Donald O. Walter

Systolic blood pressure and mortality

Summary Background The current systolic blood-pressure threshold for hypertension treatment is 140 mm Hg for all adults. WHO and the International Society of Hypertension have proposed that normal pressure be lower than 130 mm Hg, with an optimum pressure of less than 120 mm Hg. These recommendations are based largely on the assumption that cardiovascular and overall mortality depend in a strictly increasing manner on systolic blood pressure. The Framingham study was instrumental in establishing this viewpoint. We reassessed data from that study to find out whether the relation is strictly increasing or whether there is a threshold in this relation. Methods We used logistic splines to model the relation of risk of cardiovascular and all-cause death with systolic blood pressure, using age-specific and sex-specific rates. We tested for the independence of the slope parameters from age and sex, and the reduced model with common slopes was used to produce a model different from the conventional linear logistic model. Findings Against the predictions of the linear logistic model, neither all-cause nor cardiovascular deaths depended on systolic blood pressure in a strictly increasing manner. The linear logistic model was rejected by the Framingham data. Instead, risk was independent of systolic blood pressure for all pressures lower than a threshold at the 70th percentile for a person of a given age and sex. Risk sharply increased with pressure higher than the 80th percentile. Since systolic blood pressure steadily increases with age, the threshold increases with age, but more rapidly in women than in men. Interpretation The Framingham data contradict the concept that lower pressures imply lower risk and the idea that 140 mm Hg is a useful cut-off value for hypertension for all adults. There is an age-dependent and sex-dependent threshold for hypertension. A substantial proportion of the population who would currently be thought to be at increased risk are, therefore, at no increased risk.

Regional differences in brain electrical activity in dementia: use of spectral power and spectral ratio measures ☆

The pathologic changes in dementia of the Alzheimers type (DAT) commonly affect selected brain regions. The cortical areas affected in multi-infarct dementia (MID) are less predictable and may be secondary to subcortical gray or white matter damage that is widespread in MID. We compared several types of quantitative EEG power measures (absolute and relative power, and ratios of power) to determine their regional distribution, and their association with changes in cognitive status and age. We examined 49 subjects with clinically diagnosed mild-to-moderate DAT, 29 with mild-to-moderate MID, and 38 elderly controls (CON). We used discriminant analysis to identify, for each parameter type, the brain region and frequency band where the parameter best distinguished between groups of subjects. The parameters showed regional differences in distinguishing between DAT and MID subjects, and in their association with age and cognitive status. All parameters were useful for detecting differences between normal and demented subjects and correctly identified comparable proportions of subjects as having dementia. Subjects who were abnormal on several parameters were much more likely to have dementia. The additive effects of these parameters in correct classification suggest that they may be monitoring different physiologic processes. Combinations of several types of parameters may be more useful than individual parameters for distinguishing demented from non-demented subjects.

Computer techniques in correlation and spectral analyses of cerebral slow waves during discriminative behavior

Data reducing and computing techniques have been applied to EEG records taken during training from five cats with implanted electrodes and having records typical of seventy-five other implanted animals. Implanted electrodes were placed in dorsal and ventral parts of the hippocampal arch, the adjacent entorhinal cortex, and in subcortical areas, including subthalamus and mesencephalic reticular formation, and in visual and sensorimotor cortex. Animals were trained in T-maze approach and in delayed response tests, both to food rewards. EEG records were manually digitzed for presentation to a digital computer (IBM 709). Inherent rhythmicity of hippocampal records was examined in auto-correlations in “waiting” records prior to approach performance, and during approach. Pre-approach records showed a wide spectrum, with a 3 or 4 cycles/sec dominant frequency. Approach records showed a dominant frequency in a narrow range at 6 cycles/sec. Cross-correlations of approach records from different parts of the hippocampal arch in the fully trained animal showed a highly consistent phase pattern in different correct trials on the same day, and on different days. By contrast, incorrect responses were characterized by a markedly different phase pattern, which was consistent for the incorrect responses on different days. Lability of frequencies in extrahippocampal slow-wave bursts during approach minimized the value of simple cross-correlation analysis. More comprehensive cross-spectral analysis has been initiated and represents an innovation in EEG data analysis. It has confirmed phase pattern shifts between records of correct and incorrect responses. The possible role of wave processes in cerebral systems in integration and transfer of information is discussed.

