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Biomedical subjects

N B Vedder

Publications and source records attributed to N B Vedder.

29 records · Page 2Linked to original sources
PubMed1991

Mechanisms and consequences of leukocyte-endothelial interaction.

Leukocyte adhesion to endothelium is a critical event in host defense against microorganisms and in the repair of tissue damage. Under some circumstances, however, altered leukocyte-endothelial interactions may contribute to the pathogenesis of inflammatory and immune diseases. In a number of experimental models, the inhibition of leukocyte adherence to endothelium substantially reduces vascular and tissue injury. Antiadhesion therapy may represent a novel approach to the treatment of a wide spectrum of clinical disorders.

Animals↗
PubMed1990

Inhibition of leukocyte adherence by anti-CD18 monoclonal antibody attenuates reperfusion injury in the rabbit ear.

Tissue injury resulting from ischemia and reperfusion forms the basis of several important disorders including myocardial infarction, stroke, and circulatory shock. To examine the role of neutrophils in this process and to determine the extent to which injury is a consequence of reperfusion, we utilized the monoclonal antibody 60.3, directed to CD18, the human leukocyte adherence glycoprotein, to block intravascular neutrophil aggregation and neutrophil adherence to endothelium in a rabbit model of tissue ischemia and reperfusion. Antibody treatment either before ischemia or after ischemia, but prior to reperfusion, resulted in the same degree of significant protection against endothelial, microvascular, and tissue injury. We conclude that neutrophils and increased neutrophil adhesiveness are important in the development of microvascular and tissue injury after ischemia and reperfusion and that under these circumstances, injury is primarily a consequence of reperfusion.

Animals↗
PubMed1990

Inhibition of CD18-dependent neutrophil adherence reduces organ injury after hemorrhagic shock in primates.

Neutrophil adherence or aggregation may be important in the development of organ injury after hemorrhagic shock. Monoclonal antibody (MAb) 60.3 prevents both adherence and aggregation. Therefore we investigated MAb 60.3 treatment in prevention of organ injury after hemorrhagic shock in rhesus monkeys (Macaca mulatta). We performed esophagogastroscopy and placed catheters to measure cardiac output, mean arterial pressure, arterial blood gases, and urine output. Blood was removed to decrease CO to 30% of baseline for 90 minutes. Just before resuscitation, MAb 60.3 (2 mg/kg) or saline solution (control) was administered intravenously. Monitoring and fluid resuscitation continued for 24 hours, with lactated Ringer's solution given as a maintenance infusion (4 ml/kg/hr) plus additional lactated Ringer's solution to maintain CO at preshock levels. Esophagogastroscopy was repeated 24 hours after shock. There were two deaths in the control group at about 72 hours and none in the MAb 60.3 group. MAb 60.3-treated animals required less fluid (9.6 +/- 8.8 ml/kg vs 263.8 +/- 225.7 ml/kg), gained less weight (0.08 +/- 0.11 kg vs 0.70 +/- 0.37 kg), and maintained a higher hematocrit level (35.0% +/- 1.0% vs 26.9% +/- 4.9%). All five control animals had gastritis; MAb 60.3-treated animals had none (p less than 0.05; Fisher's exact test). Inhibition of neutrophil adherence or aggregation with MAb 60.3 at the time of resuscitation reduces fluid requirements and gastric injury in monkeys after hemorrhagic shock.

Animals↗
PubMed1989

Role of neutrophils in generalized reperfusion injury associated with resuscitation from shock.

