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PubMed2003

Superior colliculus stimulation enhances neocortical serotonin release and electrocorticographic activation in the urethane-anesthetized rat.

Recent evidence indicates that the superior colliculus (SC), in addition to its functions in sensory detection, also participates in controlling the generalized activation state of the forebrain, as measured by the electroencephalogram (EEG) or electrocorticogram (ECoG). The mechanisms by which the SC modulates forebrain activation are not well understood. By using in vivo microdialysis, we examined the role of serotonin release as a mechanism by which the SC can control neocortical activity in the urethane-anesthetized rat. Electrical 100 Hz stimulation of the SC increased frontal cortex serotonin output to 116, 118, and 140% of baseline levels for stimulation intensities of 0.5, 0.75, and 1.0 mA, respectively. Further, 75% of extracellularly recorded single (putative serotonergic) dorsal raphe neurons increased their discharge rate in response to 100 Hz stimulation of the SC. Stimulation of the SC also suppressed frontal cortex low frequency (1-6 Hz) synchronized ECoG activity, replacing it with high-frequency desynchronization. This activation response was resistant to cholinergic-muscarinic receptor antagonists (atropine, 50 mg/kg; scopolamine, 2 mg/kg), but was reduced or abolished by systemic treatment with the serotonergic receptor antagonists ketanserin (10 mg/kg) or methiothepin (5 mg/kg). These data suggest that efferents from the SC, possibly by an excitatory action on serotonergic dorsal raphe cells, produce an enhanced release of serotonin and ECoG activation in the neocortex. The stimulation of cortical serotonin output may constitute a mechanism by which the SC acts on the forebrain to increase cortical excitability in response to sensory stimuli processed by SC neurons.

Animals↗

PubMed1998

Thiopental induced cerebral protection during ischemia in gerbils.

Temporary interruption or reduction of cerebral blood flow during cerebrovascular surgery may rapidly result in ischemia or cerebral infarction. Thiopental has been shown to have cerebroprotective effects. However, the cerebroprotective dose of thiopental causes burst suppression of the EEG, thus this parameter cannot be used continuously for the detection of metabolic changes in the brain during thiopental anaesthesia. This study was performed in order to examine whether the multiparametric assembly (MPA), which measures energy metabolism CBF and mitochondrial (NADH) as well as extracellular ion concentrations (K+), can shed light on the mechanism of the cerebroprotective effects of thiopental. The MPA was placed on the brain of Mongolian gerbils and burst suppression of the ECoG was induced by thiopental. Cerebral ischemia was induced by occlusion of carotid arteries after burst suppression. Burst suppression of the ECoG was accompanied by a significant decrease in cerebral blood flow. In animals that received thiopental prior to ischemia, NADH increased to a lesser degree and extracellular potassium ion concentration increased to a lesser degree than in the control animals, indicating that thiopental affords protection of the brain under ischemic conditions due to improved energy metabolism. This study also demonstrates that the MPA can monitor changes occurring in the cerebral cortex even after the ECoG can no longer be used. Those findings have a significant value in the development of a new clinical monitoring device.

Animals↗

PubMed1999

Neuroprotective effect of L-lysine monohydrochloride on acute iterative anoxia in rats with quantitative analysis of electrocorticogram.

Lysine is one of the indispensible amino acids and L-lysine monohydrochloride (LMH) is widely available to public as a nonprescription oral supplement. Potential clinical usefulness of oral LMH supplements has been indicated in stroke, hypertension, and seizure induced by pentylenetetrazole (PTZ), etc. We compared the effects of LMH and flunarizine on the Electrocorticogram (EcoG) of rats intragastrically administered 1 hour before anoxia. LMH dose-dependently prolonged the time reaching the lowest ECoG average amplitude after anoxia and decreased the recovery time after recirculation in both 0.63 g/kg and 1.26 g/kg groups. There was significant difference between the LMH- and saline-pretreated groups but no significant difference between the 1.26 g/kg LMH- and 2.5 mg/kg flunarizine-pretreated groups. The difference was not significant in the 2.52 g/kg group. The ECoG average amplitude did not reach isoelectric point and the lowest average amplitude was 10 percent of that of nomoxia in the 1.26 g/kg LMH-pretreated group during 2-min anoxia. The average amplitude pretreated with LMH (0.63 and 1.26 g/kg) was lower than that of those pretreated with saline and flunarizine. The results tend to indicate that LMH can protect brain cells against anoxia by means of providing energy, reducing cerebral metabolic rate and inhibiting the effect of the excitable amino acids.

