and 9.0 x 10(4) cells per brush, respectively. There were no significant differences in cell recovery between the 3 brushes. Brush size does not appear to significantly influence cell recovery in normal peripheral airways.

Bronchi↗

Lymphocyte subsets in lung cancer.

Altered cellular immune function has been demonstrated in patients with lung cancer, including decreased numbers of circulating lymphocytes and changes in the percentage of lymphocytes in various functional subsets. We quantitated lymphocyte subsets in 54 patients with lung cancer including patients with limited (stages 1 and 2) nonsmall cell lung cancer (NSCLC, n = 23), advanced (stage 3) NSCLC (n = 16), and small cell cancer (SCLC, n = 15). Serum albumin was decreased in 15 lung cancer patients, and lymphocyte subsets were separately evaluated in these patients. Lymphocyte populations in cancer patients were compared to those of nonsmokers and a smoking patient population. No difference from smokers was noted in patients with limited NSCLC. Patients with SCLC and advanced NSCLC had significantly decreased numbers of T-helper and T-suppressor cells (p less than 0.05). Patients with lung cancer and hypoalbuminemia had the greatest decrease in number of circulating T-helper cells (p less than 0.001). B-lymphocytes were also decreased in patients with advanced NSCLC and patients with hypoalbuminemia (p less than 0.05). A decrease in population of T-lymphocytes subsets is frequent in patients with SCLC, advanced NSCLC, and lung cancer patients with hypoalbuminemia.

Adolescent↗

Neutrophil chemotactic activity generation by alveolar macrophages after bleomycin injury.

Saline lavage was performed on rat lungs after the intratracheal injection of saline or bleomycin. An increase (p less than 0.025) in total cells recovered, an increase (p less than 0.001) in neutrophils, and an increase (p less than 0.001) in albumin concentration were noted in lavage fluid recovered from rats subsequent to bleomycin injury. At 5, 10, 15, and 20 days after injury, macrophages recovered from bleomycin-treated rats generated increased (p less than 0.05) amounts of neutrophil chemotactic activity in vitro compared with macrophages recovered from saline-treated rats. The chemotactic activity was attributable to a factor or factors of low molecular weight and hydrophobic in nature, characteristics similar to previously described alveolar macrophage-derived neutrophil chemotactic factors. The generation of neutrophil chemotactic activity was suppressed (p less than 0.025) by hydrocortisone and 5,8,11,14-eicosatetraynoic acid (ETYA), suggesting that the neutrophil chemotactic activity generation is dependent upon the lipoxygenase pathway of arachidonic acid metabolism.

5,8,11,14-Eicosatetraynoic Acid↗

Advances in interstitial lung disorders.

Interstitial lung disorders are a heterogeneous group of diseases that result in a similar clinical presentation and have similar physiologic consequences on lung function. Our current understanding of these disorders indicates that there is an inflammatory component of these diseases that is reversible and that precedes the development of interstitial pulmonary fibrosis, which is irreversible. Although conclusive clinical studies are still lacking, treatment of pulmonary disease in these patients is based on the concept that treatment of the inflammatory component of the disease with immunosuppressive agents will prevent or reduce the amount of pulmonary fibrosis that develops. Because of the significant side effects associated with immunosuppressive drugs, therapy should be used only when there is likely to be therapeutic benefit. The use of immunosuppressive agents is, therefore, indicated in selected groups of patients. If there is a known precipitating agent for the interstitial disorder, such as asbestos exposure, the primary therapy is to avoid further exposure to the agent. Sarcoidosis is one of the most common systemic disorders associated with interstitial lung disease, and in this disease, corticosteroids clearly are of benefit. In pulmonary sarcoidosis, patients who are symptomatic or patients who demonstrate progressive clinical deterioration of pulmonary function should be treated. Recent studies also suggest that patients with a high degree of pulmonary inflammation as demonstrated by a positive gallium scan and a high percentage (greater than 28%) of lymphocytes obtained on lung lavage may also benefit from corticosteroid therapy. Idiopathic pulmonary fibrosis is a progressive disease and is usually symptomatic at the time of presentation, so it is reasonable to give all patients a therapeutic trial with corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Asbestosis↗

Effect of location, pH, and temperature of instillate in bronchoalveolar lavage in normal volunteers.

Bronchoalveolar lavage has not been subjected to careful standardization. We examined the variables of lung lavage location and lavage fluid composition (pH and temperature) upon the percent of fluid recovered, cell count and differential, protein and pH in normal subjects. In the first part of the study, random order lavages of the right middle lobe (RML), right lower lobe (RLL), left lingula, and left lower lobe (LLL) were performed with 100-ml aliquots of normal saline (pH, 5.5) at room temperature (25 degrees C). Percent fluid recovery was greater in the RML and lingula than in the RLL (p less than 0.05). Cell count, cell differential, and protein were similar between lobes. In the second part of the study, each lobe was lavaged with 50-ml aliquots: the RML with normal saline at 37 degrees C, the RLL with normal saline buffered to a pH of 7.0 at 37 degrees C, the left lingula with normal saline at 25 degrees C, and the LLL with normal saline buffered to a pH of 7.0 at 25 degrees C. Percent fluid recovery was greater in the RML than in the lingula and greater in both the RML and lingula than in the lower lobes (p less than 0.05). Total cell count was significantly higher in the RML than in the LLL (p less than 0.05). Cell count per milliliter and protein recovered were not different between any lobe lavaged. The pH of recovered fluid was greater with buffered saline. Complications of fever and chills occurred in almost 50% of subjects in both parts of the study. Lavage location can affect fluid recovery. Alteration of lavage fluid composition did not affect cell or protein recovery. We suggest lavage of the RML to ensure larger fluid recovery and the highest total cell count.

Adult↗

Computer-assisted versus visual lung gallium-67 index in normal subjects and in patients with interstitial lung disorders.

The pulmonary uptake of 87Ga citrate has been proposed as an index that assists clinical decision-making in patients with certain interstitial lung diseases. Such use, however, requires definition of the range of normal values, the range of values in patients with various interstitial diseases, and interobserver and intraobserver variability. We studied 9 normal subjects and 15 patients with interstitial lung diseases. The 87Ga indexes were determined by visual analysis and by a computer-assisted method. We found that the variation among experienced observers in visual index values was substantial in both normal subjects and patients, and that the computer-assisted indexes were less variable. These data suggest that if this approach is to be used in clinical decision-making: (1) the variability of visual indexes, and of normal values, should be recognized; (2) consideration should be given to a less subjective, computer-assisted method of index calculation; (3) each institution should establish standardized methodology and consider determination of its range of variability and normal index values.

Adult↗