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Cisplatin and etoposide alternating ifosfamide, vincristine, epirubicin in small cell lung cancer.

OBJECTIVE: The aim of this study was to evaluate the effects and toxicity of alternating cisplatin+etoposide (EP) and ifosfamide+vincristine+epirubicin (IVE) combination regimen in patients with small cell lung cancer (SCLC). METHODS: We have treated 38 SCLC patients with 6 courses of alternating chemotherapy consisting of cisplatin 100 mg/m2 on day one and etoposide 80 mg /m2 on the first, second and third days in courses of first, third and fifth, alternating with ifosfamide 4 g/m2, vincristine 2 mg/day and epirubicin 60 mg/m2 intravenously on day one in courses of second, forth and sixth. The courses were administrated every 3 weeks. After the sixth course of chemotherapy the patients with limited disease (LD) who had a complete response (CR) received concomitant chest irradiation. None of the patients had prophylactic cranial irradiation. The study was conducted between January 1997 and July 1997 in the Department of Chest Disease at Ondojuz Mayis University Hospital, Samsun, Turkey. RESULTS: The mean age of the 3 female and 35 male patients was 59.5 (33-72) years. Eighteen of which had LD and 20 had extensive disease (ED). Twenty patients had Eastern Cooperative Oncology Group (ECOG) 1 and 18 had ECOG 2 performance status. Objective response (OR) was obtained in 26 (68%) of the patients. While 13 patients had a CR rate, 6 patients remained stable (16%). The OR rate was observed to be 100% (CR 61%, partial response [PR] 39%) in patients with LD, whereas it was 40% (CR 10%, PR 30%) in patients with ED. The median survival was 9 months in LD and 6 months in ED. Relapses after CR occurred in 11 patients with LD (local relapse in 8; one in the brain; one in the liver; one in the bone) and one patient with ED (in the brain). The observed toxicities were grade III-IV leukopenia 13%, grade III-IV nausea and vomiting 8%, and 39% alopecia. CONCLUSION: We conclude that the described regimen is a well-tolerated, less toxic therapy for SCLC.

Adult↗

The effects of 21 or 30% O2 plus umbilical cord occlusion on fetal breathing and behavior.

We have shown previously that continuous fetal breathing can be induced by 100% O2 alone or combined with umbilical cord occlusion (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990). To know whether it could also be induced by lower O2 concentrations plus cord occlusion, we studied 9 chronically instrumented fetal sheep (16 experiments) using our window model. After a baseline cycle [1 low voltage + 1 high voltage electrocortical activity (ECoG) epoch] the fetal lung was distended via an endotracheal tube to about 30 cm H2O. Inspired N2 (control) and 21 or 30% O2 were given for one cycle each. While on 21% or 30% O2 the umbilical cord was occluded (balloon cuff). In 10 out of 16 experiments breathing output (% maximum of integral of EMGdi x f) increased after cord occlusion from 80 +/- 48 (N2) to 2871 +/- 641 (SEM; P < 0.01); in 7 of them breathing became continuous. Arterial PO2 increased from 14 +/- 1 (N2) to 33.5 +/- 5 Torr (occlusion; P < 0.01). In the other 6 experiments breathing output decreased from 319 +/- 116 (N2) to 86 +/- 38 (occlusion; P < 0.01) and arterial PO2 changed from 18 +/- 1 (N2) to 22 +/- 5 Torr (occlusion; P = 0.4). Arterial PCO2 increased similarly after occlusion in both groups, those which did respond with increased breathing (to 46 +/- 2 Torr) and those which did not respond (to 48 +/- 3 Torr; P = 0.6). The percent low voltage ECoG and the behavioral score increased after occlusion in the responder group only.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[The interhemispheric brain asymmetry of the rabbit in a state of "animal hypnosis"].

By the method of forced immobilization the rabbits were brought into the state of "animal hypnosis" (immobilization reflex), and their ECoG was recorded, which was further processed on the computer. It was found that during hypnosis a functional interhemispheric brain asymmetry was developed in rabbits with activity predominance in the right hemisphere. The "animal hypnosis" is a phasic process: in the ECoG of the rabbit under hypnosis a regular alternation of delta and theta activity takes place. Electrophysiological reconstructions in the rabbit brain during the change of its functional state correlate with the brain thermal reactions, revealed earlier.

