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Biomedical subjects

I Fried

Publications and source records attributed to I Fried.

At least 37 records · Page 2Linked to original sources
PubMed1999

Hippocampal N-methyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients.

Changes in the subunit stoichiometry of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) alters its channel properties, and may enhance or reduce neuronal excitability in temporal lobe epilepsy patients. This study determined whether hippocampal NMDA receptor subunit mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsy cases. Hippocampal sclerosis (HS; n = 16), non-HS (n = 10), and autopsy hippocampi (n = 9) were studied for NMDAR1 (NR1) and NR2A-D mRNA levels by using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, non-HS and HS patients showed increased NR2A and NR2B hybridization densities per dentate granule cell. Furthermore, non-HS hippocampi showed increased NR1 and NR2B mRNA levels per CA2/3 pyramidal neuron compared with autopsy cases. HS patients, by contrast, showed decreased NR2A hybridization densities per CA2/3 pyramidal neuron compared with non-HS and autopsy cases. These findings indicate that chronic temporal lobe seizures are associated with differential changes in hippocampal NR1 and NR2A-D hybridization densities that vary by subfield and clinical-pathological category. In temporal lobe epilepsy patients, these findings support the hypothesis that in dentate granule cells NMDA receptors are increased, and excitatory postsynaptic potentials should be strongly NMDA mediated compared with nonseizure autopsies. HS patients, by comparison, showed decreased pyramidal neuron NR2A mRNA levels, and this suggests that NMDA-mediated pyramidal neuron responses should be reduced in HS patients compared with non-HS cases.

Adolescent↗
PubMed1999

Measurements of attention deficits and impulsivity: a Swedish study of the Gordon Diagnostic System.

The Gordon Diagnostic System (GDS) is a portable easily operated computerized tool developed to measure impulse control, attention and vigilance. In 1988, it was standardized for use among American children. The aim of this study was to evaluate the GDS for use among Swedish children. A clinical sample of 71 Swedish children, mean age 10.5 y, fulfilling the ADHD criteria according to the DSM-IV was compared with a control sample of 88 children, mean age 10.2-y, with no known psychiatric diagnosis. The clinical sample showed lower GDS scores in all age groups, with some exceptions. The GDS scores were not associated with gender, but strongly associated with age, especially in the control sample. The accuracy of the GDS referring a specific child to either of the samples was, as expected, not impressive. With respect to the practical usefulness, the GDS was well accepted by the children and parents in both samples. The findings in age variation and when comparing children with ADHD and controls are in agreement with results from other studies.

Adolescent↗
PubMed1999

Hippocampal and entorhinal cortex high-frequency oscillations (100--500 Hz) in human epileptic brain and in kainic acid--treated rats with chronic seizures.

PURPOSE: Properties of oscillations with frequencies >100 Hz were studied in kainic acid (KA)-treated rats and compared with those recorded in normal and kindled rats as well as in patients with epilepsy to determine differences associated with epilepsy. METHODS: Prolonged in vivo wideband recordings of electrical activity were made in hippocampus and entorhinal cortex (EC) of (a) normal rats, (b) kindled rats, (c) rats having chronic recurrent spontaneous seizures after intrahippocampal KA injections, and (d) patients with epilepsy undergoing depth electrode evaluation in preparation for surgical treatment. RESULTS: Intermittent oscillatory activity ranging from 100 to 200 Hz in frequency and 50-150 ms in duration was recorded in CA1 and EC of all three animal groups, and in epileptic human hippocampus and EC. This activity had the same characteristics in all groups, resembled previously observed "ripples" described by Buzsáki et al., and appeared to represent field potentials of inhibitory postsynaptic potentials (IPSPs) on principal cells. Unexpectedly, higher frequency intermittent oscillatory activity ranging from 200 to 500 Hz and 10-100 ms in duration was encountered only in KA-treated rats and patients with epilepsy. These oscillations, termed fast ripples (FRs), were found only adjacent to the epileptogenic lesion in hippocampus, EC, and dentate gyrus, and appeared to represent field potential population spikes. Their local origin was indicated by correspondence with the negative phase of burst discharges of putative pyramidal cells. CONCLUSIONS: The persistence of normal-appearing ripples in epileptic brain support the view that inhibitory processes are preserved. FRs appear to be field potentials reflecting hyper-synchronous bursting of excitatory neurons and provide an opportunity to study the role of this pathophysiologic phenomenon in epilepsy and seizure initiation. Furthermore, if FR activity is unique to brain areas capable of generating spontaneous seizures, its identification could be a powerful functional indicator of the epileptic region in patients evaluated for surgical treatment.

