Biomedical subjects

T R Henry

Publications and source records attributed to T R Henry.

At least 37 records · Page 2Linked to original sources

PubMed1998

Influence of head trauma on outcome following anterior temporal lobectomy.

BACKGROUND: There is controversy in the literature regarding the importance of risk factors in developing epilepsy and seizure outcome following anterior temporal lobectomy. Some of the existing studies may be biased because of patient selection and limitations in determining predisposition. OBJECTIVE: To investigate the role of risk factors for epilepsy in determining outcome following anterior temporal lobectomy. PATIENTS AND METHODS: We identified 102 patients in a consecutive surgery series for epilepsy from a tertiary center with a minimum of 1-year postoperative follow-up. Risk factors for epilepsy were determined prospectively on at least 3 occasions before anterior temporal lobectomy. Risk factors investigated were a history of febrile convulsions, family history of epilepsy, significant head trauma, history of meningitis, history of encephalitis, or significant perinatal insult. Foreign tissue lesions on magnetic resonance imaging was also included if an anterior temporal lobectomy was performed for presumed dual pathologic findings (hippocampus and lesion). Outcome was determined using Engel's classification. For statistical analysis we used successive logistic regression analysis, chi(2) test, Fisher exact test, and t test. RESULTS: Of the 102 patients, 13 had no identified risk factor for epilepsy, 49 had 1 identified risk factor, and 40 had more than 1. Frequencies were 39 febrile convulsions (15 complex febrile convulsions), 29 head trauma, 22 with lesions seen on magnetic resonance imaging, 12 history of meningitis, 2 history of encephalitis, 19 family history of epilepsy, and 4 perinatal insult. Seventy-one (70%) were classified as Engel's class I, with 56 patients continuously free of seizures at follow-up. Those without risk factor were as likely to be rendered free of seizures following anterior temporal lobectomy as those with a risk factor (P = .27). No risk factor alone or in combination was correlated with complete freedom from seizures following anterior temporal lobectomy, but the presence of head trauma, alone or in combination, was correlated with continued seizures following anterior temporal lobectomy (P = .03; odds ratio, 2.6). Better outcomes were not seen in those with head trauma before the age of 5 years (P = .57). These findings did not change if all those with lesions on magnetic resonance imaging were excluded in the analysis. Those with a history of head trauma were as likely to have pathologic evidence of mesial temporal sclerosis as others (P = .82). CONCLUSIONS: Patients with a history of significant head trauma are less likely to become free of seizures following anterior temporal lobectomy. No other risk factor correlated with a statistically significant greater or lesser chance of freedom from seizures. This information may be used in preoperative counseling of patients.

Adult↗

PubMed1998

Nonconvulsive status epilepticus in the critically ill elderly.

PURPOSE: To describe the electrographic and clinical features of nonconvulsive status epilepticus (NCSE) in the critically ill elderly and to identify potential predictors of outcome. METHODS: We prospectively identified 25 episodes of altered mentation and NCSE in 24 critically ill elderly patients associated with generalized, focal, or bihemispheric epileptiform EEG patterns. Patients with anoxic encephalopathy were excluded. RESULTS: Of 25 hospitalizations, 13 (52%) resulted in death, and 12 (48%) patients survived to discharge. Death was associated with the number of acute, life-threatening medical problems on presentation (survivors, 1.8; fatalities, 2.8; p = 0.013) and with generalized EEG pattern (p = 0.017). Higher doses or greater number of antiepileptic drugs (AEDs) did not improve outcome. Treatment with intravenous benzodiazepines was associated with increased risk of death (p = 0.033). Ten patients with advance directives were managed outside the intensive care unit (ICU). Mean hospitalization was 39 days in the ICU group and 22 for those with advance directives (p = 0.017). CONCLUSIONS: Severity of illness correlates with mortality in critically ill elderly patients with NCSE. Treatment with intravenous benzodiazepines may increase their risk of death. Aggressive ICU management may prolong hospitalization at considerable cost, without improving outcome. It is unclear whether NCSE affects outcome in the critically ill elderly or is merely a marker for severity of disease in predisposed patients. The benefits of aggressive therapy are unclear. Carefully controlled, prospective trials will be necessary to determine the best therapies for NCSE in the critically ill elderly and the appropriate role of the ICU in their management.