Animals↗

Evaluation of cochlear function in a patient with "far-advanced" otosclerosis.

A patient with "far-advanced" otosclerosis with a profound bilateral hearing loss was evaluated for cochlear reserve using transtympanic electrocochleography (ECoG) and promontory stimulation. Results indicated that both ECoG and promontory responses were present, indicating that cochlear function was present bilaterally. A stapedectomy resulted in closure of the air-bone gap. Postoperative hearing yielded excellent aided responses compared to no measurable preoperative hearing aid benefit. This case serves to demonstrate the value of evaluating cochlear function using these electrophysiologic techniques.

Aged↗

The effect of 10% O2 on the continuous breathing induced by O2 or O2 plus cord occlusion in the fetal sheep.

Although the administration of 100% O2 alone or combined with umbilical cord occlusion induces continuous breathing and arousal in the fetal sheep (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990a), the individual contribution of O2 and cord occlusion to the response have not been determined. We hypothesized that if O2 is an important factor in the induction of continuous breathing, administration of O2 low enough (10%) to bring fetal arterial PO2 to about 20 torr while the fetus is breathing continuously should reverse these changes. Thus we subjected 12 chronically instrumented fetal sheep to 10% O2 for 10 minutes after the establishment of continuous breathing by O2 (4 fetuses; 137 +/- 1 days) or by O2 plus umbilical cord occlusion (8 fetuses; 134 +/- 1 days). Arterial PO2 decreased from about 250 torr to 20 torr during 10% O2. This induced a significant decrease in breathing output (EMGdi x f) related primarily to a decrease in frequency (f). In 3/5 experiments in 4 fetuses, with O2 alone, apnoea developed within 4 +/- 0.6 min; in 12/13 experiments in 8 fetuses, with added cord occlusion it developed at 5 +/- 0.6 min. With the decrease in PaO2, electrocortical activity (ECoG) switched from low to high-voltage within 6 minutes in 5/5 experiments (O2 alone) and in 11/13 (O2 plus cord occlusion). The findings suggest that umbilical cord occlusion alone is not sufficient to maintain breathing continuously and an increased PaO2 is needed. We speculate that in the fetus there is a vital link between PaO2, breathing and ECoG with low PaO2 inhibiting and high PaO2 favouring breathing and arousal.

Animals↗

[Venlafaxine extended release for the treatment of chronic pain. A series of 50 cases].

INTRODUCTION: The objective of this study is to investigate analgesic effectiveness and safety of venlafaxine extended release in chronic pain of any etiology. METHODS: Six month, observational, open study, carried out in two pain units. Initially, a daily dose of 75 mg of venlafaxine extended release was administered, increasing it to 150 mg, following clinical criteria. Treatment response was measured using the Visual Analogue Scale (VAS), rest and mobilization, Hospital Anxiety and Depression Scale (HAD) and Eastern Cooperative Oncology Group (ECOG) and an adverse event sheet to record adverse events occurring during the study. RESULTS: The study was carried out in a 50 patient sample with a mean age of 57.1 +/- 1.8 years, with chronic pain. A total of 85-90 % of the patients was maintained with a daily dose of 75 mg of venlafaxine extended release. This produced a gradual reduction of the VAS scores at rest (significant reduction of 5.2 +/- 1.1 to 2.7 +/- 1.5 points; (p<0.0005) and mobilization (significant reduction of 5.5 +/- 0.8 to 3.1 +- 1.6 points; p<0.0005). Pain relief increased progressively. Regarding physical activity measured by the ECOG scale, there was a reduction of the percentage of patients and increase of outpatients. Tolerability to venlafaxine was "excellent", "very good" or "good" for 72% of the patients. CONCLUSIONS: Extended release venlafaxine can be an effective and well-tolerated treatment in patients with chronic pain of any etiology, although it must be investigated in depth.

