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Background and Objective: The mechanism by which iodopovidone achieves pleurodesis is unknown. This study investigated whether iodopovidone is as effective as doxycycline in producing pleurodesis and whether systemic corticosteroids diminish its efficacy., Methods: Four groups of seven New Zealand rabbits were assigned to the following intrapleural treatment groups: 2 mL of 2% iodopovidone, 2 mL of 4% iodopovidone, 2 mL of 4% iodopovidone plus 0.8 mg/kg triamcinolone intramuscularly weekly and 10 mL/kg doxycycline in 2 mL. Pleural fluid was collected 24, 48 and 72 h after intrapleural injections and analysed for WCC, protein and LDH levels. The rabbits were killed 2 weeks after the injections. Pleurodesis was graded macroscopically on a scale from 1 to 8. The degree of microscopic pleural fibrosis and pleural inflammation was graded from the HE stain slides., Results: The mean volume of pleural fluid as well as the mean total WCC was significantly lower in the steroid-treated group than in the other groups. The degree of the resulting pleurodesis was similar in the 2% iodopovidone (7.00 +/- 1.29), 4% iodopovidone (7.71 +/- 0.76) and doxycycline (7.14 +/- 0.90) groups (P > 0.05) whereas the pleurodesis score of the steroid group (3.71 +/- 1.98) was significantly lower than all other groups (P < 0.05). The degree of microscopic pleural fibrosis and pleural inflammation was significantly lower in the steroid group than in the 2% iodopovidone or 4% iodopovidone group., Conclusions: Both 2% and 4% iodopovidone can induce pleurodesis as efficaciously as doxycycline in rabbits. Systemic corticosteroids significantly decrease the efficacy of iodopovidone in producing pleurodesis.

Objective: To determine whether the concomitant administration of ketoprofen, a non-steroidal anti-inflammatory drug (NSAID) has any effect on the pleurodesis induced by talc or doxycycline in rabbits., Methods: Four groups of seven New Zealand rabbits were assigned to receive the following treatments: 400mg/kg of talc intrapleurally only (group 1), 400mg/kg of talc plus 1mg/kg of ketoprofen intramuscularly (group 2), 10mg/kg of doxycycline intrapleurally only (group 3) and 10mg/kg of doxycycline plus 1mg/kg of ketoprofen intramuscularly (group 4). Intramuscular administration of ketoprofen began 4h before the intrapleural administration of the sclerosing agents, followed by twice daily administrations for 1 week. Pleural fluid was collected 24, 48 and 72h after intrapleural injections. Pleurodesis was evaluated macroscopically and microscopically after 14 days., Results: The concomitant use of ketoprofen at 1mg/kg does not decrease the WBC, LDH, and protein in pleural fluid at 24h following intrapleural injection of talc or doxycycline. There were no significant differences in the macroscopic pleurodesis scores, the degree of microscopic pleural fibrosis, the thickness of the pleura or the percent of the pleura occupied with angiogenesis., Conclusions: The study shows that the short-term systemic administration of NSAIDs does not affect the efficacy of pleurodesis induced by talc or doxycycline in rabbits.

Background: It has been suggested that talc and doxycycline might be acting through different pathways in creating pleurodesis. We hypothesized that combining doxycycline and talc in half the usual doses would be synergistic in inducing pleurodesis., Methods: Thirty-two rabbits were equally allocated into four groups: group 1, half-dose combination (5 mg/kg of doxycycline and 200 mg/kg of talc slurry); group 2, quarter-dose combination (2.5 mg/kg of doxycycline and 100 mg/kg of talc slurry); group 3, half-dose doxycycline (5 mg/kg of doxycycline); and group 4, half-dose talc (100 mg/kg of talc slurry). The pleurodesis scores from historical groups that received a full dose of talc (400 mg/kg) or doxycycline (10 mg/kg) were also compared to those obtained in the current study. Pleural fluid lactate dehydrogenase and protein levels were measured 24 h after the injection. Pleurodesis was graded from 1 (none) to 8 (> 50% symphysis) by two observers blinded to treatment groups. All rabbits underwent an ultrasonic examination on each side of their chest for the evaluation of pleurodesis., Results: The mean pleurodesis score in the half-dose combination group was significantly higher than that in the half-dose talc group, half-dose doxycycline group, and the historical full-dose talc group (p = 0.009, p = 0.01, and p < 0.05, respectively). The quarter-dose combination group also had a significantly higher mean pleurodesis score compared to the half-dose talc group (p = 0.013). The difference between the historical full-dose doxycycline and the half-dose combination or quarter-dose combination groups was not significant (p > 0.05). A significantly positive correlation existed between the pleurodesis score and the ultrasound scores (r = 0.876, p = 0.000000005)., Conclusions: This study demonstrates that the combination of half doses of talc and doxycycline is more effective than the half dose of either drug alone or the full dose of talc in producing pleurodesis in rabbits. In addition, ultrasound is an accurate imaging modality for the evaluation of pleurodesis, in that the absence of pleural gliding on ultrasound correlates well with the presence of a pleurodesis in rabbits.