Aged↗

PubMed1998

Ictal behaviors during nonepileptic seizures differ in patients with temporal lobe interictal epileptiform EEG activity and patients without interictal epileptiform EEG abnormalities.

PURPOSE: Ictal behaviors during psychogenic nonepileptic seizures (NES) vary considerably among individuals, and can closely resemble common semiologies of epileptic seizures (ES). We tested the hypothesis that behaviors during NES in patients who have temporal spikes would more closely resemble behaviors during ES in patients with temporal lobe epilepsy than would behaviors during NES in patients who do not have EEG spikes. METHODS: We identified 20 patients who had interictal temporal EEG spikes and EEG-video recorded NES (Study Group), 133 patients with temporal EEG spikes and recorded ES, without NES (Epileptic Group), and 24 patients with recorded NES and no epileptiform EEG abnormalities, without ES (Nonepileptic Group). RESULTS: The hypothesis was supported with regard to ictal motor behaviors. Motionless staring or complex automatisms occurred mainly during NES in the Study Group and during ES in the Epileptic Group. In contrast, convulsive movements or flaccid falls were most common during NES in the Nonepileptic Group. Duration of unresponsiveness was longer, and there were fewer postictal states in NES both in the Study and Nonepileptic Groups. Unresponsiveness was briefer and postictal states were more consistent in ES in the Epileptic Group, however. CONCLUSIONS: Stereotyped motor activities during NES presumably represent learned behaviors. Processes underlying acquisition of ictal behaviors of NES probably differ in patients with interictal epileptiform EEG abnormalities compared to those without. Prior experiences and temporal lobe dysfunctions that are associated with epilepsy, and psychological characteristics that are unrelated to interictal epileptic dysfunctions, may determine ictal behaviors during NES.

Adult↗

PubMed1998

Brain blood flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: I. Acute effects at high and low levels of stimulation.

PURPOSE: Left cervical vagus nerve stimulation (VNS) decreases complex partial seizures (CPS) by unknown mechanisms of action. We hypothesized that therapeutic VNS alters synaptic activities at vagal afferent terminations and in sites that receive polysynaptic projections from these medullary nuclei. METHODS: Ten patients with partial epilepsy underwent positron emission tomographic (PET) measurements of cerebral blood flow (BF) three times before and three times during VNS. Parameters for VNS were at high levels for 5 patients and at low levels for 5. Resting BF measurements were subtracted from measurements during VNS in each subject. Subtraction data were averaged in each of 2 groups of 5 patients. t Tests were applied to BF changes in brain regions that receive vagal afferents and projections (significant at p < 0.05, corrected for repeated measures). RESULTS: In both the low- and high-stimulation groups during VNS, brain BF was (a) increased in the rostral, dorsal-central medulla; (b) increased in the right postcentral gyrus, (c) increased bilaterally in the hypothalami, thalami, and insular cortices, and in cerebellar hemispheres inferiorly; and (d) decreased bilaterally in hippocampus, amygdala, and posterior cingulate gyri. The high-stimulation group had greater volumes of activation and deactivation sites. CONCLUSIONS: Our findings suggest that left cervical VNS acutely increases synaptic activity in structures directly innervated by central vagal structures and areas that process left-sided somatosensory information, but VNS also acutely alters synaptic activity in multiple limbic system structures bilaterally. These findings may reflect sites of therapeutic actions of VNS.

Adult↗

PubMed1998

Absence of normal activation of the left anterior fusiform gyrus during naming in left temporal lobe epilepsy.

Patients with left temporal lobe epilepsy (TLE) often have impaired naming. We studied 13 patients with left TLE and 10 healthy control subjects with [(15)O]H2O PET during visual confrontation naming. Statistical mapping detected multiple regions of significant cerebral blood flow increases within individuals. The left fusiform gyrus was activated in nine healthy subjects, but only in two patients with TLE (a significant difference, p < 0.001). Other activation sites were more variable in healthy subjects and those with TLE. Impaired naming ability may be associated with a lack of increased cerebral blood flow in the left fusiform gyrus in TLE.

Adolescent↗

PubMed1998

Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

OBJECTIVE: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. BACKGROUND: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. METHODS: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. RESULTS: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. CONCLUSIONS: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

Adolescent↗

PubMed1998

Neuropharmacological imaging in epilepsy with PET and SPECT.

