Then and now: 50 years of burn treatment.
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Adolescent↗
Biomedical subjects
W W Monafo
Publications and source records attributed to W W Monafo.
The effects of lumbar sympathectomy on regional spinal cord blood flow in rats during acute hemorrhagic hypotension.
It has not previously been determined whether the sympathetic nervous system has a role in the regulation of regional blood flow in the spinal cord. The authors used 14C-butanol distribution to measure regional spinal cord blood flow at seven cord levels, in the sciatic nerve, and in the biceps femoris muscle in 36 rats, 18 of which had undergone excision of both lumbar sympathetic chains at least 6 days previously. Blood flows were measured during pentobarbital anesthesia. Mean arterial blood pressure (MABP) was monitored and arterial pO2, pCO2, and pH were determined prior to flow measurement. Anesthetic dose and duration were controlled. Measurements were made in normotensive rats and in rats with MABP maintained at either 69 +/- 3 mm Hg or 48 +/- 3 mm Hg for 1 hour by the withdrawal of arterial blood. One-half of the rats in each group had undergone sympathectomy. The resting cord blood flow was lower than control values following sympathectomy only at the S1-4 cord level (p less than 0.01) and cauda equina (p less than 0.01), and was marginally lower at the L1-2 and L3-6 levels (p less than 0.1). Cord blood flow was unaffected by sympathectomy during moderate hypotension. During severe hypotension, cord blood flow was less than control at the C3-5 level (p less than 0.05), but did not differ from control at the other six levels. Flows in nerve and muscle were consistent with known effects of sympathectomy on peripheral tissues. It is concluded that, at most, sympathectomy may moderately decrease resting blood flow in the cord levels caudal to L-1. Sympathectomy has no major effect on regional spinal cord blood flow in rats stressed by either moderate or severe arterial hemorrhage.
Animals↗
Topical silicone gel for the prevention and treatment of hypertrophic scar.
We studied the effects of a silicone gel bandage that was worn for at least 12 hours daily on the resolution of hypertrophic burn scar. In a second cohort, the prevention of hypertrophic scar formation in fresh surgical incisions by this bandage was also evaluated. In 19 patients with hypertrophic burn scars, elasticity of the scars was quantitated serially with the use of an elastometer. An adjacent or mirror-image hypertrophic burn scar served as a control. Scar elasticity was increased after both 1 and 2 months compared with that in controls. There was corresponding improvement clinically that persisted for at least 6 months. In the other cohort, scar volume changes in 21 surgical incisions were measured before and after 1 and 2 months. Gel-treated incisions gained less volume than control incisions after both intervals. Clinical assessment corroborated this quantitative demonstration of a decrement in scar volume. We concluded that topical silicone gel is efficacious, both in the prevention and in the treatment of hypertrophic scar.
Administration, Topical↗
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.
Adult↗
Effects of 4-aminopyridine on protein phosphorylation in heat-blocked peripheral nerve.
The topical application of 4-aminopyridine (4-AP) reverses within 1-3 min the partial conduction block that results from heating 5-mm segments of rat posterior tibial, peroneal and sural nerves to 45 degrees C for several minutes. Nerves previously blocked in vitro or in vivo were incubated in vitro in the presence of [gamma-32P]ATP. The rate of phosphorylation of soluble nerve proteins that had entered the media was determined. Labeled proteins were separated electrophoretically and autoradiograms prepared. We found that 5 mM 4-AP increases the phosphorylation rate in heat-blocked nerve by approximately 50-fold. The process is calcium-dependent and is heat-labile. Soluble proteins with a molecular weight in the 53-55 kDa range are preferentially but not exclusively phosphorylated in the presence of 4-AP at levels effective in restoring conduction. The results suggest that the potassium channel blocker 4-AP may restore conduction by inducing changes in channel proteins.
4-Aminopyridine↗
Effect of adrenalectomy or sympathectomy on spinal cord blood flow in hypothermic rats.