Action Potentials↗
PubMed1999

Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy.

OBJECTIVE: Sodium-coupled transporters remove extracellular neurotransmitters and alterations in their function could enhance or suppress synaptic transmission and seizures. This study determined hippocampal gamma-aminobutyric acid (GABA) and glutamate transporter immunoreactivity (IR) in temporal lobe epilepsy (TLE) patients. METHODS: Hippocampal sclerosis (HS) patients (n = 25) and non-HS cases (mass lesion and cryptogenic; n = 20) were compared with nonseizure autopsies (n = 8). Hippocampal sections were studied for neuron densities along with IR for glutamate decarboxylase (GAD; presynaptic GABA terminals), GABA transporter-1 (GAT-1; presynaptic GABA transporter), GAT-3 (astrocytic GABA transporter), excitatory amino acid transporter 3 (EAAT3; postsynaptic glutamate transporter), and EAAT2-1 (glial glutamate transporters). RESULTS: Compared with autopsies, non-HS cases with similar neuron counts showed: 1) increased GAD IR gray values (GV) in the fascia dentata outer molecular layer (OML), hilus, and stratum radiatum; 2) increased GAT-1 OML GVs; 3) increased astrocytic GAT-3 GVs in the hilus and Ammon's horn; and 4) no IR differences for EAAT3-1. HS patients with decreased neuron densities demonstrated: 1) increased OML and inner molecular layer GAD puncta; 2) decreased GAT-1 puncta relative to GAD in the stratum granulosum and pyramidale; 3) increased GAT-1 OML GVs; 4) decreased GAT-3 GVs; 5) increased EAAT3 IR on remaining granule cells and pyramids; 6) decreased glial EAAT2 GVs in the hilus and CA1 stratum radiatum associated with neuron loss; and 7) increased glial EAAT1 GVs in CA2/3 stratum radiatum. CONCLUSIONS: Hippocampal GABA and glutamate transporter IR differ in TLE patients compared with autopsies. These data support the hypothesis that excitatory and inhibitory neurotransmission and seizure susceptibility could be altered by neuronal and glial transporters in TLE patients.

ATP-Binding Cassette Transporters↗
PubMed1999

Cerebral microdialysis combined with single-neuron and electroencephalographic recording in neurosurgical patients. Technical note.

Monitoring physiological changes in the brain parenchyma has important applications in the care of neurosurgical patients. A technique is described for measuring extracellular neurochemicals by cerebral microdialysis with simultaneous recording of electroencephalographic (EEG) and single-unit (neuron) activity in selected targets in the human brain. Forty-two patients with medically intractable epilepsy underwent stereotactically guided implantation of a total of 423 intracranial depth electrodes to delineate potentially resectable seizure foci. The electrodes had platinum alloy contacts for EEG recordings and four to nine 40-microm microwires for recording single-unit neuron activity. Eighty-six electrodes also included microdialysis probes introduced via the electrode lumens. During monitoring on the neurosurgical ward, electrophysiological recording and cerebral microdialysis sampling were performed during seizures, cognitive tasks, and sleep-waking cycles. The technique described here could be used in developing novel approaches for evaluation and treatment in a variety of neurological conditions such as head injury, subarachnoid hemorrhage, epilepsy, and movement disorders.

Adolescent↗
PubMed1998

Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients.