Functional neuroimaging with positron and single photon emitter-labeling has added considerably to the understanding of epileptic seizure activity and of the postictal and interictal cerebral dysfunctions that accompany many epilepsies. Some of these functional alterations cannot be studied in humans by any other technique, and in other instances the information is complementary to that provided by other techniques, some of which are invasive or even require tissue destruction. Available radiotracer imaging techniques have yet to be fully applied to several important epileptic syndromes (including the Lennox-Gastaut syndrome and other secondary generalized epilepsies), to physiological aspects of the natural history of temporal lobe epilepsy or any other commonly occurring epilepsy, and to the assessment of mechanisms of action and adverse effects of antiepileptic drugs and other epilepsy therapies. New radiotracers should be developed to permit study of specific excitatory amino acid receptors and other receptor sites that are known to be relevant to the development of epilepsy, to the onset of individual seizures, and to interictal dysfunctions.

Brain↗

PubMed1997

Early life stage toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish (Danio rerio).

Toxicity and histopathology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in zebrafish (Danio rerio) early life stages was characterized from 12 to 240 hr postfertilization (hpf) following water-borne exposure of newly fertilized eggs. TCDD did not increase egg mortality (0-48 hpf), nor did it affect time to hatching (48-96 hpf). Egg doses of 1.5 ng [3H]TCDD/g or greater elicited toxic responses in zebrafish larvae. Pericardial edema and craniofacial malformations were first observed at 72 hpf, followed by the onset of yolk sac edema (96 hpf) and mortality (132 hpf). At 240 hpf the ED50s for pericardial edema, yolk sac edema, and craniofacial malformations were 2.2, 2.1, and 1.9 ng [3H]TCDD/g egg, respectively. The LD50, determined at 240 hpf, was 2.5 ng [3H]TCDD/g egg. Severe hemodynamic changes, observed as slowed blood flow in vascular beds of the trunk, head, and gills and slowed heart rate, occurred in TCDD-treated zebrafish prior to or coincident with the onset of gross signs of toxicity. Histological examination of TCDD-treated zebrafish revealed a variety of epithelial tissue lesions including arrested gill development and ballooning degeneration and/or necrosis of the renal tubules, hepatocytes, pancreas, and all major brain regions. Mesenchymal tissue lesions included subcutaneous edema in the head, trunk, and yolk sac, edema of the pericardium and skeletal muscle, and underdevelopment of the swim bladder. This demonstration of zebrafish responsiveness to TCDD early life stage toxicity coupled with the considerable information on developmental biology and genetics of zebrafish provides a foundation for future investigations into the mechanism of TCDD developmental toxicity.

Abnormalities, Drug-Induced↗

PubMed1997

Electrocerebral recovery during the intracarotid amobarbital procedure: influence of interval between injections.

PURPOSE AND METHODS: During the intracarotid amobarbital procedure (IAP) at the University of Michigan, continuous scalp EEG monitoring guides the timing for presentation of memory items and postinjection testing. Most of our patients have undergone bilateral injections. The interval between injections varied from 22 to 60 min, depending on the test and recovery time, as well as the time to catheterize the second side. After noting a trend toward prolonged electrographic recovery following the second injection, we tested our clinical impression that recovery of the second hemisphere may be influenced by (a) the time between injections and (b) which hemisphere is injected first (epileptogenic or nonepileptogenic). To study these questions, we analyzed EEG recovery data from 48 consecutive IAPs. Approximately half the patients had the epileptogenic side injected first. RESULTS: We found that (a) electrographic recovery after the second injection is prolonged if the interval between bilateral injections is less than 40 minutes and (b) electrographic recovery is more rapid after injection of the epileptogenic hemisphere. CONCLUSIONS: We now recommend waiting at least 45 min between injections. The pathophysiology of more prolonged amobarbital effect on the nonepileptogenic hemisphere than on the epileptogenic hemisphere remains unclear.

Amobarbital↗

PubMed1997

Non-epileptic seizures in temporal lobectomy candidates with medically refractory seizures.

