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Biomedical subjects

F S Vargas

Publications and source records attributed to F S Vargas.

At least 19 recordsLinked to original sources

Intrapleural talc for the treatment of malignant pleural effusions secondary to breast cancer.

BACKGROUND: The management of malignant pleural effusions secondary to breast cancer is a difficult problem. In the 1980s tetracycline was probably the most commonly used sclerosing agent, but parenteral tetracycline is no longer available. Therefore, it is important to evaluate alternative sclerosing agents. This prospective study was designed to determine the efficacy of insufflated talc in producing pleurodesis in patients with pleural effusions secondary to breast cancer. METHODS: Fifty-two patients admitted between May 1985 and November 1992 to the Department of Thoracic Surgery underwent thoracoscopy and had 2 gm sterile asbestos free talc insufflated throughout the pleural space at the time of the procedure. One or two chest tubes were inserted and left in place until fluid drainage was less than 100 ml per day. RESULTS: Of the 52 patients, 5 were not evaluable. Two patients died within 30 days of the procedure. In three additional patients the lung did not expand after thoracoscopy. The intrapleural insufflation of talc was effective in preventing recurrence of pleural effusion. At 30 days there was no recurrence of the pleural fluid in 45 of the 47 (95.7%) patients. One of these patients had a recurrence of the effusion 2 months after the procedure but the remaining 44 (93.6%) had no recurrence for the duration of the study. Aerosolized talc was associated with a moderate morbidity. Six (11.5%) patients had re-expansion edema, but all recovered. Empyema developed in one patient after the procedure. No episodes of respiratory distress syndrome were observed after talc pleurodesis. CONCLUSION: The insufflation of 2 gm talc into the pleural space is an effective method to control pleural effusions secondary to breast cancer.

Adult

Temporal evolution of pleural fibrosis induced by intrapleural minocycline injection.

Minocycline is as effective as tetracycline in inducing pleural fibrosis, but the long-term pleural changes induced by minocycline are unknown. The objective of this study was to evaluate in rabbits the evolution of the pleural changes induced by the intrapleural instillation of minocycline. Under light anesthesia, minocycline at 10 mg/kg in a total volume of 2 ml of bacteriostatic saline solution was injected into the right pleural space of 25 male rabbits. The animals were sacrificed in groups of five at 15 d and 1, 2, 4, and 6 mo. Macroscopic and microscopic examinations of the pleura were performed for evidence of pleural fibrosis and inflammation. Similarly, the underlying lung was also examined for microscopic alveolar fibrosis and inflammation. During the 6-mo observation period there was no significant change in the degree of pleural fibrosis. In contrast, microscopic pleural inflammation, alveolar fibrosis, and alveolar inflammation all decreased significantly over the observation period. In conclusion, intrapleural minocycline injection results in persistent pleural fibrosis at 6 mo. It remains to be determined whether the pleural fibrosis will persist beyond this period.

Animals

Talc slurry is an effective pleural sclerosant in rabbits.

Insufflated talc is probably the most effective agent for creating a pleurodesis both in the clinical situation and in animals. However, the insufflation of talc requires an invasive procedure such as thoracoscopy or thoracotomy. Recently, there have been reports that talc in a slurry was effective in the clinical situation. The objective of this project was to determine whether talc in a slurry at varying doses is an effective sclerosant in an experimental model in rabbits. Talc, 50, 100, 200, and 400 mg/kg, in a 2-mL slurry was injected intrapleurally through a small catheter in male rabbits. Eleven rabbits received each dose. Twenty-eight days after the instillation, the animals were killed. The pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The degree of pleurodesis (on a scale of 0 to 4) after the injection of 50, 100, 200, and 400 mg/kg of talc was 1.1 +/- 0.9, 1.5 +/- 1.1, 2.7 +/- 0.6, and 3.4 +/- 0.5, respectively. The degree of microscopic fibrosis similarly increased with increasing doses of talc. These scores were similar to those we have reported with the tetracycline derivatives. In contrast to the results with tetracycline derivatives, none of the rabbits developed fibrothorax or hemothorax. From this study, we conclude that talc in a slurry is a very effective pleural sclerosant in rabbits and does not produce hemothoraces as do the tetracycline derivatives.

