Role of arginase in killing of schistosomula of Schistosoma mansoni.

Nonspecific resistance to the multicellular organism Schistosoma mansoni can be induced in mice by several infectious agents. We utilized the observed genetic restriction of such acquired resistance to study the mediators of killing of the larval stage of S. mansoni in vitro. Adherent peritoneal cell monolayers from Corynebacterium parvum-treated C57BL/6J but not from C. parvum-treated BALB/cJ mice killed an increased proportion of schistosomula in 24 h. Activated macrophages (Mphi) from both strains exhibited enhanced H(2)0(2) production after incubation with the parasites or phorbol myristate acetate. Thus H(2)0(2) production was not associated with schistosomula killing. Moreover, schistosomula killing was unaffected by catalase or superoxide dismutase. In contrast, activated C57BL/6J (but not BALB/cJ) Mphi released fourfold more arginase into supernates than control Mphi. Schistosomula killing by these Mphi correlated with arginase content of the supernates, was exaggerated in arginine-poor medium, and could be blocked by the addition of arginine. Exogenous bovine arginase added to Fischer's medium without macrophages produced comparable parasite mortality. Our data suggest that arginase is a critical mediator of in vitro killing of this multicellular organism by activated macrophages.

Computer-derived density spectral array in detection of mild analog electroencephalographic ischemic pattern changes during carotid endarterectomy.

The purpose of this prospective study was twofold: 1) to determine the sensitivity and specificity of computer-derived density spectral array in detecting analog electroencephalographic (EEG) ischemic pattern changes during carotid artery cross-clamping in patients undergoing carotid endarterectomy; and 2) to assess the ability of density spectral array to identify such changes in comparison with the degree and type of change seen in the analog EEG ischemic pattern. Sixteen channels of anteroposterior bipolar and two to four channels of referential electroencephalography with four channels of density spectral array were monitored simultaneously during carotid endarterectomy in 103 patients under general anesthesia. Two "observers" interpreted the density spectral array and the analog electroencephalograms, one during and immediately after the operations and the other 6 months after completion of all surgery. Analyses were conducted to establish both the number of patients with analog EEG ischemic changes and the number of ischemia events during carotid artery cross-clamping. Observer A indicated that the density spectral array identified analog EEG ischemic changes in 21 of 29 patients, for a sensitivity of 72% (specificity 99%), whereas Observer B's results showed that the density spectral array identified analog EEG ischemic changes in 16 of 27 patients, for a sensitivity of 59% (specificity 96%). Density spectral array detection of analog EEG ischemic changes based on severity classifications were 61% and 18% in the mild group, 70% and 71% in the moderate group, and 95% in the severe group, indicating a relationship between density spectral array sensitivity and severity of analog EEG ischemic change, with p = 0.02 and p = 0.004 for the two observers. The kappa statistics for observer reproducibility were highly significant, with k = 0.95 for analog EEG ischemic changes and 0.85 for density spectral array changes. It is concluded that density spectral array does not reliably detect mild analog EEG pattern changes of cerebral ischemia and is not a reliable substitute for 16-channel analog EEG monitoring of cerebral ischemia during carotid endarterectomy.

Anterior communicating artery collateral flow protection against ischemic change during carotid endarterectomy.

The purpose of this study was to determine whether preoperative angiographic patterns of collateral cerebral blood flow correlate with protection against intraoperative electroencephalographic (EEG) evidence of cerebral ischemia caused by carotid artery cross-clamping during carotid endarterectomy. Previous studies have shown that contralateral carotid artery occlusion and intracranial stenoses are associated with cerebral ischemia during carotid endarterectomy; however, the angiographic collateral flow patterns associated with cerebral ischemia have not been identified. This paper reports a retrospective study of 67 patients who underwent two- to four-vessel cerebral angiography followed by carotid endarterectomy with 16-channel EEG monitoring. The angiograms were reviewed for extracranial occlusive disease and collateral flow patterns, and the EEG recordings were analyzed for ischemic changes during carotid artery cross-clamping. Statistical analysis was by Fisher's exact test. Cross-filling of the anterior and middle cerebral arteries from the contralateral carotid artery through the anterior communicating artery correlated with a decreased incidence of EEG ischemic changes. Only 21% of patients with this collateral flow pattern showed ischemic changes compared to 50% of patients without this pattern (p < 0.03). Three angiographic findings occurring in combination on the side contralateral to surgery correlated with EEG ischemia: 1) occlusion of the contralateral internal carotid artery (five of seven or 71%, p < 0.03); 2) collateral flow from the external carotid circulation to the internal carotid circulation via the ophthalmic artery; and 3) collateral flow from the posterior circulation to the contralateral anterior circulation via the posterior communicating artery. The data presented here corroborate the correlation between contralateral carotid artery occlusion and cerebral ischemia during carotid endarterectomy. They also demonstrate that cross-filling of the anterior and middle cerebral arteries by the contralateral carotid artery protects against such ischemia. This collateral flow may serve as an indicator of tolerance to carotid artery cross-clamping.

