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At least 775 records · Page 43Linked to original sources

PubMed1997

MCI-225, a novel thienopyrimidine analog, enhances attentional eye tracking in midpontine pretrigeminal preparation.

The effects of MCI-225, a novel psychoactive compound, and reference drugs on attention behavior were studied using visual stimulus induced vertical eye tracking movements in midpontine pretrigeminal (PTG) feline preparation. Surgery was performed under ether anesthesia and subsequently switched to nitrous oxide-fluothane which was discontinued only during experimental sessions. In addition xylocaine was locally injected. Vertical eye movements were monitored by electrooculogram (EOG) and a TV camera. To compare the effects of drugs on eye movement, numbers of spontaneous and tracking eye movements exceeding a present amplitude in EOG were counted before and during the visual stimulation, respectively. MCI-225 (1 and 3 mg/kg, i.v.) enhanced tracking movements dose-dependently without an increase in spontaneous eye movements. No or little change of the electrocorticogram (ECoG) was seen with 1 mg/kg MCI-225 and a slight increase in low voltage fast pattern was observed with 3 mg/kg, i.v.. On the other hand, tacrine (0.3 mg/kg, i.v.), physostigmine (0.03 mg/kg, i.v.) and methylphenidate (0.3 mg/kg, i.v.) enhanced both types of eye movement and induced ECoG arousal. Desipramine (3 mg/kg, i.v.) slightly increased spontaneous eye movement without affecting tracking movements. Piracetam (100 mg/kg, i.v.) decreased spontaneous eye movements only. These data clearly show that MCI-225 enhances attention to a moving object and suggest that MCI-225 could be useful in the treatment of attentional deficits and related cognitive dysfunctions in psychiatric disorders.

Animals↗

PubMed1997

Can the Indo-1 fluorescence approach measure brain intracellular calcium in vivo? A multiparametric study of cerebrocortical anoxia and ischemia.

Indo-1 fluorescence was used to monitor intracellular calcium levels in the cat brain in vivo, using the approach proposed by Uematsu et al. [Uematsu D., Greenberg J. H., Reivich M., Karp A. In vivo measurement of cytosolic free calcium during cerebral ischemia and reperfusion. Ann Neurol 1988; 24: 420-428]. In addition, extracellular calcium and potassium levels, NADH redox state, electrocorticogram (ECoG), DC potential and relative cerebral blood flow were monitored simultaneously. Changes in the Indo-1 fluorescence ratio F400/F506 were monitored during anoxia, reversible ischemia and irreversible ischemia. Although these perturbations resulted in the expected changes in extracellular calcium and potassium levels, NADH redox state, ECoG and other physiological parameters, they did not result in significant increases in the F400/F506 ratio. The apparent insensitivity of the in vivo Indo-1 approach is due to the difficulty in obtaining accurate fluorescence signals from Indo-1 in the brain. Two reasons for this difficulty appear to be problems in loading Indo-1 into the brain, and problems in correcting Indo-1 fluorescence signals for changes in NADH fluorescence and changes in absorption of intrinsic chromophores. Under the conditions of our in vivo cat experiments, Indo-1 fluorescence is not a viable approach for measuring changes in cerebral intracellular calcium levels.

Animals↗

PubMed2000

Yawning responses induced by local hypoxia in the paraventricular nucleus of the rat.

Yawing was induced by microinjections of L-glutamate, cyanide and a nitric oxide-releasing compound (NOC12) into the paraventricular nucleus of the hypothalamus (PVN) in anesthetized, spontaneously breathing rats. To evaluate physiological aspects of yawning, we monitored intercostal electromyogram (EMG) as an index of inspiratory activity, digastric EMG, blood pressure and electrocorticogram (ECoG). Microinjection of L-glutamate in the medial parvocellular subdivision (mp) elicited a stereotyped yawning response, i.e. an initial depressor response and an arousal shift in ECoG followed by a single large inspiration with mouth opening. The same sequential events were observed during spontaneous yawning, indicating that the mp is responsible for triggering yawning. Microinjection of cyanide into the mp caused the same yawning responses as the ones elicited by microinjection of L-glutamate, suggesting that the mp is sensitive to chemical hypoxia or ischemia within the PVN. Microinjection of NOC12 into the mp elicited a single large inspiration with a variable onset delay, suggesting that diffusible nitric oxide (NO) within the mp may act as a paracrine agent to cause a yawning response. We hypothesize that the mp of the PVN contains an oxygen sensor that causes a yawning response.