Prognostic value of dobutamine stress echocardiography in predicting cardiac events in patients with known or suspected coronary artery disease

OBJECTIVES The study sought to determine the utility of dobutamine stress echocardiography (DSE) in predicting cardiac events in the year after testing. BACKGROUND Increasingly, DSE has been applied to risk stratification of patients. METHODS Medical records of 1,183 consecutive patients who underwent DSE were reviewed. The cardiac events that occurred during the 12 months after DSE were tabulated: myocardial infarction (MI), cardiac death, percutaneous transluminal coronary angioplasty (PTCA), and coronary artery bypass surgery (CABG). Patient exclusions included organ transplant receipt or evaluation, recent PTCA, noncardiac death, and lack of follow-up. A positive stress echocardiogram (SE) was defined as new or worsened wall-motion abnormalities (WMAs) consistent with ischemia during DSE. Classification and regression tree (CART) analysis identified variables that best predicted future cardiac events. RESULTS The average age was 68+/-12 years, with 338 women and 220 men. The overall cardiac event rate was 34% if SE was positive, and 10% if it was negative. The event rates for MI and death were 10% and 8%, respectively, if SE was positive, and 3% and 3%, respectively, if SE was negative. If an ischemic electrocardiogram (ECG) and a positive SE were present, the overall event rate was 42%, versus a 7% rate when ECG and SE were negative for ischemia. Rest WMA was the most useful variable in predicting future cardiac events using CART: 25% of patients with and 6% without a rest WMA had an event. Other important variables were a dobutamine EF <52.5%, a positive SE, an ischemic ECG response, history of hypertension and age. CONCLUSIONS A positive SE provides useful prognostic information that is enhanced by also considering rest-wall motion, stress ECG response, and dobutamine EF.

Comprehensive spectral analysis of human EEG generators in posterior cerebral regions

Abstract Continuous spectral analyses of several minutes of normal human EEGs were prepared by computer, and converted to compact graphic forms. This new presentation of voluminous data in contour maps gives an overview of the evolution of patterns in the EEG. Parameters graphed were spectral intensity (“power spectral density”), and coherence, a quantity expressing strength of relationship between brain areas. In one subject, the strongest relations were among longitudinally oriented parieto-occipital linkages, representing the subjects alpha wave. Wave activity in a similar frequency band, recorded across the occipital midline, was completely incoherent with the alpha wave. Thus, two independent generation processes in the same frequency band, orthogonally polarized, are required to account for these records. Low frequency activity in the O1O2 leads was related only partially to the heart-beat. In a second subject, there was somewhat greater coherence from side to side than between homolateral centro-parietal and parieto-occipital pairs of leads. The same configuration of two geometrically orthogonal and statistically uncorrelated generators was observed in this subject. Of 28 other analyzed in this way, eighteen showed the same clear perpendicularity, seven were similar but less marked, while three showed no such pattern. The second illustrative subject also showed coherences flanking his alpha-wave peaks, covering a band considerably wider (2–5 c/sec) than those of high alpha intensity (0.5–1.0 c/sec). Eighteen of 25 other subjects showed a similar disparity of width. Mathematical constraints implied by the common finding of two perpendicular alphaband generators were presented. The wide coherent bands (C3-P3/C4-P4) were interpreted as possibly due to shared “side-bands” of the alpha wave; but other features of these wide bands led to the suggestion that much of the local activity not shared between the sides is caused by the shared activity, or at least causally connected with it.

Effect of low-level, low-frequency electric fields on EEG and behavior in Macaca nemestrina

Summary A series of experiments has been done to assess the effects of low-level, low-frequency electric fields on the behavior and EEG of monkeys. Three monkeys were implanted with subcortical and cortical EEG electrodes and trained to press a panel on a fixed interval-limited hold schedule. The monkeys were rewarded for pressing the panel once every 5 sec within a 2.5 sec enable period. After the animals were performing well, they were tested under low-level electric fields (2.8 V p-p); the voltage was applied to 2 large metal plates 40 cm apart so that the monkeys head was completely within the field. Fields frequency was set at 7 or 10 c/sec within the range of typical EEG recording (0-33 c/sec). Four hour daily tests of fields-on were randomly interspersed with 4 h runs with field-off. Under the 7 c/sec fields, the monkeys showed a significantly faster interresponse time in 5 of 6 experiments. Mean differences between fields-on and fields-off were 0.4 sec or greater. The 10 c/sec fields did not produce a reliable effect on behavior. Analysis of the EEG data showed a relative peak in power at the frequency of the fields (10 c/sec and 7 c/sec) for the hippocampus in all 3 monkeys. Similar peaks were seen less consistently in the amygdala and the centre median.

