The electroencephalogram in the middle-aged and the elderly

A survey was made of the electroencephalographic (EEG) changes during the human lifespan. It was found that the EEG changes during childhood and adolescent maturation continue even between the ages of 30 and 60 years. There is a decrease in the abundance of alpha activity, with a reduction in the fast part and a relative increase in the slow part of the alpha band. In the span of life between 60 and 90, there is an increase of slow waves with a progressive slowing during the aging process and a shift in the dominant frequency from 9 cps to 7 cps. Computerization of results in the beta band (above 13 cps) enables differentiation of the waves of the lower part (13-25 cps) from those of the upper part (above 25-30 cps). The lower part of the beta band decreases parallel to the alpha activity but the upper part of the beta band increases in amount during the aging process. The meaning of the divergent behavior of these sub-groups of beta activity in the aged is discussed. The EEG seems to be an important factor in the study of aged persons.     

Spectral characteristics of sleep EEG in chronic insomnia

To determine whether the spectral characteristics of the sleep electroencephalogram (EEG) of insomniacs differ from that of healthy subjects, we compared in each of the first four non-rapid eye movement (NREM) and rapid eye movement (REM) episodes: (a) the time courses of absolute power, averaged over the subjects in each group, for the delta, theta, alpha, sigma and beta frequency bands; (b) the relationship between these time courses; and (c) the overnight trend of integrated power in each frequency band. The results show that NREM power, for all frequencies below the beta range, has slower rise rates and reaches lower levels in the insomniac group, whereas beta power is significantly increased. In REM, insomniacs show lower levels in the delta and theta bands, whereas power in the faster frequency bands is significantly increased. Thus, the pathophysiology of insomnia is characterized not only by the generally acknowledged slow wave deficiency, but also by an excessive hyperarousal of the central nervous system throughout the night, affecting both REM and NREM sleep. This hyperarousal is interpreted in terms of the neuronal group theory of sleep which provides a possible explanation for the discrepancies observed between subjective impressions and objective measures of sleep. Also, it is suggested that the progressive hyperpolarization of the thalamocortical neurons as sleep deepens is slower in the patient population and that this may explain the observed slow wave deficiency. The homeostatic control of slow wave activity, on the other hand, would appear to be intact in the patient population.     

Dynamics of the effects of levoprotiline and maprotiline on EEG in patients with major depressive episodes (DSM-III-R)

The presented study compares the effect of the well-tested antidepressant maprotiline and a new antidepressant with an atypical pharmacological profile, levoprotiline, on EEG during repeated assessment after single dose administration. From the original number of 34 patients fulfilling the criteria of a major depressive episode (DSM-III-R) on account of a low-voltage record or pathological findings 11 were eliminated. To 12 of the remaining patients levoprotiline was administered and to 11 maprotiline, after a one-week placebo period, in doses of 150 mg. The EEG was recorded after an accommodation session immediately before, 1.5, 3, 4.5, 6 and 24 hours after a single dose administration. The record was taken on a 16-channel average reference montage at rest with closed eyes. Two-minute intervals were divided into 30 four-second periods at a sampling frequency of 128 Hz. From the signal by means of FFT the spectra were estimated and the mean spectrum for the entire recording was calculated. This was then divided into 10 frequency bands. The new method of frequency analysis of alpha-entropy was also used which is a global measure of the difference between two spectra. Three hours after administration of a single dose levoprotiline had an EEG profile corresponding to the profile of tricyclic antidepressants, i.e. it increased the values of the power spectra density in the region of 5-8.5 Hz and in the entire beta band; the decline of power in the alpha band was, however, absent. As regards maprotiline, 3 hours after administration a profile typical for antidepressants was not found; obviously because of the great variance of values of power spectra density as a result of great interindividual differences in the ingestion phase. Changes of the EEG spectrum expressed as values of alpha-entropy during different periods of apparently assessment are not incidental. After the initial rise of values a decline occurs.     

