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Biomedical subjects

C Strange

Publications and source records attributed to C Strange.

At least 37 records · Page 2Linked to original sources
PubMed1995

Elevated levels of platelet derived growth factor and transforming growth factor-beta 1 in bronchoalveolar lavage fluid from patients with scleroderma.

OBJECTIVE: Systemic sclerosis (scleroderma, SSc) frequently affects the lungs, and interstitial pulmonary fibrosis is one of its major complications. The pathophysiology of SSc lung disease s poorly understood, but recent studies document an inflammatory process resembling that of idiopathic pulmonary fibrosis with increased numbers of activated alveolar macrophages and granulocytes in bronchoalveolar lavage (BAL) fluid). We determined levels of 2 potentially important mediators of fibroproliferative repair in BAL fluid from patients with SSc. METHODS: Using Western blot and ELISA techniques we measured levels of platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta in BAL fluid from patients with SSc and healthy controls. The mitogenic effect of these cytokines on SSc lung myofibroblasts was determined by [3H]thymidine incorporation. RESULTS: SSc BAL fluid contains significantly elevated levels of PDGF-AA and PDGF-BB. Where TGF-beta 1 was significantly elevated in SSc lavage fluid, the amount of TGF-beta 2 was significantly less than that observed in normal lavage fluid. Myofibroblasts cultured from SSc lavage fluid exhibited enhanced [3H]thymidine incorporation upon exposure to the growth factors present in SSc BAL fluid: PDGF and TGF-beta 1. SSc lung myofibroblasts pretreated with TGF-beta 1 exhibited an enhanced mitogenic effect upon stimulation by PDGF, due in part to the induction of the PDGF alpha receptor. CONCLUSION: Our studies support a role for PDGF and TGF-beta 1 in the pathogenesis of SSc lung disease.

Bronchoalveolar Lavage Fluid↗
PubMed1994

Scleroderma bronchoalveolar lavage fluid contains thrombin, a mediator of human lung fibroblast proliferation via induction of platelet-derived growth factor alpha-receptor.

In addition to its procoagulant properties, the serine protease thrombin increases endothelial permeability, stimulates granulocyte adherence, and serves as a fibroblast mitogen. We demonstrate that thrombin is mitogenic for human lung fibroblasts in vitro. The mitogenic effect of thrombin is associated with an increase in the expression of the ligand PDGF-AA and up-regulation of PDGF alpha-receptor. Since scleroderma (systemic sclerosis; SSc) is characterized by widespread microvascular injury and is frequently complicated by pulmonary fibrosis, we sought to determine the level of thrombin activity in bronchoalveolar lavage (BAL) fluid from SSc patients and normal controls. We report a significantly higher level of thrombin activity in BAL fluid from SSc patients compared with normal controls (P < 0.001). Taken together, the high levels of thrombin in BAL fluid and its demonstrated mitogenicity for lung fibroblasts suggest an important role for thrombin in the pathogenesis of SSc and perhaps other fibrotic lung diseases.

Adult↗
PubMed1994

Pleurodesis using talc slurry.

OBJECTIVE: To determine the efficacy and safety of talc slurry for pleurodesis. DESIGN: Retrospective. PARTICIPANTS: All patients who received talc slurry via tube thoracostomy at Memorial Sloan-Kettering Cancer Center from March 1991 to April 1992. RESULTS: Fifty-eight patients received talc slurry in 75 procedures; five patients had 2 unilateral procedures and 12 had bilateral procedures. Fifty-two patients had malignant pleural effusions with the most common cell types being breast (23 of 52, 44 percent), lung (4 of 52, 8 percent), ovarian (4 of 52, 8 percent), and endometrial (3 of 52, 6 percent). Four patients had benign conditions. The mean duration of follow-up was 171 days (range, 2 to 450 days). Success, defined as the absence of pleural fluid reaccumulation, was evaluable in 47 of 73 (64 percent) procedures. Pleurodesis was successful in 38 of 47 (81 percent). Adverse effects associated with pleurodesis included fever (46 of 73, 63 percent), empyema (4 of 73, 5 percent), atrial arrhythmia (3 of 73, 4 percent), hypotension (3 of 73, 4 percent), and hypoxemic respiratory failure (3 of 73, 4 percent). There were no deaths attributable to the procedure. CONCLUSIONS: Talc slurry instilled through a chest tube is an effective bedside method of pleurodesis. Fever occurs frequently. Respiratory failure is a rare but potentially serious complication that deserves further investigation.

