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Biomedical subjects

N B Vedder

Publications and source records attributed to N B Vedder.

At least 19 recordsLinked to original sources

Preconditioning of the distal portion of a rat random-pattern skin flap.

It has been shown that preconditioning either by proximal pedicle clamping or by pedicle intravascular drug administration, for example with adenosine, can improve flap survival. These methods, however, are not well suited to random-pattern flap transfer in the clinical setting. The aim of this study was to evaluate clinically applicable preconditioning methods for random-pattern flaps. Eighteen male Sprague-Dawley rats were used. Bipedicled dorsal skin flaps (2 x 8cm) containing panniculus carnosus were elevated. In the ischaemic preconditioning group the cranial pedicle was clamped for 20min, followed by 40min reperfusion before the cranial pedicle was cut, producing a caudally based random-pattern flap. In the pharmacologic preconditioning group adenosine was locally injected in the cranial half of the flap before the cranial pedicle was cut. In the control group saline was locally injected instead of adenosine and the pedicle was cut in the same manner. Flap survival area was evaluated at day 7. Flap survival area in both preconditioning groups was significantly higher than in the control group (P<0.05). Both preconditioning methods can improve random-pattern flap survival in rats. These methods may prove useful in the clinical setting.

Adenosine↗

A comparison of short- and long-term intravenous antibiotic therapy in the postoperative management of adult osteomyelitis.

The current standard recommendation for antibiotic therapy in the management of chronic osteomyelitis is intravenous treatment for six weeks. We have compared this regime with short-term intravenous therapy followed by oral dosage. A total of 93 patients, with chronic osteomyelitis, underwent single-stage, aggressive surgical debridement and appropriate soft-tissue coverage. Culture-specific intravenous antibiotics were given for five to seven days, followed by oral therapy for six weeks. During surgery, the scar, including the sinus track, was excised en bloc. We used a high-speed, saline-cooled burr to remove necrotic bone, and osseous laser Doppler flowmetry to ensure that the remaining bone was viable. Infected nonunions (Cierny stage-IV osteomyelitis) were stabilised by internal fixation. In 38 patients management of dead space required antibiotic-impregnated polymethylmethacrylate beads, which were exchanged for an autogenous bone graft at six weeks. Free-tissue transfer often facilitated soft-tissue coverage. These 93 patients were compared with 22 consecutive patients treated previously who had the same surgical management, but received culture-specific intravenous antibiotics for six weeks. Of the 93 patients, 80 healed without further intervention. Of the 31 Cierny-IV lesions, 27 healed without another operation, and four fractures required additional bone grafts. No more wound drainage was needed. Treatment was successful in 91% of patients, regardless of the organism involved. There was no difference in outcome in terms of these variables when the series were compared. We conclude that the long-term administration of intravenous antibiotics is not necessary to achieve a high rate of clinical resolution of wound drainage for adult patients with chronic osteomyelitis.

Administration, Oral↗

Intrafocal (Kapandji) pinning of distal radius fractures with and without external fixation.

Seventy-three patients were treated with either intrafocal pinning (Kapandji technique) alone or in combination with external fixation between 1988 and 1993 for extra-articular fractures of the distal radius (with or without a nondisplaced extension into the radiocarpal articular surface) with inadequate alignment after initial closed reduction. Sixty-one patients were available for follow-up examination at an average of 34 months (range, 24-71 months). The average age was 52 years (range, 16-84 years). Thirty-three of the patients were female. The patients all had dorsally displaced extra-articular fractures, although 56% had a nondisplaced extension of the fracture into the radiocarpal joint and 46% had a nondisplaced fracture extending into the distal radioulnar joint. The patients were separated into groups based on age, degree of comminution, and whether external fixation was also used. In the older patients, range of motion, grip strength, and pain relief were significantly better when external fixation was used, even when only 1 cortex of the radius demonstrated comminution. In the younger patients, good results in terms of range of motion, grip strength, and pain relief were obtained when percutaneous intrafocal pins were used alone in patients with comminution of only 1 surface of the radius (<50% of the metaphyseal diameter). When > or = 2 sides of the radial metaphysis were comminuted, the patients with external fixation had better results than those without external fixation. Although the correction of palmar tilt and radial tilt did result in better functional results, the restoration of radial length had the most significant effect on range of motion and grip strength.

Adolescent↗

Outcome after hemorrhagic shock in trauma patients.