Depression during interferon therapy in chronic hepatitis C patients--a prospective study

The number of patients treated with interferon (IFN) has increased markedly in Japan since 1992, when the Health and Welfare Ministry approved the use of IFN for treating chronic active hepatitis C. It is important to identify and treat depression, which is one of the psychiatric complications of IFN therapy and often leads to discontinuation of the therapy, in patients with chronic hepatitis C. In this study we prospectively investigated the incidence of depression during IFN therapy in patients with chronic active hepatitis C. The psychiatric status of 85 patients (53 men, 32 women; mean age 49.1 years) with chronic active hepatitis C who began receiving IFN at Showa University Hospital was assessed before and 2, 4, 12 and 24 weeks after the start of IFN therapy, using the major depressive episode diagnostic criteria listed in the DSM-III-R and the Hamilton Depression Scale HDS). All of the patients provided informed consent prior to participation in this study. IFN therapy was discontinued in 5 cases (5.9%) because of physical side effects and in 4 cases (4.7%) because of depression. Two, 11, 14, 25 and 16 patients were diagnosed as having major depressive episodes before and 2, 4, 12 and 24 weeks after the start of IFN therapy, respectively. The number of patients who were asymptomatic before the start of IFN therapy but were diagnosed as having a major depressive episode at least once during IFN therapy was 31 (31/83 = 37.3%). The mean HDS scores at 2, 4, 12 and 24 weeks (5.4, 6.0, 8.8 and 6.6) were significantly higher than that before the start of IFN therapy (3.0). The patients whose first diagnosed major depressive episodes occurred more than 4 weeks after the start of IFN therapy tended to be more severely depressed than those in whom it occurred less than 4 weeks after the start of IFN therapy. Compared to the 47 patients who completed 24 weeks of IFN therapy without experiencing depression, the 31 patients who were diagnosed as experiencing major depressive episodes during IFN therapy had significantly higher neuroticism scores determined using the Eysenck Personality Questionnaire, showed a more severely depressed mood and experienced more severe sleep disturbances before the start of IFN therapy. The latter group of patients also tended to have comorbid chronic physical disorders such as hypertension or diabetes mellitus and the histories of mental disorders before the IFN therapy; however these differences were not statistically significant. There were no differences between the two groups in patient age or sex, the severity of hepatitis before the IFN therapy, the type of IFN used in the therapy or the efficacy of IFN in the treatment of the hepatitis C. Our results indicate that the decision as to whether to treat chronic active hepatitis C with IFN should be made carefully and that early intervention and careful monitoring of depression are required during IFN therapy in the treatment of chronic active hepatitis C.     

Occurrence of thyroid autoimmunity and dysfunction throughout a nine-month follow-up in patients undergoing interferon-beta therapy for multiple sclerosis

Thyroid autoimmunity and dysfunction are a well known side effect of IFN alpha therapy for viral hepatitis and tumors, while the IFN beta effects on the thyroid gland in neurological patients have not been studied. The aim of this longitudinal study was to look for the appearance of thyroid autoimmunity as well as for the occurrence of overt thyroid disease in the patients affected by multiple sclerosis (MS) treated with IFN beta 1b. Eight patients (4 males, 4 females) undergoing r-IFN beta 1b treatment (8 M.U. every other day for 9 months) for relapsing remitting multiple sclerosis entered the study. We have analyzed thyroid function parameters and auto antibody levels before and after 1, 2, 3, 6 and 9 months of therapy. None of them referred to familiar thyroid pathology or presented clinically overt thyroid disease except for one patient (case 4) who showed TPO-Ab pretreatment positivity and another (case 8) who was in therapy with Levothyroxine 100 microg/die for multinodular goiter. The number of patients with appearance of thyroid antibodies has slowly increased, until the third month of therapy with 3 patients out of 7 positive for TPO-Ab. The only case of overt thyroid dysfunction reported by us appeared after nine months of therapy and consisted of a hypothyroidism. Our data suggest that short-term interferon beta treatment is able to induce thyroid autoimmunity (42.8%) and dysfunction (12.5%).     

