William W. Monafo

Clinical Evaluation of an Acellular Allograft Dermal Matrix in Full-Thickness Burns

A multicenter clinical study assessed the ability of an acellular allograft dermal matrix to function as a permanent dermal transplant in full-thickness and deep partial-thickness burns. The study consisted of a pilot phase (24 patients) to identify the optimum protocol and a study phase (43 patients) to evaluate graft performance. Each patient had both a test and a mirror-image or contiguous control site. At the test site, the dermal matrix was grafted to the excised wound base and a split-thickness autograft was simultaneously applied over it. The control site was grafted with a split-thickness autograft alone. Fourteen-day take rates of the dermal matrix were statistically equivalent to the control autografts. Histology of the dermal matrix showed fibroblast infiltration, neovascularization, and neoepithelialization without evidence of rejection. Wound assessment over time showed that thin split-thickness autografts plus allograft dermal matrix were equivalent to thicker split-thickness autografts.

Current treatment recommendations for topical burn therapy.

SummaryInfections in burn patients continue to be the primary source of morbidity and mortality. Topical antimicrobial therapy remains the single most important component of wound care in hospitalised burn patients. The goal of prophylactic topical antimicrobial therapy is to control microbial colonisation and prevent burn wound infection. In selected clinical circumstances topical agents may be used to treat incipient or early burn wound infections. At the present time silver sulfadiazine is the most frequently used topical prophylactic agent; it is relatively inexpensive, easy to apply, well tolerated by patients, and has good activity against most burn pathogens. In patients with large burns the addition of cerium nitrate to silver sulfadiazine may improve bacterial control. Mafenide acetate has superior eschar-penetrating characteristics, making it the agent of choice for early treatment of burn wound sepsis. However, the duration and area of mafenide application must be limited because of systemic toxicity associated with prolonged or extensive use. Other agents, such as nitrofurazone or chlorhexidine preparations, may be useful in isolated clinical situations. The undesirable side effects of silver nitrate solution limit its use by most clinicians at the present time.

Topical Therapy for Burns

Topical antimicrobial agents can prevent or minimize burn infections and should be used from the outset in all patients who are at significant risk from sepsis--either because of their wound severity or associated comorbid factors. All of the currently available topical agents have shortcomings; some of them have appreciable toxicity. The recent shift in emphasis toward early surgical closure of extensive deep burns in great part has resulted from appreciation of the inadequacies of currently available topical agents. Topical agents cannot substitute for timely and comprehensive physiologic support of burned patients.

Regional blood flow in resting and stimulated sciatic nerve of diabetic rats

The role of ischemia in the pathogenesis of diabetic peripheral neuropathy remains uncertain. We used the distribution of [14C]butanol to measure resting regional sciatic nerve blood flow in normal, anesthetized rats and in rats with acute experimental diabetes from streptozotocin administration. Regional flows in hind limb biceps femoris muscle and skin were simultaneously measured. In additional diabetic rats, these blood flows were compared in both limbs after proximal electrical stimulation of one sciatic trunk (10 shocks/s) for 15 min. One month after streptozotocin administration, 8 of 11 test rats were hyperglycemic. Resting nerve blood flow in the hyperglycemic rats--5.6 +/- 3.07 ml.min-1.100 g-1--was significantly less than that in the controls (9.4 +/- 3.9 ml.min-1.100 g-1, P = 0.002). Muscle blood flow was normal and skin blood flow decreased in these rats. Calculated tissue vascular resistances were elevated in all three tissues. Stimulation of one sciatic trunk in five other diabetic rats resulted in a stimulated nerve blood flow of 15.7 +/- 7.7 ml.min-1.100 g-1, and nerve blood flow in the resting control limb was 7.7 +/- 4.3 ml.min-1.100 g-1 (P = 0.009). Muscle blood flow increased approximately fourfold on the stimulated side but skin blood flow did not increase. Resting sciatic nerve blood flow is modestly decreased in acute streptozotocin-induced diabetes, but the neural blood vessels are still responsive to the increase in nerve metabolic activity associated with nerve stimulation.

Cimetidine inhibits burn edema formation

Large doses of cimetidine significantly inhibit edema formation in thermally injured rat skeletal muscle. Tissue sodium influx and potassium efflux is also sharply restricted. These effects were obtained even if the administration of cimetidine was delayed for up to 4 hours after injury, but no beneficial effect occurred if drug administration was delayed for 14 hours, when most of the edema had already accumulated. The minimal effective dose is between 0.1 to 0.2 mg/gm.

