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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

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

Pleural sclerosis for the treatment of pneumothorax and pleural effusion.

Pleural sclerosis is indicated to obliterate the pleural space when one wants to prevent the recurrence of a spontaneous pneumothorax or the reaccumulation of a pleural effusion. Although many different agents ranging from antibiotics to antiseptics to antineoplastics to talc have been advocated, none is ideal. It is interesting that in the era when we are mapping the human genome, the agent most commonly used for pleurodesis is talc. Talc is very inhomogeneous, and the mechanisms by which it produces pleurodesis are unknown. In this review we will discuss the theory and mechanism of pleurodesis, the indications and contraindications for it, the advantages and disadvantages of the agents presently used for it, and our recommendations for the procedure.

Adjuvants, Immunologic

Pulmonary function after coronary artery bypass surgery.

Coronary artery bypass graft surgery (CABG) adversely affects pulmonary function tests (PFTs). Although several previous studies have addressed these changes, none has measured the forced vital capacity (FVC) on a daily basis. The purpose of the present study was to assess serial changes in the FVC following CABG and to identify factors that may influence these changes. The FVC was obtained pre- and daily postoperatively (1-10 days) in 120 patients. Fifty-one patients received saphenous vein grafts (SVG group) while 69 received at least one internal mammary artery graft in addition to SVG (IMA group). On the first postoperative day, the FVC decreased to 33% of the pre-operative value in the SVG group and to 29% in the IMA group. The spirometry gradually improved, but after 10 days, the FVC remained reduced (SVG, 70%; IMA, 60%). Although the decreases in FVC tended to be greater in the IMA group, there was no significant difference in the two groups (P = 0.27). The changes in FVC were not significantly related to age (P = 0.48), smoking history (P = 0.65), anesthesia (P = 0.38) or pump time (0.09). From this study, it is concluded that after CABG, there is a significant worsening of the pulmonary function. The nadir of FVC occurs immediately after surgery and improves gradually thereafter. However, on the tenth postoperative day, the FVC still remains more than 30% below pre-operative values. Since there is only a slight tendency for patients undergoing IMA grafting to have larger decreases in their pulmonary function, patients with ventilatory impairment should not be excluded from IMA grafting.

Analysis of Variance

High-resolution CT scan in the evaluation of exercise-induced interstitial pulmonary edema in cardiac patients.

OBJECTIVE: To evaluate the onset of exercise-induced interstitial pulmonary edema in cardiac patients by high-resolution CT (HRCT). DESIGN: Prospective, normal controlled. PARTICIPANTS: Thirty subjects divided into three groups: group 1--10 outpatients with chronic congestive heart failure (CCHF), New York Heart Association (NYHA) class I; group 2--10 outpatients with CCHF, NYHA class II/III; and group 3 (control)--10 normal subjects. METHOD: HRCT scans were obtained at rest and 4, 8, 12, 16, and 20 min after progressive treadmill exercise test. RESULTS: The following HRCT findings consistent with interstitial edema were significantly different (p<0.05) in group 2 when compared with groups 1 and 3: artery/bronchus ratio > 1 in the upper lobes, peripheral increase in the vascular markings, interlobular septal thickening, and peribronchial "cuffing." These differences were maximal at 12 min after exercise and returned to normal values after 20 min. CONCLUSION: Interstitial pulmonary edema was present immediately after exercise in CCHF patients. It may be important in the genesis of dyspnea of these patients.

Adult

Comparison of nitrogen mustard, cytarabine and dacarbazine as pleural sclerosing agents in rabbits.

We have previously shown that the intrapleural injection of mitozantrone but not bleomycin resulted in pleural fibrosis. Mechlorethamine hydrochloride (nitrogen mustard) was used extensively in the past to control malignant effusions, with relatively good success. The objective of this study was to determine if the intrapleural injection of nitrogen mustard would produce pleural sclerosis in our experimental model in rabbits. We therefore evaluated sclerosing capabilities of nitrogen mustard as well as those of cytarabine and dacarbazine. Nitrogen mustard (0.4 and 0.8 mg x kg(-1)), cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were instilled intrapleurally into anaesthetized rabbits. 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 0.8 mg x kg(-1) nitrogen mustard was effective in creating pleural fibrosis, either grossly or microscopically. The mean degree (scale 0-4) of gross pleurodesis in the rabbits that received 0.8 mg x kg(-1) nitrogen mustard was 3.2+/-1.0 and the mean degree of microscopic pleural fibrosis was 3.5+/-0.8. The intrapleural injection of 0.4 mg x kg(-1) nitrogen mustard and the different doses of cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were ineffective in producing pleurodesis. From this study, we conclude that the intrapleural injection of 0.8 mg x kg(-1) of nitrogen mustard produces clinically significant pleurodesis in rabbits. Consideration should be given to future clinical studies utilizing 0.6-0.8 mg x kg(-1) nitrogen mustard intrapleurally for the treatment of malignant pleural effusion.

