An approach to neuraxial anaesthesia for the severely scoliotic spine.

We report on a case in which computed tomography was used to guide placement of an epidural catheter in a patient with severe scoliosis and congenital dwarfism. In addition, the computed tomograms were corroborated with ultrasound and fluoroscopic images in the patient. Three years later, the patient had a spinal anaesthetic performed with only the use of ultrasound-guidance. Ease of placement of the epidural and spinal was greatly enhanced by imaging. We present an algorithmic approach to neuraxial anaesthesia in the patient with scoliosis to help guide placement. The algorithm first directs the provider to determine the type and severity of the scoliosis from the patient's history, physical examination, and any prior radiologic studies. If the anaesthesia provider understands and is comfortable with the patient's anatomy, then the provider may cautiously proceed with placement. Depending upon the degree of lateral curvature (Cobb angle), idiopathic scoliosis is classified as mild (11-25°), moderate (25-50°), or severe (>50°). Mild idiopathic scoliosis is managed with good positioning. Moderate idiopathic scoliosis is managed with a paramedian approach on the convex-side of the curve or a midline approach with angulation towards the convex-side or with the aid of imaging such as ultrasound. Severe idiopathic scoliosis is managed with the assistance of imaging or an alternative form of pain management should be considered. A systematic approach may facilitate safe, efficient, and successful neuraxial anaesthesia procedures in the scoliotic patient.

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.

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.

Comparing transforming growth factor beta-2 and fibronectin as pleurodesing agents.

BACKGROUND: We have recently demonstrated that transforming growth factor beta-2 (TGF-beta2) 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-beta2 and fibronectin in inducing pleurodesis in rabbits. METHODOLOGY: New Zealand white rabbits (1.5-2.0 kg) were given 1.7 microg of TGF-beta2 (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-beta2 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-beta2 produced large amounts of pleural fluid initially (< 4 days). Microscopically, the pleura of rabbits in the TGF-beta2 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-beta, did not induce effective pleurodesis, as did the intrapleural administration of TGF-beta2. CONCLUSIONS: The present study suggests that the mechanism by which TGF-beta2 induces pleurodesis is not predominantly dependent on the production of fibronectin.

Dynamics of actin-based movement by Rickettsia rickettsii in vero cells.

Actin-based motility (ABM) is a virulence mechanism exploited by invasive bacterial pathogens in the genera Listeria, Shigella, and Rickettsia. Due to experimental constraints imposed by the lack of genetic tools and their obligate intracellular nature, little is known about rickettsial ABM relative to Listeria and Shigella ABM systems. In this study, we directly compared the dynamics and behavior of ABM of Rickettsia rickettsii and Listeria monocytogenes. A time-lapse video of moving intracellular bacteria was obtained by laser-scanning confocal microscopy of infected Vero cells synthesizing beta-actin coupled to green fluorescent protein (GFP). Analysis of time-lapse images demonstrated that R. rickettsii organisms move through the cell cytoplasm at an average rate of 4.8 +/- 0.6 micrometer/min (mean +/- standard deviation). This speed was 2.5 times slower than that of L. monocytogenes, which moved at an average rate of 12.0 +/- 3.1 micrometers/min. Although rickettsiae moved more slowly, the actin filaments comprising the actin comet tail were significantly more stable, with an average half-life approximately three times that of L. monocytogenes (100.6 +/- 19.2 s versus 33.0 +/- 7.6 s, respectively). The actin tail associated with intracytoplasmic rickettsiae remained stationary in the cytoplasm as the organism moved forward. In contrast, actin tails of rickettsiae trapped within the nucleus displayed dramatic movements. The observed phenotypic differences between the ABM of Listeria and Rickettsia may indicate fundamental differences in the mechanisms of actin recruitment and polymerization.