Oncological Screening of Kidney Tumors After Renal Transplantation.

BACKGROUND: Among renal transplant recipients, renal cell carcinoma in the native kidneys represents the most common solid tumor. At the Department of Surgery, Transplantation and Gastroenterology of Semmelweis University annual control abdominal ultrasound examination is recommended for transplant patients. Our goal was to evaluate the effectiveness of the ultrasound screening program at our institute and to learn about the characteristics of shrunken kidney tumors. METHODS: Retrospectively, we processed the results of abdominal and pelvic ultrasound examinations of 1687 kidney transplant patients, which were performed at our institute between January 1, 2012 and December 31, 2016. RESULTS: A total of 26 tumors were detected during the abovementioned period of time, of which 18 were renal cancers. Renal cancer was significantly (P = 0.029) more common in men. Seventeen renal cancers were classified as stage I and one as stage IV disease. The mean time of dialysis was 37.73 ± 24.37 months. The mean time between kidney transplantation and tumor recognition was 7.9 ± 6.29 years. The 5-year survival was 66%; however, it should be noted that only 1 patient lost his life due to his tumor disease. The mean time between the last 2 ultrasound examinations was 27.8 ± 23.89 months. Only 57% of tumors were detected by screening. No significant differences in tumor size, stage, and survival could be detected between screened and nonscreened renal cancer patients. CONCLUSIONS: Ultrasound examination at least every 2 years is an effective tool for the early detection of renal cell carcinoma of the shrunken kidneys.

Shear-wave elastography for the assessment of liver fibrosis in liver transplant recipients treated for hepatitis C virus recurrence.

OBJECTIVES: Direct-acting antiviral agents have revolutionized hepatitis C therapy, and are also found to be effective in the liver transplant setting. The extent of liver fibrosis influences patient management and is used to monitor therapeutic effects. Shear-wave elastography (SWE) is a relatively new imaging-based method that has not yet been studied extensively in liver transplant patients. Our aim was to study the effect of direct-acting antivirals in heaptitis C recurrence on liver stiffness determined by SWE. PATIENTS AND METHODS: A total of 23 liver transplant patients with hepatitis C recurrence were enrolled in this prospective study. The patients underwent 24 weeks of ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin combination therapy. Elastographic examinations, serological tests and laboratory tests were performed, and serum biomarkers of liver fibrosis were calculated the day before treatment (baseline) and at the end of the treatment. RESULTS: All our patients became hepatitis C virus RNA negative by the end of the treatment. Median liver stiffness values decreased significantly after treatment compared with baseline (8.72±3.77 vs. 7.19±2.4 kPa; P<0.001). Among the studied laboratory values, a significant decrease was observed in the levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase, whereas international normalized ratio levels increased. Serum biomarkers, namely aspartate aminotransferase-to-platelet ratio index and Fibrosis-4, decreased significantly after treatment compared with baseline. CONCLUSION: In the present study, SWE was succesfully used to monitor the beneficial therapeutic effects of direct-acting antivirals in hepatitis C recurrence following liver transplantation. We believe that SWE is a useful noninvasive diagnostic tool in the follow-up of hepatitis C treatment in liver transplant patients.

Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--imaging predictors of success.

PURPOSE: To retrospectively assess the magnetic resonance (MR) imaging predictors of success at reducing uterine leiomyoma volume and achieving patient symptom relief 12 months after MR imaging-guided focused ultrasound surgery. MATERIALS AND METHODS: This single-center retrospective analysis of 71 symptomatic fibroids in 66 women was approved by the institutional review board and was HIPAA-compliant. Patients were treated with MR imaging-guided focused ultrasound surgery. The volume of treated fibroid and nonperfused volume (NPV) were calculated with software, while symptom outcome was assessed with a symptom severity score (SSS). Fibroids were classified as hyperintense or hypointense relative to skeletal muscle on pretreatment T2-weighted MR images. RESULTS: Baseline volume of treated fibroids was 255.5 cm(3) +/- 201.7 (standard deviation), and baseline SSS was 61.5 +/- 14.9. Both pretreatment fibroid signal intensity (SI) and posttreatment NPV predicted 12-month volume reduction independently: Fibroids with an NPV of at least 20% or with low SI both showed significantly larger volume reduction (17.0% +/- 13.0 and 17.2% +/- 20.1, respectively) than fibroids with an NPV less than 20% or with high SI (10.7% +/- 18.2 and no significant change, respectively). Patients whose fibroids demonstrated an NPV of at least 20% also experienced a larger decrease in SSS than did patients with fibroids with an NPV less than 20% (50.1% +/- 19.8 vs 32.6% +/- 29.9). CONCLUSION: Fibroids with low SI on pretreatment T2-weighted MR images were more likely to shrink than were ones with high SI. The larger the NPV immediately after treatment, the greater the volume reduction and symptom relief were. These findings may help both in selecting appropriate patients for MR-guided focused ultrasound surgery and in predicting patient outcome.

