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Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Cardiovascular regulation during exercise, described using time series analysis, is expected to be attenuated after bed rest (BR) and this effect will be dampened by a reactive jumps countermeasure. Methods: Twenty subjects (29 ± 6 years, 23.6 ± 1.7 kg m−2) were tested on a cycle ergometer 9 days (BDC-9) before the beginning of BR as well as 2 (R + 2) and 13 days (R + 13) after the end of BR, applying moderate pseudo-random binary (PRBS) work rate changes. Heart rate (HR) and mean arterial blood pressure (mBP) were measured beat-to-beat and interpolated to 1 s intervals. HR and mBP were cross-correlated [CCF(HR-mBP)] during the PRBS. Eleven subjects participated in a reactive jump countermeasure (JUMP) during the BR period, the other part of the group served as control group (CTRL). Results: In the CTRL group, significantly lower CCF(HR-mBP) values during BDC-9 were observed compared to R + 2 during the lags 20–25 s and significantly higher values during the lags − 39 s to − 35 s. In the JUMP group, significantly lower CCFs were only observed at R + 2 compared with BDC-9 during the lags 23 s and 24 s, whereas the CCFs for BDC-9 were significantly higher at several lags compared with R + 13. Conclusion: Attenuations in the regulation of the cardiovascular system during cycling exercise after BR were found in the CTRL group of the RSL study. Cardiovascular regulation in the JUMP group was improved compared to values before the beginning of BR, suggesting the effectiveness of the reactive jumps countermeasure to mitigate the deleterious effects of prolonged BR. [ABSTRACT FROM AUTHOR]

Copyright of Gefaesschirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The aim of the study was to test whether or not the arteriovenous oxygen concentration difference (avDO2) kinetics at the pulmonary (avDO2pulm) and muscle (avDO2musc) levels is significantly different during dynamic exercise.Methods: A re-analysis involving six publications dealing with kinetic analysis was utilized with an overall sample size of 69 participants. All studies comprised an identical pseudorandom binary sequence work rate (WR) protocol-WR changes between 30 and 80 W-to analyze the kinetic responses of pulmonary ([Formula: see text]) and muscle ([Formula: see text]) oxygen uptake kinetics as well as those of avDO2pulm and avDO2musc.Results: A significant difference between [Formula: see text] (0.395 ± 0.079) and [Formula: see text] kinetics (0.330 ± 0.078) was observed (p < 0.001), where the variables showed a significant relationship (rSP = 0.744, p < 0.001). There were no significant differences between avDO2musc (0.446 ± 0.077) and avDO2pulm kinetics (0.451 ± 0.075), which are highly correlated (r = 0.929, p < 0.001).Conclusion: It is suggested that neither avDO2pulm nor avDO2musc kinetic responses seem to be responsible for the differences between estimated [Formula: see text] and measured [Formula: see text] kinetics. Obviously, the conflation of avDO2 and perfusion ([Formula: see text] ) at different points in time and at different physiological levels drive potential differences in [Formula: see text] and [Formula: see text] kinetics. Therefore, [Formula: see text] should, in general, be considered whenever oxygen uptake kinetics are analyzed or discussed. [ABSTRACT FROM AUTHOR]

