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PubMedDate not supplied

Summating-potential/action-potential ratio in normal ears: effects of dehydration.

INTRODUCTION: Studies using electrocochleography (ECoG) in patients with Meniere's disease and in patients with perilymph fistula have demonstrated abnormally large summating-potential (SP) components compared with the amplitude of the action-potential (AP). The possible influence of normal physiological variation, methodological differences, and test-retest variations are often difficult to interpret. The purpose of this study is to specify what constitutes a clinically important change in the SP/AP ratio in normal hearing subjects under the condition of dehydration induced by urea. MATERIALS AND METHODS: Baseline ECoG was performed on 20 normal hearing volunteer subjects after an 8 hour fast. Urea, 20 g, was administered orally, following which recordings were made at 60 and 90 minutes. The majority of subjects were found to have maximal SP/AP changes at 60 minutes post dehydration; therefore, only these results were included in the final analysis. Subsets of data were statistically evaluated. RESULTS: In all ears but one, the preingestion SP/AP ratio was less than or equal to 0.37. Male and female data were shown to comprise separate populations both before and following dehydration. The 95% upper limit for baseline SP/AP ratio was 0.39 for males and was 0.25 for females. The gender-related difference remained after dehydration. The mean male SP/AP ratio showed a statistically significant but slight decrease whereas the female SP/AP ratio was unaltered. CONCLUSION: These data demonstrate a statistically significant gender-related difference in SP/AP ratio in normals. The upper limit of normal is 0.39 for males and 0.25 for females. A basis for the gender difference is puzzling and requires further investigation. Dehydration produces a statistically significant reduction in SP/AP ratio in men. This change was not observed in women.

Action Potentials↗

PubMed1991

Are 5-HT2 antagonists endowed with anxiolytic properties in rodents?

The precise role of serotonin (5-HT) in anxiety remains unclear. We report here on the effects of RP 62203, a new 5-HT2 antagonist, and ritanserin in different animal models of anxiety. In the elevated plus-maze in mice, RP 62203 increased dose-dependently the percentage of entries onto, and time spent on open arms, over the dose range 0.25-4 mg.kg-1 p.o. By contrast, ritanserin was ineffective up to the dose of 4 mg.kg-1 p.o. In addition, both compounds were tested against the anxiogenic compound FG 7142 (20 mg.kg-1, i.p.) in the plus-maze test in mice and via electrocorticographic recordings (ECoG) in rats. The anxiolytic effect of RP 62203 is antagonized by FG 7142 at a dose devoid of anxiogenic properties. A similar interaction between RP 62203 and FG 7142 is observed in ECoG studies. In contrast, ritanserin seemed to potentiate the anxiogenic and awakening activities of FG 7142. These results demonstrate that RP 62203, a selective 5-HT2 antagonist, possesses anxiolytic properties in rodents suggesting that 5-HT2 receptors are involved in the control of anxiety.

Animals↗

PubMed1991

Biological actions of beta-hydroxy-l-glutamic acid, a synthesized structural analogue of glutamic acid.

1. Biological actions of beta-hydroxy-L-glutamic acid (BHGA), a synthesized analog of L-glutamic acid (Glu), were examined using voltage-clamp, electrophysiological and binding assay techniques. 2. Application of BHGA to the voltage-clamped snail neurons elicited an inward current which was blocked by Na(+)-free saline but not by Co(2+)-substituted Ca(2+)-free saline in the voltage-clamped snail neurons. 3. This response exhibited a potency about 10 times stronger than Glu, and was not completely blocked by DL-2-amino-5-phosphonovaleric acid or kynurenic acid. 4. Intraventricular injection of BHGA caused burst discharges in the electrocorticograph (ECoG) of rats whose pattern was similar to that elicited by Glu, but quite different from the ECoG charges induced by NMDA, quisqualic acid, or kainic acid. 5. Receptor binding assays using specific radioactive ligands showed that the binding affinity of BHGA to the Glu receptor was different from that of other agonists tested.

Animals↗

PubMed1996

Analysis of outcome in patients reirradiated for brain metastases.

