Biomedical subjects

W Mileski

Publications and source records attributed to W Mileski.

7 recordsLinked to original sources

PubMed1996

The role of neutrophils in peritoneal adhesion formation.

The most common cause of intraperitoneal adhesions is previous abdominal surgery. Postoperative adhesion formation results from a fibroproliferative inflammatory reaction that begins with an influx of polymorphonuclear leukocytes (PMNs) into the peritoneal cavity. Adherence of the PMNs to the endothelial cells (EC) is necessary for PMN migration into the tissue in response to a stimulus. Several receptor-counterreceptor pairs of ligands such as CD11/CD18 on the PMN and ICAM-1 (CD54) on EC have been identified. Monoclonal antibody against CD11/CD18 (R15.7) inhibits PMN adherence and migration and consequently protects against PMN-induced tissue injuries. We therefore studied the effect of preventing PMN-EC adherence, using anti-CD18 monoclonal antibody, on postoperative adhesion formation in rabbits. Group 1 was a control receiving physiologic saline, and group 2 received anti-CD18 antibody (R15.7, 2 mg/kg). The treatment was administered iv at the end of surgery and repeated on the first and second postoperative days. Peritoneal adhesions were induced at laparotomy by repairing two peritoneal defects, by oversewing the defect (model 1), and by resuturing the removed parietal peritoneum in its place as an ischemic graft (model 2). Adhesions were evaluated blindly at 10 days after operation by measuring the percentage of the suture line covered with adhesions (model 1) or by a scoring system (model 2). All control animals developed intraperitoneal adhesions and the percentage of the suture line covered with adhesions was 25 +/- 5.9% (mean +/- SEM) and the mean score in model 2 was 0.9 +/- 0.2. Anti-CD18 antibody, R15.7, increased the degree of postoperative adhesion formation in both models, but the results were significant only in model 2. Also, anti-CD18 antibody significantly decreased peritoneal neutrophils from 11.1 x 10(7) +/- 1.8 x 10(7) to 2.2 x 10(7) +/- 0.4 x 10(7) (P < 0.001) on the first postoperative day. It is concluded that inhibition of PMN-EC adherence does influence the postoperative adhesion formation. These results might suggest that PMNs have a role in modulating postoperative adhesion formation.

Animals↗

PubMed1995

Enhancement of peritoneal macrophages reduces postoperative peritoneal adhesion formation.

Postoperative adhesion formation results from a fibroproliferative inflammatory reaction. Macrophages are critical in the final resolution of the inflammatory process and tissue repair, including modulation of proliferation and differentiation of fibroblasts and secretion of neutral proteases like plasminogen activator. We, therefore, studied the influence of peritoneal macrophage enhancement on postoperative adhesion formation in five groups of rabbits. Group 1 was a control with normal peritoneum. Animals in group 2 had increased macrophage population in their peritoneum by intraperitoneal injection of protease peptone 3 days before adhesion induction. In group 3, animals were treated by protease peptone as in group 2 and then depleted of the increased macrophage population by peritoneal lavage before adhesion induction. In group 4 macrophages were transplanted from animals enriched as in group 2 into a nonenriched peritoneum at the time of adhesion induction. Group 5 had a normal peritoneum with peritoneal lavage before adhesion induction. Peritoneal adhesions were induced at laparotomy by repairing a peritoneal defect in two different models. It was found that enhancement of peritoneal macrophages by protease peptone reduced markedly the degree of postoperative adhesion formation. After depletion of the enhanced peritoneal macrophages by peritoneal lavage the degree of adhesion formation was equivalent to that of controls. Finally, macrophage transplantation into a nonenhanced macrophage peritoneum also reduced the degree of postoperative adhesion formation. It is concluded that enhancement of peritoneal macrophages reduces postoperative peritoneal adhesion formation.

Animals↗

PubMed1992

Inhibition of leukocyte-endothelial adherence following thermal injury.

Progressive microvascular damage in the tissue adjacent to a cutaneous burn injury results in extension of burn size. The role of neutrophils (PMNs) in the pathogenesis of microvascular injury was investigated by inhibition of PMN adherence to the microvascular endothelium using monoclonal antibodies directed to the leukocyte CD18 adhesion complex or its endothelial ligand, intercellular adhesion molecule-1 (ICAM-1, CD54). A model of thermal injury was developed using New Zealand White rabbits. Under general anesthesia two sets of three full-thickness burns separated by two 5 x 30-mm zones were produced by applying brass probes heated to 100 degrees C to the animals' backs for 30 sec. Cutaneous blood flow determinations were obtained for 72 hr. Blood flow measurements were performed using a laser doppler blood flowmeter (PF3, Perimed, Piscataway, NJ). There were five experimental groups; controls given saline alone, n = 12; animals given monoclonal antibody to the PMN CD18 complex, R 15.7 prior to burn injury (pre-R15.7, n = 5); animals given R 15.7 30 min after burn injury (post-R 15.7, n = 6); animals given the anti ICAM-1 antibody, R 6.5 prior to burn (pre-R 6.5, n = 6); and animals given the R 6.5 30 min postburn injury (post-R 6.5, n = 6). BF in the marginal "zone of stasis" between burn contact sites was significantly higher in the antibody-treated animals and administration of the antibodies 30 min after injury was as effective as preburn administration in preserving blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Streptococcus pneumoniae-stimulated macrophages induce neutrophils to emigrate by a CD18-independent mechanism of adherence.

