Noncontusive segmental spinal cord injury using radiofrequency current.

OBJECTIVE: To develop a nondisruptive model for the study of spinal cord injury. METHODS: A 2-MHz radiofrequency heating chamber was mounted over the rat T13-L1 vertebral column via a short dorsal incision. Epidural temperature at chamber level was monitored via a small proximal laminotomy. Forty-three rats were studied using time-temperature heating regimens from 45 to 48.5 degrees C and 4 to 15 minutes. A blinded numerical hind limb impairment score (Neurologic Impairment Score) was determined at intervals up to 2 weeks after injury. Segmental spinal cord blood flow was measured using [14C]butanol tissue uptake in injured and control rats. RESULTS: Above the injury threshold, increasing the time-temperature regimens was associated with a progressively worse Neurologic Impairment Score (r = 0.73-0.87 up to 24 hours after injury). Cord blood flow was unchanged at 2 hours but was 44% depressed at the injury level 6 hours after injury (p < 0.01). Histologically, injury extended minimally beyond the injured segment. Vascular thrombosis was not seen. CONCLUSION: This comparatively noninvasive model does not mechanically disrupt cord components and results in progressive neurologic impairment that correlates with the time-temperature regimen used for injury. It should be useful in identifying secondary phenomena that worsen functional status after cord trauma.

Diabetes impairs sciatic nerve hyperemia induced by surgical trauma: implications for diabetic neuropathy.

The most widely used methods to assess nerve blood flow in diabetics rats are hydrogen clearance polarography and laser Doppler flowmetry, techniques requiring surgical exposure of the nerve. In these experiments, we examined the hypothesis that the trauma of surgical exposure introduces an important and hitherto largely unrecognized variable that could account for discordant reports on nerve blood flow changes induced by diabetes. We used the noninvasive (for sciatic nerve) reference sample microsphere method to quantify sciatic nerve blood flow in unexposed va. surgically exposed nerves in rats with streptozotocin-induced diabetes (at different temperatures and after curarization) and in unexposed vs. surgically exposed nerves in galactose-fed rats. Baseline resting blood flow in unexposed nerves in both animal models of diabetes was either normal or increased (but was decreased in diabetic rats given d-tubocurarine). Furthermore, the normal brisk hyperemic nerve blood flow response to the minimal trauma associated with surgical exposure of the nerve was markedly impaired in diabetic and in galactose-fed rats. Normalization of the blood flow response to trauma in galactose-fed rats by an aldose reductase inhibitor suggests that the impairment is linked to increased polyol pathway metabolism. These findings 1) confirm our previous findings that sciatic nerve blood flow in diabetic rats is increased or unchanged in unexposed nerves, while also confirming reports that in surgically exposed nerves blood flow is higher in control than in diabetic rats, and 2) indicate that blood flows in surgically exposed nerves are largely a measure of vascular responses to injury rather than (patho)physiological blood flow in undisturbed nerves.

Surgical management of calcinosis cutis universalis in systemic lupus erythematosus.

Calcinosis cutis is common in several connective tissue diseases but rare in systemic lupus erythematosus (SLE). A 43-year-old woman with a 12-year history of SLE who presented with calcinosis cutis at the time of SLE diagnosis developed a large, ulcerated, draining mass on her left hip. The lesion was excised and skin was grafted, with an excellent early result. The clinical variants and mechanisms of ectopic calcification are discussed, as well as the proposed medical therapies for calcinosis cutis.

Effect of norepinephrine on regional sciatic nerve blood flow.

The purpose of this study was to explore further adrenergic regulation of peripheral nerve blood flow (NBF) before and after surgical stress. We applied norepinephrine (NE) to one sciatic nerve of rats either immediately after the nerve had been exposed or 2 hr later. Regional NBF was then measured using [14C]butanol distribution. Biceps femoris muscle flow (MBF) was measured simultaneously. The effect of NE on endoneurial NBF was also measured. Contralateral limbs were controls. Control NBF was 11.9 +/- 1.9 total, 9.1 +/- 1.5 endoneurial (units: ml min-1 100 g-1). If 10(-5) M NE was applied immediately postexposure, neither total nor endoneurial NBF was affected. If 10(-5) M NE was applied 2 hr postexposure, however, total NBF on the control side was 21 +/- 2.3 vs 8.3 +/- 1.2 on the NE side (P < 0.001). In all surgically exposed limbs, MBF was elevated and fell sharply in response to 10(-5) M NE. We conclude that under basal conditions, neither total nor endoneurial NBF is affected by topical NE. When NBF is already elevated from surgical trauma, however, NE reduces it.