PURPOSE: Patients with newly diagnosed brain metastases generally benefit from whole brain radiation therapy (WBRT). However, the role of reirradiation for patients who develop progressive brain metastases has been controversial. This retrospective study examines our experience with reirradiation of patients for progressive brain metastases after an initial+ course of WBRT. METHODS AND MATERIALS: From 1975-1993, 2658 patients received WBRT for brain metastases at our institution. Eighty-six patients were subsequently reirradiated for progressive brain metastases. The median age of these patients was 58 (range: 31-81). The most common primary sites were breast and lung. Fifty patients had metastatic disease at other sites. Most patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 (40 patients) or 3 (38 patients). The median dose of the first course of irradiation was 30 Gy (range: 1.5-50.6 Gy). The median dose of the second course of irradiation was 20 Gy (range: 8.0-30.6 Gy). RESULTS: Twenty-three patients (27%) had resolution of neurologic symptoms, 37 patients (43%) had partial improvement of neurologic symptoms, and 25 patients (29%) had either no change or worsened after reirradiation. The median survival following reirradiation was 4 months (range: 0.25-72 months). The majority of patients had no significant toxicity secondary to reirradiation. Five patients had radiographic abnormalities of their brain consistent with radiation-related changes. One patient had symptoms of dementia that was thought to be caused by radiotherapy. Various potential prognostic factors were evaluated for possible associations with survival, including age, sex, primary site, ECOG performance status, RTOG neurologic functional class, absence of extracranial metastases, and dose of irradiation. Absence of extracranial metastasis, solitary brain metastasis, and retreatment dose > 20 Gy were associated with improved survival in univariate analysis (p=0.025, 0.033, and 0.061, respectively). The absence of extracranial disease was the only significant factor in multivariate analysis (p=0.05). CONCLUSION: The majority of patients in our series had favorable symptomatic responses. Clinically significant complications were minimal. Reirradiation should be offered to patients who develop progressive brain metastases.

Adult↗

PubMed1982

Delta opiate receptors are involved in the endopioid-induced myoclonic contractions.

Morphine, the prototype mu opiate receptor agonist, decreased the spontaneous and [D-Ala2]-Met-enkephalinamide (DALA)-induced myoclonic contractions (MC) of submandibular muscles in the anaesthetized rat. The proposed kappa receptor agonists ketocyclazocine, ethylketocyclazocine and bremazocine failed to induce MC. In addition, bremazocine inhibited the spontaneous and DALA induced MC. Cyclazocine, the so-called sigma opiate receptor agonist, had a weak potency in generation of MC, but without step dose response tendency. The most potent opioid peptide in inducing the MC and electrocortical (ECoG) epileptic pattern was the delta opiate receptor agonist [D-Ala2,D-Leu5]-enkephalin (DADL). All drugs were administered intraventricularly. The results indicate that myoclonic phenomena induced by DADL and probably by other endopioids are mediated by delta opiate receptors in the rat brain. It is suggested that the combined ECoG and EMG method used in this study offers an opportunity to define further the biological role of opiate receptors and to identify the potential delta opiate receptor acting drugs, which might provide a new approach to the therapy of some seizure disorders.

Analgesics↗

PubMed1994

Age-related electrocorticographic and respiratory adaptation to repeated hypoxia.

Severe hypoxia is known to produce depression in electrical brain activity and perturbation of respiratory pattern. In piglets undergoing chronic recording of brain and respiratory muscle activities, a depressed electrocorticogram (ECoG) was observed in response to rapidly induced (< 30 s), brief (10 min), and moderate hypoxia (10% O2 in 90% N2) in 16 out of 42 study sessions in young (3- to 11-day-old) animals only. Responses to hypoxia were monitored over 4 consecutive days. In five cases, the latency to the onset of the ECoG depression increased progressively over the 4 test days, and its duration decreased progressively. An associated respiratory gasping pattern also exhibited gradual remission over consecutive days. These changes in the responses to repeated hypoxia demonstrate adaptation of mechanisms underlying neuronal perturbation by oxygen deprivation.

