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Biomedical subjects

R W Light

Publications and source records attributed to R W Light.

At least 55 records · Page 3Linked to original sources
PubMed2000

Vascular endothelial growth factor level correlates with transforming growth factor-beta isoform levels in pleural effusions.

BACKGROUND: Recent studies have demonstrated high levels of vascular endothelial growth factor (VEGF) in exudative pleural effusions and a possible etiologic role. The factors regulating VEGF accumulation in the pleural space are unknown. Transforming growth factor (TGF)-beta is a potent stimulator of VEGF expression in vitro. We hypothesized that TGF-beta induces VEGF production in pleural tissues, and, hence, the pleural fluid VEGF levels should correlate with the levels of TGF-beta in pleural fluid of different etiologies. METHODS: Seventy pleural fluid samples were analyzed. These included 20 malignant, 13 post-coronary artery bypass grafting (CABG), 8 parapneumonic, 11 miscellaneous exudative, and 18 congestive heart failure (CHF) pleural effusions. RESULTS: Pleural fluid VEGF levels showed good correlation with those of TGF-beta(1) (r = 0.58; p < 0. 0001), TGF-beta(2) (r = 0.43; p < 0.001), and lactate dehydrogenase (r = 0.65; p < 0.001). The levels of TGF-beta(1) and TGF-beta(2) also were correlated (r = 0.60; p < 0.0001). The median levels of TGF-beta(1) (2,480 pg/mL) and TGF-beta(2) (266 pg/mL) in the CHF group were significantly lower than those in the malignant (TGF-beta(1), 4,902 pg/mL; TGF-beta(2), 428 pg/mL), post-CABG (TGF-beta(1), 5,456 pg/mL; TGF-beta(2), 377 pg/mL), parapneumonic (TGF-beta(1), 5,024 pg/mL; TGF-beta(2), 464 pg/mL), and miscellaneous exudate groups (TGF-beta(1), 7,690 pg/mL; TGF-beta(2), 369 pg/mL). There was no significant difference in TGF-beta(1) and TGF-beta(2) levels among the four exudate groups. CONCLUSIONS: VEGF levels in pleural effusions are significantly correlated with the levels of TGF-beta(1) and beta(2) isoforms. VEGF, TGF-beta(1), and TGF-beta(2) levels were all higher in exudative effusions than in effusions secondary to CHF.

Endothelial Growth Factors↗
PubMed2000

Management of pleural effusions.

This review summarizes current strategies in the treatment of patients with pleural effusion. To determine whether a patient has a transudative or exudative pleural effusion, Light's criteria should be applied to measure the concentrations of protein and lactate dehydrogenase (LDH) in the pleural fluid and serum. If the effusion is transudative, therapy should be directed toward the underlying congestive heart failure, cirrhosis, or nephrosis. Consideration should be given to pleurodesis with a sclerosant if patients with recurrent transudative effusion have severe dyspnea due to their effusion. If the effusion is exudative, attempts should be made to define the etiology. The diagnosis of pleural malignancy is most easily established via pleural fluid cytology. If this is negative and the patient is suspected of having pleural malignancy, thoracoscopy is indicated. The concentrations of adenosine deaminase and gamma-interferon in pleural fluid are useful in the diagnosis of pleural tuberculosis. Patients with pneumonia and pleural effusion should undergo therapeutic thoracentesis; the pleural fluid should be Gram-stained and cultured, and the differential cell count, glucose and LDH concentration, and pH should be determined. Indicators of a poor prognosis include the presence of frank pus, a positive Gram-stain, a pleural glucose concentration of less than 2.2 mmol/L, a pH less than 7.00, the presence of pleural loculations, and an LDH concentration greater than three times the upper limit of normal in serum. If the pleural fluid cannot be completely evacuated because of loculations, intrapleural thrombolytic therapy should be considered. If thrombolytics are ineffective, thoracoscopy or thoracotomy with decortication should be performed. Dyspneic patients with malignant pleural effusions whose dyspnea is relieved with therapeutic thoracentesis should be considered for pleurodesis using a tetracycline derivative. Talc is not recommended because it induces acute respiratory distress syndrome in about 5% of patients, with an overall mortality of 1%.

Biopsy, Needle↗
PubMed1999

A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions.