BACKGROUND: It is essential to identify patients at high risk of death and complications for future studies of interventions to decrease reperfusion injury. METHODS: We conducted an inception cohort study at a Level I trauma center to determine the rates and predictors of death, organ failure, and infection in trauma patients with systolic blood pressure < or = 90 mm Hg in the field or in the emergency department. RESULTS: Among the 208 patients with hemorrhagic shock (blood pressure < or = 90 mm Hg), 31% died within 2 hours of emergency department arrival, 12% died between 2 and 24 hours, 11% died after 24 hours, and 46% survived. Among those who survived > or = 24 hours, 39% developed infection and 24% developed organ failure. Increasing volume of crystalloid in the first 24 hours was strongly associated with increased mortality (p = 0.00001). CONCLUSION: Hemorrhage-induced hypotension in trauma patients is predictive of high mortality (54%) and morbidity. The requirement for large volumes of crystalloid was associated with increased mortality.

Adolescent↗

Mild hypothermia during reperfusion reduces injury following ischemia of the rabbit ear.

Ischemia and reperfusion causes tissue injury that can be partially prevented by mild hypothermia. In this study we postulated that hypothermic protection could occur if imposed only during reperfusion. Rabbit ears were partially amputated, the central artery occluded for 6 h followed by reperfusion at an ambient temperature of either 20 or 24 degrees C resulting in ischemic ear temperatures of 22.5 vs. 24.7 degrees C. Ear temperature of rabbits remaining in the 24 degrees C room increased with reperfusion to 32.4 degrees C whereas those moved to the 20 degrees C room increased to 30.0 degrees C by 2 h of reperfusion. Ear volume was used as a measure of tissue edema and was measured for 7 days after the ears were allowed to reperfuse. Normalized myeloperoxidase content (polymorphonuclear cell accumulation) was significantly greater in the 24 degrees C ischemia-24 degrees C reperfusion group compared with the other groups. Ear edema was significantly less in the two groups exposed to 20 degrees C reperfusion compared with the 24 degrees C ischemia-24 degrees C reperfusion group. Peak ear volume was 5.0 times baseline for the 24 degrees C ischemia-24 degrees C reperfusion, 4.0 times baseline for the 20 degrees C ischemia-24 degrees C reperfusion, 3.4 times baseline for the 24 degrees C ischemia-20 degrees C reperfusion, and 3.3 times baseline for the 20 degrees C ischemia-20 degrees C group. We conclude that mild hypothermia reduces PMN accumulation and is more effective in preventing tissue injury when imposed during reperfusion compared with during ischemia.

Animals↗

Failure of cast immobilization for thumb ulnar collateral ligament avulsion fractures.

To determine if small avulsion fractures of the thumb ulnar collateral ligament (UCL) with minimal (< or = 2.0 mm) displacement can successfully be treated by cast immobilization, the authors reviewed 9 patients with minimally displaced fractures initially treated by casting. Despite immobilization within an average of 2 days of the initial injury (range, 0-6 days), a minimum of 6 weeks of immobilization in a cast, and adequate rehabilitation, all 9 patients had persistent thumb pain, especially with activities requiring strong pinch. After undergoing open reduction and internal fixation, the patients had relief of thumb pain and pinch strength improved from 36% of the contralateral side to 89% (p < .01). Grip strength increased from 77% to 93% (p < .05), but the ranges of motion of the thumb metacarpophalangeal and interphalangeal joints were not significantly altered. Minimally displaced UCL avulsion fractures frequently have significant rotation that prevents successful fracture healing even with prompt cast immobilization.

Adolescent↗

Leukocyte and endothelial adhesion molecules in ischaemia/reperfusion injuries.

Tissue ischaemia and/or reperfusion cause some of the injury seen in several clinical disorders and are responsible for considerable mortality and morbidity in humans. Part of the injury occurring after reperfusion of ischaemic tissue is the result of interactions between leukocytes adhering to vascular endothelium. Blocking the function of the leukocyte adhesion beta 2 integrin complex (CD11/CD18) leads to improved outcome following ischaemia and reperfusion. Functional blockade of either P-selectin or L-selectin prevents leukocyte rolling. Blocking leukocyte adherence at one of several levels may provide improved outcome in a variety of diseases associated with ischaemia and reperfusion.

CD11 Antigens↗

Factors affecting functional outcome of displaced intra-articular distal radius fractures.