Adaptation, Physiological↗

PubMed1995

Adenosines scavenged hydroxyl radicals and prevented posttraumatic epilepsy.

Intracortical injection of iron ions has been used as a model of posttraumatic epilepsy. Oxidation of lipids in neural membranes by reactive oxygen species, especially hydroxyl radicals (OH), is involved in the mechanisms responsible for iron-induced seizures. We examined the scavenging effects of adenosine (Ado) and 2-chloroadenosine (Cl-Ado) on OH radicals and superoxide (O2.-) using an electron spin resonance (ESR) spectrometer, and the occurrence of epileptic discharges in electrocorticogram (ECoG) induced by FeCl3 injection into the sensorimotor cortex of rats. Though DMPO-O2.- spin adducts generated by the hypoxanthine-xanthine oxidase system were not quenched by Ado or Cl-Ado, 5 mM of each showed a quenching effect on DMPO-OH spin adducts (5.3 x 10(16) spins/ml) generated by the Fenton reagent. In ECoG of rats, spike discharges appeared 15-45 min after FeCl3 injection (500 nmol) into the sensorimotor cortex, and polyspikes and/or ictal patterns were observed 70-90 min after the injection. Cl-Ado (1 mg/kg) or Ado (5 mg/kg) injected intraperitoneally 30 min prior to the FeCl3 injection suppressed or delayed the occurrence of epileptic discharges induced by FeCl3. Cl-Ado and Ado may suppress the occurrence of epileptic discharges by scavenging OH and by their anticonvulsant effect.

2-Chloroadenosine↗

PubMed1995

Response of human epileptic temporal lobe cortical blood flow to hyperventilation.

Bilateral long-term surface cortical cerebral blood flow (CBF) and electrocorticographic (ECoG) monitoring were performed in eight patients with complex partial seizures. In each patient, the epileptic temporal lobe was localized using ictal ECoG. Mean seizure interval (frequency-1) off anticonvulsant medication, a clinical measure of epileptogenicity, was 1.0 +/- 0.3 h (range: 0.4 to 2.5 h). During 13 interictal hyperventilation periods, 3.6 +/- 0.6 min in duration, the mean decrease in epileptic and nonepileptic temporal cortical CBF was 13.7 +/- 2.3 versus 6.4 +/- 1.9 ml/(100 g min) (t = 2.230, d.f. = 16, P < 0.05), representing 20.9% and 10.8% reduction from baseline CBF during hyperventilation, respectively. Seizure interval decreased (i.e. frequency increased) with increasing magnitude of seizure focus CBF reduction during hyperventilation. Seizure interval was significantly correlated with epileptic temporal lobe CBF decrease during hyperventilation (R = 0.763, d.f. = 5, P < 0.05). The data suggest that, compared to nonepileptic brain, epileptic temporal lobe is particularly prone to hypoperfusion during hyperventilation. Epileptogenicity is a function of this seizure focus susceptibility to ischemia. The finding of abnormal seizure focus autoregulation during hyperventilation has implication for epileptic focus localization with cerebral blood flow analysis.

Adolescent↗

PubMed1992

Can Karnofsky performance status be transformed to the Eastern Cooperative Oncology Group scoring scale and vice versa?

There is no consensus regarding the equivalence of performance status between the Karnofsky (KPS) and the Eastern Cooperative Oncology Group (ECOG) scales. In the present study KPS and ECOG scores were compared in 150 consecutive cancer patients. An empirical relation was established through regression analysis in a subsample of 75 patients and the results tested in the second subsample. Transformation tables including 95 and 66% confidence intervals were calculated. Both performance scales are highly correlated, but inferences about individual patients were subject to a high level of error. These results stress the difficulty of translating one score to another, especially in the range of lower performance status where a wide spread is observed.

Adult↗

PubMed2006

Video-assisted thoracic surgery pulmonary resection for lung cancer in patients with poor lung function.