Animals

Comparison of silver nitrate and tetracycline as pleural sclerosing agents in rabbits.

The ideal agent to produce pleurodesis has not been identified. Tetracycline, the drug used most commonly in the 1980s, is no longer available. Talc either aerosolized or in a slurry is the agent used just most commonly at the present time, but there are concerns about its safety. Another possibility is silver nitrate, which was widely used in the past, but was abandoned on account of side effects. We hypothesized that lower concentrations of silver nitrate than had been used in the past would be effective in creating a pleurodesis in rabbits. The following medications in a total volume of 2 mL were instilled intrapleurally in three groups of ten anesthetized rabbits: 0.25% or 0.50% silver nitrate and 35 mg/kg tetracycline. Twenty-eight days after the injection, the animals were sacrificed and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of 0.50% silver nitrate produced an effective pleurodesis. The mean degree of gross pleurodesis in the rabbits that received 0.50% silver nitrate (3.4 +/- 1.2) did not differ significantly from that of the rabbits that received tetracycline (3.5 +/- 0.7) (scale 0 to 4). The mean degree of microscopic pleural fibrosis in the rabbits that received 0.50% silver nitrate (3.4 +/- 0.7) did not differ significantly from that of the rabbits that received tetracycline (3.9 +/- 0.3). However, 0.25% silver nitrate was ineffective in creating pleural fibrosis, either grossly or microscopically. No rabbits died after the intrapleural injection of the drugs. There were no observed side effects after the injection of silver nitrate. The present study demonstrates that 0.50% silver nitrate instilled into the pleural space is an effective agent for producing pleurodesis in the rabbit; its effect is comparable to tetracycline 35 mg/kg. This agent should be compared with tetracycline derivatives and talc in studies in humans.

Analysis of Variance

Scimitar sign with normal pulmonary venous drainage and systemic arterial supply. Scimitar syndrome or bronchopulmonary sequestration?

The classic definition of the scimitar syndrome is a triad of hypoplasia of the right lung with anomalous venous drainage and a systemic arterial supply of a variable degree. We report a case in which a scimitar-shaped anomalous vein was observed on the plain chest radiograph, but subsequently a pulmonary angiogram showed that it drained normally into the left atrium.

Adult

Relationship between pleural effusion and pericardial involvement after myocardial revascularization.

The explanation for the high incidence of pleural effusion after cardiac surgery is unclear. There is a high incidence of left pleural effusion with inflammatory pericardial disease. We hypothesized that after coronary artery bypass grafting (CABG) there would be a higher incidence of pleural effusions in patients with pericardial involvement. We prospectively studied 47 patients undergoing elective CABG; 17 had only saphenous vein grafts (SVG group) and 30 received at least one internal mammary artery graft (IMA group) in addition to SVG. Patients had a chest radiograph, chest ultrasound, and an echocardiogram on the 7th, 14th, and 30th postoperative days. Seven days after the surgery, 42 to 47 patients (89.4 percent) had a pleural effusion and 36 (76.6 76.6 percent) pericardial involvement. No relationship was found between the presence of a pleural effusion and a pericardial effusion (p > 0.05). On the 14th postoperative day, 36 patients (76.6 percent) had a pleural effusion while 33 patients (70.2 percent) had a pericardial effusion. There was a significant relationship between the presence of a pleural effusion and a pericardial effusion (p < 0.05). On the 30th postoperative day, 27 patients (57.4 percent) had a pleural effusion and 25 (53.2 percent) had a pericardial effusion. Again, there was a significant relationship between a pleural effusion and a pericardial effusion (p < 0.05). Finally, there was no relationship between the ejection fraction and the presence of pleural effusion at any time (p > 0.05). From this study, we conclude that there is a high prevalence of both pleural and pericardial effusion postoperatively in patients undergoing CABG. Both types of effusions tend to be asymptomatic, gradually disappear, and are more common in the IMA group. Patients who have a persistent pericardial effusion are more likely to have a persistent pleural effusion.