This study determined whether hippocampal kainate (KA) receptor mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsies. Hippocampal sclerosis (HS; n = 17), nonsclerosis (non-HS; n = 11), and autopsy hippocampi (n = 9) were studied for KA1-2 and GluR5-7 mRNA levels using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, HS and non-HS cases showed decreased GluR5 and GluR6 hybridization densities per CA2 and/or CA3 pyramid. Furthermore, HS patients demonstrated increased KA2 and GluR5 hybridization densities per granule cell compared with autopsy hippocampi. These findings indicate that chronic temporal lobe seizures were associated with differential changes in hippocampal KA1-2 and GluR5-7 hybridization densities that vary by subfield and pathology group. In temporal lobe epilepsy patients, these results support the hypothesis that pyramidal cell GluR5 and GluR6 mRNA levels are decreased as a consequence of seizures, and in HS patients granule cell KA2 and GluR5 mRNA levels are increased in association with aberrant fascia dentata mossy fiber sprouting and/or hippocampal neuronal loss.

Adult↗
PubMed1998

Increased hippocampal AMPA and NMDA receptor subunit immunoreactivity in temporal lobe epilepsy patients.

This study determined if hippocampal AMPA and NMDA subunit immunoreactivity (IR) in temporal lobe epilepsy patients was increased compared with nonseizure autopsies. Hippocampi from hippocampal sclerosis patients (HS; n = 26) and nonsclerosis cases (non-HS: n = 12) were compared with autopsies (n = 6) and studied for GluR1, GluR2/3, NMDAR1, and NMDAR2 IR gray values (GV) along with fascia dentata and Ammon's horn neuron densities. Compared with autopsies, non-HS cases with similar neuron densities and HS patients with decreased neuron densities showed: (a) Increased GluR1 GVs in the fascia dentata molecular layer: (b) increased NMDAR1 GVs in the CA3-1 stratum radiatum and greater IR within pyramids; and (c) increased GluR2/3 and NMDAR2 GVs throughout all hippocampal subfields. Furthermore, HS patients showed that relative to the outer molecular layer: (a) GluR1 GV differences were decreased in the CA4/hilar region and CA1 stratum radiatum compared with autopsies; and (b) NMDAR2 GV differences were increased in the inner molecular layer compared with non-HS cases. In temporal lobe seizure patients, these results indicate that AMPA and NMDA receptor subunit IR was increased in HS and non-HS hippocampi compared with nonseizure autopsies. In humans, these findings support the hypothesis that glutamate receptor subunits are increased in association with chronic temporal lobe seizures, which may enhance excitatory neurotransmission and seizure susceptibility.

Adult↗
PubMed1998

The asleep-awake-asleep anesthetic technique for intraoperative language mapping.

OBJECTIVE: We evaluated a combined technique designed for procedures requiring intraoperative language mapping. We planned to induce general anesthesia with endotracheal intubation and hyperventilation and then to awaken and extubate the patient for speech testing. After the latter, endotracheal reintubation and general anesthesia were planned. METHODS: With the patient under intravenously induced sedation, we topically anesthetized the airway with lidocaine that was delivered through a spraying catheter. Fiberoptic endotracheal intubation was then performed on the awake patient, using a modified endotracheal tube. General anesthesia with intravenous propofol or sodium thiopental was induced, the patient's head was attached to a Mayfield holder, and the pin and operative sites were infiltrated with 0.5% bupivacaine with epinephrine. In anticipation of speech mapping, general anesthesia was discontinued and lidocaine was injected into the catheter that was spirally attached to the endotracheal tube. After speech mapping, the awake patients were endotracheally intubated, guided with the fiberoptic laryngoscope or tube changer, and general anesthesia was induced and maintained until termination of the surgery. RESULTS: We did not observe any complications, such as coughing or head movements, during the preparation for general anesthesia, awakening and endotracheal extubation for speech mapping, and post-testing reintubation or induction of general anesthesia. CONCLUSION: The combined technique that we describe abolished the potential discomfort of surgical stimulation on a sedated patient, reduced the duration of wakefulness, and provided a secure airway and the means to hyperventilate our patients before dural opening.

