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Biomedical subjects

D H Evans

Publications and source records attributed to D H Evans.

At least 55 records · Page 3Linked to original sources
PubMed1999

Transcranial Doppler directed dextran therapy in the prevention of carotid thrombosis: three hour monitoring is as effective as six hours.

BACKGROUND: Six hours' monitoring by transcranial Doppler (TCD) has been successful in directing Dextran therapy in patients at high risk of thrombotic stroke after carotid endarterectomy (CEA). OBJECTIVES: Is 3 h of routine monitoring as effective as 6 h in the prevention of early postoperative thrombotic stroke? DESIGN: Prospective, consecutive study in all patients with an accessible cranial window. METHODS: One hundred and sixty-six patients undergoing CEA underwent 3 h of postoperative monitoring by TCD. Any patient with > 25 emboli detected in any 10 min period or those with emboli that distorted the arterial waveform were commenced on an incremental infusion of dextran 40. RESULTS: The majority of patients destined to embolise will do so within the first 2 postoperative hours. Dextran therapy was instituted in nine patients (5%) and rapidly controlled this phase of embolisation although the dose had to be increased in three (33%). No patient suffered a postoperative carotid thrombosis but one suffered a minor stroke on day 5 and was found to have profuse embolisation on TCD; high dose dextran therapy was again instituted, the embolus count rate fell rapidly and he made a good recovery thereafter. Overall, the death and disabling stroke rate was 1.2% and the death/any stroke rate was 2.4%. CONCLUSION: Three hours of postoperative TCD monitoring is as effective as 6 h in the prevention of postoperative carotid thrombosis.

Adult↗
PubMed1999

Effects of CO2 on dynamic cerebral autoregulation measurement.

Arterial pCO2 is known to influence cerebral autoregulation but its effect on the dynamic relationship between mean arterial blood pressure (ABP) and mean cerebral blood flow velocity (CBFV), obtained from spontaneous fluctuations in ABP, has not been established. In 16 normal subjects, ABP was measured non-invasively (Finapres), CBFV was estimated with Doppler ultrasound in the middle cerebral artery, and end-tidal CO2 (EtCO2) was measured with an infrared capnograph. Recordings were made before, during and after breathing a mixture of 5% CO2 in air. The coherence function, amplitude and phase frequency responses, and impulse and step responses for the effects of ABP on CBFV were calculated by spectral analysis of beat-to-beat changes in mean ABP and CBFV before (mean CO2 5.55 +/- 0.38 kPa), during (6.43 +/- 0.31 kPa) and after 5% CO2 (5.43 +/- 0.26 kPa). During 5% CO2, the coherence function and the amplitude frequency response were significantly increased for frequencies below 0.05 Hz and the phase was reduced for the frequency range 0.02-0.1 Hz. The impulse and step responses indicated that 5% CO2 reduces the efficiency of the autoregulatory mechanism. A 20.7% average increase in CBFV induced by a 14.4% increase in EtCO2 was found to be mediated by a 25.9% reduction in critical closing pressure, while the change in resistance area product was non-significant.

Adult↗
PubMed1999

Cerebral blood flow velocity during neonatal seizures.

AIM: To determine if cerebral blood flow velocity increases during all types of neonatal seizure, and whether the effect is due solely to an increase in blood pressure, transmitted to the cerebral circulation when autoregulation is impaired. METHODS: Seizures were diagnosed in 11 high risk neonates using cotside 16 channel video-EEG polygraphy. EEG, cerebral blood flow velocity (CBFV) using transcranial Doppler ultrasound, and arterial blood pressure (ABP) measurements were made. At least two 5-10 minute epochs of simultaneous measurements were performed on each infant. These epochs were then reviewed to eliminate artefacts, and one minute data periods containing a clear seizure onset were created. Each period contained 20 seconds before the seizure. Data periods without seizures from the same infants were also analysed and compared with seizure periods. RESULTS: Four infants had purely electrographic seizures-without clinical manifestations. Six infants had electroclinical seizures. One infant displayed both seizure types. A random effects linear regression analysis was used to determine the effect of seizures on CBFV and ABP. A significant increase was found in mean CBFV in those periods containing seizures. The mean percentage change in velocity for all infants was 15.6%. Three infants showed a significant increase in mean ABP after seizures but the overall increase in ABP for all infants was not significant. CONCLUSION: Electroclinical and electrographic neonatal seizures produce an increase in CBFV. In some infants the increase is not associated with an increase in blood pressure. These preliminary results suggest that electrographic seizures are associated with disturbed cerebral metabolism. Treatment of neonatal seizures until electrographic seizure activity is abolished may improve outcome for these infants.