Purpose: The effects of 60 days of head down tilt bed rest (HDBR) with and without the application of a reactive jump countermeasure were investigated, using a method which enables to discriminate between pulmonary ([Formula: see text]O2pulm) and muscular ([Formula: see text]O2musc) oxygen uptake kinetics to control for hemodynamic influences.Methods: 22 subjects were randomly allocated to either a group performing a reactive jumps countermeasure (JUMP; n = 11, male, 29 ± 7 years, 23.9 ± 1.3 kg m- 2) or a control group (CTRL; n = 11, male, 29 ± 6 years, 23.3 ± 2.0 kg m- 2). Heart rate (HR) and [Formula: see text]O2pulm were measured in response to repeated changes in work rate between 30 and 80 W before (BDC-9) and two times after HDBR (R+ 2, R+ 13). Kinetic responses of HR, [Formula: see text]O2pulm, and [Formula: see text]O2musc were assessed applying time series analysis. Higher maxima in cross-correlation functions (CCFmax(x)) between work rate and the respective parameter indicate faster kinetics responses. Statistical analysis was performed applying multifactorial analysis of variance.Results: CCFmax([Formula: see text]O2musc) and CCFmax([Formula: see text]O2pulm) were not significantly different before and after HDBR (P > 0.05). CCFmax(HR) decreased following bed rest (JUMP: BDC-9: 0.30 ± 0.09 vs. R+ 2: 0.28 ± 0.06 vs. R+13: 0.28 ± 0.07; CTRL: 0.35 ± 0.09 vs. 0.27 ± 0.06 vs. 0.33 ± 0.07 P = 0.025). No significant differences between the groups were observed (P > 0.05). Significant alterations were found for CCFmax of mean arterial blood pressure (mBP) after HDBR (JUMP: BDC-9: 0.21 ± 0.07 vs. R+ 2: 0.30 ± 0.13 vs. R+ 13: 0.28 ± 0.08; CTRL: 0.25 ± 0.07 vs. 0.38 ± 0.13 vs. 0.28 ± 0.08; P = 0.008).Conclusions: Despite hemodynamic changes, [Formula: see text]O2 kinetics seem to be preserved for a longer period of HDBR, even without the application of a countermeasure. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Hypotension due to spinal anesthesia is a well-known side effect in pregnant women receiving caesarean section. Little is known about its impact on fetal blood circulation.Methods: 40 women with uncomplicated singleton term pregnancies prepared for caesarean section were prospectively evaluated by Doppler sonography before and immediately after spinal anesthesia.Results: In 90% of the women, blood pressure significantly decreased after spinal anesthesia and 42.5% of the patients suffered from severe hypotension. We found a significant negative correlation between maternal blood pressure change and the resistant index (RI) of the umbilical artery (rs = - 0.376, p = 0.017) and a significant positive correlation between maternal blood pressure and fetal middle cerebral artery.Conclusion: Healthy fetuses seem to compensate well in situations with decreased uteroplacental blood flow due to maternal hypotension measured by means of RI changes in the fetal umbilical and middle cerebral artery. This raises the question if growth-restricted and/or preterm fetuses are able to compensate similarly or if general anesthesia would be a method of choice. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to test for significant differences in non-invasively estimated muscle oxygen uptake ([Formula: see text]) kinetics, assessed by a square-wave exercise protocol (STEP) as well as by a time series approach with pseudorandom binary sequence (PRBS) work rate (WR) changes.Methods: Seventeen healthy and active individuals (10 women, 7 men; 23 ± 2 years old; height 175 ± 11 cm; body mass 73 ± 14 kg [mean ± SD]) completed five repetitions of WR transitions from 30 to 80 W for the STEP approach and two sequences of pseudorandom binary WR changes between 30 and 80 W for the PRBS approach. Pulmonary oxygen uptake ([Formula: see text]) was measured breath by breath. [Formula: see text] kinetics were estimated during phase II [Formula: see text] in the STEP approach and during the pseudorandom binary sequence WR changes in the PRBS approach.Results: No significant differences were observed between different models of the STEP and the PRBS approach for estimation of [Formula: see text] kinetics (p > 0.05). In addition, a very high variability between the models was determined for [Formula: see text] kinetics [mean time constants (τ) difference: - 2.5 ± 11.4 s]. A significant correlation for τ of [Formula: see text] between the STEP approach with experimentally determined phase I [Formula: see text] lengths and the PRBS approach was noticed (r = 0.536; p < 0.05).Conclusions: Both approaches (STEP and PRBS) are not significantly different for estimating the [Formula: see text] kinetics, but the very high variability impairs the predictability between the models. However, the determination of the length of phase I [Formula: see text] should be as appropriate as possible because predefined duration lengths can result in overestimations in [Formula: see text] kinetics. [ABSTRACT FROM AUTHOR]

