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PubMed1988

Effects of diphenhydramine in the fetal lamb after maternal or fetal administration.

The effects of diphenhydramine on fetal behavioral states, breathing activity, blood gas status, arterial pressure and heart rate have been investigated in the fetal lamb after maternal or fetal drug administration to steady state in chronically instrumented pregnant sheep. During maternal drug infusion there were declines in the percentage of low voltage electrocorticographic (ECoG) pattern 55-46%), the percentage of low voltage ECoG activity containing rapid eye movements (80-55%), the overall incidence of fetal breathing (42-21%) and in the amount of breathing during low voltage ECoG activity (67-36%). These sedative like effects occurred at fetal plasma drug concentrations (approximately 36 ng/ml) lower than those resulting in discernable central nervous system effects in adults. Drug infusion to fetus achieved higher fetal plasma drug levels (approximately 448 ng/ml) and resulted in a transient decline in arterial Po2 and pH, associated with transient tachycardia and vigorous breathing movements during the initial portion of the infusion. There was also a significant fall in the amount of low voltage ECoG pattern (51-26%) and marked increases in the amount of intermediate voltage pattern (8-46%), and an increase in the occurrence of rapid eye movements during this intermediate voltage pattern (8-63%). In summary, diphenhydramine elicits significant effects in the fetal lamb, the precise nature of which varies with drug concentration.

Animals↗

PubMed1988

[Electric response audiometry in retrocochlear hearing disorders].

The intensive clinical use of Electric Response Audiometry (ERA) has recently improved the diagnosis of sensorineural hearing loss. The Auditory Evoked Potentials (AEP) allow a precise topodiagnosis of the whole auditory system. However, specific limitations of the different potentials (cochlear, neural, brainstem, thalamic, cortical) have to be considered to avoid an overestimation of ERA. Based on the author's own material of more than 3500 recordings, most cases of a retrocochlear hearing loss are located at the auditory nerve and the brainstem. Therefore, brainstem electric response audiometry (BERA) and electrocochleography (ECoG) are the two most important methods of ERA. Typical Brainstem AEP (BAEP) features of retrocochlear disorders are shown. They are of different diagnostic value. A prolongation of the central conduction time or a break down of the later BAEP, both unequivocal signs of a retrocochlear lesion, were found in only 62 per cent of 100 cases of acoustic neuroma. However, diagnostic sensitivity can be improved to 96 per cent by additional use of ECoG and electrical promontory testing of the excitability of the auditory nerve. This value cannot be attained by any other audiometric test. These results show that BERA and ECoG are essential screening methods of high sensitivity in the differential diagnosis of sensorineural hearing loss. Additional values for diagnostic specificity and efficacy are also given in comparison with a group of patients initially suspected of having a cerebellopontine angle tumour. These values exceed those of conventional audiometric tests by far. Therefore, BERA and ECoG are reliable predictors of a retrocochlear lesion and can be judged as the best indicators for a CT scan or magnetic resonance imaging at present.

Audiometry, Evoked Response↗

PubMedDate not supplied

Model of global forebrain ischemia in the unanesthetized rat.

Global forebrain ischemia was induced in unanesthetized rats by electrocauterization of the vertebral arteries and transient occlusion of the common carotid arteries for 30 minutes. Local cerebral blood flow (l-CBF), cortical tissular pO2 (tpO2), electrocorticogram (ECoG), mean arterial pressure, pH and blood gas determinations and neurologic deficit were evaluated during and after ischemia. Cerebral ischemia induced a substantial decrease in l-CBF and tpO2 and the ECoG was flattened. One hour after ischemia, the neurologic deficit was at its maximum, l-CBF was still decreased and ECoG depressed. Twenty-four hours later, the neurologic deficit was still present but ECoG, l-CBF and tpO2 had returned to their preischemic values. Treatments with naloxone were performed during, after or during and after ischemia. When naloxone was administered during or after ischemia, postischemic neurologic deficit was not influenced by the treatment. A slight but significant improvement of the neurologic score was observed when naloxone was injected during ischemia and infused thereafter. Our results show that this experimental model of cerebral ischemia is suitable for quantification of neurologic alterations during the postischemic period. The slight improvement observed with naloxone suggests that endogenous opioids may have a minor role in the neurologic consequences of ischemia.