Blood Flow Velocity↗
PubMed1999

Effect of caffeine on neonatal splanchnic blood flow.

Doppler ultrasound was used to study the effect of the first intravenous dose of caffeine on splanchnic haemodynamics in preterm neonates. Peak systolic velocity in the superior measenteric artery and coeliac axis was significantly reduced for 6 hours after caffeine infusion. The effect of this reduction in blood flow to the neonatal gut is not known.

Blood Flow Velocity↗
PubMed1999

Characterization of an endothelin ET(B) receptor in the gill of the dogfish shark Squalus acanthias.

Endothelins (ETs) are potent vasoconstrictive peptides that are secreted by the vascular endothelium and other tissues in vertebrates. Previous studies have demonstrated that ETs are expressed in a variety of fish tissues and contract various blood vessels. In order to determine if receptors for ET are expressed in fish gill tissue, we examined the binding kinetics of (125)I-labeled, human ET-1 to membrane fragments isolated from the gill of the dogfish shark, Squalus acanthias. (125)I-ET-1 bound at a single site, with a dissociation constant (K(d)) and binding site number (B(max)) very similar to those described in a variety of mammalian blood vessels. ET-1 and ET-3 competed equally with (125)I-ET-1, suggesting that the receptor was ET(B), which has been shown in mammalian systems to bind to both ligands equally. The ET(B)-specific agonists sarafotoxin S6c, IRL-1620, and BQ-3020 also competed against (125)I-ET-1 at a single site, supporting this hypothesis. We conclude that the shark gill expresses an ET(B) receptor with substantial homology to the mammalian receptor and that ET may play an important role in modulating such vital gill functions as gas exchange, ion regulation, acid-base balance, and excretion of nitrogen.

Animals↗
PubMed1998

Frequency-domain analysis of cerebral autoregulation from spontaneous fluctuations in arterial blood pressure.

The dynamic relationship between spontaneous fluctuations of arterial blood pressure (ABP) and corresponding changes in cerebral blood flow velocity (CBFV) is studied in a population of 83 neonates. Static and dynamic methods are used to identify two subgroups showing either normal (group A, n = 23) or impaired (group B, n = 21) cerebral autoregulation. An FFT algorithm is used to estimate the coherence and transfer function between CBFV and ABP. The significance of the linear dependence between these two variables is demonstrated by mean values of squared coherence > 0.50 for both groups in the frequency range 0.02-0.50 Hz. However, group A has significantly smaller coherences than group B in the frequency ranges 0.02-0.10 Hz and 0.33-0.49 Hz. The phase response of group A is also significantly more positive than that of group B, with slopes of 9.3 +/- 1.05, and 1.80 +/- 1.2 rad Hz-1, respectively. The amplitude frequency response is also significantly smaller for group A in relation to group B for the frequency range 0.25-0.43 Hz. These results suggest that transfer function analysis may be able to identify different components of cerebral autoregulation and also provide a deeper understanding of recent findings by other investigators.

Brain↗
PubMed1998

DNA ligase gene disruptions can depress viral growth and replication in poxvirus-infected cells.

Poxvirus-encoded DNA ligases are assumed to play a role in viral DNA replication; however mutational inactivation of vaccinia ligase has not been reported to affect viral growth rates in culture. This communication re-examines this surprising aspect of poxviral biology using both Shope fibroma virus (SFV) and vaccinia virus. SFV and vaccinia ligase deficiencies create essentially identical phenotypes. In particular, ligase-deficient SFV strains are mildly UV sensitive and etoposide resistant, phenotypes previously shown to characterize ligase-deficient vaccinia strains. Moreover, we find that ligase mutations can inhibit the growth of both SFV and vaccinia virus in vitro. The poor growth observed in the absence of a viral ligase is correlated with a two- to tenfold reduction in viral and extragenomic DNA synthesis. This phenotype is host dependent. No differences in viral growth or DNA yield were seen when vaccinia strains were cultured on rabbit (SIRC) cells, but ligase deficiencies reduced growth and DNA yields when vaccinia was plated on BSC-40 cells or SFV on SIRC cells. Despite these replicative defects, mutational inactivation of SFV ligase produced no detectable increase in the number of viral DNA breaks and had no effect on virus-catalyzed extragenomic DNA recombination or UV repair. We conclude that poxviral ligases do play a role in viral DNA replication, but the replicative defect is obscured in some cell lines.

Animals↗
PubMed1998

Time domain analysis of embolic signals can be used in place of high-resolution Wigner analysis when classifying gaseous and particulate emboli.

