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At least 757 records · Page 42Linked to original sources

PubMed2005

Docetaxel and cyclooxygenase-2 inhibition with celecoxib for advanced non-small cell lung cancer progressing after platinum-based chemotherapy: a multicenter phase II trial.

PURPOSE: To assess the overall and progression-free survival, response rate, and toxicity of combined docetaxel and celecoxib in the treatment of patients with non-small cell lung cancer progressing after initial chemotherapy for advanced disease. PATIENTS AND METHODS: Patients with non-small cell lung cancer and either measurable or evaluable disease experiencing progression after one or more platinum-based chemotherapy regimens given for advanced or metastatic disease, ECOG performance status 0-2, and adequate hematologic and biochemistry parameters were eligible for study inclusion; exclusion criteria included symptomatic brain metastases and full dose anti-coagulation. Therapy consisted of docetaxel 75 mg/m(2) every 21 days for a maximum of six cycles and celecoxib 400 mg orally twice daily commencing 7 days prior to docetaxel and continuing until disease progression. RESULTS: A total of 41 patients were enrolled of whom 39 were deemed eligible and received at least one course of docetaxel. The mean age of enrolled patients was 60.5 years (range, 44-77); 67% were men and 79% white. All but one patient had an Eastern Clinical Oncology Group (ECOG) performance status of 0 or 1. Most (72%) had been treated with a prior taxane. Overall survival was 11.3 months (95% confidence interval [CI]: 7.9, 15.7) and progression-free survival 19.6 weeks (95% CI: 13.5, 25.0). A response rate of 10.2% (95% CI: 3%, 24%) for all eligible and treated patients was found. Grade 3 or 4 neutropenia occurred in 10/39 patients (25.6%); one death due to neutropenic sepsis occurred. No grade 3 or 4 renal or hepatic toxicities were documented. CONCLUSION: Treatment with combination celecoxib and docetaxel is a safe regimen with a toxicity profile similar to that of docetaxel alone. Survival data are encouraging compared to historical controls and may prolong time to disease progression compared with single-agent docetaxel.

Administration, Oral↗

PubMed2005

Asian ethnicity and adenocarcinoma histology continues to predict response to gefitinib in patients treated for advanced non-small cell carcinoma of the lung in North America.

Institutional series suggest specific subgroups of patients with non-small cell lung cancer (NSCLC); female, Asian, non-smokers, respond preferentially to gefitinib. Vancouver, BC, has a large Asian population and therefore is an ideal location to study this differential effect in a Western setting. We performed a retrospective analysis of patients treated with single agent gefitinib to determine if our experience reflects this observation. The pathology, radiology, laboratory investigations and clinical records of 61 patients treated with gefitinib at the BCCA between April 2002 and May 2004 were reviewed. Partial radiologic response was defined as per SWOG response criteria. Symptom responses were subjectively evaluated from chart review. Baseline characteristics at diagnosis; 62% Caucasian, 38% Asian, male 47%, smokers 67%, non-smokers 33%, ECOG 0/1 59%; tumor histology: 57% adenocarcinoma, 13% bronchoalveolar variant, 7% squamous, 23% other. Median treatment duration was 2 months. On radiologic review, 14 patients had a partial response, 25 had stable disease, 21 progressed, and 1 unknown. Twenty patients reported improved symptoms after>/=1 month, 23 had no change, 17 had symptom progression and 1 unknown. Toxicity was minimal; one patient had grade 3 hepatotoxicity that resolved with treatment cessation. Of the 14 radiological responders, 10 were Asian, 10 ECOG 0/1, 10 female, 8 non-smokers, 8 adenocarcinoma and 4 bronchoalveolar variant. At the BCCA, in a select number of patients with advanced NSCLC, gefitinib demonstrated radiologic evidence of anti-tumor activity and provided clinical benefit with minimal side effects. Most of the responders were patients of Asian ethnicity who had immigrated to Canada from China, Taiwan or Hong Kong. Our results suggest that the preferential response to gefitinib seen in the Asian population is preserved in a Western setting. The molecular basis of the improved response rate observed in the subset of female, Asian, non-smokers with adenocarcinoma or bronchoalveolar variant is currently being explored by gene sequencing studies at the British Columbia Cancer Agency Genome Science Centre.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2006

Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial.