Animals↗

PubMed2002

Brain electrical activity during combined hypoxemia and hypoperfusion in anesthetized rats.

In order to investigate the effects of moderate hypoxemia on brain electrical activity and the consequences of an altered cerebro-vascular response to hypoxemia, we recorded changes in electrical activity of the brain in anesthetized rats following unilateral carotid artery ligation (UCAL). In these animals, on the clamped side, cerebral blood flow, whilst normal during normoxia, shows less augmentation during hypoxemia. Six anesthetized (Halothane) Sprague-Dawley rats with UCAL were studied during 20 min periods of baseline (FI(O(2))=30%), hypoxemia (FI(O(2))=9.5%) and recovery (FI(O(2))=30%): mean arterial pressure of oxygen (PA(O(2))) achieved was 177.0, 37.6 and 160.1 mmHg, respectively. A significant decrease in the frequencies of the ECoG was observed bilaterally during hypoxemia: centroid frequency (fc)=3.37+/-0.14 and 2.85+/-0.13 Hz on the intact and clamped hemisphere respectively during hypoxemia versus fc=4.09+/-0.20 Hz (mean+/-S.E.M.) during baseline, which was not reversed during recovery (3.27+/-0.11 Hz) (ANOVA, P<0.01). The total power of the signal (Pw) was unaffected on the intact hemisphere but diminished on the clamped side during hypoxemia. Our results show that a significant slowing of ECoG is observed during hypoxemia of moderate intensity (40 mmHg) even when cerebro-vascular response to hypoxemia is preserved and that total power of the ECoG signal is severely diminished when the cerebro-vascular response to hypoxemia is impaired.

Animals↗

PubMed2000

Melanoma. A multidisciplinary approach for the general surgeon.

Advances in the understanding of the biology and treatment of melanoma have moved the care of melanoma patients into an increasingly multidisciplinary environment. Surgeons must understand these advances because they will often be responsible for directing the overall care of these patients. Most patients with melanomas more than 1 mm in diameter and no evidence of metastatic disease should be offered SLNB to more accurately stage them and direct decisions about participation in postoperative adjuvant therapy trials. Until the results of the MSLT are known, the effect of SLNB and ELND on outcome remains unknown. SLNs should be analyzed with serial sectioning and immunohistochemistry to avoid missing micro-metastatic disease. Based on the results of the ECOG-1684 trial, the FDA approved IFN-alpha 2b for the adjuvant treatment of melanoma patients with thick primary tumors (> 4 mm) or resected nodal disease. IFN-alpha 2b treatment is expensive and potentially toxic. The data from ECOG-1684 do not support the use of IFN-alpha 2b in patients with node-negative disease. In light of the ECOG-1690 trial results, the role of high-dose IFN-alpha 2b in the management of patients with resected nodal disease is considerably less clear. Any recommendations for treatment with high-dose IFN-alpha 2b should be made only after weighing the costs, side effects, and potential benefits for individual patients. Numerous, less toxic, promising, adjuvant immunotherapeutic strategies have been developed and are being tested in multicenter, prospective, randomized trials. These strategies include GMK, PMCV, and Melacine. If the results of any of these trials show a survival advantage compared with placebo or equivalent survival compared with IFN-alpha 2b, these immunotherapeutic agents will become the adjuvant treatment of choice for patients with resected high-risk melanoma. RT-PCR detection of tyrosinase in SLNs can identify patients with submicroscopic nodal disease who may be at increased risk for recurrence or death from melanoma. An ongoing, prospective, randomized trial will determine whether patients with histologically negative but RT-PCR-positive SLNs will benefit from lymphadenectomy or adjuvant IFN-alpha 2b therapy. RT-PCR can also identify minimal residual disease in peripheral blood and bone marrow from patients with high-risk melanoma, but RT-PCR analysis of peripheral blood and bone marrow is still experimental, and procedural details need to be standardized and prospectively validated in large patient groups before its use can be considered the standard of care.

