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Biomedical subjects

L R Teixeira

Publications and source records attributed to L R Teixeira.

At least 19 recordsLinked to original sources

Transforming growth factor beta2 induced pleurodesis is not inhibited by corticosteroids.

BACKGROUND: Talc and tetracyclines induce pleurodesis by directly injuring the pleura. The injury results in intense inflammation which subsequently leads to fibrosis. Corticosteroids can inhibit talc pleurodesis by reducing the inflammatory process. We hypothesised that transforming growth factor beta2 (TGFbeta2), a fibrogenic cytokine with immunomodulatory functions, could induce effective pleurodesis without generating significant pleural inflammation and therefore remain effective despite co-administration of corticosteroids. METHODS: Thirty rabbits were divided into two groups. Rabbits in the steroid group received weekly intramuscular injections of triamcinolone diacetate (0.8 mg/kg). Ten rabbits in each group were given 5.0 microg TGFbeta2 intrapleurally via a chest tube while the remaining five received 1.7 microg TGFbeta2. Pleurodesis was graded macroscopically after 14 days from 1 (none) to 8 (>50% symphysis). RESULTS: TGFbeta2 produced excellent pleurodesis at both 5.0 microg and 1.7 microg doses. The pleural effusions produced after the injection were low in all inflammatory markers. No significant differences were seen between the steroid group and controls in macroscopic pleurodesis scores (7.2 (1.3) v 7.1 (1.2)), levels of inflammatory markers in the pleural fluids (leucocyte 1107 (387)/mm(3) v 1376 (581)/mm(3); protein 3.1 (0.3) mg/dl v 2.9 (0.3) mg/dl, and LDH 478 (232) IU/l v 502 (123) IU/l), and the degree of microscopic pleural fibrosis and pleural inflammation. CONCLUSIONS: TGFbeta2 can induce effective pleurodesis and remains effective in the presence of high dose parenteral corticosteroids.

Animals↗

Transforming growth factor-beta2 induces pleurodesis significantly faster than talc.

Transforming growth factor-beta2 (TGF-beta2) has recently been shown to produce effective pleurodesis in rabbits. Conventional pleurodesing agents such as talc act by inducing pleural injury, which results in acute inflammation and fibrosis. TGF-beta2 is a profibrotic cytokine capable of producing fibrosis without inducing significant pleural inflammation. We hypothesize that intrapleural administration of TGF-beta2 would (1) produce an effective pleurodesis faster; (2) stimulate more collagen deposition, and (3) induce less inflammation when compared with intrapleural injection of talc. Thirty rabbits were divided into two groups and given either TGF-beta(2) (1.7 microg) or talc slurry (400 mg/kg) via a chest tube. Five rabbits from each group were killed at Days 1, 4, and 7. Gross pleurodesis was graded from 1 (none) to 8 (complete symphysis). The microscopic pleural inflammation and fibrosis were graded from 0 to 4. Pleural thickening and the total area of collagen deposition were compared. Intrapleural injection of TGF-beta2 produced effective pleurodesis within 7 d (median pleurodesis score = 7 at Day 7). At Day 7, TGF-beta2 induced significantly more collagen deposition (19.4 +/- 19.6% versus 4.6 +/- 2.9% of total area of pleura at Day 7), higher pleural fibrosis score (3.0 +/- 1.0 versus 1.8 +/- 0.5), and pleural thickness (286 +/- 191 versus 85 +/- 37 microm) than did talc. There was no difference in the degree of pleural inflammation between the two groups at Day 7 (2.6 +/- 0.9 for TGF-beta2 versus 2.4 +/- 0.6 for talc) or at any other time points. In conclusion, the intrapleural administration of TGF-beta2 produced excellent pleurodesis in rabbits at a rate faster than talc slurry and all other pleurodesing agents investigated before. TGF-beta2 stimulated more collagen deposition without inducing excess inflammation when compared with talc slurry. TGF-beta2 may have advantages over talc slurry in the management of recurrent pleural effusion and pneumothorax.

Animals↗

Relationship between pleural fluid and serum cholesterol levels.

