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Acute hippocampal recording and pathology at temporal lobe resection and amygdalo-hippocampectomy for epilepsy.

An electrocorticographic (ECoG) study is reported of patients undergoing surgery for epilepsy of temporal lobe origin. During 22 en bloc resections and six out of a total of 18 amygdalo-hippocampectomies, the activity of the hippocampus was also recorded by a multipolar strip electrode placed along its axis on the ventricular surface. Patients with mesial temporal pathology, chiefly mesial temporal sclerosis, made up the majority of those selected for amygdalo-hippocampectomy. They showed a characteristic ECoG pattern, with spikes localised to the mid part of the second and third convolutions and inferior aspect of the temporal lobe. Typically, this was associated with hippocampal discharges showing an anterior maximum. Pathology involving lateral temporal neocortex and non-specific findings were associated with more widespread temporal spikes and a maximum discharge amplitude over the mid and posterior parts of the hippocampus. It is suggested that intraoperative recording of the ECoG and hippocampal activity may provide a guide to the choice between en bloc resection and amygdalo-hippocampectomy.

Action Potentials↗

Central neuropeptide Y stimulates ingestive behavior and increases urine output in the ovine fetus.

We hypothesized that central neuropeptide Y (NPY) increases swallowing activity and alters renal function in the near-term ovine fetus. Six ewes with singleton fetuses (130 +/- 2 days of gestation; 148 days = term) were chronically prepared with arterial and venous catheters, a fetal lateral cerebroventricular cannula, and fetal bladder and amniotic fluid catheters. For determination of fetal swallowing, electromyogram wires were placed in the fetal thyrohyoid muscle and the upper and lower nuchal esophagus. Electrodes were implanted on the parietal dura for determination of fetal electrocorticogram (ECoG). After 5 days of recovery, fetal swallowing, ECoG, blood pressure, and heart rate were monitored during a 3-h basal period. At t = 3 h, ovine NPY (0.05 mg/kg) was administered into the lateral ventricle, and fetuses were monitored for an additional 8 h. A control study of central administration of artificial cerebral spinal fluid was performed on an alternate day. Central NPY significantly increased swallowing activity during low-voltage ECoG from basal activity (1.26 +/- 0.15 swallows/min) at 4 h (1.93 +/- 0.37 swallows/min), 6 h (1.69 +/- 0.27 swallows/min), and 8 h (2.38 +/- 0.31 swallows/min). NPY significantly increased fetal urine flow (basal: 0.13 +/- 0.02; 4 h: 0.21 +/- 0.04; 6 h: 0. 19 +/- 0.03 ml.kg(-1).min(-1)). These results demonstrate that central NPY stimulates fetal swallowing activity and increases urine output, which may contribute to the in utero development of ingestive behavior.

Animals↗

Nitric oxide modulates spontaneous swallowing behavior in near-term ovine fetus.

Human and ovine fetuses demonstrate an enhanced rate of swallowing, an activity critical for amniotic fluid regulation. Fetal swallowing may be modulated by both systemic and central factors. Nitric oxide (NO) is a central neuromodulator that has been localized to brain regions regulating thirst and swallowing. We sought to determine if NO contributes to the regulation of spontaneous ovine fetal swallowing. Six time-dated pregnant ewes with singleton fetuses (129 +/- 1 day) were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram (ECoG) and esophageal electromyogram electrodes. After a 2-h control period, fetuses were given lateral ventricle injection of NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME) and monitored for 2 h. NO precursor L-arginine was then injected into the lateral ventricle, and fetuses were monitored for a final 2 h. All fetuses received an additional control study of fetal swallowing before and after lateral ventricle injection of artificial cerebrospinal fluid (aCSF). Data were analyzed with repeated-measures ANOVA and paired t-test (P < 0.05). Suppression of a central NO with central L-NAME significantly reduced mean (+/-SE) spontaneous fetal swallowing (1.2 +/- 0.1-0.6 +/- 0.1 swallows/min low-voltage ECoG; P < 0.01). Restoration of central NO by L-arginine significantly increased fetal swallowing to pre-L-NAME levels (1.2 +/- 0.1 swallows/min low voltage). There were no changes in fetal swallowing during the control study of aCSF. Fetal ECoG activity and blood pressure did not change during the study or control aCSF injection. We conclude that NO is an important neuromodulator of fetal swallowing activity. Central NO synthase activity may contribute to the heightened level of spontaneous fetal swallowing and thus amniotic fluid regulation.