Coronary Artery Bypass

Subclinical surface alterations of human pleura. A scanning electron microscopic study.

Pleuritis or pleural effusion frequently develops in patients with pneumonia or heart failure. Most of these pleural changes regress without intrapleural intervention. The detailed mechanisms of the regression of the pleural changes in humans are not well documented. We studied the parietal pleura of nine patients with lung cancer and two patients with coronary artery disease by scanning electron microscopy (SEM). All patients had neither radiographic nor gross evidence of pleural disease but all had mixed surface alterations by SEM. Focal denudation of mesothelial cells was common. Deeper injuries exposed thick and thin interweaving collagen bundles. Patchy depositions of amorphous or crystallized fibrin covered normal and damaged pleural surfaces, frequently admixed with macrophages, red blood cells, and tissue debris. Reactive mesothelial cells appeared to proliferate over the fibrin. Our findings suggest that subclinical pleural alterations occur often in patients with pulmonary or cardiac diseases and that an intact pleural surface in those patients is restored mainly by the proliferation of reactive mesothelial cells.

Coronary Disease

Comparison of the effectiveness of tetracycline and minocycline as pleural sclerosing agents in rabbits.

Parenteral tetracycline, one of the most commonly used agents for producing pleurodesis, is no longer available because of stricter regulations governing the manufacturing process. The objective of this project was to determine whether minocycline, a tetracycline derivative, is an effective sclerosant in an experimental model in rabbits. We also studied the relationship of the dose and the volume injected to the degree of pleurodesis. The following medications were instilled intrapleurally in anesthetized male rabbits: tetracycline, 35 mg/kg; or minocycline, 4, 7, 10, or 20 mg/kg, diluted to a total volume of 1 or 2 ml of bacteriostatic saline solution; or minocycline, 40 mg/kg, diluted to a total volume of 2 ml of the solution. Twenty-eight days after the instillation, the animals were killed. The pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The degree of pleurodesis grossly and microscopically after the injection of 7, 10, 20, or 40 mg/kg of minocycline was comparable to that after the injection of 35 mg/kg of tetracycline, while the dose of 4 mg/kg was less effective. In the animals who received the higher doses of minocycline intrapleurally (ie > or = 20 mg/kg), there was an excess mortality both early (chi 2 = 3.61, 0.05 < p < 0.10) and late (chi 2 = 11.0, p < 0.005) which appeared to be related to the development of hemothorax. The intrapleural injection of the tetracycline derivatives was significantly (p < 0.05) more effective when the total volume of the solution was 2 ml rather than 1 ml. The present study demonstrates that minocycline is an effective agent for producing pleurodesis in the rabbit. Minocycline given intrapleurally at doses of 7 mg/kg or above is comparable to tetracycline, 35 mg/kg. Higher doses of minocycline (> or = 20 mg/kg) produce a high mortality that seems to be related to hemothorax. Since, in humans, a large experience confirms only 20 mg/kg of tetracycline is needed to produce adequate pleurodesis safely, we recommend a dose of 4 mg/kg of minocycline for the production of pleurodesis.

Animals

Intrapleural talc for the prevention of recurrent pneumothorax.

The ipsilateral recurrence rate after the first spontaneous pneumothorax treated with tube thoracostomy is reported to be between 23 percent and 52 percent. The incidence of recurrence after the first recurrence is substantially higher. Chemical pleurodesis has been attempted to decrease the recurrence rate. Tetracycline has been widely utilized, but parenteral tetracycline is no longer available. Therefore, alternative sclerosing agents have been used. Talc has been demonstrated to be effective in preventing recurrences and it has minimal long-term effects. This prospective study was designed to determine the efficacy of talc pleurodesis in patients with recurrent spontaneous pneumothorax. Eighteen patients admitted between May 1985 and March 1993 to the Department of Thoracic Surgery underwent thoracoscopy and were treated by tube thoracostomy with chemical pleurodesis. All the patients had had at least two pneumothoraces and six had had at least six pneumothoraces. Sterile asbestos-free talc, 2g, was aerosolized throughout the pleural surface. One or two chest tubes were inserted, left clamped for 2 h, and unclamped after this time. The tubes were removed when no air had escaped for 24 h. Only one (5.6 percent) patient had recurrence of the pneumothorax, and a second insufflation of talc resulted in no new recurrence after a follow-up of 10 months. The remaining 94.4 percent did not have recurrence of pneumothorax within an observation period of 38.5 +/- 28.1 months. The follow-up was more than 2 years for 66.7 percent with no recurrence and was more than 5 years for 33.3 percent. We conclude from these observations that the insufflation of 2 g of talc into the pleural space is a safe effective treatment for control of recurrent spontaneous pneumothorax.