Power spectral analysis of electroencephalographic desynchronization induced by cocaine in the rat

Whereas it is well-known that cocaine induces EEG desynchronization and behavioral excitation in animals and human subjects, the detailed effect of cocaine on EEG activity remains to be fully elucidated. This communication reports our attempts in quantifying the effect of cocaine on EEG signals recorded from the somatosensory cortex of adult male Sprague-Dawley rats under chloral hydrate anesthesia (400 mg/kg i.p.). Continuous, on-line and real-time power spectral analysis revealed that i.v. administration of two doses of cocaine (1.5 or 3.0 mg/kg) dose-dependently induced EEG desynchronization, as indicated by a decrease in the root mean square and an increase in the mean power frequency values. More interestingly, whereas both doses of cocaine promoted a reduction in the alpha (8-13 Hz), theta (4-8 Hz) and delta (1-4 Hz) spectral components, the beta band (13-32 Hz) underwent differential alterations. The lower dose of cocaine elicited a transient increase, followed by a decrease in the power of the beta band. A prolonged increase in the power of the beta band, on the other hand, was observed after the higher dose of cocaine. These results suggest that subtle changes in the individual EEG spectral components, which are dose-dependent, may underlie the EEG desynchronization induced by cocaine.     

EEG characteristics prior to and following the evoked K-Complex.

Examined if the K-Complex reflects an arousal from sleep or a sleep protection mechanism. Ten 18–34-yr-old participants were presented auditory stimuli every 20 sec while asleep. Trials were sorted according to the presence or absence of a K-Complex. A fast Fourier Transformation of the data was computed on EEG segments prior to and following stimulus onset. The log power of activity in delta, theta, alpha, sigma, and beta bandwidths was computed. Results indicate that when a K-Complex was elicited, there were no differences in EEG activity prior to and following the stimulus. However, during slow wave sleep, when a K-Complex was not elicited, there was a significant overall increase in theta, alpha, sigma, and beta activity following stimulus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Signal transduction: specificity of growth factors explained by parallel distributed processing

The effects of noxious surgical stimulation on the electroencephalogram (EEG) in 15 horses anesthetized with isoflurane were evaluated during orthopedic (group 1) and soft tissue (group 2) procedures. The quantitative EEG variables theta/delta ratio (T/D), alpha/delta ratio (A/D), beta/delta ratio (B/D), median power frequency (MED), and 80% spectral edge frequency (SEF 80) recorded during Surgeries at 1.7% end-tidal concentration of isoflurane (ET(iso)) were compared with values from five nonstimulated control horses anesthetized at 1,7% ET(iso). The EEG variables T/D, A/D, MED, and SEF 80 from surgically stimulated horses were significantly higher compared with controls. These differences in measured EEG variables were accompanied by a significantly lower relative power in the delta frequency band and a concomitant significantly higher alpha activity. Because the A/D ratio, MED, and SEF 80 in surgically stimulated horses were significantly higher than in nonstimulated control horses these measured EEG variables may provide a valuable tool for identification of nociceptive transmission in isoflurane anesthetized horses.     

Quantitative spectral electroencephalography in predicting survival in patients with early Alzheimer disease

OBJECTIVE: To determine whether measures of quantitative spectral electroencephalography (EEG) can predict survival in patients with early Alzheimer disease. DESIGN: Prospective cohort study; median duration of follow-up was 4.4 years in survivors and 2.6 years in nonsurvivors. Cox proportional hazards models, with adjustment for age and sex were used to estimate relationships between EEG measures and survival. Log relative percentage values of EEG bands were used as predictors. SETTING: Outpatient university memory clinic. PARTICIPANTS: One hundred one consecutively referred patients with early probable Alzheimer disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria were studied with EEG at the time of diagnosis. The mean age of the patients was 79.2 years, which was higher than in previous EEG studies. MAIN OUTCOME MEASURE: Mortality. RESULTS: Fifty-one patients (50.5%) died during follow-up, with a median survival time in all patients of 4.1 years. The following EEG variables were significantly associated with increased risk of mortality: from parieto-occipital leads, higher theta (hazard ratio, 2.05; 95% confidence interval, 1.15-3.66; P<.05), lower alpha (hazard ratio, 0.43; 95% confidence interval, 0.25-0.76; P<.01), and lower beta (hazard ratio, 0.38; 95% confidence interval, 0.22-0.68; P<.001) activity; and from frontocentral leads, higher theta activity (hazard ratio, 2.07; 95% confidence interval, 1.17-3.66; P<.05). Stepwise Cox regression analysis showed that loss of parieto-occipital beta (P<.01) and alpha (P<.05) power were independent and significant predictors of mortality. Both beta (12.6-35.4 Hz) and alpha (7.5-12.5 Hz) activity remained significantly associated with mortality after adjustment for education, dementia severity, symptom duration, level of cognitive function, presence of extrapyramidal symptoms or hallucinations, presence of vascular risk factors, and presence of leukoaraiosis or local cortical atrophy. CONCLUSIONS: Decreases of beta and alpha activity on quantitative spectral EEG are independent predictors of mortality in patients with early Alzheimer disease. In the clinical context, the use of EEG technology for prediction of survival in individual patients remains to be determined.     