Nerve and muscle blood flow during hindlimb ischemia and reperfusion in rats.

Animal models of peripheral nerve ischemia have yielded variable results. The question of whether post-ischemia re-establishment of blood flow to the nerves augments injury has not been examined. To study this question, the ipsilateral common iliac and femoral arteries were occluded with arterial snares for 3 hours in rats; 14C-butanol tissue distribution was then used to measure blood flow in both sciatic and posterior tibial nerve trunks and in both biceps femoris muscles during occlusion and reperfusion. Clinical limb function was graded serially, with the undisturbed contralateral limb serving as the study control. Nerve blood flow was reduced throughout the ischemic period and was only 20% of the control value in the posterior tibial nerve. Muscle blood flow was unchanged. All rats had functional impairment, with an average limb function score of 7.5 (normal score < 2). During reperfusion, blood flow in the distal sciatic and posterior tibial nerves was approximately double that of control nerves at 2 hours, and muscle blood flow was also elevated. At 21 hours, tibial nerve blood flow was still twice that of the control nerve, but flows in the distal sciatic nerve and muscle were unchanged from control levels. Clinically, limb function improved progressively after reperfusion. It was concluded that nerve ischemia is attended by a relatively prolonged hyperemic flow response during reperfusion.

Limb ischemia and reperfusion: relationship of functional recovery to nerve and muscle blood flow.

UNLABELLED: The relative importance of nerve versus muscle injury in limb ischemia-reperfusion is poorly understood. We used 14C-butanol tissue distribution to measure regional blood flow simultaneously in the proximal and distal sciatic, the posterior tibial nerve trunk (NBF), and biceps femoris muscle (MBF) of rats during 3 hours of occlusion of the ipsilateral iliac and femoral arteries and subsequently for up to 9 days of reperfusion. Limb motor function was also serially assessed. The contralateral limbs served as controls. Experimental groups were untreated control (n = 16); methylprednisolone, 30 mg/kg (n = 13); the lazaroid U74389F, 3 mg/kg (n = 13); and lazaroid vehicle (n = 13), i.v. 15 minutes before occlusion and 15 minutes after reperfusion. RESULTS: One hour after occlusion, NBF was -77% of the control value (p < 0.02) but MBF was unchanged (control NBF 15.2 +/- 3.3, control MBF 6.3 +/- 0.9, units mL.min-1 x 100 g-1). At both 2 and 21 hours of reperfusion, NBF was double that of control in all groups (p < 0.01); but MBF, which had been modestly elevated to 10.5 +/- 0.5 at 2 hours (p < 0.01), was already normal at 21 hours in all groups. During days 5 to 9 of reperfusion, NBF was still numerically elevated (NS); MBF remained at control. Functionally, test. limb scores were always grossly abnormal during occlusion (range: 7.1-8.5, normal = < 2). After 1 hour of reperfusion, all test limb scores were improved versus occlusion (p < 0.001, Wilcoxon rank-sum). Subsequently, there was gradual improvement in all groups, scores at 6 days ranging from 1.9 to 2.5. CONCLUSION: NBF is rapidly and severely reduced during ischemia. During reperfusion, the hyperemic flow response in nerve is more prolonged than in muscle. Limb dysfunction during ischemia and reperfusion may be largely the result of axonal or neuromuscular junction injury or both. Neither of the two treatments had effects on blood flow or limb function.

Effect of surgical trauma on regional blood flow in rat sciatic nerve.

UNLABELLED: The factors affecting peripheral nerve blood flow (NBF) are not well defined. We used [14C]butanol distribution to quantitate NBF in rat sciatic nerve following either (1) simple surgical exposure (EXP) or (2) EXP plus nerve mobilization and isolation (ISOL). Undisturbed contralateral nerves were controls. The epineurial contribution to NBF after EXP was also assessed. Results (units: ml.min-1 x 100 g-1): Within 1 to 6 h after EXP (N = 7), NBF was 22.1 +/- 2.7 vs 11.9 +/- 1.5 control (P < 0.01). Seven to 24 h after EXP (N = 6), NBF was unchanged from control. Two hours following EXP, both endoneurial NBF and total (epineurial plus endoneurial) NBF were elevated (P < 0.05, P < 0.02, respectively). Within 48 h after ISOL (N = 6) NBF was 30.3 +/- 3.9 vs 13.2 +/- 2.1 control (P < 0.005). Three to seven days after ISOL (N = 8), NBF was unchanged from control. CONCLUSION: Surgical trauma induces a brisk flow response in peripheral nerve that is proportionate in duration to the trauma severity. Measurements of NBF after EXP or ISOL are therefore potentially misleading if the changes in NBF due to the trauma are not accounted for.

