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1.
AJNR Am J Neuroradiol ; 28(2): 387-9, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17297019

ABSTRACT

Appropriately sized 0.010- and 0.018-inch complex framing coils were placed in a wide-necked silicone aneurysm replica, and their stability was evaluated at variable physiologic flow rates using video recording. After detachment, the 0.010-inch coils demonstrated instability/prolapse that was proportional to flow rate. In contrast, 0.018-inch coils held their 3D configuration regardless of flow rate. The findings support the use of 0.018-inch coils (when possible) in aneurysms with unfavorable geometry, particularly in circulations with higher flow rates.


Subject(s)
Aneurysm/therapy , Embolization, Therapeutic/instrumentation , Embolization, Therapeutic/adverse effects , Humans , In Vitro Techniques , Materials Testing , Models, Anatomic , Prosthesis Failure , Silicones
2.
AJNR Am J Neuroradiol ; 22(1): 19-26, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11158882

ABSTRACT

BACKGROUND AND PURPOSE: The management of broad-necked cerebral aneurysms by Guglielmi detachable coils (GDCs) is technically challenging owing to a variety of factors, including difficulty in defining the aneurysm/parent vessel interface angiographically and problems in achieving complete occlusion, later predisposing the aneurysm to regrowth/recanalization. We sought to determine whether the use of intraluminal balloons to remodel the parent vessel/aneurysm interface during GDC embolization would provide a safe means of improving the efficacy of endovascular treatment of broad-necked aneurysms. METHODS: Twenty-two saccular aneurysms of the internal carotid artery were treated with GDCs by using balloon remodeling techniques. All aneurysms were characterized by wide necks or were small with unfavorable neck/fundus ratios and required balloon assistance for coil embolization. Patients were followed up both clinically and angiographically. RESULTS: By using a microcatheter-mounted nondetachable balloon to provide a temporary barrier across the aneurysmal neck, we were able to deploy GDCs safely within a variety of aneurysms. Among the 22 patients treated, aneurysmal occlusion on follow-up angiography (mean, 19 months) was found in 17 of 20 patients (two patients died and no follow-up studies were available). Observed or suspected thromboembolic events occurred in four of 22 patients, resulting in one permanent deficit. Twenty of the 22 patients had good to excellent clinical outcomes. CONCLUSION: Although balloon-assisted coiling of cerebral aneurysms requires manipulation of a second microcatheter and an inflatable balloon, increasing its technical complexity, we believe that this method has utility in treating broad-necked aneurysms and small aneurysms that are otherwise suboptimally managed by conventional GDC deployment.


Subject(s)
Carotid Artery Diseases/therapy , Catheterization , Cerebral Angiography , Embolization, Therapeutic/methods , Intracranial Aneurysm/therapy , Adult , Aged , Carotid Artery Diseases/diagnostic imaging , Carotid Artery, Internal/diagnostic imaging , Cohort Studies , Embolization, Therapeutic/adverse effects , Female , Follow-Up Studies , Humans , Intracranial Aneurysm/diagnostic imaging , Male , Middle Aged , Prospective Studies
3.
J Neurosurg ; 88(3): 506-12, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9488305

ABSTRACT

OBJECT: The authors studied the relationships between tumor size, location, and topographic position relative to the intact facial nerve bundles in acoustic neurinomas to determine the influence of these factors on hearing preservation postoperatively. Consistent topographic relationships were found. METHODS: Four hundred fifty-two patients with acoustic neurinoma treated via a retrosigmoid approach were analyzed with respect to hearing preservation and facial nerve function. One hundred fifteen tumors were identified as small and were categorized as Grades I and II. Patients with Grade I tumors, that is, purely intracanalicular lesions, all had good hearing preoperatively, defined by a less than 50-dB pure tone average and 50% speech discrimination score. All 14 Grade I tumors were removed, resulting in preservation of the patient's hearing by these criteria. There were no particular topographic anatomical relationships associated with these tumors that affected hearing preservation. Grade II tumors, defined as those protruding into the cerebellopontine angle without contacting the brainstem, were found in 101 patients and were divided by size into two grades: IIA (< 1 cm) and IIB (1-1.8 cm). In 90 patients with Grade IIA tumors, 72 (89%) of 81 who had preserved hearing preoperatively maintained it postoperatively, and in the 11 patients with Grade IIB tumors, six of whom had good hearing preoperatively, four (67%) had preserved hearing postoperatively. Six morphological types were identified based on their neurotopographic relationships to the elements of the vestibulocochlear nerve. CONCLUSIONS: Hearing preservation postsurgery by tumor type was as follows: 1A, 92%; 1B, 88%; 1C, 100%; 2A, 83%; 2B, 92%; and 3, 57%. Combined, this represents a hearing preservation rate of 87% after surgical treatment of Grade II acoustic neurinomas. Full nerve function was maintained in 88% of patients with anatomically preserved facial nerves in both Grade I and II tumors. The remaining 12% of patients retained partial function of the facial nerve. Two patients in the series lost anatomical integrity of the nerve due to surgery.