We used [14C]butanol distribution to measure regional spinal cord blood flow (RSCBF) in three groups of pentobarbital-anesthetized rats: 1) normals (n = 16); 2) after bilateral adrenalectomy (n = 18); and 3) after excision of the abdominal sympathetic chains (n = 12). Half of the rats in each group were maintained near normothermia; the remainder were colled to a rectal temperature of 25-27 degrees C. In intact rats, there was a 24-37% increase in RSCBF during hypothermia in the cord region C3-L6 inclusive. Neither operative procedure altered RSCBF during normothermia. In hypothermic adrenalectomized rats, RSCBF was elevated only in the C3-C5 cord segment. After sympathectomy, RSCBF was unchanged during hypothermia. In the cauda equina, flow fell in all hypothermic rats. The hypothermia-associated increases in RSCBF were not related to changes in mean arterial blood pressure. We conclude that adrenalectomy near-totally ablates the hypothermia-associated increase in RSCBF measured in intact rats and that abdominal sympathectomy totally ablates it. This evidence complements morphological evidence for adrenergic innervation of the spinal cord vasculature.
Adrenalectomy↗
Patient tolerance study of topical chlorhexidine diphosphanilate: a new topical agent for burns.
Effective topical antimicrobial agents decrease infection and mortality in burn patients. Chlorhexidine phosphanilate (CHP), a new broad-spectrum antimicrobial agent, has been evaluated as a topical burn wound dressing in cream form, but preliminary clinical trials reported that it was painful upon application. This study compared various concentrations of CHP to determine if a tolerable concentration could be identified with retention of antimicrobial efficacy. Twenty-nine burn patients, each with two similar burns which could be separately treated, were given pairs of treatments at successive 12-h intervals over a 3-day period. One burn site was treated with each of four different CHP concentrations, from 0.25 per cent to 2 per cent, their vehicle, and 1 per cent silver sulphadiazine (AgSD) cream, an antimicrobial agent frequently used for topical treatment of burn wounds. The other site was always treated with AgSD cream. There was a direct relationship between CHP concentration and patients' ratings of pain on an analogue scale. The 0.25 per cent CHP cream was closest to AgSD in pain tolerance; however, none of the treatments differed statistically from AgSD or from each other. In addition, ease of application of CHP creams was less satisfactory than that of AgSD. It was concluded that formulations at or below 0.5 per cent CHP may prove acceptable for wound care, but the vehicle system needs pharmaceutical improvement to render it more tolerable and easier to use.
Administration, Topical↗
Regional spinal cord blood flow during local cooling.
We used the tissue distribution of [14C]butanol to quantitate regional blood flow in the spinal cord (RSCBF) of pentobarbital-anesthetized, normothermic rats in which segmental local cooling pentobarbital-anesthetized, normothermic rats in which segmental local cooling of the spinal cord (to 25-28 degrees C) at vertebral levels C4-C6 (n = 6) or T13-L1 (n = 6) was induced. Thirty minutes later, blood flow measurements were made at seven levels of the spinal cord and in the sciatic nerve trunks and biceps femoris muscles. Sham-cooled rats served as controls (n = 12). In control rats, RSCBF varied between 41.5 +/- 2.4 and 65.1 +/- 3.2 ml.min-1.100 g-1. Local cooling of the C4-C6 cord segment reduced RSCBF by 32%, from 65.1 +/- 3.2 to 44.4 +/- 3.5 ml.min-1.100 g-1 (P less than 0.01). Tissue vascular resistance (R) in the cooled C4-C6 segment was elevated versus control. There were no other changes in RSCBF at the other cord levels or in the cauda equina. Similarly, local cooling of the T13-L1 segment resulted in a 40% fall in RSCBF in that segment, from 57.1 +/- 2.4 to 34.1 +/- 4.3 ml.min-1.100 g-1 (P less than 0.001). R in the cooled T13-L1 segment was elevated versus control. RSCBF was reduced by 30% in the adjacent proximal T12 segment (P less than 0.001) and by 21% in the adjacent distal L2-L3 segment (P less than 0.05). R was increased in both of these adjacent segments. RSCBF was not altered elsewhere in the cord.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Regional blood flow in transected rat spinal cord during hypothermia.