Animals↗

Effect of increased arterial CO2 on fetal breathing and behavior in sheep.

We studied breathing and behavioral response to increased arterial CO2 (PaCO2) in 12 fetal sheep between 130 and 145 days of gestation. Of these 12 fetuses, 10 had an increase in PaCO2 through maternal rebreathing of CO2; in the other 2 fetuses CO2 was increased via an endotracheal tube and application of continuous distending airway pressure. We used our window technique to observe and videotape fetal behavior. The experiments consisted of recording breathing activity and behavior during resting conditions (1 low- and high-voltage ECoG cycle) and during administration of CO2. We measured electrocortical activity (ECoG), eye movements (EOG), electromyography of the diaphragm (EMGdi) and neck muscles, tracheal (Ptr), amniotic, and carotid arterial pressures. Administration of CO2 by the rebreathing technique produced an increase in the amplitude of breathing activity as reflected by an increase in Ptr from 5.0 +/- 0.6 to 12 +/- 1.9 mmHg (P less than 0.01) and an increase in SEMGdi from 32 +/- 4 to 77 +/- 8% max (P less than 0.001). Frequency increased due to a decrease in inspiratory (TI) and expiratory duration. Ptr/TI increased from 11.0 +/- 2.0 to 37.4 +/- 9.0 mmHg/s (P less than 0.05) and SEMGdi/TI increased from 67 +/- 7 to 221 +/- 28% max/s (P less than 0.001). Although the response was at times prolonged into the transitional high-voltage zone, it did not persist during established high-voltage ECoG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Central angiotensin II stimulation of ovine fetal swallowing.

In the late-gestation ovine fetus, spontaneous swallowing occurs primarily during fetal low-voltage electrocortical (ECoG) activity in association with fetal breathing movements. Fetal swallowing activity may be stimulated in response to systemic or carotid plasma hyperosmolality, although not to increased plasma angiotensin II (ANG II) levels. In view of the potent dipsogenic effects of central, but not peripheral, ANG II in adult sheep, the present study investigated the effect of intracerebroventricular (ICV) ANG II on fetal swallowing activity. Six ovine fetuses (127 +/- 1 days) were chronically prepared with electromyogram and cortical electrodes and with vascular and lateral ventricle catheters. After a 2-h control period, fetuses received ICV injections of artificial cerebrospinal fluid and increasing concentrations of ANG II (0.1, 1.0, 10, 100, and 500 ng/kg). Fetal ECoG activity did not change, although fetal swallowing activity significantly increased in response to the 100- and 500- ng/kg ANG II doses (1.20 +/- 0.14 to 3.34 +/- 0.59 and 3.46 +/- 0.81 swallows/min of low-voltage ECoG, respectively). In response to the highest ANG II dose, fetal plasma arginine vasopressin levels significantly increased (5.7 +/- 1.2 to 17.2 +/- 4.6 pg/ml). ICV ANG II stimulation of fetal swallowing and arginine vasopressin secretion demonstrates that central ANG II dipsogenic mechanisms are intact by 0.9 of ovine gestation.

Amniotic Fluid↗

Ovine fetal swallowing response to intracerebroventricular hypertonic saline.

In the near-term ovine fetus, systemic hyperosmolality stimulates dipsogenic responses. Putative systemic dipsogens (hypertonicity, angiotensin II) may initiate responses by stimulation of select cerebral circumventricular nuclei lacking a blood-brain barrier. To investigate whether central osmotic-dipsogenic mechanisms are functional in utero, fetal swallowing responses to intracerebroventricular (i.c.v.) hypertonic saline were examined. Five pregnant ewes with singleton fetuses (128 +/- 1 days gestation) were prepared with fetal lateral cerebral ventricle and vascular catheters, electrocortical (ECoG) electrodes, and electromyogram wires on the fetal thyrohyoid muscle, nuchal and thoracic esophagus, and diaphragm and studied for a minimum of 5 days postoperatively. After a 2-h basal period, fetuses received an i.c.v. infusion of artificial cerebrospinal fluid followed by successive 30-min infusions of hypertonic NaCl in artificial cerebrospinal fluid (500 and 700 mosmol/kgH2O). In response to the i.c.v. hypertonic NaCl infusions, fetal swallowing significantly increased (1.4 +/- 0.4 to 3.9 +/- 1.4 and 2.9 +/- 0.5 swallows/min low-voltage ECoG, respectively). Plasma arginine vasopressin levels increased, although the change was not statistically significant (9.1 to 24.2 pg/ml; P = 0.07), and there was no change in fetal plasma osmolality, sodium concentration, or ECoG activity. Together with previous studies, these results indicate that both central and systemic osmotic dipsogenic mechanisms are functional in utero.