Chemotherapy, Adjuvant↗

PubMed1998

In-flight electrocorticograms compared to ground controls in behaving monkeys: differences in attentional states?

Electrocorticographic recordings were taken from the posterior parietal cortical area in monkeys performing a variety of tasks on ground and in space flight. The question addressed here was whether ECoG analysis would be a reliable index of attention to the learned task. It is shown that measuring the instantaneous frequency, rather than instrumentally evaluating the spectral content of the ECoG, may provide useful information on the attentional states of the animals. Investigations on Rhesus performed in Paris provided a useful database to evaluate the more complex results obtained in the Russian experiments with space flights, during which, according to the ECoG marker, some attentional disorders occurred. It is not unreasonable to envisage using similar evaluation in the scalp EEG in human flights in the future.

Animals↗

PubMed2000

Spatial spectral analysis of human electrocorticograms including the alpha and gamma bands.

Spatial spectral analysis is essential for deriving spatial patterns from simultaneous recordings of electrocorticograms (ECoG), in order to determine the optimal interval between electrodes in arrays, and to design spatial filters, particularly for extraction of information about the dynamics of human gamma activity. ECoG were recorded from up to 64 electrodes 0.5 mm apart in a linear array 3.2 cm long, which was placed on the exposed superior temporal gyrus or motor cortex of volunteers undergoing diagnostic surgery. Visual displays of multiple traces revealed broad spectrum oscillations in episodic bursts having a common aperiodic wave form with recurring patterns of spatial amplitude modulation (AM patterns) on selected portions of the array. The one-dimensional spatial spectrum of the human ECoG was calculated at successive time samples and averaged over periods of up to 20 s. Log power decreased monotonically with increasing log spatial frequency in cycles/mm (c/mm) to the noise level approximately 2 log units below maximal power at minimal frequency (0.039+/-0.002 c/mm). The inflection point at 0.40+/-0.05 c/mm specified an optimal value for a low pass spatial filter to remove noise, and an optimal interelectrode spacing of 1.25 mm to avoid undersampling and aliasing. An 8 x 8 array with that spacing would be 10 x 10 mm.

Adolescent↗

PubMed1997

The effects of 'sleep promoting agents' on behavioural state in the ovine fetus.

Fetal behavioural states, with similarities to adult sleep states, exist in both the human and ovine fetus near term. The purpose of the present study was to determine the effects of intracerebral administration of pharmacologic agents, known to affect sleep states in the adult, on fetal behavioural states and physiologic correlates using the chronically catheterized ovine fetus near term. Each drug was infused into either the cisterna magna or lateral ventricle for 90 min in one of two doses. Carbachol (1.35 x 10(-5) and 4.25 x 10(-6) M) led to an increase in low-voltage ECOG, eye movement and FBM activities, while scopolamine (4.68 x 10(-4) and 1.56 x 10(-4) M) led to a decrease in low-voltage ECOG and eye movement activity with an increase in high-voltage ECOG activity. L-5-Hydroxytryptophan (5-HTP) (2.04 x 10(-3) and 6.81 x 10(-4) M) infusion led to an increase in FBM, while VIP (3.00 x 10(-7) and 1.00 x 10(-7) M) infusion had no effect on fetal behavioural state parameters. Study results indicate that fetal behavioural states can be altered pharmacologically and in a manner similar to that seen in the adult but with notable differences that may relate to species, developmental or dose-response issues.

5-Hydroxytryptophan↗

PubMed1997

Carotid blood flow changes with behavioral states in the late gestation llama fetus in utero.