BACKGROUND: The aim of this study is to evaluate the early outcome of patients with poor lung function who underwent video-assisted thoracic surgery (VATS) pulmonary resection for primary non-small cell lung carcinoma. METHODS: We reviewed retrospectively the records of patients with lung cancer undergoing VATS lung resection over a period of 5 years. Twenty-five patients with preoperative poor lung function defined as forced expiratory volume in 1 second less than 0.8 L or the percentage predicted value for forced expiratory volume in 1 second less than 50% were identified. Thirteen patients underwent VATS lobectomies and 12 VATS wedge resections. Data were analyzed with respect to demographics, risk factors, and early postoperative outcome and survival. RESULTS: There were 8 cases of morbidities (29%) and no surgical mortality. Five of these 8 patients had respiratory-related complications after surgery. A deterioration in pulmonary performance as indicated by the Eastern Cooperative Oncology Group (ECOG) score was seen in 7 patients (28%), with only 1 patient having an ECOG score greater than 2. No patient required home oxygen supplementation beyond the third month postoperatively. After a median follow-up period of 15.1 months (range, 1 to 24), 5 patients died. Only 1 patient (4%) died of a respiratory complication (pneumonia 6 weeks after surgery). The other 4 deaths were due to recurrent or metastatic disease. The actuarial survival rates at 1 and 2 years were 80% and 69%, respectively. CONCLUSIONS: Video-assisted thoracic surgery pulmonary resection for cancer in patients with poor lung function can achieve acceptable functional and oncologic outcome.

Aged↗

PubMed2006

Corticotropin-releasing factor neurons in the hypothalamic paraventricular nucleus are involved in arousal/yawning response of rats.

Our previous studies have suggested that activation of the hypothalamic paraventricular (PVN) descending oxytocinergic projections is involved in the induction of yawning accompanied by an arousal response, but the possibility that neural systems other than the oxytocinergic system in the PVN also mediate the arousal/yawning response cannot be ruled out. We assessed the activity of corticotropin-releasing factor (CRF) neurons during yawning induced by the PVN stimulation in anesthetized, spontaneously breathing rats using double-staining for c-Fos and CRF. Yawning response was evaluated by monitoring an intercostals electromyogram as an index of inspiratory activity and a digastric electromyogram as an indicator of mouth opening. We also recorded the electrocorticogram (ECoG) to determine the arousal response during yawning. Microinjection of l-glutamate (2-5 nmol) into the PVN produced a frequent yawning accompanied by an arousal shift in the ECoG, and these behavioral effects were associated with a significant increase of c-Fos positive CRF neurons in the medial parvocellular subdivision of the PVN. In addition, a marked enhancement in the c-Fos expression was found in the both locus coeruleus (LC) and global area in the cortex when the frequency of yawning response was increased by the PVN stimulation, suggesting that the arousal response during yawning might be mediated by the activation of LC neurons. The present study suggests that an activation of CRF neurons in the PVN is responsible for the arousal response accompanied by yawning behavior.

Analysis of Variance↗

PubMed2004

Cortical control of generalized absence seizures: effect of lidocaine applied to the somatosensory cortex in WAG/Rij rats.

The role of the somatosensory cortex (SmI) in the incidence of spike-wave discharges (SWDs) was studied in a genetic model of absence epilepsy, WAG/Rij rats. SWDs were recently shown to initiate at the perioral area of the SmI and spread over the cortex and thalamus within a few milliseconds [J. Neurosci. 22 (2002) 1480]. It was hypothesized that functional deactivation of the SmI might reduce the appearance of SWDs. This was tested using unilateral microinjections (1 microl) of 2% lidocaine into the SmI in 13 WAG/Rij rats. Electrocorticogram (ECoG) was recorded in free moving animals from four cortical sites after lidocaine and control (saline) injections. Lidocaine effectively diminished the power of the ECoG spectra mostly in the area surrounding the injection site. Deactivation of the perioral region of the SmI reduced the incidence of SWDs at the entire cortex in both hemispheres. The number of SWDs gradually reached control level at the end of the second hour after injections of lidocaine. These data show that proper functioning of SmI is important for the occurrence of SWDs, supporting the idea that absence seizures might have a focal cortical origin.

Animals↗

PubMed2006

Anticonvulsant effects of melatonin on penicillin-induced epileptiform activity in rats.