BACKGROUND: The purpose of this study was to compare the effectiveness and safety of a chronic indwelling pleural catheter with doxycycline pleurodesis via tube thoracostomy in the treatment of patients with recurrent symptomatic malignant pleural effusions (MPE). METHODS: In this multi-institutional study conducted between March 1994 and February 1997, 144 patients (61 men and 83 women) were randomized in a 2:1 distribution to either an indwelling pleural catheter or doxycycline pleurodesis. Patients receiving the indwelling catheter drained their effusions via vacuum bottles every other day or as needed for relief of dyspnea. RESULTS: The median hospitalization time was 1.0 day for the catheter group and 6.5 days for the doxycycline group. The degree of symptomatic improvement in dyspnea and the quality of life was comparable in each group. Six of 28 patients who received doxycycline (21%) had a late recurrence of pleural effusion, whereas 12 of 91 patients who had an indwelling catheter (13%) had a late recurrence of their effusions or a blockage of their catheter after the initially successful treatment (P = 0.446). Of the 91 patients sent home with the pleural catheter, 42 (46%) achieved spontaneous pleurodesis at a median of 26.5 days. CONCLUSIONS: A chronic indwelling pleural catheter is an effective treatment for the management of patients with symptomatic, recurrent, malignant pleural effusions. When compared with doxycycline pleurodesis via tube thoracostomy, the pleural catheter requires a shorter hospitalization and can be placed and managed on an outpatient basis.

Catheters, Indwelling↗
PubMed1999

Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group.

BACKGROUND AND METHODS: Although their clinical efficacy is unclear and they may cause serious adverse effects, systemic glucocorticoids are a standard treatment for patients hospitalized with exacerbations of chronic obstructive pulmonary disease (COPD). We conducted a double-blind, randomized trial of systemic glucocorticoids (given for two or eight weeks) or placebo in addition to other therapies, for exacerbations of COPD. Most other care was standardized over the six-month period of follow-up. The primary end point was treatment failure, defined as death from any cause or the need for intubation and mechanical ventilation, readmission to the hospital for COPD, or intensification of drug therapy. RESULTS: Of 1840 potential study participants at 25 Veterans Affairs medical centers, 271 were eligible for participation and were enrolled; 80 received an eight-week course of glucocorticoid therapy, 80 received a two-week course, and 111 received placebo. About half the potential participants were ineligible because they had received systemic glucocorticoids in the previous 30 days. Rates of treatment failure were significantly higher in the placebo group than in the two glucocorticoid groups combined at 30 days (33 percent vs. 23 percent, P=0.04) and at 90 days (48 percent vs. 37 percent, P=0.04). Systemic glucocorticoids (in both groups combined) were associated with a shorter initial hospital stay (8.5 days, vs. 9.7 days for placebo, P=0.03) and with a forced expiratory volume in one second that was about 0.10 liter higher than that in the placebo group by the first day after enrollment. Significant treatment benefits were no longer evident at six months. The eight-week regimen of therapy was not superior to the two-week regimen. The patients who received glucocorticoid therapy were more likely to have hyperglycemia requiring therapy than those who received placebo (15 percent vs. 4 percent, P=0.002). CONCLUSIONS: Treatment with systemic glucocorticoids results in moderate improvement in clinical outcomes among patients hospitalized for exacerbations of COPD. The maximal benefit is obtained during the first two weeks of therapy. Hyperglycemia of sufficient severity to warrant treatment is the most frequent complication.

Administration, Oral↗
PubMed1999

Large pleural effusions occurring after coronary artery bypass grafting. Cardiovascular Surgery Associates, PC.

BACKGROUND: Large pleural effusions sometimes occur after coronary artery bypass grafting (CABG), but their characteristics and clinical course are largely unknown. OBJECTIVE: To describe the clinical course and pleural fluid findings in patients with large pleural effusions occurring after CABG. DESIGN: Retrospective case series. SETTING: Tertiary care, university-affiliated, nonprofit teaching hospital. PATIENTS: 3707 patients who had CABG between 1 February 1996 and 1 August 1997. MEASUREMENTS: Chest radiographs were reviewed, and information on pleural fluid findings, pleural effusion treatment, and cardiac surgery was obtained from medical records and a cardiac surgery database. RESULTS: Pleural effusions that occupied more than 25% of the hemithorax were found in 29 patients (0.78%). Seven of the effusions were attributed to congestive heart failure, 2 were attributed to pericarditis, and 1 was attributed to pulmonary embolism. The explanation for the remaining 19 effusions was unclear. All but 2 effusions were predominantly left-sided. Of these 19 effusions, 8 were bloody and 11 were nonbloody. Bloody effusions usually occurred earlier, contained higher lactic acid dehydrogenase levels, and were frequently eosinophilic. Nonbloody effusions tended to be more difficult to manage. CONCLUSIONS: Large pleural effusions may develop in a small proportion of patients after CABG. The cause of many of these effusions is unclear. Most bloody effusions can be managed with one to three therapeutic thoracenteses. Resolution of nonbloody effusions may require anti-inflammatory agents, tube thoracostomy, or intrapleural injection of sclerosing agents.