Recent studies suggest that neutrophils are an important factor in the organ injury associated with ischemia and shock. Increased neutrophil-endothelial adhesiveness is essential for neutrophil-mediated vascular injury. To examine the role of neutrophils and neutrophil adhesiveness in the development of injury after hypovolemic shock, and to determine whether this injury is a consequence of reperfusion, we used the monoclonal antibody (MAb) 60.3 (directed to the primary human neutrophil adherence glycoprotein, CD18) to block neutrophil adherence functions at the time of resuscitation in a rabbit model of hemorrhagic shock. None of the unanesthetized control animals subjected to 2 hours of shock (cardiac output, 30% of baseline) followed by resuscitation survived 5 days. All had gross and histologic evidence of injury to lungs, liver, and gastrointestinal mucosa. In contrast, 71% of the animals that received MAb 60.3 immediately before resuscitation survived 5 days (p less than 0.005), and visceral organ injury was absent or markedly attenuated. We conclude that a significant proportion of injury resulting from shock and resuscitation occurs after the ischemic insult and that increased neutrophil adhesiveness plays an important role in the development of multiple organ injury and death following shock and resuscitation (in this model). This injury may be significantly reduced by blocking neutrophil adherence functions with the MAb 60.3--even if administration is delayed until resuscitation.

Acidosis↗
PubMed1988

Increased surface expression of CD11b/CD18 (Mac-1) is not required for stimulated neutrophil adherence to cultured endothelium.

The mechanism whereby the human neutrophil membrane heterodimer, CD11b/CD18 (Mac-1, Mo1), mediates neutrophil adherence is not known. We studied the role of CD11b/CD18 surface expression in the promotion of neutrophil adhesiveness. We found that phorbol myristate acetate (PMA), calcium ionophore (A23187), and FMLP caused a three- to sevenfold increase in surface expression of both CD11b (alpha M) and CD18 (beta) as assayed by binding of MAbs 60.1 (anti-CD11b) and 60.3 (anti-CD18). Increased binding of MAbs was temporally associated with the promotion of neutrophil aggregation and adherence to cultured endothelial monolayers. Pretreatment of neutrophils with the anion channel-blocking agent, DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid), inhibited the increased surface expression of CD11b and CD18 after stimulation by PMA, A23187, or FMLP and resulted in nearly complete inhibition of neutrophil aggregation. However, pretreatment with DIDS did not diminish either PMA-, A23187-, or FMLP-stimulated neutrophil adherence to endothelial monolayers. We also observed that stimulation of granule-depleted neutrophil cytoplasts by PMA, A23187, or FMLP induced aggregation and adherence to endothelial monolayers without increasing surface expression of CD11b or CD18. We conclude that the increased surface expression of CD11b/CD18 that occurs after stimulation is neither sufficient nor necessary for enhanced adherence to endothelium. Moreover, though both are CD11b/CD18-dependent, the mechanisms involved in neutrophil aggregation are different from those involved in neutrophil adherence to endothelium.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits.

Leukocytes have been shown to play an important role in the development of isolated organ injury after experimental ischemia and reperfusion. To examine the role of leukocytes in generalized ischemia-reperfusion injury we used the MAb 60.3 (directed to the human leukocyte adherence glycoprotein, CD18) to block leukocyte adherence functions in a rabbit model of hemorrhagic shock and resuscitation. In control animals subjected to 1 h of shock (mean blood pressure 45 torr and mean cardiac output 30% of baseline) followed by resuscitation, only 29% survived 5 d. All had gross and histologic evidence of injury to lungs, liver, and gastrointestinal mucosa. In contrast, 100% of the MAb 60.3-treated animals survived 5 d (P less than 0.01) and organ injury was absent or markedly attenuated. The control animals also had a persistent acidosis, lost more weight, and had evidence of continued gastrointestinal bleeding in contrast to MAb 60.3-treated animals. We conclude that increased leukocyte adhesiveness plays an important role in the development of multiple organ injury and death after generalized ischemia-reperfusion and that this injury may be significantly reduced by blocking leukocyte adherence functions with the MAb 60.3.

Animals↗
PubMedDate not supplied

Treatment of fourth-degree hand burns.

Fourth-degree hand burns are rare but devastating injuries. They cannot be grafted readily but often require flaps and amputation, and impairment is significant. We report our 10-year experience (1981 to 1990) with deep hand burns to characterize our treatment and outcome. A total of 25 patients (35 hands) were treated. Eight local flaps, nine distant flaps, and two free-tissue transfers were performed. Eleven hands were treated with K-wire immobilization and grafting. Thirty-three amputations were done. Postburn function was evaluated in 25 salvaged hands. Eleven hands had good outcomes, whereas seven had moderate sequelae and seven were severely affected. Patients who were treated with flap coverage of exposed tendons and joints had better functional outcomes than those treated with delayed closure with immobilization and grafting. The excellent outcomes in the flap coverage group justifies the added commitment of technical and therapeutic resources that this treatment requires.