Animals↗

PubMed1987

Brainstem auditory evoked potentials in the fetal sheep, in utero.

We studied brainstem auditory evoked potentials (BAEPs) in 8 fetal sheep in utero, ranging in gestational age from 105 to 142 days gestation (normal term 147 days). We could not elicit BAEPs prior to 117 days of gestation. After this age rapid maturation was seen, with three discernible peaks observed prior to 120 days and five peaks after 120 days. A significant (P less than 0.05) gestational age related fall in peak latencies and interpeak latencies was observed. The rate of stimulus presentation that could be tolerated without significant changes in wavepeak latency or amplitude also increased with advancing gestational age. In older fetuses (greater than 125 days), where a differentiated electrocorticogram (ECOG) was observed, differences were seen in latency and amplitude of several of the BAEP wavepeaks dependent upon the state. In high voltage ECOG states the amplitudes of wave IV and V were significantly (P less than 0.05) greater than in the low voltage ECOG state and the latencies of wave I, II and V were significantly (P less than 0.05) longer in low as compared to high voltage ECOG state. The BAEP, being obtainable over very short periods of time, appears to provide a useful indice of neural maturation for the sheep fetus in utero.

Acoustic Stimulation↗

PubMed1987

High-dose lymphoblastoid interferon in advanced renal cell carcinoma: an Eastern Cooperative Oncology Group Study.

This report describes a phase II Eastern Cooperative Oncology Group (ECOG) study of high-dose lymphoblastoid interferon (IFN alpha-n1) in 39 patients with measurable, advanced renal cell carcinoma. The original treatment plan was 30 X 10(6) units/m2 (30 mU) of IFN alpha-n1 im daily X 10 days; treatments were repeated every 21 days. This dose and schedule proved intolerable, with none of seven patients able to complete greater than 10 days of therapy because of fever, lassitude, hepatic dysfunction, and myelosuppression. Patients were subsequently treated with the following regimen: 3 mU/m2 on Day 1; 5 mU/m2 on Day 2; 10 mU/m2 on Day 3; and 20 mU/m2 on Days 4-10. Thirty-three new patients received this regimen and two patients received this schedule after having received 30 mU/m2. Using this second regimen, 30% of the patients were able to complete two cycles of treatment without dose reduction or interruption. Five patients (13%) had partial response (ECOG criteria) of measurable tumor. Median time to response was 140 days. Responses were documented in lung metastases in four patients and in a pelvic soft tissue mass in the fifth. Response rates and survival times are similar to those seen in prior ECOG phase II trials in advanced renal cell carcinoma. Eight of 39 patients are still alive greater than 2 years after beginning therapy. Only two of these patients had had an objective response, however. Such prolonged survival is more frequent than has been seen in previous ECOG studies. The relative contribution of patient selection and interferon therapy to this survival is uncertain.

Aged↗

PubMed1979

Ontogenetic development of electrocorticogram in the rat.

Spontaneous electrocorticogram (ECoG) was recorded in frontal (sensorimotor) temporal (auditory) and occipital (visual) cortical regions of 86 male rats (immobilized with d-tubocurarine) aged from 3 days to adulthood. Activity which could be classified as ECoG was for the first time recorded in 5-day-old rats; it was formed by groups of slow waves with unstable frequency intermingled with periods of isoelectric line. Discontinuous ECoG activity was regularly registered even in 10-day-old rats, exceptionally in 12-day-old rats. During further maturation of the continuous ECoG an increase in frequency and an establishment of a basic rhythmic activity synchronous over both hemispheres took place, so that 25- and 30-day-old rats did not differ from the adult ones. Autocorrelagrams and power frequency spectra demonstrated a broad frequency range of the basic rhythm as well as delay in the development of occipital cortical areas in comparison to frontal areas.

Aging↗

PubMed1977

[Dimer-X in the intracranial subarachnoid space - electrocorticographic study (author's transl)].