Adult

Distribution of pleural injectate. Effect of volume of injectate and animal rotation.

It is controversial whether rotation is necessary for patients undergoing pleurodesis. In addition, the optimal volume of the injectate remains to be determined. The purpose of this study was to determine the importance of rotation and the volume of the agent on the intrapleural dispersion of agents injected into the pleural space of rabbits. Technetium 99m pertechnetate (99mTc) in 0.5, 1.0, or 2.0 ml of saline solution was injected into ten lightly anesthetized rabbits, half of whom were rotated for 1 min after the injection. Static images were obtained in the anterior projection 1 and 5 min after the injection. After the second scan, the limits of the lung were defined by obtaining a perfusion scan immediately after the intravenous injection of macroaggregates of 99mTc-labeled serum albumin. The degree of dispersion was significantly greater in the nonrotated groups both at 1 min (F = 8.11, p = 0.0085) and at 5 min (F = 5.89, p = 0.0274). In addition, the homogeneity of the distribution of the injectate was not improved with rotation. From this study, we conclude that rotation of the animal for 1 min after the intrapleural injection does not improve the distribution of the injectate throughout the pleural space. Furthermore, a volume of 0.5 ml is sufficient for all pleural surfaces to be exposed.

Animals

Intrapleural talc for the prevention of recurrence in benign or undiagnosed pleural effusions.

Chemical pleurodesis has become the preferred treatment for definitive management of malignant pleural effusions. The treatment of patients with recurrent benign or undiagnosed pleural effusions, however, remains a difficult clinical problem. Tetracycline has been widely used as a sclerosing agent, but parenteral tetracycline is no longer available. Therefore, alternative sclerosing agents are needed. Talc was used for the first time in 1935, and subsequently there have been several reports documenting its effectiveness in the treatment of malignant pleural effusion and pneumothorax. The objective of this study is to present our experience with a low dose of aerosolized talc for controlling nonmalignant pleural effusions. Between May 1985 and October 1992, twenty-two patients underwent talc pleurodesis at the time of thoracoscopy for control of a nonmalignant effusion. The cause of the effusion was cirrhosis in six patients, systemic lupus erythematosus in two, chylothorax in five, and no diagnosis in nine patients. Follow-up has ranged from 18 days to 5 years. Only two patients (9 percent), one with cirrhosis and another with an undiagnosed pleural effusion, had a recurrence of the effusions. We conclude that the intrapleural administration of 2 g of aerosolized talc is an effective treatment for recurrent benign (including chylothorax) or undiagnosed pleural effusions.

Adolescent

Arrhythmogenic effects of combined orally administered theophylline and albuterol in patients with chronic obstructive pulmonary disease.

1. Studies in asthmatic subjects have reported conflicting results about the arrhythmogenic effects of beta agonist and theophylline. The purpose of the present study was to evaluate the effects of the combination of these drugs in patients with chronic obstructive pulmonary disease (COPD). 2. Twelve COPD patients (FEV1 = 1.2 +/- 0.3 L; PaO2 = 65.7 +/- 9.0 mmHg) were evaluated by 24-h Holter monitoring on three different days. The first evaluation was done after the patient had been without any treatment for at least 24 h, the second after sustained-release theophylline for one week and the third after oral beta agonist (albuterol) and theophylline for one week. 3. Mean serum level of theophylline was 1.9, 15.6 and 11.7 micrograms/ml, and mean heart rate was 78.3, 82.0 and 84.5 beats/min for the first, second and third period, respectively. Four patients showed more than 10 premature atrial contractions/h in the baseline Holter, and this rate did not increase after either treatment. Three patients had more than 10 premature ventricular contractions/h (PVC) at baseline, with no increase while receiving theophylline or the combination of theophylline and albuterol. However, one patient did have worsening of the arrhythmia while taking both drugs. There were 5 single PVCs/h at baseline and 150 single and 9 coupled PVCs/h plus 1 episode of non-sustained ventricular tachycardia during combined therapy. 4. We conclude that the combination of theophylline and a beta agonist (albuterol) may increase the premature ventricular contraction rate and the complexity of ectopic activity in COPD patients.

