European collaborative trial of multifactorial prevention of coronary heart disease.
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Clinical Trials as Topic↗
Biomedical subjects
G Rose
Publications and source records attributed to G Rose.
Risk of stroke in non-rheumatic atrial fibrillation.
Estimates of the risk of stroke for men with non-rheumatic atrial fibrillation were obtained from two large cohort studies--the Whitehall Study of London Civil Servants and the British Regional Heart Study. The first cohort provided an estimated relative risk of stroke of 6.9 compared with controls. This increased risk confirms that of the other prospective estimate, 5.6, found in the Framingham study. In the second cohort only one of the men at risk had a stroke, and the risk estimate did not differ significantly from unity. The absolute rates of stroke in both cohorts were lower than those reported in the Framingham study, implying a lesser potential benefit from preventive measures. These lower rates should be considered in the planning of trials. The risk of stroke was significantly associated with raised systolic or diastolic blood pressure but not with age or coronary heart disease.
Adult↗
Implications of genetic research for control measures.
Coronary heart disease and hypertension are 'mass' diseases to which nearly all individuals are in varying degree susceptible. Incidence rates, population differences and time trends are determined by environment and lifestyle. Within populations the different levels of precursors in individuals are probably genetically determined to a large degree. Genetic and environmental approaches to research are interdependent, but the contribution of genetic advances to control measures is currently confined to less common conditions or to individuals at exceptionally high risk.
Coronary Disease↗
'Ancestral' neural mechanisms of electrolocation suggest a substrate for the evolution of the jamming avoidance response.
The genus Sternopygus, believed to reflect ancestral traits of gymnotiform electric fish, is closely related to the more 'modern' genus Eigenmannia (Mago-Leccia 1978; Fink and Fink 1981). Sternopygus is the only known genus of electric fish that does not perform a jamming avoidance response (JAR) to minimize the potentially detrimental effects of signal interference between discharging neighbors (Bullock et al. 1972, 1975), and its ability to electrolocate objects is rather immune to jamming (Matsubara and Heiligenberg 1978). By studying the responses of midbrain neurons to stimulus regimes effective in eliciting the JAR in Eigenmannia, we found that Sternopygus has neurons capable of discriminating the sign of the difference frequency between interfering electric organ discharges (EODs). These 'sign-selective' neurons, which are believed to be important elements in the control of the JAR in Eigenmannia, may, therefore, fulfill a more general function in the detection of moving objects and conspecifics but could potentially be assembled for the evolution of a JAR in Sternopygus. The relative immunity to jamming in this genus may result, in part, from a stronger reliance upon the ampullary electrosensory system which operates in the DC and low-frequency range, outside the EOD spectrum of these fish.
Action Potentials↗
Review of primary prevention trials.
The main threat to patients with mild to moderate hypertension is coronary heart disease (CHD), but controlled trials of antihypertensive drug therapy have given disappointing results: overall, the reduction in CHD mortality (11%) and morbidity (10%) were small and nonsignificant. Recent trials comparing a beta blocker with other antihypertensive drugs have not shown the "cardioprotection" expected from their pharmacologic actions and from their effectiveness after myocardial infarction; but two large trials have suggested some reduction in CHD among male nonsmokers. Relaxation with biofeedback possibly lowers CHD risk. Although the trials indicate that drugs generally do little to reduce CHD in hypertensive patients, control of smoking and serum cholesterol may be more effective.
Antihypertensive Agents↗
Neonatal exposure to a high level of ACTH4-10 impairs adult learning performance.
Male offspring of Sprague-Dawley dams were injected with 25 micrograms of ACTH4-10 or the vehicle on days 2 through 7 postpartum. Peptide treated animals exhibited a marked motor response to the peptide injection. Adrenal weights of these animals were consistently heavier than littermate controls in both the developing and adult animals. ACTH4-10 treated neonates exhibited significantly poorer learning performance in the shuttle box and were slower to acquire the reversal learning problem of a visual discrimination task under light shock levels. In addition, these animals also exhibited an exaggerated startle response and a stronger thigmotaxis response in the open field than controls. These results indicate that exposing the developing nervous system to relatively high levels of ACTH4-10 can produce marked long-term effects on behavior.
Acoustic Stimulation↗
Twenty year follow up of patients in the Medical Research Council trial of anticoagulants in acute myocardial infarction.
A 20 year follow up of 1330 patients in the Medical Research Council trial of short term anticoagulant treatment in myocardial infarction showed no long term benefits; but it provided interesting data on the outcome in such patients. Sixteen per cent of the patients were alive 20 years later. The excess mortality rate in trial participants over that expected for England and Wales as a whole declined rapidly after the early months, but some excess persisted throughout the follow up. Three quarters of all the deaths were from coronary heart disease; 70% of these coronary deaths occurred after the patients had left hospital. This finding emphasises the importance of secondary prevention.