Background: Left atrial appendage (LAA) closure (LAAC) by implantation of an occlusion device is an established cardiac intervention to reduce risk of stroke while avoiding intake of oral anticoagulation medication during atrial fibrillation. Cardiac interventions can alter local or systemic gene and protein expression. Effects of LAAC on systemic metabolism have not been studied yet. Objectives: We aimed to study the effects of interventional LAAC on systemic metabolism. Methods: Products of glycolysis, tricarboxylic acid and urea metabolism were analyzed by ESI-LC-MS/MS and MS/MS using the AbsoluteIDQ™ p180 Kit in plasma of 44 patients undergoing successful interventional LAAC at baseline (T0) and after 6 months (T1). Results: During follow up, plasma concentrations of several parameters of glycolysis and tricarboxylic acid cycle (TCA) and urea metabolism increased (alanine, hexose, proline, sarcosine), while others decreased (aspartate, glycine, SDMA, serine). Multivariate linear regression analysis showed that time after interventional LAAC was an independent predictor for metabolite changes, including the decrease of SDMA (beta −0.19, p < 0.01) and the increase of sarcosine (beta 0.16, p < 0.01). Conclusions: Successful interventional LAAC affects different pathways of the metabolome, which are probably related to cardiac remodeling. The underlying mechanisms as well as the long term effects have to be studied in the future. [ABSTRACT FROM AUTHOR]

Objectives: The ageing population implicates an increasing numbers of older adults attending Emergency Departments (ED). We assessed the effect of estimated glomerular filtration rate as a predictor of clinical outcomes in oldest-old patients ≥ 85 years attending the ED in an university teaching hospital. Design: Within three years, 81831 patient contacts were made in our ED. 7799 (9.5%) were older than 85 years, in whom we analyzed the impact of renal function on various outcome parameters. Furthermore, this patient group was compared to the patients > 85 years. Results: Within the group of patients ≥ 85 years, not older age, but as denominator decreased glomerular filtration rate led to significant longer hospital stays. In addition, impaired kidney function was associated with lower heart rates, lower blood pressure, lower oxygenation, a higher rate of established ambulant care setting, as well as higher mortality. Compared to younger patients, the oldest-old significantly differed with regard to medical attribution (e.g. internal medicine, surgery), sex distribution, length of hospital stay, Manchester triage score, Glasgow Coma Scale, visual analogue pain scale, heart rate, blood pressure, oxygen saturation as well as fall prophylaxis, outpatient care, and presence of relatives. Conclusion: In conclusion, in this large collective of oldest-old patients, impaired kidney function seems to be a more important determinant in adverse outcome and thus increased health care costs than age per se. Adapted strategies in EDs to adjust diagnostic and treatment strategies for this population are thus warranted. [ABSTRACT FROM AUTHOR]

Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Gynäkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Nephrologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Herz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The aim of the study was to compare the kinetics responses of heart rate (HR), pulmonary ([Formula: see text]O2pulm), and muscular ([Formula: see text]O2musc) oxygen uptake during dynamic leg exercise across different body positions (-6°, 45°, and 75°).Methods: Ten healthy individuals [six men, four women; age 23.4 ± 2.8 years; height 179.7 ± 8.3 cm; body mass 73 ± 12 kg (mean ± SD)] completed pseudo-random binary sequence (PRBS) work rate (WR) changes between 30 and 80 W in each posture. HR was measured beat-to-beat by echocardiogram and [Formula: see text]O2pulm by breath-by-breath gas exchange. [Formula: see text]O2musc kinetics were assessed by the procedure of Hoffmann et al. (Eur J Appl Physiol 113:1745-1754, 2013) applying a circulatory model and cross-correlation functions (CCF).Results: For [Formula: see text]O2pulm kinetics significant differences between -6° (CCF-values: 0.292 ± 0.040) and 45° (0.256 ± 0.034; p < 0.01; n = 10) as well as between -6° and 75° (0.214 ± 0.057; p < 0.05; n = 10) were detected at lag '40 s' of the CCF course as interaction effects (factors: Lag × Posture). HR and [Formula: see text]O2musc kinetics yield no significant differences across the postures.Conclusions: The analysis of cardio-dynamic and respiratory kinetics, especially with an emphasis on muscular and cellular level, has to consider venous return and cardiac output distortions. Simplified observations of kinetics responses resulting in time constants and time delays only should be replaced by the time-series analysis for a more sophisticated evaluation. The results illustrate that isolated [Formula: see text]O2pulm measurements without cardio-dynamic influences may not represent the kinetics responses originally revealed at muscular level. [ABSTRACT FROM AUTHOR]

