Search PubMed⌕ Search

Biomedical subjects

L T Happel

Publications and source records attributed to L T Happel.

17 recordsLinked to original sources
PubMed2002

Accumulation of PN1 and PN3 sodium channels in painful human neuroma-evidence from immunocytochemistry.

BACKGROUND: The axolemmal distribution and density of voltage-gated sodium channels largely determines the electrical excitability of sprouting neurites. Recent evidence suggests that accumulation of sodium channels at injured axonal tips may be responsible for ectopic axonal hyperexcitability and the resulting abnormal sensory phenomena of pain and paresthesias. For future improvement in pain management it is necessary to identify structurally significant generators of autorhythmicity. A first step in this regard will be to determine the predominant types of sodium channels in injured axons. The opportunity to test human specimens from painful and non-painful neuroma is of great value. METHODS: We employed immunocytochemical methods to investigate if two types of highly specific voltage-gated sodium channel subtypes could be detected in sections of human neuroma. FINDINGS: Both subtypes of sodium channels PN1 and PN3 accumulated abnormally in human neuromas. The immunoreactive pattern was more pronounced in painful neuromas. This is in contrast to previous reports that focused either on PN1 or PN3 as main generators of hyperexcitability induced pain. INTERPRETATION: Both, PN1 and PN3 seem to be involved in hyperexcitability induced pain. It can be expected that a variety of other highly specific voltage gated sodium channel subtypes will be detected in regenerating peripheral nerve in the near future, which contribute to the development of neuropathic pain states. Thus, in order to therapeutically control hyperexcitability induced neuropathic pain, it might be worthwhile to develop pharmaceuticals that can selectively block different sodium channel subtypes and subunits.A review of the role of sodium channels in neuropathic pain is implemented in the discussion.

Humans↗
PubMed2000

Neuronal platelet-activating factor receptor signal transduction involves a pertussis toxin-sensitive G-protein.

In most nonneural systems, platelet-activating factor (PAF) receptor effects are mediated by G-proteins that are often pertussis toxin-sensitive. The activation of pertussis toxin-sensitive G-proteins linked to PAF receptors results in the mobilization of intracellular calcium, at least in part, through the second messenger inositol triphosphate. We have sought to determine if a pertussis toxin-sensitive G-protein is involved in the PAF receptor-mediated phenomena of growth cone collapse and of synaptic enhancement in primary neuronal culture. Using infrared differential interference contrast microscopy and patch-clamp recording techniques, pertussis toxin, but not the inactive B oligomer of the toxin, was found to block both the growth cone collapse and the enhanced synaptic release of excitatory transmitter induced by a nonhydrolyzable PAF receptor agonist, making it likely that Go, Gq, or Gi is the G-protein transducer of PAF receptors in primary neurons. We believe that PAF acts directly on neuronal receptors, which are linked to pertussis toxin-sensitive G-proteins, on the tips of developing neurites, and on presynaptic nerve terminals, leading to growth cone collapse and enhanced synaptic release of transmitter.

Animals↗
PubMed1998

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.

Axons↗
PubMed1996

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.

Action Potentials↗
PubMed1996

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.

Amino Acid Sequence↗
PubMed1993

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.

Action Potentials↗
PubMed1992

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.

Animals↗
PubMed1990

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.

Athletic Injuries↗
PubMed1989

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.

Animals↗
PubMed1987

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.

Axons↗
PubMed1986

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.

Adolescent↗
PubMed1980

Visual evoked potentials in two forms of hereditary spastic paraplegia.

Visual evoked potentials (VEPs) were used to study two forms of hereditary spastic paraplegia. We recorded the VEP in 6 homozygotes and 5 obligate heterozygotes in one family with recessively transmitted disease and in 5 persons with dominantly transmitted hereditary spastic paraplegia. The VEPs in the affected persons from both families were similar; both had delayed conduction times and changes in the wave form. The VEPs of the obligate heterozygotes were indistinguishable from those of the unaffected control subjects. Comparison of our findings with those of other disease processes that affect the VEPs suggest that the conduction delays in our patients' VEPs may be associated with changes in myelin.

Adult↗
PubMed1977

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.

Acoustic Stimulation↗
PubMed1975

Spinal cord potentials evoked by peripheral nerve stimulation.

Lumbar, thoracic, and cervical spinal cord responses evoked by sciatic nerve stimulation were measured in 20 cats at the skin level and directly from the dorsal surface of the cord. Computer averaging techniques were used for both skin level recordings and cord surface recordings at all levels. Recordings made directly from the cord surface at lumbar levels were large and were characterized by a large, initial, negative transient, followed by a more complicated and variable waveform. As recording electrodes were moved rostrally, the initial large spike decreased in amplitude and the duration and latency of the response increased. At cervical levels were large and were characterized by a large, initial, negative transient, followed by a more complicated and variable waveform. As recording electrodes were moved rostrally, the initial large spike decreased in amplitude and the duration and latency of the response increased. At cervical levels the responses were polyphasic, of long duration and small amplitude. Deafferentation by posterior rhizotomy of all lumbar and sacral roots ipsilateral to sciatic nerve stimulation abolished the response at all levels. Thoracic cord section also abolished the response over the cervical cord. Skin level recordings were of shorter latency than direct recordings, especially at cervical levels. Response configurations were similar for both recording techniques at lumbar levels, but had different waveforms at both thoracic and cervical levels. Clinical implications of the techniques and possible explanations of the waveforms recorded are discussed.

Animals↗
PubMedDate not supplied

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.

Animals↗