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Biomedical subjects

R D Linden

Publications and source records attributed to R D Linden.

At least 19 recordsLinked to original sources

Incidence rates and populations at risk for spinal cord injury: A regional study.

STUDY DESIGN: A 6 year retrospective study was conducted. OBJECTIVES: The populations at risk for spinal cord injury (SCI) in the northwestern Kentucky (KY) and southern Indiana (IN) regions were identified following examination of the causes and factors associated with SCI. SETTING: The database included patients primarily from the surrounding KY and IN counties admitted to the University of Louisville (U of L) Hospital. METHOD: Specification of SCI patient demographics, injury causes and related factors was achieved utilizing the hospital's trauma institute database and an extensive review of patient medical records. RESULTS: An adjusted average incidence rate of 27.1 cases per million per year was obtained for this region. A high rate of SCI was found for the youngest age group, 14-24 year olds, and for African Americans. A high frequency of injuries was also observed for adults between the ages of 25-39 years. Motor vehicle accidents (MVA) were the leading cause of SCI. Contributing factors included alcohol and widespread non-use of vehicle safety precautions. CONCLUSIONS: In addition to the high proportion of youth at risk for SCI, a higher proportion of older adults with SCI was observed for this region compared to other studies. Because the primary source of transportation in this area is the use of private vehicles, rather than public transportation, greater effort is warranted in emphasizing the potential risks of combining driving with alcohol consumption and non-use of seatbelts.

Adolescent↗

A laryngoscope designed for intubation of the rat.

We successfully intubated 257 rats with a laryngoscope that we designed for this purpose. Orotracheal intubation with this laryngoscope can be performed quickly and without harm to the animal. This instrument provides direct visualization of the vocal cords, allowing rapid, safe intubation of the rat. Maintenance of an adequate airway with endotracheal intubation is superior to tracheostomy for repeated experiments, and therefore this laryngoscope makes such studies easier and safer to perform.

Animals↗

Magnetic motor evoked potential monitoring in the rat.

OBJECT: The authors conducted a study to provide an objective electrophysiological assessment of descending motor pathways in rats, which may become a means for predicting outcome in spinal cord injury research. METHODS: Transcranial magnetic motor evoked potentials (TMMEPs) were recorded under various conditions in awake, nonanesthetized, restrained rats. Normative data were collected to determine the reproducibility of the model and to evaluate the effect of changing the stimulus intensity on the evoked signals. In addition, an experiment was performed to determine if the TMMEPs produced were the result of auditory startle response (ASR) potentials elicited by the sound generated by the movement of the copper coil inside its casing during magnetic stimulation. Transcranial magnetic motor evoked potentials were elicited after magnetic stimulation. At 100% stimulus intensity, the mean forelimb onset latency was 4.2 +/- 0.39 msec, and the amplitude was 9.16 +/- 3.44 mV. The hindlimb onset latency was 6.5 +/- 0.47 msec, and the amplitude was 11.47 +/- 5.25 mV. As the stimulus intensity was decreased, the TMMEP onset latency increased and the response amplitude decreased. The ASR potentials were shown to have longer latencies, smaller amplitudes, and were more variable than those of the TMMEPs. CONCLUSIONS: These experiments demonstrate that TMMEPs can be recorded in awake, nonanesthetized rats. The evoked signals were easy to elicit and reproduce. This paper introduces noninvasive TMMEPs as a new technique for monitoring the physiological integrity of the rat spinal cord.

Animals↗

An evaluation of motor-evoked potentials for detection of neurologic injury with correction of an experimental scoliosis.