Administration, Oral

Influence of atelectasis on pulmonary function after coronary artery bypass grafting.

The purpose of this study was to determine the influence of atelectasis on pulmonary function 6 days following coronary artery bypass grafting (CABG). After 6 days, 30 patients had normal chest radiographs, 38 had atelectasis, and 57 had pleural changes. In 11 patients, atelectasis only was observed in the radiograph, and in 27 it was in combination with pleural changes. The decrease in FVC and FEV1 in the patients with atelectasis was 33.4 and 33.5 percent in the SVG group and 34.8 and 34.3 percent in the IMA group, while in those patients with a normal radiograph, the decrements were 26.3 and 26.9 percent in SVG group and 26.1 and 26.9 percent in IMA group, respectively. Thus, patients with atelectasis on the 6th postoperative day have a larger decrement in pulmonary function post CABG than the patients with normal chest radiograph and this reduction reflects a higher degree of thoracic trauma.

Coronary Artery Bypass

Effectiveness of bleomycin in comparison to tetracycline as pleural sclerosing agent in rabbits.

The two agents most commonly used for producing a pleurodesis are tetracycline and bleomycin. Tetracycline is no longer available due to more stringent requirements on the manufacturing process. The objective of this project was to determine whether bleomycin is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anesthetized male rabbits: tetracycline, 35 mg/kg, or bleomycin, 1.5 or 3.0 IU/kg diluted to a total volume of 1 ml with bacteriostatic saline solution. Twenty-eight days after the instillation, the animals were killed, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of bleomycin was ineffective in creating pleural fibrosis, either grossly or microscopically. The mean degree of gross pleurodesis in the six rabbits who received tetracycline was 2.7 +/- 1.5 (scale 0 to 4), while that in the rabbits who received the highest dose of bleomycin was 0.0 +/- 0.0. Based on this study, we recommend that bleomycin not be used as a pleural sclerosant in patients with nonneoplastic pleural disease, eg, those with pneumothorax, congestive heart failure or cirrhosis, and pleural effusion.

Analysis of Variance

Theophylline metabolism in patients with hepatosplenic mansoniasis and cirrhosis.

The pharmacokinetics of theophylline were studied in 12 patients with hepatosplenic mansoniasis, 14 patients with cirrhosis and 16 normal controls. Following a single intravenous dose of aminophylline volumes of distribution, serum half-lives and body clearances were determined. Volumes of distribution of theophylline in patients with schistosomiasis (mean 0.624 l/kg) did not differ from cirrhotic patients (mean 0.616 l/kg) or normal controls (mean 0.593 l/kg). Cirrhotic patients had a prolonged half-life compared to normal subjects (mean 22.1 vs. 9.9 h), while patients with schistosomiasis did not substantially differ from normal controls (15.8 vs. 9.9 h). Body clearance in patients with schistosomiasis was similar to controls (34.02 vs. 49.20 ml/h per kg) but decreased (29.24 ml/h per kg) in patients with cirrhosis. Individual analysis of the group with schistosomiasis disclosed three patients with reduced theophylline elimination. No relationship was found between laboratory tests of liver function and the pharmacokinetics of theophylline in any group. The administration of theophylline to patients with hepatosplenic schistosomiasis, although less dangerous than in cirrhosis, must be closely followed.

Adolescent

Postoperative pleural changes after coronary revascularization. Comparison between saphenous vein and internal mammary artery grafting.