Regional blood flow (RBF) increases in the spinal cord and sciatic nerve of acutely hypothermic rats. To determine whether cord transection affects this response, we measured RBF in rat spinal cord and sciatic nerve 2 h after cord transection at vertebrae T8 (n = 18 rats) and T11 (n = 18 rats) using [14C]butanol distribution. Nine in each group were normothermic controls. In T11 transection-hypothermia (25-27 degrees C rectal temperature), RBF increased in the three rostral cord segments by 28-40% (P less than 0.05); caudally, cord RBF was depressed in two segments (P less than 0.05), unchanged in the other; RBF fell in nerve (P less than 0.05). In T8 transection-hypothermia, RBF was unchanged in the two rostral cord segments; caudally, RBF was depressed in one cord segment (P less than 0.05) and unchanged in the others; RBF was unchanged in nerve. We conclude that RBF does not rise in caudal spinal cord segments or in sciatic nerve during hypothermia in rats with prior spinal cord transection.
Animals↗
Current treatment recommendations for topical burn therapy.
Infections 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.
Administration, Topical↗
Regional blood flow in the brain and spinal cord of hypothermic rats.
[14C]butanol tissue uptake was used to measure simultaneously regional blood flow in three regions of the brain (cerebral and cerebellar hemispheres and brain stem) and in five levels of the spinal cord in 10 normothermic rats (group A) and in 10 rats in which rectal temperature had been lowered to 27.7 +/- 0.3 degrees C by applying ice to the torso (group B). Pentobarbital sodium anesthesia was used. Mean arterial blood pressure varied minimally between groups as did arterial pH, PO2, and PCO2. In group A, regional spinal cord blood flow (rSCBF) varied from 49.7 +/- 1.6 to 62.6 +/- 2.1 ml.min-1.100 g-1; in brain, regional blood flow (rBBF) averaged 74.4 +/- 2.3 ml.min-1.100 g-1 in the whole brain and was highest in the brain stem. rSCBF in group B was elevated in all levels of the cord by 21-34% (P less than 0.05). rBBF, however, was lowered by 21% in the cerebral hemispheres (P less than 0.001) and by 14% in the brain as a whole (P less than 0.05). The changes in calculated vascular resistance tended to be inversely related to blood flow in all tissues. We conclude that rBBF is depressed in acutely hypothermic pentobarbital sodium-anesthetized rats, as has been noted before, but that rSCBF rises under these experimental conditions. The elevation of rSCBF in hypothermic rats confirms our previous observations.
Animals↗
The effect of hypothermia on regional spinal cord blood flow in rats.
Spinal cord ischemia may accompany surgical procedures on the aorta or vertebral column. Regional spinal cord blood flow (SCBF) was measured at five vertebral levels in the spinal cords of pentobarbital-anesthetized rats based on the distribution of intravenously injected carbon-14-labeled butanol. In seven normal rats, mean SCBF (+/- standard error of the mean) ranged from 52.7 +/- 5.4 to 68.5 +/- 4.9 ml.min-1.100 gm-1 (depending on the level, being lowest at the thoracic levels) and mean arterial blood pressure (MABP) was 126 mm Hg. Corporal hypothermia (mean rectal temperature 28.1 degrees +/- 0.6 degrees C) was induced by cold exposure in seven other rats, and SCBF, measured immediately thereafter, was significantly elevated at all five levels by 52% to 69% compared to the normal group. However, MABP was elevated in the hypothermic group to 165 +/- 4 mm Hg (p less than 0.0001). Therefore, in seven additional hypothermic rats, MABP was maintained at the control level by withdrawal of arterial blood as necessary. In these animals, SCBF at all levels was still significantly elevated compared with the normal group and the values were nearly identical to those measured in the hypertensive hypothermic rats. It was concluded that hemodynamic autoregulation of SCBF is impaired in the presence of moderate systemic hypothermia in pentobarbital-anesthetized rats.
Animals↗
Topical silicone gel: a new treatment for hypertrophic scars.