Purpose: Heart rate (HR), pulmonary and muscle oxygen uptake ([Formula: see text]O2pulm, [Formula: see text]O2musc) kinetics after changes of work rate (WR) indicate regulatory characteristics related to aerobic metabolism. We analysed whether the kinetics of HR, [Formula: see text]O2pulm and [Formula: see text]O2musc are slowed after missions to the International Space Station (ISS). The changes of the kinetics were correlated with [Formula: see text]O2peak data.Methods: 10 astronauts [4 females, 6 males, age: 48.0 ± 3.8 years, height: 176 ± 7 cm, mass: 74.5 ± 15.9 kg (mean ± SD)] performed an incremental test to determine [Formula: see text]O2peak (before missions on L-110 days, after return on R+1/+10/+36 days), and a cardio-respiratory kinetics test (CRKT) with randomized 30-80 W WR changes to determine HR, [Formula: see text]O2pulm and [Formula: see text]O2musc kinetics by time-series analysis (L-236/-73, R+6/+21). Kinetics were summarized by maximum and related lag of cross-correlation function (CCFmax, CCFlag) of WR with the analysed parameter.Results: Statistically, significant changes were also found for CCFmax([Formula: see text]O2musc) between L-236 and R+6 (P = 0.010), L-236 and R+21 (P = 0.030), L-72 and R+6 (P = 0.043). Between pre-to-post mission change in [Formula: see text]O2peak and CCFmax(HR), a correlation was shown (r SP = 0.67, P = 0.017).Conclusion: The [Formula: see text]O2musc kinetics changes indicate aerobic detraining effects which are present up to 21 days following space flight. The correlations between changes in [Formula: see text]O2peak and HR kinetics illustrate the key role of cardiovascular regulation in [Formula: see text]O2peak. The addition of CRKT to ISS flight is recommended to obtain information regarding the potential muscular and cardiovascular deconditioning. This allows a reduction in the frequency of higher intensity testing during flight. [ABSTRACT FROM AUTHOR]

Purpose: The study compared the kinetic responses of heart rate (HR), pulmonary ( $$\dot V$$ Opulm) and muscular oxygen uptake ( $$\dot V$$ Omusc) for upper (UpBody) and lower body (LoBody) exercise. Methods: Eleven healthy men (24 ± 2 years, 184 ± 8 cm, 79 ± 7 kg) performed pseudo-random binary sequence (PRBS) work rate (WR) changes on a semi-recumbent cycle ergometer (30 and 80 W) and an arm cranking exercise device (20 and 50 W); followed by stepwise increases in WR (UpBody: 20 W 5 min; LoBody: 50 W 5 min). $$\dot V$$ Opulm was measured breath-by-breath and HR beat-to-beat. $$\dot V$$ Omusc was estimated by the approach as reported by Hoffmann et al. (Eur J Appl Physiol 113:1745-1754, ), accounting for circulatory distortions. Time constants ( τ) for HR ( τHR), $$\dot V$$ Opulm ( τ $$\dot V$$ Opulm) and $$\dot V$$ Omusc ( τ $$\dot V$$ Omusc) were estimated during the PRBS phases by time-series analysis. Results: Peak oxygen uptake differed significantly between UpBody (37.8 ± 5.0 ml min kg) and LoBody exercises (56.1 ± 7.4 mL min kg; p < 0.001). Significant differences were observed for τ $$\dot V$$ Omusc (UpBody: 41.1 ± 11.3 s vs LoBody: 29.5 ± 5.2 s; p < 0.05), but not for τ $$\dot V$$ Opulm (49.1 ± 17.1 s vs 39.6 ± 11.2 s; p > 0.05) and τHR (29.1 ± 15.6 s vs 25.6 ± 8.0 s; p > 0.05). Conclusions: Meaningful dissociations between $$\dot V$$ Opulm and $$\dot V$$ Omusc kinetics exist for both UpBody and LoBody exercise during rapid work rate changes. Therefore, isolated $$\dot V$$ Opulm kinetic estimations without the consideration of the circulatory distortions may not allow a reliable assessment of $$\dot V$$ Omusc kinetics. [ABSTRACT FROM AUTHOR]

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Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