Animals↗

PubMed2002

Yawning/cortical activation induced by microinjection of histamine into the paraventricular nucleus of the rat.

The effects of microinjection of histamine into the paraventricular nucleus (PVN) of the hypothalamus on yawning responses were investigated in anesthetized, spontaneously breathing rats. Yawning responses were evaluated by monitoring the intercostal electromyogram (EMG) as an index of inspiratory activity and digastric EMG as an indicator of mouth opening. We also recorded the electrocorticogram (ECoG) to determine the arousal response during yawning. Autonomic function was evaluated by measuring blood pressure and heart rate. Microinjection of histamine into the medial parvocellular subdivision (mp) of the PVN elicited a yawning response, i.e. a single large inspiration with mouth opening, and an arousal shift in ECoG to lower voltage and faster rhythms. Microinjection of HTMT dimaleate, an H1 receptor agonist, into the PVN also caused the yawning/arousal response. Pretreatment with pyrilamine, an H1 receptor antagonist, inhibited the histamine induced yawning behavior. These data demonstrate that a histamine receptive site for triggering yawning/arousal responses exists in the PVN, and suggest that these responses are mediated by activation of H1 receptor within the PVN.

Animals↗

PubMed2003

Light induces cortical activation and yawning in rats.

We examined the effects of light stimulation on cortical activation and yawning response in anesthetized, spontaneously breathing rats. Cortical activation was assessed by means of an electrocorticogram (ECoG) and yawning response was evaluated by monitoring an intercostal electromyogram as an index of inspiratory activity and a digastric electromyogram as an indicator of mouth opening. Light stimulation elicited an arousal shift in the ECoG to faster rhythms. This arousal response was followed by a single large inspiration with mouth opening, i.e. a yawning response. Higher light intensity significantly reduced the onset latency of the arousal/yawning response. Pretreatment with pyrilamine, an H1-histamine receptor antagonist, injected into the lateral ventricle blocked both the cortical activation and the yawning response induced by light stimulation, suggesting a role of brain histaminergic neurotransmission in modulating the light-induced arousal/yawning responses.

Animals↗

PubMed2002

Cost-minimisation analysis of three regimens of chemotherapy (docetaxel-cisplatin, paclitaxel-cisplatin, paclitaxel-carboplatin) for advanced non-small-cell lung cancer.

PURPOSE: To compare the efficiency (the evaluation of efficacy in relation to costs) of three first-line treatment options for advanced non-small cell lung cancer (stage IIIB and IV) used in the Eastern Cooperative Oncology Group (ECOG) study: docetaxel/cisplatin (75/75 mg/m(2)/day, 1 h intravenous (i.v.) infusion of docetaxel), paclitaxel/cisplatin (175/75 mg/m(2)/day, 3 or 24 h i.v. infusion of paclitaxel) and paclitaxel/carboplatin (175/400 or 225/400 mg/m(2)/day, 3 h i.v. infusion of paclitaxel). METHODS: The results of the ECOG 1594 phase III clinical trial (Proc. Am. Soc. Clin. Oncol. 19 (2000) 2) demonstrated equivalent efficacy (survival, objective response) between the treatment options. To differentiate between the treatment options, we performed a cost-minimisation analysis, using a pharmacoeconomic model. RESULTS: The average estimated treatment cost per patient (median, 4 cycles) with docetaxel/cisplatin would be 1067836 Spanish pesetas (Ptas) (6418 Euros; 5741 US dollars (USD)), 1365304 or 1439369 Ptas (8205 or 8651 Euros; 7340 or 7738 USD) with paclitaxel/cisplatin (3 or 24 h infusions, respectively), and 1417995 or 1616784 Ptas (8522 or 9717 Euros; 7623 or 8692 USD) (paclitaxel dose of 175 or 225 mg/m(2)/day, respectively) with paclitaxel/carboplatin. CONCLUSION: According to our study, the treatment option docetaxel/cisplatin, with equal efficacy, would result in a cost saving of between 297468 and 548948 Ptas (1788 and 3299 Euros; 1599 and 2951 USD) per patient treated. This difference is mainly due to the lower treatment cost of docetaxel.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Chemotherapy for advanced non-small cell lung cancer: standards.