This study tested the hypothesis that in the llama fetus changes in cerebral blood flow are closely associated with changes in cerebral oxidative metabolism such as occur during transitions between electrocortical states. For the first time reported in any species, instantaneous changes in common carotid blood flow, employed as a continuous index of cerebrovascular perfusion, were related to instantaneous changes in electrocortical activity. Three late gestation fetal llamas were surgically prepared under general anesthesia with vascular catheters, a tracheal and amniotic catheter, and with electrodes implanted to monitor the fetal electrocorticogram (ECoG). In addition, Transonic flow probes were placed around a common carotid artery and a femoral artery. At least 4 days after surgery fetal arterial blood, amniotic and tracheal pressures, carotid and femoral blood flows and the fetal ECoG were recorded continuously. Our results suggest a close association between increases in common carotid blood flow and low voltage ECoG in the llama fetus. Close coupling between instantaneous changes in carotid blood flow and electrocortical states together with the lack of an increase in brain blood flow without increased cerebral oxygen extraction during hypoxemia in the llama fetus supports a fall in cerebral oxidative metabolism in this species during hypoxemic episodes.

Animals↗

PubMed2002

Cortical arousal induced by microinjection of orexins into the paraventricular nucleus of the rat.

Orexin-A is a neuropeptide which has been suggested to be involved in sleep and arousal mechanisms. Orexin-A, for example, stimulates arousal when administrated intracerebroventricularly to rats. We attempted to identify specific neural sites of orexin-A and orexin-B action. Orexin-A and orexin-B were microinjected into the medial parvocellular subdivision of the paraventricular nucleus (PVN) in anesthetized, spontaneously breathing rats, and cortical arousal and yawning responses were assessed. Cortical arousal responses were monitored with the electrocorticogram (ECoG), and yawning responses were evaluated by monitoring intercostal electromyograms as an index of inspiratory activity and digastric electromyograms as an indicator of mouth opening. We also measured blood pressure and heart rate during yawning responses, since yawning is accompanied by changes in autonomic activity. Microinjection of orexin-A into the PVN elicited an arousal shift in the ECoG to lower voltage and faster rhythms. This cortical arousal response was followed by a single large inspiration with mouth opening, i.e. a yawning response. On the other hand, microinjection of orexin-B into the PVN elicited an arousal shift in the ECoG without yawning responses. These results demonstrate that an orexin receptive site for triggering arousal/yawning responses exists in the PVN, and suggest that the PVN is involved in arousal mechanisms.

Animals↗

PubMed1992

Effects of mediodorsalis thalamic nucleus lesions on vigilance and attentive behaviour in cats.

In this study performed on 10 cats we analysed the effects of limited lesions of nucleus medialis dorsalis of the thalamus (MD) on behaviour and on some specific electrocorticographic (ECoG) patterns, known from previous works to accompany various states of waking attentiveness. The animals were tested during 90 min in three distinct behavioural situations; a neutral one (NS) where they simply explored their environment and then usually went to sleep; a second one (FA) where they could watch a mouse (but not catch it), which favoured 'focussed' attentiveness accompanied by the development of rhythmic ECoG activities in the anterior frontoparietal cortex ('beta rhythms' at 40 Hz); a third one (EX) with a hidden mouse whose appearance the cat was waiting for ('expectancy') which rather than favouring the development of beta rhythms elicited the appearance of another rhythmic activity dominating in somatic area SI, 'mu rhythms' at 14 Hz. The duration of each waking behaviour and its ECoG concomitant as well as that of slow wave and of paradoxical sleep were compared in each cat before and after lesion. Our results showed that MD lesions situated in the posterior part of the nucleus tended to increase the time occupied by focussed attentive behaviour and the accompanying beta rhythms. On the other hand, anteriorly located MD lesions elicited a concomitant reduction of both manifestations, behavioural and electrocortical. No such contrasting effects could be systematically noticed for the durations of expectancy, of slow sleep and of paradoxical sleep. These findings were discussed considering previous data showing that at least two systems project upon MD, that play distinct--in a way even antagonistic--roles in focussed attention upon a target. Both originate from the ventral tegmental mesencephalic area; one reaches MD through the ventral striatum (nucleus accumbens), the other one through the amygdala. The MD nucleus thus receiving contrasting information may participate in a final adjustment of the attentive state of the animal to its environment.