Loss of somatosensory evoked potentials during intramedullary spinal cord surgery predicts postoperative neurologic deficits in motor function [corrected].

STUDY OBJECTIVES: To estimate the sensitivity and specificity of somatosensory evoked potentials (SSEPs) for predicting new postoperative motor neurologic deficits during intramedullary spinal cord surgery; to establish whether SSEPs more accurately predicted postoperative deficits in position and vibration sense than in strength. DESIGN: Prospective open and retrospective study. SETTING: University-affiliated hospital. PATIENTS: 20 patients with intramedullary spinal cord tumors scheduled for surgery with intraoperative SSEPs. INTERVENTIONS: Median, ulnar, and tibial nerve cortical and subcortical SSEPs were recorded continuously. MEASUREMENTS AND MAIN RESULTS: Conventional intraoperative SSEP criteria considered indicative of neurologic injury were modified and defined as either the complete and permanent loss of the SSEP or the simultaneous amplitude reduction of 50% or greater in the nearest recording electrode rostral to the surgical site and 0.5 millisecond increase in the central latency. Our definition required confirmation of both amplitude and latency changes on a repeated average. All patients had 1 or more SSEPs, which were reproducible and sufficiently stable for analysis throughout the operation. Six patients developed new postoperative neurologic deficits. One had new motor deficits in an extremity from which no baseline SSEPs could be elicited. In each of the other 5 patients, significant SSEP changes preceded the postoperative motor deficits in the extremity or extremities monitored. In no patient without a new postoperative motor deficit was there a significant change in the SSEP. In only 2 of these 5 patients was there a documented postoperative loss or diminution in vibration or position sense. CONCLUSIONS: Intraoperative SSEP changes during intramedullary spinal cord surgery are a sensitive predictor of new postoperative motor deficits, but such changes may not correlate reliably with postoperative deficits in position or vibration sense. In this setting SSEP monitoring serves primarily to reassure the operating team that, when the SSEPs remain constant, the surgery has not caused additional injury.

Somatosensory evoked potentials sensitivity relative to electroencephalography for cerebral ischemia during carotid endarterectomy.

BACKGROUND AND PURPOSE: The relation between electroencephalographic pattern changes and cerebral ischemia during carotid endarterectomy under general anesthesia is well established. Pattern changes seen on somatosensory evoked potentials under the same conditions are reported to be more sensitive indicators of cerebral ischemia. We estimated the sensitivity and specificity of somatosensory evoked potentials relative to electroencephalography for detecting cerebral ischemia during carotid endarterectomy under general anesthesia. METHODS: We simultaneously monitored electroencephalographs and somatosensory evoked potentials in 53 carotid endarterectomies performed on 51 patients under general anesthesia, and we determined the extent to which somatosensory evoked potentials detected cerebral ischemia defined by electroencephalographic pattern changes at the time of carotid cross-clamp. RESULTS: Twenty-three of the 53 cases studied had electroencephalographic evidence of ischemia following carotid cross-clamp. Ten of these 23 cases had an increased somatosensory evoked potential latency of 0.1 msec or greater (sensitivity 0.43). One of these 23 patients had a decrease in somatosensory evoked potential amplitude of 50% or greater (sensitivity 0.04). Of the 30 subjects who had no electroencephalographic evidence of ischemia, 13 had either no change or a decrease in somatosensory evoked potential latency (specificity 0.45). None of these 30 cases had a significant decrease in somatosensory evoked potential amplitude (specificity 1.0). If somatosensory evoked potential latencies were a sensitive method for detecting cerebral ischemia (true sensitivity of 0.95 or higher), the probability of only 10 subjects having somatosensory evoked potential latency increases would be less than 0.001. Therefore, our observed sensitivity cannot be attributed to chance. CONCLUSIONS: We conclude that measuring somatosensory evoked potentials is not a sensitive method for detecting cerebral ischemia during carotid endarterectomy.

Bispectral analysis of the electroencephalogram predicts conscious processing of information during propofol sedation and hypnosis.

