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Biomedical subjects

P L Perot

Publications and source records attributed to P L Perot.

At least 19 recordsLinked to original sources

Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up. Results of the third National Acute Spinal Cord Injury randomized controlled trial.

OBJECT: A randomized double-blind clinical trial was conducted to compare neurological and functional recovery and morbidity and mortality rates 1 year after acute spinal cord injury in patients who had received a standard 24-hour methylprednisolone regimen (24MP) with those in whom an identical MP regimen had been delivered for 48 hours (48MP) or those who had received a 48-hour tirilazad mesylate (48TM) regimen. METHODS: Patients for whom treatment was initiated within 3 hours of injury showed equal neurological and functional recovery in all three treatment groups. Patients for whom treatment was delayed more than 3 hours experienced diminished motor function recovery in the 24MP group, but those in the 48MP group showed greater 1-year motor recovery (recovery scores of 13.7 and 19, respectively, p=0.053). A greater percentage of patients improving three or more neurological grades was also observed in the 48MP group (p=0.073). In general, patients treated with 48TM recovered equally when compared with those who received 24MP treatments. A corresponding recovery in self care and sphincter control was seen but was not statistically significant. Mortality and morbidity rates at 1 year were similar in all groups. CONCLUSIONS: For patients in whom MP therapy is initiated within 3 hours of injury, 24-hour maintenance is appropriate. Patients starting therapy 3 to 8 hours after injury should be maintained on the regimen for 48 hours unless there are complicating medical factors.

Activities of Daily Living↗

Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study.

OBJECTIVE: To compare the efficacy of methylprednisolone administered for 24 hours with methyprednisolone administered for 48 hours or tirilazad mesylate administered for 48 hours in patients with acute spinal cord injury. DESIGN: Double-blind, randomized clinical trial. SETTING: Sixteen acute spinal cord injury centers in North America. PATIENTS: A total of 499 patients with acute spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS) centers within 8 hours of injury. INTERVENTION: All patients received an intravenous bolus of methylprednisolone (30 mg/kg) before randomization. Patients in the 24-hour regimen group (n=166) received a methylprednisolone infusion of 5.4 mg/kg per hour for 24 hours, those in the 48-hour regimen group (n=167) received a methylprednisolone infusion of 5.4 mg/kg per hour for 48 hours, and those in the tirilazad group (n=166) received a 2.5 mg/kg bolus infusion of tirilazad mesylate every 6 hours for 48 hours. MAIN OUTCOME MEASURES: Motor function change between initial presentation and at 6 weeks and 6 months after injury, and change in Functional Independence Measure (FIM) assessed at 6 weeks and 6 months. RESULTS: Compared with patients treated with methylprednisolone for 24 hours, those treated with methylprednisolone for 48 hours showed improved motor recovery at 6 weeks (P=.09) and 6 months (P=.07) after injury. The effect of the 48-hour methylprednisolone regimen was significant at 6 weeks (P=.04) and 6 months (P=.01) among patients whose therapy was initiated 3 to 8 hours after injury. Patients who received the 48-hour regimen and who started treatment at 3 to 8 hours were more likely to improve 1 full neurologic grade (P=.03) at 6 months, to show more improvement in 6-month FIM (P=.08), and to have more severe sepsis and severe pneumonia than patients in the 24-hour methylprednisolone group and the tirilazad group, but other complications and mortality (P=.97) were similar. Patients treated with tirilazad for 48 hours showed motor recovery rates equivalent to patients who received methylprednisolone for 24 hours. CONCLUSIONS: Patients with acute spinal cord injury who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone is initiated 3 to 8 hours after injury, patients should be maintained on steroid therapy for 48 hours.

Adolescent↗

MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter Animal Spinal Cord Injury Study.