During non-steady-state exercise, dynamic changes in pulmonary oxygen uptake (VO₂pulm) are dissociated from skeletal muscle VO₂ (VO₂musc) by changes in lung and venous O₂ concentrations (CvO₂), and the dynamics and distribution of cardiac output (CO) between active muscle and remaining tissues (Qrem). Algorithms can compensate for fluctuations in lung O₂ stores, but the influences of CO and CvO₂ kinetics complicate estimation of VO₂musc from cardio-pulmonary measurements. We developed an algorithm to estimate VO₂musc kinetics from VO₂pulm and heart rate (HR) during exercise. 17 healthy volunteers (28 ± 7 years; 71 ± 12 kg; 7 females) performed incremental exercise using recumbent cycle ergometry (VO₂peak 52 ± 8 ml min(-1) kg(-1)). Participants completed a pseudo-random binary sequence (PRBS) test between 30 and 80 W. VO₂pulm and HR were measured, and CO was estimated from HR changes and steady-state stroke volume. VO₂musc was derived from a circulatory model and time series analyses, by solving for the unique combination of venous volume and the perfusion of non-exercising tissues that provided close to mono-exponential VO₂musc kinetics. Independent simulations showed that this approach recovered the VO₂musc time constant (τ) to within 7% (R(2) = 0.976). Estimates during PRBS were venous volume 2.96 ± 0.54 L; Qrem 3.63 ± 1.61 L min(-1); τHR 27 ± 11 s; τVO₂musc 33 ± 8 s; τVO₂pulm 43 ± 14 s; VO₂pulm time delay 19 ± 8 s. The combination of stochastic test signals, time series analyses, and a circulatory model permitted non-invasive estimates of VO₂musc kinetics. Large kinetic dissociations exist between muscular and pulmonary VO₂ during rapid exercise transients. [ABSTRACT FROM AUTHOR]

During non-steady-state exercise, dynamic changes in pulmonary oxygen uptake ( $$\dot{V} {\text{O}_{\text{2pulm}}}$$) are dissociated from skeletal muscle $$ \dot{V} {\text{O}_2}$$ ( $$\dot{V} {\text{O}_{\text{2musc}}}$$) by changes in lung and venous O concentrations (CvO), and the dynamics and distribution of cardiac output (CO) between active muscle and remaining tissues ( $$ \dot{Q}_{\text{rem}}$$). Algorithms can compensate for fluctuations in lung O stores, but the influences of CO and CvO kinetics complicate estimation of $$\dot{V} {\text{O}_{\text{2musc}}}$$ from cardio-pulmonary measurements. We developed an algorithm to estimate $$\dot{V} {\text{O}_{\text{2musc}}}$$ kinetics from $$\dot{V} {\text{O}_{\text{2pulm}}}$$ and heart rate (HR) during exercise. 17 healthy volunteers (28 ± 7 years; 71 ± 12 kg; 7 females) performed incremental exercise using recumbent cycle ergometry ( $$\dot{V} {\text{O}_{\text{2peak}}}$$ 52 ± 8 ml min kg). Participants completed a pseudo-random binary sequence (PRBS) test between 30 and 80 W. $$\dot{V} {\text{O}_{\text{2pulm}}}$$ and HR were measured, and CO was estimated from HR changes and steady-state stroke volume. $$\dot{V} {\text{O}_{\text{2musc}}}$$ was derived from a circulatory model and time series analyses, by solving for the unique combination of venous volume and the perfusion of non-exercising tissues that provided close to mono-exponential $$\dot{V} {\text{O}_{\text{2musc}}}$$ kinetics. Independent simulations showed that this approach recovered the $$\dot{V} {\text{O}_{\text{2musc}}}$$ time constant (τ) to within 7 % ( R = 0.976). Estimates during PRBS were venous volume 2.96 ± 0.54 L; $$ \dot{Q}_{\text{rem}}$$ 3.63 ± 1.61 L min; τHR 27 ± 11 s; τ $$\dot{V} {\text{O}_{\text{2musc}}}$$ 33 ± 8 s; τ $$\dot{V} {\text{O}_{\text{2pulm}}}$$ 43 ± 14 s; $$\dot{V} {\text{O}_{\text{2pulm}}}$$ time delay 19 ± 8 s. The combination of stochastic test signals, time series analyses, and a circulatory model permitted non-invasive estimates of $$\dot{V} {\text{O}_{\text{2musc}}}$$ kinetics. Large kinetic dissociations exist between muscular and pulmonary $$\dot{V} {\text{O}_{\text{2}}}$$ during rapid exercise transients. [ABSTRACT FROM AUTHOR]