Aged↗
PubMed1999

Useful tests on the pleural fluid in the management of patients with pleural effusions.

Examination of the pleural fluid is useful in establishing the etiology of a pleural effusion. Transudative pleural effusions can be differentiated from exudative pleural effusions by measuring the levels of protein and lactic acid dehydrogenase in the pleural fluid and serum. If a patient clinically appears to have a transudative pleural effusion, but the pleural fluid meets exudative criteria, demonstration that the albumin levels is more than 1.2 gm/dl higher in the serum than in the pleural fluid provides evidence that the effusion is transudative. The gross appearance of the pleural fluid should always be noted. Other tests that routinely should be obtained on exudative pleural fluids are Gram stain and cultures, cell counts and differential, glucose, amylase, lactic acid dehydrogenase, cytology, and a marker for tuberculous pleuritis. The diagnosis of tuberculous pleuritis is strongly suggested by a pleural fluid adenosine deaminase level above 45 IU/L or a gamma interferon level above 3.7 U/ml.

Diagnosis, Differential↗
PubMed1999

Chemokine involvement in tetracycline-induced pleuritis.

Sclerosants such as tetracycline (TCN) have often been used in the control of malignant pleural effusions. Although the resultant inflammatory response is probably important in the ensuing pleural fibrosis, the signals responsible for the cellular influx into the pleural space following TCN instillation are not well understood. This study, therefore, sought to determine whether the chemokines interleukin-8 (IL-8), growth-related protein (Gro), and monocyte chemotactic protein-1 (MCP-1) were locally elaborated within the first 72 h following intrapleural TCN administration. TCN induced an exudative effusion with high lactate dehydrogenase activity. Although there was no significant change in the pleural fluid total leukocyte content, the median polymorphonuclear neutrophil concentration decreased from 1.067x10(6) to 2.03x10(5) cells x mL(-1) between 24 and 72 h, whereas the median macrophage concentration increased from 1.44x10(5) to 5.98x10(5) cells x mL(-1) over the same period. Furthermore, IL-8, Gro and MCP-1 concentrations decreased between 24 and 72 h. Immunocytochemistry indicated expression of IL-8 by pleural mesothelial cells 24 h, but not 72 h, following TCN administration. The data suggest that local elaboration of interleukin-8 and growth-related protein, in part of mesothelial origin, may influence neutrophil recruitment in tetracycline-induced pleuritis.

Analysis of Variance↗
PubMed1999

Effects of sodium bicarbonate administration on the exercise tolerance of normal subjects breathing through dead space.

STUDY OBJECTIVE: The purpose of this study was to determine whether the administration of sodium bicarbonate to normal individuals would increase their PaCO2 and thereby decrease the ventilatory requirements at a given workload. DESIGN: In this double-blind crossover study, six normal men ingested either 3 mEq/kg NaHCO3 or 1 mEq/kg NaCl once a day for 5 days, in addition to 40 mg of furosemide and 40 mEq KCl. After each 5-day treatment, the subjects underwent a symptom-limited maximal bicycle ergometer exercise test while breathing through external dead space (with a volume of approximately 50% of their FEV1), a second exercise test without any external dead space, and an assessment of their respiratory response to hypercapnia. RESULTS: The administration of the NaHCO3 resulted in a significant increase in the arterial HCO3- from 20.8 to 24.0 mEq/L and a significant increase in the PaCO2 from 31.7 to 36.9 mm Hg at rest that persisted during exercise. During exercise periods with the added dead space, the Borg scores were significantly lower at each workload after the subjects received bicarbonate, but the maximal exercise level did not increase. The mean (+/-SD) slope of the mouth occlusion pressure response to hypercapnia was significantly lower after the administration of NaHCO3 than after NaCl, respectively: 0.73+/-0.41 vs 1.27+/-0.97 cm H2O/mm Hg. CONCLUSION: From this study we conclude that the administration of NaHCO3 results in a significant increase in the PaCO2, decreases the ventilation and the Borg score at equivalent workloads, and decreases the hypercapnic response in normal individuals.

Adult↗
PubMed1999

Vascular endothelial growth factor in pleural fluid.