BACKGROUND: Gefitinib has demonstrated activity in patients with non-small cell lung cancer (NSCLC). Clinical trials have not demonstrated a relationship between response to gefitinib and over-expression of the epidermal growth factor receptor (EGFR). Although, EGFR is not over-expressed in small cell lung cancer (SCLC), we postulated that gefitinib might affect tumor growth through other mechanisms. Agents that are active in NSCLC usually are also effective in SCLC. METHODS: The primary objective was to assess the clinical control rate: complete response (CR) partial response (PR) and stable disease (SD > 90 days), of gefitinib in patients with chemo-resistant and chemo-sensitive small cell cancers. Eligibility criteria included pathologic proof of a neuroendocrine tumor, especially small cell cancer, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, prior treatment with one or two prior chemotherapy regimens and adequate end-organ function. Patients received gefitinib, 250 mg p.o. daily until disease progression or intolerable side effects. RESULTS: From April 2003 to March 2004, 19 patients were enrolled. Small cell lung cancer accounted for 18 of the 19 patients and one patient had metastatic Merkel cell carcinoma. Twelve patients (63%) had chemo-sensitive disease, defined as progression greater than three months from completion of prior chemotherapy; 7 (37%) had chemo-refractory disease; 13 (68%) had one prior chemotherapy regimen. Other patient characteristics: mean age 64 years (range 52-79 years); ECOG PS 0/1/2 = 7/9/3, M:F = 9:10. Grade 3 toxicities included: fatigue in three patients (15.8%), pulmonary toxicities in three (15.8%) and one patient (5.3%) each with hyperglycemia or pain. Four patients had grade four toxicities: one patient (5.3%) with fatigue and three patients (15.8%) with dyspnea. There were no patients with grade 3 or 4 rash or diarrhea. Two patients had stable disease (<90 days) and 17 had progressive disease as their best response. This study was a two-stage design and because the continuing criterion for stage one was not met, stage 2 was not performed. Median time to progression (TTP) was 50 days (95% CI = 21-58 days). One year overall survival (OS) was 21% (95% CI = 6-45.6%). CONCLUSION: Although gefitinib has activity in select patients with NSCLC, this study failed to demonstrate benefit in patients with small cell lung cancer.

Aged↗

PubMed2006

A phase I/II trial of weekly docetaxel and gefitinib in elderly patients with stage IIIB/IV non-small cell lung cancer.

BACKGROUND: Phase III trials in elderly patients with advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC) reveal treatment with single agent chemotherapy improves survival. The role of double agent therapy in this patient population is an area of investigation. METHODS: A phase I/II trial was performed in elderly patients (age>or=70 years) with stage IIIB/IV disease and Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients were treated with gefitinib 250 mg daily. Patients received docetaxel on a treatment schedule of days 1, 8, 15 of an every 28 days schedule. The phase I portion of the trial consisted of dose escalation docetaxel from 30 to 36 mg/m2 using a three patient cohort design. The trial design contained continuous monitoring for excessive toxicity with pre-selected toxicity boundaries. RESULTS: Twenty-six patients were evaluable for efficacy and toxicity analysis. The median age was 75.5 years. The majority of the patients had stage IV disease (85%), ECOG functional status of 0-1 (81%), were male (65%), and current or former smokers (88%). Eleven patients experienced National Cancer Institute Common Toxicity Criteria grades 3-5 non-hematologic toxicity during the first cycle. The toxicity was determined to be unexpected, and the trial was discontinued. Overall response rate (complete+partial responses) was 31%, and the median survival was 6.5 months (95% confidence interval (CI) (3.6-9.0)), and estimated 1-year survival rate was 27% (95% CI (13-55%)). CONCLUSIONS: The combination of weekly docetaxel and gefitinib had activity; however, unexpected toxicity was observed in the elderly patient population.

Aged↗

PubMed2004

Theta oscillation in the human anterior cingulate cortex during all-night sleep: an electrocorticographic study.