Coronary artery bypass grafting (CABG) is commonly performed with a saphenous vein graft (SVG) and/or an internal mammary artery graft (IMA). We hypothesized that there would be a higher incidence of pleural changes after CABG in patients who underwent IMA grafting because pleurotomy is usually performed. In the present study, the pre and the 6th postoperative day chest roentgenograms of 122 patients who received CABG were reviewed. The incidence of effusion in the patients who received only SVG was 43 percent (23/54) and did not differ significantly (p greater than 0.05) from the incidence in the patients who also had IMA 41 percent (28/68). Almost all of the patients (43/51) had unilateral left-sided pleural effusions. Most of the effusions were small and did not require treatment. The incidence of effusion was not higher in patients with enlargement of their cardiac silhouette or atelectasis and was not related to the presence of chest tubes. The incidence of pleural thickening was higher in the IMA group (49 percent) than in the SVG group (31 percent) but the difference did not achieve statistical significance (p greater than 0.05). We conclude that there is a high (approximately 40 percent) incidence of small effusions and thickening after CABG. The incidence of pleural effusion and pleural thickening do not appear to be influenced by the type of surgery (IMA vs SVG). We speculate that the effusions are due to pericardial inflammation.

Coronary Artery Bypass

Effect of inhaled furosemide on the bronchial response to lysine-aspirin inhalation in asthmatic subjects.

It has been demonstrated recently that inhaled furosemide inhibits bronchoconstriction induced by cold air, physical exercise, various antigens, and metabisulfite. The goal of the present study was to determine if the inhalation of furosemide would inhibit the bronchoconstriction resulting from the inhalation of lysine-aspirin in aspirin-sensitive asthmatics. Six female subjects with known hypersensitivity to aspirin participated in this crossover study comparing 20 mg of inhaled furosemide and placebo. The volunteers inhaled increasing concentrations of lysine-aspirin after the inhalation of furosemide or placebo. The geometric mean provocative dose causing a 20 percent decrease in the FEV1 (PD20) after the inhalation of placebo was 30.4 mg/ml and the PD20 was equal or below 90 mg/ml in all patients. In contrast, the FEV1 did not decrease by 20 percent in any of the patients pretreated with furosemide when the inhaled concentration was increased to 360 mg/ml. From this study, we conclude that the administration of furosemide blocks the bronchospasm induced by the inhalation of lysine-aspirin in aspirin-sensitive asthmatics.

Administration, Inhalation

Relationship between pleural changes after myocardial revascularization and pulmonary mechanics.

It is known that coronary artery bypass grafting (CABG) results in impairment of postoperative pulmonary function. There is also a high incidence of pleural changes (pleural effusion or pleural thickening) after CABG. We hypothesized that those patients with pleural changes in the postoperative period would have a greater decrease in pulmonary function test (PFTs) results. The present study reports the results of 110 male patients who underwent CABG. The chest films and the PFT results obtained preoperatively and on the sixth postoperative day were reviewed. The relationship between pleural changes and PFTs was analyzed in patients who received saphenous vein graft alone (SVG group: 50 patients) or in combination with internal mammary artery grafting (IMA group: 60 patients). In the IMA group, the patients who had pleural changes had significantly greater decreases in their pulmonary function than did the patients without pleural changes. The decrease in the FVC, TLC and FEV1 in the patients with pleural effusions (37.6, 27.8 and 36.8 percent) was similar to that in patients with pleural thickening (34.6, 28.3 and 35.0 percent) and both were significantly greater (p < 0.05) than the changes in the patients with a normal radiograph (26.1, 17.6 and 26.9 percent). In the SVG group, the presence of pleural changes was not significantly related to the decrement in pulmonary function. The values of RV, FRC, Cst, and blood gases were not affected in the SVG or IMA group by the presence of pleural changes. We conclude that the presence of pleural changes on the chest radiograph is associated with a larger decrement of pulmonary function after CABG in the IMA group. This larger decrease probably reflects added thoracic trauma and is not due to the presence of pleural changes per se.

Coronary Artery Bypass