Intravenous administration of activated protein C in Pseudomonas-induced lung injury: impact on lung fluid balance and the inflammatory response.

BACKGROUND: Acute lung injury (ALI) induces a coagulation/fibrinolysis imbalance and leads to fibrin deposition. The protein C pathway is an important regulator of the coagulation system and reduces the inflammatory response. The aim of the study was to examine the effects of recombinant human activated protein C (rhAPC) in the early phase of Pseudomonas aeruginosa (Pa)-induced lung injury. METHODS: The study was conducted in vivo on a rat model of Pa-induced ALI. Continuous intravenous (IV) rhAPC was administrated simultaneously with intratracheal (IT) Pa. We instilled into the airspaces a 5% bovine albumin solution with 1 mu(Ci of (125)I-albumin and injected IV 1 mu(Ci of (111)In-albumin to measure lung liquid clearance (LLC) and endothelial injury. Cytokines levels (TNFalpha and IL-6) and thrombin-antithrombin (TAT) complexes were measured in blood and bronchoalveolar lavage fluid (BALF) at 4 hours. Four groups were compared: control (CTR), pneumonia (PNP) receiving IT Pa (0.5 ml/kg of 1 x 10(9) cfu), APC: IV rhAPC (300 microg/kg/h), A-PNP: IT Pa /IV rhAPC. RESULTS: Alveolar-capillary permeability was increased in the PNP versus the CTR group (0.28 +/- 0.08 vs. 0.03 +/- 0.01, p < 0.05). IV rhAPC in Pa-induced ALI led to further injury (0.47 +/- 0.17 vs. 0.28 +/- 0.08, p = 0.2). The LLC was significantly decreased in the A-PNP group compared to PNP group (9.1 +/- (4.3% vs. 33.4 +/- 2.6%, p < 0.05). The lung wet to dry weight ratio was significantly increased in the PNP group (4.62 +/- 0.31) compared to the CTR group (3.87 +/- 0.22, p < 0.05). IV rhAPC administration tends to increase this parameter in Pa-induced ALI (5.80 +/- 0.66, p = 0.07). These findings were associated with a loss of inflammatory response compartmentalization measured by TNFalpha and IL-6 systemic levels. TAT complexes in BALF were increased in the A-PNP group (23.17 +/- 2.89 ng/ml) compared to the CTR group (0.92 +/- 0.17 ng/ml, p < 0.05) and the PNP group (11.06 +/- 2.76 ng/ml, p < 0.05). CONCLUSION: rhAPC reduces LLC following Pa-induced ALI and may influence pulmonary edema formation. The early massive fibrin formation is probably beneficial in ALI limiting both the extent of injury and permeability disorders.

Long-chain polyunsaturated fatty acids modulate lung inflammatory response induced by Pseudomonas aeruginosa in mice.

Polyunsaturated fatty acid (PUFA) immunomodulatory properties have been studied extensively in chronic infections. Few studies have focused on acute infection; thus, PUFA effects in a mouse model of Pseudomonas aeruginosa (PA)-induced lung injury were evaluated. C57BL/6 mice were randomized to be fed for 3 wk with an eicosapentaenoic acid (EPA) diet, an arachidonic acid (AA) diet, or a control diet [saturated fatty acids]. Lung injury was induced by intratracheal instillation of 10(7) CFU of PA per mouse. In each diet group, animals were studied either without or after PA-inducing lung injury. Evaluation criteria were early mortality; inflammatory response assessed with tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and IL-10 levels in bronchoalveolar lavage; lung injury evaluation; and extravascular lung water, assessed 24 h after the injury. After PA-induced lung injury, no difference in early mortality was observed; TNF-alpha level was significantly higher in the EPA diet than in the other two diet groups. No difference for the other cytokines was found among the groups. Lung edema was also more important in the EPA group, consistent with the variations of TNF-alpha levels. Our study clearly shows that in PA-induced acute lung injury, n-3 PUFA induces differences in the inflammatory response with a higher level of lung edema. Modulation of the inflammatory response with n-3 PUFA can influence the response to a bacterial challenge.

[Contribution of fluorescence immunocytochemistry (uCyt+TM) in the postoperative surveillance of bladder cancer]. / Apport de l'immunocytochimie en fluorescence (uCyt+TM) dans la surveillance après résection des tumeurs vésicales.

OBJECTIVE: To assess 1) the value of fluorescence immunocytochemistry (uCyt+ test, DiagnoCure Inc., Quebec) in the detection of recurrent bladder tumour after transurethral resection (TUR) and 2) the predictive value of a positive uCyt+ test in patients with negative cystoscopy. MATERIAL AND METHODS: This study was based on 132 patients with a mean follow-up of 21.9 weeks after TUR. The initial tumours were pTa G1-2 in 66.7% of cases, and G3 in 28.8% of cases. Cystoscopy, urine cytology (UC) and uCyt+ test data were collected on the day of the first control visit (D0), and the patients were then reviewed at 6 and 12 months. All lesions detected on cystoscopy were biopsed. RESULTS: The mean sensitivity of UC was 47.4% and the mean sensitivity of uCyt+ was 73.7% (84.2% in combination). In patients with negative cystoscopy on D0, a positive uCyt+ test has no predictive value at 6 months. At 12 months, 20.0% of patients with positive UC had relapsed, versus 16.7% of patients with negative UC (p = ns). On the other hand, at 12 months, 50.0% of patients with negative cystoscopy but positive uCyt+ test had relapsed, versus 16.4% of patients with a negative uCyt+ test (p < 0.01). CONCLUSIONS: The uCyt+ test allows assessment of the risk of recurrence at I year, while UC alone only has a diagnostic value. These results raise the possibility of combining the tests in order to decrease the frequency of follow-up cystoscopy.

[Spermatocytic seminoma. A clinicopathological and immunohistochemical study of 7 cases]. / Le séminome spermatocytaire. Etude anatomo-clinique et immunohistochimique de 7 cas.

Spermatocytic seminoma is an uncommon tumor, representing less than 1% of the testicular tumors, occurring most often in old patients. We report 7 cases of this entity. The average age at presentation was 66 years. Tumors had a polymorphic appearance with small, intermediate and large cells, and "spireme" figures. They were pure, with no sarcomatous component. In all cases, the tumor was limited to the testis. In the peritumoral tissue, there was no intratubular germ cell proliferation, and no atrophic testis. Immunostaining was negative for all the classical antibodies tested (cytokeratins, PLAP, lymphoid markers), but all the cases expressed c-kit (100%). This membranous positivity was focal in 4 cases, very strong, and diffuse in the 3 others. Spermatocytic seminoma must be recognized, because its favorable evolution in absence of a sarcomatous component. Adequate treatment consists of orchidectomy alone. Positive staining for c-kit may be helpful for the diagnosis of spermatocytic seminoma.