Purposes: We investigated whether oral tetracyclines could produce an efficient and safe pleurodesis as does parenteral doxycycline, which is currently unavailable in many countries., Methods: Parenteral doxycycline (10 mg/kg), oral tetracycline (35 mg/kg), or doxycycline (10 mg/kg) was injected intrapleurally through a right chest tube in rabbits. The oral forms were dissolved in saline solution and passed through a sterile membrane filter. When daily aspirated pleural fluid was < 5 mL/24 h, the chest tube was removed. Fluid WBC, lactate dehydrogenase (LDH), and protein levels were measured 24 h after the injection. After the death of the animals on day 14, pleurodesis was graded from 1 (none) to 8 (> 50% symphysis) by two observers blinded to treatment groups., Results: The right pleurodesis score of the combined oral groups (median, 7.0; interquartile range [IQR], 4.0; n = 26) did not differ significantly (p = 0.349) from that of the parenteral group (median, 7.5; IQR, 6.0; n = 10). Oral tetracycline (capsule or tablet, n = 6 in each group) and doxycycline (capsule or tablet, n = 7 in each group) were as effective as parenteral doxycycline in producing pleurodesis: tetracycline capsule (median, 7.50; IQR, 6.00); tetracycline tablet (median, 6.50; IQR, 6.00); doxycycline capsule (median, 4.00; IQR, 1.00); doxycycline tablet (median, 8.00; IQR, 5.00), and parenteral doxycycline (median, 7.50; IQR, 6.00) [p = 0.235]. The left pleurodesis scores were 1.00 in all 36 rabbits. Fluid total volume, WBC, LDH, and protein levels were comparable between each oral and parenteral group, excluding WBCs in the tetracycline tablet group (p = 0.047). The complications were nonfatal (right hemothorax: tetracycline capsule [n = 3]/tetracycline tablet [n = 2], doxycycline tablet [n = 2], parenteral doxycycline [n = 2]; left hemothorax: tetracycline capsule [n = 1]; ascites: parenteral doxycycline [n = 1]). There was no growth on all filtrate cultures. Oral forms cost less than parenteral doxycycline (<1 US dollar vs 4.72 US dollars per rabbit). Filtering costs were 1.12 US dollars per rabbit., Conclusion: Oral tetracycline or doxycycline is as effective and safe as parenteral doxycycline in producing pleurodesis in rabbits; thus, they may also be used in humans.

Study Objectives: The intrapleural injection of transforming growth factor (TGF)-beta2 produces pleurodesis in rabbits associated with large pleural effusions. This study investigated whether anti-vascular endothelial growth factor (VEGF) antibody has any effect on the fluid production or the pleurodesis induced by TGF-beta2., Interventions and Measurements: Three groups of seven New Zealand white rabbits were administered TGF-beta2 5.0 microg intrapleurally. Two groups received anti-VEGF antibody (10 mg/kg and 25 mg/kg) IV 24 h before TGF-beta2 injection, and the third group received no antibody. The rabbits were killed at 2 weeks, and the macroscopic pleurodesis score was determined. The degree of pleural angiogenesis was assessed by immunohistochemical staining for factor VIII., Results: The administration of anti-VEGF antibodies had no significant effect on the pleural fluid volume or the characteristics of the fluid. The mean pleurodesis score of the seven rabbits in the control group (7.71 +/- 0.76) was significantly (p < 0.05) higher than that for seven rabbits in the low-dose treatment group (4.43 +/- 2.37) and the seven rabbits in the high-dose treatment group (4.57 +/- 2.36) [+/- ]. The percentage of pleural tissue demonstrating angiogenesis in the control group (4.87 +/- 0.43%) was significantly (p < 0.05) higher than that for the low-dose (2.94 +/- 0.68%) or high-dose (2.67 +/- 0.64%) antibody groups. When all rabbits were considered, there was a highly significant correlation between the pleural vascular density scores and the pleurodesis scores (r = 0.84, p < 0.01)., Conclusion: VEGF and angiogenesis appear to play a pivotal role in the production of a pleurodesis.