In the present study, we investigated the effects of melatonin on penicillin-induced epileptiform activity in female Wistar rats. The left cerebral cortex was exposed by craniotomy under urethane anesthesia for the induction of epilepsy by intracortical microinjection of penicillin (200 IU) into the left sensorimotor cortex. The epileptiform activity was analyzed by electrocorticogram (ECoG). Ten minutes before the penicillin injection, 20, 40 or 80 microg of melatonin was administered intracerebroventricularly and ECoG was monitored for 1 h. Forty or 80 microg of melatonin significantly increased the latency to epileptiform activity. Furthermore, melatonin significantly decreased the frequency of spike and spike-wave activity, whereas the amplitude of spikes remained unchanged. In conclusion, data obtained from the present study suggest that melatonin suppresses penicillin-induced epileptiform activity, and it may be an endogenous anticonvulsant.

Action Potentials↗

PubMed2005

Acute and subchronic effects of lead on the central and peripheral nervous systems in rats in combination with alcohol.

Humans are exposed, either simultaneously or sequentially, to various chemicals, including the neurotoxicants lead and ethanol. The aim of the present work was to investigate the changes in the spontaneous cortical activity (electrocorticogram; ECoG) and in the stimulus-dependent evoked potentials (EPs) recorded from rats pre-treated with alcohol and treated with lead acutely (intraperitoneally) or subchronically (by gavage). The measured parameters were spectral composition of the ECoG, amplitude and the latency of the stimulus-evoked cortical potential, as well as compound action potential amplitude, conduction velocity, and relative and absolute refractory period in a peripheral nerve. With subchronic lead and alcohol treatment, significant increase in the frequency of spontaneous activity and slight decrease in the EP amplitude were seen. In acute administration, EP amplitude increased and conduction velocity of the tail nerve decreased significantly. Our results showed that, in a combined exposure situation which is likely to happen also in humans, the known effects of neurotoxic heavy metals can be more severe.

Administration, Oral↗

PubMedDate not supplied

Impulse response function based on multivariate AR model can differentiate focal hemisphere in temporal lobe epilepsy.

The purpose of this study is to propose and investigate a new approach for discriminating between focal and non-focal hemispheres in intractable temporal lobe epilepsy, based on applying multivariate time series analysis to the discharge-free background brain activity observed in nocturnal electrocorticogram (ECoG) time series. Five unilateral focal patients and one bilateral focal patient were studied. In order to detect the location of epileptic foci, linear multivariate autoregressive (MAR) models were fitted to the ECoG data; as a new approach for the purpose of summarizing these models in a single relevant parameter, the behavior of the corresponding impulse response functions was studied and described by an attenuation coefficient. In the majority of unilateral focal patients, the averaged attenuation coefficient was found to be almost always significantly larger in the focal hemisphere, as compared to the non-focal hemisphere. Also the amplitude of the fluctuations of the attenuation coefficient was significantly larger in the focal hemisphere. Moreover, in one patient showing a typical regular sleep cycle, the attenuation coefficient in the focal hemisphere tended to be larger during REM sleep and smaller during Non-REM sleep. In the bilateral focal patient, no statistically significant distinction between the hemispheres was found. This study provides encouraging results for new investigations of brain dynamics by multivariate parametric modeling. It opens up the possibility of relating diseases like epilepsy to the properties of inconspicuous background brain dynamics, without the need to record and analyze epileptic seizures or other evidently pathological waveforms.

Adult↗

PubMed2006

Relationship between age at diagnosis and clinicopathologic features of renal cell carcinoma.