Adult↗
Flow properties of modified packed red cells.
We investigated free gravitational blood flow of modified packed red cells. Variables affecting free flow included final haematocrit, duration of blood storage at 4-6 degrees C and the centrifugal force required in preparation of this blood component. Irrespective of the duration of storage, free blood flow of modified packed red cells was not different from whole blood, provided the haematocrit did not exceed 0.63.
Blood Flow Velocity↗
Nigral and adrenal grafts in parkinsonism: recent basic and clinical studies.
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Plasma cholesterol concentration and death from coronary heart disease: 10 year results of the Whitehall study.
Ten year mortality from coronary heart disease in 17,718 middle aged men was related to their initial plasma cholesterol concentrations. The relative risk of death from coronary heart disease declined with age, but the absolute excess risk did not. The risk gradient was continuous over the whole range of cholesterol concentrations, the lowest mortality being among men with concentrations below the lowest decile. It seems that, as with blood pressure, the average cholesterol concentration in the blood pressure, the average cholesterol concentration in the population is too high: lowest concentrations are prognostically the best. A quarter of all deaths from coronary heart disease related to cholesterol occurred among men with concentrations above the top decile, but 55% occurred among men with concentrations in the middle three fifths of the distribution; this figure of 55% could be reduced only by a policy aimed at lowering concentrations in the whole population.
Adult↗
European collaborative trial of CHD prevention.
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Clinical Trials as Topic↗
Preventive medicine and morality.
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Health Promotion↗
Limits of phase and amplitude sensitivity in the torus semicircularis of Eigenmannia.
Eigenmannia can detect modulations in the time disparity of signals received by different regions of the body surface as small as several hundred nanoseconds. This study presents recordings of single units in the torus semicircularis that are sensitive to time disparities (differential-phase) between a sinusoidal signal received by the head region and a similar signal received by the body surface caudal to the fish's pectoral fins. The sensitivity of units to differential phase, measured by the change in spike rate per unit change in time disparity, was greatest when small phase modulations, rather than stationary phase differences, were presented. Thresholds of differential-phase coders ranged from 6.5 microseconds to several hundred microseconds, with approximately 20% of the units having thresholds in the 5-10 microseconds range. For most cells, sensitivity to small modulations of differential-phase was relatively unaffected by time disparity 'offsets' within a range of several hundred microseconds. A threshold of 5-10 microseconds is still an order of magnitude higher than that measured in the Jamming Avoidance Response (JAR). Neurons that were sensitive to amplitude modulations (AMs) had thresholds as low as 0.05%. This value is comparable to that observed at the behavioral level.
Animals↗
Neural coding of difference frequencies in the midbrain of the electric fish Eigenmannia: reading the sense of rotation in an amplitude-phase plane.
Eigenmannia is able to discriminate the sign of the difference, Df, between the frequency of a neighbor's electric organ discharge (EOD) and that of its own EOD. This discrimination can be demonstrated at the level of individual neurons of the midbrain. Intracellular and extracellular recordings of such sign-selective cells revealed the following: Units preferring positive Dfs and units preferring negative Dfs were found with equal frequency. The degree of selectivity was also similar for these two classes of neurons. All sign-selective units were sensitive to the magnitude of the frequency difference, i.e. the beat rate. Most units responded best to beat rates in the 4-8 Hz range. Sign-selectivity was observed only when the jamming signal (S2) was presented through electrodes other than those used to deliver the mimic (S1) of the fish's EOD, i.e. only when amplitude modulations were accompanied by modulations of differential phase. Intracellular studies suggest that most sign-selective neurons of the tectum are large, multipolar cells in the stratum album centrale. These cells send projections to the reticular formation, to lamina 9 of the torus semicircularis and to the N. electrosensorius.
Animals↗
Gating of sensory information: joint computations of phase and amplitude data in the midbrain of the electric fish, Eigenmannia.