STUDY DESIGN: Controlled correction of scoliosis in a rat model was used to assess the accuracy of intraoperative motor-evoked potential monitoring. OBJECTIVES: The purpose of this study was to develop a model in which motor-evoked potential changes could be compared with neurologic function after surgery, such that a threshold for responding to motor-evoked potential changes may be established. SUMMARY OF BACKGROUND DATA: Intraoperative motor-evoked potential monitoring has become technically feasible. Clinical application now depends on the development of useful interpretation parameters and correlation with neurologic sequelae. METHODS: Experimental scoliosis was produced in 30 rat pups. After growth, the rats underwent correction of their scoliosis by distraction. Changes in tcMMEP onset latency and amplitude were measured. Distraction was applied either until a 10% delay in tcMMEP onset latency (Group 1), until tcMMEP responses were ablated (Group 2), or for 10 minutes after the loss of transcranial magnetic stimulation response (Group 3). RESULTS: In Group 1 (n = 10), all animals had tcMMEP with normal onset latency and normal neurologic examinations 24 hours after surgery. In Group 2 (n = 10), tcMMEP were normal in four rats, markedly delayed in three rats, and absent in three rats 24 hours after surgery. neurologic examination was normal in the four rats with normal tcMMEP. Moderate deficit was noted in two of the three rats with prolonged onset latency 24 hours after surgery; the third was intact. Moderate neurologic injury was noted in two of three rats with absent tcMMEP 24 hours after surgery; the third rat was paralyzed. In Group 3 (n = 10), vertebral dislocation was noted on lateral radiographs in eight of 10 animals. Twenty-four hours after surgery, tcMMEP remained absent, and paralysis was noted in the eight rats with dislocation. The two rats without dislocation had delayed tcMMEP but some return of neurologic function. CONCLUSIONS: Comparison of the three groups shows a significant correlation between tcMMEP and endpoint neurologic outcome. None of the rats in Group 1 had a neurologic deficit after surgery as opposed to five of 10 rats in Group 2 and 10 of 10 rats in Group 3 with significant neurologic injury. These findings suggest that a 10% delay in onset latency would be an appropriate threshold for responsing to changes in tcMMEP.

Analysis of Variance↗

A prospective analysis of intraoperative electromyographic monitoring of pedicle screw placement with computed tomographic scan confirmation.

STUDY DESIGN: In a prospective study of 90 patients undergoing lumbar pedicle screw instrumentation, 512 screws were tested intraoperatively using electrical stimulation. The accuracy of this technique was verified after surgery by computed tomography. OBJECTIVES: Computed tomographic scans taken after surgery were used to evaluate the efficacy of intraoperative screw stimulation and electromyographic monitoring of pedicle screw placement. SUMMARY OF BACKGROUND DATA: Previous cadaveric and clinical studies showed the risk of pedicle screw malposition and the inadequate reliability of intraoperative radiographs to identify misplaced screws. METHODS: Screws (total, 512) in 90 patients were stimulated intraoperatively, and stimulation threshold was recorded. Computed tomographic scans were taken after surgery to document pedicle screw position. Electromyographic thresholds and computed tomographic data were evaluated independently and compared to assess the accuracy of the electromyographic screw stimulation technique. RESULTS: Intraoperative screw stimulation was extremely accurate in confirming the adequacy of screw position. A stimulation threshold greater than 15 mA provided a 98% confidence that the screw was within the pedicle. In eight of 90 patients (9%), electromyographic monitoring detected a screw malposition that was not identified on lateral radiograph. CONCLUSIONS: Screw stimulation monitoring is a valuable and efficacious adjunct to lumbar pedicle screw instrumentation. A stimulation threshold greater than 15 mA reliably indicates adequate screw position. A stimulation threshold between 10 and 15 mA was generally associated with adequate screw position, although exploration of the pedicle is recommended. A stimulation threshold less than 10 mA was associated with a significant cortical perforation in most instances.

Bone Screws↗

Occult filum terminale syndrome.

Thirty-two pediatric patients presenting with symptoms of urinary dysfunction, stool incontinence and/or severe back and/or leg pain are described. In patients with urological dysfunction, urodynamic testing was consistent with a neurogenic etiology. Imaging studies demonstrated the tip of the conus medullaris to lie above the L2 vertebral body, and the filum terminale to be of normal diameter ( < 2 mm) in all patients. A diagnosis of an occult filum terminale syndrome was made based on clinical presentation in the absence of associated imaging abnormalities and section of the filum terminale was performed. Postoperatively, the majority of patients (97%) experienced significant ( > 50%) relief of their symptoms. The management of these patients is discussed.

Adolescent↗

The effects of propofol on rat transcranial magnetic motor evoked potentials.