Subject(s)
Facial Nerve/pathology , Hearing/physiology , Microsurgery , Neuroma, Acoustic/surgery , Vestibulocochlear Nerve/pathology , Audiometry, Pure-Tone , Brain Stem/pathology , Cerebellopontine Angle/pathology , Cochlear Nerve/pathology , Cochlear Nerve/physiopathology , Facial Nerve/physiopathology , Facial Nerve/surgery , Follow-Up Studies , Humans , Mastoid/surgery , Neuroma, Acoustic/classification , Neuroma, Acoustic/pathology , Petrous Bone/surgery , Speech Perception/physiology , Treatment Outcome , Vestibular Nerve/pathology , Vestibular Nerve/physiopathology , Vestibulocochlear Nerve/physiopathology , Vestibulocochlear Nerve/surgery
4.
Neurosurgery ; 42(1): 186-91; discussion 191-3, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9442523

ABSTRACT

OBJECTIVE AND IMPORTANCE: We describe two patients, with progressing neurological deficits, who showed improvement after revascularization of their carotid arteries using stents. CLINICAL PRESENTATION: One patient presented clinically with the symptoms of a middle cerebral artery territory stroke. Angiography demonstrated total occlusion of the right internal carotid artery (ICA), with evidence of clot from the origin of the ICA to the middle cerebral artery trifurcation. The second patient presented with bilateral ICA occlusions and evidence of a progressing left hemispheric deficit; she was receiving therapeutic levels of heparin at the time of deterioration of her condition. INTERVENTION: Thrombolysis and stenting successfully recanalized the occluded vessels, and the deficits of the first patient were reversed. With the second patient, a dissected carotid loop was encountered. Straightening of the loop with a wire and stenting of the carotid artery using two stents allowed revascularization of the left hemisphere and resolution of most of the deficits of this patient. CONCLUSION: This report demonstrates the technical feasibility of placing stents in high-risk patients with carotid artery occlusions from either dissection or atherosclerosis. Both patients sustained much smaller infarctions than would have been expected if the carotid artery territory had been infarcted. We report on the technical feasibility of reopening acutely closed ICAs by using endovascular methods.


Subject(s)
Arterial Occlusive Diseases/surgery , Carotid Artery Diseases/surgery , Cerebrovascular Disorders/surgery , Splints , Adult , Aged , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/therapy , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/therapy , Cerebral Angiography , Cerebrovascular Disorders/diagnostic imaging , Female , Humans , Male , Syndrome , Thrombolytic Therapy , Tomography, X-Ray Computed
5.
Neurosurgery ; 41(4): 979-82, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9316066

ABSTRACT

OBJECTIVE AND IMPORTANCE: Although surgical treatment of saccular aneurysms continues to be the gold standard of care, certain situations arise for which surgery may not be the best option. In these cases, electrically detachable coils have proven to provide superior outcomes in aneurysms left to medical management alone. An anterior communicating artery aneurysm with an anatomic neck wider than the fundus of the aneurysm failed to accommodate an initial attempt at Guglielmi detachable coil placement and was treated with an adjunctive balloon technique that allowed safe and effective aneurysm occlusion. CLINICAL PRESENTATION: The patient presented with an asymptomatic anterior communicating artery aneurysm that was detected incidentally on angiography after rupture of a giant middle cerebral artery aneurysm. INTERVENTION: Transarterial embolization of the patient's aneurysm was attempted with Guglielmi detachable coils. Although this procedure initially failed, it was then successfully performed when combined with a balloon angioplasty technique. CONCLUSION: The Guglielmi detachable coils were able to be placed when a nondetachable balloon was used to occlude the neck of the aneurysm and allow for the coils to be deposited into the aneurysm while protecting the parent vessel.