As a sequel to our first report, we are now presenting the results of the ECoG examination of the rats in about 15 min. after injecting Dimer-X into their cisternae magnae. The injection of 28% iodine Dimer-X into the cisterna magna causes the multiple bursts of spikes, but the occurrence is less frequent when the low concentration of Dimer-X are injected. The ECoGs show occurence of a few spikes with the premedication of Valium or Decadron, and very few spikes are seen on the ECoG, when Valium and Decadron are given as a premedication. From these results as seen on ECoG, we conclude that during Dimer-X ventriculography lw concentration of Dimer-X should be used with premedication of Valium and Decadron.

Animals↗

PubMed1983

Influence of certain stimulation parameters on the character of the cortical self-sustained after-discharge.

The ECoG pattern of self-sustained after-discharges (SSADs) evoked by rhythmic electrical stimulation of the cerebral cortex is far from uniform. In acute experiments on male rats the authors studied the significance of the frequency, intensity and length of stimulation for the character of the resultant SSAD. In the first group (11 rats), a stimulation frequency of 8 Hz was used; the stimulation series, which lasted 10 and 20 s, always led to the formation of a SSAD composed of spike-and-wave rhythm right from the outset. Shortening the time of stimulation markedly reduced its effectiveness. In the second group (10 animals), stimulation with 50 Hz frequency often evoked a complex SSAD starting with desynchronization, which was followed by fast spike activity of increasing amplitude and only later by spike-and-wave rhythm or by polyspike-and-wave rhythm. Towards the end, serrated waves--i.e. graphoelements typical of SSADs evoked by electrical stimulation of limbic structures--often appeared in the SSAD. A higher stimulation intensity increased the incidence of this complex SSAD. In this group a minimum duration of stimulation was also essential (series of less than 2 s were not reliably effective). When this second type of SSAD ended, depression of ECoG activity was followed in 27% of the cases by a spontaneous recurrent seizure (RS). The ECoG character of these RS can be very variable. The two types of seizures evoked by slow and fast stimulation differ from each other not only in respect of their ECoG pattern (where the difference is probably due to more pronounced propagation to subcortical structures after faster stimulation), but also as regards the presumed mechanism of their onset.

Animals↗

PubMed1982

Effects of hyperbaric oxygen on heart, brain, and lung functions in rat.

Electrocardiogram (ECG), electrocorticogram (ECoG), and respiratory rate (RR) were monitored in awake, unrestrained rats during continuous exposure to 1, 3, and 5 ATA O2 until death. The RR showed a consistent pattern at 1 and 3 ATA O2, while no pattern at 5 ATA O2 was observed. A characteristic pattern in heart rate (HR) was demonstrated at 3 ATA O2. At 5 ATA O2 a continuous reduction in HR occurred, while at 1 ATA O2 no significant change was found. The ECG at 3 ATA O2 showed various arrhythmias prior to convulsions, which were severely intensified concurrently with and following convulsions and respiratory distress. The ECG arrhythmias at 1 ATA O2 occurred after the first day of exposure and were intensified during respiratory distress and increased RR. The ECG arrhythmias at 5 ATA O2 usually occurred following the appearance of the first paroxysmal cortical electrical discharges (FED), and were extremely intensified following the onset of the first generalized clinical convulsions. Increased slow-wave activity in ECoG preceded the onset of the FED at 3 and 5 ATA O2. During days 2 and 3 at 1 ATA O2 the ECoG mostly contained slow and low-amplitude waves. The different levels of oxygen in this study often showed different effects on a particular physiological parameter. It is concluded that alterations in ECG, ECoG, HR, and RR at some pressures signal the appearance of severe pathophysiological changes during prolonged hyperbaric oxygen exposure in rats, and that the relations of these effects are not uniform at all oxygen pressures.

Animals↗

PubMed1995

Doxorubicin/paclitaxel combination chemotherapy for metastatic breast cancer: the Eastern Cooperative Oncology Group experience.

