The mutual interactions of culture and emotion.
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Biomedical subjects
Publications and source records attributed to H Markus.
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Hyperventilation results in a fall in carbon dioxide concentration, a fall in cerebral blood flow, and slowing of activity on the electroencephalogram. The temporal relationship and duration of these responses are uncertain, and were investigated using simultaneous monitoring of cerebral blood flow velocity and of the electroencephalograph, with end-tidal carbon dioxide monitoring. Sixteen patients and 9 normal volunteers were studied. Cerebral blood flow velocity in the middle cerebral artery was measured using transcranial Doppler sonography during 3 minutes of hyperventilation and during a 3-minute recovery period. Electroencephalographic recordings were rated by both visual score and measurement of the dominant posterior frequency. End-tidal expired carbon dioxide tension was monitored during the same hyperventilation protocol in the volunteers. Flow velocity fell rapidly during active hyperventilation. Electroencephalographic slowing closely correlated with the decrease in flow velocity (r = 0.86), but lagged behind it. In healthy volunteers capnographic records showed a very tight coupling between end-tidal carbon dioxide concentration and flow velocity (r = 0.94). Three minutes after hyperventilation, carbon dioxide concentration, cerebral blood flow velocity, and electroencephalographic activity were still not back to the resting state. The fall in both cerebral blood flow velocity and carbon dioxide concentration are related to but precede electroencephalographic slowing. The abnormalities persist for at least 3 minutes after hyperventilation and this must be taken into account in clinical electroencephalography. Transcranial Doppler sonography is well suited to monitoring short-term changes in the cerebral circulation.
BACKGROUND AND PURPOSE: The detection of asymptomatic embolic signals by Doppler ultrasound may offer a powerful investigational tool in the management of cerebrovascular disease. However, early studies, particularly in patients with carotid artery disease, have reported very different frequencies of embolic signals. While this may reflect differences in patient groups and the criteria used for embolic signal identification, the degree of time-window overlap may be important. If this is insufficient, some embolic signals may fall between two time windows and not appear on the spectral display. Furthermore, the use of nonrectangular time windows, such as the Hanning window, may result in variation of the intensity of an embolic signal depending on where it is detected within the time window. METHODS: To test the importance of this potential problem, the same 25 embolic signals recorded as the audio signal on digital audiotape were each played repeatedly through a transcranial Doppler ultrasound (TCD) system using fast Fourier transform analysis. An older system with no time-window overlap was used, and a more modern system was also used in which three different degrees of overlap were used: -9%, 27%, and 57%. The number of signals audible but not appearing on the spectral display was recorded. The variability in the relative intensity increase for the same embolic signal played repeatedly was estimated by calculating the coefficient of variation of the relative intensity increase. RESULTS: With the older system, 39/500 (7.8%) of embolic signals were missed. With the newer system, the number of embolic signals missed was fewer and decreased with increasing degrees of overlap (10/500 for -9% overlap, 1/500 for 27% overlap, and 0/500 for 57% overlap). For those setups in which embolic signals were missed, there was a highly significant relationship between duration of embolic signal and number of signals missed. In parallel with these results, the coefficient of variation of the relative intensity increase became progressively less with increasing degrees of time-window overlap. For all processing setups, the coefficient of variation was greater for the less intense and shorter duration signals, but this dependence, as estimated by the slope of the regression line, became less strong with higher degrees of overlap. CONCLUSIONS: Inadequate degrees of fast Fourier transform time-window overlap will result in the failure of current TCD machines to detect embolic signals. Furthermore, this and the time windowing currently usually used may result in variability in the relative intensity increase of identical embolic signals. These factors need to be taken into account when comparing data on the frequencies of embolic signals recorded by different researchers and in the design of future TCD equipment.