INTRAOPERATIVE MONITORING OF motor evoked potentials (MEPs) may become a valuable test of spinal cord function during surgery. Unfortunately, MEP responses are affected by most common anesthetics. We studied the effect of intravenous propofol on transcranial magnetic MEPs (tcMMEPs) in the rat. Baseline tcMMEPs were recorded before administration of the drug. Each rat then received three induction doses of propofol, 10, 5, and 5 mg/kg (totaling 10, 15, and 20 mg/kg) and three successive 20-minute infusion doses at rates of 10, 20, and 40 mg/kg/h, respectively. An MEP intensity series was performed after each induction dose, during each infusion, and during a 20-minute recovery period. tcMMEPs recorded during the induction period demonstrated a significant, dose-dependent increase in onset latency and a marked decrease in amplitude. Infusion tcMMEPs displayed increased onset latencies but demonstrated a significant change in amplitudes only after the largest infusion dose. The MEPs approached baseline levels after discontinuation of the propofol. This study demonstrates that tcMMEPs can be successfully recorded from the rat during propofol anesthesia.

Anesthetics, Intravenous↗

Transcranial magnetic motor-evoked potentials in scoliosis surgery.

Spinal cord monitoring using SSEPs is an accepted adjunct in the surgical correction of spinal deformities, but does not directly assess motor function. Motor-evoked potentials have been introduced in an effort to meet this important need. In this series of 18 patients, the feasibility of intraoperative monitoring using transcranial magnetic motor-evoked potentials is documented. The potential value of this neurophysiologic monitoring technique, as well as the pitfalls in interpretation, are reviewed.

Adolescent↗

A fixed-dose study of adinazolam-SR tablets in generalized anxiety disorder.

1. This four-week, randomized, double-blind, multicenter study compared the efficacy and safety of adinazolam-SR, at three dosage levels, with placebo. Forty (40) patients were randomized at our site: 10 to adinazolam 30 mg/day, 10 to 60 mg/day, 10 to 90 mg/day, and 10 to placebo. All patients were moderately anxious with Hamilton Anxiety Scale (HAM-A) scores of > or = 21 at baseline. 2. The data were analyzed by pooling the three adinazolam groups and comparing them with the placebo group using t-tests. HAM-A scores decreased significantly more in the pooled adinazolam-SR treatment group than in the placebo group at both Week one (p < .02) and at Week two (p < .01), as well as at endpoint (p < .03). 3. At endpoint the adinazolam-treated group included 8 "responders" (> or = 50% reduction on the baseline HAM-A score) while none of the placebo patients were responders (p < .05). Dose-response effects were evaluated and relationships were not statistically significant. 4. The results indicate that adinazolam-SR was clearly superior to placebo for the treatment of patients suffering from Generalized Anxiety Disorder.

Adolescent↗

Are selective serotonin reuptake inhibitors well tolerated in somatizing depressives?

This retrospective evaluation included 89 patients who participated in two independent clinical investigations of the antidepressant medications paroxetine and fluoxetine. Baseline gastrointestinal (GI) somatic symptoms, as indicated by the baseline scores on the Hamilton Rating Scale for Depression (HAM-D) items 11, 12, and 16, the Symptom Checklist (SCL) items 19 and 40, and the Covi Anxiety Scale somatic anxiety item were analyzed for their discriminative ability in predicting which patients would subsequently develop adverse GI side effects on medication. Subjects with baseline complaints of nausea or upset stomach (SCL #40), GI somatic symptoms (HAM-D #11 and #12, Covi somatic anxiety), or weight loss (HAM-D #16) were not statistically more likely to develop GI side effects on paroxetine or fluoxetine. Only a baseline complaint of appetite loss (SCL #19) was associated with subsequent GI side effects on paroxetine to a statistically significant degree (p < .05).

Adult↗

Anesthetic effects on motor evoked potentials in dogs.

The effects of the various anesthetic agents on the production of transcranial magnetic motor evoked potentials (tcMMEP) were studied in a canine model. Pre-anesthetic baseline tcMMEPs demonstrated consistency in onset latency measurements and variability in measurement of peak-to-peak amplitudes. Changes in tcMMEPs were evaluated following the individual administrations of sodium pentothal, etomidate, halothane, fentanyl, and ketamine. For induction of anesthesia, etomidate was compatible with tcMMEP production, whereas sodium pentothal resulted in loss of hindlimb potentials for a period of 45 minutes. For maintenance of anesthesia, halothane was incompatible with the measurement of tcMMEPs. Fentanyl administration was consistent with the recording of reliable tcMMEPs, with consistent onset latencies but widely variable peak-to-peak amplitudes. Ketamine was compatible with stable and reproducible tcMMEP production. The results of this study suggest that anesthetic agents have a predictable and consistent effect on tcMMEP responses.