Ten epileptic patients each with subdural electrodes surgically attached to the anterior cingulate cortex (ACC; two cases), the orbitofrontal cortex (OFC; seven cases), or both (one case) were included in this study. We recorded each patient's ACC or OFC electrocorticogram (ECoG) during the time period that the patient was awake and naturally asleep. We performed a Fast Fourier Transformation (FFT) power spectral analysis on each ECoG to examine its frequency component. We found that the ACC showed regular and continuous theta oscillation (5-7Hz) during wakefulness and rapid eye movement (REM) sleep, but not during slow wave sleep. Theta waves observed in REM sleep were not as distinct as those found in wakefulness. We also discovered that the orbitofrontal signals represented spectral peaks in the theta band only during wakefulness. This suggests the coexistence of theta oscillation in the ACC. Considering our previous observations of gamma and beta oscillations in the human hippocampus, we hypothesize that the human limbic system manifests two oscillatory activities. The results obtained in this study suggest that electrophysiological activity in the ACC could be related to particular psychological functions in wakefulness and in REM sleep. These results are useful in elucidating the human brain mechanism.

Adult↗

PubMed2005

Trends in the diagnosis and the management of Meniere's disease: results of a survey.

OBJECTIVE: To determine the practices of the American Neurotology Society (ANS) membership in the evaluation and treatment of the Meniere's patient. STUDY DESIGN: Prospective. INTERVENTION: Questionnaire. MAIN OUTCOME MEASURE: Respondents' response to questions pertaining to the diagnostic and therapeutic practices in the management of Meniere's disease. RESULTS: Three hundred members of ANS were mailed a 15-item questionnaire. Two hundred three responded, for a 67.7% response rate. For the diagnosis of Meniere's disease, 1 in 3 practitioners relied solely on history, physical exam, and audiometry, whereas 2 in 3 relied in part on adjunctive tests, such as electrocochleography (ECOG) and electronystagmography (ENG). Two in 3 practitioners pursued retrocochlear studies on initial evaluation, with the overwhelming majority using MRI. In treating Meniere's disease, conservative medical management was preferred. For medically recalcitrant Meniere's disease, endolymphatic sac surgery (ESS) was the most commonly employed initial intervention (50%), followed by transtympanic gentamicin (38%). Currently, <10% routinely recommend the Meniett device. Eighty-three percent include ESS as a therapeutic option for medically recalcitrant Meniere's disease. The vast majority continue to perform surgical labyrinthectomies and vestibular nerve sections for Meniere's disease. CONCLUSIONS: Meniere's disease continues to pose a difficult diagnostic and therapeutic problem, resulting in heterogeneous approaches to both evaluation and treatment. Despite the 1995 American Academy of Otolaryngology guidelines in the diagnosis of Meniere's disease, most clinicians rely in part on ENG or ECOG in diagnosing Meniere's disease. Furthermore, despite the passing of 20 years since the publications claiming a purely placebo effect, ESS is the most commonly employed initial surgical treatment for Meniere's disease.

Audiometry, Evoked Response↗

PubMed2006

Analysis of synchrony demonstrates 'pain networks' defined by rapidly switching, task-specific, functional connectivity between pain-related cortical structures.

Imaging studies indicate that experimental pain is processed in multiple cortical areas which are often characterized as a network. However, the functional connectivity within the network and the other properties of the network is poorly understood. Substantial evidence demonstrates that synchronous oscillations between two cortical areas may indicate functional connectivity between those areas. We test the hypothesis that cortical areas with pain-related activity are functionally connected during attention to a painful stimulus. We stimulated with a painful, cutaneous, laser stimulus and recorded the response directly from the cortical surface (electrocorticography--ECoG) over primary somatosensory (SI), parasylvian (PS), and medial frontal (MF) cortex through subdural electrodes implanted for treatment of epilepsy. The results demonstrate synchrony of ECoGs between cortical structures receiving input from nociceptors, as indicated by the occurrence of laser-evoked potentials (LEPs) and/or event-related desynchronization (ERD). Prior to the stimulus, directed attention to the painful stimulus consistently increased the degree of synchrony between SI and PS regions, as the subject anticipated the stimulus. After the laser stimulus, directed attention to the painful stimulus consistently increased the degree of synchrony between SI and MF cortex, as the subject responded by counting the stimulus. Therefore, attention to painful stimuli always enhanced synchrony between cortical pain-related structures. The pattern of this synchrony changed as the patient switched tasks from anticipation of the stimulus to counting the stimulus. These results are the first compelling evidence of pain networks characterized by rapidly switching, task-specific functional connectivity.

Adult↗

PubMed2004

Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model of juvenile absence epilepsy.