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Genetic influences in cerebrovascular disease (CVD) may act either independently or by predisposing to, or modulating, the effect of risk factors such as hypertension. Factors involved in the pathogenesis of atherosclerosis, thrombosis and vasoconstriction are important in CVD. The angiotensinogen gene has recently been linked with essential hypertension in affected sibships and a particular polymorphism in exon 2 of the angiotensinogen gene, a threonine to methionine substitution at position 235 (M235T), has been associated with pre-eclampsia and hypertension. In this study we examined the relation of M235T polymorphism to cerebrovascular disease and carotid atheroma in 100 consecutive Caucasian patients with internal carotid artery territory ischaemia (TIA or stroke), presenting to a carotid ultrasound service. Forty five age-matched controls (mostly patients' spouses) were also studied. Hypertension was defined as current treatment with anti-hypertensive agents, or SBP > 160 mm Hg or DBP > 95 mm Hg. Twelve of 100 cases (12%) and eight of 45 controls (12%) were homozygous for the T235 allele. T:M allele ratios were 0.34:0.66 in cases and 0.34:0.66 in controls. There was no relation between the polymorphism and either internal carotid stenosis or common carotid artery intima-media thickness. In the cases, mean percentage internal carotid artery stenosis was TT 18.3 (SD 18.7)%, MT 38.0 (27.1)% and MM 36.8 (30.2)%. Mean intima-media thickness was TT 0.87 (0.18) mm, MT 0.95 (0.34) mm and MM 0.88 (0.23) mm. There was no relation between the polymorphism and hypertension (TT 11 of 100 cases, six of 45 controls).(ABSTRACT TRUNCATED AT 250 WORDS)
We describe a validation study of a new technique for detecting circulating pathological cerebral emboli. Theoretically one would expect solid emboli to be detectable as high intensity signals on the Doppler waveform, and such signals have been reported in humans with potential embolic sources. Pathological cerebral emboli (thrombi, platelet aggregates and atheroma) were introduced into the proximal carotid artery of an in vivo sheep model, and their passage detected in the cerebral circulation using Doppler ultrasound. All of 74 emboli, with a maximum dimension as small as 0.24 mm, were detected as short duration high intensity signals. Smaller pathological emboli could not be made but glass microspheres as small as 5-20 micron resulted in high intensity signals. A significant positive correlation was found between embolus size and relative intensity increase of the embolic signal. A significant positive correlation was also found between embolus size and duration of embolic signal. This study demonstrates that detection of circulating cerebral emboli is possible in vivo. This technique may allow selection of patients at particularly high risk of cerebral embolisation so that they can be given specific prophylactic treatment. Analysis of the Doppler signal may give information on the size of the embolus, although using current signal analysis it is impossible to distinguish between the signals produced by say a larger platelet embolus or a smaller thrombus embolus.
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Cerebral angiography is associated with a risk of neurological complications and air embolism may contribute towards this risk. To test this hypothesis, transcranial doppler ultrasonography was used to monitor the presence of air emboli in the middle cerebral arteries of 7 patients undergoing cerebral angiography. Doppler signals consistent with numerous air emboli were noted during each injection of radiographic contrast. This phenomenon was studied further in sheep. Radiographic contrast medium was injected into the carotid artery while a major carotid branch was insonated transorbitally. Embolic signals similar to those seen in patients were noted. Air was introduced at two points. First, at the time of drawing up the contrast into the syringe, especially with more viscous media. Standing the media before injection resulted in a highly significant reduction of air embolism, reducing the total mean duration of emboli from 1.32 (SD 0.60) s after immediate injection to 0.04 (0.05) s after ten minutes standing for iohexol 340 mg/mL (p < 0.001). Second, air was introduced at the time of injection, possibly by the formation of cavitation bubbles under pressure. This occurred most prominently with the less viscous contrast media and with saline, and was significantly reduced by slow injection (mean duration of emboli for saline 2.85 [2.43] s with fast injection compared with 0.32 [0.37] s with slow injection, p = 0.004). Air embolism may contribute towards neurological dysfunction after angiography. Measures should be taken to reduce this by allowing contrast media to stand prior to injection, and by flushing catheters with saline injected slowly.
A fourth ventricular dermoid cyst examined by CT, MRI and angiography is reported. The combination of CT density and MRI signal indicated the presence of hair within the cyst, which was confirmed at surgery.
BACKGROUND AND PURPOSE: Transcranial Doppler ultrasound can detect circulating cerebral emboli. Monitoring of patients with potential embolic sources may allow identification of high-risk patients who can then be selected for prophylactic treatment. However, practical patient monitoring will require automated programs that can detect emboli and differentiate them from artifact. METHODS: A new off-line algorithm for the detection of emboli, which detects the characteristic relative power increase occurring with an embolus, was evaluated in both an animal model and in patients. (1) In a sheep model, solid embolic materials (thrombus, platelet aggregates, and atheroma) were introduced into the proximal carotid artery while the distal carotid artery or a major branch was insonated. The signals resulting from 77 emboli (mean size, 1.77 mm) were studied and compared with the Doppler signals resulting from artifact. (2) In patients, 100 embolic signals occurring in three patients were analyzed and compared with signals associated with artifact in the same patients. RESULTS: (1) In the sheep model, emboli resulted in a short-duration, high-intensity signal, but intensity increase alone did not distinguish between emboli and artifact. In contrast, the algorithm discriminated embolus from artifact with a sensitivity of 98.7% and a specificity of 98.0%. (2) In patient studies, embolic signals were differentiated from artifact with a sensitivity of 97.2% and a specificity of 97.0% by the algorithm. CONCLUSIONS: Using such an algorithm, detection of cerebral emboli and discrimination from artifact are possible with a high sensitivity and specificity. Incorporation of such an algorithm into an on-line system should make prolonged patient monitoring practical.