Use of generalized transfer function-derived central blood pressure for the calculation of baroreflex gain.

BACKGROUND: Peripheral blood pressure measurement underestimates pressure changes during baroreflex testing, resulting in an overestimation of baroreflex gain. This error might be reduced by measuring central blood pressure; the invasive measurement, however, may represent ethical and practical problems. The solution may be the derivation of central blood pressure from the peripheral pulse using a generalized transfer function. METHODS: In the current study, we tested the agreement between catheter-measured and generalized transfer function derived central blood pressure measurements and corresponding baroreflex gains. ECG and blood pressure waveforms were monitored continuously during a phenylephrine-induced pressure rise in 22 subjects undergoing cardiac catheterization. Pressure was measured with a catheter positioned in the aorta and with applanation tonometry in the radial artery. Radial pressure waveforms were subject to a generalized transfer function built in the SphygmoCor device to derive central pressure waveforms. Radial tonometric signal was calibrated with catheter-measured (invasive) and sphygmomanometric (noninvasive) pressures. Baroreflex gains were calculated from the linear regressions between heart period and systolic pressure changes. RESULTS: When radial tonometric signal was calibrated invasively, there was no group difference between baroreflex gains calculated from SphygmoCor-derived and catheter-measured pressures (8.2 +/- 1.2 vs. 7.2 +/- 1.2 ms/mmHg, P = NS). When radial tonometric signal was calibrated noninvasively, however, baroreflex gains calculated from SphygmoCor-derived pressures overestimated those calculated from catheter-measured pressures. CONCLUSION: Using a generalized transfer function is an accurate method to derive central pressure changes for baroreflex gain calculation. The technique, however, requires invasive pressure measurements for calibration, leaving the problem of a fully noninvasive central pressure measurement unresolved.

Echocardiographic parameters in athlete and nonathlete offspring of hypertensive parents.

BACKGROUND: According to several reports, some cardiovascular signs of hypertension (left ventricular [LV] hypertrophy, impaired diastolic filling) can be found in the normotensive offspring of hypertensive parents. It is also well known that regular physical exercise decreases the risk of hypertension. AIM: The aim of the present study is to determine whether or not regular physical training influences these early hypertensive traits in the offspring of hypertensive parents. METHODS: Echocardiographic data of 215 (144 males, 71 females) 22- to 35-year-old nonathlete and athlete offspring of hypertensive (positive family history, FH+) and normotensive parents (negative family history, FH-) were compared in a cross-sectional design. RESULTS: In the nonathlete FH+ males and females, LV dimensions were not larger than in the FH- subjects. The E/A quotient was lower in the FH+ subjects in both genders. Absolute and heart rate adjusted isovolumetric relaxation times were slightly longer in the FH+ men than in their FH- peers. No differences were seen between athlete FH- and FH+ subjects. CONCLUSION: Regular physical exercise decreases the incidence of the adverse cardiac signs, which can be associated with hypertension in the normotensive offspring of hypertensive parents.

Transposition of great arteries is associated with increased carotid artery stiffness.