Diagnosis of epileptic seizures is often based on temporal lobe epileptiform abnormalities appearing on interictal EEG, when reported ictal semiologies are consistent with temporal lobe seizures. It is unclear how often such patients have non-epileptic seizures. We studied 145 patients who had temporal interictal EEG spikes and reported ictal semiology characteristic of temporal lobe seizures, with long-term EEG-video-monitoring (LTM) for presurgical evaluation of medically refractory seizures. Nonepileptic seizures were unexpectedly recorded in 12 of these patients (8%). Outcomes after LTM in patients who had both epileptic seizures and nonepileptic seizures demonstrated that the epileptic seizures usually were controlled with medications. Our observations support LTM as useful in diagnosis of non-epileptic seizures in this group of patients. We suggest that ictal recordings always should be performed before epilepsy surgery, in part to avoid unintentional surgical treatment of nonepileptic seizures.

Adolescent↗

PubMed1996

Differential mechanisms of cell killing by redox cycling and arylating quinones.

The role of mitochondrial dysfunction in the mechanisms of cell killing by quinones of differing chemical reactivities was investigated. Freshly isolated hepatocyte suspensions were exposed to 2,3-dimethoxy-1,4-naphthoquinone, 2-methyl-1,4-naphthoquinone, 1,4-naphthoquinone or 1,4-benzoquinone in the presence or absence of cyclosporine A, ruthenium red, fructose or the combination of fructose plus oligomycin. All of the quinones caused concentration-dependent cell killing as assessed by the leakage of lactate dehydrogenase. However, only 2,3-dimethoxy- and 2-methyl-naphthoquinone caused a depolarization of mitochondrial membrane potential; cell killing by 1,4-naphthoquinone or 1,4-benzoquinone was not accompanied by mitochondrial depolarization. Neither cyclosporine A nor ruthenium red protected against cell killing or loss of mitochondrial membrane potential caused by any of the quinones examined. In contrast, fructose protected cells against all four quinones. For the redox cycling naphthoquinones, oligomycin reversed the protection afforded by fructose. However, the cytoprotective effect of fructose against the arylating quinones, 1,4-naphthoquinone and 1,4-benzoquinone, was not reversed by oligomycin. The results suggest that cell killing by redox cycling naphthoquinones is a manifestation of mitochondrial depolarization, not ATP depletion. In contrast, the fructose-mediated protection from arylating quinones is consistent with ATP depletion being a critical event leading to cell death. According, although a vast array of quinone compounds are known to be cytotoxic, the mechanism of cell killing by individual members of this chemical class differs and is determined primarily by the chemical reactivity of the individual quinone.

Animals↗

PubMed1996

Intracerebral depth electrode monitoring in partial epilepsy: the morbidity and efficacy of placement using magnetic resonance image-guided stereotactic surgery.

OBJECTIVE: To determine the indications for, efficacy of, and safety of depth electrode placement using magnetic resonance imaging (MRI)-guided stereotactic surgery in patients with intractable epilepsy. METHODS: We analyzed retrospectively the results of depth electrode usage in 50 consecutive patients at the University of Michigan Hospitals studied in the years 1991 through 1994, using MRI-guided stereotactic implantation, in conjunction with simultaneous subdural strip electrode recordings. RESULTS: There were no deaths, no infections, and no new neurological deficits. One small subdural hematoma adjacent to a subdural strip electrode was evacuated to prevent interference with ictal recording. Two cylindrical subdural electrodes were found to be intraparenchymal, as revealed by postoperative MRI, and were removed. One patient was unintentionally left alone briefly, and he pulled out the electrodes while confused postictally, requiring a subsequent operation for replacement. Ictal onset zones were successfully localized in 47 patients. CONCLUSION: We have found intracerebral electrode placement to be as safe as subdural strip electrode placement and have found combined depth and strip electrode monitoring to be highly effective in localizing the onset zones of complex partial seizures. Intracranial monitoring was particularly useful in the detection of a single ictal onset zone in the absence of neuroimaging abnormality and in the definitive diagnosis of bilateral independent ictal onset zones in the temporal lobe epilepsy syndrome. The specific technical aspects of the procedure that contribute to a successful outcome are reviewed. A comparison with earlier reported series suggests that MRI-guided stereotaxy and pial inspection may reduce complications of depth electrode placement.

Brain Mapping↗

PubMed1996

Functional neuroimaging with positron emission tomography.