INTRODUCTION: Since the criteria of Light and colleagues for differentiating transudates and exudates were described, other tests, including the pleural fluid (PF) cholesterol test, have been proposed for the same purpose. However, the factors influencing PF cholesterol levels have not been clearly delineated. PURPOSE: To analyze the relationships among total cholesterol (CHOL), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TRIG) in serum (S) and PF. METHODS: PF and S from 99 patients (transudates, 13 patients; exudates, 86 patients) were analyzed for CHOL, HDL, LDL, TRIG, apolipoprotein AI, apolipoprotein B, and protein. The relationship between the PF and S level for each of these measurements was analyzed with linear regression and multiple regression using the ratio of PF to S protein for that measurement as a second independent variable. RESULTS: This study demonstrated that CHOL levels in PF are related to S cholesterol levels and to the permeability of the pleura (r = 0.88; p < 0.001). However, the percentage of CHOL associated with LDL and HDL (56%) in the PF was much lower than that associated with LDL and HDL in S (93%), suggesting that lipoproteins are modified once they enter the pleural space. The PF TRIG was not closely related to its S level or to the PF/S protein ratio (r = 0.49). CONCLUSION: PF cholesterol levels can be closely predicted from the S cholesterol levels and the permeability of the pleura, as reflected by the ratio of PF protein to S protein. Therefore, the CHOL ratio should not provide additional information to that provided by the protein ratio when trying to differentiate transudates from exudates. PF lipoproteins (LDL and HDL) undergo metabolic alterations once they enter the pleural space. PF TRIG levels are not closely related to S levels or to the permeability of the pleura.

Apolipoprotein A-I↗

Thoracoscopy talc poudrage : a 15-year experience.

OBJECTIVES: To review our experience with thoracoscopy and talc poudrage during the previous 15 years with regards to efficacy, side effects, morbidity, and mortality. METHODS: Six hundred fourteen consecutive patients (58.6% female; mean age, 54.5 years) underwent thoracoscopy with talc poudrage from August 1983 to May 1999. Of these, 457 patients had malignant pleural effusions, 108 patients had benign pleural effusions, and 49 patients had spontaneous pneumothorax. RESULTS: Sixty-four patients were excluded from evaluation for efficacy: 30 patients (4.9%) because the lung did not expand at the time of the procedure and 34 patients (5.5%) because they died within 30 days of the thoracoscopy. All exclusions were in the malignant group. The overall success rate of the 393 patients with malignant pleural effusions was 93.4%, while the overall success for the 108 patients with benign effusions was 97%, although 7 patients (7%) with benign effusions required a second thoracoscopy. The success rate with pneumothorax was 100%. Major morbidity included empyema in 4%, reexpansion pulmonary edema in 2.2%, and respiratory failure 1.3%. CONCLUSION: Thoracoscopy with talc poudrage is effective in producing a pleurodesis in malignant and benign pleural effusion and in spontaneous pneumothorax. However, it should be noted that the insufflation of talc has a systemic distribution associated with a low rate of morbidity and perhaps does induce ARDS, which is sometimes fatal in a small percentage of patients. Because of these side effects, the search for a better agent should be continued.

Female↗

Experimental pleurodesis in rabbits induced by silver nitrate or talc: 1-year follow-up.

STUDY OBJECTIVE: To compare the pleurodesis results from the intrapleural injection of silver nitrate and talc slurry over an observation period of 12 months in rabbits. DESIGN: Rabbits were randomized to receive 2 mL of 0.5% silver nitrate or 400 mg/kg of talc slurry in 2 mL intrapleurally. Ten rabbits in each group were killed at 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, and 12 months after intrapleural injection. The degree of gross pleurodesis and the amount of microscopic pleural fibrosis and inflammation were graded on a scale of 0 to 4. RESULTS: The mean +/- SEM gross pleurodesis score in the 70 rabbits that received silver nitrate was 3.34 +/- 0.08, which was significantly higher than the score of 2.32 +/- 0.09 in the 70 rabbits that received talc. The mean gross pleurodesis score was significantly higher at each of the observation times (p < 0.05), except at 2 months, in the rabbits that received silver nitrate. The pleurodesis was distributed throughout the thorax in the rabbits that received silver nitrate, while it was only in the ventral thorax in the rabbits that received talc slurry. The gross pleurodesis scores showed no tendency to decrease during the 12-month observation period in either treatment group. The persistence of talc in the pleural space did not lead to chronic inflammatory changes because the inflammation scores were similar in both groups at all observation times. The microscopic pleural fibrosis score tended to decrease with time in the silver nitrate group but not in the talc slurry group. CONCLUSIONS: The intrapleural injection of 2 mL of 0.5% silver nitrate produces a better pleurodesis than does the intrapleural injection of 400 mg/kg of talc slurry in rabbits. The pleurodesis induced by silver nitrate persists for at least 1 year. The efficacy of silver nitrate as a sclerosing agent in humans should be evaluated.