Cereal-based oral rehydration solutions in Sudanese children with diarrhoea: a comparative clinical trial of rice-based and sorghum-based oral rehydration solutions

We describe 4 patients with onset or aggravation of thyroid dysfunction induced by interferon (IFN) treatment of hepatitis type C. All 4 patients were females; 2 had hyperthyroidism and 2 had hypothyroidism during or after IFN therapy. The onset or aggravation of thyroid dysfunction occurred during administration of IFN in 1 patient and 4 weeks after the end of IFN therapy in the remaining 3 patients. The 2 patients who demonstrated hyperthyroidism were euthyroid and negative for thyroid autoantibodies before receiving IFN therapy. The remaining 2 patients who demonstrated hypothyroidism were positive for thyroid autoantibodies before IFN therapy. One of these patients had a slight decrease in thyroid function before IFN therapy. Anti-thyroid stimulating hormone (TSH) receptor antibodies became positive in all 4 patients. Since there may have been a causal relationship between IFN therapy and the onset or aggravation of thyroid dysfunction, IFN therapy should be administered with caution.     

Autoimmune endocrine disease induced by recombinant interferon-alpha therapy for chronic active type C hepatitis

To elucidate the role played by interferon-alpha (IFN alpha) in the pathogenesis of autoimmune endocrine disease, we determined the autoantibody status, thyroid function test results, hemoglobin-A1c levels, and clinical symptoms of 58 patients who received IFN alpha for treatment of chronic active type C hepatitis. Each patient was treated for 6 months with a total dose of 391 +/- 140 x 10(6) U (mean +/- SD). Thyroid microsomal and/or thyroglobulin antibodies newly appeared or were increased in titer in 6 patients, 2 of whom developed hypothyroidism during IFN alpha therapy. Neither islet cell antibodies nor insulin-dependent diabetes mellitus developed during IFN alpha therapy, although hemoglobin-A1c levels were increased in 2 patients. One patient became positive for antimitochondrial antibodies, and another patient with preexisting antimitochondrial antibodies also manifested deterioration in liver function test results. Parietal cell antibodies and smooth muscle cell antibodies were the most frequent newly developed antibodies in 7 patients. Adrenal medullary cell antibodies and nuclear antibodies newly developed in 2 and 1 patients, respectively. At least 1 of 8 autoantibodies newly appeared in 19 patients (32.8%) and hypothyroidism developed in 2 patients (3.4%) during IFN alpha therapy. On the other hand, in 19 age- and sex-matched patients who did not receive IFN alpha, no autoantibody appeared, and no autoimmune disease developed during a follow-up period of 3 months. These findings suggest that IFN alpha acts as an immunomodulatory agent, inducing autoantibody production and the development of autoimmune disease in susceptible patients. Special attention should be paid to the development of hypothyroidism during IFN alpha therapy.     

Efficacy of ribavirin plus interferon alpha on viraemia of GB virus-C/hepatitis G virus: comparison with interferon alpha alone

We investigated the efficacy of ribavirin plus interferon (IFN) alpha on GB virus-C (GBV-C)/hepatitis G virus (HGV) viraemia and compared it with that of interferon alpha alone in patients coinfected with hepatitis C virus (HCV) and GBV-C/HGV. Serum HCV and GBV-C/HGV-RNA were studied in eight patients with HCV and GBV-C/HGV coinfection, five received IFN alpha and three received oral ribavirin plus IFN alpha. Mean serum GBV-C/HGV titre at the end of therapy was significantly lower than the titre just before therapy and patients with lower pretreatment titre had a better sustained response rate. Sustained virological response of GBV-C/HGV to IFN alpha alone and ribavirin plus IFN alpha at the end of follow up was observed in one each, respectively. Thus, GBV-C/HGV in patients with HCV and GBV-C/HGV coinfection does respond to IFN alpha and ribavirin plus IFN alpha may not induce a higher sustained response.     