Subject(s)
Embolization, Therapeutic/instrumentation , Intracranial Aneurysm/therapy , Catheterization/instrumentation , Cerebral Angiography , Equipment Design , Humans , Intracranial Aneurysm/diagnostic imaging , Male , Middle Aged , Neurologic Examination , Postoperative Complications/diagnostic imaging , Postoperative Complications/therapy , Retreatment
6.
J Neuroimaging ; 7(3): 187-90, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9237440

ABSTRACT

A patient with bilaterally occluded internal carotid arteries had a right hemispheric stroke followed by a left cerebral infarction, secondary to dissection from fibromuscular dysplasia, seen also in the vertebral arteries. The occluded left carotid was reopened and stents placed, with apparent reestablishment of left hemispheric blood flow. The speech and other deficits resolved. Although its use is under investigation, percutaneous balloon angioplasty with stents may be an appropriate intervention when other measures do not prevent progressive ischemic events.


Subject(s)
Carotid Artery Diseases/therapy , Fibromuscular Dysplasia/therapy , Stents , Adult , Angioplasty, Balloon , Carotid Artery Diseases/complications , Carotid Artery Diseases/diagnosis , Carotid Artery, Internal , Cerebral Angiography , Cerebrovascular Disorders/etiology , Female , Fibromuscular Dysplasia/complications , Fibromuscular Dysplasia/diagnosis , Humans , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Tomography, X-Ray Computed
7.
J Neurosurg ; 86(4): 724-7, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9120640

ABSTRACT

Saccular intracranial aneurysms are a common and often fatal lesion. Whereas surgical treatment of these aneurysms continues to be the gold standard of care, certain situations arise for which surgery may not be the best option. In some of these cases, electrolytically detachable coils have been proven to provide outcomes superior to those seen for medical management alone. The authors present two cases of ophthalmic artery aneurysms that would not hold the Guglielmi detachable coils on the initial attempt. One aneurysm was 7 mm and one 4 mm, both with wide necks relative to the aneurysm sac. By using a balloon-assisted technique and blocking the parent artery with a nondetachable balloon, the coils could be safely placed in these aneurysms without herniation when the balloon was deflated. Both patients exhibited embolic symptoms after the procedure, one with a mild but permanent deficit. Although this technique requires manipulation of a second microcatheter and balloon, which increases its technical difficulties and is a higher risk procedure than standard coil placement, it has utility in patients who are not candidates for surgery.


Subject(s)
Catheterization , Embolization, Therapeutic/methods , Intracranial Aneurysm/therapy , Adult , Cerebral Angiography , Female , Humans , Intracranial Aneurysm/diagnostic imaging , Middle Aged
8.
Biophys J ; 71(6): 3157-66, 1996 Dec.
Article in English | MEDLINE | ID: mdl-8968586

ABSTRACT

Recovery from C-type inactivation of Kv1.3 can be accelerated by the binding of extracellular potassium to the channel in a voltage-dependent fashion. Whole-cell patch-clamp recordings of human T lymphocytes show that Ko+ can bind to open or inactivated channels. Recovery is biphasic with time constants that depend on the holding potential. Recovery is also dependent on the voltage of the depolarizing pulse that induces the inactivation, consistent with a modulatory binding site for K+ located at an effective membrane electrical field distance of 30%. This K(+)-enhanced recovery can be further potentiated by the binding of extracellular tetraethylammonium to the inactivated channel, although the tetraethylammonium does not interact directly with the K(+)-binding site. Our findings are consistent with a model in which K+ can bind and unbind slowly from a channel in the inactivated state, and inactivated channels that are bound by K+ will recover with a rate that is fast relative to unbound channels. Our data suggest that the kinetics of K+ binding to the modulatory site are slower than these recovery rates, especially at hyperpolarized voltages.