Animals

Comparison of mitoxantrone and tetracycline as pleural sclerosing agents in rabbits.

Bleomycin is the antineoplastic agent used most commonly for the treatment of malignant pleural effusion. It is absorbed rapidly from the pleural space and does not elicit pleurodesis in the normal rabbit pleura. Mitoxantrone is a new antineoplastic that differs from bleomycin in that it binds to membranes. Accordingly it might remain in the pleural space for a longer period and produce a pleurodesis. The objective of this project was to determine whether mitoxantrone is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anesthetized male rabbits: 35 mg/kg tetracycline or 0.5, 1.0, or 2.0 mg/kg mitoxantrone. The animals were killed at 28 days and the pleural spaces assessed grossly for pleurodesis and microscopically for fibrosis and inflammation. The mean degree of gross pleurodesis did not differ significantly in the rabbits that received tetracycline (3.8 +/- 0.4) and in the rabbits that received 2 mg/kg mitoxantrone (3.2 +/- 1.3). The degree of pleural and lung inflammation was significantly greater after mitoxantrone than after tetracycline, both ipsilaterally and contralaterally. The mortality after the highest dose of mitoxantrone was 50%. From this study we conclude that the intrapleural administration of mitoxantrone in rabbits can produce a pleurodesis. The histologic picture after mitoxantrone administration differs markedly from that after tetracycline injection. After mitoxantrone injection there are many more inflammatory cells present on the side that received the injection, and there is much more fibrosis and inflammation in the contralateral pleura and lung. The model of pleural fibrosis following intrapleural mitoxantrone may be useful for the study of pleural fibrosis.

Animals

Effectiveness of sodium hydroxide as a pleural sclerosing agent in rabbits: influence of concomitant intrapleural lidocaine.

The two agents that have been used most commonly to produce a pleurodesis are tetracycline and bleomycin. Tetracycline is no longer generally available because of more stringent requirements on the manufacturing process. Bleomycin is very expensive. Therefore, alternative agents are necessary particularly in developing countries. The objective of this project was to determine whether 0.5% sodium hydroxide is an effective sclerosant in an experimental model in rabbits. Sodium hydroxide (NaOH) (2 ml of 0.5%) was instilled intrapleurally in 24 anesthetized male rabbits. Half the rabbits received 1 ml of 2% lidocaine 3-5 min before the NaOH. Twenty-eight days after the instillation, the animals were sacrificed, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The results indicated that the intrapleural injection of NaOH was effective in creating a pleurodesis only if the animals were not premedicated with lidocaine. The mean (+/- S.D.) degree of gross pleurodesis after NaOH alone 2.8 (1.0) was significantly (p < 0.001) greater than after that following the combination 1.3 (0.5). We conclude that NaOH is an effective pleural sclerosant but that it is ineffective if it is injected concomitantly with lidocaine.

Anesthetics, Local

Hepatic and pulmonary biopsy by mini-thoracotomy and transdiaphragmatic access.

Frequently, immunodeficient patients have more than one organ or system affected by opportunistic infection or neoplasia, requiring quick and precise diagnostic investigation. In some situations, different invasive diagnostic procedures may be necessary. Open lung biopsy is sometimes necessary to clarify the pulmonary diagnosis. Laparoscopy may be useful to clarify liver or other peritoneal diseases. Some specific patients might require both procedures. In this way it is proposed that the surgeon, through a microthoracotomy used for the pulmonary biopsy, has access to the diaphragm. A small phrenotomy is performed and then a liver needle biopsy under direct vision. The described technique of simultaneous open lung and hepatic biopsy permits better handling of the needle and hemostasis of the hepatic lesion at the puncture site. This method has been used since 1994 on 16 HIV-positive patients, all having clinical and laboratory manifestations of lung disease associated with liver disease of unknown etiology. No complications related to the method were observed. It is significant that different etiologies for the lung and liver disease were found in 50% of the cases. We conclude that the presented technique is simple, useful, and safe.

AIDS-Related Opportunistic Infections

Gallium-67 lung imaging and pulmonary clearance of 99mTc-DTPA aerosol in patients with amiodarone pneumonitis.