Correlation analysis of the changes of EEG mapping and the changes of CT scan in patients with senile dementia

OBJECTIVE: To observe the changes of EEG mapping and CT scan and analyse the correlation between the changes of the function presented by EEG mapping and morphology presented by CT. METHODS: The absolute power of EEG mapping and 9 parameters of CT in 30 normal controls and 31 patients with senile dementia were measured. The correlation was analysed quantitatively with multiple stepwise regression method. RESULTS: The EEG mapping of senile dementia revealed a diffuse increase in delta, theta power and decreased alpha power in most areas. CT scan showed cortical and subcortical atrophy in brain. There were positive correlations between the increase of delta power and lateral fissure, and between the increase of delta power and average cerebral sulcus. There was a negative correlation between the decrease of alpha power and the increase of lateral fissure. CONCLUSION: The EEG mapping and CT in patients with senile dementia are different from those in normal elderly. There is a correlation between the changes of EEG mapping and CT scan.     

Spectral analysis in cyclic changes of human sleep evaluation

In this study cyclic changes of human sleep structure were examined. For whole-night polysomnograms of 35 healthy volunteers of both sexes, manual hypnograms were created and divided into NREM-REM cycles. EEG signals from C3-A2 derivation were analysed by computer using a Fast Fourier Transform (FFT). For consecutive NREM-REM cycles of individual sleep stages, EEG power density contents for delta, theta, alpha, sigma and beta waves were analysed. For consecutive sleep cycles, a clear decrease in NREM sleep duration, especially slow wave sleep duration, was obtained. In addition, a decrease in power density of delta waves was observed. For consecutive sleep cycles, increases in REM sleep duration and in power density of theta and alpha waves were obtained. In consecutive sleep cycles, high amplitude delta slow waves are replaced by higher frequency and lower amplitude waves. Thus stages of NREM sleep are replaced by stages of REM.     

Cortisol secretion is related to electroencephalographic alertness in human subjects during daytime wakefulness

To determine whether human hypothalamo-pituitary-adrenal axis activity is related to the alertness level during wakefulness, 10 healthy young men were studied under resting conditions in the daytime (0900-1800 h) after an 8-h nighttime sleep (2300-0700 h). A serial 70-sec gaze fixation task was required every 10 min throughout the daytime experimental session. The corresponding waking electroencephalographic (EEG) segments were submitted to quantitative spectral analysis, from which EEG beta activity (absolute power density in the 13-35 Hz frequency band), an index of central alertness, was computed. Blood was collected continuously through an indwelling venous catheter and sampled at 10-min intervals. Plasma cortisol concentrations were measured by RIA, and the corresponding secretory rates were determined by a deconvolution procedure. Analysis of individual profiles demonstrated a declining tendency for EEG beta activity and cortisol secretory rate, with an overall temporal relationship indicated by positive and significant cross-correlation coefficients between the two variables in all subjects (average r=0.565, P < 0.001). Changes in cortisol secretion lagged behind fluctuations in EEG beta activity, with an average delay of 10 min for all the subjects. On the average, 4.6+/-0.4 cortisol secretory pulses and 4.9+/-0.5 peaks in EEG beta activity were identified by a detection algorithm. A significant, although not systematic, association between the episodes in the two variables was found: 44% of the peaks in EEG beta activity (relative amplitude, near 125%; P < 0.001) occurred during an ascending phase of cortisol secretion, cortisol secretory rates increasing by 40% (P < 0.01) 10-min after peaks in EEG beta activity. However, no significant change in EEG beta activity was observed during the period from 50 min before to 50 min after pulses in cortisol secretion. In conclusion, the present study describes a temporal coupling between cortisol release and central alertness, as reflected in the waking EEG beta activity. These findings suggest the existence of connections between the mechanisms involved in the control of hypothalamo-pituitary-adrenal activity and the activation processes of the brain, which undergoes varying degrees of alertness throughout daytime wakefulness.     