Adult↗

Treatment of advanced non-small cell lung cancer with vinorelbine in elderly Thai patients.

UNLABELLED: The present study evaluated the efficacy and toxicity of vinorelbine as single chemotherapy for elderly Thai patients with advanced non-small cell lung cancer (NSCLC). Twenty-eight patients with no prior chemotherapy and ECOG performance status of 0-2 were enrolled in the study. There were 20 males and 8 females with a median age of 72 years, and the median ECOG performance status was 1. Eight cases were stage IIIB and 20 cases were stage IV. Fourteen cases were adenocarcinoma, 13 were squamous cell and one was large cell NSCLC. These patients received vinorelbine 25 mg/m2 on day 1 and 8. This treatment produced partial response in 5 of 25 evaluable patients (20%). Median survival time was 40 weeks. Hematologic toxicity caused 9% grade 3 anemia, 1.5% grade 4 neutropenia and 0.5% grade 4 neutropenia. CONCLUSION: Chemotherapy is a valuable treatment option for elderly patients with advanced NSCLC. Single agent vinorelbine is able to induce an overall response with a low toxicity level in elderly Thai patients with advanced NSCLC.

Aged↗

Effects of prognostic factors and treatment on survival in advanced non-small cell lung cancer.

In this study, 304 stage III-B and IV non-small cell lung cancer (NSCLC) cases diagnosed and followed up in our hospital between January 2000 and December 2002 are retrospectively analysed. The effects of demographic, clinical, laboratory findings and different therapeutic modalities on survival were investigated. Of the cases, 31 (10.2%) were women, 273 (89.8%) were men and mean age was 60.59 +/- 10.73. Analysis by the Kaplan-Meier method revealed that median survival was 6.0 +/- 0.5 (95% CI: 5.1-6.9) months and 12 and 24-month survival rates were 25.27 +/- 2.99% and 11.48 +/- 2.77% respectively. By univariate analysis of 33 parameters, 12 of them were found to be effective on survival and this relationship was statistically significant (p< 0.05). These parameters indicating poor prognosis were age > 70, ECOG performance score > 1, dyspnea, peripheral lymphadenomegaly (LAM), mediastinal invasion, pleural effusion, distant metastasis, elevated serum LDH, CA 19.9, CA-125 values, not receiving curative radiotherapy (RT) (> 50 Gy) or chemotherapy (CT). A multivariate analysis by Cox regression method revealed that advanced age, mediastinal invasion and metastatic disease were not independent prognostic factors on survival whereas ECOG performance score > 1 (p= 0.000), absence of CT (p= 0.000) and curative RT (p= 0.018), dyspnea (p= 0.035), peripheral LAM (p= 0.022) and pleural effusion (p= 0.043) were independent prognostic factors on survival.

Aged↗

[Pathological and pathophysiological studies on central nervous system in experimental cerebral ischemia of the rat].

The present study was undertaken to elucidate the pathological and pathophysiological characteristics of experimental cerebral ischemia in rats. The purpose of this study was also to clarify whether this animal model is useful for the research of multiple cerebral infarction. In order to create a cerebral ischemia model, arterioles were embolized by injecting 2000 carbon-microspheres (50 microns in diameter) into the right internal carotid artery of ketamine anesthetized rats. Pathological studies and pathophysiological evaluations were performed by electrocorticography (ECoG) and by measuring regional cortical blood flow (CBF) in embolized rats. An attempt was also made to examine learning ability: embolized rats were subjected to the passive avoidance test. Pathophysiological studies revealed most microspheres to be located in the ipsilateral hemisphere with a few in the contralateral hemisphere. Most foci of cerebral infarction were distributed in the area fed by the ipsilateral middle cerebral artery and the anterior cerebral artery, while a few of them were found in the area fed by the contralateral anterior cerebral artery. Regions of cerebral infarction consisted of microcerebral infarctions, some of which were fused to each other. The pathological characteristics of this experimentally induced cerebral ischemia were those of multifocal cerebral infarction. Both ECoG and CBF decreased after injection of carbon-microspheres, and these two parameters did not recover for more than 60 min in both hemispheres. Seven days after cerebral embolization, the shortened response latency in the passive avoidance test, possibly indicating memory impairment, was observed. Our findings suggest that cerebral ischemia of the rat produced by carbon-microspheres (50 microns in diameter) is useful in the pathophysiological investigation of multiple cerebral infarction.