Adult↗
PubMed1994

Granulomatous pneumonitis following intravesical BCG. What therapy is needed?

A 68-year-old man developed fever, cough, and dyspnea after intravesical bacillus Calmette-Guerin (BCG). Chest radiograph revealed diffuse reticulonodular infiltrates with caseating granulomas on transbronchial biopsy specimen. Cultures were negative and the patient's condition improved with corticosteroids. The mechanism for BCG-induced granulomatous inflammation is poorly understood. Optimal therapy includes corticosteroids.

Administration, Intravesical↗
PubMed1993

Pleural effusions in hospitalized patients with AIDS.

OBJECTIVE: To determine the incidence, cause, and characteristics of pleural effusions in hospitalized patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Retrospective. PARTICIPANTS: A total of 222 patients with AIDS hospitalized between January 1986 and January 1992 at the Medical University of South Carolina hospitals. RESULTS: Pleural effusions occurred in 59 patients for an overall incidence of 27%. The mean age of the patients was 35 +/- 2 years (SE) and the male to female ratio was 5:1. The cause was infectious in 39 (66%) patients, noninfectious in 18 (31%), and unknown in 2 (3%). Pleural effusions were caused by bacterial pneumonia in 18 (31%) patients, Pneumocystis carinii pneumonia in 9 (15%), Mycobacterium tuberculosis in 5 (8%), septic embolism in 2 (3%), Nocardia asteroides in 2 (3%), cryptococcus neoformans in 2 (3%), and Mycobacterium arium intracellulare in 1 (2%). Among noninfectious causes (n = 18), hypoalbuminemia was the cause in 11 patients (19%), cardiac failure in 3 (5%), and atelectasis, Kaposi sarcoma, uremic pleurisy, and adult respiratory distress syndrome in 1 (2%) each. Patients with AIDS who had pleural effusions had significantly lower serum albumin levels and had lower CD4 counts than did those without pleural effusions (P < 0.001). CONCLUSIONS: Pleural effusions are common in hospitalized patients with AIDS. Bacterial pneumonia is the most common cause for pleural effusion in AIDS. Large effusions are associated with Kaposi sarcoma and tuberculosis. Hypoalbuminemia is a common cause of noninfectious pleural effusions.

AIDS-Related Opportunistic Infections↗
PubMed1993

Pleural macrophages differentially alter mesothelial cell growth and collagen production.

Intrapleural tetracycline (TCN) results in pleural macrophage influx and pleural fibrosis; intrapleural carrageenan (CAR) induces macrophage influx without fibrosis. Because macrophage products can modulate mesothelial cell activity, we investigated the role of TCN- and CAR-induced pleural macrophages on mesothelial cell growth can collagen production. Rabbit pleural macrophages, isolated by plastic adherence 72 h after 20 mg/kg TCN or 10 mg CAR instilled intrapleurally, were cultured for 20 h. Macrophage-conditioned media (MCM) from TCN-or CAR-induce pleural macrophages (TCN MCM, CAR MCM, respectively), were added to non-confluent or confluent rat visceral pleural mesothelial cells and compared to the effects of TCN and CAR. Nonconfluent mesothelial cells were harvested 72 h later for hemacytometry cell counts. A 20-h pulse of [3H] proline (1 mu Ci, 30 Ci/mM) preceded 72-h-cell harvesting of confluent cells. Collagen content was determined in the cell fraction and cell media separately after bacterial collagenase exposure. Mesothelial cells exposed to TCN MCM were found to have decreased numbers when compared to all groups (P < 0.05) except CAR. Cell media collagen content was increased in all macrophage-conditioned-media and chemical-exposed groups compared with control, with TCN MCM having a larger increase than TCN alone (P < 0.05). We conclude that stimulated pleural macrophages release a factor(s) that alters mesothelial cell growth and collagen production and that TCN- and CAR-stimulated pleural macrophages are functionally different. These in vitro mesothelial cell alterations may be important in the genesis of TCN pleurodesis.