OBJECTIVES: To analyse the influence of age at diagnosis on tumour characteristics and cancer-specific survival in renal cell carcinoma (RCC). METHODS: Data on age, tumour characteristics, and survival for 4774 patients from 12 European RCC databases were recorded. Patients were divided into four groups according to age at diagnosis: < or =40, >40 and <60, > or =60 and <80, and > or =80 yr. The following variables were analysed: TNM stage, Fuhrman grade, tumour size, symptoms at diagnosis, ECOG performance status (PS), and cancer-specific survival. The groups were compared for usual clinical and pathologic variables, and cancer-specific survival. RESULTS: The four groups accounted for 288 (6%), 1839 (38.5%), 2499 (52.3%), and 148 cases (3.2%), respectively. Differences were found among groups for tumour stage, symptoms at diagnosis, ECOG PS, Fuhrman grade (p<0.001), tumour size, M stage, and histologic subtype (p: 0.02). Patients < or =40 yr were more likely to have papillary or chromophobe RCCs and less likely to have clear-cell RCCs. No significant difference was found among groups for N stage (p: 0.15). The 5-yr cancer-specific survival rates for the four age categories were 85%, 74%, 70%, and 69%, respectively. In multivariate analysis age category remained an independent prognostic parameter (p<0.001). CONCLUSIONS: Renal tumours diagnosed in younger age are characterized by lower tumour stages and grades as well as favourable histologic patterns compared with tumours in older patients. Basic research is required for explaining such a relationship between age, tumour aggressiveness, and therefore tumour biology.

Adult↗

PubMed2004

A combination of distribution- and anchor-based approaches determined minimally important differences (MIDs) for four endpoints in a breast cancer scale.

OBJECTIVE: To determine distribution- and anchor-based minimal important difference (MID) estimates for four scores from the Functional Assessment of Cancer Therapy-Breast (FACT-B): the breast cancer subscale (BCS), Trial Outcome Index (TOI), FACT-G (the general version), and FACT-B. STUDY DESIGN AND SETTING: We used data from a Phase III clinical trial in metastatic breast cancer (ECOG study 1193; n=739) and a prospective observational study of pain in metastatic breast cancer (n=129). One third and one half of the standard deviation and 1 standard error of measurement were used as distribution-based criteria. Clinical indicators used to determine anchor-based differences included ECOG performance status, current pain, and response to treatment. RESULTS: FACT-B scores were responsive to performance status and pain anchors, but not to treatment response. By combining the results of distribution- and anchor-based methods, MID estimates were obtained: BCS=2-3 points, TOI=5-6 points, FACT-G=5-6 points, and FACT-B=7-8 points. CONCLUSION: Distribution- and anchor-based estimates of the MID do show convergence. These estimates can be used in combination with other measures of efficacy to determine meaningful benefit and provide a basis for sample size estimation in clinical trials.

Adult↗

PubMed2006

Travelling waves and EEG patterns during epileptic seizure: analysis with an integrate-and-fire neural network.

Epilepsy is characterized by paradoxical patterns of neural activity. They may cause different types of electroencephalogram (EEG), which dynamically change in shape and frequency content during the temporal evolution of seizure. It is generally assumed that these epileptic patterns may originate in a network of strongly interconnected neurons, when excitation dominates over inhibition. The aim of this work is to use a neural network composed of 50 x 50 integrate-and-fire neurons to analyse which parameter alterations, at the level of synapse topology, may induce network instability and epileptic-like discharges, and to study the corresponding spatio-temporal characteristics of electrical activity in the network. We assume that a small group of central neurons is stimulated by a depolarizing current (epileptic focus) and that neurons are connected via a Mexican-hat topology of synapses. A signal representative of cortical EEG (ECoG) is simulated by summing the membrane potential changes of all neurons. A sensitivity analysis on the parameters describing the synapse topology shows that an increase in the strength and in spatial extension of excitatory vs. inhibitory synapses may cause the occurrence of travelling waves, which propagate along the network. These propagating waves may cause EEG patterns with different shape and frequency, depending on the particular parameter set used during the simulations. The resulting model EEG signals include irregular rhythms with large amplitude and a wide frequency content, low-amplitude high-frequency rapid discharges, isolated or repeated bursts, and low-frequency quasi-sinusoidal patterns. A slow progressive temporal variation in a single parameter may cause the transition from one pattern to another, thus generating a highly non-stationary signal which resembles that observed during ECoG measurements. These results may help to elucidate the mechanisms at the basis of some epileptic discharges, and to relate rapid changes in EEG patterns with the underlying alterations at the network level.

Computer Simulation↗