Introduction: The treatment of recurrent pleural effusion or recurrent pneumothorax frequently involves the creation of a pleurodesis. Ultrasound is being used more frequently to assess the presence of pleural fluid or pneumothorax. With ultrasound, the gliding sign displays the gliding of the visceral pleura over the parietal pleura during respiration. The absence of a gliding sign is indicative of a pneumothorax., Hypothesis: We hypothesized that the presence of pleurodesis would be indicated by the absence of a gliding sign on ultrasound., Methods: To create a pleurodesis, a single intrapleural injection of transforming growth factor-beta2 at a dosage of 1.70 microg/kg or doxycycline at a dosage of 10 mg/kg in a volume of 2.0 mL was administered randomly to one side of a New Zealand White rabbit. Prior to death on day 14 after intrapleural injection, all rabbits underwent an ultrasonic examination at three marked sites on each side of the chest. At each site, three ultrasonic features (gliding sign, pleural thickening, and pleural effusion) were evaluated and graded. The gliding sign was graded as follows: 0 = gliding sign definitely present, 1 = gliding sign questionable, 2 = gliding sign absent., Results: In a preliminary study for developing skill in assessing the gliding sign, the correlation between the gliding sign and the pleurodesis score in 16 rabbits was highly significant (r = 0.568, p = 0.02). In the subsequent main study with 18 additional rabbits, the correlation between the gliding sign score and the pleurodesis score was even better (r = 0.806, p = 0.00009). The gliding sign was definitely present on the noninjected side in all rabbits., Conclusions: The presence of a pleurodesis is indicated by the absence of a pleural guiding sign on ultrasound.

Study Objective: The aim of this study was to examined whether transforming growth factor (TGF)-beta(3) induces pleurodesis in rabbits and collagen production by human pleural mesothelial cells in vitro., Design: A combined animal and in vitro study., Methods: TGF-beta(3) was injected intrapleurally in rabbits at the following doses: 0.167 mug, 0.5 mug, 1.67 mug, and 5 mug (five rabbits per group). The rabbits were killed 14 days following injection, and pleurodesis was graded from 1 (none) to 8 (complete symphysis). Pleural mesothelial cell cultures were established from benign pleural effusions and treated with TGF-beta(3) for 48 h at the following doses: 0 (control), 5 ng/mL, 1.5 ng/mL, 5 ng/mL, and 15 ng/mL and 50 ng/mL (two independent experiments). Collagen I messenger RNA (mRNA) expression was quantified using real-time polymerase chain reaction., Results: The median pleurodesis score was 5 (interquartile range [IQR], 4.5) in the 0.167-mug group, 6 (IQR, 5) in the 0.5-mug group, 8 (IQR, 1) in the 1.67-mug group, and 8 (IQR, 0.5) in the 5-mug group (p = 0.012). Higher TGF-beta(3) doses induced the production of significantly more pleural fluid than the lower doses (p = 0.005). The pleural fluid induced by higher doses contained significantly lower numbers of nucleated cells (p = 0.014) and lactate dehydrogenase levels (p = 0.013) than the pleural fluid induced by lower doses of the agent. TGF-beta(3) markedly enhanced collagen I mRNA expression by the human pleural mesothelial cells. This effect peaked at 5 ng/mL TGF-beta(3). With this dose of TGF-beta(3), the collagen I mRNA expression was increased 16-fold over control levels., Conclusion: TGF-beta(3) causes a dose-dependent pleurodesis when administered intrapleurally in rabbits, and induces collagen messenger RNA synthesis from human pleural mesothelial cells.