Animals↗
PubMed1993

Failure of the circulatory system limits exercise performance in patients with systemic sclerosis.

OBJECTIVE: To determine the mechanisms for exercise impairment in symptomatic patients with systemic sclerosis (SSc) using breath-by-breath expired-gas analysis with incremental exercise testing. DESIGN: Prospective, open trial. PATIENTS AND METHODS: Fifteen consecutive patients with SSc seen at the Medical University Hospital (a tertiary referral center) with complaints of exercise intolerance underwent pulmonary function testing (spirometry, helium dilution lung volumes, and diffusing capacity of carbon monoxide) and incremental exercise testing on a cycle ergometer measuring oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (R), oxygen saturation, blood pressure, and heart rate (HR). Values for oxygen uptake at anaerobic threshold (VO2AT) were derived graphically by blinded clinicians experienced in exercise testing, and the results were averaged. Ventilatory reserve and oxygen pulse were calculated from measured values, and all data were subjected to analysis by standard clinical algorithms. MEASUREMENTS AND MAIN RESULTS: Of 15 patients studied, 14 had either restrictive lung disease or normal results of spirometry on pulmonary function testing. One patient with a history of tobacco use had evidence of airways obstruction. Three patients were unable to exercise maximally (as determined by maximum respiratory exchange ratio [Rmax] greater than 1.09 or maximum heart rate [HRmax] greater than 85% predicted), and exercise testing was terminated in one with Mobitz type II atrioventricular block. The following data (mean +/- SEM) were obtained from 11 maximally exercising patients: VO2max 795 +/- 75 mL oxygen (O2)/min, R 1.34 +/- 0.05, VO2AT/VO2max predicted 0.21 +/- 0.02, O2 pulse 5.1 +/- 0.4 mL O2/beat, ventilatory reserve 0.52 +/- 0.06, and tidal volume/forced vital capacity ratio 0.46 +/- 0.02. Of the 11 patients completing breath-by-breath expired-gas analysis, all had circulatory impairment to exercise, as determined by low O2 pulse and low VO2 at anaerobic threshold, and circulatory impairment was limiting in 9 of 11 patients. Of those nine patients, four had evidence of impaired gas exchange compatible with pulmonary vascular disease. Arterial oxygen desaturation occurred in 2 of 11 patients. CONCLUSION: Circulatory impairment to exercise is common in SSc patients with exercise intolerance. Restrictive lung disease, although also common, does not limit exercise tolerance in patients capable of maximal effort.

Adult↗
PubMed1993

Intrapleural streptokinase in experimental empyema.

Intrapleural streptokinase has been used in multiloculated empyemas to enhance pleural space drainage, presumably by causing fibrinolysis of the interlocular septae. We evaluated the efficacy and safety of daily administration of 10,000 U intrapleural streptokinase or equal volumes of saline to enhance resolution of experimental empyema in the rabbit pleural space. Seventy-two hours after intrapleural turpentine, 10(8) colony-forming units each of Escherichia coli, Peptostreptococcus anaerobius, and Bacteroides fragilis were injected into the sterile pleural effusion of all animals. Immediately after bacterial inoculation, and daily for 3 days, animals received 10,000 U streptokinase or saline intrapleurally. Animals that achieved a pleural fluid pH < 7.30 and either glucose < 50 mg/dl or LDH > 500 IU/L were included for data analysis. At Day 4 after bacterial inoculation, the streptokinase-treated empyemic rabbits had more pleural fluid (18.8 +/- 5.1 ml) (mean +/- SEM) than did saline-treated control animals (4.8 +/- 1.7 ml) (p = 0.015), fewer interpleural adhesions (8.2 +/- 2.7) than did saline-treated control animals (25.1 +/- 3.6) (p = 0.002), and comparable amounts of visceral and parietal pleural plaque than did saline-treated control animals (p = NS). No evidence of systemic fibrinolysis was observed at 1 h after intrapleural streptokinase administration. We conclude that intrapleural streptokinase decreases interpleural adhesion numbers but fails to reduce the amount of pleural plaque observed in experimental empyema in rabbits. The increases in pleural fluid volume observed after streptokinase administration may be due to mechanisms other than fibrinolytic activity.