The succinic semialdehyde dehydrogenase (SSADH) null mouse represents a viable animal model for human SSADH deficiency and is characterized by markedly elevated levels of both gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acid (GABA) in brain, blood, and urine. GHB is known to induce absence-like seizures and absence seizures have been reported to occur in children with SSADH deficiency. We tested the hypothesis that the phenotype of the SSADH(-/-) mouse shows absence-like seizures because of the inordinately high levels of GHB in the brain of this mutant animal. Sequential electrocorticographic (ECoG) and prolonged video ECoG recordings from chronically implanted electrodes were done on SSADH(-/-), SSADH(+/-), and SSADH(+/+) mice from postnatal day (P) 10 to (P) 21. Spontaneous, recurrent absence-like seizures appeared in the SSADH(-/-) during the second week of life and evolved into generalized convulsive seizures late in the third week of life that were associated with an explosive onset of status epilepticus which was lethal. The seizures in SSADH null mice were consistent with typical absence seizures in rodent with 7 Hz spike-and-wave discharge (SWD) recorded from thalamocortical circuitry, the onset/offset of which was time-locked with ictal behavior characterized by facial myoclonus, vibrissal twitching and frozen immobility. The absence seizures became progressively more severe from P14 to 18 at which time they evolved into myoclonic and generalized convulsive seizures that progressed into a lethal status epilepticus. The absence seizures in SSADH(-/-) were abolished by ethosuximide (ETX) and the GABA(B)R antagonist CGP 35348. The seizure phenotype in the SSADH(-/-) recapitulates that observed in human SSADH deficiency. Hence, SSADH(-/-) may be used to investigate the molecular mechanisms that underpin the pathogenesis of absence and generalized tonic-clonic seizures associated with SSADH deficiency. As well, the SSADH(-/-) may represent a unique animal model of the transition from absence to myoclonic and generalized convulsive seizures that is observed in up to 80% of patients with juvenile absence epilepsy.

Aldehyde Oxidoreductases↗

PubMed2004

Surgical treatment of temporal lobe epilepsy associated with subcortical ectopic gray matter under the guidance of intraoperative electrocorticography.

We describe a dual pathology presenting as intractable temporal lobe epilepsy associated with subcortical ectopic gray matter. The patient was a 28-year-old male with a 12-year history of refractory temporal lobe epilepsy. Preoperative diagnostic imaging revealed right hippocampal sclerosis, in addition to subcortical ectopic gray matter extending from the posterior end of the inferior horn of the right lateral ventricle to the cerebral parenchyma in the temporoparietal lobe. As surgical therapy for epilepsy, right anterior temporal lobectomy with amygdalohippocampectomy was initially performed. Intraoperative electrocorticography (ECoG) was extremely useful at this point in determining the range of excision of ectopic gray matter after resection of mesial temporal lobe structures. Based on ECoG findings, about 50% of the ectopic gray matter was excised. As of 2 years postoperatively, the patient has remained seizure free with no medication. In cases concomitantly manifesting hippocampal sclerosis and subcortical ectopic gray matter, epilepsy may be associated with dual pathology. This case report raises the potentially important issue of the possible presence of areas of structural abnormality that are non-epileptogenic.

Adult↗

PubMed2005

Microdialysis of the lateral and medial temporal lobe during temporal lobe epilepsy surgery.

BACKGROUND: This study was undertaken to establish whether, in temporal lobe epilepsy (TLE), there are relative differences between the lateral and ipsilateral medial temporal lobe in the extracellular levels of 3 of the human brain's major neuroactive amino acids. METHODS: Seven generally anesthetized patients with TLE undergoing anatomically standardized resective surgery had at operation microdialysis catheters inserted within the middle temporal gyrus (ie, lateral temporal lobe) and anterior hippocampus (ie, medial temporal lobe). Surface electrocorticography (ECoG) recordings were also obtained. Samples of 10-minute dialysate were quantified for glutamate, aspartate, and gamma-aminobutyric acid (GABA) using high-performance liquid chromatography; corresponding ECoG data were assessed for epileptiform activity. Where available, resection tissue was subjected to histopathological analysis. RESULTS: The ratio of mean "sample 3" dialysate levels of glutamate, aspartate, and GABA was approximately 20:2:1, respectively, in both the minimally epileptiform lateral (n = 7) and medial (n = 5) temporal lobe; between the 2 sets of samples, these levels were not significantly different (P > 0.05 for each amino acid studied). From the vigorously epileptiform medial temporal lobe of 2 patients, sample 3 dialysate levels of the excitatory amino acids glutamate and aspartate were found in considerably greater concentrations (between 15- and 37-fold) with correspondingly less dramatic increases of the inhibitory amino acid GABA (more than 11- and 13-fold). Laterally resected tissue (obtained in 3 cases) did not demonstrate significant cortical or subcortical abnormalities; medial resection tissue from all patients demonstrated, in varying degrees, hippocampal sclerosis. CONCLUSIONS: In the absence of significant tissue hyperexcitability, despite known differences in local cellular and/or histopathological architecture, the extracellular relationship among glutamate, aspartate, and GABA is not dissimilar in both the lateral and ipsilateral medial temporal lobe of TLE patients. Considerable disparity in dialysate levels recovered (eg, from the vigorously epileptiform medial temporal lobe) may be related to the functional (ie, hyperexcitable) status of the sampled tissue.