Background: Transforming growth factor (TGF)-beta2 can produce effective pleurodesis in animals, but its efficacy has not been compared with commonly used pleurodesing agents in sheep, which have a thick pleura resembling that of humans. The acute physiological effects and the level of systemic TGF-beta absorption after its intrapleural administration have not been studied. The aims of the present study were to compare: (i) the effectiveness of TGF-beta2, talc and bleomycin in producing pleurodesis in sheep; (ii) the acute side-effects and systemic TGF-beta levels following the intrapleural administration of these agents; and (iii) histological changes after intrapleural injections of these agents., Methodology: Twelve sheep were divided into three groups and were given a single intrapleural dose of TGF-beta2 (0.25 microg/kg), talc slurry (5 g) or bleomycin (60 IU) via a chest tube. Saline or buffer was injected into the contralateral side, which served as the control. Arterial blood gases and respiratory and heart rates were monitored for the first 24 h. Plasma levels of TGF-beta1 and TGF-beta2 were measured. Pleurodesis was graded macroscopically from 1 (none) to 8 (symphysis > 50% of hemithorax) at day 14., Results: At day 14, the pleurodesis score of the TGF-beta2 group (7.7+/-0.6) was similar to that of the talc (7.0+/-1.7) group and significantly higher than that of the bleomycin group (3.3+/-2.3; P < 0.05). No significant differences were seen in arterial blood gas analysis, vital signs and plasma TGF-beta1 and TGF-beta2 concentrations among the three groups., Conclusions: Transforming growth factor-beta2 was as effective as talc and more so than bleomycin in inducing pleurodesis in sheep. Intrapleural administration of TGF-beta2 appeared safe. No acute changes in gaseous exchange or macroscopic abnormalities were seen following intrapleural TGF-beta2. Importantly, there was no evidence of an increase in systemic TGF-beta levels following its intrapleural administration.

Vascular endothelial growth factor (VEGF) increases vascular permeability and is important in pleural effusion formation. In studies using transforming growth factor beta (TGF-beta) to produce pleurodesis, we observed that although TGF-beta was more effective than talc or doxycycline, it induced transient production of large pleural effusions. We hypothesized that TGF-beta stimulates VEGF production in pleural tissues in vivo, and by mesothelial cells in vitro. New Zealand White rabbits (n = 33) were given TGF-beta(2) (1.7 or 5.0 microg), talc (400 mg/kg), doxycycline (10 mg/kg), or buffer intrapleurally. Pleural fluid was collected at 24 h. Intrapleural injection of TGF-beta(2) induced a dose-dependent increase in VEGF production. The pleural fluid VEGF level was 2-fold higher in rabbits given 5.0 microg of TGF-beta(2) than in those given 1.7 microg of TGF-beta(2) and 3-fold higher than in those given buffer. VEGF levels were higher after the injection of TGF-beta(2) than after administration of talc or doxycycline. The pleural fluid VEGF correlated significantly with the volume of pleural effusions (r = 0.79, p < 0.00001). In vitro, TGF-beta(2) stimulated a dose-dependent increase in VEGF production from murine pleural mesothelial cells. At 4 and 24 h, TGF-beta(2), but not talc or doxycycline, induced a significant increase in VEGF, when compared with controls. The mesothelial cell VEGF production was significantly reduced by anti-TGF-beta antibody in the TGF-beta(2), talc, and control (buffer and medium) groups. In conclusion, mesothelial cells are an important source of VEGF. TGF-beta increases the VEGF production by mesothelial cells in vivo and in vitro.