BACKGROUND: The bispectral index (BIS) measures changes in the interfrequency coupling of the electroencephalogram (EEG). The purposes of this study were (1) to determine whether BIS correlates with responses to command during sedation and hypnosis induced by propofol or propofol and nitrous oxide, and (2) to compare BIS to targeted and measured concentrations of propofol in predicting participants' responses to commands. METHODS: Twenty volunteers (15 men and 5 women, aged 22-50 yr) were given propofol by computer-controlled infusion, and EEG was recorded for off-line analysis of BIS. Responses to randomly ordered verbal commands or voice plus touch were measured with two categorical scales (CS1 and CS2, respectively). All subjects received a propofol infusion targeted to achieve effect site concentrations of 1, 2, 4, 2, 1, and 0 microg/ml. Ten participants had repeated infusion, whereas 10 others breathed 30% nitrous oxide and oxygen and received a propofol infusion targeted for 0.5, 1, 2, 4, 2, 1, 0.5, and 0 microg/ml. Five minutes after each targeted concentration had been reached, CS1, CS2, and arterial propofol concentration were determined. The area under the receiver operating characteristic curve was used to compare the accuracy of (1) BIS, (2) targeted propofol concentration, (3) measured concentration, and (4) treatment history as predictors of response. RESULTS: Bispectral index was a strong predictor of CS1 and CS2 (P < 0.0001) and significantly more accurate than targeted or measured propofol concentrations (P < 0.0003 and P < 0.003, respectively). It also provided additional predictive power when combined with treatment history (P < 0.02). Nitrous oxide slightly decreased the probability of response at a given value of BIS (P < 0.05), but accuracy was unaffected. CONCLUSIONS: Bispectral index accurately predicts response to verbal commands during sedation and hypnosis with propofol or propofol plus nitrous oxide. Accuracy is maintained in situations likely to be encountered during clinical use: when propofol concentrations are increasing or decreasing and when repeated measurements are made over time.

Epileptiform activity during opioid anesthesia.

The proconvulsant properties of exogenously administered opioids in man are not established. We prospectively evaluated relationships between epileptiform activity and opioid dose in 20 patients undergoing coronary artery revascularization. Baseline electroencephalograms were performed before surgery. Ten subjects were given fentanyl and 10 sufentanil, at 100 micrograms/kg and 10 micrograms/kg, respectively, in 4 divided doses, 3 min apart. Midazolam (4 mg) was given 3 min after the last dose of narcotic. Serum opioid concentrations were measured by radioimmunoassay. Within 3 min of the first opioid dose, 19 of 20 patients developed epileptiform activity, characterized by generalized single and multiphasic, low-to-moderate voltage spike discharges, similar in appearance to benign epileptiform transients of sleep (BETS). Despite continuously increasing serum concentrations of opioid, the number of spike discharges initially increased during the first and second dose intervals and then declined during the third and fourth dose intervals. This dissociation between epileptiform discharges and measured serum opioid concentration was unexpected and remained unexplained. Spike activity was consistently attenuated (P = 0.000003) within 20 sec of midazolam administration. Abrupt cessation of discharges after administration of the anticonvulsant, midazolam, suggests an epileptogenic mechanism for the opioid-induced activity.

Bispectral analysis of the electroencephalogram correlates with patient movement to skin incision during propofol/nitrous oxide anesthesia.

BACKGROUND: Bispectral analysis is a signal-processing technique that determines the harmonic and phase relations among the various frequencies in the electroencephalogram. Our purpose was to compare the accuracy of a bispectral descriptor, the bispectral index, with that of three power spectral variables (95% spectral edge, median frequency, and relative delta power) in predicting patient movement in response to skin incision during propofol-nitrous oxide anesthesia. METHODS: Forty-four adult patients scheduled for elective noncranial surgery were studied. Gold cup electroencephalographic electrodes were placed on each patient in a frontoparietal montage (Fp1, Fp2, P3, and P4) referred to Cz, and the electroencephalogram was recorded continuously and processed off-line. Conventional frequency bands were used to describe power spectrum variables. Anesthesia was induced with propofol (1.5-3.0 mg-1.kg-1) and maintained with 60% nitrous oxide in oxygen and with propofol at one of three randomized infusion rates (100, 200, or 300 micrograms.kg-1.min-1). Inadequate anesthetic depth was defined as patient movement in response to a 2-cm skin incision at the planned site of surgery. Plasma propofol concentrations were measured within 2 min after skin incision. RESULTS: Complete data were available for 38 patients, of whom 17 moved in response to skin incision. Analysis of the area under the receiver operating characteristic curves showed that only for bispectral index and drug dose group was there a significant predictive relation (area > 0.5). Furthermore, the bispectrum was significantly predictive even after stratification by dose group. CONCLUSIONS: The bispectral index of the electroencephalogram is a more accurate predictor of patient movement in response to skin incision during propofol-nitrous oxide anesthesia than are standard power spectrum parameters or plasma propofol concentrations.

Preoperative cerebrovascular symptoms and electroencephalographic abnormalities do not predict cerebral ischemia during carotid endarterectomy.