The sample-volume length (SVL) of an embolic signal has previously been used to differentiate between gaseous and particulate emboli and has been calculated using high-resolution Wigner analysis. Although successful, this method of analysis is not widely available to other groups using transcranial Doppler ultrasound (TCD) to classify emboli. The SVL of embolic signals can also be calculated using time domain analysis, which is a far simpler method and potentially available to all TCD users. The aim of this study was to compare the SVL of embolic signals calculated using Wigner analysis and time domain analysis to assess whether or not time domain analysis can replace Wigner analysis to classify emboli. In total, 215 particulate and 100 gaseous emboli were recorded onto digital audiotape and analysed off-line. Two SVLs for each embolic signal were calculated by measuring embolic duration and velocity in the time domain and with Wigner analysis. Receiver operator characteristic (ROC) curves were plotted to assess the optimum SVL threshold for each method, and levels of sensitivity and specificity were defined. The optimum SVL threshold using Wigner analysis was 1.28 cm, yielding 93% sensitivity and 97% specificity. Using time domain analysis, the optimum threshold was 1.12 cm, yielding 90% sensitivity and 96% specificity. The methods were compared statistically (chi2) using their optimum thresholds, and were found not to be statistically different for classifying particles p=0.283) or gaseous emboli (p=0.700). This study has shown that the SVL of embolic signals, used to differentiate particulate from gaseous emboli, can be calculated more simply in the time domain, which yields as accurate results as calculating the SVL using Wigner analysis.

Blood Flow Velocity↗
PubMed1998

Metabolic activation of aromatic amine mutagens by simultaneous expression of human cytochrome P450 1A2, NADPH-cytochrome P450 reductase, and N-acetyltransferase in Escherichia coli.

We describe the construction of a new strain of Escherichia coli designed to bioactivate aromatic amines and to detect their mutagenicity with high sensitivity. Strain DJ4309 bears two plasmids, a pACYC184-derived plasmid which expresses Salmonella typhimurium acetyl CoA:arylamine N-acetyltransferase (NAT) and a pBR322-derived plasmid which expresses human cytochrome P450 1A2 and NADPH-cytochrome P450 reductase. The combined actions of these enzymes convert aromatic amines into reactive, mutagenic N-acetoxy esters. The strain also carries a mutated copy of the lacZ gene (on an F' factor) which reverts to the wild-type gene by a -(GpC) frameshift mutation. Strain DJ4309 expresses high levels of NAT and cytochrome P450 1A2 and is very sensitive to mutagenesis induced by representative aromatic amines. Mutagenicity of 2-aminoanthracene in strain DJ4309 is higher than can be obtained by rat liver homogenate 9000g supernatant (S9) activation in the parent strain lacking the P450 expression vector. Strain DJ4309 provides a useful system for detecting mutagenic aromatic amines and for studying their metabolism by human P450 1A2.

Arylamine N-Acetyltransferase↗
PubMed1998

Experience with transcranial Doppler monitoring reduces the incidence of particulate embolization during carotid endarterectomy.

BACKGROUND: The aim of this study was to investigate whether the introduction of routine transcranial Doppler (TCD) ultrasonography during carotid endarterectomy reduces the incidence of microembolization by altering operative technique. METHODS: The number and nature of microemboli detected during the first 75 consecutive carotid endarterectomies performed with TCD monitoring during 1992-1993 (group 1) were compared with those in a similar series of 75 consecutive patients undergoing carotid endarterectomy in 1995 (group 2), after substantial experience (210 patients) with TCD monitoring. Emboli were classified as either particulate or gaseous. RESULTS: In patients with evidence of particulate emboli during the dissection phase of the operation, the total number of particulate emboli fell significantly in patients in group 2 (P = 0.019). Similarly, in patients in whom microembolization was detected on immediate opening of the shunt, the total number of microemboli also fell significantly in group 2 (P = 0.003). Overall, the median (95 per cent confidence interval) number of particulate emboli detected during the entire procedure fell significantly from 21 (16-29) in group 1 to 9 (7-14) in group 2 (P = 0.0008). CONCLUSIONS: TCD monitoring plays an important role in the training and quality control of carotid endarterectomy and helps significantly to reduce the amount of microembolization.

Aged↗
PubMed1998

Effect of feed interval and feed type on splanchnic haemodynamics.