Animals↗

PubMed1989

Effect of DSP4, a neurotoxic agent, on attentive behaviour and related electrocortical activity in cat.

Six behaving cats were administered N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) (i.p. 10 mg/kg), a neurotoxic agent known to destroy noradrenergic endings in the CNS. They were placed, both before (control) and after treatment in 3 different situations, each time for 90 min: (1) a 'neutral' one (N) with no significant stimuli; (2) another one eliciting focused attention (F); (3) a third one, creating a situation of 'expectancy of an event to occur' (E), with the animal usually displaying a posture of quiet waking. Simultaneously, the electrocorticogram (ECoG) was recorded from the sensorimotor and parietal cortex through implanted electrodes. We already knew and were able to confirm that the normal animals (i.e. before treatment) displayed distinct behavioural patterns depending on the situation and distinct accompanying parietofrontal ECoG activities, with a dominance of drowsiness and sleep during N, that of a 36-Hz 'beta' rhythms in condition F, and of 14-Hz 'mu' rhythms in condition E. It was shown that the prevailing attitude of the animals after treatment was now, in all 3 situations, that of 'quiet waking and/or expectancy-like watching', with a large if not exclusive dominance of only one ECoG pattern, namely mu. These changes were considered as due to a release of the mu system from a noradrenergic modulatory blockade, in accordance with some of our previous data. An immunohistochemical study with anti-tyrosine hydroxylase antibody was also performed; it confirmed that after DSP4 treatment there were substantial alterations in the immunoreactivity of locus coeruleus cells, the structure which is likely to be involved in this NAergic control of the mu rhythms and of its concomitant behaviour.

Animals↗

PubMed2003

Sleep spindles in human prefrontal cortex: an electrocorticographic study.

To investigate the sleep spindle activity of the human prefrontal cortex (PFC), we simultaneously recorded whole nights of polysomnographic and electrocorticographic (ECoG) activities during the natural sleep of epileptic patients. Subjects were nine patients with intractable epilepsy who had subdural electrodes surgically attached to the orbital (seven cases), medial (three cases), or dorsolateral (two cases) PFC, and in one case to the frontal pole. To examine spindle frequencies, fast Fourier transformation (FFT) and auto-correlation analyses were performed on the PFC ECoG and Cz EEG data, primarily on epochs of stage 2 sleep. Lower sigma band ECoG oscillations of about 12 Hz were widely distributed across all prefrontal cortical areas including the frontal limbic regions, but none of the PFC sigma frequency peaks coincided with the faster (about 14 Hz) Cz EEG sleep spindles. Combining our results with anatomical and electrophysiological facts, it is suggested that the thalamofrontal circuit involving the rostral reticular and the mediodorsal nucleus of the thalamus is responsible for the generation of 12 Hz frontal spindles in humans.

Adult↗

PubMedDate not supplied

Palliative and therapeutic activity of IL-2 immunotherapy in unresectable malignant pleural mesothelioma with pleural effusion: Results of a phase II study on 31 consecutive patients.

Malignant pleural mesothelioma is often unresectable at diagnosis, is refractory to cytotoxic agents and is frequently complicated by pleural effusion. The expected survival range for patients with or without involvement of visceral pleura is respectively 1-9 and 9-12 months; mesothelioma-related pleural effusion severely impairs the patients' quality of life and easily relapses after conservative treatments. Intrapleural administration of IL-2 is reported to be effective both in tumor-associated malignant pleurisy and on primary mesothelioma, whereas few data exist about IL-2 systemic administration. In order to assess the palliative and therapeutic activity of IL-2 in unresectable pleural malignant mesothelioma with pleural effusion, we performed a phase II study on 31 consecutive patients (M/F 16/15; median age 61 years, range 40-84; PS ECOG 0 n=7; ECOG 1 n=15; ECOG 2 n=9; stage IA n=13; IB n=9; II n=7; IV=2) who received first-line therapy with intrapleural repeated instillation of 9000000 I.U. IL-2 twice/weekly for 4 weeks, after needle thoracenthesis. In nonprogressing patients, 3000000 I.U. IL-2 were subcutaneously administered thrice weekly for up to 6 months. Toxicity (WHO criteria) with intrapleural IL-2 consisted of grade 3 fever in 6/31 (19%) patients and of cardiac toxicity (failure) grade 3 in one patient (3%); toxicity during subcutaneous treatment was mild to moderate, mainly a flu-like syndrome. In 28/31 (90%) of patients there was no further or minimal (asymptomatic) pleural fluid collection (according to Paladine criteria); pleurisy relapsed only in 1/28 patients after 19 months. Tumor objective response (WHO criteria), evaluated by CT, occurred in seven patients (one CR and six PR; ORR 22%); ten patients achieved SD and 14 patients progressed. Median overall survival was 15 months (range 5-39) in all patients. IL-2 intrapleural administration followed by low-dose IL-2 subcutaneously in pleurisy-complicated malignant mesothelioma is feasible and active both in palliation of pleural effusion and on primary tumor, with manageable toxicity. The overall survival observed in nonprogressing patients warrants further randomized studies with IL-2 aimed to the patient outcome.

