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P Sikes

Publications and source records attributed to P Sikes.

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↗
PubMed1996

Role of CD14 in hemorrhagic shock-induced alterations of the monocyte tumor necrosis factor response to endotoxin.

OBJECTIVE: To determine if the shock-induced alterations in whole blood monocyte tumor necrosis factor (TNF) response are mediated by the CD14 receptor. DESIGN: Prospective controlled animals experiments. MATERIALS AND METHODS: New Zealand White rabbits (n = 15) were subjected to hemorrhage and resuscitation. Blood samples obtained before shock and 24, 72, and 120 hours after shock were stimulated with lipopolysaccharide in the presence or absence of the anti-CD14 monoclonal antibody, 63D3. Tumor necrosis factor was assayed using L929 cells. MEASUREMENTS AND MAIN RESULTS: There are no detectable TNF activity in unstimulated blood. The CD14 inhibition resulted in a 55% reduction in baseline TNF activity. After shock, there was a marked increase in TNF activity with lipopolysaccharide stimulation. Addition of 63D3 resulted in a dose-dependent 95% reduction in TNF activity at 24 and 72 hours after shock, (p < 0.05). CONCLUSION: The enhanced whole blood monocyte TNF response after hemorrhage is CD14 dependent.

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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↗
PubMed1994

Effect of inhibiting leukocyte integrin (CD18) and selectin (L-selectin) on susceptibility to infection with Pseudomonas aeruginosa.

Leukocyte (WBC) adherence to endothelial cells has been implicated in the pathogenesis of microvascular injury. The process of leukocyte adherence is mediated by both the integrin and selectin families of molecules, and their interaction with specific endothelial ligands. Antibodies directed against the leukocyte integrin CD18 and L-selectin have been developed and functionally inhibit leukocyte adherence in models of inflammatory injury. We asked the question: Does inhibition of leukocyte adherence by administration of monoclonal antibody directed against either CD18, integrins (R15.7, R7.1) or against L-selectin (DREG 200) increase susceptibility to infection? New Zealand white rabbits were shaved and injected subcutaneously on their dorsum with Pseudomonas aeruginosa (ATCC#27853) at two sites each of 10(8) and 10(7) colony forming units. Animals were monitored with daily determination of weight, temperature, WBC counts, hematocrit, and killed at 1 week for determination of abscess formation. There were four blinded experimental groups: (1) Saline (2 mL/kg); (2) DREG 200 (2 mg/kg); (3) R7.1 (2 mg/kg); or (4) R15.7 (2 mg/kg). At the 10(7) and 10(8) injection sites the R15.7 group had an increased rate and size of abscess formation compared with controls. The R7.1 group had an increased rate at the 10(8) injection site. There was no significant difference in the percentage of the abscess formation or mean area between the controls and DREG 200-treated groups. We conclude that giving antibody to CD18 increased susceptibility to infection while giving antibody to L-selectin does not.

Animals↗
PubMed1993

Inhibition of leukocyte adherence and susceptibility to infection.

Leukocyte (WBC) adherence to endothelial cells (EC) has been implicated in the pathogenesis of microvascular injury. WBC-EC adherence is largely dependent on interaction between the WBC-CD18 complex and the endothelial ligand, intercellular adhesion molecule-1 (ICAM-1). Administration of monoclonal antibodies directed against CD18 and/or ICAM-1 inhibit WBC-EC adherence and have been reported to modulate ischemia-reperfusion and inflammatory injury. We asked the question, does inhibition of WBC-EC adherence by administration of monoclonal antibody directed against either CD18 (R15.7) or against ICAM-1 (R6.5) increase susceptibility to infection. New Zealand white rabbits were shaved and injected subcutaneously on their dorsum with Staphylococcus aureus (ATCC No. 25923) at two sites each with 10(9), 10(8), 10(7), and 10(6) colony-forming units (CFUs). A second set of rabbits were injected subcutaneously with Pseudomonas aeruginosa (ATCC No. 27853) at two sites each of 10(8) and 10(7) CFUs. Animals were monitored for 1 week with daily determination of weight, temperature, WBC counts, hematocrit, and gross evidence of abscess formation. There were three blinded experimental groups; animals given R15.7 (2.0 mg/kg), animals given R6.5 (2.0 mg/kg), and controls given saline (2.0 ml/kg). Administration of the anti-CD18 antibody, R15.7, resulted in significantly increased rates of abscess formation following innoculation with S. aureus and with P. aeruginosa, compared to controls and to the animals given the antibody to ICAM-1, R6.5. The administration of R6.5 did not increase the incidence or severity of abscess formation.

Abscess↗
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.

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