Acute Disease↗

Psychostimulants and G tolerance in rhesus monkeys: effects of oral modafinil and injected caffeine.

INTRODUCTION: Caffeine and modafinil are psychostimulants that may be taken by fighter aircraft pilots to reduce fatigue. Fighter pilots are subjected to high positive G loads that reduce cerebral blood flow and consequently may induce G-LOC. The aim of the experiment was to determine whether these drugs may reduce tolerance to G stress. METHODS: Seven adult male rhesus monkeys participated in the experiment. Five were equipped with ECoG and ECG wires and underwent two G tests (A and B). Each experiment consisted of five centrifuge runs. Before the runs, the monkeys received no drug (control) or were given either 7.5 mg x kg(-1) caffeine IM or 64 mg x kg(-1) modafinil PO or the corresponding vehicles. The runs were performed up to +13 Gz with an onset rate of 0.1 G x s(-1) (test A) or 3 G x s(-1) (test B). The run was ended when the electrical activity of one ECoG channel had disappeared (i.e., G-LOC). RESULTS: In experiment A, drug administration had no significant effect. In experiment B, the injection of the caffeine-free solvent caused a delay in G-LOC compared with the control condition (no administration). Caffeine solvent also induced an increase in plasma osmolality. DISCUSSION: Modafinil administration has no significant effect on the G tolerance of rhesus monkeys. Regarding caffeine, the drug seems to have caused the reverse effect compared with the solvent. CONCLUSIONS: Caffeine and modafinil administration had no significant effect on the G-tolerance of rhesus monkeys when compared with controls. This result needs to be confirmed in humans.

Acceleration↗

Cortical dysplasia: zones of epileptogenesis.

Cortical dysplasia describes a wide range of cerebral cortex structural anomalies and is a condition attributed to multiple etiologies including disruption in the migration of the maturing neurons, disturbance of the process of programmed cell death in the fetal brain, and even noxious environmental influence. Cortical dysplasia can be focal or diffuse and the insult depends more on the timing of the defect in neural development and to a lesser extent the cause. Identification of cortical dysplasia can be done using high resolution magnetic resonance imaging (MRI), histological examination of affected tissue, and EEG. Dysplastic lesions have shown intrinsic epileptogencity. Scalp EEG and electrocorticography (ECoG) reveal several unique patterns including continuous spikes or sharp waves, abrupt runs of high frequency spikes, and periodic spike complexes that occur during sleep. EEG and ECoG can help to guide the surgical resection. Developments in the understanding and treatment of epilepsy caused by cortical dysplasia are occurring rapidly. This article will attempt to provide a brief overview of cortical dysplasia to hopefully prepare and encourage the reader to further investigate cortical dysplasia.

Cerebral Cortex↗

[Neuronavigation and electrocorticography monitoring in resection of brain cavernous malformations].