BACKGROUND AND PURPOSE: The purpose of this prospective study was to establish (1) whether patients with neurological symptoms scheduled for carotid endarterectomy had an increased incidence of electroencephalographic (EEG) abnormalities during awake baseline recordings, (2) whether these symptoms and EEG abnormalities predicted ischemic EEG pattern changes at carotid artery cross-clamp, and (3) whether there was an association between age, presence of EEG baseline abnormalities, and ischemic pattern changes at carotid artery cross-clamp. METHODS: We reviewed the medical record of each patient scheduled to undergo carotid endarterectomy and recorded the patient's age and history of previous neurological symptoms. We then continuously monitored and analyzed 16 channels of anteroposterior bipolar EEG and two of referential derivations from at least 5 minutes before induction of anesthesia and throughout the operation. RESULTS: We completed 394 consecutive studies. Preoperative neurological symptoms were related to EEG abnormalities in awake patients (P < .001) and to EEG asymmetries in anesthetized patients (P < .001). Abnormal awake EEG findings were associated with asymmetries after anesthesia (P < .0001). Twenty-eight percent of both symptomatic (70/249) and asymptomatic (41/145) patients had EEG ischemic pattern changes at carotid artery cross-clamp. Neither neurological symptoms nor EEG abnormalities were associated with age or the development of EEG ischemic pattern changes at carotid artery cross-clamp. CONCLUSIONS: Despite the strong association between a history of cerebral ischemic symptoms and preoperative EEG abnormalities in patients undergoing carotid endarterectomy, patients who have suffered strokes or transient ischemic events are at no greater risk of having EEG evidence of cerebral ischemia during carotid artery cross-clamp than patients without symptoms and with normal baseline EEGs. We conclude that preoperative EEG abnormalities in symptomatic patients are not due to age or to insufficiency of regional cerebral blood flow.

Alfentanil-induced epileptiform activity: a simultaneous surface and depth electroencephalographic study in complex partial epilepsy.

PURPOSE: Alfentanil is a high potency mu opiate receptor agonist commonly used during presurgical induction of anesthesia. This and other opiate receptor agonists have demonstrated proconvulsant effects in animals, but these properties have been less consistently demonstrated in humans. Most human scalp EEG studies have failed to demonstrate induction of epileptiform activity with these agents, which is inconsistent with findings using intracranial EEG. Simultaneous scalp and depth EEG recordings have yet to be performed in this setting. The relationship between opiate dose and proconvulsant activity is unclear. METHODS: Simultaneous scalp and depth electrode recordings were performed on five patients with complex partial epilepsy (CPE) who underwent alfentanil anesthesia induction before depth electrode removal. Consecutive equal bolus doses of alfentanil were administered to each patient according to strict time intervals so as to assess their correlation with any induced epileptiform activity. RESULTS: Epileptiform activity was induced by alfentanil in three of five patients. Two of these patients had electrographic seizures. Epileptiform activity was only detected from the depth electrodes, occurring within 2 min of the first bolus dose in all three cases. Further increase or spread of epileptiform activity did not occur despite cumulative bolus doses of alfentanil. CONCLUSIONS: Alfentanil is proconvulsant in patients with CPE. Induced seizures may be subclinical and lack a scalp EEG correlate. There is a complex dose-response relationship. Alfentanil induction of anesthesia should be approached with caution in patients with CPE.

Bispectral analysis of the electroencephalogram during induction of anesthesia may predict hemodynamic responses to laryngoscopy and intubation.

The use of electroencephalography as a measure of adequacy of anesthesia has achieved limited success. Our purpose was to determine whether the non-linear properties of the electroencephalogram (EEG) as defined by the bispectral index was a better predictor of autonomic responses to endotracheal intubation during opioid-based anesthesia than the linear statistical properties of the EEG formulated by power spectral analysis. Thirty-nine adults scheduled for elective non-cranial surgery had a continuous EEG recorded during induction of anesthesia and endotracheal intubation. Anesthesia consisted of thiopental and nitrous oxide in oxygen, followed by 1 of 5 randomized opioid dose regimens. The EEG was continuously recorded and blood pressure was measured every minute. All electroencephalographic parameters were derived for the 3 min before and after intubation and were compared to the blood pressure and heart rate responses. Responders were defined by 2 analyses: patients who had a 20% or greater increase (1) in blood pressure or (2) in heart rate to laryngoscopy. Responders and non-responders were compared using Student's unpaired t test, and differences due to dose regimens were examined with logistic regression. Based on the criterion for blood pressure change, there were 27 responders and 12 non-responders. Heart rate changes did not differentiate between the two groups. There was a significant difference between response groups as measured by the bispectral index which distinguished responders from non-responders independently of the amount of drug given. None of the variables of power spectral analysis accurately distinguished responder from non-responder.(ABSTRACT TRUNCATED AT 250 WORDS)