Subject(s)
Potassium Channels, Voltage-Gated , Potassium Channels/physiology , Potassium/metabolism , Potassium/pharmacology , T-Lymphocytes/physiology , Cell Membrane/physiology , Cells, Cultured , Humans , Hydrogen-Ion Concentration , Kinetics , Kv1.3 Potassium Channel , Membrane Potentials/drug effects , Models, Biological , Tetraethylammonium , Tetraethylammonium Compounds/pharmacology
9.
Biophys J ; 70(2): 798-805, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8789096

ABSTRACT

Extracellular potassium modulates recovery from C-type inactivation of Kv1.3 in human T lymphocytes. The results of whole-cell patch clamp recordings show that there is a linear increase in recovery rate with increasing [K+]o. An increase from 5 to 150 mM K+o causes a sixfold acceleration of recovery rate at a holding potential of -90 mV. Our results suggest that 1) a low-affinity K+ binding site is involved in recovery, 2) the rate of recovery increases with hyperpolarization, 3) potassium must bind to the channel before inactivation to speed its recovery, and 4) recovery rate depends on external [K+] but not on the magnitude of the driving force through open channels. We present a model in which a bound K+ ion destabilizes the inactivated state to increase the rate of recovery of C-type inactivation, thereby providing a mechanism for autoregulation of K+ channel activity. The ability of K+ to regulate its own conductance may play a role in modulating voltage-dependent immune function.


Subject(s)
Potassium Channels, Voltage-Gated , Potassium Channels/drug effects , Potassium Channels/metabolism , Potassium/metabolism , Potassium/pharmacology , Binding Sites , Biophysical Phenomena , Biophysics , Cells, Cultured , Extracellular Space/metabolism , Humans , Kinetics , Kv1.3 Potassium Channel , Membrane Potentials , Potassium Channel Blockers , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
10.
J Neurosurg ; 83(3): 453-60, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7666222

ABSTRACT

A retrospective study of external lumbar subarachnoid drainage in 16 pediatric patients with severe head injuries is presented. All patients had Glasgow Coma Scale scores of 8 or lower at 6 hours postinjury and were initially treated with ventriculostomy. Five patients required surgical evacuation of focal mass lesions. All patients manifested high intracranial pressures (ICPs) refractory to aggressive therapy, including hyperventilation, furosemide, mannitol, and in some cases, artificially induced barbiturate coma. After lumbar drainage was instituted, 14 patients had an abrupt and lasting decrease in ICP, obviating the need for continued medical management of ICP. In no patient did transtentorial or cerebellar herniation occur as a result of lumbar drainage. It was also noted retrospectively that the patients in this study had discernible basilar cisterns on computerized tomography scans. Fourteen patients survived; eight made good recoveries, three are functional with disability, and three have severe disabilities. Two patients died, most likely from uncontrolled ICP before the lumbar drain was placed. It is concluded that controlled external lumbar subarachnoid drainage is a useful treatment for pediatric patients with severe head injury when aggressive medical therapy and ventricular cerebrospinal fluid evacuation have failed to control high ICP. Selected patients with elevated ICP, which may be a function of posttraumatic cerebrospinal fluid circulation disruption and/or white matter cerebral edema, can be treated with this modality, which accesses the cisternal spaces untapped by ventriculostomy.