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Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims/hypothesis: The anatomic location of excess body fat has an impact on associated cardiometabolic morbidity, and visceral adipose tissue (VAT) is more pathogenic than subcutaneous adipose tissue (SAT). However, VAT or SAT alone provides little information regarding the relative distribution of body fat. We hypothesised that the propensity to store energy in VAT relative to SAT depots may be a correlate of cardiometabolic risk, and tested this hypothesis using the VAT/SAT ratio as a metric of fat distribution. Methods: We investigated associations of the VAT/SAT ratio with cardiometabolic traits in 3,223 participants (48% women) from the Framingham Heart Study. Fat depots were quantified by multidetector computed tomography (CT) scanning. Results: In women and men, higher VAT/SAT ratio was associated ( p < 0.05) with most assessed cardiovascular risk factors reflecting blood pressure, dyslipidaemia and insulin resistance. Additional adjustment for BMI did not materially change the findings in women, and generally strengthened associations in men. Further adjustment for VAT attenuated some associations in women, but those with lower HDL-cholesterol, higher triacylglycerol (both p < 0.0001) and higher prevalence of hypertension ( p = 0.02), diabetes ( p = 0.01) and the metabolic syndrome ( p = 0.005) remained significant. Similarly, in men, associations with higher systolic ( p = 0.006) and diastolic blood pressure ( p = 0.03), higher fasting glucose ( p = 0.0005), lower HDL-cholesterol and higher triacylglycerol (both p < 0.0001) and higher prevalence of diabetes ( p = 0.006) remained significant. Conclusions/interpretation: VAT/SAT ratio is a correlate of cardiometabolic risk, above and beyond BMI and VAT. The propensity to store fat viscerally versus subcutaneously may be a unique risk factor independent of absolute fat volumes. [ABSTRACT FROM AUTHOR]

Copyright of Der Kardiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To systematically assess inter-technique and inter-/intra-reader variability of coronary CT angiography (CTA) to measure plaque burden compared with intravascular ultrasound (IVUS) and to determine whether iterative reconstruction algorithms affect variability.Methods: IVUS and CTA data were acquired from nine human coronary arteries ex vivo. CT images were reconstructed using filtered back projection (FBPR) and iterative reconstruction algorithms: adaptive-statistical (ASIR) and model-based (MBIR). After co-registration of 284 cross-sections between IVUS and CTA, two readers manually delineated the cross-sectional plaque area in all images presented in random order.Results: Average plaque burden by IVUS was 63.7 ± 10.7% and correlated significantly with all CTA measurements (r = 0.45-0.52; P < 0.001), while CTA overestimated the burden by 10 ± 10%. There were no significant differences among FBPR, ASIR and MBIR (P > 0.05). Increased overestimation was associated with smaller plaques, eccentricity and calcification (P < 0.001). Reproducibility of plaque burden by CTA and IVUS datasets was excellent with a low mean intra-/inter-reader variability of <1/<4% for CTA and <0.5/<1% for IVUS respectively (P < 0.05) with no significant difference between CT reconstruction algorithms (P > 0.05).Conclusion: In ex vivo coronary arteries, plaque burden by coronary CTA had extremely low inter-/intra-reader variability and correlated significantly with IVUS measurements. Accuracy as well as reader reliability were independent of CT image reconstruction algorithm.Key Points: • IVUS is deemed the gold standard in-vivo coronary plaque assessment • But coronary CT angiography findings correlate strongly with IVUS results • Coronary CT angiography now allows plaque quantification close to IVUS • Iterative image reconstruction algorithms do not alter accuracy or reproducibility • Plaque quantification is more challenging in smaller eccentric calcified lesions. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The primary aim of this study was to compare the results of HbA measurements with those of an OGTT for early diagnosis of 'silent diabetes' in patients with coronary artery disease (CAD) undergoing angiography without prediagnosed diabetes. A secondary aim was to investigate the correlation between the extent of CAD and the glycaemic status of the patient. Methods: Data from 1,015 patients admitted for acute ( n = 149) or elective ( n = 866) coronary angiography were analysed. Patients with known diabetes were excluded from the study. Using the OGTT results, patients were classified as having normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or diabetes. According to the results of the HbA measurements, patients were classified into three groups: normal (HbA <5.7% [<39 mmol/mol]), borderline (HbA 5.7-6.4% [39-47 mmol/mol]) and diabetes (HbA ≥6.5% [≥48 mmol/mol]). Results: Based on the OGTT, 513 patients (51%) were classified with NGT, 10 (1%) with IFG, 349 (34%) with IGT and 149 (14%) were diagnosed with diabetes. According to HbA measurements, 588 patients (58%) were classified as normal, 385 (38%) as borderline and 42 (4%) were diagnosed with diabetes. The proportion of patients with IGT and diabetes increased with the extent of CAD (IGT ρ = 0.14, p < 0.001, diabetes ρ = 0.09, p = 0.01). No differences in HbA were seen among the groups with different extents of CAD ( p = 0.652). Conclusions/interpretation: An OGTT should be performed routinely for diagnosis of diabetes in patients with CAD undergoing coronary angiography, since HbA measurement alone appears to miss a substantial proportion of patients with silent diabetes. A limitation of the study is that the OGTT was not performed before the angiography. [ABSTRACT FROM AUTHOR]