Open reduction and internal fixation is often required in comminuted, displaced intra-articular fractures of the distal radius when closed manipulation has failed to restore articular congruity. 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 with a mean age of 37 years (range, 17-79 years) were available for evaluation. The mean follow-up time was 38 months (range, 22-69 months). When rated by the system proposed by the Association for the Study of Internal Fixation (ASIF), 19 were ASIF type C2 and 21 were ASIF type C3. An injury score system based on the initial injury x-ray films was used to classify severely comminuted intra-articular fractures and to identify those associated with carpal injury. Postoperative fracture alignment, articular congruity, and radial length were significantly improved following surgery. Grip strength averaged 69 +/- 22% of the contralateral side, and range of motion averaged 75 +/- 18% of the contralateral side after surgery. A combined outcome rating system that included grip strength, range of motion, and pain relief averaged 76 +/- 19% of the contralateral side. Using regression analysis, a significant decrease was found in the combined rating with more severe fracture patterns as defined by the ASIF system, Malone classification, and the injury score system. The injury score system presented here and, in particular, the number of fracture fragments correlated most closely with the outcome of all classification systems examined. Operative treatment of complex distal radius fractures with reconstruction of articular congruity with internal fixation and/or external fixation can significantly improve functional outcome. The degree to which articular step-off, 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.

Adult↗

Improved survival rates of random flaps in rabbits with a monoclonal antibody that blocks leukocyte adherence.

To examine the role of neutrophil adhesiveness in the tissue injury involving the ischemic "at risk" area of random flaps, we used the monoclonal antibody 60.3, which binds selectively to the primary neutrophil adherence-mediating glycoprotein CD18 in a random cutaneous flap model. Control animals that had flaps elevated and replaced (n = 12) had a mean distal necrosis of 31.9 +/- 9.3 percent of the total flap surface area. Treatment with monoclonal antibody 60.3 (n = 12) reduced distal necrosis to 10.6 +/- 7.5 percent (p < 0.005). Inhibiting inosculation by interposing a thin silicone sheet decreased distal flap survival; however, the protective effect of monoclonal antibody 60.3 on improving flap survival was unchanged. Control isolated flaps (n = 13) had a mean distal necrosis of 49.0 +/- 15.5 percent compared with 22.2 +/- 5.6 percent for the antibody-treated (n = 8) isolated flaps (p < 0.05). We conclude that increased neutrophil adhesiveness plays an important role in the tissue injury involving the ischemic "at risk" area of random flaps and the transient, specific inhibition of leukocyte adherence by monoclonal antibody 60.3 improves the distal survival of random flaps in this model. Moreover, we conclude that "graft inosculation" contributes to "flap" survival in this model; however, conclusions regarding the effect of treatment are not altered by blocking inosculation.

Animals↗

Reduction of burn injury by inhibiting CD18-mediated leukocyte adherence in rabbits.

The progressive nature of dermal ischemia and subsequent tissue destruction within the "zone of stasis" is a central focus in burn research. To examine the role of neutrophils and neutrophil adherence within the zone of stasis, we utilized the monoclonal antibody (MAb) 60.3, directed to the human leukocyte adherence glycoprotein CD18 to block neutrophil adherence to endothelium and intravascular aggregation in a rabbit model of partial-thickness burn. Burns were created by applying an 80 degrees C brass template to the dorsal rabbit skin for 5 or 10 seconds. Animals treated with MAb 60.3 thirty minutes following a 5-second burn had less edema, thinner eschar, and earlier elevation of the eschar than control animals. Histologic analysis revealed an eightfold increase in live hair follicles (p < 0.05) and 43 percent greater reepithelialization at 8 days (p < 0.05) and a 15 percent reduction in burn surface area at 24 hours (p < 0.0001) in the antibody-treated group. There was no significant difference between treatment and control groups exposed to 10-second burns. We conclude that neutrophils and increased neutrophil adherence play important roles in the progressive tissue destruction within the zone of stasis in burns. Furthermore, moderate burn injury may be significantly attenuated by blocking neutrophil adherence functions with a CD18 MAb.

Animals↗

Ipsilateral fractures of the scaphoid and radius.

From 1985 to 1990, six patients were treated for ipsilateral fractures of the scaphoid and radius. All these injuries resulted from falls from a substantial height, with multiple injuries occurring in all patients. Two of the patients had minimally displaced fractures (1.0 mm), whereas the other four patients had moderately displaced scaphoid fractures (2.0 mm). The treatment for fracture of the distal radius was dependent on the fracture type, but all the scaphoid fractures were treated with internal fixation. All the fractures united, with the radial fractures healing in 6 weeks and the scaphoid fractures healing in an average of 13 weeks. The follow-up time averaged 2.9 years (range, 1.0 to 4.6 years). Internal fixation of the scaphoid in these combined injuries allowed for earlier and more aggressive therapy to maximize wrist and forearm motion.