Animals↗

Cerebral cortical respiratory-related evoked potentials elicited by inspiratory occlusion in lambs.

Respiratory-related evoked potentials (RREP) elicited by inspiratory mechanical loads have been recorded in humans. Early RREP peaks were hypothesized to be generated by activation of neurons in the somatosensory cortex. An animal model was developed to test this hypothesis in chronically instrumented, awake, spontaneously breathing lambs. Electrocorticogram (ECoG) was recorded bilaterally with ball electrodes on the dural surface over the somatosensory region. Inspiratory occlusions were presented through a face mask or endotracheal tube as interruptions of inspiration. Occlusion-elicited evoked potentials were obtained by computer-signal averaging the ECoG activity. A short-latency positive peak was observed bilaterally in the averaged occlusion-elicited evoked potentials in all animals breathing with the facemask and 5 of 8 lambs with the endotracheal tube. Postmortem identification of the electrode location demonstrated that the ECoG was recorded in the caudal-lateral portion of the somatosensory cortex. These results demonstrate that inspiratory occlusion elicits an evoked potential in the somatosensory cortical region of awake, spontaneously breathing lambs. The lamb cortical RREP is similar to human RREP.

Air Pressure↗

Brain state-dependency of coherent oscillatory activity in the cerebral cortex and basal ganglia of the rat.

The nature of the coupling between neuronal assemblies in the cerebral cortex and basal ganglia (BG) is poorly understood. We tested the hypothesis that coherent population activity is dependent on brain state, frequency range, and/or BG nucleus using data from simultaneous recordings of electrocorticogram (ECoG) and BG local field potentials (LFPs) in anesthetized rats. The coherence between ECoG and LFPs simultaneously recorded from subthalamic nucleus (STN), globus pallidus (GP), and substantia nigra pars reticulata (SNr) was largely confined to slow- ( approximately 1 Hz) and spindle- (7-12 Hz) frequency oscillations during slow-wave activity (SWA). In contrast, during cortical activation, coherence was mostly restricted to high-frequency oscillations (15-60 Hz). The coherence between ECoG and LFPs also depended on BG recording site. Partial coherence analyses showed that, during SWA, STN and SNr shared the same temporal coupling with cortex, thereby forming a single functional axis. Cortex was also tightly, but independently, correlated with GP in a separate functional axis. During activation, STN, GP, and, to a lesser extent, SNr shared the same coherence with cortex as part of one functional axis. In addition, GP formed a second, independently coherent loop with cortex. These data suggest that coherent oscillatory activity is present at the level of LFPs recorded in cortico-basal ganglia circuits, and that synchronized population activity is dynamically organized according to brain state, frequency, and nucleus. These attributes further suggest that synchronized activity should be considered as one of a number of candidate mechanisms underlying the functional organization of these brain circuits.

Action Potentials↗

Stereotyped yawning responses induced by electrical and chemical stimulation of paraventricular nucleus of the rat.

Yawning was evoked by electrical or chemical stimulation in the paraventricular nucleus (PVN) of anesthetized, spontaneously breathing rats. To evaluate physiological aspects of yawning, we monitored polygraphic measures as follows; a coordinated motor pattern of yawning was assessed by monitoring breathing [intercostal electromyogram (EMG)], mouth opening (digastric EMG), and stretching of the trunk (back EMG). We also recorded blood pressure (BP), heart rate, and the electrocorticogram (ECoG) to evaluate autonomic function and arousal responses during yawning. A stereotyped yawning response was reproducibly evoked by electrical stimulation or microinjection of -glutamate or NOC-7, a nitric oxide (NO)-releasing compound, into the PVN. The stereotyped yawning response consisted of two sequential events, an initial response represented a depressor response and an arousal shift in the ECoG to lower voltage and faster rhythms. These initial changes were followed by a yawning behavior characterized by a single large inspiration with mouth opening and stretching of the trunk. A similar sequence of events occurred during spontaneous yawning; a fall in BP and ECoG arousal preceded a yawning behavior. An increase in the frequency of spontaneous yawns was also observed after microinjection of -glutamate or NOC-7 into the PVN. Intravenous administration of NG-monomethyl--arginine, an inhibitor of nitric oxide synthase (NOS), prevented the stereotyped yawning response evoked by chemical stimulation of the PVN. Histological examination revealed that effective sites for the yawning responses were located in the medial part of the rostral PVN, the site of parvocellular and magnocellular neurons. NADPH-diaphorase histochemistry showed the existence of NOS-containing cells in yawning-evoked sites of the PVN. In summary, the sequential events of yawning may be generated by NOS-containing parvocellular neurons in the medial part of the rostral PVN projecting to the lower brain stem.