For non-small cell lung Cancer (NSCLC) patients in good clinical condition (PS 0-1), Platin-based combination chemotherapy is currently recommended to prolong survival, prevent or reduce tumor-related symptoms, and maintain the quality of life. Nonetheless, the clinical availability of newer cytotoxic drugs has considerably increased the chemotherapeutic options for Platin-based chemotherapy and, at the same time, increased the difficulties in choosing the most appropriate regimen. These difficulties became especially clear when oncologists were confronted with the disappointing results from ECOG 1594, a study which tested four popular Platin-based combinations. Since no survival advantages could be shown by any of the four combinations used in ECOG 1594, one of the pertinent question seems to be whether, and in what form, a Platin-free combination regimen with newer agents should replace the currently recommended Platin-based therapy? A strong indication that non-Platin-containing regimens are not inferior came from at least two randomized trials. However, first results from EORTC 08975 -trial, did not confirm these observations, since the trend seems to be towards better results for the patients on Platin-containing regimens. A number of trials have shown that patients with PS >1 do not benefit from combination regimens. For these and for elderly patients, single agent therapy with newer cytotoxic agents may be for various reasons an attractive chemotherapeutic alternative for palliation. Several cooperative studies have proven that single agent therapy is superior to best supportive care. Vinorelbine was the first new agent tested in randomized, controlled trials in the elderly population, and was found to give statistically significant survival advantages in comparison to best supportive care only. As chemotherapy gains wider acceptance for advanced and early stage NSCLC, the need for an effective second-line chemotherapy is also growing. On the basis of two randomized, phase III studies, Docetaxel has recently become the first cytotoxic agent to be registered for second-line therapy in NSCLC. Both studies demonstrated that Docetaxel 75 mg/m2 given every 3 weeks significantly prolongs survival, and offers clinically meaningful benefits to patients who have an acceptable performance status.

Antineoplastic Agents, Phytogenic↗

PubMed1995

Phase II study with paclitaxel for the treatment of advanced inoperable non-small cell lung cancer.

Paclitaxel is a plant product isolated from the bark of the Western yew (Taxus brevifolia) that promotes the formation and stabilization of microtubules. This leads to growth arrest in the G2/M phase of the cell cycle. Paclitaxel has demonstrated significant antineoplastic activity in different tumor types, most notably in ovarian and breast carcinoma. In two Phase II trials (Eastern Cooperative Oncology Group [ECOG]/M.D. Anderson) in patients with previously untreated Stage IIIB-IV non-small cell lung cancer (NSCLC), response rates of 21% and 24% were reported. We are performing a Phase II trial investigating the efficacy of paclitaxel in patients with inoperable Stage IIIB-IV NSCLC. Forty-three patients were treated, 31 males and 12 females, with a median age of 59 years (range, 29-75), ECOG performance status 0-2, Stage IIIB 30%, Stage IV 70%. Patients were treated every 3 weeks with 225 mg/m2 as a 3-h infusion with standard premedication. Preliminary efficacy results from 37 patients include partial remissions in eight (21.6%) patients, no change in 22 (59.5%) and disease progression in seven (19%) patients. Eight patients are still receiving therapy. The hematologic toxicities (n = 43) were mild, and no World Health Organization (WHO) Grade 4 neutropenia was observed. Nonhematologic toxicities were Grade 1/2 polyneuropathy in 97.6%, Grade 1-3 myalgia/arthralgia in 76%, and Grade 1-3 nausea/vomiting in 18.6% of the patients. In conclusion, paclitaxel is an active single agent in this patient population. Mild hematologic toxicities were observed in the 3-h infusion setting (compared with 24-h infusion) and therapy was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2002

Early stage nasal NK/T-cell lymphoma: clinical outcome, prognostic factors, and the effect of treatment modality.