Epilepsy research using positron emission tomography (PET) has provided considerable new information about ictal and interictal dysfunctions in human epilepsy. Neuroreceptor mapping with PET ligands has revealed altered central benzodiazepine receptor and opiate receptor densities in partial epilepsies interictally, and regional increases in endogenous opioid peptide concentrations during absence seizures. Imaging of perfusion and glucose metabolism during cognitive processing has shown interictal abnormalities of regional activation in partial and generalized epilepsies. The diagnostically robust patterns of interictal glucose hypometabolism are not adequately explained by macrostructural and microstructural alterations in temporal lobe epilepsy. Current investigations of the pathophysiology of interictal hypometabolism must address ultrastructural and neurochemical factors. Clinical PET in presurgical evaluation of medically refractory epilepsies remains an active area of research, but remarkably little antiepileptic drug research has exploited PET techniques.

Anticonvulsants↗

PubMed1995

Enhanced induction of the mitochondrial permeability transition following acute menadione administration.

Induction of the mitochondrial permeability transition in vitro is well-characterized and widely implicated in the mechanism of oxidant-induced cell death. Despite an abundance of in vitro evidence, implication of mitochondrial dysfunction in the mechanism of chemical toxicity in vivo awaits demonstration of the induction of the mitochondrial permeability transition in tissues from intoxicated animals. Menadione (2-methyl-1,4-naphthoquinone), an agent known to induce the permeability transition in isolated liver mitochondrial in vitro, was administered as a single bolus to adult male rats, and hepatic mitochondria were isolated 24 h later. Mitochondria from menadione-treated rats exhibited an increased sensitivity to calcium-induced inhibition of state 3 respiration and loss of respiratory control, as well as a greater sensitivity to calcium-induced calcium release that was inhibited by cyclosporine A. Associated with this was the depolarization of membrane potential and swelling of mitochondria from menadione-treated animals, but not control animals. Both the calcium-dependent depolarization and swelling of mitochondria from menadione-treated rats were inhibited by adding either cyclosporine A or ruthenium red. The results are consistent with the induction of the mitochondrial permeability transition and provide the first evidence for the manifestation of an increased sensitivity to this response as a result of chemical exposure in vivo.

Animals↗

PubMed1995

Differential mechanisms of induction of the mitochondrial permeability transition by quinones of varying chemical reactivities.

A nonspecific increase in permeability of the inner mitochondrial membrane is implicated in the mechanism of cell killing by a number of structurally diverse agents possessing vastly different chemical reactivities. The objective of this investigation was to distinguish the mechanisms by which quinones of varying redox cycling and arylating reactivities induce this mitochondrial permeability transition in vitro. All of the naphthoquinones examined caused a dose-dependent release of calcium from hepatic mitochondria. Associated with this was the calcium-dependent depolarization of membrane potential and mitochondrial swelling. For substituted naphthoquinones, 2-methyl-, 2,3-dimethyl-, and 2,3-dimethoxy-1, 4-naphthoquinone, induction of the mitochondrial permeability transition correlated with the rate of mitochondrial redox cycling and was strongly inhibited by cyclosporine A. In contrast, unsubstituted 1,4-naphthoquinone induced the permeability transition at concentrations where redox cycling was minimal. Induction of the permeability transition by 1,4-benzoquinone, which does not redox cycle, required that the mitochondria be preloaded with calcium and was not inhibited by cyclosporine A. With benzoquinone, the initiating event was a calcium-independent depolarization of mitochondrial membrane potential. In summary, the evidence indicates that redox cycling naphthoquinones induce the mitochondrial permeability transition by altering the regulation of the cyclosporine A-sensitive pore. In contrast, arylating quinones directly depolarize the mitochondrial membrane which, depending on the availability of matrix calcium, may be expressed as a cyclosporine A-insensitive permeability transition. These results reveal distinct mechanisms for inducing the mitochondrial permeability transition in vitro by quinones of varying chemical reactivities, which may be manifested as different mechanisms of cell killing.

Animals↗

PubMed1995

The role of redox cycling versus arylation in quinone-induced mitochondrial dysfunction: a mechanistic approach in classifying reactive toxicants.