Transposition of great arteries is the consequence of abnormal aorticopulmonary septation. Animal embryonic data indicate that septation and elastogenesis are related events, but human and clinical data are not available. We tested the hypothesis that large artery elastic function was impaired in patients with transposition of great arteries. We studied 34 patients aged 9 to 19 years, 12+/-3 years after atrial switch operation; 14 patients aged 7 to 9 years, 8+/-1 years after arterial switch operation; and 108 healthy control subjects matched for age. Carotid artery diastolic diameter and pulsatile distension were determined by echo wall-tracking; carotid blood pressure was measured by tonometry. Systolic pressure was higher and diastolic pressure was lower in patients than in controls. Patients with atrial and arterial switch repair were compared with their respective controls by 2-factor ANOVA. For patients with atrial switch repair versus control, stiffness index beta was 4.9+/-1.5 versus 3.1+/-1.0 (P<0.001); for patients witch arterial switch versus control, stiffness index beta was 3.8+/-1.1 versus 2.1+/-0.6 (P<0.001). Similar differences were observed for carotid compliance, distensibility, and incremental elastic modulus as well. The interaction term was not significant for any of the elastic variables, indicating that carotid stiffening was a characteristic of the condition and not the consequence of different hemodynamics. Carotid artery is markedly stiffer in patients, suggesting that impaired elastogenesis may constitute part of the congenital abnormality. Since carotid artery stiffness has been established as an independent cardiovascular risk factor, this condition may have consequences in the clinical management of these patients.

[Investigation of cerebral autoregulation in Parkinson's disease--a transcranial Doppler study]. / Az agyi autoreguláció vizsgálata Parkinson-betegségben.

BACKGROUND AND PURPOSE: The frequent orthostatic intolerance in Parkinson's disease could be the consequence of cardiovascular autonomic failure and/or a damaged cerebral autoregulation (AR). To clarify this question the regulation of cerebral circulation was investigated by polygraphic method. METHODS: On a tilt table simultaneous and continuous registrations were made of MCA velocity (V(MCA)) by transcranial Doppler, arterial blood pressure by non-invasive method, and end-tidal CO2, in supine and in tilted positions of 10 degrees, 30 degrees, 70 degrees grades. The cerebral autoregulation was characterized by the slope of the curve of the arterial blood pressure at the level of the Willis-circle (BP(W) as MCA perfusion pressure) plotted against the MCA velocity, achieved by linear regression (y = ax + b function, a=AR, or index of autoregulation). PATIENTS: The data of 17 parkinsonian patients (PP) and eight age-matched controls (C) were analyzed. RESULTS: The decrease of blood pressure in parkinsonian patients was significantly lower than in the controls when supine position was restored from 70 degrees (deltaABP 70 degrees - 0 degree pp = -3.1 +/- 7.5 Hgmm; deltaABP 70 degrees - 0(C) degrees = -11.1 +/- 7.3 Hgmm; p < 0.05), which suggests a damage to the sympathetic cardiovascular system. A disturbance of the cerebral autoregulation in patients was suggested by a 'progressively decreasing MCA average velocity (V(MCA)) during graded tilt, which was significant at 70 degrees (deltaV(ACM) = 9.8 +/- 8.82% cms(-1); p(C-PP) P 0.5), and by a higher slope of pressure-velocity curve (AR(C) = 0.143 +/- .125% cms(-1)/Hgmm; AR(PP) = 0.38 +/- 0.25% cms(-1)/Hgmm; p(C-PP) < 0.05). CONCLUSIONS: The results show that the cerebral blood flow of patients is more dependent on perfusion pressure compared to healthy controls. The disturbance of the sympathetic cardiovascular system and of cerebral autoregulation could be the consequence of a damage to the postganglionic structures in Parkinson's disease. These results could explain the frequent orthostatic intolerance of patients even with normal blood pressure.

Opposite changes in carotid versus aortic stiffness during healthy human pregnancy.

Systemic arterial compliance has been known to increase during healthy pregnancy, whereas, recently, the carotid artery has been reported to stiffen. To clarify this controversy, we simultaneously measured aortic PWV (pulse wave velocity) and carotid artery elastic parameters in a cohort of pregnant women. Twelve normotensive pregnant women were studied longitudinally during the three trimesters of pregnancy (T1, T2 and T3 respectively) and 12 weeks PP (postpartum). Carotid artery diastolic diameter and pulsatile distension was measured by an echo-wall tracking method and carotid pulse pressure by applanation tonometry. Carotid strain, compliance, distensibility coefficient, stiffness index beta, Einc (incremental elastic modulus) and augmentation index were calculated. Aortic PWV was determined to estimate aortic distensibility. All carotid artery elastic parameters indicated significant stiffening from T1 to T3 (1.8+/-0.2 versus 2.9+/-0.3 mmHg for Einc), which was reversed after delivery (2.3+/-0.2 mmHg). Aortic PWV decreased during pregnancy (6.2+/-0.2 versus 5.4+/-0.2 m/s) and increased in the PP period (6.7+/-0.2 m/s). No correlation was found between changes in carotid artery elastic parameters and changes in aortic PWV either from T1 to T3 or from T3 to PP. The carotid artery exhibits regionally specific stiffening during pregnancy, which appears to represent a qualitatively different change in arterial elastic behaviour.