Background and objective: The mechanism by which iodopovidone achieves pleurodesis is unknown. This study investigated whether iodopovidone is as effective as doxycycline in producing pleurodesis and whether systemic corticosteroids diminish its efficacy. Methods: Four groups of seven New Zealand rabbits were assigned to the following intrapleural treatment groups: 2 mL of 2% iodopovidone, 2 mL of 4% iodopovidone, 2 mL of 4% iodopovidone plus 0.8 mg/kg triamcinolone intramuscularly weekly and 10 mL/kg doxycycline in 2 mL. Pleural fluid was collected 24, 48 and 72 h after intrapleural injections and analysed for WCC, protein and LDH levels. The rabbits were killed 2 weeks after the injections. Pleurodesis was graded macroscopically on a scale from 1 to 8. The degree of microscopic pleural fibrosis and pleural inflammation was graded from the HE stain slides. Results: The mean volume of pleural fluid as well as the mean total WCC was significantly lower in the steroid-treated group than in the other groups. The degree of the resulting pleurodesis was similar in the 2% iodopovidone (7.00 ± 1.29), 4% iodopovidone (7.71 ± 0.76) and doxycycline (7.14 ± 0.90) groups ( P > 0.05) whereas the pleurodesis score of the steroid group (3.71 ± 1.98) was significantly lower than all other groups ( P < 0.05). The degree of microscopic pleural fibrosis and pleural inflammation was significantly lower in the steroid group than in the 2% iodopovidone or 4% iodopovidone group. Conclusions: Both 2% and 4% iodopovidone can induce pleurodesis as efficaciously as doxycycline in rabbits. Systemic corticosteroids significantly decrease the efficacy of iodopovidone in producing pleurodesis. [ABSTRACT FROM AUTHOR]

Intrapleural fibrin deposition and subsequent fibrosis characterize evolving empyema and contribute to the morbidity associated with this condition. Single-chain urokinase (scuPA) is proenzyme form of the urokinase plasminogen activator, which has recently been shown to effectively clear intrapleural loculation in tetracycline-induced pleurodesis in rabbits. The authors therefore hypothesized that scuPA could likewise improve intrapleural injury associated with empyema. The authors used a rabbit model of empyema induced by intrapleural administration of Pasturella multocida to test this hypothesis and determined the effects of intrapleural scuPA on pleural fluids indices of inflammation and intrapleural fibrosis. The authors found that intrapleural administration of scuPA was well tolerated, generated readily detectable fibrinolytic activity in the empyema fluids and did not induce intrapleural or systemic bleeding. Pleural fluid volume, intrapleural protein, and D-dimer concentrations were increased at 24 and 48 hours (P < .01, respectively) after induction of empyema. Intrapleural loculation did not occur in the scuPA- or vehicle control-treated animals and there was no significant change in the pleural empyema or thickening scores. These findings confirm that intrapleural scuPA generates fibrinolysis in empyema fluids but does not alter fibrotic repair at the pleural surface or the intensity of intrapleural inflammation in this empyema model. [ABSTRACT FROM AUTHOR]

The article reports on the efficacy of ultrasound in the diagnosis of pleurodesis in rabbits. The treatment of recurrent pleural effusion or recurrent pneumothorax frequently involves the creation of a pleurodesis. Ultrasound is being used more frequently to assess the presence of pleural fluid or pneumothorax. Pleurodesis usually results from pleural inflammation produced by an injury to the pleura. The assessment of the presence of a pleurodesis is difficult. Advances in technology have greatly improved the imaging capabilities of ultrasound. Using ultrasound, the parietal pleura and the visceral pleura are normally seen as two thin, bright echogenic lines just beneath the chest wall.

Study objective: The aim of this study was to examined whether transforming growth factor (TGF)-β3 induces pleurodesis in rabbits and collagen production by human pleural mesothelial cells in vitro. Design: A combined animal and in vitro study. Methods: TGF-β3 was injected intrapleurally in rabbits at the following doses: 0.167 =g, 0.5 =g, 1.67 =g, and 5 =g (five rabbits per group). The rabbits were killed 14 days following injection, and pleurodesis was graded from 1 (none) to 8 (complete symphysis). Pleural mesothelial cell cultures were established from benign pleural effusions and treated with TGF-β3 for 48 h at the following doses: 0 (control), 5 ng/mL, 1.5 ng/mL, 5 ng/mL, and 15 ng/mL and 50 ng/mL (two independent experiments). Collagen I messenger RNA (mRNA) expression was quantified using real-time polymerase chain reaction. Results: The median pleurodesis score was 5 (interquartile range [IQR], 4.5) in the 0.167-µg group, 6 (IQR, 5) in the 0.5-µg group, 8 (IQR, 1) in the 1.67-µg group, and 8 (IQR, 0.5) in the 5-µg group (p = 0.012). Higher TGF-β3 doses induced the production of significantly more pleural fluid than the lower doses (p = 0.005). The pleural fluid induced by higher doses contained significantly lower numbers of nucleated cells (p = 0.014) and lactate dehydrogenase levels (p = 0.013) than the pleural fluid induced by lower doses of the agent. TGF-β3 markedly enhanced collagen I mRNA expression by the human pleural mesothelial cells. This effect peaked at 5 ng/mL TGF-β3. With this dose of TGF-β3, the collagen I mRNA expression was increased 16-fold over control levels. Conclusion: TGF-β3 causes a dose-dependent pleurodesis when administered intrapleurally in rabbits, and induces collagen messenger RNA synthesis from human pleural mesothelial cells. [ABSTRACT FROM AUTHOR]