Action Potentials↗

PubMed2005

Anticonvulsant treatment of sarin-induced seizures with nasal midazolam: an electrographic, behavioral, and histological study in freely moving rats.

Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 +/- 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsant effect (53 +/- 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA resulted in brain damage. The addition of scopolamine to midazolam did not alter the above observation. In summary, nasal midazolam treatment briefly after initiation of OP-induced seizure leads to cessation of EGSA and prevented brain lesions and behavioral deficiencies in the rat model.

Administration, Intranasal↗

PubMed2000

Mediastinal lymph node dissection improves survival in patients with stages II and IIIa non-small cell lung cancer. Eastern Cooperative Oncology Group.

BACKGROUND: Mediastinal lymph node dissection (MLND) is an integral part of surgery for non-small cell lung cancer (NSCLC). To compare the impact of systematic sampling (SS) and complete MLND on the identification of mediastinal lymph node metastases and patient survival, the Eastern Cooperative Oncology Group (ECOG) stratified patients by type of MLND before participation in ECOG 3590 (a randomized prospective trial of adjuvant therapy in patients with completely resected stages II and IIIa NSCLC). METHODS: Eligibility requirements for study entry included a thorough investigation of the mediastinal lymph nodes with either SS or complete MLND. The former was defined as removal of at least one lymph node at levels 4, 7, and 10 during a right thoracotomy and at levels 5 and/or 6 and 7 during a left thoracotomy, while the latter required complete removal of all lymph nodes at those levels. RESULTS: Three hundred seventy-three eligible patients were accrued to the study. Among the 187 patients who underwent SS, N1 disease was identified in 40% and N2 disease in 60%. This was not significantly different than the 41% of N1 disease and 59% of N2 disease found among the 186 patients who underwent complete MLND. Among the 222 patients with N2 metastases, multiple levels of N2 disease were documented in 30% of patients who underwent complete MLND and in 12% of patients who had SS (p = 0.001). Median survival was 57.5 months for those patients who had undergone complete MLND and 29.2 months for those patients who had SS (p = 0.004). However, the survival advantage was limited to patients with right lung tumors (66.4 months vs 24.5 months, p<0.001). CONCLUSIONS: In this nonrandomized comparison, SS was as efficacious as complete MLND in staging patients with NSCLC. However, complete MLND identified significantly more levels of N2 disease. Furthermore, complete MLND was associated with improved survival with right NSCLC when compared with SS.

Carcinoma, Non-Small-Cell Lung↗

PubMed1999

Analysis of MEG signals of spreading cortical depression with propagation constrained to a rectangular cortical strip. II. Gyrencephalic swine model.

Currents produced during spreading cortical depression (SCD) in a gyrencephalic species (swine) were studied with magnetoencephalography (MEG) and electrocorticography (ECoG). SCD, initiated using electrical stimulation of the cortex, was constrained to propagate within a rectangular cortical strip in order to simplify the interpretation of the underlying currents. The ECoG signals monitored along the strip revealed that SCD propagated from an initiation site on the gyrus at a rate of 7.9+/-3.2 mm/min (n=23), entered the deep coronal sulcus and in most cases emerged from the other side of the sulcus, continuing to propagate across the next gyrus at a rate of 5.9+/-2.7 mm/min (n=22). The apparent propagation velocity within the sulcus was reduced to 1.7+/-0.8 mm/min (n=21). Strong MEG signals were observed as SCD entered the sulcus. The direction of magnetic field was opposite for SCD's on opposite banks of the sulcus. The currents were directed from a superficial layer to deeper layers of the cortex. The characteristics of SCD and associated MEG patterns from a gyrencephalic species may be similar to those in human patients during migraine aura.