The aim of this study was to compare gallium-67 citrate lung imaging with the pulmonary clearance of 99mTc-DTPA (technetium 99m diethylenetriaminepentaacetic acid) in 9 patients with amiodarone pneumonitis (8 males and 1 female, aged 58 to 76 years). The diagnosis of amiodarone pneumonitis was based on clinical and radiological grounds in all patients, and histological changes in seven. The mean values for the effective half-life of the pulmonary clearance of 99mTc-DTPA aerosol were below the normal range in all 9 patients, and lower than the values obtained previously for patients on a long-term amiodarone regimen without side effects. Positive gallium-67 accumulation was demonstrated in 7 of the 9 patients. Two patients had negative gallium-67 imaging and increased alveolar-capillary 99mTc-DTPA clearance; with corticosteroid therapy and discontinuation of amiodarone, their radiological changes and clearance became normal within 120 days. In conclusion, when compared to gallium-67 lung imaging, the 99mTc-DTPA aerosol clearance is more advantageous because it is a much faster test than the gallium scan. This is essential for those patients suspected of amiodarone pneumonitis who need specific therapy as soon as possible. Moreover, the 99mTc-DTPA aerosol clearance test appears to be a more useful diagnostic tool because it is positive even in those patients who have normal gallium-67 lung imaging.

Adult

Pleural malignancies.

Carcinoma of the lung, metastatic breast carcinoma, and lymphoma are responsible for approximately 75% of all malignant pleural effusions. The presence of malignant cells in the pleural fluid or in the parietal pleura confirms the diagnosis. Recently, several authors have proposed the combination of morphometric procedures and quantitative analysis of nucleolar organizer regions stained by silver nitrate. Videothoracoscopy is recommended for patients suspected of having a malignant pleural effusion in whom the diagnosis is not established after two cytologic studies of the fluid and one needle biopsy. The standard treatment is the intrapleural instillation of a chemical agent to produce a pleurodesis. The recommended sclerosant is talc, a tetracycline derivative, or Corynebacterium parvum where it is available. When a patient is not an ideal candidate for chemical pleurodesis, the options include symptomatic treatment, serial thoracentesis, implantation of a pleuroperitoneal shunt, and pleurectomy.

Anti-Bacterial Agents

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

Corynebacterium parvum versus tetracycline as pleural sclerosing agents in rabbits.

Tetracycline has been one of the most commonly used agents for producing a pleurodesis. However, it is no longer available due to more stringent requirements on the manufacturing process. The objective of this project was to determine whether Corynebacterium parvum is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anaesthetized male rabbits: tetracycline 35 mg.kg-1 or C. parvum 4 or 8 mg, all diluted with bacteriostatic saline solution. Twenty eight days after the instillation, the animals were sacrificed and the pleural spaces assessed macroscopically for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of C. parvum was ineffective in creating pleural fibrosis. The mean degree of pleurodesis in the 10 rabbits who received tetracycline was 3.5 +/- 0.7 (scale 0-4) whilst in the 10 rabbits that received 4 mg C. parvum it was 0.0 +/- 0.0, and in the 10 rabbits that received 8 mg C. parvum it was 0.5 +/- 0.8. Based on this study, we recommend that C. parvum should not be used as a pleural sclerosant in patients with normal pleura.

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

Theophylline-ranitidine interaction in elderly COPD patients.

Most controlled studies in humans indicate that ranitidine does not alter theophylline metabolism, even at high doses. However, there have been several case reports published recently which demonstrate the development of theophylline toxicity mostly in older patients receiving stable oral doses of this drug when ranitidine was administered simultaneously. We studied eleven elderly (mean age, 69.0 +/- 6.2 years) patients with chronic obstructive pulmonary disease (COPD). During one week the patients took slow-release theophylline, 200 mg every 12 h, followed by one week intake of the same dose of theophylline plus ranitidine tablets, 150 mg every 12 h. At the end of each period, blood samples were obtained 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12 h after the morning dose for the determination of serum theophylline levels. The peak theophylline concentration (Tmax) was achieved after 4.1 +/- 0.9 h while the patients were taking theophylline, and after 2.9 +/- 1.4 h with the combined regimen. This difference was statistically significant (P < 0.01). In only 3/11 subjects did Tmax remain unchanged during both phases of the study. The mean theophylline clearance rates while the patients were receiving theophylline alone (39.58 +/- 19.89 ml/min) and when they were receiving both medications (34.42 +/- 10.55 ml/min) were similar. The mean serum levels while the patients were receiving theophylline alone were slightly higher but not statistically different. These results suggest that the reported increases in serum theophylline levels in older patients receiving theophylline and ranitidine cannot be ascribed to slower theophylline metabolism in the geriatric patients with COPD who is also given ranitidine.

Age Factors