Adult↗

PubMed2002

Does chemotherapy have a role as palliative therapy for unfit or elderly patients with non-small-cell lung cancer?

Elderly patients and younger "unfit" patients with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) (> or = 2) suffering from advanced non-small-cell lung cancer (NSCLC) are two different populations--both of which require palliative treatments. Elderly patients frequently experience progressive decline of organ function and multiple comorbidities, which need to be considered when choosing therapy. ECOG 1594 showed that advanced NSCLC patients with an ECOG PS of 2 did not tolerate platinum-based chemotherapy (cisplatin/paclitaxel, carboplatin/paclitaxel, cisplatin/docetaxel, carboplatin/paclitaxel). These data confirm that treatments designed specifically for this patient subset are needed. Single-agent chemotherapy seems to be a reasonable approach, and non-platinum-based combination chemotherapy should also be investigated. The oncology community has become increasingly aware of the magnitude of the problem of cancer in the elderly. More than 30% of lung cancers arise in patients > or = 70 years old. Elderly patients tolerate chemotherapy poorly, according to the few published papers, and are not considered eligible for aggressive cisplatin-based chemotherapy in clinical practice. A phase III randomized trial (ELVIS [Elderly Lung Cancer Vinorelbine Italian Study]) demonstrated survival and quality-of-life benefits with single-agent vinorelbine versus best supportive care. Among the newer drugs, gemcitabine has demonstrated activity and low toxicity in phase II studies. With this background, we performed a randomized, multicenter phase III trial (MILES [Multicenter Italian Lung Cancer in the Elderly Study]) in 707 advanced NSCLC elderly patients. The MILES study compared single-agent chemotherapy with vinorelbine or gemcitabine versus polychemotherapy with gemcitabine plus vinorelbine. Results showed no benefit in response rate, time to progression, survival, and quality of life for the combination. Single-agent chemotherapy remains the standard treatment approach for elderly NSCLC patients with advanced disease.

Aged↗

PubMedDate not supplied

Changes in power and coherence of brain activity in human sensorimotor cortex during performance of visuomotor tasks.

Electrocorticograms (ECoG) were recorded using subdural grid electrodes in forearm sensorimotor cortex of six human subjects. The subjects performed three visuomotor tasks, tracking a moving visual target with a joystick-controlled cursor; threading pieces of tubing; and pinching the fingers sequentially against the thumb. Control conditions were resting and active wrist extension. ECoGs were recorded at 14 sites in hand- and arm-sensorimotor area, functionally identified with electrical stimulation. For each behavior we computed spectral power of ECoG in each site and coherence in all pair-wise sites. In three out of six subjects, gamma-oscillations were observed when the subjects started the tasks. All subjects showed widespread power decrease in the range of 11-20 Hz and power increase in the 31-60 Hz ranges during performance of the visuomotor tasks. The changes in gamma-range power were more vigorous during the tracking and threading tasks compared with the wrist extension. Coherence analysis also showed similar task-related changes in coherence estimates. In contrast to the power changes, coherence estimates increased not only in gamma-range but also at lower frequencies during the manipulative visuomotor tasks. Paired sites with significant increases in coherence estimates were located within and between sensory and motor areas. These results support the hypothesis that coherent cortical activity may play a role in sensorimotor integration or attention.