OBJECTIVE: To investigate the indications, technical considerations, and effects of neuronavigation and electrocorticography (ECOG) monitoring in resection of brain cavernous malformations (CM). METHODS: From 1997 to 2003, 70 patients with CM, 53 males and 17 females, aged 33 (8 - 62), underwent resection of CM using neuronavigation and neurophysiological monitoring. The first episodes included hemorrhage (31 cases, 44.3%), seizure (29 cases, 41.4%), headache (5 cases, 7.1%), and focal neurological deficit (4 cases, 5.7%). One case was asymptomatic (1.4%), only discovered during physical examination. The size of CM focus was 21 mm (5-50 mm). The depth of tumor measured from the surface was 3-70 mm. Six patients had multiple lesions. The foci were located deep in the white matter of hemispheres in 39 cases, within the brainstem in 9 cases, within the basal ganglia or thalamus in 11 cases, within the cerebellum in 5 cases, and within the optic nerve in 1 case. Preoperatively a MRI procedure using 5 skin markers was performed with the data transferred to a neuronavigation workstation, thus reconstructing a three-dimensional image of the tumor. Supratentorial subcortical lobar cavernomas underwent microsurgery through sulcus and fissure approach. ECOG monitoring was performed on 29 patients with seizure during the operation and bipolar electrocoagulation on functional cortex was conducted. Follow-up was conducted for 19.4 months (6-24 months). RESULTS: No intraoperative death was found. Postoperative disability rate was 8.6%. Complete removal of the lesion demonstrated by postoperative MRI was obtained in all patients. New transitory neurological deficits occurred in 4 patients after operation and recovered within 1 month. Hemiparesis developed in 1 patient with thalamus CM (1.4%) and facial paralysis developed in 1 patient with pons CM, and both recovered in 6 mouths. Nineteen out of the 24 patients with preoperative seizure history (79.2%) were postoperatively free of seizure, five (20.8%) of them showed improvement. CONCLUSION: Patients with asymptomatic CM can be kept under observation. CM deep in brain after the first bleeding is the indication of surgical treatment. Combination of neuronavigation and neurophysiological monitoring contributes to safety of operation and decrease of postoperative disability rate.

Adolescent↗

[Intraoperative monitoring with transtympanic electrocochleography].

Transtympanic electrocochleography (ECoG) enables auditory evoked potentials to be recorded directly from the peripheral organ, and ECoG recordings can be used as a routine during operations. Examples of cochlear and eighth nerve monitoring in middle ear, inner ear, and cerebellopontine angle surgery are given. This monitoring tool provides a continuous feedback to the surgeon of the effects of the operation on the cochlea and the auditory pathway.

Acoustic Stimulation↗

[Frontal seizures recorded by magnetoencephalography. Case report].

INTRODUCTION: This paper reports the usefulness of magnetoencephalography (MEG) in the anatomical localization of the onset and spread of seizures. CASE REPORT: In a 34-year-old male patient who suffered from drug-resistant complex partial seizures (sometimes generalized) with loss of awareness, magnetic resonance imaging revealed a probable left frontobasal cortical dysplasia. Ictal scalp electroencephalogram showed left frontotemporal theta waves. Electrocorticography (ECoG) registered interictal polyspike discharges and located the seizure onset in the lateral orbital side of the left frontal lobe. Three seizures were registered by MEG, clinically similar to the ones usually experienced by the patient. MEG ictal spike dipole location showed seizure onset coming from the left inferior frontal gyrus (as the ECoG), spreading on to other frontal areas, insula and temporal lobe, all in the left hemisphere. CONCLUSION: MEG may be considered as a useful diagnosis modality in the study of partial seizure physiopathology as well as in its presurgical evaluation.

Adult↗

Surgical outcomes and seizure control rates after resection of dysembryoplastic neuroepithelial tumors.

OBJECT: In this study the authors review the outcomes in pediatric patients who presented with seizures and underwent resection of dysembryoplastic neuroepithelial tumors (DNETs). The authors focus on the diagnostic evaluation and surgical techniques that facilitate gross-total tumor resection and subsequent freedom from seizures. METHODS: Eighteen patients between the ages of 1 month and 13 years who presented with seizures underwent resection of DNETs between January 1992 and December 2004. Preoperative evaluation included magnetic resonance (MR) imaging and interictal scalp electroencephalography (EEG) in all patients, functional MR imaging in eight patients, video monitoring with ictal scalp EEG in 12 patients, interictal single-photon emission computerized tomography (SPECT) scanning in one patient, and ictal SPECT scanning in two patients. Thirteen patients underwent one-stage procedures, whereas five underwent two-stage procedures (implantation of monitoring electrodes followed by tumor resection), either for functional language mapping (three patients) or due to inconclusive preoperative data (two patients). Intraoperative electrocorticography (ECoG) was performed in 17 patients and led to resection of the cerebral cortex beyond the tumor margins in 10 of them. According to operative reports, gross-total tumor resections were achieved in all patients, but one child had minimal residual tumor on postoperative MR images that has remained stable. The only surgical complication was a transient third cranial nerve palsy. Over a median follow-up duration of 1.6 years, all patients are seizure free and without radiographically detected tumor recurrence. CONCLUSIONS: Dysembryoplastic neuroepithelial tumors are a highly treatable cause of epilepsy in children. Excellent rates of complete tumor resection and seizure control with minimal morbidity can be attained using intraoperative ECoG and two-stage surgical procedures when appropriate.

