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Biomedical subjects

D I Levy

Publications and source records attributed to D I Levy.

16 recordsLinked to original sources
PubMed1997

Balloon-assisted coil placement in wide-necked aneurysms. Technical note.

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.

Adult↗
PubMed1996

A voltage-dependent role for K+ in recovery from C-type inactivation.

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.

Cell Membrane↗
PubMed1996

Recovery from C-type inactivation is modulated by extracellular potassium.

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.

Binding Sites↗
PubMed1995

Radiosurgery in the treatment of cerebral AVMs.

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.

Adolescent↗
PubMed1995

Controlled lumbar drainage in pediatric head injury.

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.

Adolescent↗
PubMed1994

Titanium dural clip testing. Technical note.

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.

Aneurysm↗
PubMed1993

Injuries resulting from bungee-cord jumping.

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.

Adult↗
PubMed1992

Diverse K+ channels in primary human T lymphocytes.

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.

Adult↗
PubMed1991

Glutathione prevents N-methyl-D-aspartate receptor-mediated neurotoxicity.

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.

Animals↗
PubMed1990

Redox modulation of NMDA receptor-mediated toxicity in mammalian central neurons.

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)

2-Amino-5-phosphonovalerate↗
PubMed1990

Midbrain areas required for locomotion initiated by electrical stimulation of the lateral hypothalamus in the anesthetized rat.

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.

Animals↗
PubMed1990

Comparison of delayed administration of competitive and uncompetitive antagonists in preventing NMDA receptor-mediated neuronal death.

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.

2-Amino-5-phosphonovalerate↗
PubMed1989

Discitis caused by the Centers for Disease Control microorganism Group Ve-1.

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.

Anti-Bacterial Agents↗
PubMed1987

Some emerging principles underlying the physical properties, biological actions, and utility of vitrification solutions.

Vitrification solutions are aqueous cryoprotectant solutions which do not freeze when cooled at moderate rates to very low temperatures. Vitrification solutions have been used with great success for the cryopreservation of some biological systems but have been less successful or unsuccessful with other systems, and more fundamental knowledge about vitrification solutions is required. The purpose of the present survey is to show that a general understanding of the physical behavior and biological effects of vitrification solutions, as well as an understanding of the conditions under which vitrification solutions are required, is gradually emerging. Detailed nonequilibrium phase diagram information in combination with specific information on the tolerance of biological systems to ice and to cryoprotectant at subzero temperatures provides a quantitative theoretical basis for choosing between vitrification and freezing. The vitrification behavior of mixtures of cryoprotective agents during cooling is predictable from the behavior of the individual agents, and the behavior of individual agents is gradually becoming predictable from the details of their molecular structures. Progress is continuing concerning the elucidation of mechanisms and cellular sites of toxicity and mechanisms for the reduction of toxicity. Finally, important new information is rapidly emerging concerning the crystallization of previously vitrified cryoprotectant solutions during warming. It appears that vitrification tendency, toxicity, and devitrification all depend on subtle variations in the organization of water around dissolved substances.

Animals↗