Anesthetics↗

Correlation of motor-evoked potentials, somatosensory-evoked potentials, and the wake-up test in a case of kyphoscoliosis.

The ability to monitor the descending motor pathways of the spinal cord during surgery is an important goal in neurophysiologic monitoring of spinal deformities. This report describes a case of a severe spinal deformity for which instrumentation and reduction carried a significant risk of neurologic complications. During the procedure, changes in neurologic status were monitored simultaneously using both SSEPs and tcMMEPs. The reliability of these two complimentary modalities was then verified by concurrent wake-up tests. This case provides documentation of the reliability of tcMMEP responses when an accurate assessment of motor function was necessary.

Adult↗

Swallowing and upper esophageal sphincter contraction with transcranial magnetic-induced electrical stimulation.

This study in three dogs explores the effect of magnetically induced electrical stimulation of the brain to induce swallowing and produce contraction of the upper esophageal sphincter (UES). Single stimuli were delivered at intervals from 15 s to 3 min. Studies were performed with and without perfusion of fluid into the pharynx and upper esophagus. Results showed that magnetic stimulation produced a twitch contraction of the UES when stimulus intensity was above a threshold that varied between 14 and 20% of the stimulator output. Increasing stimulus intensity progressively increased twitch amplitude. Magnetic stimulation also induced swallowing, above a stimulus threshold similar to that for induction of the UES twitch contraction. Fluid perfusion augmented the ability of the magnetic stimulus to induce swallowing. We concluded that a magnetically induced single electrical stimulus of the cerebral cortex produces UES contraction and induces swallowing. The effect on swallowing is facilitated by sensory stimulation of the pharynx. This technique holds the potential for further study of 1) motor and sensory neural mechanisms involved in the control of swallowing and 2) the assessment and management of oropharyngeal dysphagia in humans.

Animals↗

High-resolution magnetic resonance imaging of experimental spinal cord injury in the rat.

The ability of magnetic resonance imaging (MRI) to display the anatomic changes after spinal cord injury in the rat were examined in postmortem specimens. With the clip compression technique, acute spinal cord injuries of three grades of severity were produced in adult male rats. One hour after injury, during which time physiological parameters were measured and maintained within the normal range, the rats were killed by transcardiac perfusion of formalin. The vertebral column containing the cervical and upper thoracic segments was excised and, after further formalin fixation, 20 contiguous MRI scans centered on the injury site were obtained using a spin-echo imaging sequence. The volume of signal acquisition for each image was 15 x 15 x 1.0 mm thick. The spinal cords were then removed from the vertebral column, sectioned, and stained for histological examination. Ten-micrometer serial sections of each cord were examined microscopically. MRI scans and microscopic sections at comparable levels were examined to determine the quality of anatomical detail and spatial resolution of the MRI scans. MRI scans with resolution of about 75 microns per pixel edge were obtained. At the site of injury, there was disruption of the normally well demarcated gray-white interface and variable areas of low signal intensity. Because of the resolution achieved, it was possible to determine that these low signal intensity areas were post-traumatic hemorrhages. Indeed, hemorrhages with dimensions of the order of 100 microns were detected on the MRI scans. Furthermore, by examining the serial sections of the cord, the extent of the injury along the cord could be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evoked potentials from direct cerebellar stimulation for monitoring of the rodent spinal cord.