Adolescent↗
PubMed1998

Is your organization's market ready for a Medicare PSO?

Provider organizations interested in forming a Medicare PSO should first determine their market's readiness to accept a new Medicare risk product. How a Market might receive a new Medicare PSO depends on numerous factors. These factors include size and demographic characteristics of the Medicare Population; capitation rate; level of commercial and Medicare managed care enrollment; market concentration; provider supply, capabilities, and attitudes toward managed care; and prevalence of large employers and their level of interest in Medicare risk products.

Capitation Fee↗
PubMed1997

Olfactory bedside test. A simple approach to identify temporo-orbitofrontal dysfunction.

BACKGROUND: Olfactory memory and discrimination are processed by the anteromesial temporal cortex and the orbitofrontal cortex. Both functions may therefore be impaired in limbic epilepsy. METHODS: Twenty-seven patients with mesial temporal lobe seizures (MTLS), 10 patients with neocortical seizures (NS), and 10 matched healthy control subjects underwent evaluation for olfactory quality discrimination (OD) and delayed recognition memory (OM). All patients were referred for presurgical evaluation. The olfactory tests were performed in a same-different paradigm with 10 seconds (OD) and 60 minutes (OM) between presentations of the odors, using the standardized University of Pennsylvania Smell Identification Test. The presentations were monorhinal in the OD and birhinal in the OM tests. The results were related to regional glucose metabolism measured with fludeoxyglucose F 18 positron emission tomography. RESULTS: Patients with MTLS had an impaired OD ipsilateral to the epileptogenic region (P < .001) and a higher total number of errors (including both tests) (P = .002). They also had lower OM scores, but not significantly lower than those of patients with NS (P = .05). The combined OM and OD tests correctly identified patients with MTLS with a sensitivity of 85% and a specificity of 90%, offering a correct lateralization in 74% of patients. Patients with MTLS whose OD was more impaired than OM differed from those with more impaired OM by having a significant hypometabolism not only over the neocortex of the epileptogenic temporal lobe (P = .02) but also in the ipsilateral anterior (P = .008) and orbitofrontal cortex (P = .007) (2-way analysis of variance). CONCLUSIONS: Tests of olfactory function are useful in distinguishing between NS and MTLS. The impairments of OM and OD can be dissociated in pathological states and therefore mediated by different structures.

Adult↗
PubMed1997

Single neuron activity in human hippocampus and amygdala during recognition of faces and objects.

The hippocampus and its associated structures play a key role in human memory, yet the underlying neuronal mechanisms remain unknown. Here, we report that during encoding and recognition, single neurons in the medial temporal lobe discriminated faces from inanimate objects. Some units responded selectively to specific emotional expressions or to conjunctions of facial expression and gender. Such units were especially prevalent during recognition, and the responses depended on stimulus novelty or familiarity. Traces of exposure to faces or objects were found a few seconds after stimulus removal as well as 10 hr later. Some neurons maintained a record of previous stimulus presentation that was more accurate than the person's conscious recollection. We propose that the human medial temporal lobe constructs a "cognitive map" of stimulus attributes comparable to the map of the spatial environment described in the rodent hippocampus.

Amygdala↗
PubMed1997

Human hippocampal AMPA and NMDA mRNA levels in temporal lobe epilepsy patients.