The addition of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to the therapeutic armamentarium for breast cancer has resulted in novel opportunities and challenges for the clinician. In a series of trials that began in 1992, the Eastern Cooperative Oncology Group (ECOG) investigated the role of paclitaxel in combination with doxorubicin for the treatment of patients with advanced breast cancer. The design of the first trial, a limited-institution pilot study, involved alternating doxorubicin and paclitaxel as single agents. The alternating schedule was well tolerated and associated with objective responses in seven of 12 patients entered into the trial. In the second trial, a limited-institution phase I trial, bolus doxorubicin was combined with paclitaxel administered over a 24-hour infusion, with administration of the two drugs separated by 4 hours. While no dose-limiting toxicity was seen at doses of 50 and 150 mg/m2 of doxorubicin and paclitaxel, respectively, dose-limiting mucositis occurred at respective doses of 60 and 175 mg/m2. Mucositis was more common when administration of paclitaxel preceded that of doxorubicin than when doxorubicin preceded paclitaxel. Based on these results, the ECOG initiated a phase III trial comparing single-agent paclitaxel, single-agent doxorubicin, and the combination of paclitaxel and doxorubicin. This study, now an Intergroup trial of ECOG, the Southwest Oncology Group, and the North Central Cancer Treatment Group, is designed to accrue 730 patients. This trial will close to accrual in September 1995, and analysis of the trial should provide useful information regarding the potential synergy of doxorubicin and paclitaxel, the degree of cross-resistance between the two compounds, and the relationship between steady-state paclitaxel levels and response to therapy. In addition, ECOG is currently conducting a trial designed to confirm the striking activity of cisplatin and paclitaxel seen in the British Columbia trials. Future trials by the group will examine means of combining paclitaxel with other active agents.

Antibiotics, Antineoplastic↗

PubMed1995

[Research on prognostic factors in large-cell lymphomas].

BACKGROUND: To carry out a study on the prognostic factors in large cell lymphomas (LCL) treated during the last decade and validate the international prognostic index (IPI). METHODS: One hundred twenty-four cases of newly diagnosed LCL, treated from 1978 to 1990, with a mean follow up of 27 months (1-142) were included in the study. The chemotherapy used was: CHOP (65%), ProMACE-CytaBOM (17%) and others (C-MOPP, MACOP-B). RESULTS: Complete remission (CR) was achieved in 71% of the cases and partial in 11%. Logistic analysis allowed the identification of three adverse factors to CR: Ann Arbor stage III, IV (p = 0.004; odds ratio, OR = 0.19), elevated tumoral load (p = 0.006; OR = 0.22) and age > or = 60 years (p = 0.02; OR = 0.31). Recurrence free survival (RFS) at 3 years was 67% (CI 95%; 55-79) with the median not having been achieved. Cox analysis allowed the identification to the ECOG > or = 2 scale as the only independent adverse factor (p = 0.0006; RR = 4.85) while Ann Arbor staging demonstrated marginal influence (p = 0.08). Global survival (GS) at 5 years was 45% (CI 95%; 35-55) with a median of 38 months. Multivariant analysis of independent adverse factors of GS were ECOG scale > or = 2 (p < 0.00001; RR = 6.07), Ann Arbor stage (p = 0.004; RR = 2.64) and hypoalbuminemia (p = 0.01; RR = 2.28). On inclusion of therapeutic response (TR) in the analysis, the factors chosen were absence of CR (p < 0.00001; RR = 9.58) and ECOG > or = 2 (p = 0.0004; RR = 4.24). CONCLUSIONS: Three variables evaluated at diagnosis, general state (ECOG), Ann Arbor stage and albumin, determined the prognosis in this series of large cell lymphoma. A prognostic model was designed from the same with three risk groups. The application of the international prognostic index to this series separated the patients into 4 groups of differentiated prognosis.

Adolescent↗

PubMedDate not supplied

Electrocortical desynchronization after microinfusion of kainic acid into the locus coeruleus in rats.