Cardiovagal autonomic function in sedentary and trained offspring of hypertensive parents.

In young normotensive subjects, parental hypertension is associated with stiffening of the carotid artery and reduction in cardiovagal outflow and baroreflex gain. In subjects without parental hypertension regular exercise training was found to attenuate age-related reduction in carotid compliance and baroreflex gain. The aim of the present study was to test the hypothesis that regular physical activity is associated with better parameters of carotid artery elasticity, increased cardiovagal outflow and higher baroreflex gain in normotensive offspring of hypertensive parents. We studied 98 healthy, sedentary or endurance exercise trained subjects (49 men, 18-27 years of age) with or without family history of hypertension (FH(+) and FH(-), respectively) in a cross-sectional design. In the sedentary group spontaneous baroreflex indices (sequence method and spectral techniques) were lower in FH(+) subjects than in their FH(-) peers, while in trained subjects these indices were not different between FH(+) and FH(-). Furthermore, in the FH(+) group trained subjects had higher baroreflex indices than their sedentary peers, while in the FH(-) group no significant differences were found. Carotid compliance and distensibility coefficient (echo-tracking ultrasound and applanation tonometry) were not different in FH(-) sedentary and trained subjects, but were higher in FH(+) trained subjects as compared to their sedentary peers. Significant but modest relationships were found between spontaneous baroreflex indices and carotid artery elastic parameters across all subjects. Our present data indicate that in subjects with parental hypertension aerobic exercise training is associated with higher levels of cardiovagal outflow and baroreflex gain, which finding, however, is not explained by greater elasticity of the carotid artery.

Maturation of cardiovagal autonomic function from childhood to young adult age.

BACKGROUND: Cardiovagal autonomic control declines with age in adult subjects, which is related in part to increasing stiffness of the barosensory vessel wall. It is not known, however, whether autonomic function changes with age in children. METHODS AND RESULTS: We studied 137 healthy subjects divided into 4 age groups: group 1, 7 to 14 years; group 2, 11 to 14 years; group 3, 15 to 18 years; and group 4, 19 to 22 years. Brachial artery pressure was measured by sphygmomanometry and continuous radial artery pressure and carotid artery pulse pressure (DeltaP) by applanation tonometry. The R-R interval was derived from the ECG. Autonomic function was assessed by spontaneous sequence and frequency-domain indices, which indicate the extent of coupling between fluctuations in heart rate and systolic pressure. Carotid artery diastolic diameter (DD) and pulsatile distension (DeltaD) were measured by echo wall tracking; carotid compliance coefficient (CC) was defined as DeltaD/DeltaP and distensibility coefficient as 2DeltaD/DD . DeltaP. From group 1 to group 3, spontaneous indices increased significantly (18.1+/-1.7 versus 33.3+/-4.0; 14.4+/-1.1 versus 25.5+/-22; 12.9+/-1.1 versus 20.8+/-2.0; and 6.4+/-0.6 versus 16.2+/-1.4 ms/mm Hg [mean+/-SEM] for Seq+, Seq-, LFalpha, and LF(gain), respectively), with no significant changes afterward. CC and DC were inversely proportional to age (r=-0.49 and -0.62, respectively, P<0.001). The efficiency of neural integrative mechanisms, estimated as the ratio of spontaneous indices and CC, more than doubled from group 1 to group 3. Spontaneous indices were linearly related to measures of cardiac vagal activity. CONCLUSIONS: The increase in spontaneous indices from early childhood to adolescence, despite gradual stiffening of the carotid artery, may indicate improved cardiovagal autonomic function, which is most likely a result of maturation of neural mechanisms, attaining peak level at adolescence.

Effect of vitamin E on carotid artery elasticity and baroreflex gain in young, healthy adults.