Animals↗

A new look at old agents for pleurodesis: nitrogen mustard, sodium hydroxide, and silver nitrate.

In this review we analyze the evolution of pleurodesis. In spite of the fact that this procedure started in the beginning of the 20th century, the ideal sclerosing agent is not yet known. Emphasis is placed on the current tendency toward minimally invasive procedures in which insertion of catheters is favored over surgical procedures such as placement of chest tubes or thoracoscopy. Among the sclerosing agents, talc is preferred throughout the world. However, the possible development of acute respiratory distress syndrome, which is sometimes fatal, caused the awakening of interest in other drugs. Nitrogen mustard induces pleurodesis but causes important side effects. Sodium hydroxide and silver nitrate are effective and may be used in humans beings.

Alkylating Agents↗

Antibiotic levels in empyemic pleural fluid.

OBJECTIVE: To determine the degree to which bioactive penicillin, metronidazole, ceftriaxone, clindamycin, vancomycin, and gentamicin penetrate into empyemic pleural fluid using our new rabbit model of empyema. METHODS: An empyema was created via the intrapleural injection of 10(8)()Pasteurella multocida bacteria into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, penicillin, 24,000 U/kg; metronidazole, 37 mg/kg; ceftriaxone, 30 mg/kg; clindamycin, 9 mg/kg; vancomycin, 15 mg/kg; or gentamicin, 1 mg/kg, were administered IV. Antibiotic levels in samples of pleural fluid and serum, collected serially for up to 480 min, were then determined using a bioassay. RESULTS: The degree to which the different antibiotics penetrated into the infected pleural space was highly variable. Penicillin penetrated most easily, followed by metronidazole, ceftriaxone, clindamycin, vancomycin, and gentamicin. Of the antibiotics tested, penicillin and metronidazole equilibrated the most rapidly with the infected pleural fluid. Penicillin levels remained elevated in pleural fluid even after serum levels had decreased. CONCLUSIONS: Using this rabbit model of empyema, there was marked variation in the penetration of antibiotics into the empyemic fluid. Although there are species differences between rabbit and human pleura, the variance in degree of penetration of antibiotics into the pleural space should be considered when antibiotics are selected for the treatment of patients with empyema.

Animals↗

Silver nitrate is superior to talc slurry in producing pleurodesis in rabbits.

STUDY OBJECTIVE: The ideal agent for producing pleurodesis has not been identified. Although talc is the agent most commonly used at the present time, there are concerns about its safety. Silver nitrate is a possible alternative agent. The purpose of the present study was to compare the effectiveness of intrapleural silver nitrate and talc slurry in producing pleurodesis in rabbits. Additionally, the total amount of pleural collagen and the distribution of thick and thin collagen fibers were studied. DESIGN: Two groups of 10 rabbits received either 0.50% silver nitrate or 400 mg/kg talc in a total volume of 2 mL intrapleurally. The animals were killed 28 days after injection, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of inflammation and fibrosis. Collagen was assessed with the van Gieson's and picrosirius stains. RESULTS: The macroscopic pleurodesis (scale, 0 to 4; mean +/- SEM) resulting from the intrapleural injection of silver nitrate (3.4+/-0.2) was significantly better (p<0.001) than that resulting from talc (1.6+/- 0.1). The mean degree of microscopic pleural fibrosis induced by silver nitrate (3.3+/-0.3) was significantly higher (p = 0.003) than that induced by talc (1.8+/-0.1). The mean amount of microscopic pleural collagen (van Gieson's) was significantly greater (p<0.001) in the rabbits that received silver nitrate (3.0+/-0.2) than in those that received talc (1.6+/-0.2). The distribution of thick and thin collagen fibers did not differ between the groups. CONCLUSIONS: We conclude that, in our rabbit model, intrapleural silver nitrate was more effective than talc in producing a pleurodesis.

Animals↗

The utility of daily therapeutic thoracentesis for the treatment of early empyema.