Eigenmannia is able to determine whether the electric organ discharge (EOD) of a neighbor is of higher or lower frequency than its own EOD. For small frequency differences, Df, the fish avoids jamming by shifting its frequency away from that of its neighbor. This jamming avoidance response (JAR), therefore, requires that the fish discriminate the sign of Df. The interference pattern of two EODs of similar frequency is characterized by local modulations of the instantaneous amplitude and the spatial difference of the instantaneous phase, or 'differential phase', of the mixed signal. When amplitude and differential phase are plotted in a two-dimensional state plane, circular graphs are obtained with a sense of rotation that reflects the sign of Df. Behavioral studies have shown that both amplitude and differential phase modulations are required for the control of the JAR. Considering two regions of the body surface, A and B, that receive strong and weak contamination by the jamming signal, respectively, rises and falls of the signal amplitude in A will be accompanied by respective advances and delays of the signal in A relative to that in B if the jamming signal is of lower frequency, i.e. if Df is negative. A plot of amplitude versus different phase yields a clockwise sense of rotation in this case. The opposite relation between amplitude and phase modulations, resulting in a counterclockwise rotation, holds for a positive Df. For the less strongly contaminated area B, however, the relation between the sign of Df and the sense of rotation is reversed, so that for a negative Df, a rise of amplitude in B will coincide with a delay of the signal in B relative to that in A. By independent experimental control of amplitude and differential-phase modulations, we explored midbrain neurons that discriminate the sense of rotations in the amplitude-phase plane. We found that these neurons achieve this discrimination by gating amplitude inputs by differential-phase information, thus exploiting the particular combinations of amplitude and differential phase that characterize a given sense of rotation. Since the response properties of such neurons only reflect the sense of rotation, and since the same sense of rotation can be obtained for either sign of Df (depending upon the relative contamination of the receptive fields involved), individual neurons do not yet provide unambiguous information about the sign of Df.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Neurophysiological studies of sensory gating in rats: effects of amphetamine, phencyclidine, and haloperidol.
Central mechanisms of sensory gating were assessed in Sprague-Dawley rats by an evoked potential technique similar to one that we have previously used to show diminished sensory gating in psychotic patients. Middle latency (15-50 msec) auditory evoked potential responses were recorded at the skull in unanesthetized freely moving animals. Gating mechanisms were assessed in a conditioning-testing paradigm by measuring the suppression of response to a 74 dB click test stimulus following an earlier identical conditioning stimulus at 0.5-sec intervals. The rats demonstrated significant suppression of the N50 response to the second auditory stimulus. Amphetamine treatment significantly interfered with the suppression of the response to the second stimulus; haloperidol, injected after the amphetamine, returned the conditioning-testing ratio toward normal values. Phencyclidine caused a similar decrease in suppression and was similarly antagonized by haloperidol. During some periods of hyperarousal, animals showed spontaneous loss of suppression; this condition could be reversed by haloperidol treatment. These results with psychotomimetic drugs in an animal model parallel abnormalities in sensory gating previously observed in psychotic human subjects.
Animals↗
The relationship between both sodium and potassium intake and blood pressure in London Civil Servants. A report from the Whitehall Department of Environment Study.
The relationship was examined in 459 male London Civil Servants between the casual lying systolic and diastolic (phase V) blood pressures measured in the clinic, and 24-hr urinary sodium and potassium excretion collected an average of 6 weeks later. Systolic and diastolic pressures, after adjusting for age and weight, were both negatively associated with the 24 hr potassium excretion (r = -0.17 [p less than 0.001, 95% confidence limits -0.07, -0.27) and r = -0.11 (p less than 0.05, 95% CL 0.00, -0.21) for systolic and diastolic pressure respectively]. Adjusted systolic but not diastolic pressure was also negatively associated with plasma potassium estimated at the time of blood pressure measurement (r = -0.15, p less than 0.001, 95% CL -0.06, -0.24). In 159 female London Civil Servants both systolic and diastolic pressures were negatively correlated with plasma potassium. However, there was no evidence for a negative relationship between urinary potassium excretion and blood pressure in women. Urinary sodium excretion was not related to blood pressure either in men or women. Blood pressure was also measured by the subjects at home over a one week period during which time the urine collection was made. There was no evidence for an association between blood pressure measured at home 6 weeks after the time of drawing blood, and plasma sodium. On the other hand, in men, the negative relationship between blood pressure and urinary potassium excretion was consistent and independent of the time and place of measuring blood pressure. This is consistent with a true effect of diet, a low potassium intake being associated with an increased blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Distribution and determinants of the difference between diastolic phase 4 and phase 5 blood pressure.
Auscultatory blood pressure measurements from 18 325 male British civil servants were used to examine the relationship between diastolic phase 4 (D4) and phase 5 (D5). The two measures are highly correlated (r = 0.98) and this is unaffected by age. The distribution of the difference between the two indices is skewed with a median difference of 1 mmHg. Phase 4 and D5 were recorded at the same level in 31% of subjects. The difference was 5 mmHg or more in 9% of subjects, and 10 mmHg or more in 1%. The difference between the two diastolic indices depends partly on the level of blood pressure and body mass index.
Adult↗