Animals↗

PubMed1998

Electrocorticography and outcome in frontal lobe epilepsy.

The prognostic significance of epileptiform activity (EA) recorded at electrocorticography (ECOG) was examined in a group of 60 consecutive non-tumoral patients with intractable frontal lobe epilepsy (FLE). Pre-excision EA was documented as absent, focal (one gyrus), regional (two gyri), lobar (3 gyri) or multilobar (frontal + temporal gyri). Post-excision EA was documented as absent, restricted to the resection border, or recorded distant to the resection border, and was quantitated by spike frequency. Pre-excision EA from < or = 2 gyri and absence of post-resection EA correlated with Class I or II (Engel classification) outcome while pre-excision EA from > or = 3 gyri and persistent post-resection EA, especially distant to the resection border, correlated with Class III or IV outcome (P < 0.001). A significant correlation between poorer outcomes and increased abundance of distant post-resection EA was observed (P < 0.001). EA restricted to the resection border was not significantly correlated with outcome. Presence of a circumscribed lesion correlated with Class I outcome (P < 0.01) and absence of pathological abnormality correlated with Class IV outcome (P < 0.05). Neither side nor extent of surgical excision correlated with outcome. EA recorded at ECOG is of prognostic significance in FLE. A lobar or multilobar distribution of pre-excision EA and persistent post-excision EA distant to the resection border, especially when abundant, are highly unfavorable prognostic indicators. In contrast, a restricted distribution of pre-excision EA and absence of post-resection EA both herald a favorable outcome.

Adolescent↗

PubMed1999

Comparison of MEG and EEG on the basis of somatic evoked responses elicited by stimulation of the snout in the juvenile swine.

OBJECTIVE: Some basic characteristics of magnetoencephalographic (MEG) and electroencephalographic (EEG) signals were studied by comparing somatic evoked fields (SEFs) and potentials (SEPs) elicited by electrical stimulations of different areas of the snout in piglets. METHODS: SEFs were measured with and without an intact skull, whereas SEPs were measured on the skull and cortex (Electrocorticograms - ECoG) and within the cortex of the same animal. RESULTS: The SEFs above the skull and dura were very similar to each other in temporal waveform and spatial topography, indicating small effects of the skull. They both revealed very similar somatotopic projections of the snout. The SEPs on the skull and cortex were, in contrast, clearly different in their amplitudes as well as temporal and spatial morphologies, indicating significant effects of the skull. However, an early component of the SEP on the skull revealed a somatotopic representation of the snout, indicating that EEG can be also useful for inferring cortical projection areas. Discrepancies in their maps were due to predominance of the potentials produced by currents in the gyral cortex. The projection sites inferred from SEFs were quite accurate in comparison to those inferred from ECoGs and intracortical SEPs. CONCLUSION: The similarities and differences clearly point out the complementary nature of MEG and EEG.

Animals↗

PubMed1999

Effects of diazepam on extracellular brain neurotransmitters in pilocarpine-induced seizures in rats.

The present study was undertaken to gain insights into the mechanism of action of diazepam in focally-evoked pilocarpine-induced seizures by concomitantly assessing the changes produced in the extracellular levels of glutamate, GABA (gamma-aminobutyric acid) and dopamine. In vivo microdialysis, coupled to continuous monitoring of electrocorticographic (ECoG) recordings, was performed in freely moving rats. Intrahippocampal perfusion with 10 mM pilocarpine (40 min, 2 microl/min) produced limbic seizures. A single dose of intraperitoneal diazepam (5 mg/kg) was administered 2 h after pilocarpine perfusion was started. Dialysates were sampled both from hippocampus and cerebellum and analysed by microbore liquid chromatography. Diazepam produced instant inhibition of behavioural and ECoG seizure activity. Pilocarpine-induced increases in the extracellular levels of glutamate and dopamine in hippocampus were promptly reduced by diazepam. No concurrent alterations in pilocarpine-induced increases in the extracellular levels of GABA in either hippocampus or cerebellum were seen. Pilocarpine enhanced cerebellar glutamate levels only transiently and levels returned to baseline before diazepam administration. No further changes in cerebellar glutamate levels were observed with diazepam. Our findings suggest that the anti-convulsant action of diazepam against pilocarpine-induced seizures is associated with a prompt attenuation of extracellular hippocampal glutamate overflow without concurrent alteration of pilocarpine-induced increases in endogenous GABA levels. Diazepam also significantly decreased pilocarpine-induced increases in extracellular dopamine levels within the hippocampus. No immediate alterations of the basal levels of the neurotransmitters monitored were observed with diazepam.