In this study we tested the hypothesis that dietary vitamin E supplementation can improve carotid artery elasticity and cardio-vagal baroreflex gain in young, healthy individuals. A total of 20 subjects were studied in a double-blind, placebo-controlled, randomized study. Subjects in the active treatment group received 700 IU/day vitamin E for 1 month. Each subject was studied three times: before, during and 1 month after treatment. Plasma vitamin E levels were determined using high-performance liquid chromatography. Carotid artery diameter was measured by ultrasound and radial artery pressure by tonometry. Baroreflex function was assessed by time and frequency domain spontaneous indices. Plasma vitamin E levels increased by 123%, which was associated with a 20% increase in carotid artery compliance and a 30-60% increase in baroreflex indices. All these changes regressed 1 month after cessation of vitamin E supplementation. Significant correlations were observed across conditions (control, treatment and recovery), among plasma vitamin E concentrations, carotid artery compliance and distensibility values and two of the baroreflex gain indices in the treatment group. Our results demonstrate that vitamin E supplementation can increase carotid artery compliance and baroreflex gain in young, apparently healthy adults.

Carotid artery stiffening does not explain baroreflex impairment in pre-eclampsia.

Stiffening of the barosensory vessel wall in hypertension has been suggested to play a role in the associated baroreflex impairment. The carotid distensibility-BRS (baroreflex sensitivity) relationship, however, has not been studied in pre-eclampsia, a condition where hypertension is spontaneously reversible. Twelve normotensive pregnant women and 12 patients with pre-eclampsia matched for maternal age and week of gestation were studied in the third trimester and 3 months postpartum. Carotid artery diastolic diameter and pulsatile distension was measured by echo-wall tracking and carotid pulse pressure by applanation tonometry, and the carotid distensibility coefficient was calculated. Spontaneous BRS was determined by the sequence and spectral methods from 10 min continuous recording of ECG and finger arterial blood pressure. In the third trimester, carotid distensibility was lower in patients with pre-eclampsia than in normotensive pregnant women (2.47+/-0.17 compared with 4.08+/-0.16 x 10(-3)/mmHg); postpartum, it increased moderately in patients, but remained below normotensive values (3.25+/-0.12 compared with 4.25+/-0.19 x 10(-3)/mmHg). In the third trimester, both patients and healthy pregnant women had equally low BRS values; postpartum, the various BRS indices increased markedly (by 60-190%) and to the same level in both groups. No correlation was found between changes in carotid artery distensibility and those in BRS from the third trimester to postpartum period in patients and healthy pregnant women. The lack of association between changes in carotid distensibility and BRS suggest that stiffening of the carotid artery in pre-eclampsia is not responsible for baroreflex dysfunction.

Static and dynamic changes in carotid artery diameter in humans during and after strenuous exercise.

Arterial baroreflex function is altered by dynamic exercise, but it is not clear to what extent baroreflex changes are due to altered transduction of pressure into deformation of the barosensory vessel wall. In this study we measured changes in mean common carotid artery diameter and the pulsatile pressure : diameter ratio (PDR) during and after dynamic exercise. Ten young, healthy subjects performed a graded exercise protocol to exhaustion on a bicycle ergometer. Carotid dimensions were measured with an ultrasound wall-tracking system; central arterial pressure was measured with the use of radial tonometry and the generalized transfer function; baroreflex sensitivity (BRS) was assessed in the post-exercise period by spectral analysis and the sequence method. Data are given as means +/- S.E.M. Mean carotid artery diameter increased during exercise as compared with control levels, but carotid distension amplitude did not change. PDR was reduced from 27.3+/-2.7 to 13.7+/-1.0 microm mmHg(-1). Immediately after stopping exercise, the carotid artery constricted and PDR remained reduced. At 60 min post-exercise, the carotid artery dilated and the PDR increased above control levels (33.9+/-1.4 microm mmHg(-1)). The post-exercise changes in PDR were closely paralleled by those in BRS (0.74< or = r < or =0.83, P<0.05). These changes in mean carotid diameter and PDR suggest that the mean baroreceptor activity level increases during exercise, with reduced dynamic sensitivity; at the end of exercise baroreceptors are suddenly unloaded, then at 1 h post-exercise, baroreceptor activity increases again with increasing dynamic sensitivity. The close correlation between PDR and BRS observed at post-exercise underlies the significance of mechanical factors in arterial baroreflex control.