Coordinated Motion of Epithelial Layers on Curved Surfaces.

Coordinated cellular movements are key processes in tissue morphogenesis. Using a cell-based modeling approach we study the dynamics of epithelial layers lining surfaces with constant and varying curvature. We demonstrate that extrinsic curvature effects can explain the alignment of cell elongation with the principal directions of curvature. Together with specific self-propulsion mechanisms and cell-cell interactions this effect gets enhanced and can explain observed large-scale, persistent, and circumferential rotation on cylindrical surfaces. On toroidal surfaces the resulting curvature coupling is an interplay of intrinsic and extrinsic curvature effects. These findings unveil the role of curvature and postulate its importance for tissue morphogenesis.

Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor.

The biologically active lipid platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine; PAF) is a mediator of inflammatory and immune responses, and it accumulates in the brain during convulsions or ischemia. We have examined whether PAF may play a second messenger role in the central nervous system by studying effects on synaptic transmission in cultured hippocampal neurons. Carbamyl-PAF, a nonhydrolyzable PAF analog with a similar pharmacologic profile, augmented glutamate-mediated, evoked excitatory synaptic transmission and increased the frequency of spontaneous miniature excitatory synaptic events without increasing their amplitude or altering their time course. This compound had no significant effect on gamma-aminobutyric acid-mediated inhibitory synaptic responses. Lyso-PAF, the biologically inactive metabolic intermediate, had no effect on synaptic transmission. Moreover, the enhancement of excitatory synaptic transmission by carbamyl-PAF was blocked by a PAF receptor antagonist. These results indicate a specific presynaptic effect of PAF in enhancing excitatory synaptic transmission in cultured rat hippocampal neurons.

Surgery for lesions of the brachial plexus.

Current diagnostic workup and surgical management of stretch injuries, gunshot wounds, lacerations, iatrogenic injuries, tumors, and thoracic outlet syndromes involving the brachial plexus are reviewed. Use of appropriate radiologic and electrodiagnostic studies to work up such patients is summarized as is selected literature concerning the more controversial aspects of their management. Some of the arguments both for and against operation on stretch injuries are presented and it is concluded that surgery can be of value for well-selected patients. Although a number of patients with gunshot wounds involving the plexus recover spontaneously, many still require an operation. Experience with tumors arising from the plexus suggests the need for early and relatively aggressive removal. Use of magnification and intraoperative recording permits removal of some but not all neurofibromas without further deficit. Timing for repair of lacerating injuries to the plexus, as well as iatrogenic injuries, selection of the few patients with thoracic outlet syndrome who require operation, and a brief review of plexus neuropathy are also presented. Importance of evaluating individual plexus injuries in terms of how complete or incomplete loss is in the distribution of each individual element is stressed. Development of intraoperative stimulation and recording methods to help sort out lesions, use of magnification for repair, and improved grafting techniques where gaps result from resection have helped to restimulate interest in managing these patients.

Sodium channel accumulation in humans with painful neuromas.

Painful neuromas from 16 patients were examined using site-specific antisodium channel antibodies employed in immunocytochemical and radioimmunoassay methods. Normal sural nerves from six of these patients served as controls. Immunocytochemistry showed abnormal segmental accumulation of sodium channels within many axons in the neuromas. Dens immunolocalization was especially apparent within the axonal tips. Radioimmunoassay confirmed a significantly greater density of sodium channels in the neuromas as compared with the sural nerves. Thus, sodium channel accumulate abnormally within the axons of neuromas in humans. This alteration of the sodium channels may underlie the generation of axonal hyperexcitability and the resulting abnormal sensory phenomena (pain and paresthesias), which frequently occur after peripheral nerve injury.

Abnormal distributions of potassium channels in human neuromas.

Twenty-seven human traumatic neuromas were examined immunocytochemically using highly specific antibodies directed against the voltage-gated delayed-rectifier potassium channel, Kv1.1. Normal sural nerves from six of the above-noted patients served as control specimens. Additionally, nine of the neuromas and two of the sural nerves were immunostained for voltage-gated calcium channels using an antibody that reacts with a wide spectrum of calcium channels. Normal myelinated fibers showed Kv1.1 specific immunoreactivity only at the juxtaparanodal regions. In contrast, within the neuromas approximately 30% of the myelinated fibers exhibited Kv1.1 specific immunoreactivity in dense patches along internodal axonal regions. The clustering of Kv1.1 channels along myelin-ensheathed internodal segments of axon was highly specific for the neuromas, and was never seen in normal nerve. Specific calcium channel immunoreactivity was not detectable in either the neuromas or sural nerves. Taken together with prior studies on sodium channels, these results suggest that selective and specific mechanisms control the distribution of ion channels within neuromas. Further investigation of ion channel changes within neuromas should provide a better understanding of the abnormal axonal hyperexcitability that frequently develops after nerve injury.