Subject(s)
Brain Edema/therapy , Craniocerebral Trauma/complications , Drainage/methods , Adolescent , Brain Edema/etiology , Brain Edema/physiopathology , Child , Child, Preschool , Craniocerebral Trauma/mortality , Craniotomy , Emergencies , Female , Glasgow Coma Scale , Hematoma, Epidural, Cranial/diagnostic imaging , Hematoma, Epidural, Cranial/etiology , Hematoma, Epidural, Cranial/surgery , Humans , Infant , Intracranial Pressure/physiology , Lumbosacral Region , Male , Radiography , Retrospective Studies , Survival Rate , Ventriculostomy
11.
Acta Neurochir Suppl ; 63: 60-7, 1995.
Article in English | MEDLINE | ID: mdl-7502731

ABSTRACT

Radiosurgery of AVM's is gaining in popularity and is advocated by many for the treatment of lesions less than 3 cm in diameter. During a 17 month period 33 patients with cerebral AVM's were treated with radiosurgery. All regions of the brain were represented in the series including brain stem. A mean follow-up of 10.8 months revealed a 6% rebleed rate and a 9% total complication rate. Multimodality therapy including embolization and surgery is recommended for the treatment of AVM's and radiosurgery is seen as an important adjunctive treatment option.


Subject(s)
Intracranial Arteriovenous Malformations/surgery , Radiosurgery , Adolescent , Adult , Aged , Cerebral Angiography , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/surgery , Combined Modality Therapy , Embolization, Therapeutic , Female , Follow-Up Studies , Humans , Intracranial Arteriovenous Malformations/diagnostic imaging , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Recurrence , Tomography, X-Ray Computed
12.
J Neurosurg ; 81(6): 947-9, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7965130

ABSTRACT

Spinal dural lacerations can be a difficult part of spinal surgery. A dural tear can result in complications that include meningitis and pseudocyst formation. Appropriate treatment for these tears is generally suturing, using 4.0, 5.0, or 6.0 suture. For successful closure of dural lacerations, the authors have collaborated in the design of a titanium clip, which resembles an aneurysm clip in appearance and is applied with standard aneurysm clip appliers. The titanium clip was tested against suture and Weck hemostatic vascular clips and found to have excellent tissue-approximating capacity and a rapid application time. It is believed that this is an appropriate device for the repair of spinal dural lacerations.


Subject(s)
Dura Mater/surgery , Neurosurgery/instrumentation , Titanium , Aneurysm/surgery , Animals , Dogs , Equipment Design , Hemostasis, Surgical/instrumentation , Humans , Pressure , Suture Techniques
13.
Ann Emerg Med ; 22(6): 1060-3, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8503527

ABSTRACT

A 19-year-old woman sustained a nonfatal hanging injury and a 28-year-old man sustained a unilateral locked facet with resultant quadriplegia as a result of bungee jumping. Injuries due to this sport have not been reported previously.


Subject(s)
Athletic Injuries/etiology , Quadriplegia/etiology , Adult , Athletic Injuries/physiopathology , Athletic Injuries/therapy , Female , Humans , Male , Quadriplegia/diagnostic imaging , Quadriplegia/therapy , Radiography
14.
J Gen Physiol ; 99(5): 771-93, 1992 May.
Article in English | MEDLINE | ID: mdl-1376766

ABSTRACT

We used patch clamp techniques to identify and characterize a variety of K+ channels in primary human peripheral T lymphocytes. The most common channel observed in cell-attached configuration was voltage gated and inactivating. In ensemble averages, the kinetics of its activation and inactivation were similar to those of the whole-cell, voltage-gated K+ current described previously (Cahalan, M. D., K. G. Chandy, T. E. DeCoursey, and S. Gupta. 1985. J. Physiol. [Lond.]. 358:197-237; Deutsch, C., D. Krause, and S. C. Lee. 1986. J. Physiol. [Lond.]. 372:405-423), suggesting that this channel underlies the major portion of the outward current in lymphocytes. A small fraction of the time, this or another very similar channel was observed to inactivate significantly more slowly. Another channel type observed in cell-attached recording was seen less frequently and was transient in its appearance. This channel has a unitary conductance of approximately 10 pS, similar to the voltage-gated channel, but its voltage-independent gating, lack of inactivation, and different kinetic parameters showed it to be distinct. In whole-cell recording there is often a significant plateau current during sustained depolarization. Experiments using whole-cell and excised outside-out configurations indicate that at least part of this residual current is carried by K+ and, as opposed to the predominant voltage-gated current, is charybdotoxin insensitive. These findings are consistent with evidence that implicates charybdotoxin-sensitive and -insensitive components in T lymphocyte proliferation and volume regulation.