The Multicenter Animal Spinal Cord Injury Study (MASCIS) adopted a modified 21-point open field locomotor scale developed by Basso, Beattie, and Bresnahan (BBB) at Ohio State University (OSU) to measure motor recovery in spinal-injured rats. BBB scores categorize combinations of rat hindlimb movements, trunk position and stability, stepping, coordination, paw placement, toe clearance, and tail position, representing sequential recovery stages that rats attain after spinal cord injury. A total of 22 observers from 8 participating centers assessed 18 hindlimbs of 9 rats at 2-6 weeks after graded spinal cord injury. The observers were segregated into 10 teams. The teams were grouped into 3 cohorts (A, B, and C), consisting of one experienced team from OSU and two non-OSU teams. The cohorts evaluated the rats in three concurrent and sequential sessions. After viewing a rat for 4 min, individual observers first assigned scores without discussion. Members of each team then discussed and assigned a team score. Experience (OSU vs. non-OSU) and teamwork (individual vs. team) had no significant effect on mean scores although the mean scores of one cohort differed significantly from the others (p = 0.0002, ANOVA). However, experience and teamwork significantly influenced reliability of scoring. OSU team scores had a mean standard deviation or discordance of 0.59 points, significantly less than 1.31 points for non-OSU team scores (p = 0.003, ANOVA) and 1.30 points for non-OSU individual scores (p = 0.001, ANOVA). Discordances were greater at the upper and lower ends of the scale, exceeding 2.0 in the lower (< 5) and upper (> 15) ends of the scale but were < 1.0 for scores between 4 and 16. Comparisons of non-OSU and OSU team scores indicated a high reliability coefficient of 0.892 and a correlation index (r2) of 0.894. These results indicate that inexperienced observers can learn quickly to assign consistent BBB scores that approach those given by experienced teams, that the scores are most consistent between 4 and 16, and that experience improves consistency of team scores.

Animals↗

The neuroprotective effect of high-dose methylprednisolone in rat spinal cord hemisection.

Multiple studies support a neuroprotective effect for high-dose methylprednisolone (MP) in acute blunt spinal cord injury. We know of no study that addresses the role of MP in prophylaxis for surgical trauma to the spinal cord or for the treatment of non-missile penetrating injuries to the spinal cord. We examined the neuroprotective effect of MP as measured by the retrograde transport of the fluorescent tracer Fluoro-Gold in 20 rats undergoing C-2 hemisection. Mean cell counts of retrogradely labeled rubrospinal neurons were determined 1 week post-injury. The group receiving MP had a significantly higher (P < 0.0001) number of labeled cells (x = 594) compared to controls (x = 387). The highly significant increase in mean cell counts in rats receiving steroids suggests less secondary axonal injury in the MP group. These findings are the first report of a neuroprotective effect of MP in rat spinal cord hemisection. We suggest that MP may be beneficial as prophylaxis during planned or incidental surgical trauma to the spinal cord and after non-missile penetrating injuries to the spinal cord.

Animals↗

Rubrospinal neurons and retrograde transport of fluoro-gold in acute spinal cord injury--a dose-response curve.

Using the fluorescent tracer Fluoro-Gold, we studied the relationship between severity of spinal cord trauma and the number of retrogradely labeled rubrospinal neurons in the rat. We compared the mean cell counts of retrogradely labeled rubrospinal neurons in rats receiving 0, 20, 40, and 60 g/cm concussive spinal cord traumas. For each incremental increase in trauma a significant reduction in mean cell counts took place (P < 0.0001). We demonstrate a dose-response relationship between trauma severity and Fluoro-Gold retrogradely labeled rubrospinal neurons in acute spinal cord injury of the rat. This relationship may be helpful in quickly assessing the efficacy of therapeutic interventions in acute spinal cord injury. Previous studies with HRP failed to demonstrate such a dose-response curve. Fluoro-Gold may be a more sensitive indicator of neuronal survival than HRP in the traumatized rat spinal cord.

Acute Disease↗

Protective effect of methylprednisolone on vascular injury in rat spinal cord injury.

High-dose methylprednisolone (MP) given to patients within 8 h of traumatic spinal cord improved neural function at 6 and 12 months, suggesting a probable secondary injury process that may be amenable to therapeutic intervention. Vascular injury plays an important role in the secondary injury process of CNS trauma. We have examined the effect of MP on vascular changes, including tissue edema, vascular permeability, and polymorphonuclear (PMN) cell infiltration in a rat model of spinal cord impact injury. MP significantly reduced extravasation of fluorescein isothiocyanate dextran (FITC-D), a macromolecular tracer, by 64.3% and 50.7% with trauma forces of 20 and 40 g-cm, respectively, when MP was administered IV immediately after trauma at a bolus of 165 mg/kg, with a subsequent continuous MP infusion at 31.5 mg/kg/h for 23 h. MP reduced the water content in the 40 g-cm traumatic cord lesion to 73.0% compared to the traumatic control (74.3%, p < 0.001) at the same schedule of large dose 24-h infusion. The same doses of MP showed a trend to decrease the extent of neutrophil infiltration as determined by myeloperoxidase (MPO) activity, but the change was not significant. MP had little effect in decreasing FITC-D extravasation and cord edema when given at a lower dose (bolus of 30 mg/kg with continued infusion of 1.3 mg/kg/h for 23 h). MP did not reduce extravasation of FITC-D and edema when administered IV as one bolus injection at high (165 mg/kg) or low (30 mg/kg) doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A sensitive fluorometric method for measurement of vascular permeability in spinal cord injury.