Guanethidine chemical sympathectomy: spinal cord and sciatic nerve blood flow.

The spinal cord vasculature is innervated by noradrenergic nerve fibers, the role of which in the regulation of regional spinal cord blood flow (RSCBF) is presently unclear. We used the distribution of [14C]butanol to simultaneously measure RSCBF at seven cord levels and the regional blood flow in sciatic nerve (NBF), truncal skin, and biceps femoris muscle. The subjects were control rats and rats that had been given parenteral guanethidine sulfate for 5 wk to induce selective postganglionic "chemical sympathectomy." Flows were measured under basal conditions (group I) and immediately after an arterial hemorrhage (group II). The results indicate that RSCBF was unchanged from control after guanethidine administration in both groups; however, NBF was elevated after guanethidine by 47% in group I and by 41% in group II. We conclude that in the spinal cord as in the brain, sympathetic inflow does not appear to have an important role in the regulation of regional blood flow. Sympathetic inflow appears to partly regulate NBF, however, probably by varying vascular tone.

Methylprednisolone treatment of experimental spinal cord injury.

UNLABELLED: Lipid peroxidation has been identified as a deleterious consequence of contusive spinal cord trauma and of thermal injury. The L3-L6 spinal cord segment was thermally injured using a radiofrequency heating chamber mounted on the vertebral column of anesthetized rats. Hind limb function was assessed 2 hours later. A bolus of methylprednisolone (MP, 30 mg/kg) was then given intravenously, followed by 5.4 mg/kg/hr MP for 6 or 24 hours. Cord water content and regional spinal cord blood flow (RSCBF, 14C-butanol distribution) were measured at seven cord levels after function had been reassessed following treatment. Untreated rats were given vehicle. The study was randomized and blinded. RESULTS: Edema in heated segments was progressive over 24 hours, but was the same in treated vs untreated rats. RSCBF in heated segments was the same in treated vs uninjured controls at 6 and 24 hours. In untreated rats, RSCBF in the heated segment was elevated by 30% at 6 hours, but was the same as uninjured control by 24 hours. In the unheated segments of untreated rats, RSCBF was elevated at 24 hours. At 24 hours, RSCBF was lower in treated vs untreated rats at all levels, including the heated one. Limb function deteriorated equivalently in both groups. CONCLUSION: MP obviated the early rise in RSCBF in heated segments and the elevations in RSCBF in uninjured segments, but had no effect on cord edema or on limb function.

Role of extended resection in the initial treatment of locally advanced colorectal carcinoma.

The focus of this review is the role of extended resection in the initial treatment of primary colorectal carcinoma. About 10% of patients with newly diagnosed colorectal cancer will have locally advanced disease without evident distant or discontiguous intraabdominal metastases. En bloc resection of such tumors, including attached tissues or organs, provides a 5-year survival rate of about 40%, if the microscopic margins are tumor free. As many as 60% of these large tumors are node negative; in this circumstance the 5-year survival rate approaches 70%. These results are achievable when there is a meticulous preoperative and intraoperative search for metastases, a wide anatomic resection, including en bloc lymphadenectomy, is performed, and tumor manipulation is minimized. Blunt separation of structures adherent to the primary tumor should be avoided because adhesions will be neoplastic in about 50% of cases, and cancer recurrence is virtually certain when tumor is transected. The mortality from multivisceral resection, including total pelvic exenteration, should be 10% or less. We emphasize the importance of including these patients in prospective trials to define their optimal adjuvant therapy. There is a disturbing recurring theme in published series, failure to extend the scope of resection in potentially curable patients. The management of these locally advanced lesions typically receives but cursory notice in otherwise highly detailed reviews or textbook chapters. In the present era of emerging multimodality treatment for colorectal cancer, the adequacy of the one most important treatment component--surgical resection--is seldom emphasized. Furthermore, our perusal of the recent literature disclosed no diminution in the incidence of inadequate resection, suggesting that this subject requires more emphasis in postgraduate surgical education.

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.

Benefits and limitations of burn wound excision.

This review is intended to provide a balanced view of the role of surgical burn wound excision and closure within the larger context of the total care and rehabilitation of patients with burn injury. The historical background leading to present practice is outlined. The salient technical and logistical problems associated with the performance of wound excision are discussed, with emphasis on the necessity for expeditiously completing these procedures which are associated with major blood loss. A realistic analysis of the results of excisional therapy in patients with burns of varying severity is presented. Benefits attributable to the surgical phase of therapy become progressively more difficult to identify as the size of deep burns increases beyond 20% of total body surface area.

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.

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.

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.