STUDY OBJECTIVES: The purpose of this study was to analyze the relationship of the pleural fluid vascular endothelial growth factor (VEGF) level with the diagnostic category and with the pleural fluid characteristics in a group of 70 patients. DESIGN: The VEGF levels of consecutive patients undergoing therapeutic thoracentesis were determined with an enzyme-linked immunosorbent assay. SETTING: University-affiliated tertiary care center. RESULTS: The median level of pleural fluid VEGF in the patients with congestive heart failure (150 pg/mL) was significantly (p < 0.05) lower than the median level in the patients with coronary artery bypass grafting (357 pg/mL), which in turn was significantly lower (p < 0.05) than the median levels in the patients with malignancy (1,097 pg/mL). The overlap between groups, however, limits the diagnostic usefulness of pleural fluid VEGF levels. The VEGF level was most closely correlated with the lactate dehydrogenase level (r = 0.42, p < 0.001) and was also significantly correlated with the total pleural fluid protein level. The median VEGF levels in the pleural fluid of patients with breast cancer were significantly lower (p = 0.017) than in those with lung cancer. The VEGF level was very high (3,294 pg/mL) in the one patient with pulmonary embolism. CONCLUSIONS: We conclude that the VEGF levels in pleural fluid differ significantly from one diagnostic category to another with the highest median levels occurring in patients with malignant pleural effusions. We speculate that VEGF may be responsible for the pleural fluid accumulation in at least some situations.

Breast Neoplasms↗
PubMed1999

Contralateral tension pneumothorax following unilateral chest tube drainage of bilateral pneumothoraces in a heart-lung transplant patient.

Bilateral pneumothoraces can result from unilateral air leak after heart-lung transplantation. The recommended initial management of such patients is insertion of a unilateral chest tube. We report a patient who developed bilateral pneumothoraces after undergoing transbronchial biopsies 2 years after a heart-lung transplant. The unilateral chest tube failed to drain the contralateral pneumothorax and a tension pneumothorax developed. The advocated approach should be used with caution.

Adult↗
PubMed1998

Acute and chronic pleural changes after the intrapleural instillation of mitoxantrone in rabbits.

A previous study demonstrated that the intrapleural injection of 2 mg/kg mitoxantrone in rabbits resulted in a degree of pleurodesis which is comparable to that seen after 35 mg/kg tetracycline but that the animals had a high mortality rate after this dose of mitoxantrone. The objective of the present study was to assess the acute pleural fluid findings, the acute gross and microscopic pleural findings, and the chronic gross and microscopic findings in rabbits that received mitoxantrone. Mitoxantrone, 1.5 mg/kg, was instilled intrapleurally in 70 lightly anesthetized male rabbits. Groups of rabbits were sacrificed 1, 2, 4, 7, 15, 28, and 60 days after the injection. The intrapleural injection of mitoxantrone resulted in an exudative effusion on day 1. The pleural fluid contained predominantly neutrophils and had a mean lactate dehydrogenase (LDH) level that exceeded 4,000 IU/liter. Over the following week the volume of fluid diminished, the predominant cell became the macrophage, and the LDH levels decreased to less than 400 IU/liter. Macroscopic examination of the pleural space revealed that the mean degree of pleurodesis increased progressively over the 60-day observation period. With microscopy, the mean degree of pleural fibrosis also increased progressively. There were also substantial fibrosis and inflammation of the underlying lung and the contralateral lung. The mortality rates were low in the first 28 days (3/70) but subsequently increased and exceeded 80% in the period between 60 and 120 days. This experimental model of pleurodesis should be useful in future studies directed toward uncovering the mechanisms of pleurodesis.

Animals↗
PubMed1998

Serial observations after high dose talc slurry in the rabbit model for pleurodesis.

The mechanisms leading to a pleurodesis after the intrapleural injection of a sclerosing agent are not completely understood. The purpose of the present study was to make serial observations over 28 days on the pleural fluid findings and the gross and microscopic changes in the pleura after talc slurry administered intrapleurally at a high dose. Sixty-six rabbits received 400 mg/kg talc slurry. Ten to 12 rabbits were sacrificed 1, 2, 4, 7, 14, and 28 days after the intrapleural injection. At sacrifice the pleural fluid was measured and analyzed, and the pleural surfaces were studied grossly and microscopically. The intrapleural injection of 400 mg/kg talc slurry resulted in an acute exudative pleural effusion that persisted for 4 days. There was a progressive increase in the gross and microscopic fibrosis over the 28 days. Talc was present at the time of sacrifice in all animals. At 28 days there was a clinically significant pleurodesis in all rabbits; pleurodesis was not observed before this time. From this study we conclude that the intrapleural injection of 400 mg/kg talc slurry leads to an acute exudative pleural effusion and clinically significant pleurodesis that is present on day 28 but not day 14. It appears that the production of a pleurodesis requires higher doses of talc in rabbits without a chest tube than in humans with a chest tube.