AIM: To study the effect of enteral feeding on splanchnic blood flow velocity in preterm infants. METHOD: Coeliac axis and superior mesenteric artery (SMA) blood flow velocity were measured longitudinally in a cohort of 61 babies using Doppler ultrasound. RESULTS: Babies fed 1 hourly had significantly higher preprandial SMA peak systolic velocity (PSV) than those fed 3 hourly (70 vs 53 cm/s). Those fed 1 hourly showed no postprandial change whereas those fed 3 hourly showed significant postprandial hyperaemia. This hyperaemia had longer latency (42 vs 27 mins) and smaller amplitude (31 vs 25 mins) after expressed breast milk compared with preterm formula. The addition of long chain polyunsaturated fatty acids to the formulas had no effect on the postprandial response. CONCLUSION: Hourly bolus feeding leads to a persistent hyperaemic state in the SMA. The composition of feeds is an important determinant of the postprandial response of the SMA to 3 hourly feeding.

Blood Flow Velocity↗
PubMed1998

A prostaglandin, not NO, mediates endothelium-dependent dilation in ventral aorta of shark (Squalus acanthias).

In mammals, the vascular endothelium releases a variety of paracrine factors, including the vasodilatory prostaglandin (PG)I2 and nitric oxide (NO), which is generally accepted as the major endothelium-derived relaxing factor (EDRF) in mammals. Current evidence for the vascular NO-EDRF system in fishes is contradictory. In addition, the role of PGs in the control of fish vascular tension is also unclear. We have utilized isolated rings of the ventral aorta of the spiny dogfish shark to examine the ability of various components of the NO system to dilate this vessel. Neither the NO precursor L-arginine, the NO donor sodium nitroprusside, nor NO itself dilated the rings. The Ca2+ ionophore A-23187 did produce an endothelium-dependent dilation that was not inhibited by the NO synthase inhibitor NG-nitro-L-arginine methyl ester but was inhibited by the cyclooxygenase inhibitor indomethacin, suggesting that PGs are involved. PGE1 and carbaprostacyclin, but not PGI2, produced concentration-dependent dilation, and intact aortic rings secreted five times as much PGI2 as PGE in both the unstimulated state and after stimulation with A-23187. Our data suggest strongly that a PG, most probably PGI2, is the EDRF in the ventral aorta of this shark species.

Alprostadil↗
PubMed1998

Grading of cerebral dynamic autoregulation from spontaneous fluctuations in arterial blood pressure.

BACKGROUND AND PURPOSE: Assessment of cerebral autoregulation has been traditionally performed with static changes in arterial blood pressure. Newer dynamic methods require the induction of sudden drops in arterial blood pressure with the sudden release of bilateral thigh cuffs. An alternative method is proposed, based on the spontaneous variability of arterial blood pressure that does not require its manipulation. We compared this method with the established thigh cuff method in patients with carotid artery stenosis. METHODS: Cerebral blood flow velocity (determined by transcranial Doppler) and arterial blood pressure (determined by noninvasive servo-controlled plethysmograph) were recorded in 20 patients with carotid artery stenosis and 18 age-matched controls. At rest, grading of dynamic autoregulation was estimated from the impulse response of the blood pressure-velocity dynamic relationship. This was compared with the autoregulatory index (ARI) provided by the thigh cuff method and with the degree of stenosis. The critical closing pressure was derived from the fitted models and was also correlated with degree of stenosis. RESULTS: The 2 ARIs were significantly correlated (r=0.76) and reduced in subjects with carotid stenosis (baseline ARI, 3.65+/-3.11 versus 6.68+/-1.88, P<0. 0001; thigh cuff ARI, 3.78+/-2.32 versus 6.35+/-1.06, P<10(-5)). The critical closing pressure (relative to mean arterial blood pressure) was also significantly reduced (-0.24+/-1.06 versus 0.50+/-0.31, P<0. 0001) and correlated with the thigh cuff ARI (r=0.68). Both the baseline ARI and critical closing pressure were correlated with degree of stenosis (P<10(-6)). CONCLUSIONS: Grading of dynamic autoregulation with the use of undisturbed recordings of arterial blood pressure and cerebral blood flow velocity might provide a safer technique for assessment of patients in whom a sudden drop of arterial blood pressure is not desirable, such as patients with heart or autonomic failure.

Analysis of Variance↗
PubMed1998

Consensus on microembolus detection by TCD. International Consensus Group on Microembolus Detection.

Transcranial Doppler ultrasound is capable of detecting microembolic material, both gaseous and solid, within the intracranial cerebral arteries. To avoid discrediting this promising and exciting new technique, experts in this field met in January 1997 in Frankfurt, Germany, to discuss the limitations and problems of embolus detection and to determine guidelines for its proper use in clinical practice, as well as in scientific investigations. In particular, the authors suggest that studies report the following parameters: (1) ultrasound device, (2) transducer type and size, (3) insonated artery, (4) insonation depth, (5) algorithms for signal intensity measurement, (6) scale settings, (7) detection threshold, (8) axial extension of sample volume, (9) fast Fourier transform (FFT) size (number of points used), (10) FFT length (time), (11) FFT overlap, (12) transmitted ultrasound frequency, (13) high-pass filter settings, and (14) recording time. There was agreement that no current system of automatic embolus detection has the required sensitivity and specificity for clinical use.