Adolescent↗

Anti-P-selectin monoclonal antibody attenuates reperfusion injury to the rabbit ear.

Neutrophil adherence and/or aggregation has been implicated in ischemia reperfusion injuries. We examined the role of P-selectin in PMN-mediated injury after reperfusion of the rabbit ear. The ear was partially amputated, and then reattached leaving the central artery and vein intact. To induce ischemia the central artery was then occluded. Treatment was at reperfusion with either saline or one of two murine P-selectin mAbs, designated PB1.3 and PNB1.6 mAb PB1.3 cross-reacts with rabbit P-selectin and prevents histamine-induced leukocyte rolling, whereas PNB1.6 does not. Using a peroxidase-antiperoxidase system P-selectin was detected in the ischemic ear, but not in the nonischemic ear. Ear volume increased to 5.3 times baseline in the saline-treated animals (n = 8), 6.6 times baseline in the nonblocking mAb PNB1.6-treated animals (n = 2), and 3.7 times baseline in the blocking mAb PB1.3-treated animals (n = 8). Estimated tissue necrosis of the combined saline- and PNB1.6-treated animals was 46 vs. 2.7% for the mAb PB1.3-treated animals. We conclude that: (a) P-selectin is expressed in ischemia reperfusion; (b) P-selectin participates in PMN-endothelial cell interactions in ischemia reperfusion; and (c) inhibiting P-selectin adhesion significantly reduces reperfusion injury.

Animals↗

Monoclonal antibodies to leukocyte and endothelial adhesion molecules attenuate ischemia-reperfusion injury.

Neutrophils have been implicated as the cause of vascular injury that can lead to organ dysfunction and organ failure following a variety of initiating events. In particular, neutrophils have been shown to be necessary for vascular or tissue damage to occur in ischemia-reperfusion injuries of some organs and in the generalized ischemia-reperfusion injury resulting from hemorrhagic shock. Adherence of neurotrophils to endothelium or homotypic aggregation of neutrophils is thought to be necessary for injuries of this type to occur and these cell-cell interactions are mediated by adhesion molecules on both endothelial cells and leukocytes. In our completed studies, monoclonal antibodies that recognize functional epitopes of the leukocyte CD11/CD18 provided protection from ischemia-reperfusion injury. In addition, preliminary studies investigating leukocyte L-selectin and endothelial P-selectin appear to provide protection from ischemia-reperfusion injury.

Animals↗

The role of adhesion molecules in reperfusion injury.

Leukocytes can produce vascular injury following ischemia and reperfusion of tissue resulting in thrombosis, edema and necrosis. Leukocyte adhesion to endothelial cells allows formation of a protected microenvironment where inflammatory molecules can exceed anti-inflammatory molecules thus resulting in injury. Blocking adherence with monoclonal antibodies to adherence molecules can prevent reperfusion injury to a variety of organs. In particular, antibodies to CD18 and P-selectin have been shown to be effective in ameliorating injury.

Animals↗

Misleading fractures after profundus tendon avulsions: a report of six cases.

From 1986 to 1990, twelve patients were treated for avulsions of the flexor digitorum profundus in either the ring or the long finger. Six patients had misleading x-ray films because the tendon had retracted farther than the fracture pattern had suggested. All of these patients had avulsion fractures from the palmar aspect of the distal phalanx. Although the classification of Leddy and Packer is very helpful in determining the prognosis for these injuries, the fracture patterns are not reliable in predicting the location of the retracted tendon end preoperatively. Therefore all flexor digitorum profundus tendon avulsions should be surgically repaired as soon as possible.

Adolescent↗

Use of radial forearm flaps to treat complications of closed pilon fractures.

Between 1986 and 1990, five patients have been treated for full-thickness skin loss proximal to the level of the anterior joint line of the ankle following open reduction and internal fixation of closed C3 (ASIF) pilon fractures. The average delay from injury to the initial open reduction and internal fixation was 4.6 days. Anteromedial and posterolateral incisions were used to expose the fractures, resulting in a bipedicle flap over the anterior aspect of the ankle joint at the time of the initial surgery. The minimum distance between these two incisions for these five patients was 6.0 to 9.0 cm (average of 7.4 cm). Free tissue transfers using the radial forearm flap were effective in providing durable but thin coverage for this difficult problem of soft-tissue coverage in an area requiring a thin flap with a long vascular pedicle. The risk for skin necrosis at the time of surgery may be minimized by spacing the incisions up to 12.0 cm apart in addition to avoiding the period of maximal tissue ischemia occurring 3 to 6 days after the injury.

Adult↗