A sensitive fluorometric method was modified for the evaluation of drug action upon vascular permeability in rat spinal cord injury. Fluorescein isothiocyanate-conjugated dextran (FITC-D MW 71,200), used as a macromolecular tracer, was injected iv 2 hours before sacrifice. The optimal pH for FITC-D fluorescence was 8.2. The recovery in spinal cord was 101.4 +/- 4.0% (mean +/- SD). The extent of FITC-D extravasation, expressed as the vascular injury index (VII), was increased in proportion to the trauma force. The peak of VII after trauma was at 2 hours. This fluorometric method is sensitive, simple, and reliable for evaluation of drug effects upon vascular permeability in CNS trauma.

Animals↗

Leukotriene B4 release and polymorphonuclear cell infiltration in spinal cord injury.

Activation of arachidonic acid occurs after spinal cord injury. Leukotriene B4 is a lipoxygenase metabolite of arachidonic acid. In a rat model of experimental spinal cord injury, we found that the leukotriene B4 content was less than the sensitivity of our assay (8 pg/mg of protein) in non-traumatized spinal cord. Leukotriene B4 was detectable in traumatized cord (mean +/- SE, 25 +/- 5 pg/mg of protein; n = 3). Release of leukotriene B4 from spinal cord slices into the incubation medium was also noted after trauma (9 +/- 1 pg/mg of protein; n = 12) and was enhanced by exposure of traumatized spinal cord slices to the calcium ionophore A23187 (375 +/- 43 pg/mg of protein; n = 12). The amount of leukotriene B4 released corresponded to the extent of post-traumatic polymorphonuclear cell infiltration determined by a myeloperoxidase assay. Results from this study suggest that the source of leukotriene B4 in spinal cord injury is infiltrating polymorphonuclear cells.

Animals↗

Establishing brain death in South Carolina: a clinician's guide.

With recent technological and medical advances, basic cardiopulmonary function can now be prolonged in many patients. Concurrently, organ transplantations have become more common and interest in living wills has increased. As a result, the South Carolina physician is increasingly obligated to determine whether a patient receiving cardiopulmonary support is dead due to irreversible cessation of brain function (ICBF) (brain dead). Here we review the bedside clinical valuation of brain death (ICBF), the adjunctive use of the EEG and other tests, and the South Carolina laws pertaining to this complex decision.

Brain Death↗

Intracranial fibro-osseous lesion. Case report.

A rare tumor closely associated with the trigeminal ganglion produced a syndrome of atypical facial pain in a 44-year-old man. Two previous reports have designated similar tumors as "fibro-osseous lesions." The distinctive morphological appearance is illustrated and possible histogenesis discussed.

Adult↗

Therapeutic model for experimental spinal cord injury in the rat: I. Mortality and motor deficit.

In the course of establishing a therapeutic model for experimental spinal cord injury in the rat, we determined the effects of trauma dose (20, 30, 40, 50, and 60 g-cm) on the mortality and motor deficit in the 4 weeks following injury. Mortality was dependent upon the trauma dose: 20 g-cm, 11%; 30 g-cm, 14%; 40 g-cm, 27%; 50 g-cm, 32%; 60 g-cm, 41%. Statistical analysis by linear regression is highly significant for increasing mortality with increasing trauma dose. The motor deficit determined by a modified Tarlov scale also was dependent upon trauma dose. A trauma dose-response curve based on this study indicates that a drug which reduces the motor deficit from that found at 40 g-cm to that at 30 g-cm may be detected at a significant level of 0.05 with a power of 0.8 if 30 rats are included in each of placebo and treated groups. The same sample size would detect a significant reduction of mortality from that of 40 g-cm to 30 g-cm.

Animals↗

Alteration of thromboxane and prostacyclin levels in experimental spinal cord injury.

We measured levels of thromboxane B2 and 6-keto-PGF1 alpha in rabbit spinal cord and cat CSF after impact injury to spinal cord. Rabbit tissue thromboxane B2 levels increased more than 6-keto-PGF1 alpha. In cat, CSF thromboxane B2 was higher the first hour postinjury; CSF 6-keto-PGF1 alpha also increased, but less so. These results imply activation of arachidonic acid metabolism. The relatively greater increase of thromboxane B2 suggests that thromboxane-prostacyclin imbalance may contribute to post-traumatic ischemia.