Adolescent↗

N omega-nitro-L-arginine-methyl ester inhibits electrocortical recovery subsequent to transient global brain ischemia in Mongolian gerbil.

Electrocorticographic (ECoG) activity remains isoelectric for about 15 min after transient (10 min) bilateral carotid arteries occlusion in mongolian gerbils. In this model of global forebrain ischemia N omega-Nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, significantly delays the recovery of ECoG amplitude. Thus, the present experiments suggest that NO is involved in the cerebrovascular physiological response to brain ischemia.

Animals↗

[Study on the relationship among the international scales for quality of life evaluation in patients with lung cancer, the East Cooperative Oncology Group Status and Lung Cancer Symptoms Lists of TCM].

OBJECTIVE: To investigate the relationship among international scales for quality of life (QOL), physical performance assessment and Lung Cancer Symptoms Lists of Traditional Chinese Medicine (LCSL) from the viewpoint of clinical observation. METHODS: QOL of 363 patients with lung cancer was estimated with two international scales, the European Organization for Research and Treatment of Cancer QOL Questionnaire LC-43 (EORTC QLQ-LC43) and the Functional Assessment of Cancer Therapy General and Lung (FACT-L). In the same time, scores calculated by Karnofsky Performance Status (KPS), East Cooperative Oncology Group Status (ECOG) and LCSL were recorded. Correlation and consistency among them were analyzed. RESULTS: EORTC QLQ-C43, FACT-L were correlated with KPS, ECOG and LCSL, but the correlation coefficient was small. All these indexes were consistent. CONCLUSION: QOL should be assessed by QOL questionnaire, not by physical performance indexes, although they can be the simply forecast indexes of QOL. There is certain consistency between LCSL, QOL and physical performance.

Activities of Daily Living↗

Evaluation of epoetin supplemented with oral iron in patients with solid malignancies and chronic anemia not receiving anticancer treatment.

OBJECTIVE: To evaluate the effectiveness and improvement in quality of life (QOL) of epoetin alfa administration supplemented with oral iron as a therapeutic regimen for patients with solid malignancies and anemia of chronic disease (ACD), not receiving chemotherapy and/or radiotherapy. PATIENTS AND METHODS: A total of 100 patients with cancer-related anemia, not subjected to chemotherapy and/or radiotherapy, were randomized to receive for a maximum of 24 weeks either oral iron, equivalent to 200 mg elemental iron once daily, or epoetin alfa 40,000 IU subcutaneously once weekly plus oral iron once daily. RESULTS: Patients in the epoetin alfa group had, from baseline to study end, a mean increase in hemoglobin (Hb) levels of 2.4 g/dL, whereas in the control group the mean Hb level decreased by 0.1 g/dL, (p<0.001). Improvement in QOL as assessed by the LASA and the FACT-An questionnaire were greater in patients in the epoetin alfa group than in the control group (mean change, LASA-energy level: 30.4 mm vs. 0.4 mm, -daily activities: 31.7 mm vs. 0.4 mm, -overall well-being. 32.4 mm vs. 4.9, FACT-An: 43.3 vs. 13.4, respectively). As for ECOG score, patients in the epoetin alfa group had a mean improvement of 0.16 from baseline to study end (control group: 0.06). Improvement in QOL parameters and in ECOG scores correlated positively with increased hemoglobin levels. CONCLUSION: Our results suggest that weekly epoetin alfa therapy supplemented with daily oral iron increases Hb levels and improves QOL in patients with solid malignancies and ACD who are not receiving chemotherapy and/or radiotherapy. This regimen offers optimal therapy in this population taking into consideration physician's convenience and patient's compliance.

Administration, Oral↗