PURPOSE: To determine the clinical outcome, prognostic factors, and effect of adding combination chemotherapy to radiation therapy on disease control and survival in early stage nasal natural killer (NK)/T-cell lymphoma. METHODS AND MATERIALS: A retrospective "intent to treat" analysis was carried out on 79 patients treated consecutively with curative intent between 1977 and June 2001. They all had early stage (Ann Arbor Stage I(E): 63, II(E):16) nasal NK/T-cell lymphoma. Sixty-one were planned for combined modality treatment (CMT); radiotherapy alone (RT) was intended for 18. Three to 6 cycles of anthracycline-containing regimens were aimed at for patients intended for CMT. Patients selected for RT were generally older or treated during the earlier part of the study period. RESULTS: The overall complete response (CR) rate was 68.4% (54/79), of whom 44.4% (24/54) relapsed after 54.9 months median follow-up of the survivors. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 35.5% and 37.9%, respectively. On multivariate analysis, good performance status (Eastern Cooperative Oncology Group [ECOG] <2) was shown to be a significant favorable factor for DFS (p = 0.011), whereas good performance status (ECOG <2) and Ann Arbor Stage I(E) disease were shown to be significant favorable factors for OS (p = 0.001 and p = 0.013, respectively). The type of intended treatment was not a significant factor for DFS (5-year DFS CMT vs. RT = 35.8% vs. 30.5%, p = 0.795) or OS (5-year OS CMT vs. RT = 40.3% vs. 29.8%, p = 0.693) though only 2 of the 16 Stage II(E) patients were intended for RT alone. Resistance to treatment, especially to chemotherapy, was common. Of 61 patients intended to be given CMT, 31 showed disease progression while receiving chemotherapy, of whom 17 progressed locoregionally. Nine of the latter group were rendered CR by salvage radiotherapy. CONCLUSIONS: The overall outcome in early stage nasal NK/T-cell lymphoma is poor. Performance status and Ann Arbor stage are significant factors influencing DFS and OS. The addition of anthracycline-containing chemotherapy to radiotherapy does not appear to confer any survival benefit in Stage I(E) patients. Therefore, radiation therapy remains the mainstay of treatment for this lymphoma type.

Adolescent↗

PubMed1998

Treatment of locally recurrent rectal carcinoma--results and prognostic factors.

PURPOSE: To assess the local control and survival in patients who received pelvic irradiation for locally recurrent rectal carcinoma. METHODS AND MATERIALS: The records of 519 patients with locally recurrent rectal carcinoma treated principally with external-beam radiation therapy between 1975 to 1985 at a single institute were retrospectively reviewed. These included 326 patients who relapsed locally following previous abdominoperineal resection, 151 after previous low anterior resection, and 42 after previous local excision or electrocoagulation for the primary. No patients had received adjuvant radiation therapy or chemotherapy for the primary disease. Concurrent extrapelvic distant metastases were found in 164 (32%) patients at local recurrence and, in the remaining 355, the relapse was confined to the pelvis. There were 290 men and 229 women whose age ranged from 23 to 91 years (median = 65). Median time from initial surgery to radiation therapy for local recurrence was 18 months (3-138 months). Radiation therapy was given with varying dose-fractionation schedules, total doses ranging from 4.4 to 65.0 Gy (median = 30 Gy) over 1 to 92 days (median = 22 days). For 214 patients who received a total dose > or = 35 Gy, radiation therapy was given in 1.8 to 2.5 Gy daily fractions. RESULTS: The median survival was 14 months and the median time to local disease progression was 5 months from date of pelvic irradiation. The 5-year survival was 5%, and the pelvic disease progression-free rate was 7%. Twelve patients remained alive and free of disease at 5 years after pelvic irradiation. Upon multivariate analysis, overall survival was positively correlated with ECOG performance status (p = 0.0001), absence of extrapelvic metastases (p = 0.0001), long intervals from initial surgery to radiation therapy for local recurrence (p = 0.0001), total radiation dose (p = 0.0001), and absence of obstructive uropathy (p = 0.0013). Pelvic disease progression-free rates were positively correlated with ECOG performance status (p = 0.0001), total radiation dose (p = 0.0001), and previous conservative surgery for the primary (p = 0.02). CONCLUSIONS: Survival is poor for patients who develop local recurrence following previous surgery for rectal carcinoma. Pelvic radiation therapy provides only short-term palliation, and future efforts should be directed to the use of effective adjuvant therapy for patients with rectal carcinoma who are at high risk of local recurrence.