Humans↗
PubMed1998

Can cerebrovascular reactivity be assessed without measuring blood pressure in patients with carotid artery disease? .

BACKGROUND AND PURPOSE: Conventional methods of assessing cerebrovascular reactivity (CVR) omit the influence of blood pressure (BP). This study demonstrates the significant influence of BP during the assessment of CVR in patients with carotid artery disease. METHODS: In 56 subjects the CVR was bilaterally assessed by measurement of cerebral blood flow velocity change in response to inhalation of 5% CO2 in air while BP was continuously monitored. Three methods of calculating the CVR were used: the conventional ratio between relative cerebral blood flow velocity and end-tidal CO2, simple linear regression, and multiple linear regression analysis (MLRA). The clinical significance of the difference in CVR indices was evaluated. The Bland-Altman test was applied to quantify the comparability and bias between measurements. The magnitude and significance of a change in BP during the CVR assessment were calculated in conjunction with an estimate of the velocity change attributed to the BP. The statistical significance of the data segment length on the variability and magnitude of the CVR index was computed. RESULTS: The value of the CVR index was reduced by 20% and 6% in comparison to the conventional ratio approach when MLRA and linear regression were applied, respectively. With the use of MLRA, in 96% of cases the value of the BP coefficient was statistically significant, and in four patients the increase in velocity was primarily attributed to the increase in BP. CONCLUSIONS: The influence of BP is significant and requires consideration when the CVR index is calculated in patients with carotid artery disease.

Aged↗
PubMed1998

A comparison of four methods for distinguishing Doppler signals from gaseous and particulate emboli.

BACKGROUND AND PURPOSE: Many reports in the medical literature have proposed methods of differentiating between gaseous and particulate emboli detected with the use of transcranial Doppler ultrasound. The purpose of this study was to compare the previously published methods with our own sample volume length (SVL) parameter to assess the accuracy of each method in classifying emboli. METHODS: A pure source of gaseous and particulate emboli was obtained from in vitro and in vivo studies, respectively, and recorded onto digital audiotape for off-line analysis. In total, 100 gaseous emboli and 215 particulate emboli were analyzed to measure four embolic parameters, namely, embolic duration, embolic velocity, relative signal intensity increase (measured embolic power [MEP]), and SVL of the embolic signal (= Duration x Velocity). Receiver operator characteristic analysis was used to assess the optimum threshold for each parameter to differentiate between particulate and gaseous emboli, and levels of sensitivity and specificity were calculated. RESULTS: Embolic duration and velocity produced the poorest levels of sensitivity and specificity compared with the MEP and SVL parameters. The optimum thresholds for embolic duration and velocity were 35 ms and 1 m/s, respectively, which produced a sensitivity (specificity) of 85.1% (87%) and 87% (67%), respectively. The optimum MEP and SVL thresholds were 30 dB and 12.8 mm, respectively, which produced a sensitivity (specificity) of 86.5% (95%) and 93% (97%), respectively. The SVL and MEP parameters were compared statistically (chi 2) at chosen specificity values of 90%, 95%, 97%, 99%, and 100%, which showed that the SVL sensitivities were statistically greater than MEP sensitivities (P < 0.01). CONCLUSIONS: SVL is the best parameter for differentiating between gaseous and particulate emboli but needs to be calculated with the use of a high-temporal-resolution spectral analyzer to measure embolic duration and velocity.

Diagnosis, Differential↗
PubMed1997

Variability in cerebral blood flow velocity: observations over one minute in preterm babies.

Cerebral blood flow velocity (CBFV) was measured using Doppler ultrasound on the first day of life in a consecutively admitted cohort of 52 very low birthweight infants. Recordings were made for a period of 1 min. The coefficient of variation for the area under the curve of 20 successive cardiac cycles was calculated, and a 20 cycle moving window then applied to the whole recording. This showed that the coefficient of variation varied widely during 1 min in any individual, the range being from 2% to 28% (median 8%). There was a strong correlation between the variability in CBFV and that in systemic blood pressure (BP). Variability in CBFV was significantly higher in babies with hypotensive episodes (P = 0.026). Babies who died had a higher maximum coefficient of variation than those who survived (P = 0.05), but we were unable to confirm any association with brain injury or patent ductus arteriosus.

Birth Weight↗