This study was designed to determine whether hippocampal neuronal AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and NMDA (N-methyl-D-aspartate) mRNA levels were differentially increased in temporal lobe epilepsy patients compared with those measured in control tissue from non-seizure autopsies. Hippocampi from hippocampal sclerosis patients (n = 28) and temporal mass lesion cases (n = 12) were compared with those from the autopsies (n = 4), and studied for AMPA GluR1-3 and NMDAR1-2 mRNAs using semi-quantitative in situ hybridization, along with fascia dentata and Ammon's horn neuron densities. Compared with the autopsies, and without correction for neuron counts, the mass lesion cases with neuron densities similar to autopsies showed: (i) significantly increased NMDAR2 hybridization densities for fascia dentata granule cells; (ii) increased AMPA GluR3 mRNA densities for Ammon's horn pyramids; and (iii) similar or numerically increased mRNAs for all other subunits and hippocampal subfields. Compared with the autopsies, hippocampal sclerosis cases with decreased neuron densities showed: (i) significantly decreased AMPA GluR1-2 and NMDAR1-2 hybridization densities for Ammon's horn pyramids and (ii) similar or numerically decreased mRNAs for all other subunits and subfields. However, correcting for changes in neuron densities showed that hippocampal sclerosis patients had increased AMPA and NMDA mRNA levels per neuron compared with autopsies, and in the CA2 resistant sector GluR2 mRNA levels were numerically greater than autopsies and mass lesion cases. Furthermore, relative to autopsies both sclerosis and mass lesion hippocampi showed that, in the stratum granulosum, the greatest mRNA increases were in AMPA GluR1 and NMDAR2 compared with the other mRNAs. In chronic temporal lobe seizure patients these results indicate that mass lesion and sclerosis cases show differential increases in hippocampal AMPA and NMDA mRNA levels per neuron compared with autopsies, especially for AMPA GluR1 and NMDAR2 in fascia dentata granule cells. These findings support the hypothesis that temporal lobe seizures are associated with increased ionotropic glutamate receptor mRNA levels and alterations in receptor subunit composition that probably contribute to neuronal hyperexcitability, synchronization and seizure generation.

Adult↗
PubMed1997

Glutamate currents in morphologically identified human dentate granule cells in temporal lobe epilepsy.

Glutamate-receptor-mediated synaptic transmission was studied in morphologically identified hippocampal dentate granule cells (DGCs; n = 31) with the use of whole cell patch-clamp recording and intracellular injection of biocytin or Lucifer yellow in slices prepared from surgically removed medial temporal lobe specimens of epileptic patients (14 specimens from 14 patients). In the current-clamp recording, low-frequency stimulation of the perforant path generated depolarizing postsynaptic potentials that consisted of excitatory postsynaptic potentials and phase-inverted inhibitory postsynaptic potentials mediated by the gamma-aminobutyric acid-A (GABA(A)) receptor at a resting membrane potential of -62.7 +/- 2.0 (SE) mV. In the voltage-clamp recording, two glutamate conductances, a fast alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-receptor-mediated excitatory postsynaptic current (EPSC; AMPA EPSC) and a slowly developing N-methyl-D-aspartate (NMDA)-receptor-mediated EPSC (NMDA EPSC), were isolated in the presence of a GABA(A) receptor antagonist. NMDA EPSCs showed a voltage-dependent increase in conductance with depolarization by exhibiting an N-shaped current-voltage relationship. The slope conductance of the NMDA EPSC ranged from 1.1 to 9.4 nS in 31 DGCs, reaching up to twice the size of the AMPA conductance. This widely varying size of the NMDA conductance resulted in the generation of double-peaked EPSCs and a nonlinear increase of the slope conductance of up to 37.5 nS with positive membrane potentials, which resembled "paroxysmal currents," in a subpopulation of the neurons. In contrast, AMPA EPSCs, which were isolated in the presence of an NMDA receptor antagonist (2-amino-5-phosphonovaleric acid), showed voltage-independent linear changes in the current-voltage relationship and were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione. The AMPA conductance showed little variance, regardless of the size of the NMDA conductance of a given neuron. The average AMPA slope conductance was 5.28 +/- 0.65 (SE) nS in 31 human DGCs. This value was similar to AMPA EPSC conductances in normal rat DGCs (5.35 +/- 0.52 nS, mean +/- SE; n = 55). Dendritic morphology and spine density were quantified in the individual DGCs to assess epileptic pathology. Dendritic spine density showed an inverse correlation (r2 = 0.705) with a slower rise time and a longer half-width of the excitatory postsynaptic potentials mediated by the NMDA receptor. It is concluded that both AMPA and NMDA EPSCs contribute to human DGC synaptic transmission in epileptic hippocampus. However, a wide range of changes in the slope conductance of the NMDA EPSCs suggests that the NMDA-receptor-mediated conductance could be altered in human epileptic DGCs. These changes may influence the generation of chronic subthreshold epileptogenic synaptic activity and give rise to pathological excitation leading to epileptic seizures and dendritic pathology.