Nerve action potential recording method and equipment.

OBJECTIVE: Nerve action potential (NAP) recording is a proven and useful tool in the surgical management of nerve injury. Understanding its materials and methods as well as its pitfalls and limitations is necessary for successful and routine use of this tool. METHODS: The basic electrophysiology of nerve and its implications in the setting of nerve trauma and regeneration are reviewed. Electrode design and electrode placement are discussed. The use of simple electromyographic/nerve conduction machines for intraoperative recording of NAPs is developed, along with some of the technical problems that result from electrophysiological recording in an electrically hostile environment. RESULTS: NAP recording is a good indicator of useful recovery in nerve trauma. The presence and demonstration of an NAP is associated with a 90% chance of recovery to a useful motor state. CONCLUSION: NAP recording provides useful information regarding the regenerative potential of a damaged nerve long before that potential is clinically evident. This information is critical in the optimal management of nerve injuries. The techniques of NAP recording are straightforward, but attention to detail is important, and full understanding of the method is required.

Experimental missile wound to the brain.

Among civilians in the United States, 33,000 gunshot wound deaths occur each year; probably half of these involve the head. In combat, head wounds account for approximately half of the immediate mortality when death can be attributed to a single wound. No significant reduction in the neurosurgical mortality associated with these wounds has occurred between World War II and the Vietnam conflict, and very little research into missile wounds of the brain has been undertaken. An experimental model has been developed in the anesthetized cat whereby a ballistic injury to the brain may be painlessly reproduced in order that the pathophysiological effects of brain wounding may be studied and better treatments may be designed to lower the mortality and morbidity rates associated with gunshot wounds. Prominent among physiological effects observed in this model was respiratory arrest even though the missile did not injure the brain stem directly. The incidence of prolonged respiratory arrest increased with increasing missile energy, but arrest was often reversible provided respiratory support was given. It is possible that humans who receive a brain wound die from missile-induced apnea instead of brain damage per se. The mortality rate in humans with brain wounding might be reduced by prompt respiratory support. Brain wounding was associated with persistently increased intracranial pressure and reduced cerebral perfusion pressure not entirely attributable to intracranial bleeding. The magnitude of these derangements appeared to be missile energy-dependent and approached dangerous levels in higher-energy wounds. All wounded cats exhibited postwounding increases in blood glucose concentrations consistent with a generalized stress reaction. A transient rise in hematocrit also occurred immediately after wounding. Both of these phenomena could prove deleterious to optimal brain function after injury.

Intraforaminal repair of plexus spinal nerves by a posterior approach: an experimental study.

Many spinal nerve roots injured due to stretch or other types of lesions are not reparable. Some spinal nerves might be repaired if they could be exposed in their intraforaminal course. A posterior subscapular approach for a more lateral exposure of the brachial plexus was combined with a facetectomy to expose intraforaminal nerves in a series of Macaca rhesus monkeys. This approach exposed a 6- to 10-mm segment of spinal nerve not approachable by a more classic anterior operation. Sural grafts were placed from the dural exit of the spinal nerves to the cord level of the plexus. Nine surviving animals were followed for 36 to 54 months and observed for clinical evidence of return of function. In each animal at least one electromyogram (EMG) was performed. The plexus was then re-exposed and intraoperative nerve action potentials were recorded across graft sites. Evoked muscle action potential and cortical potentials were recorded in six animals. Despite the proximal level of repair, adequate regeneration was shown by clinical, electrical, and histological studies. Functional return was best to the supraspinatus and biceps muscles and to wrist and finger flexors. Clinical recovery was present, but less effective, for deltoid, wrist, and finger extensors and intrinsic muscles of the hand, despite evidence on EMG of reinnervation. Recovery of the infraspinatus muscle was poor. Nerve action potentials could be recorded across each graft site. Reinnervational activity was recorded by EMG and evoked muscle action potential studies in most of the muscles studied, despite the persistence of some denervational changes 3 years or more after injury and repair. Histological studies confirmed the presence of a large number of axons of moderate size and myelination even at the forearm level.

Neural anatomy of the human anterior cruciate ligament.

The histology of the anterior cruciate ligament was studied by a modified technique of the Gairns gold chloride stain for neural elements. Three morphological types of mechanoreceptors and free nerve-endings were identified: two of the slow-adapting Ruffini type and the third, a rapidly adapting Pacinian corpuscle. Rapidly adapting receptors signal motion and slow-adapting receptors subserve speed and acceleration. Free nerve-endings, which are responsible for pain, were also identified within the ligament. These neural elements comprise 1 per cent of the area of the anterior cruciate ligament.