Adult↗

PubMed2002

Elevated summating potential in a case of posterior fossa meningioma was normalized by tumor removal.

OBJECTIVE: A change in the summating potential (SP) obtained from a patient with posterior fossa meningioma associated with surgical removal of the tumor was reported and possible mechanisms underlying the change are discussed. METHODS: This paper is a retrospective case review. A tertiary care referral center was the setting for the study. The authors present a 46-year-old female patient with posterior fossa meningioma, which was removed surgically. Pure tone audiometry and electrocochleography (ECoG) were performed before and after surgical removal of the tumor. RESULTS: Pure tone audiogram showed normal hearing levels before surgery, and there were no apparent postoperative changes in hearing levels. ECoG showed a normal compound action potential (AP) level and an elevated SP/AP ratio (0.53) before surgery. After the tumor removal, the SP/AP ratio became 0.16, which was a normal level in our department. CONCLUSIONS: The increased SP/AP ratio was normalized after surgery. Possible mechanisms underlying the increase in SP/AP ratio are an inhibition of the olivocochlear bundle function and endolymphatic hydrops.

Audiometry, Evoked Response↗

PubMed1999

Dipole analysis in a case with tumor-related epilepsy.

In order to evaluate the effectiveness of presurgical dipole analysis of interictal spikes as a non-invasive technique for the determination of epileptogenic area, we compared the results of this method with those of electrocorticography (ECoG) localization in the diagnosis of a patient with tumor-related epilepsy. A preoperative MRI revealed a temporal lobe tumor on the right side. The individual dipoles estimated from the interictal spikes were located mainly in the anterolateral region of the right temporal lobe, although some were located in the mesial side. The ECoG recorded frequent spikes in the anterolateral region of the right temporal lobe consistent with the location estimated by dipole analysis. After surgery, the patient suffered from residual seizures. Therefore, the residual epileptogenic area was examined by dipole analysis using a four-layered head model instead of the previous three-layered head model. As a result, the dipole analysis was able to pinpoint the epileptic focus in the area directly adjacent to the resected area, and in the mesial temporal lobe. In conclusion, EEG dipole analysis appears to hold promise as a non-invasive presurgical evaluation technique for locating epileptogenic areas as well as for postsurgical evaluation of residual epileptic focus.

Adolescent↗

PubMed1997

The Edmonton Functional Assessment Tool: preliminary development and evaluation for use in palliative care.

The purpose of this article is to report the development and psychometric testing of the Edmonton Functional Assessment Tool (EFAT). The EFAT was developed as a functional outcome measure for use with a palliative care population. The assessment identified ten functional activities important to patients even in the terminal stage of their illness. In addition, a global performance status rating (PS) asked for an overall judgment of functional status after the ten EFAT functions were evaluated. Tests for interrater reliability and concurrent validity were conducted on a sample of 25 inpatients on the Palliative Care Unit (PCU) at the Edmonton General Hospital (EGH) who were evaluated independently by two raters. Interrater reliability of the EFAT expressed as an intraclass correlation (ICC) was established at 0.88. The interrater reliability of these two raters was 0.71 for the Karnofsky Performance Status (KPS) and 0.81 for the performance status measure of the Eastern Cooperative Oncology Group (ECOG). Concurrent validity of the EFAT was demonstrated by correlating the total EFAT score with the KPS (r = -0.79, P = 0.0001) and the ECOG (r = 0.85, P = 0.0001). The total EFAT score was also strongly correlated with the global PS rating scale (r = 0.90, P = 0.0001). Construct validity of the EFAT was tested with a sample of 101 patients admitted to the unit, which was later divided into the unit group (N = 88) and the home group (N = 13). Our findings provided initial evidence that the EFAT distinguished between the functional status of these two groups. The results of this preliminary study suggest that the EFAT requires further research and development, but shows potential to evolve as a useful clinical tool in palliative care.