Sciatic nerve function following hindlimb thermal injury

Peripheral neuropathy occurs in approximately 20% of patients with major burns and seriously impairs rehabilitation. We describe an experimental model which permits elevation of the tissue temperature in the region of the distal sciatic nerve trunk of rats at a reproducible rate to a predetermined level without inflicting concomitant major cutaneous injury. Radiofrequency current is delivered through parallel copper electrodes mounted in a chamber into which the limb has been inserted. In the present experiments, tissue temperature was arbitrarily elevated to 47 degrees C for 30 sec in 62 rats. There were 43 normal controls. The posterior tibial branch was the most intensively studied, as some of its conduction characteristics can be serially assessed percutaneously. Conduction block, which was apparently irreversible, was present in 67% of posterior tibials by 24 hr postinjury. In branches which were still excitable, prolongation of the absolute refractory period was the most consistent abnormality noted. Slowing of conduction, as evidenced by prolongation of inflection velocity or peak velocity, was never observed. However, this injury resulted in selective conduction failure of sural--but not of peroneal--fibers which conducted at 40 m/sec or greater. Fiber modality is an important determinant of the vulnerability to direct thermal injury of peripheral nerve in vivo.

Differential effects of in vitro heating on rat sciatic nerve branches and spinal nerve roots

Locally applied heat induces nerve conduction block. Conflicting observations have been made regarding the relation of fiber conduction velocity to heat sensitivity. This study utilized sciatic nerve branches and spinal nerve roots which were heated until a substantial conduction block occurred. The results indicated that sensory fibers conducting at greater than 40 m/s are more heat-sensitive than motor fibers of the same conduction velocity.

Squamous cell carcinoma of the anal canal

Between 1979 and 1988, 33 patients with squamous cell carcinoma of the anal canal were treated with chemoradiation. There were 24 women and 9 men, from 37 to 90 years of age (median: 63 years). Complete tumor regression occurred in 29 of the 33 patients (88%), only one of whom later developed recurrence. In the other four patients, there was persistent tumor after 3 months; three of these patients died within 2 years; and one is alive with distant metastases 2 years later. During the first 5 years of the study, seven patients with complete tumor regression underwent planned abdominoperineal resection following chemoradiation. Four of the abdominoperineal resection specimens were free of tumor, but three were not. These three patients, who had abdominoperineal resection within 3 months of chemoradiation, are disease-free. Ten of the 29 patients who had complete tumor regression had biopsies of the primary site 3 months after treatment. All biopsies were negative for residual carcinoma. At present, 26 patients (79%) are alive and disease-free from 2 to 10 years post-treatment (median: 4 years). Two patients died of unrelated causes, four of cancer, and one is alive with cancer. Complications of the chemoradiation required surgical intervention in two patients, and two others developed severe hematologic toxicity, for a complication rate of 12% (4 of 33 patients). There was no treatment-related mortality. These results support the efficacy of chemoradiation treatment for carcinoma of the anal canal. They suggest that abdominoperineal resection no longer need be part of the planned initial management, and that posttreatment biopsy of the primary site is unnecessary, unless palpable or visible abnormalities are present 3 months after treatment.

Potassium ion channel blockade restores conduction in heat-injured nerve and spinal nerve roots

Compound action potentials were recorded in vitro from rat peroneal and sural nerves and from dorsal and ventral roots of the cauda equina before and after radiofrequency heating of 5-mm-length segments of these nerves to 41 to 45 degrees C. The heating was continued for intervals sufficient to reduce response amplitude by 50%. Inflection velocity, potential duration at 1/2 peak height, and the proportion of conducting A alpha fibers were also measured. The topical application of 4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA) to the previously heated segments immediately following the radiofrequency injury completely or near-completely restored amplitude height to the preheat value in all experiments. A alpha sensory fibers were the most susceptible to the conduction block. Conduction in these fibers was also the most readily restored by the application of 4-AP or TEA. The effects of TEA, but not of 4-AP, could be reversed by saline or buffer washing. Topical application of verapamil and of magnesium or calcium ions had no discernible effect on heated nerves. We suggest that the mechanism of heat-induced conduction block may be similar to that from early demyelination or stretch injury. Further, motor and sensory A alpha fibers differ both in their vulnerability to heat and in their subsequent response to the application of potassium channel blockers.

Fluid resuscitation in a porcine burn shock model

Abstract Miniature swine are sensitive and responsive animals for the study of burn shock resuscitation. In this model the sodium loads requisite for resuscitation of burned swine can exert roughly the same effect although with slower restoration of cardiac output when administered in volumes of 50–75% less than those commonly employed clinically. Sodium excretion is more dependent upon the sodium load than upon the concentration of the saline solution. Plasma had no demonstrable resuscitative effect over and above that provided by its volume and sodium content.