Animals↗

Prognostic factors for survival in metastatic renal cell carcinoma: retrospective analysis from 109 consecutive patients.

OBJECTIVE: Metastatic renal cell cancer (RCC) portends a bad prognosis, but survival is quite different among different patients. The objective of this study was to determine prognostic factors for survival with the aim to offer patients proper therapeutic options. METHODS: A consecutive series of 109 metastatic RCC patients admitted to our department since 1988 was reviewed, and survival from the time of diagnosis with metastases recognition was considered. The role of age, sex, disease-free interval (DFI), ECOG performance status (PS), stage at diagnosis, grading, number and type of metastatic sites, nephrectomy, blood levels of hemoglobin, creatinine, albumin, calcium, lactate dehydrogenase (LDH), ferritin, alkaline phosphatase, triglycerides was assessed in univariate and multivariate analysis. RESULTS: In our study, the following variables were found to be statistically significant at the univariate analysis (p < 0.01): DFI, ECOG PS, stage at diagnosis, grading, nephrectomy, sites of metastases, blood hemoglobin, serum albumin, calcium, LDH, alkaline phosphatase. Indeed, only an ECOG PS of 2-3 (relative risk 1.82; p = 0.003) and blood hemoglobin levels < or = 10 g/100 ml (relative risk 1.20; p = 0.017) retained their value as independent risk factors for poor survival at multivariate analysis. According to the number of independent risk factors, three groups of patients were identified, with significantly different median survival (21.7 vs. 8.6 vs. 3.5 months; log-rank test: p = 0.00004, p = 0.04126 and p = 0.00047, respectively). CONCLUSIONS: Poor performance status and anemia at diagnosis of metastatic RCC predict the worst outcome in our series. These factors could be taken into account to stratify patients in clinical trails and to select the proper treatment option in oncological practice.

Adult↗

Spreading and synchronous depressions of cortical activity in acutely injured human brain.

BACKGROUND AND PURPOSE: Cortical spreading depression (CSD) has been much studied experimentally but never demonstrated unequivocally in human neocortex by direct electrophysiological recording. A similar phenomenon, peri-infarct depolarization, occurs in experimental models of stroke and causes the infarct to enlarge. Our current understanding of the mechanisms of deterioration in the days after major traumatic or ischemic brain injury in humans has not yielded any effective, novel drug treatment. This study sought clear evidence for the occurrence and propagation of CSD in the injured human brain. METHODS: In 14 patients undergoing neurosurgery after head injury or intracranial hemorrhage, we placed electrocorticographic (ECoG) electrodes near foci of damaged cortical tissue. RESULTS: Transient episodes of depressed ECoG activity that propagated across the cortex at rates in the range of 0.6 to 5.0 mm/min were observed in 5 patients; this rate of propagation is characteristic of CSD. We also observed, in 8 of the 14 patients, transient depressions of ECoG amplitude that appeared essentially simultaneous in all recording channels, without clear evidence of spread. CONCLUSIONS: These results indicate that CSD or similar events occur in the injured human brain and are more frequent than previously suggested. On the basis of these observations, we suggest that the related phenomenon, peri-infarct depolarization, is indeed likely to occur in boundary zones in the ischemic human cerebral cortex.

Blood Flow Velocity↗

Local cerebral blood flow following transient cerebral ischemia. I. Onset of impaired reperfusion within the first hour following global ischemia.

Using the hydrogen clearance technique, local cerebral blood flow (LCBF) in 22 dogs was estimated at 6 parietal sites prior to and following 5 min of total global ischemia. Ischemia was immediately followed by an initial reactive hyperemia during which the electrocorticogram (ECoG) usually began to recover, and within the first 30 min, most of the LCBF's decreased to subnormal values. This onset of hypoperfusion was accompanied by a concomitant decrease in ECoG activity. Two animals that maintained normal local perfusion after the initial hyperemia recovered ECoG activity quickly. These results suggest that the subsequent poor reperfusion was caused by an increased microvascular resistance rather than by blood aggregates, increased blood viscosity, or a variety of other mechanism which have been proposed. Increased vascular tonus was, at least, partly responsible for the increased vascular resistance. This report supports the hypothesis that impaired reperfusion (which occurs some time after an initial hyperemia) may be responsible for ultimate neuronal death, rather than the period of global ischemic hypoxia per se.