Aged↗

PubMed1999

Validation of the German version of the Brief Pain Inventory.

The Brief Pain Inventory is a comprehensive instrument for pain assessment and has been validated in several languages. A validated German version was not available until now. From March to May 1995 all outpatients of the pain clinic of the Department of Anesthesiology completed a questionnaire with the German versions of the Brief Pain Inventory (BPI) and the SF-36 quality-of-life questionnaire. The BPI was repeated after the consultation. The physician assessed the performance status score of the Eastern Cooperative Oncology Group (ECOG). The questionnaire was completed by 151 patients. Forty-two patients were excluded from evaluation for methodological reasons, so 109 patients were evaluated. As in the original version of the BPI, factor analysis showed a common factor for pain intensity and a second factor for pain-related interference with function. The comparative fit index of 0.86 confirmed this model. Responses before and after consultation correlated closely for the sum scores of the pain intensity items (Perarson correlation r = 0.976) as well as for the interference with function items (r = 0.974). Pain intensity in the BPI correlated with bodily pain in the SF-36 (r = 0.585). Sum scores of the pain interference items were higher in patients with deteriorated ECOG performance status, whereas sum scores of the intensity items were not changed. Validity and reliability of the German BPI were comparable to the original version. The BPI may be advantageous for palliative care patients, as it places only a small burden on the patient and offers easy criteria for evaluation. However, further research is needed to differentiate the impact of pain-related and disease-related interference with function on the BPI, and to find an algorithm for the evaluation of the BPI when values are missing.

Adult↗

PubMed2000

Focal microinjection of carbachol into the periaqueductal gray induces seizures in the forebrain of the rat.

Previous studies have reported that the repetition of running-bouncing and tonic-clonic seizures mediated by brainstem structures eventually elicits seizure activity in the forebrain. The purpose of the present study was to determine if the periaqueductal gray (PAG) region is a component of the neural network through which brainstem seizures elicit forebrain seizures. Bilateral microinjection of 40 nmol carbachol into the PAG region of rats induced arrested, staring behavior accompanied by epileptiform electrocorticogram (ECoG) afterdischarge recorded from the parietal cortex. In two animals limbic seizure activity similar to kindled amygdala seizures was also induced. The carbachol effect was dose-related as the 40 nmol dose induced a significantly greater duration of ECoG afterdischarge than a 20 nmol dose. The carbachol effect was mediated by muscarinic receptors as bilateral 50 nmol atropine microinjection 1 min prior to 40 nmol carbachol microinjection inhibited all seizure activity. Immunohistochemical detection of the proto-oncogene c-fos was used to verify that seizure activity was induced in forebrain regions. Rats with seizures induced by PAG carbachol microinjections exhibited dense c-fos-like immunoreactivity in the dentate gyrus but not the CA(1) or CA(3) regions, amygdala, piriform cortex, perirhinal cortex or hypothalamus. In addition, PAG microinjection of 10 nmol N-methyl-D-aspartic acid (NMDA) induced wild-running convulsions while 400 pmol bicuculline induced clonic spasms, myoclonic activity or limbic seizures. These results indicate that stimulation of the PAG, a brainstem structure, is sufficient to induce forebrain seizures. Since the forebrain seizures were induced by a single carbachol administration, it is proposed that the PAG serves as a pathway for caudal-rostral seizure generalization.

Animals↗

PubMed2002

The intracerebral administration of phenytoin using controlled-release polymers reduces experimental seizures in rats.