Delayed paraplegia complicating sublaminar segmental spinal instrumentation.

The cases of two patients with delayed paraplegia after segmental spinal instrumentation with sublaminar wiring are reported. Both patients had complex spinal deformities and had transient neural deficits after the first-stage procedure of anterior release and spine fusion. They had uneventful spinal-cord monitoring during the second-stage procedure of posterior instrumentation and fusion, and function of the lower extremities was present immediately after that operation. Paraplegia then ensued, and was recognized thirty hours later in one patient and six days later in the other. Considering our reproducible and reliable experience (no false-negative results) with spinal cord monitoring in 307 operations, we propose that the delayed onset of paraplegia resulted from a progression of ischemic and edema-producing events that had not developed sufficiently intraoperatively to be reflected by the monitoring. The paraplegia became evident only when the subarachnoid space was obstructed because of progressive postoperative neural edema. The presence of sublaminar implants in narrow, kyphotic segments of the spinal canal probably exacerbated the neural irritation by dural impingement, which was seen myelographically.

Penfield Lecture. A quarter century's experience with intraoperative nerve action potential recording.

The rationale, basic considerations, and technique of intraoperative nerve action potential (NAP) recording have been reviewed. Experience using this technique in several thousand patients over a 25 year period has been summarized. The most frequent serious nerve injury is one that leaves it in continuity. Resection of such a lesion that is regenerating does the patient a great disservice as does exploration without repair of one with little or no potential for useful spontaneous recovery. The frequency of lesions in continuity as well as the difficulties in evaluating them in the early months by electromyography let alone by surgical inspection has led to the development of intraoperative NAP recording. Where neurolysis was based on a recordable NAP across a lesion in continuity, 93% recovered good function. Where resection of the lesion was based on absence of an NAP, the injury was, without exception, neurotmetic and/or one with poor potential for useful recovery without repair. Some lesions had an NAP across their lesion but a portion of the cross-sectional area appeared more seriously injured. By use of NAP recordings, a split repair was done and usually with good results.

Temperature effects on feline cortical and spinal evoked potentials.

To evaluate the effects of hypothermia on the somatosensory evoked potentials, baseline cortical and spinal evoked responses were obtained following induction of anesthesia at normal body temperature in five cats. The body temperature was lowered between 5 degrees and 6 degrees C and repeat cortical and spinal evoked responses were obtained. The cats were warmed to their original normal temperatures and the cortical and spinal evoked responses were repeated. After cooling the spinal evoked responses showed an average 40% increase in the latency (range 29-51%). Three of the animals showed a change in the normal waveform with the development of two distinct peaks instead of a single waveform. This was thought to be due to the varied vulnerability of the different cortical tracts to the lower temperature. Upon rewarming, the average latency returned to within 2.7% of the initial value, and the double waveform reunited to form a single wave. With cooling, the cortical evoked responses showed a similar consistent increase in latency. However, there was a much larger variability in the appearance of the waveforms. There was a range from an almost nonexistent wave in two cats to various waveform changes in the other cats. After rewarming there was a much slower return to normal latency in waveform than was found with the spinal evoked potentials. These experimental findings revealed an apparent deleterious, although reversible, effect on the somatosensory evoked potentials. Until the physiologic effects of cooling on the spinal cord are better understood, it is recommended that the temperature of patients undergoing spinal instrumentation be kept as close to normal as possible.

Evidence of reinnervation of free patellar tendon autograft used for anterior cruciate ligament reconstruction.

We studied six adult male dogs to determine whether free patellar tendon grafts show evidence of reinnervation when used for anterior cruciate ligament reconstruction. Histologic return of neural elements and return of a somatosensory-evoked potential defined evidence of reinnervation. Before removal, the native anterior cruciate ligament was electrically stimulated with a bipolar electrode and a somatosensory-evoked potential was recorded from a scalp electrode. The ligament was excised and reconstructed using an autogenous patellar tendon graft. Somatosensory-evoked potential was attempted immediately after reconstruction. Histology for nerve endings was performed on the native ligaments. Each animal underwent repeat arthrotomy 6 months later. The grafts were isolated and somatosensory-evoked potentials were attempted. An evoked potential was seen in all six dogs before reconstruction. No graft demonstrated a somatosensory-evoked potential acutely; however, 6 months postoperatively, the somatosensory-evoked potential returned in two cases. Histology of native ligaments showed that 25% of the 100 sections evaluated contained neural elements. Of the receptors present, 89% were mechanoreceptors and 11% were free nerve endings. Histologic examination of the graft tissue 6 months postoperatively revealed that all six grafts also contained neural elements. Mechanoreceptors and free nerve endings were present in approximately equal numbers in the grafts. The results of histology and somatosensory-evoked potential demonstrate that in at least some cases, free patellar tendon grafts show evidence of reinnervation when used for anterior cruciate ligament reconstruction.