Epilepsy↗

PubMed2002

Failure of T stage to predict survival in patients with non-small-cell lung cancer treated by radiotherapy with or without concomitant chemotherapy.

PURPOSE: Because T stage does not consistently reflect tumor size in non-small-cell lung cancer (NSCLC), we hypothesized that T stage may be of limited prognostic value in patients with locoregional NSCLC treated by nonsurgical means. METHODS AND MATERIALS: The study population consisted of 243 patients with histologically or cytologically proven NSCLC treated in three consecutive prospective trials between 1989 and 1998. The eligibility criteria for this analysis included planned for and began treatment at 60 Gy; Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; weight loss < or = 10%; no prior treatment; and no supraclavicular nodes, pleural effusion, or distant metastases. In the first study, 204 patients were randomized to receive conventional or accelerated radiotherapy (RT) with or without concomitant carboplatin. In the second, 15 patients were treated with concomitant cisplatin, etoposide, and RT in a single-arm study. In the third, 24 patients were treated with concomitant carboplatin, 5-fluorouracil, and RT in a dose-escalation study. RESULTS: A total of 231 patients for whom the T and N stage were known met the eligibility criteria. The patient characteristics were 77% male, 64% squamous histologic features, 33% ECOG status of 0, and 69% no weight loss. The nodal status was 36% N0, 7% N1, 52% N2, and 5% N3. The estimated median survival for all patients was 1.4 years (95% confidence interval 1.2-1.6), with an estimated 10% surviving 5 years (95% confidence interval 7-15). No significant difference was found in survival among the three trials (p = 0.16). The estimated median survival time and 5-year survival rate according to T stage were as follows: T1 (n = 29), 1.6 years and 16%; T2 (n = 88), 1.3 years and 9%; T3 (n = 59), 1.4 years and 9%; and T4 (n = 55), 1.4 years and 9%. No significant trend was found in overall survival according to T stage (p = 0.85, log-rank). To test whether a significant effect of T stage on overall survival existed after adjusting for N stage, trial, ECOG status, and weight loss, a multifactor analysis using Cox proportional hazards regression analysis was carried out. There was still no significant effect of T stage on survival (p = 0.66) when all factors were taken into account. CONCLUSION: Although there is some evidence that T stage is an independent prognostic factor in patients with NSCLC treated surgically, it did not appear to be of value in this series of patients treated with RT with and without concomitant chemotherapy.

Adult↗

PubMed1999

Intrinsic epileptogenicity of focal cortical dysplasia as revealed by magnetoencephalography and electrocorticography.

Focal cortical dysplasia (FCD) is often associated with severe partial epilepsy. In this study, we performed magnetoencephalography (MEG) and electrocorticogrsphy (ECoG) on four patients with FCD-associated epilepsy to confirm the 'intrinsic' epileptogenicity of FCD. In all patients, we determined the three-dimensional locations of the magnetic sources of the interictal paroxysmal activities by a single dipole model, and then the estimated dipole localization was superimposed on the magnetic resonance image. The dipole clusters were located in the T2-prolonged lesions, namely in the FCD lesions themselves. All patients underwent surgery for their medically intractable epilepsy, and the acute and/or chronic ECoG were thereafter recorded. Either frequent or continuous paroxysmal activities were recorded from the ECoG electrodes which were placed over the surface of the FCD lesion, while few paroxysmal activities were observed on the normal appearing adjacent cortex. Intraoperative depth recordings were performed in a patient with the needle electrode inserted into the FCD lesion and they revealed these paroxysmal foci to be located not on the cortical surface but at a depth of 15 mm from the cortical surface where both abnormal giant neurons and bizarre large eosinophilic cells (so-called balloon cells) were also prominently observed on the postoperative histological sections. Following a lesionectomy combined with the removal of the underlying white matter, three patients demonstrated a favorable seizure outcome. Our findings thus suggest the FCD lesions to be highly and intrinsically epileptogenic lesions.

Adult↗