Background: Transforming growth factor (TGF)-β2 can produce effective pleurodesis in animals, but its efficacy has not been compared with commonly used pleurodesing agents in sheep, which have a thick pleura resembling that of humans. The acute physiological effects and the level of systemic TGF-β absorption after its intrapleural administration have not been studied. The aims of the present study were to compare: (i) the effectiveness of TGF-β2, talc and bleomycin in producing pleurodesis in sheep; (ii) the acute side-effects and systemic TGF-β levels following the intrapleural administration of these agents; and (iii) histological changes after intrapleural injections of these agents. Methodology: Twelve sheep were divided into three groups and were given a single intrapleural dose of TGF-β2 (0.25 μg/kg), talc slurry (5 g) or bleomycin (60 IU) via a chest tube. Saline or buffer was injected into the contralateral side, which served as the control. Arterial blood gases and respiratory and heart rates were monitored for the first 24 h. Plasma levels of TGF-β1 and TGF-β2 were measured. Pleurodesis was graded macroscopically from 1 (none) to 8 (symphysis > 50% of hemithorax) at day 14. Results: At day 14, the pleurodesis score of the TGF-β2 group (7.7 ± 0.6) was similar to that of the talc (7.0 ± 1.7) group and significantly higher than that of the bleomycin group (3.3 ± 2.3; P < 0.05). No significant differences were seen in arterial blood gas analysis, vital signs and plasma TGF-β1 and TGF-β2 concentrations among the three groups. Conclusions: Transforming growth factor-β2 was as effective as talc and more so than bleomycin in inducing pleurodesis in sheep. Intrapleural administration of TGF-β2 appeared safe. No acute changes in gaseous exchange or macroscopic abnormalities were seen following intrapleural TGF-β2. Importantly, there was no evidence of an increase in systemic... [ABSTRACT FROM AUTHOR]

Background: We have recently demonstrated that transforming growth factor beta-2 ( TGF-β2 ) can produce effective pleurodesis. Whether this effect can be reproduced by the use of its downstream proteins is not known. This study compared the effectiveness of TGF-β2 and fibronectin in inducing pleurodesis in rabbits. Methodology: New Zealand white rabbits (1.5–2.0 kg) were given 1.7 μg of TGF-β2 (n = 5) or 2.0 mg of cellular fibronectin (n = 4) intrapleurally via a chest tube. The induced pleural fluid was collected and analyzed. The rabbits were sacrificed after 14 days. The pleurodesis was graded macroscopically from 1 (none) to 8 (symphysis > 50%). Results: All rabbits in the TGF-β2 group developed effective pleurodesis while none in the fibronectin group had scores > 2 (pleurodesis scores 7.0 ± 0.6 vs 1.3 ± 0.3, P < 0.001). Rabbits that received TGF-β2 produced large amounts of pleural fluid initially (< 4 days). Microscopically, the pleura of rabbits in the TGF-β2 group showed prominent spindle cell proliferation and collagen deposition, but no significant inflammation or mesothelial proliferation. Pleural tissues of rabbits in the fibronectin group had occasional thin collagen deposits only. The intrapleural administration of 2.0 mg of fibronectin, a downstream product of TGF-β, did not induce effective pleurodesis, as did the intrapleural administration of TGF-β2 . Conclusions: The present study suggests that the mechanism by which TGF-β2 induces pleurodesis is not predominantly dependent on the production of fibronectin. [ABSTRACT FROM AUTHOR]