Adult↗
PubMedDate not supplied

The use of the Millard "crane" flap for deep hand burns with exposed tendons and joints.

Deep hand burns with exposed tendons and joints are rare but devastating injuries. They cannot be grafted and require flaps. Abdominal or groin flaps are commonly used, but they are bulky and require separation of the digits. We tried the Millard "crane" flap for these burns and compared our patients' results with those of patients who had received standard abdominal skin flaps. Eleven deep hand burns that had been treated with flaps were evaluated. Six patients had been treated with the crane flap and 5 had been treated with conventional abdominal skin flaps. All crane procedures provided graftable wound beds. The total active ranges of motion of all 11 patients 6 months after the surgical procedures showed no statistical difference. The crane method also provides good cosmetic results. None of the hands treated with crane flaps required procedures to separate the digits or debulk the flaps, but all of the hands treated with conventional abdominal skin flaps required these types of procedures.

Abdomen↗
PubMedDate not supplied

Dexter: a tool to facilitate impairment ratings.

Calculating impairment in burn patients is crucial to understanding outcome. However, it is rarely reported after burns, presumably because the process of calculating impairment ratings is complicated and tedious. Computerized systems have been developed that facilitate the process, but it has not been established in burn patients that these systems reduce the time required to calculate impairment. We evaluated the Dexter Evaluation and Therapy System by Cedaron Medical Inc (Davis, CA). A sample of 10 manually recorded ratings was compared with 10 performed on the Dexter. Mean time for the manual technique was 65 +/- 35 minutes versus 37 +/- 13 minutes for the Dexter (P < .05, Mann-Whitney). The time taken to perform impairment ratings in burn survivors is significantly reduced by the use of the Dexter system. Time saving occurs primarily at three points: (1) electronic data entry directly from the measuring instruments, (2) compilation of data, and (3) rapid generation of reports.

Adult↗
PubMedDate not supplied

Internal fixation of pilon fractures of the distal radius.

When closed manipulation fails to restore articular congruity in comminuted, displaced fractures of the distal radius, open reduction and internal fixation is required. Results of surgical stabilization and articular reconstruction of these injuries are reviewed in this retrospective study of 49 patients with 52 displaced, intra-articular distal radius fractures. Forty-three patients (87%) with a mean age of 37 years (range of 17 to 79 years) were available for evaluation. The mean follow-up time was 38 months (range 22-69 months). When rated according to the Association for the Study of Internal Fixation (ASIF), 19 were type C2 and 21 were type C3. We devised an Injury Score System based on the initial injury radiographs to classify severely comminuted intra-articular fractures and to identify those associated with carpal injury (3 patients). Post-operative fracture alignment, articular congruity, and radial length were significantly improved following surgery (p < .01). Grip strength averaged 69% +/- 22% of the contralateral side, and the range of motion averaged 75% +/- 18% of the contralateral side post-operatively. A combined outcome rating system that included grip strength, range of motion, and pain relief averaged 76% +/- 19% of the contralateral side. There was a statistically significant decrease in the combined rating with more severe fracture patterns as defined by the ASIF system (p < .01), Malone classification (p < .03), and the Injury Score System (p < .001). The Injury Score System presented here, and in particular the number of fracture fragments, correlated most closely with outcome of all the classification systems studied. Operative treatment of these distal radius fractures with reconstruction of the articular congruity and correction of the articular surface alignment with internal fixation and/or external fixation, can significantly improve the radiographic alignment and functional outcome. Furthermore, the degree to which articular stepoff, gap between fragments, and radial shortening are improved by surgery is strongly correlated with improved outcome, even when the results are corrected for severity of initial injury, whereas correction of radial tilt or dorsal tilt did not correlate with improved outcome.

Adolescent↗