Neutrophil adherence to and emigration across endothelium are in large part dependent upon the neutrophil membrane CD11/CD18 glycoprotein complex. Recently, however, we have demonstrated that some stimuli can elicit neutrophil emigration in the lung by a CD18-independent pathway. We examined further the mechanism involved in CD18-independent emigration in a rabbit model of inflamed peritoneum. Neutrophil emigration in the peritoneum induced by instillation of E. coli and S. pneumoniae was studied under four experimental conditions: Group 1--normal peritoneum, Group 2--peritoneum primed with protease peptone to increase the number of macrophages, Group 3--peritoneum treated by protease peptone instillation and then depleted of the increased macrophage population, and Group 4--peritoneum with macrophages transplanted from animals enriched as in Group 2. Experiments were run in pairs with animals in each group assigned to receive either saline (control) or monoclonal antibody (MAb) 60.3 prior to bacterial instillation in the peritoneum. Neutrophil emigration in response to E. coli was greater than 86% inhibited by MAb 60.3 in both the normal and the macrophage-enriched peritoneum. Neutrophil emigration in response to S. pneumoniae was inhibited greater than 85% in the normal peritoneum and the macrophage-enriched and the transplanted macrophage peritoneum. These data indicate that macrophages can augment PMN emigration by a non-CD18 mechanism, and may explain the increased sensitivity of organs with large resident macrophage populations, liver and lung, to injury following shock and sepsis.

Animals↗

PubMedDate not supplied

Inhibition of leukocyte adherence in a rabbit model of major thermal injury.

Leukocytes and the process of leukocyte adherence have been implicated in the pathogenesis of organ dysfunction after ischemic injury and inflammation. We asked the question: Will inhibition of leukocyte adherence by administration of a monoclonal antibody to intercellular adhesion molecule alter the systemic response to major thermal injury? New Zealand white rabbits instrumented to measure mean arterial pressure, cardiac output, urine output, and arterial oxygenation were deeply anesthetized, and 30% total body surface area full-thickness burn was created by applying brass probes heated to 100 degrees C to the animals' backs for 15 seconds. The animals were continuously monitored, resuscitated, and given analgesic for 24 hours. There were three experimental groups: I-controls (n = 7), anesthetized and monitored; II-30% burn (n = 7) given 30% total body surface area + vehicle (saline solution 1.0 ml/kg every 8 hours); III-30% burn + R6.5 (n = 6) animals given a monoclonal antibody (R6.5, 2.0 mg/kg every 8 hours) directed against the intercellular adhesion molecule beginning 30 minutes after burn. This model of a 30% total body surface area burn injury resulted in hypotension and hypoxemia in the burn group. The animals given the antibody R6.5 maintained higher mean arterial pressure and arterial oxygenation at several points. These results suggest that leukocytes and leukocyte adherence may be involved in the pathogenesis of the systemic sequellae of major thermal injury.

Animals↗

PubMedDate not supplied

Laser Doppler flowmetry in burn wounds.

Traditional methods for judgment of burn depth by clinical evaluation of the wound based on appearance and sensation remain in wide use but are subject to individual variation by examiner. In addition to the clinical difficulties with burn wound management, observer dependency of wound assessment complicates clinical trials of burn wound therapy. A laser Doppler flowmeter with a newly designed multichannel probe was used to measure burn wound perfusion as a tool to predict wound outcome. Wounds that healed spontaneously in fewer than 21 days showed higher average perfusion levels than those that required excision and grafting or that were not healed by day 21 after the burn. Laser Doppler flowmetry had a positive predictive value of 100% for nonhealing wounds on postburn days 1 and 3. These data suggest that laser Doppler flowmetry is a potentially useful tool for burn wound assessment.

Adolescent↗

PubMedDate not supplied

Early assessment of pediatric burn wounds by laser Doppler flowmetry.

Evaluation of burn wound depth in pediatric patients is often difficult. A Laser Doppler Flowmeter with a temperature-controlled multichannel probe was used to measure burn wound perfusion as a tool to predict wound outcome. The average perfusion levels for wounds that healed spontaneously in fewer than 21 days was significantly higher than the average perfusion levels for wounds that required excision and grafting or were not healed by day 21 after burn injury. Laser Doppler Flowmetry showed high positive predictive values for "nonhealing" wounds on postburn days 1, 2, and 3. These results suggest that Laser Doppler Flowmetry is a useful tool for burn wound assessment in pediatric patients.

Adolescent↗