Functional imaging of headache - first steps in an objective quantitative classification of migraine

A highly sensitive quantitative-topographical EEG was used in order to define first steps in an objective classification of migraine. A 17-channel quantitative EEG was recorded in 30 patients suffering from migraine with or without aura during the painfree interval. These EEG s were compared to EEGs of age related healthy norm groups using a new statistical tool called the Aberration Index. A focal aberration in the area of pain was detected in 26 out of the 30 patients mostly due to an increase of alpha1 EEG power (23 patients). Alpha2 or theta power were also increased in several patients. Furthermore, a decrease in alpha power neighbouring the focus was found in 18 patients and a contralateral reduction of alpha power was seen in 16 patients. No difference was detected between migraine with aura and migraine without aura.     

EEG power spectra of normal preadolescent twins. Gender differences of quantitative EEG maturation

To determine developmental changes of quantitative EEG maturation, we investigated the electroencephalogram (EEG) power spectra in a sample of 72 pairs of healthy twins (144 subjects, 75 girls and 69 boys) ranging in age from 7-15 years. Main spectral parameters were measured in 16 EEG channels. The statistical significance of differences in the EEG power spectra was compared in relation to age and gender. Gender differences were tested by comparing the EEG parameters of boys and girls in the whole sample and separately in the subgroup of dizygotic twins of the opposite sex (DZO twin pairs). A statistically significant decrease of absolute power occurred with increasing age. A significant redistribution of relative power also appeared in higher age, mainly consisting of a progressive increase of alpha 2 power inversely related to relative alpha 1 and theta power. Polynomial regression models of the relation between alpha 2 and theta relative power with age were best described by a 5-order function. The mean frequency of activity across all spectra also increased with age and was maximal in the eldest subjects (13-15 years), with a significantly higher mean frequency of alpha 2 power in females. Similar age and gender differences were less marked in the subgroup of DZO twin pairs. The topographic distribution of spectral bands in normal subjects suggested an earlier maturation of midparietal or occipital than frontocentral regions, and indicated that the growth spurt does not occur simultaneously over homologous right and left hemisphere regions at the same age.     

Spindle-cell lipoma of the preseptal eyelid

To identify immunological markers that could be used to monitor relapsing-remitting multiple sclerosis (RRMS) course/activity during interferon beta 1b (IFN beta 1b) therapy, we longitudinally studied HLA-DR and CD25 expression by T lymphocytes in 15 IFN beta 1b-treated RRMS patients. Peripheral blood T cell subsets were analysed before therapy (T0), and after 1 (T1), 2 (T2), 3 (T3), 6 (T4) and 12 (T5) months after therapy initiation. HLA-DR expression and the CD3+HLA-DR+ T cell number showed a peculiar trend in almost all (14/15) the patients: a significant decrease at T1 and T2 followed by a return to pre-treatment levels from T3 to T5. At T1 and T2, eight patients showed an up-regulation of CD25 on CD4, as well as an increase in the CD4+CD25+ cell number. However, a marked, significant reduction of this T cell subset was observed in all the patients at T3, followed by the progressive return to pre-treatment values from T4 to T5. All the patients developed anti-IFN beta 1b 'binding' antibodies within the first three months of therapy. Our findings demonstrate that: (1) the expression of HLA-DR and CD25 on T cells, as well as the number of circulating CD3+HLA-DR+ and CD4+CD25+ cells, are only transiently reduced in vivo in IFN beta 1b-treated RRMS patients, (2) the expression of HLA-DR and CD25 on T lymphocytes cannot be used to monitor MS course/activity during IFN beta 1b therapy, (3) the long-lasting beneficial effect of IFN beta 1b on RRMS reported in the literature cannot be explained by the down-regulation of MHC class II antigens and/or interleukin-2 receptor expression induced by this cytokine.     

Hyperdynamic hemodynamics following high-dose interleukin 2-interferon alpha therapy in patients with metastatic renal cell carcinoma. Immunotherapy as a clinical sepsis model?