In an attempt to distinguish between the mechanisms by which electrophilic and redox cycling quinones induce the cyclosporine A (CyA)-sensitive mitochondrial membrane permeability transition, the ability of a series of quinones that span a broad range of electrophilic and redox cycling reactivities has been examined. The order of potency of quinone-induced Ca2+ release was 1,4-naphthoquinone (NQ) > 1,4-benzoquinone (BQ) > 2-methyl-1,4-naphthoquinone (MQ) > 2,3-dimethoxy-1,4-naphthoquinone (DiOMeNQ) > 2,3-dimethyl-1,4-naphthoquinone (DiMeNQ). Quinones with predominantly redox cycling reactivity, NQ ( < or = 4 microM), MQ, DiOMeNQ and DiMeNQ, induced the CyA-sensitive membrane permeability transition. In contrast, NQ ( > 4 microM) and BQ, induced rapid and complete Ca2+ release and membrane depolarization, but not swelling. Furthermore, BQ and NQ ( > 4 microM)-induced effects were not prevented by CyA. Therefore, we maintain that, unlike MQ, DiOMeNQ, DiMeNQ and NQ ( < or = 4 microM), effects of BQ and NQ( > 4 microM) on calcium flux and membrane potential are manifest via a mechanism independent of altering the regulation of the cyclosporine A-sensitive PTP. These findings suggest that stereoelectronic descriptors for soft electrophilicity and one electron reduction potential may be useful in differentiating and predicting mechanisms of quinone toxicity.

Animals↗

PubMed1995

Channel-specific induction of the cyclosporine A-sensitive mitochondrial permeability transition by menadione.

It is well established that menadione, 2-methyl-1,4-naphthoquinone, impairs the ability of rat liver mitochondria to accumulate and retain calcium. However, it remains unclear whether this reflects inhibition of mitochondrial calcium uptake or stimulation of calcium release by menadione. The purpose of the current investigation was to determine whether interference with mitochondrial calcium homeostasis by menadione reflects a selective activation of the cyclosporine A-sensitive pore, independent of actions on other mitochondrial calcium channels. Mitochondrial calcium flux was monitored using the metallochromic dye arsenazo III. Treatment of mitochondria with menadione caused a concentration-dependent decrease in net calcium accumulation followed by a delayed release of the accumulated calcium and concurrent mitochondrial swelling. Both the maximum steady-state accumulation of calcium and the delay preceding calcium release decreased as a function of calcium concentration. The release of calcium did not occur via the Na+/Ca2+ antiport or reversal of the uptake uniport, as neither diltiazem nor ruthenium red prevented the menadione-stimulated calcium release. In contrast, cyclosporine A, a potent inhibitor of the permeability transition pore, completely inhibited menadione-induced calcium release and the associated swelling. Furthermore, the menadione-induced inhibition of calcium accumulation was completely prevented in the presence of cyclosporine A, indicating a selective stimulation of calcium release by menadione, rather than inhibition of calcium uptake. These data provide the first definitive description of a specific action of menadione to stimulate mitochondrial calcium release through a cyclosporine A-sensitive pathway, independent of altering the regulation of other recognized calcium channels associated with the inner mitochondrial membrane.

Animals↗

PubMed1995

Effects of propofol sedation on seizures and intracranially recorded epileptiform activity in patients with partial epilepsy.

BACKGROUND: Case reports suggesting both pro- and anticonvulsant effect(s) of propofol have been published in recent years. The effects of sedative doses of propofol on epileptiform activities in patients suffering from intractable partial epilepsy were systematically investigated. METHODS: Fourteen patients suffering from complex partial seizures were studied. Electroencephalogram (EEG) was recorded from intracranial electrodes implanted in the hippocampi and temporal neocortex. Propofol was given as a computer-controlled infusion in four steps to achieve target plasma propofol concentrations of 0.3, 0.6, 0.9, and 1.2 micrograms/ml. Each concentration was maintained for 30 min, and steady-state kinetics were confirmed by blood levels drawn at 10th and 30th min at each level. Between the 15th and 30th min of each concentration of propofol, EEG was analyzed for presence of electroencephalographic seizure activity and/or number of interictal spikes (IIS). Effects of propofol on IIS frequency at different electrode sites were compared using a two-way repeated measures analysis of variance. A value of P < 0.05 was considered significant. RESULTS: None of the patients developed a seizure during the 2 h of propofol infusion. No "false spikes" (spikes developing with propofol infusion in areas where no spikes were seen in baseline EEG) were seen. Although effects of propofol on IIS frequency were highly variable across patients and at different propofol doses in the same patient, there was no statistically significant effect of propofol on any electrode site with any of the doses studied. CONCLUSIONS: We were unable to demonstrate a significant change in epileptiform activity with sedative doses of propofol in patients suffering from complex partial epilepsy.

Adult↗