STUDY OBJECTIVES: To determine if therapeutic thoracentesis is as effective as early chest tube placement or no drainage procedure in the treatment of early empyema in rabbits. DESIGN AND INTERVENTIONS: An empyema, as evidenced by gross pleural pus and a decreased pleural fluid pH and glucose level, was induced in 49 rabbits. The rabbits were divided into three groups: 16 underwent daily therapeutic thoracentesis starting at 48 h, 14 underwent chest tube placement at 48 h, and 19 served as controls. RESULTS: The mortality rate in the therapeutic thoracentesis group (0/16) did not differ significantly from that in the chest tube group (3/14) or that in the control group (6/19). At autopsy at 10 days, the gross empyema score in the therapeutic thoracentesis group (2.1 +/- 0.3) was significantly lower (p < 0.05) than that in the chest tube group (2. 8 +/- 0.3) or the control group (3.5 +/- 0.2). The mean pleural peel score of 5.8 +/- 1.1 in the therapeutic thoracentesis group was significantly less (p < 0.05) than the score for the nonintervention control group (13.4 +/- 1.6). CONCLUSIONS: From this study, we conclude that therapeutic thoracentesis is at least as effective as early chest tube placement for the treatment of early empyema using our rabbit model of empyema.

Animals↗

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↗

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↗

Antibiotic treatment of patients with pneumonia and pleural effusion.

Despite all medical advances of this century, pneumonia is still a common condition and the sixth leading cause of mortality in the United States. A pleural effusion develops in up to 40% of cases of pneumonia and empyema in 5% to 10% of those patients. The morbidity and mortality rates in patients with pleural effusions as a consequence of pneumonia are higher than in patients with pneumonia alone. In this review we discuss the classification, bacteriology, and the appropriate antibiotic treatment of patients with parapneumonic pleural effusions.

Adolescent↗

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↗

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↗

Doxycycline pleurodesis in rabbits: comparison of results with and without chest tube.

We have reported previously that there is a high incidence of hemothorax and substantial mortality in rabbits that are given tetracycline derivatives intrapleurally. However, such complications have not been reported in humans when pleurodesis is attempted with tetracycline derivatives. One primary difference in the two situations is that a chest tube is placed only in humans. The objective of this study was to evaluate the hypothesis that chest tube placement would prevent the development of hemothoraces and lead to better pleurodesis in rabbits given doxycycline intrapleurally. Eighty New Zealand White male rabbits received doxycycline, 20 mg/kg, in a total volume of 2 mL. One half of the rabbits were randomized to receive a chest tube at the time of the injection and were subjected to pleural fluid aspiration twice daily. The remaining rabbits (control group) received no chest tube and no aspiration. Ten rabbits from each group were killed on days 4, 7, 14, and 28. The intrapleural injection of doxycycline induced the production of large exudative effusions. The insertion of chest tubes prevented the development of hemothorax (0/20 in chest tube group, 15/20 in control group, p<0.001). The insertion of chest tubes was also associated with a significant reduction in mortality and a significant improvement in pleurodesis. When pleurodesis is attempted in rabbits with intrapleural doxycycline, the insertion of a chest tube will prevent hemothorax and lead to a better pleurodesis.

Animals↗

Effect of pneumothorax on pleurodesis induced with talc in rabbits.

OBJECTIVE: The purpose of this study was to determine if a small pneumothorax would influence the pleurodesis resulting from talc instillation. METHODS: Sixty rabbits received an intrapleural injection of 400 mg/kg talc slurry. One half also received 10 mL of air intrapleurally after the talc. Ten rabbits in each group were killed 2, 14, and 28 days after instillation. RESULTS: Two days after the injection, the mean volume of air in the animals that had received the air was 7.5+/-0.4 mL. There was no air present in any other rabbits. The volume of pleural fluid and the pleural fluid glucose, protein, cell count, and differential were similar in both groups on day 2, while the LDH level was significantly higher in the air group (p<0.05). The degree of gross adhesions and microscopic fibrosis was similar in both groups and increased with time. CONCLUSIONS: A small pneumothorax does not decrease the efficacy of talc pleurodesis in our experimental model. These results suggest that the presence of a small amount of intrapleural air is not a contraindication to talc pleurodesis in humans.

Animals↗

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↗