Although the assessment of spinal cord function by electrophysiological techniques has become important in both clinical and research environments, current monitoring methods do not completely evaluate all tracts in the spinal cord. Somatosensory and motor evoked potentials primarily reflect dorsal column and pyramidal tract integrity, respectively, but do not directly assess the status of the ventral funiculus. The present study was undertaken to evaluate the use of evoked potentials, elicited by direct cerebellar stimulation, in monitoring the ventral component of the rodent spinal cord. Twenty-nine rats underwent epidural anodal stimulation directly over the cerebellar cortex, with recording of evoked responses from the lower thoracic spinal cord, both sciatic nerves, and/or both gastrocnemius muscles. Stimulation parameters were varied to establish normative characteristics. The pathways conducting these "posterior fossa evoked potentials" were determined after creation of various lesions of the cervical spinal cord. The evoked potential recorded from the thoracic spinal cord consisted of five positive (P1 to P5) and five negative (N1 to N5) peaks. The average conduction velocity (+/- standard deviation) of the earliest wave (P1) was 53 +/- 4 m/sec, with a latency of 1.24 +/- 0.10 msec. The other components followed within 4 msec from stimulus onset. Unilateral cerebellar stimulation resulted in bilateral sciatic nerve and gastrocnemius muscle responses; there were no significant differences (p greater than 0.05) in the thresholds, amplitudes, or latencies of these responses elicited by right- versus left-sided stimulation. Recordings performed following creation of selective lesions of the cervical cord indicated that the thoracic response was carried primarily in the ventral funiculus while the sciatic and gastrocnemius responses were mediated through the dorsal half of the spinal cord. It is concluded that the posterior fossa evoked potential has research value as a method of monitoring pathways within the ventral spinal cord of the rat, and should be useful in the study of spinal cord injury.

Animals↗

Predictors of placebo response: a retrospective analysis.

This retrospective evaluation involved 197 patients from independent clinical investigations of four antidepressant medications. Six variables were analyzed for their discriminative utility in predicting placebo response rates: gender; marital status; age; education; duration of illness; and severity of depressive symptomatology, as measured by Hamilton Rating Scale for Depression (HAM-D or HDRS) scores. Men were slightly more responsive to placebo than were women (29.8%, n = 94 vs. 24.3%, n = 103). Married patients demonstrated the highest probability of a positive placebo response (38.15%, n = 76), as compared with widowed/separated/divorced (21.9%, n = 73) or single (16.7%, n = 48) patients. A trend toward an increased probability of placebo response was detected for patients aged 60 and above (35.7%, n = 14). Educational level achieved and duration of illness were not predictive. Severity of illness proved most noteworthy, with the placebo response rate higher in the more mild patients (40.8%, n = 27 vs. 23.4%, n = 77).

Adolescent↗

The effect of nimodipine and dextran on axonal function and blood flow following experimental spinal cord injury.

There is evidence that posttraumatic ischemia is important in the pathogenesis of acute spinal cord injury (SCI). In the present study spinal cord blood flow (SCBF), measured by the hydrogen clearance technique, and motor and somatosensory evoked potentials (MEP and SSEP) were recorded to evaluate whether the administration of nimodipine and dextran 40, alone or in combination, could increase posttraumatic SCBF and improve axonal function in the cord after acute SCI. Thirty rats received a 53-gm clip compression injury on the cord at T-1 and were then randomly and blindly allocated to one of six treatment groups (five rats in each). Each group was given an intravenous infusion of one of the following over 1 hour, commencing 1 hour after SCI: placebo and saline; placebo and dextran 40; nimodipine 0.02 mg/kg and saline; nimodipine 0.02 mg/kg and dextran 40; nimodipine 0.05 mg/kg and saline; and nimodipine 0.05 mg/kg and dextran 40. The preinjury physiological parameters, including the SCBF at T-1 (mean +/- standard error of the mean: 56.84 +/- 4.51 ml/100 gm/min), were not significantly different (p greater than 0.05) among the treatment groups. Following SCI, there was a significant decrease in the SCBF at T-1 (24.55 +/- 2.99 ml/100 gm/min; p less than 0.0001) as well as significant changes in the MEP recorded from the spinal cord (MEP-C) (p less than 0.0001), the MEP recorded from the sciatic nerve (MEP-N) (p less than 0.0001), and the SSEP (p less than 0.002). Only the combination of nimodipine 0.02 mg/kg and dextran 40 increased the SCBF at T-1 (43.69 +/- 6.09 ml/100 gm/min; p less than 0.003) and improved the MEP-C (p less than 0.0001), MEP-N (p less than 0.04), and SSEP (p less than 0.002) following SCI. With this combination, the changes in SCBF were significantly related to improvement in axonal function in the motor tracts (p less than 0.0001) and somatosensory tracts (p less than 0.0001) of the cord. This study provides quantitative evidence that an increase in posttraumatic SCBF can significantly improve the function of injured spinal cord axons, and strongly implicates posttraumatic ischemia in the pathogenesis of acute SCI.

Animals↗