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Biomedical subjects

L Kornet

Publications and source records attributed to L Kornet.

7 recordsLinked to original sources

Pseudoxanthoma elasticum maps to an 820-kb region of the p13.1 region of chromosome 16.

We have performed linkage analysis on 21 families with pseudoxanthoma elasticum (PXE) using 10 polymorphic markers located on chromosome 16p13.1. The gene responsible for the PXE phenotype was localized to an 8-cM region of 16p13.1 between markers D16S500 and D16S3041 with a maximum lod score of 8.1 at a recombination fraction of 0.04 for marker D16S3017. The lack of any locus heterogeneity suggests that the major predisposing allele for the PXE phenotype is located in this region. Haplotype studies of a total of 36 PXE families identified several recombinations that further confined the PXE gene to a region (< 1 cM) between markers D16S3060 and D16S79. This PXE locus was identified within a single YAC clone and several overlapping BAC recombinants. From sequence analysis of these BAC recombinants, it is clear that the distance between markers D16S3060 and D16S79 is about 820 kb and contains a total of nine genes including three pseudogenes. We predict that mutations in one of the expressed genes in the locus will be responsible for the PXE phenotype in these families.

Alleles

In the femoral artery bifurcation, differences in mean wall shear stress within subjects are associated with different intima-media thicknesses.

In elastic arteries, intima-media thickening is more pronounced in areas with low than with high mean and peak wall shear stress. These findings in elastic arteries are not necessarily representative of the situation in muscular arteries. The former arteries have to store volume energy, whereas the latter are mainly conductive vessels. It was the aim of the present study to investigate noninvasively whether differences in wall shear stress within a muscular artery bifurcation, if any, were associated with different intima-media thicknesses (IMTs). The effect of age on the possible differences was assessed as well. We determined IMT and mean, peak systolic, and the maximum cyclic change in shear stress near the posterior wall in the common (FC) and the superficial (FS) femoral artery 20 to 30 mm from the flow divider in 54 presumed healthy subjects between 21 and 74 years of age. Results were considered in terms of intrasubject differences. Before the study, the reliability of the ultrasonic system to assess wall shear rate and IMT was determined in terms of intrasubject variability. IMT at the posterior wall was significantly larger in the FC than in the FS, probably owing to the significantly lower mean wall shear stress at this site in the FC. The relative differences in IMT and mean wall shear stress between FC and FS were independent of age. The difference in wall shear stress between both arteries can likely be explained by a different influence of reflections. In both the FC and FS, mean, peak systolic, and maximum cyclic change in shear stress near the posterior wall did not change significantly with age, whereas IMT did increase significantly with age.

Adult

The compliance of the porcine pulmonary artery depends on pressure and heart rate.

1. The influence of mean pulmonary arterial pressure (mean Ppa) on dynamic (Cd) and pseudo-static compliance (Cps) of the pulmonary artery was studied at a constant and a changing heart rate. Cd is the change in cross-sectional area (CSA) relative to the change in Ppa throughout a heart cycle. Cps is the change in mean CSA relative to the change in mean Ppa. If Cd is known, pulmonary blood flow can be computed from the Ppa using a windkessel model. We investigated whether Cps can be interchanged with Cd. 2. In nine anaesthetized pigs, we determined the mean CSA and Cd of the pulmonary artery at various Ppa levels, ranging from approximately 30 to 10 mmHg, established by bleeding. Two series of measurements were carried out, one series at a spontaneously changing heart rate (n = 9) and one series at a constant heart rate (n = 6). To determine CSA a conductance method was used. 3. Cps depended on pressure. The mean CSA versus mean Ppa curves were sigmoid and steepest in the series with the increasing heart rate (established by bleeding). The CSA versus Ppa loop during a heart cycle, giving Cd, was approximately linear and almost closed. The Cd versus mean Ppa relationship was bell shaped. Its width was smaller if the heart rate increased during the series of measurements. The pressure, where Cd was maximum, was higher at higher heart rates. Furthermore, the maximum Cd was not affected by the heart rate. 4. Because the pulmonary artery constricts with increasing heart rate, Cps will be overestimated during procedures where heart rate increases. Cd should be determined on a beat-to-beat basis to calculate flow because it changes with mean pulmonary arterial pressure and heart rate.

Algorithms

Differences in near-wall shear rate in the carotid artery within subjects are associated with different intima-media thicknesses.

In the common carotid artery, reflections originating from the periphery and the flow divider may affect the shape of the flow velocity profile and, hence, near-wall shear rate (WSR) differently just before the bifurcation (location B) than 20 to 30 mm farther upstream (location A). Recent developments in ultrasound technology allow the assessment of WSR and intima-media thickness (IMT) at the same site in the carotid artery in vivo. We therefore determined WSR at locations A and B and investigated whether the differences between both sites, if any, were associated with different IMTs and different mechanical properties of the arterial wall. The effect of age on the possible differences was assessed as well. The study was performed on presumably healthy volunteers (n=53). In all individuals, IMT was larger at location B than at location A. The relative difference in IMT between both locations was not affected by age. No significant differences in diameter and distension were found between locations. Near peak systolic and near mean WSR at the posterior wall (PWSRp and MWSRp, respectively) were significantly lower at location B than at location A. The relative differences in PWSRp and MWSRp between both locations within subjects were independent of age. The velocity profiles were more blunted at location A than at location B. PWSRp and MWSRp significantly decreased and IMT significantly increased with age at both locations. IMT was negatively correlated with PWSRP and MWSRP at location B, but this correlation was not significant at location A. In summary, in the common carotid artery, the lower WSR near the bifurcation, as compared with 20 to 30 mm upstream, is associated with a larger IMT than at the more proximal site. The relative difference between both locations within subjects is independent of age.