Animals↗
PubMed1993

The clinician's perspective on parapneumonic effusions and empyema.

Respondents at an interactive symposium on pleural space infections (n = 339) at the 1991 American College of Chest Physicians Annual Scientific Assembly recorded their personal management preferences for hypothetical patients with empyema. The group's preference was to treat pleural sepsis from an anaerobic multiloculated empyema by pleural decortication (49 percent); however, open thoracotomy with directed chest tube placement (22 percent), chest tube placement with intrapleural streptokinase (14 percent), placement of a single chest tube into the largest pleural loculus (8 percent), and placement of multiple small-bore catheters with computed tomographic guidance (7 percent) all had proponents. In the case of a multiloculated empyema not completely drained by a first chest tube in a nontoxic patient, the preference was drainage by a second chest tube, either a small-bore (42 percent) or a large-bore (36 percent) tube. The heterogeneity of responses suggests that prospective trials comparing treatment modalities are needed.

Attitude of Health Personnel↗
PubMed1993

Early inflammatory response of minocycline and tetracycline on the rabbit pleura.

The histopathologic findings were compared from 20 mg/kg intrapleural tetracycline hydrochloride (TCN) and three doses of intrapleural minocycline hydrochloride (5, 10, and 20 mg/kg) (MCN) in New Zealand white rabbits. Both TCN and MCN produced an early neutrophilic predominant pleural effusion that became mononuclear over 48 h. There was no difference in pleural fluid accumulation, number of adhesions, or histologically measured visceral and parietal pleural thickness between TCN and MCN (all p = ns). The TCN, 20 mg/kg, produced more visceral pleural plaque than MCN, 5 mg/kg (p < 0.05). Increasing MCN doses resulted in greater pleural fluid neutrophil accumulation. With higher dose MCN, greater mesothelial cell desquamation and fibroblast proliferation was evident compared to the 5 mg/kg dose. The MCN and TCN produce similar histopathologic condition in the rabbit pleura which suggests that MCN should cause a similar clinical response in humans.

Analysis of Variance↗
PubMed1993

A comparison of rotation and nonrotation in tetracycline pleurodesis.

Previously, we have shown rapid and complete dispersion of tetracycline hydrochloride in the pleural space following chest tube instillation. To assess the clinical relevance of this observation, we randomized patients with symptomatic pleural effusions to rotation (R) (n = 19) and nonrotation (NR) (n = 21) groups following administration of tetracycline hydrochloride, 20 mg/kg (n = 30); 300 mg of minocycline hydrochloride (n = 6); and 500 mg of doxycycline hydrochloride (n = 4) through a chest tube. Patients in the R group were maneuvered through six positions for the 2 h that the chest tube remained clamped. The NR patients remained supine for 2 h. Rotation and nonrotation groups were similar in demographics, source of pleural effusion, symptoms, and serum and pleural fluid analyses (all p = NS). A chest radiograph was scored based on pleural fluid recurrence throughout survival or up to 12 months. Survival, duration of chest tube instillation, and success of pleurodesis assessed by radiographic pleural fluid reaccumulation (73.7 vs 61.9 percent; R vs NR) were similar (p = NS). Rotational maneuvers appear to offer no benefit to the success of pleural symphysis after intrapleural instillation of tetracycline class agents.

Aged↗
PubMed1993

Cyclophosphamide and low-dose prednisone therapy in patients with systemic sclerosis (scleroderma) with interstitial lung disease.