A prospective, controlled clinical trial was designed to assess the efficacy of a new treatment of hypertrophic scars. Silicone gel sheeting was applied to 14 hypertrophic scars in 10 adults for 8 weeks. The treated scars and untreated, mirror-image or adjacent control scars were photographed, biopsy specimens were taken, and they were measured elastometrically before and after treatment. Photography and elastometry were repeated 4 weeks after treatment was discontinued. All the scars that had been treated for at least 12 hours a day were improved clinically after 4 weeks. There was further clinical improvement during the second 4 weeks of treatment. Elastometrically, the treated scars were improved significantly at 4, 8, and 12 weeks, compared with both their own treatment value and the control scars (p less than 0.05). Control scars were unchanged elastometrically. Clinical improvement persisted for at least 4 weeks after treatment was discontinued. The silicone gel sheeting was well tolerated, except for occasional transient rashes or superficial maceration--both of which resolved promptly when treatment was withdrawn. There was no histologic evidence of inflammation or foreign body reaction suggesting that silicone had entered the treated tissues. We conclude that this simple method of treating hypertrophic scar is efficacious, even in relatively chronic cases. The mechanism of action of silicone gel, which is apparently not related to compression, remains to be determined.
Administration, Topical↗
HIV exposure in the emergency department.
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Adult↗
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.
Animals↗
[14C]butanol distribution: a new method for measurement of spinal cord blood flow.
[14C]butanol distribution was used to quantitate regional blood flow (SCBF) in the spinal cord (levels T3-5, T7-9, L1-2, L3-S) and in the sciatic nerves (NBF) of control pentobarbital sodium-anesthetized rats (group A), after 1 h of hemorrhagic hypotension (group B), after 15 min of stimulation of one sciatic nerve (group C-1), and after stimulation of one sciatic nerve plus hemorrhage, which maintained mean arterial pressure (MAP) at control (130 mmHg). Group A SCBF ranged from 52.3 +/- 3.5 (L3-S) to 67.4 +/- 2.7 (L1-2) ml.min-1.100 g-1. NBF was 8.0 +/- 0.9 ml.min-1.100 g-1. Group B SCBF was unchanged. NBF fell to 4.0 +/- 0.4 ml.min-1.100 g-1. Group C-1 SCBF was markedly elevated (range 122 +/- 23.1 to 150.1 +/- 18.7 ml.min-1.100 g-1). NBF was 33.5 +/- 4.1 ml.min-1.100 g-1 (stimulated side) and 14.7 +/- 1.4 ml.min-1.100 g-1 (nonstimulated). MAP was elevated (163 +/- 6 mmHg). In group C-2 (MAP was 130 +/- 4 mmHg), SCBF was still elevated at T3-5, L3-S, and marginally elevated at L1-2. NBF was 22.6 +/- 4.7 ml.min-1.100 g-1 (stimulated) but unchanged contralaterally. [14C]butanol distribution provides a sensitive reproducible measure of SCBF and NBF. Autoregulation of SCBF (but not of NBF) occurred in the range 60-160 mmHg MAP. Spinal cord stimulation via the sciatic nerve increased SCBF two- to threefold, but when hypertension was avoided by blood withdrawal, a modest (38%) increase in SCBF still occurred.
Animals↗
Elevated regional sciatic nerve blood flow in hypothermic anesthetized rats.
The effect of corporal hypothermia on regional blood flow in peripheral nerve is unknown. We compared blood flow in resting sciatic nerves of anesthetized, normothermic rats with that of rats whose rectal temperatures had been acutely lowered to 28 to 30 degrees C. Peripheral nerve regional blood flow in normothermic rats in which one hind limb was cooled was also measured, as were simultaneous flow changes in biceps femoris muscle and thigh skin. Flows were quantitated by the fractional distribution of [14C]butanol. Hypothermia was associated with increased peripheral nerve blood flow and a simultaneous decrease in muscle and skin blood flow. Nerve vascular resistance was not consistently altered in hypothermia, but muscle and skin vascular resistances were elevated. Topical cooling of one limb did not affect the tissue blood flows in either limb. The regulation of resting nerve blood flow in hypothermic rats differs appreciably from that in biceps femoris muscle and skin. Nerve blood flow did not increase with local cooling in normothermic rats. Central, neurally mediated mechanisms may be responsible for the increased regional nerve blood flow in hypothermic rats.
Animals↗
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.
Administration, Topical↗