Animals↗
PubMed1997

Auras and experiential responses arising in the temporal lobe.

Complex partial seizures and the auras that precede them are often manifestations of localized temporal lobe activity. Auras, unlike complex partial seizures, are reportable, since memory for them is retained. Similar experiences can be elicited by local electrical stimulation of mesial or lateral temporal cortex. Auras and "experiential phenomena" arising in the temporal lobe reflect dissociation of human experience into perceptual, mnemonic, and affective components, which in some cases can be specifically localized. Auras often persist following medial temporal lobe surgery, even when patients are rendered seizure-free. This suggests that these auras, like formed memories, are widely distributed and may eventually become consolidated in the neocortex.

Humans↗
PubMed1997

Long-term follow-up after temporal lobe resection for lesions associated with chronic seizures.

A follow-up study was conducted on 60 patients who had standard en bloc anterior temporal lobe resection, including mesio-temporal structures, as treatment for temporal lobe lesions associated with chronic, medically intractable seizures. Lesions were identified as glial tumors, hamartomas, or vascular malformations. Long-term outcome was assessed in terms of seizure frequency and certain psychosocial sequelae. Seizure onset occurred at an average age of 15 years (median = 13.5 years), and patients experienced seizures for an average of 13 years prior to surgery. The mean time of follow-up was 8.4 years post-surgery (median = 6 years). The Kaplan-Meier curve at median follow-up showed a seizure-free rate of 80%. Late seizure recurrence was documented for three patients; two had been seizure free for 10 years and one for 15 years after surgery before re-onset of seizures in the absence of tumor recurrence. A prolonged history of seizures prior to surgery was associated with a poorer seizure outcome (p = 0.06), suggesting that secondary epileptogenesis at sites distant to the lesion may develop with years of uncontrolled seizures. There was a low tumor recurrence rate of 3.3% (two cases). The psychosocial outcome was generally good, with 67% working or engaged in educational studies, and improvement noted in 59% of cases for one or more of the psychosocial factors investigated. This study confirms that anterior temporal lobe resection for temporal lesions associated with chronic seizures is a successful treatment with a high seizure-free rate following surgery and good psychosocial outcome.

Adaptation, Psychological↗
PubMed1997

Long-term follow-up after temporal lobe resection for lesions associated with chronic seizures.

A follow-up study was conducted on 60 patients who had standard en bloc anterior temporal lobe resection, including mesiotemporal structures, as treatment for temporal lobe lesions associated with chronic, medically intractable seizures. Lesions were identified as glial tumors, hamartomas, or vascular malformations. Long-term outcome was assessed in terms of seizure frequency and certain psychosocial sequelae. Seizure onset occurred at an average age of 15 years (median = 13.5 years), and patients experienced seizures for an average of 13 years prior to surgery. The mean time of follow-up was 8.4 years postsurgery (median = 6 years). The Kaplan-Meier curve at median follow-up showed a seizure-free rate of 80%. Late seizure recurrence was documented for three patients; two had been seizure-free for 10 years and one for 15 years after surgery, before re-onset of seizures in the absence of tumor recurrence. A prolonged history of seizures prior to surgery was associated with a poorer seizure outcome (p = 0.06), suggesting that secondary epileptogenesis at sites distant to the lesion may develop with years of uncontrolled seizures. There was a low tumor recurrence rate of 3.3% (two cases). The psychosocial outcome was generally good, with 67% working or engaged in educational studies, and improvement noted in 59% of cases for one or more of the psychosocial factors investigated. This study confirms that anterior temporal lobe resection for temporal lesions associated with chronic seizures is a successful treatment with a high seizure-free rate following surgery and good psychosocial outcome.

Adaptation, Psychological↗