PURPOSE: An alternative strategy for the treatment of intractable seizures may be to administer anticonvulsants directly into the brain near the site of a seizure focus using controlled-release polymers. We describe the pharmacokinetics of a phenytoin-ethylene-vinyl acetate (EVAc) controlled-release polymer and report the reduction of seizures in a cobalt-induced rat model of epilepsy with the intracerebral delivery of phenytoin using surgically implanted polymers. METHODS: In the pharmacokinetics study, the drug release rate of 50%-loaded phenytoin-EVAc polymers (n=3) was determined in vitro over 15 weeks initially and then several months later (over a 2-week period after 1 year of in vivo release). In the efficacy study, 85 rats underwent implantation of skull-mounted cortical electrodes for electrocorticography (ECoG) and then underwent application of cobalt chloride to the cerebral cortex for the induction of seizures. Rats in the treatment group (n=9) underwent surgical implantation of phenytoin-EVAc polymers and rats in the control group (n=10) underwent implantation of empty EVAc polymers. In the morbidity study, the potential histologic pathology of the intracerebral delivery of increasing doses of phenytoin from the polymer (10, 20, 30, and 50% loading) was assessed. RESULTS: Phenytoin was released in vitro from EVAc polymers in a controlled fashion with an initial release of 0.20% of the total loaded dose per week and a continued release of 0.70% of the total loaded dose per week after 365 days of implantation in the brain. The intracerebral controlled-release of phenytoin resulted in a statistically significant reduction in seizure activity in the treatment group as evidenced by lower Racine scores. The four groups of rats (n=5 per group) that underwent intracerebral implantation of 10, 20, 30, or 50%-loaded phenytoin-EVAc polymers displayed expected average weight gain and normal behavior over 365 days. One rat in the 50% group, however, died 354 days after polymer implantation for undetermined reasons. CONCLUSIONS: The intracerebral delivery of phenytoin using an EVAc polymer, which will release this drug for a calculated period of 3.5 years, resulted in a significant reduction in seizures in a rat model of cobalt-induced epilepsy by both behavioral and ECoG criteria. In rats, the long-term interstitial delivery of phenytoin in the brain was not associated with any deleterious effects.

Animals↗

PubMed2002

Ictal electrocorticographic findings related with surgical outcomes in nonlesional neocortical epilepsy.

PURPOSE: To characterize ictal electrocorticographic features related to surgical outcomes in nonlesional neocortical epilepsy (NE). METHODS: We analyzed 187 ictal electrocorticograms (ECoG) obtained from 18 patients who had undergone presurgical evaluation and subsequent neocortical resections (frontal: seven, parietal: one, occipital: four, multilobar: six). None of them had any MRI-detectable lesions. Various ECoG data sets recorded from eight patients who achieved a favorable surgical outcome (either seizure free or more than 90% reduction of seizure frequencies) were compared with that from ten patients with unfavorable outcome (less than 90% reduction of seizure frequencies) (follow up duration: 47+/-11 months). RESULTS: Reproducible ictal onset zone (IOZ) in recurrent seizures (P=0.013) and persistent ictal discharges in IOZ from the onset to the end of seizure (P=0.004) were found more frequently in the patients with good outcome. Ictal onset patterns consisting of low voltage fast or high amplitude beta spikes predicted a good surgical outcome while rhythmic sinusoidal activity or rhythmic spike/sharp waves of slow frequency were predictive of poor outcome (P=0.01). The ictal onset rhythm consisting of gamma or beta frequencies was more prevalent in the favorable group (P=0.015). CONCLUSIONS: The presence of stable ictal circuit suggested by the consistent earliest activation of specific electrodes in the repetitive seizures (reproducible IOZ) and the active participation of IOZ throughout the attack were valuable prognostic factors in addition to the morphology and frequency of ictal onset rhythm.

Adolescent↗

PubMed1998

Electrocorticographic changes during generalized convulsive status epilepticus in soman intoxicated rats.

Generalized convulsive status epilepticus (GCSE) is the most common and potentially most damaging form of status epilepticus (SE). It has been previously reported, in both human GCSE and animal models of GCSE, that the electroencephalographs (EEGs) and electrocorticographs (ECoGs) recorded during GCSE contain an ordered sequence of five identifiable patterns: discrete seizures (phase 1), waxing and waning ictal discharges (phase 2), continuous ictal discharges (phase 3), continuous activity with flat periods (phase 4), and periodic epileptiform discharge on a flat background (phase 5). In this paper, we report the same pattern of ECoG changes in 15 rats exposed to soman, an acetylcholinesterase (AChE) inhibitor. Phase 1 was observed in 12 of 15 animals, but phases 2-5 were recorded in all the animals. Taken together, these findings suggest that the sequence of EEG changes is independent of the initiating cause, represent a common electrical response to GCSE, and reflect a common underlying neurochemical mechanism.

Animals↗