Subject(s)
Potassium Channels/metabolism , T-Lymphocytes/metabolism , Adult , Charybdotoxin , Electric Conductivity , Humans , In Vitro Techniques , Ion Channel Gating , Kinetics , Membrane Potentials , Potassium Channels/drug effects , Scorpion Venoms/pharmacology
15.
Surg Neurol ; 37(3): 216-8, 1992 Mar.
Article in English | MEDLINE | ID: mdl-1536027

ABSTRACT

The authors present a unique case of an intradural extramedullary ganglioneuroma in the thoracic spine of an adult. Intraspinal ganglioneuromas are rare, benign tumors of sympathetic nervous tissue origin, but exclusively intradural ganglioneuromas have not been reported.


Subject(s)
Ganglioneuroma/pathology , Spinal Cord Neoplasms/pathology , Ganglioneuroma/surgery , Humans , Male , Middle Aged , Spinal Cord Neoplasms/surgery
16.
Neuroreport ; 2(6): 345-7, 1991 Jun.
Article in English | MEDLINE | ID: mdl-1832987

ABSTRACT

N-methyl-D-aspartate(NMDA) antagonists afford possible therapeutic modalities for stroke, trauma, and various neurodegenerative conditions thought to be mediated by excessive stimulation of NMDA receptors in the brain. To date, however, no drug has been demonstrated to be a safe NMDA antagonist at a dosage necessary for neuroprotection. In the present study, we use an in-vitro preparation to show that glutathione is capable of attenuating neuronal damage mediated by NMDA receptor activation. Both oxidized and reduced glutathione are protective, and an extracellular mechanism of action on the NMDA receptor-channel complex is suggested.


Subject(s)
Glutathione/therapeutic use , Nervous System Diseases/drug therapy , Receptors, N-Methyl-D-Aspartate/physiology , Animals , Glutathione/metabolism , Nervous System Diseases/physiopathology , Oxidation-Reduction , Rats , Retinal Ganglion Cells/drug effects
17.
Neurology ; 40(5): 852-5, 1990 May.
Article in English | MEDLINE | ID: mdl-1970428

ABSTRACT

Activation of N-methyl-D-aspartate (NMDA) receptors is thought to mediate toxic damage to central neurons due to hypoxia-ischemia, hypoglycemia, and trauma. We studied identified rat retinal ganglion cell neurons in vitro, a useful system for the study of excitotoxicity, and compared the protective effects of delayed administration of a competitive antagonist, 2-amino-5-phosphonovalerate (APV), and of an uncompetitive antagonist, MK-801, after glutamate-induced injury. We used maximally protective doses of the 2 antagonists. Under these conditions, both antagonists were able to prevent neuronal cell death if they were present within minutes of exposure to an endogenous glutamate-related toxin. In contrast, MK-801, but not APV, protected significantly against NMDA-mediated neurotoxicity when administered 1 to 4 hours after the initial insult. Thus, at least under certain conditions, an uncompetitive NMDA antagonist may offer a distinct advantage over a competitive antagonist when given several hours after a neurologic injury.


Subject(s)
2-Amino-5-phosphonovalerate/pharmacology , Cell Survival/drug effects , Dibenzocycloheptenes/pharmacology , Receptors, Neurotransmitter/toxicity , Retina/drug effects , Retinal Ganglion Cells/drug effects , Animals , Cells, Cultured , Dizocilpine Maleate , Rats , Receptors, N-Methyl-D-Aspartate , Time Factors
18.
Neurosci Lett ; 110(3): 291-6, 1990 Mar 14.
Article in English | MEDLINE | ID: mdl-1970145