Fourteen patients with systemic sclerosis (SSc, scleroderma) and interstitial lung disease were treated with oral cyclophosphamide (1-2 mg/kg/day) and low dose prednisone (< 10 mg/day). There was a significant improvement in FVC after 6 months compared to entry values (2.21 +/- 0.19 l vs. 2.03 +/- 0.15 l, p < 0.02). Improvement was maintained at 12 months (2.27 +/- 0.27 l, p < 0.05) and 18-24 months (2.60 +/- 0.28 l, p < 0.001). In 12 cases followed for 18-24 months, FVC was stable or improved. No significant improvement or decline was noted for the DLCO. Side effects included cytopenia (2), infection (1), and hemorrhagic cystitis (2), and one possible related malignancy. A controlled prospective trial of cyclophosphamide is warranted in patients with SSc and active interstitial lung disease.

Adult↗
PubMed1992

Pulmonary hypertension and human immunodeficiency virus infection. Two reports and a review of the literature.

Pulmonary hypertension may be primary (idiopathic) or secondary. While the etiologies for secondary pulmonary hypertension are diverse, infection with the human immunodeficiency virus (HIV) has not been included. To date there have been 16 reported cases of pulmonary hypertension in the HIV-infected population. Plexogenic arteriopathy was the most common pathologic finding. We report two HIV-infected patients who were concomitantly found to have pulmonary hypertension with plexogenic arteriopathy. One patient had lymphocytic interstitial pneumonitis, an entity not previously associated with pulmonary hypertension. We review the 16 previous cases of pulmonary hypertension and HIV infection and discuss this association.

Adult↗
PubMed1992

Chylous transport of amiodarone.

A patient receiving amiodarone for longstanding ventricular dysrhythmias presented with idiopathic chylothorax. During drainage of chylothorax for pleurodesis, serial plasma amiodarone concentrations declined while pleural fluid concentrations remained stable. Chylous transport of amiodarone and other lipid-bound drugs should be recognized to avert complications during chylothorax drainage.

Aged↗
PubMed1992

A prospective study of amylase-rich pleural effusions with special reference to amylase isoenzyme analysis.

By analysis of pleural effusions from 200 patients, 25 cases of amylase-rich effusions were identified, for an overall incidence of 13 percent. Four of the 25 patients (16 percent) had evidence of pancreatitis. These patients had higher mean ratios of pleural fluid to serum amylase levels (18 +/- 6.3 [SEM] vs 4.8 +/- 1.3) compared to patients with nonpancreatic diseases (p = 0.003); all four exhibited a predominant pancreatic isoenzyme profile. Of the 21 patients with nonpancreatic amylase-rich effusions, lung cancer was the most commonly associated condition (8 patients). In 14 of the 21 patients in whom an isoenzyme profile was obtained, salivary-type amylase was predominant. Amylase-rich pleural effusions occur frequently, and pleural fluid isoamylase determination is specific for pancreatitis-associated effusions. The finding of a pleural effusion rich in salivary isoamylase should prompt an evaluation for carcinoma (particularly of lung primary), but may also be seen in other pleural inflammatory conditions.

Amylases↗
PubMed1992

Growth and characterization of fibroblasts obtained from bronchoalveolar lavage of patients with scleroderma.

We describe the detection and the growth of fibroblasts with human smooth muscle cell differentiation features from bronchoalveolar lavage (BAL) fluid of 53% of patients with scleroderma, but not from healthy controls. The binding of alpha-actin, vimentin and desmin antibodies by scleroderma lung fibroblasts exceeded that of normal adult lung fibroblasts, indicating that scleroderma lung fibroblasts express some markers of human smooth muscle cell differentiation (myofibroblasts), which may account for differences in biological behavior. A mesenchymal cell phenotype was documented by mRNA analysis, showing high expression of collagen type I and fibronectin in these cells. Fibronectin is also released in significantly higher amounts by scleroderma alveolar macrophages than by macrophages from healthy donors.

Actins↗