Animals↗

What do Italian hospital physicians know about quality of life assessment in oncology?

AIMS: To assess the current level of information and use of quality of life assessment instruments by Italian physicians involved in oncologic patient care. METHODS: Specifically trained scientific representatives of a pharmaceutical company interviewed 2237 hospital physicians all over Italy. RESULTS: A total of 1390 physicians (62.1%) had some knowledge of quality of life assessment tools in oncology, but 364 of them (26.2%) were unable to recall the name of any instruments. The one that was most frequently recalled by the 1026 physicians who knew of the existence of one or more instruments was the Karnofsky Performance Status (KPS) (91%) followed by the Eastern Cooperative Oncology Group performance scale (ECOG) (35.5%) whereas the Quality of Life Index and Visual Analogue Scale were at the very bottom of the list (5.9% and 3.7%, respectively). Physician age and type of department were found to be strong predictors of knowledge of the instruments, which was greater among young physicians and those working in oncological departments. Of the physicians aware of the KPS, 56.6% used it, whereas the percentage of physicians using ECOG was higher (69.5%). CONCLUSIONS: The collected data indicate a poor knowledge of quality of life assessment instruments in Italian physicians. Most physicians tend to use so-called << objective >> instruments where the assessment is made by the physician and not by the patient (KPS, ECOG Quality of Life index), are practically unaware of the new generation of "subjective" self-rating instruments. The use of such instruments in particular might provide greater insights into the impact of the disease and related treatments on the quality of life of cancer patients.

Adult↗

Neurotoxic effects induced by intracerebral and systemic injection of paraquat in rats.

1 The neurotoxic effects elicited by paraquat after systemic and intracerebral injection were studied in rats. 2 Intrahippocampal microinfusion of paraquat (0.1 mumol) produced behavioural stimulation and electrocortical (ECoG) excitation followed, at 24 h, by multifocal brain damage. Similarly, microinfusion of paraquat (0.2-0.4 mumol) into the locus coeruleus, substantia nigra or into the raphe nuclei, where noradrenergic, dopaminergic and serotonergic neurons are present, respectively, elicited potent excitotoxic effects (n = 6 rats per dose and area). A lower dose (0.01 mumol) of the herbicide or injection of the vehicle (1.0 microliter) did not produce any behavioural, ECoG or neurodegenerative effect. 3 After systemic administration, paraquat (20 mg kg-1 s.c.) evoked limbic motor seizures and ECoG epileptogenic discharges; in 10 out of 15 treated rats neuronal cell death was observed in the pyriform cortex, but not in other brain regions. A dose of 5 mg kg-1 was ineffective. 4 Among the regions of the brain studied, high concentrations of paraquat were detected in the pyriform cortex 24 h after systemic administration (5.0 and 20 mg kg-1 s.c.) lower levels being observed in the caudate nucleus. 5 In conclusion, paraquat, given systemically or intracerebrally in rats produces neurodegenerative effects.

Animals↗

Two magneto-encephalographic epileptic foci did not coincide with the electrocorticographic ictal onset zone in a patient with temporal lobe epilepsy.

To evaluate the usefulness and limitations of magneto-encephalography (MEG) for epilepsy surgery, we compared 'interictal' epileptic spike fields on MEG with ictal electrocorticography (ECoG) using invasive chronic subdural electrodes in a patient with intractable medial temporal lobe epilepsy (MTLE) associated with vitamin K deficiency intracerebral hemorrhage. A 19-year-old male with an 8-year history of refractory complex partial seizures, secondarily generalized, and right hemispheric atrophy and porencephaly in the right frontal lobe on MRI, was studied with MEG to define the interictal paroxysmal sources based on the single-dipole model. This was followed by invasive ECoG monitoring to delineate the epileptogenic zone. MEG demonstrated two paroxysmal foci, one each on the right lateral temporal and frontal lobes. Ictal ECoG recordings revealed an ictal onset zone on the right medial temporal lobe, which was different from that defined by MEG. Anterior temporal lobectomy with hippocampectomy was performed and the patient has been seizure free for two years. Our results indicate that interictal MEG does not always define the epileptogenic zone in patients with MTLE.

Adult↗

Localization of ictal and interictal bursting epileptogenic activity in focal cortical dysplasia: agreement of magnetoencephalography and electrocorticography.