Acute Disease↗
PubMed1998

Management of parapneumonic effusions.

When a patient with a parapneumonic pleural effusion is first evaluated, a therapeutic thoracentesis should be performed if more than a minimal amount of pleural fluid is present. Fluid obtained at the therapeutic thoracentesis should be gram-stained and cultured and analyzed for glucose, pH, LDH, white blood cells, and differential cell count. If the fluid cannot be drained because of loculations, a chest tube should be inserted and thrombolytic agents administered. If the pleural fluid recurs after the initial therapeutic thoracentesis but the patient is doing well clinically and the initial pleural fluid glucose was greater than 60 mg/dL; the pH, greater than 7.2; the LDH, less than three times the upper normal limit for serum and the cultures are negative; he or she can be observed. If one or more of the aforementioned criteria are not met, a second therapeutic thoracentesis should be performed, with repeat diagnostic evaluations of the pleural fluid. If the fluid recurs a second time, a small chest tube should be placed if the pleural fluid glucose and pH were lower and the LDH higher on the second thoracentesis than on the first thoracentesis. Patients with loculated-parapneumonic effusions should be treated with tube thoracostomy and thrombolytic agents. If drainage is incomplete, thoracoscopy, with breakdown of adhesions and debridement of the pleural space, is indicated. If thoracoscopy is unsuccessful, then thoracotomy, with decortication, is indicated unless the patient is too debilitated.

Anti-Bacterial Agents↗
PubMed1998

Effectiveness of ethanolamine oleate as a pleural sclerosing agent in rabbits.

The ideal pleural sclerosing agent should be easily administered, without significant side effects, inexpensive, and widely available. None of the agents presently used meets all of these criteria. Ethanolamine oleate (ETH) is a sclerosing agent used in the sclerotherapy treatment of varicose veins of the legs and esophagus. The objective of the present study was to assess the efficacy of ETH as a pleural sclerosant in rabbits. An additional objective was to assess if better results were obtained when dextrose 50% (D50) as opposed to saline was used as the diluent. Each group of 10 rabbits received a total volume of 2 ml intrapleurally. The eight treatments were as follows: (1) 2 ml saline; (2) 2 ml D50; (3) 25 mg ETH plus 1.5 ml saline; (4) 25 mg ETH plus 1.5 ml D50; (5) 50 mg ETH plus 1.0 ml saline; (6) 50 mg ETH plus 1 ml D50; (7) 75 mg ETH plus 0.5 ml D50, and (8) 100 mg ETH. The rabbits were sacrificed 28 days after the injection. The intrapleural instillation of ETH resulted in evident pleurodesis, which was dose-dependent; 100 mg ETH induced significantly (p<0.05) more adhesions than did any other treatment. The selection of the diluent had no effect on the pleurodesis. The microscopic examination of the right visceral pleura showed that the mean degree of fibrosis after 100 mg ETH was significantly (p<0.05) greater than that after the other solutions. The mean degree of pleural inflammation, lung inflammation and lung fibrosis was minimal in all the groups. From this study we conclude that undiluted ETH produces pleurodesis in our experimental model. At the doses used, the pleurodesis was less than that produced after talc, tetracycline derivatives or silver nitrate in the same model.

Analysis of Variance↗
PubMed1998

Systemic corticosteroids decrease the effectiveness of talc pleurodesis.

Corticosteroids can inhibit the inflammatory process and the formation of fibrosis. The purpose of this study was to determine whether the concurrent use of steroids at the time of talc-slurry pleurodesis would influence the development of the pleurodesis. One group of rabbits received an intrapleural injection of talc (400 mg/kg) and an intramuscular injection of triamcinolone (0.8 mg/kg) 1 d before talc instillation and weekly thereafter, whereas a control group received only talc. Ten rabbits in each group were killed at 6 h and at 1, 2, 4, 7, 14, and 28 d after instillation. The mean volume of pleural fluid was significantly lower in the group receiving corticosteroids at 6 h through 4 d after talc slurry than in the other groups. The degree of pleural adhesion was significantly smaller in the group receiving corticosteroids from Day 2 through Day 28. At Day 28, all 10 rabbits that received talc only had a pleurodesis score of 3 or 4, whereas only four of the 10 rabbits that also received steroids had a pleurodesis score of 3 or 4. This study shows that the use of corticosteroids at the time of talc-slurry pleurodesis markedly decreases the inflammatory reaction to the talc, and essentially prevents a pleurodesis from developing.

Animals↗