ABSTRACT

Acute neurological injury from hypoxia-ischemia, hypoglycemia, and trauma is thought to be predominantly mediated by activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor in the brain and the subsequent influx of calcium ions through receptor-operated channels. Several chronic degenerative diseases, such as Huntington's disease and the amyotrophic lateral sclerosis-Parkinsonism-dementia complex found on Guam, may share a similar pathogenesis due to a glutamate-like toxin. This laboratory recently reported that exposure to a reducing agent, such as dithiothreitol (DTT), selectively increases ionic current flow through NMDA-activated channels in several types of central neurons; conversely, oxidizing agents reverse this effect. To investigate the novel influence of redox modulation on NMDA neurotoxicity, in the present in vitro study we monitored survival of an identified central neuron, the retinal ganglion cell, approximately 24 h after a brief exposure to DTT. To determine the degree of killing specifically related to activation of the NMDA receptor, 2-amino-5-phosphonovalerate (APV, a selective NMDA antagonist) was added to sibling cultures. APV-preventable, glutamate-induced death was increased 70 +/- 9% with DTT treatment. This effect was totally blocked by the concomitant addition of an oxidizing agent, 5,5-dithiobis-2-nitrobenzoic acid (DTNB). These findings suggest that the enhanced killing following chemical reduction with DTT is mediated at the NMDA receptor site, and that the redox state of the NMDA receptor is crucial for the survival of neurons facing glutamate-related injury.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Dithiothreitol/toxicity , Receptors, Neurotransmitter/physiology , Retina/physiology , Retinal Ganglion Cells/physiology , 2-Amino-5-phosphonovalerate/pharmacology , Action Potentials/drug effects , Animals , Cells, Cultured , Dithionitrobenzoic Acid/pharmacology , Oxidation-Reduction , Rats , Receptors, N-Methyl-D-Aspartate , Receptors, Neurotransmitter/drug effects , Retinal Ganglion Cells/cytology , Retinal Ganglion Cells/drug effects
19.
Neuroscience ; 39(3): 665-74, 1990.
Article in English | MEDLINE | ID: mdl-2097520

ABSTRACT

Locomotor stepping in the Nembutal-anesthetized rat was elicited by electrical stimulation of either of two sites in the right or left posterolateral hypothalamus. Essential midbrain loci were identified by reversibly blocking the elicited locomotion through local injections of the anesthetic procaine (15%, 0.5 microliter). Two types of critical midbrain sites were found. At ipsilateral block sites (n = 21), procaine blocked only that locomotion elicited by ipsilateral stimulation. These sites could be along the course of a direct descending ipsilateral pathway although a possible bidirectional pathway is not to be excluded. At bilateral block sites (n = 21), procaine blocked locomotion elicited by both ipsilateral and contralateral stimulation. These sites could be involved in functions prerequisite for the initiation of locomotion or in the generation of the stepping pattern. Procaine injections in 35 sites had no effect on locomotion. Ipsilateral and bilateral block sites were intermixed and generally located in regions ventral to the midbrain central gray: chiefly the anterior ventromedial midbrain, the pontis oralis nucleus and the pedunculopontine nucleus. Negative sites were located in both the dorsal and ventral midbrain. Ipsilateral block sites were relatively prevalent in the anterior midbrain, indicating that the locomotor initiation signals are lateralized at this level. Bilateral block sites were more prevalent in the posterior levels, suggesting that the initiation signals are proximal to, or interact with, circuits that have a bilateral influence on locomotion.


Subject(s)
Hypothalamic Area, Lateral/physiology , Mesencephalon/physiology , Motor Activity , Procaine/pharmacology , Animals , Electric Stimulation , Functional Laterality , Hypothalamus/anatomy & histology , Hypothalamus/physiology , Male , Motor Activity/drug effects , Procaine/administration & dosage , Rats , Rats, Inbred Strains , Stereotaxic Techniques
20.
Neurosurgery ; 25(4): 655-7, 1989 Oct.
Article in English | MEDLINE | ID: mdl-2797404

ABSTRACT

An unusual case of discitis in a 60-year-old, insulin-dependent, diabetic man is presented. Radiographs of the lumbar spine demonstrated changes associated with infection of the intervertebral disc space. Cultures from the L5-S1 disc space grew the microorganism designated by the Centers for Disease Control as Group Ve-1, an organism that has had questionable clinical significance in the past, and has not been reported as a pathogen in an intervertebral disc space.


Subject(s)
Bacterial Infections/complications , Discitis/microbiology , Gram-Negative Bacteria , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Discitis/surgery , Humans , Male , Middle Aged
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