Receptors for the endogenous excitatory amino acid, 1-glutamate, occur in the rat locus coeruleus (LC), an area of the brain involved in the control of sleep/arousal mechanisms and other behavioral functions. However, the functional role of this neurotransmitter system in the LC has yet to be clarified. Therefore, to address this question we have studied the gross behavioral changes and the effects on the electrocortical (ECoG) spectrum power in rats receiving focal injections into the LC of kainic acid, an agonist at the non-N-methyl-D-aspartate (non-NMDA) glutamate receptor subtype. Unilateral injection of kainic acid (25, 50, 100 and 200 pmol) into the rat LC produced contralateral turning, circling and stereotypes; these effects were accompanied by dose-dependent ECoG desynchronization and by a significant decrease in total voltage power and in 6-9, 9-12 and 12-16 Hz bands of the ECoG spectrum. A pretreatment (15 min before) with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) (50 and 100 pmol), a competitive non-NMDA receptor antagonist, or with dizocilpine meleate (MK-801) (1 pmol) and 3-(2-carboxy-piperazine-4-yl)-1-propenyl-1-phosphonic acid) (CP-Pene) (10 pmol), two selective NMDA receptor antagonists, injected directly into the LC, abolished the behavioral and ECoG spectrum power effects typically elicited by kainic acid (50 pmol). Similar results were observed in rats pretreated with diazepam (0.5 mg/kg given i.p. 15 min before kainic acid).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

[An amplitude-interval analysis of the electrocorticogram of the normal rat and under the action of fenamine and buspirone].

The ECoG effects of natural vigilance changes were analysed on a microcomputer in rats. In addition, the effects of the psychostimulant phenamine (1 mg/kg, i.p.) and the anxiolytic buspirone (1.5 mg/kg, i.p.) were studied. The ECoG data were processed using the amplitude-interval analysis technique. The two drugs significantly modified ECoG: the maximum effect was observed within the first 30 min after buspirone administration and at 30-60 min after phenamine. Each drug affected the ECoG in its own particular manner, which was similar to their natural activation, but not identical to it. The findings provide evidence for the assumption that the activation processes play an important role in making buspirone show its psychotropic effects.

Algorithms↗

PubMed1993

Prenatal nicotine exposure evokes changes in the incidence and degree of fetal electrocortical activation.

The effects of acute and chronic nicotine (N) administration on fetal electrocorticogram (ECoG) were investigated with spectral analysis. Fetal lambs were instrumented surgically to permit unanesthetized ECoG monitoring and N administration. Acute exposure studies used 4-hr constant-rate infusions at 0.6, 3 or 10 mg/hr. Chronic exposure studies used continuous infusions at 1.2 mg/hr for 7 days. The fast Fourier transform and several derivative parameters were used to quantitate the fetal ECoG during both control records and N infusions. Four states were identified and quantitated in the control ECoG: high-voltage slow activity (State I); low-voltage, fast activity (State IV); and two transitional states of intermediate amplitude and frequency. Acute N infusions elicited changes in the incidence and degree of electrocortical activation that were biphasically dose-related. The 0.6-mg/hr infusion evoked electrocortical activation through an increase in the incidence of State IV. Higher infusion rates elicited progressively less electrocortical activation. The 3-mg/hr infusion affected marginal activation, through a reduction in the incidence of State I. The 10-mg/hr infusion elicited mixed activation and depression, as assessed by multiple parameter changes. Desensitization of several responses diminished the magnitude of depressive effect observed during the 3- and 10-mg/hr infusions. Chronic nicotine infusions elicited progressive augmentation of electrocortical activation, through increases in the incidence and frequencies of State IV. Tolerance to this activating response was not observed.

Animals↗

PubMed1996

Modulation of forebrain electroencephalographic activity in halothane-anesthetized rat via actions of noradrenergic beta-receptors within the medial septal region.

The locus coeruleus (LC)-noradrenergic system modulates forebrain electroencephalographic (EEG) activity in halothane-anesthetized rat. For example, unilateral enhancement of LC neuronal activity increases cortical EEG (ECoG) and hippocampal EEG (HEEG) indices of arousal bilaterally (Berridge and Foote, 1991). Conversely, bilateral suppression of LC discharge activity increases EEG measures of sedation (Berridge, et al., 1993b). The EEG-activating effects of LC stimulation appear to involve noradrenergic beta-receptors (Berridge and Foote, 1991). Two candidate sites at which LC efferents could influence ECoG and HEEG are the medial septum/vertical limb of the diagonal band of Broca (MS) and the substantia innominata/nucleus basalis of Meynert (SI). To determine whether norepinephrine mediates such actions within either of these regions, the EEG effects of small infusions of a beta-agonist or antagonist into MS or SI were examined in halothane-anesthetized rat. Unilateral infusions (150 nl) of the beta-agonist isoproterenol (ISO) (3.75 microg, 17 nmol) into MS, but not SI (150-450 nl), elicited robust bilateral activation of ECoG and HEEG. Infusions of glutamate (0.5 microg, 3.0 nmol) into either MS or SI elicited bilateral ECoG and HEEG activation. Neither vehicle infusions into MS nor infusions of ISO into regions adjacent to MS altered forebrain EEG activity. Bilateral, but not unilateral, MS infusions of the beta-antagonist timolol (3.75 microg, 8.7 nmol) decreased EEG indices of arousal in the lightly anesthetized preparation. Power spectral analyses provided quantitative confirmation of these qualitative observations. These results indicate that under these experimental conditions, noradrenergic efferents, presumably arising from LC, modulate forebrain EEG state via actions at beta-receptors located within MS. The results presented in the accompanying report extend these observations to the unanesthetized preparation and incorporate additional measures of behavioral state.