BACKGROUND: The identification of gaseous emboli using Doppler ultrasound was described as early as the 1960s. Recently it has been demonstrated that this method can also detect solid emboli such as thrombi and platelet aggregates. This may make this technology useful in a large number of patients with, or at risk of, embolic stroke. SUMMARY OF REVIEW: Emboli appear as short-duration, high-intensity signals in the Doppler spectrum. The intensity of the Doppler signal from an artery containing an embolus depends on the density difference between the embolic material and blood. This difference is greatest for gaseous emboli, which are therefore the most easy to detect. Gaseous emboli have been demonstrated during deep-sea diving, and their presence correlates with the occurrence of decompression sickness. Similar signals have been detected during cardiopulmonary bypass. A relation has been demonstrated between the number of emboli detected by transcranial Doppler and a decline in neuropsychological function after cardiopulmonary bypass. Solid emboli such as thrombi and platelet aggregates result in less intense signals than air emboli. Their detection, using Doppler ultrasound, has recently been described in patients with prosthetic heart valves, atrial fibrillation, and carotid artery disease. It may also help in the detection and localization of embolic sources in patients with stroke. Studies in in vitro and in vivo models demonstrate that this technique provides information on the size and type of emboli. Larger emboli produce signals of greater intensity and duration. Practical patient monitoring will require automatic emboli detectors incorporated into the Doppler machine; such programs are being developed. CONCLUSIONS: Detection of solid emboli using Doppler techniques offers an exciting new diagnostic tool. It has been demonstrated that the technique can detect solid emboli. The prognostic significance of such emboli remains to be determined. It is hoped that the technique will allow detection of patients at high risk of embolic stroke in whom appropriate prophylactic treatment can then be instituted.
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Nutritional status was assessed in a group of patients with Parkinson's disease. Weight loss since the onset of disease occurred in 52% of the patients and 22% had lost more than 12.8 kg. Although 67% of patients experienced eating difficulties of some kind, dietary intakes of protein and energy were not significantly lower than recommended intakes. Plasma levels of albumin (44.2 g/l vs 45.7 g/l), vitamin A (2.61 vs 2.94 mumol/l), vitamin E (22.0 vs 32.0 mumol/l), iron (15.3 vs 18.3 mumol/l) and zinc (14.2 vs 18.7 mumol/l) were significantly lower (P < 0.05) in the patients than in healthy controls. Levels of ferritin, total iron-binding capacity and copper were similar between groups. The potential significance of low levels of vitamin E and zinc are discussed in relation to oxidative stress in the pathogenesis of this disease.
The acute central haemodynamic and neuroendocrine effects of intravenous flosequinan were studied in a group of 10 patients with severe heart failure. Flosequinan improved cardiac output by a maximum of 1.59 l.min-1, it reduced pulmonary capillary wedge pressure by 11.9 mm Hg and it also caused a reduction in right atrial pressure by a maximum of 7.2 mm Hg. It tended to cause a fall in plasma adrenaline levels but not in plasma noradrenaline. There was little fall in blood pressure in response to flosequinan and no patient developed an adverse event. Intravenous flosequinan may be a useful candidate drug for controlled clinical studies in patients with severe heart failure.
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In a previous paper, we showed that chronic denervation of the sciatic nerve for more than 21 days in adult rats caused expansion of the saphenous nerve into sciatic territory in the spinal cord (medial L4, L5 and L6). To try to explain this expansion in the present paper, we tested the hypothesis that weak ineffective synapses of saphenous terminals are always present in sciatic territory. For this purpose the sciatic nerve was acutely denervated, the cord mapped with microelectrodes and responses evoked in single cells with natural (mechanical cutaneous) or electrical (pulses to saphenous nerve) stimulation. In the sciatic territory, no natural responses occurred but electrically evoked responses from the saphenous were everywhere. When drugs were applied to potentiate synaptic activity, many of the silent neurons in the sciatic territory in L4, L5 and L6 responded to natural inputs mediated by the saphenous. Picrotoxin was more effective than 4-aminopyridine which was more effective than strychnine in expressing these weak somatotopically inappropriate saphenous inputs. All together, these results support the hypothesis that weak ineffective saphenous inputs exist in sciatic territory of the spinal cord. They can be artificially expressed with electrical volleys or chemical potentiation and may be naturally expressed several weeks after chronic lesions of the sciatic nerve.