Focal cortical dysplasia (FCD) is often associated with severe partial epilepsy. In such cases, interictal frequent rhythmic bursting epileptiform activity (FBREA) on both scalp electroencephalography (EEG) and electrocorticography (ECoG) is generally accepted to be identical to the ictal epileptiform activity. We used magnetoencephalography (or Magnetic Source Imaging (MSI)) to determine the epileptogenic zone in a 6-year-old patient with histopathologically proven FCD and normal magnetic resonance imaging (MRI). MSI was used to localize the sources of both ictal activity and FRBEA, which was then compared with ECoG findings. The intracranial sources of both types of activity co-localized in the left inferior frontal and superior temporal gyri. The location and extent of the epileptogenic area determined by MSI was essentially identical to that determined directly through extra-operative ECoG. In the absence of structural abnormalities detectable on MRI, the noninvasive method of MSI provided valuable information regarding the location and extent of the primary epileptogenic area. This was critical for pre-surgical planning regarding placement of intracranial electrodes and for risk-benefit evaluation.

Cerebral Cortex↗

Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group.

During the last decade, the Eastern Cooperative Oncology Group (ECOG) has studied a series of combination chemotherapy regimens in metastatic (stage IV) non-small-cell lung cancer (NSCLC). In January 1984, the ECOG activated a randomized study, EST 1583, which concluded the evaluation of combination regimens in phase III trials and initiated the evaluation of single agents exclusively in previously untreated patients. The treatment regimens in EST 1583 consisted of: (1) mitomycin, vinblastine, and cisplatin (MVP); (2) vinblastine and cisplatin (VP); (3) MVP alternating with the regimen cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP); (4) carboplatin followed by the MVP regimen at the time of progression; and (5) iproplatin followed by MVP at the time of progression. From January 1984 to July 1985, 743 patients were entered on this trial and 699 fulfilled the eligibility requirements. The following objective response rates (complete plus partial remissions) were observed: first-line MVP, 20%; VP, 13%; MVP/CAMP, 13%; carboplatin, 9%; iproplatin, 6%; and second-line MVP, 6%. First-line MVP produced a significantly higher response rate than the other treatments (P = .03) adjusted for prognostic variables. Using analyses that were adjusted for prognostic covariates, survival for patients treated on a given regimen was compared with survival for all remaining patients. These analyses showed that treatment with carboplatin was associated with longer survival (median survival time, 31.7 weeks; P = .008) while initial treatment with MVP was associated with a trend for shorter survival (median survival time, 22.7 weeks; P = .09). It should be noted that none of these regimens appear to have produced a clinically meaningful prolongation of survival. Similar analyses evaluating time to progression disclosed that carboplatin-treated patients had a significantly longer time to progression (median time to progression, 29 weeks) than all remaining patients (P = .01). Life-threatening and lethal toxicities (toxicity grades 4 and 5) were greater on the combination regimens than on the single agents (P less than .0001). Based on these results, current group-wide ECOG trials in stage IV NSCLC consist of randomized phase II trials evaluating single agents.

Antineoplastic Combined Chemotherapy Protocols↗

Predictive initial parameters for response of stage D prostate cancer to treatment with the luteinizing hormone-releasing hormone agonist goserelin.

One hundred eighteen patients with stage D (D1 or D2) prostate cancer with a mean age of 69 years were treated with monthly goserelin (Zoladex; ICI 118, 630; ICI Americas Inc, Wilmington, DE, property of Imperial Chemical Industries PLC) injections and the data were analyzed for predictive parameters for best response and time to treatment failure (National Prostatic Cancer Project [NPCP] and Eastern Cooperative Oncology Group [ECOG] criteria). For best response in a univariate analysis, the performance status (PS 0-1 v 2-3) (P = .01), hematocrit (P = .04), and pain (P = .04) were significant. For time to treatment failure by univariate analysis, ECOG performance status (0-1 v 2-3) was most predictive (P less than .0001), followed by pain at entry (P = .0002), initial testosterone (T) level (greater than 250 ng/dL) (P = .0005), age less than 69 years (P = .02), alkaline phosphatase (less than 115 IU/L) (P = .03), hemoglobin (less than 14 g/dL) (P = .03), whereas normal acid phosphatase (less than 3 IU/mL) (P = .29) was not predictive. In multivariate analysis for time to treatment failure, only the ECOG performance status was of significance (P = .01). Estimated median time to treatment failure for PS of 0-1 was 88 weeks and for PS of 2-3 was 31 weeks.

Age Factors↗