Adolescent

Determination of the mean cross-sectional area of the thoracic aorta using a double indicator dilution technique.

A double indicator dilution technique for determining the mean cross-sectional area (CSA) of a blood vessel in vivo is presented. Analogous to the thermodilution method, dilution of hypertonic saline was measured by an electrical conductance technique. Because the change in conductance rather than absolute conductance was used to calculate CSA, pulsatile changes in shear rate of blood and conductance of surrounding tissues had no effect on the data. To calculate CSA from an ion mass balance, cardiac output was needed and estimated from the thermodilution curve using the same "cold" (hypertonic) saline injection. The mean CSA, obtained from this double indicator dilution method (CSAGD), was compared with the CSA obtained from the intravascular ultrasound method (IVUS) in 44 paired observations in six piglets. The regression line is close to the line of identity (CSAGD = -1.83 + 1.06 . CSAIVUS, r = 0.96). The difference between both CSAs was independent of the diameter of the vessel, on average -0.99 mm2 +/- 2.64 mm2 (mean CSAGD = 46.84 +/- 8.21 mm2, mean CSAIVUS = 47.82 +/- 9.08 mm2) and not significant. The results show that the double indicator dilution method is a reliable technique for estimating the CSA of blood vessels in vivo.

Anatomy, Cross-Sectional

Single injection thermodilution. A flow-corrected method.

BACKGROUND: Application of the Stewart-Hamilton equation in the thermodilution technique requires flow to be constant. In patients in whom ventilation of the lungs is controlled, flow modulations may occur leading to large errors in the estimation of mean cardiac output. METHODS: To eliminate these errors, a modified equation was developed. The resulting flow-corrected equation needs an additional measure of the relative changes of blood flow during the period of the dilution curve. Relative flow was computed from the pulmonary artery pressure with use of the pulse contour method. Measurements were obtained in 16 patients undergoing elective coronary artery bypass surgery. In 11 patients (group A), pulmonary artery pressure was measured with a catheter tip transducer, in a partially overlapping group of 11 patients (group B), it was measured with a fluid-filled system. For reference cardiac output we used the proven method of four uncorrected thermodilution estimates equally spread over the ventilatory cycle. RESULTS: A total of 208 cardiac output estimates was obtained in group A, and 228 in group B. In group B, 48 estimates could not be corrected because of insufficient pulmonary artery pressure waveform quality from the fluid-filled system. Individual uncorrected Stewart-Hamilton estimates showed a large variability with respect to their mean. In group A, mean cardiac output was 5.01 l/min with a standard deviation of 0.53 l/min, or 10.6%. After flow correction, this scatter decreased to 5.0% (P < 0.0001). With no bias, the corresponding limits of agreement decreased from +/- 1.06 to +/- 0.5 l/min after flow correction. In group B, the scatter decreased similarly and the limits of agreement also became +/- 0.5 l/min after flow correction. CONCLUSION: It was concluded that a single thermodilution cardiac output estimate using the flow-corrected equation is clinically feasible. This is obtained at the cost of a more complex computation and an extra pressure measurement, which often is already available. With this technique it is possible to reduce the fluid load to the patient considerably.

Adult

Conductance method for the measurement of cross-sectional areas of the aorta.

A modified conductance method to determine the cross-sectional areas (CSAs) of arteries in piglets was evaluated in vivo. The method utilized a conductance catheter having four electrodes. Between the outer electrodes an alternating current was applied and between the inner electrodes the induced voltage difference was measured and converted into a conductance. CSA was determined from measured conductance minus parallel conductance, which is the conductance of the tissues surrounding the vessel times the length between the measuring electrodes of the conductance catheter divided by the conductivity of blood. The parallel conductance was determined by injecting hypertonic saline to change blood conductivity. The conductivity of blood was calculated from temperature and hematocrit and corrected for maximal deformation and changes in orientation of the erythrocytes under shear stress conditions. The equations to calculate the conductivity of blood were obtained from in vitro experiments. In vivo average aortic CSAs. determined with the conductance method CSA(G) in five piglets, were compared to those determined with the intravascular ultrasound method CSA(IVUS). The regression equation between both values was CSA(G)=-0.09+1.00 x CSA(IVUS), r=0.97, n=53. The mean difference between the values was -0.29%+/-5.57% (2 standard deviations). We conclude that the modified conductance method is a reliable technique to estimate the average cross-sectional areas of the aorta in piglets.

Animals