Human recombinant interleukin 2 (IL-2), alone or in combination with other cytokines, is currently under investigation for the immunotherapy of metastatic tumours. Objective responses of 20-35% have been reported in patients with disseminated melanoma and renal cell carcinoma who received high-dose intravenous IL-2 in combination with interferon-alpha (IFN alpha). However, treatment with IL-2 is complicated by a syndrome of life-threatening adverse reactions such as disseminated vascular leakage, fluid retention, severe hypotension, and (reversible) multiple organ dysfunction (MODS). A systemic inflammatory reaction (SIRS/sepsis sepsis-like haemodynamic pattern has been described in patients after IL-2 bolus application alone. Our purpose was to study the haemodynamic changes in patients treated with high-dose IL-2 administered as a constant infusion and in combination with IFN alpha. PATIENTS AND METHODS: Haemodynamic variables were obtained during therapy courses of 11 patients (aged 48 to 71 years, median 61) with metastatic renal cell carcinoma receiving immunotherapy with IL-2/IFN alpha. Therapy consisted in IFN alpha 10 x 10(10) IU/m2 body surface area (BSA) once daily on days 1-5 i.m. on a regular ward, followed by IL-2 as a constant infusion of 18 x 10(6) IU/m2 BSA on days 6-11 in an intensive care unit (ICU). Haemodynamics were first measured after 5 days of IFN alpha application and transfer to the ICU on day 6, a further 24 h after the beginning of IL-2 infusion (day 7), and the end of the therapy course (days 10 and 11). Mean arterial pressure (MAP) was measured noninvasively using an oscillometric device (Dinamap, Critikon). Mixed-venous oxygen saturation (sv O2) was measured using an CO-oxymeter (OSM 3, Radiometer) and peripheral arterial oxygen saturation (psaO2) was recorded continuously with a pulse oximeter (Oxyshuttle, Critikon). In case of haemodynamic instability, stabilisation had priority over invasive haemodynamic measurements, so that nadir values of blood pressure (BP) did not influence mean MAP and are reported separately. Lactate values and criteria for SIRS were obtained before and during IL-2 infusion. Lactate measurements were performed using an enzymatic essay (Abbot FLx). The mean effect size of the haemodynamic values, SIRS criteria, and lactate concentrations during IL-2 infusion (days 6-11) were calculated, and 95% confidence intervals for the effect sizes are indicated. RESULTS: After their daily i.m. injections of IFN alpha, patients had short episodes of fever and tachycardia without significant drops in BP. A few hours after transfer to the ICU and continuous infusion of IL-2, they developed a syndrome of fever, tachycardia and tachypnoea. The haemodynamic values after 5 days of IFN alpha therapy remained in the normal range, whereas those during IL-2 infusion strongly resembled SIRS and sepsis, with a decrease in MAP (98 to 28 mm Hg) and systemic vascular resistance (SVR, 1477 to 805 dyn.s.cm-5) and an increase in cardiac output (cardiac index 2.8 to 4.3 l.min-1.m-2). MAP often had to be stablilized with colloids during the last 48 h of therapy; 5 patients had nadir values below 60 mm Hg, or 30% below basic values in hypertensive patients. Catecholamine therapy became mandatory in 1 patient and therapy had to be discontinued. Surprisingly, some patients already had elevated plasma lactate concentrations after IFN alpha therapy. During IL-2 infusion mean plasma lactate levels increased from 2.3 to 3.2 mmol.l-1 and all patients had lactate concentrations above 2.0 mmol.l-1 at the end of therapy. During the last 48 to 72 h of IL-2 infusion, patients suffered from MODS with altered mental state (7 patients), oliogoanuria (all patients), cardiac dysrhythmias (4 patients), congestive heart failure (1 patient, which led to a second case of therapy interruption), elevated bilirubin (4 patients), and pulmonary dysfunction. In 9 patients supplementary oxygen was necessary when psaO2 fell below 92     

Stimulus-induced gamma oscillations: harmonics of alpha activity?

Event-related changes of spectral power of the EEG were studied for each integer frequency between 5 and 100 Hz in three subjects during memory storage and retrieval. Spectra were calculated for successive, overlapping time epochs in seven channels. In one subject a stimulus-locked increase of power was observed at 12 Hz, while in the other two alpha power decreased at the individual peak frequencies of 9 and 11 Hz, respectively. In all subjects corresponding changes of power appeared at frequencies which were integer multiples of the individual dominant alpha frequencies. An analysis of the cross covariance of the alpha, beta and gamma activity revealed high coefficients for harmonic frequencies only while all other covariances were negligibly small. It is argued that event-related gamma activity may be an epiphenomenon of event-related changes within the alpha band.