Adrenergic beta-1 Receptor Agonists↗

PubMed1997

Long-term survival in acute myeloid leukemia: the Eastern Cooperative Oncology Group experience.

BACKGROUND: The data base of the Eastern Cooperative Oncology Group (ECOG) provides access to data on a large adult patient population drawn from more than 25 major university institutions and hundreds of participating hospitals. Extensive medical files are maintained at the ECOG Coordinating Center and are updated regularly. METHODS: Data on 1414 eligible patients with acute myeloid leukemia (AML), treated on 6 ECOG protocols during the period 1976-1994, were reviewed to determine the number of long-term survivors (LTS) and to identify factors that predicted LTS. Disease free survival and factors impacting quality of life were examined as well. RESULTS: Of the 1414 patients, 274 survived for > or = 3 years and were considered LTS. A logistic regression analysis revealed that factors predicting LTS included age < 55 years, female gender, treatment between 1985 and 1990, white blood cell count < 10,000 cells/mm3, and hemoglobin > 10 g/dL. Disease free survival improved with escalating intensity of therapy. Quality-of-life data showed that infections were fairly common. Significant graft-versus-host disease occurred in 6 of 40 patients who received allogeneic bone marrow transplantation and contributed to the deaths of 4 individuals. Information on employment, insurance, social or marital difficulties, and psychosocial issues was more difficult to obtain. CONCLUSIONS: Prognosis in AML is a complex interaction involving the cellular origin of the malignant clone, morphology, and evolving therapeutic strategies. The most recent ECOG studies incorporate these variables and should provide additional insights into factors affecting LTS in patients with AML.

Acute Disease↗

PubMed1988

Evaluation of pathology review of malignant lymphomas and Hodgkin's disease in cooperative clinical trials. The Eastern Cooperative Oncology Group experience.

Although central expert pathology review for quality assurance in cooperative clinical trials involving malignant lymphomas and Hodgkin's disease was put in place by the NCI two decades ago, its impact upon patient eligibility for given treatment protocols has never been assessed. We reviewed diagnoses from contributing pathologists, the Eastern Cooperative Oncology Group (ECOG) review pathologists and the Pathology Panel for Lymphoma Clinical Studies in 2019 cases from 14 ECOG protocols. Although we found high rates of disagreements in diagnoses, the vast majority of these represented differences which did not impact on protocol eligibility. A total of 221 cases (10.9%) were excluded from protocols, representing a range of 2.8 to 36.7% of cases per protocol. Eighty-six percent of the exclusions resulted from the initial review by the ECOG hematopathologists. Our data indicate that while central pathology review is mandatory for quality assurance in malignant lymphoma (ML) and Hodgkin's disease (HD) protocols, a two-tier review mechanism is not necessary for adequate quality control.

Clinical Trials as Topic↗

PubMed1990

Performance status assessment in cancer patients.

Performance status assessment, Karnofsky performance status (KPS), and Eastern Cooperative Oncology Group (ECOG) scales were performed in 100 consecutive patients independently by two physicians and by the patients themselves to evaluate the scales' validity and reliability. Findings of Kendall's correlation were highly significant between physicians (0.76 for KPS, 0.75 for ECOG) and between physicians and patients (0.65 for KPS, 0.59 for ECOG). The authors point out that patients' self evaluation could provide a valuable and reliable assessment.

Activities of Daily Living↗