Animals↗

PubMed2006

Prognostic value of thrombocytosis in renal cell carcinoma.

PURPOSE: We correlated platelet count to renal tumor characteristics, and evaluated the potential prognostic value of thrombocytosis in localized and metastatic tumors. MATERIALS AND METHODS: A total of 804 patients operated on for a renal tumor in 2 French centers were included in this study. In all cases TNM stage, Fuhrman grade, tumor size, nodal invasion, ECOG score, histological subtype and platelet count were recorded. Survival estimates were compared with the Kaplan-Meier method and multivariate analysis was performed using a Cox model. RESULTS: There were 538 (66.9%) males and 266 (33%) females (ratio 2.02) in the patient group. Median age was 62 years. T stages were T1, T2, T3 and T4 in 284 (35.3%), 116 (14.4%), 387 (48.1%) and 17 (2.1%), respectively. There were 112 (13.9%) and 126 (15.7%) patients with nodal and metastatic invasion, respectively. Platelet count was strongly correlated with T stage (p < 0.001), Fuhrman grade (p < 0.001), tumor size (p < 0.001), nodal invasion (p < 0.001) and the presence of distant metastasis (p = 0.01). In univariate analysis all studied factors were significantly predictive of survival (p = 0.0001). Thrombocytosis had an impact on prognosis in localized (p < 0.001) and metastatic (p = 0.003) disease. Several factors were retained in multivariate analysis, namely TNM stage, Fuhrman grade, tumor size, ECOG score and platelet count. In cases with a platelet count of less than 450,000/mm3, the 5-year survival rate was 70%, compared to 38% when the platelet count was 450,000/mm3 or greater. CONCLUSIONS: Platelet count appears to be an independent prognostic factor in renal cell carcinoma. It reflects a cascade of biological events correlated with tumor aggressiveness. This observation opens new perspectives for exploring carcinogenesis mechanisms and tumor progression in renal cell carcinoma.

Aged↗

PubMed1999

Effects of pregnanolone on behavioural parameters and the responses to GABA(A) receptor antagonists in the late gestation fetal sheep.

Placental progesterone metabolites may suppress fetal behaviour by interacting with GABA(A) receptors. In an initial study, the effect of 5beta-pregnan-3alpha-ol-20-one (pregnanolone) given as a bolus (2.5 and 5.0 mg) or infused at a rate of 25 mg/h was investigated in unanaesthetized, catheterized fetal sheep, 127-135 days gestation. The incidence of fetal breathing movements (FBM) and behavioural arousal activity, defined as nuchal muscle electromyographic (EMG) activity during low voltage electrocortical (LV ECoG) activity were suppressed by pregnanolone administered as a bolus, while the pregnanolone infusion produced a significant decrease in arousal and EOG activity, and an increase in the presence of HV ECoG. The effect of pregnanolone on fetal behaviour and arousal induced by the GABA(A) antagonist picrotoxin was also investigated. Picrotoxin was given as a bolus (approximately 300 microg/kg) and pregnanolone was subsequently administered as a bolus (5.0 mg), and behavioural parameters were recorded and analysed. The incidence of arousal and FBM were 1.1 +/- 1.6 min/10 min and 2.5 +/- 2.3 min/10 min, respectively, before picrotoxin treatment and increased during the 10-20 and 20-30 min epochs after picrotoxin treatment (arousal: 5.0 +/- 2.2 and 6.5 +/- 3.6 min/10 min, respectively, n = 6, P < 0.05; FBM: 7.3 +/- 3.2 and 9.3 +/- 1.2 min/10 min, respectively, n = 6, P < 0.05). The picrotoxin-induced increases in arousal and FBM were significantly suppressed (n = 6, P < 0.05) by pregnanolone treatment to 1.6 +/- 1.5 min/10 min and 4.6 +/- 2.3 min/10 min, respectively. We conclude that; (i) the GABA(A) active steroid pregnanolone suppresses basal and picrotoxin-induced fetal arousal and FBM; and (ii) steroid sensitive GABA(A) receptors may regulate fetal behaviour and breathing.

Animals↗