Changes in sleep-wakefulness in female rats during circadian and estrous cycles.

Abstract Continuous EEG records from chronically implanted cerebral electrodes have been made of sleep-wakefulness in 5 female rats throughout their 4-day or 5-day estrous cycles, under controlled lighting conditions with 14 h light and 10 h darkness per day. Percentages of alertness, slow wave sleep (SS) and paradoxical sleep (PS) in each 10-min period were punched on IBM cards and introduced to a computer system capable of plotting these percentages daily in each rat and averaging across animals for each time period on corresponding days of the estrous cycle. The results reveal rapid shifts from relative alertness to sleep after the lights come on in the morning. Highest levels of alertness generally occur during the early evening and PS during the afternoon, including the afternoon of proestrus. The day of vaginal cornification (‘estrus’) shows a high percentage of PS — after a night characterized by alertness and virtual absence of PS,i.e., the night of behavioral estrus and ovulation. The female rat, like the male, sleeps on the average about two-thirds of the daylight hours and only one-third of the dark period. Hormonal changes during the day of proestrus appear to increase alertness that night, compensated by an increase in sleep, especially PS, the following day.

Application of phase detection and averaging techniques in computer analysis of EEG records in the cat

Abstract Consistency of phase patterns in EEG records from the hippocampal system and midbrain reticular formation have been examined in the course of behavioral training in five cats with implated electrodes. These studies have involved novel application of computing techniques, including continuous measurement of phase and amplitude characteristics of single wave trains by digital filtering techniques, the use of cross-spectral analyses with calculation of complex transfer functions, and averaging of records during repeated behavioral performances with calculation of coherence functions in cross-spectral examinations. It was found that rhythmicity appeared in the computed average at the rate of the dominant EEG frequency as T-maze performance reached a high level, and was related to a reduction in scatter in phase patterns at high performance levels. Reversal of behavioral cues was associated with an immediate brief increase in rhythmicity of the average, then a decline followed by a progressive reemergence of rhymicity at the end of retraining. Continuous phase-and-amplitude examinations during delayed response performance indicated a rhythmic phase modulation on wave trains with an apparently single frequency appearing during periods of discrimination. Comparison of probability bounds in cross-spectral analysis with use of a polar coordinate display have indicated major differences in phase relations between different hippocampal regions between correct responses in certain circumstances, with consistency in different examinations. These findings are discussed in relation to a stochastic model of the cerebral system, with reference to the possible role of the wave process in handling and storage of information.

The Maturation of Vestibular Nystagmus in Infancy and Childhood

The displacements, durations, and velocities of the slow and fast components of both the primary and secondary nystagmus induced by constant angular acceleration were measured in 46 normal children 1 month to 11 years old. There were significant changes in nystagmus parameters in respect to maturation. The young infant had larger amplitude, higher velocity beats than the older child during both the primary and the secondary nystagmus. Parameters describing both the primary and the secondary nystagmus reached their peak values and terminated earlier in the infant than in the older child. Although the slow component velocity during secondary nystagmus was much slower than during the primary nystagmus at all ages, the secondary nystagmus/primary nystagmus ratio was significantly greater in early infancy. Thus, in infancy, as compared with later childhood, the vigor of the secondary nystagmus was disproportionately greater than the primary nystagmus. These results were discussed in relation to the maturation both of vestibular responsiveness and of vestibular adaptation.

Local regulation of the threshold for calcium sparks in rat ventricular myocytes: role of sodium‐calcium exchange

1 To determine whether Na+‐Ca2+ exchange modulates Ca2+ sparks, we studied enzymatically isolated patch clamped rat ventricular myocytes loaded with the Ca2+‐sensitive indicator fluo‐3, using confocal microscopy at 20–22 °C. Two‐dimensional images of Ca2+ sparks were recorded at 240 Hz using a laser scanning confocal microscope, allowing observation of a large area of the cell (820 μm2) at one time. 2 At a holding potential of −75 mV, spontaneous sparks were infrequent. Removal of extracellular Na+ for 520 ms, which in the absence of pipette Na+ should block Na+‐Ca2+ exchange bidirectionally, was associated with a fourfold increase in spark frequency, without a significant change in cytoplasmic [Ca2+], sarcoplasmic reticulum (SR) Ca2+ content, or spark intensity, size or time course. 3 These findings are consistent with a model of excitation‐contraction coupling in which Na+‐Ca2+ exchange locally regulates the resting Ca2+ concentration in the diadic cleft (T‐tubule‐SR junction), thereby modulating the threshold for triggering Ca2+ sparks.