6-Ketoprostaglandin F1 alpha↗

Evaluation of acute nonpenetrating cervical spinal cord injuries with CT metrizamide myelography.

Computerized tomography metrizamide myelography was performed in 46 patients with acute, nonpenetrating cervical spinal cord injuries. By visualizing the spinal canal, spinal cord, and any compressive lesion, the study proved valuable in the decision as to whether surgical decompression was indicated and what approach should be used. Eleven patients were found to have significant spinal cord compression, 10 of whom were treated surgically. The technique, results, and complications resulting from the study are discussed.

Adolescent↗

Efficacy of methylprednisolone in acute spinal cord injury.

A multicenter double-blind randomized trial was conducted to examine the efficacy of a high dose of methylprednisolone (1,000-mg bolus and daily thereafter for ten days) compared with a standard dose (100-mg bolus and daily thereafter for ten days) in 330 patients with acute spinal cord injury. No difference in neurological recovery of motor function or pinprick and light touch sensation was observed between the two treatment groups six weeks and six months after injury. The lack of a treatment effect was independent of the severity of the initial lesion or the time from injury to starting treatment. Although not statistically significant, early case fatality was greater in the high-dose protocol (relative risk of 3.1 and 1.9, less than or equal to 14 and 15 to 28 days after injury, respectively) but not from 29 to 210 days after injury. Wound infections of both trauma and operative sites were more prevalent in the high-dose regimen (relative risk of 3.6).

Acute Disease↗

Orthostatic hypotension with brainstem tumors.

Three patients with brainstem tumors had orthostatic hypotension as the major presenting manifestation. Two patients had primary tumors that involved the dorsal medulla, pons, and rostral spinal cord; one was a malignant astrocytoma and the other a hemangioblastoma. The third patient had an oat cell carcinoma of the lung with subependymal spread to the medulla, pons, hypothalamus, and thalamus. Evaluation of baroreceptor function in the patient with the malignant astrocytoma showed a defect in the efferent sympathetic limb of the baroreceptor reflex arc.

Adolescent↗

Elimination of EMG interference during recording of somatosensory evoked potentials elicited by posterior tibial nerve stimulation in patients with cervical spinal cord injury.

Recording SEPs to PTN stimulation in some patients with acute injuries of the cervical spine can be difficult due to the presence of involuntary activity of the neck and jaw muscles. The electrical potentials derived from this myogenic activity have a distribution along the sagittal line of the head which is uniform in amplitude while the amplitude of the SEPs recorded from points along this sagittal line is maximal over a point close to the vertex and less in front and behind this point. This fact has been utilized to devise a 'bipolar' derivation with one electrode on the vertex and two electrodes, one in front and one behind it on the sagittal line tied together as a reference. This effectively eliminates potentials of muscle origin from the SEP record. Other 'bipolar' combinations are not as effective in obtaining evoked potentials free of this muscle interference.

Electroencephalography↗

Scalp recorded somatosensory evoked potentials to posterior tibial nerve stimulation in humans.

The somatosensory evoked potentials (SEPs) produced by stimulation of the right and left posterior tibial nerves individually and also by their simultaneous stimulation were recorded in 84 adult normal subjects up to 150 msec after the stimulus by electrodes placed on the cranial vertex and by rows of electrodes over the sagittal and coronal lines using references on the ear or in the nasopharynx. The statistical distribution of the latencies of their different peaks was established. The effect of simultaneous stimulation of right and left posterior tibial nerves on the early SEP components was described. Some details of the anatomy of the rolandic sulcus were inferred from the amplitude distribution of these potentials.

Adult↗

Dural plasmacytoma.

Dural plasmacytoma is an unusual form of myeloma. We describe a woman with plasmacytoma of the tentorium cerebelli that was managed successfully with surgical decompression and radiotherapy. Computed tomography, not previously reported in cases of dural plasmacytoma, was useful in her management. Another unique feature was the restoration of a normal immunoglobulin G content in the blood and cerebrospinal fluid after local treatment of the neoplasm. Two previously reported cases showed similar normalization of cerebrospinal fluid immunoglobulin G after local radiotherapy. Dural plasmacytoma presents a characteristic clinical syndrome. The typical patient is a woman (92% of the reported cases) in the 5th decade of life. Clinical findings reflect intracranial hypertension, often with focal neurological signs, consistent with the usual dural or tentorial origin of the tumor. Immunoglobulin abnormalities may be found in serum or cerebrospinal fluid. The prognosis is good after surgical decompression and local radiotherapy.

Adult↗