Hypsarhythmia-infantile spasms in near-drowning: clinical, EEG, CT scan and evoked potential studies.

A 13-month-old child developed hypsarhythmia-infantile spasms after nearly drowning. Serial EEG, multimodality evoked potential, and CT scan of the brain revealed hypsarhythmia, disruption of ascending and descending tracts rostral to the mesencephalon, and a fairly severe degree of dilation of the ventricular system and subarachnoid space. We speculate that deafferentiation of the cerebral cortex is critical in the genesis of the hypsarhythmic pattern.

[Comparison of the value of angioscopy, angiography and ultrasonography in detection of pathologic vascular processes]. / Gegenüberstellung der Wertigkeit von Angioskopie, Angiographie und Sonographie zur Erfassung pathologischer Gefässwandprozesse.

AIMS: The ability of angioscopy, angiography and sonography to evaluate arteriosclerotic vascular lesions were compared to determine if angioscopy is a valuable addition in the diagnostic armamentarium. METHODS: An in-vitro study was selected to enable microscopic assessment of the arteries. Angiography was followed by sonography and endoscopy and finally the vessels were evaluated macro- and microscopically. RESULTS: The configuration of the vascular stenosis (plaque-shape, semicircular-eccentric, circular-concentric) was more reliably defined with angioscopy as compared to angiography and sonography. Intense calcification of plaque was detected sonographically with a high sensitivity (90%) using the acoustic shadowing and high amplitude criteria. Angioscopy was superior in differentiating between simple and complicated plaques and the assessment of ulcerations, while the visualization of the entire vascular tree with potential collaterals remained the domain of angiography. CONCLUSIONS: Angioscopy seems to be valuable addition in the evaluation of arterial vascular disease. It can be used in the quality control after interventional radiology and surgery.

Joint innervation in joint injury.

When considering joint innervation, it is important to appreciate that the joint receptors and the muscle tendon units about the joint interact in a complimentary manner forming a single afferent system. This system remains complex, and its overall function is still relatively unclear. Although the role of joint afferents can not be explicitly described, it is important to appreciate that alterations in joint innervation caused by athletic trauma can occur and can markedly affect joint function.

Cortical evoked potentials in spinal surgery.

Few complications of surgery are as devastating as paraplegia in a patient who has been operated on for correction of a spinal abnormality. Early warning of potential damage to the spinal cord is highly desirable. This is possible with cortical evoked potentials. It measures electroencephalographic activity after peripheral nerve stimulation, and may be used during surgery without interrupting the procedure.In this report, 42 patients were studied by means of cortical evoked potentials. Findings in 35 patients were unremarkable. Six showed changes that made the test valuable; four of these six patients had changes that were ominous. In three of the four, the changes were appreciated and corrections were made to avoid paralysis. In one, changes were not appreciated and the patient became paralyzed. In one case, improvement in conduction was evident when the deformity of the spine was corrected. In another case, the latency was momentarily prolonged when a feeder artery to the cord was ligated.Although this technique requires special training and equipment, its value justifies the trouble and expense. Certainly its common use in spinal surgery is inevitable.

Cerebral cortical isolation in infantile neuroaxonal dystrophy.

Three patients with infantile neuroaxonal dystrophy (INAD, Seitelberger's disease) studied between ages 2 and 5 years, with the characteristic electroencephalographic pattern of high-voltage, fast (16-24 c/sec) rhythms and absence of reactivity on eye-opening or closure (Radermecker and Dumon-Radermecker 1972), also showed no changes in response to intermittent photic stimulation and absence of evoked potentials to flashes, clicks or median nerve stimuli. Although some theta rhythms and delta activity appeared during drowsiness and sleep, the fast rhythms persisted as the dominant feature. There were no central transients or K-complexes. When the patients cried, with hyperventilation, and also during breath-holding spells, slow rhythms appeared and the fast rhythm was reduced. These findings are interpreted as evidence of cerebral cortex isolation, the fast rhythm representing the spontaneous ("idling") activity of the cortex largely disconnected from subcortical or remote cortical influences by the slowly progressive, selective degeneration of axons, characteristic of the pathology of INAD, but the cortex remains responsive to chemical influences. These electrophysiological features become established furing the third year of age, prior EEGs being normal and later ones showing paroxysmal and other abnormal features in addition to the fast rhythm.