Objective: To prospectively examine coronary artery plaques as predictors of myocardial ischaemia using cardiac magnetic resonance (CMR).Methods: Fifty-two patients (46 men; age 64 ± 10) with suspected coronary artery disease (CAD) referred for catheter coronary angiography (CA) underwent CMR and computed tomography coronary angiography (CTCA). All coronary segments were evaluated for morphological stenosis based on CA. Any plaque according to its composition was assessed based on CTCA.Results: Numbers of total and calcified coronary artery plaques represented the best predictors of myocardial ischaemia (AUC = 0.87; [95%CI: 0.77-0.97] and AUC = 0.87; [95%CI: 0.77-0.96], respectively, p = 0.56) with the total plaque number significantly higher in patients with corresponding ischaemia than those without (p < 0.01, p < 0.05 adjusted for pre-test probability and stenosis). Compared with the AUC of coronary stenosis assessment by CA (AUC = 0.90; [95%CI: 0.80-1.00]), AUCs were equivalent using either the total number or the number of calcified plaques alone (p = 0.73 and p = 0.69). Multivariate logistic regression analyses demonstrated the total plaque number as an independent predictor of ischaemia (odds +20%; [95%CI: 1.096-1.368]), improving a model including clinical probability estimates of CAD (c-statistics, 0.66 to 0.89).Conclusion: Coronary artery plaque number according to CTCA is a significant, independent predictor of myocardial ischaemia with similar accuracy to stenosis assessment. [ABSTRACT FROM AUTHOR]

Introduction: Bacterial infection of endovascular stent grafts is a serious condition, regularly leading to graft replacement by open bypass surgery. Case Report: We describe the case of a staphylococcal infection of a 150-mm covered stent graft (Gore Viabahn), placed in the superficial femoral artery. Stent graft infection was successfully treated by oral administration of penicillinase-resistant flucloxacillin and the lipopeptide daptomycin with complete graft preservation, not requiring surgical treatment. During 1-year follow-up, the graft infection did not reappear. However, the patient developed restenosis at the proximal margin of the stent with recurrence of mild claudication, so far treated conservatively. Conclusion: With the increased use of covered stent grafts in the peripheral vasculature, the frequency of graft infection will increase. We demonstrate that with newly developed antibiotics, it is possible to treat this severe complication conservatively, with complete graft preservation and without the need for bypass surgery in selected cases. [ABSTRACT FROM AUTHOR]

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Summary: Two radiologists evaluated images of the spine from computed tomography (CT) scans on two occasions to diagnose vertebral fracture in 100 individuals. Agreement was fair to good for mild fractures, and agreement was good to excellent for more severe fractures. CT scout views are useful to assess vertebral fracture. Introduction: We investigated inter-reader agreement between two radiologists and intra-reader agreement between duplicate readings for each radiologist, in assessment of vertebral fracture using a semi-quantitative method from lateral scout views obtained by CT. Methods: Participants included 50 women and 50 men (age 50-87 years, mean 70 years) in the Framingham Study. T4-L4 vertebrae were assessed independently by two radiologists on two occasions using a semi-quantitative scale as normal, mild, moderate, or severe fracture. Results: Vertebra-specific prevalence of grade ≥1 (mild) fracture ranged from 3% to 5%. We found fair ( κ = 56-59%) inter-reader agreement for grade ≥1 vertebral fractures and good ( κ = 68-72%) inter-reader agreement for grade ≥2 fractures. Intra-reader agreement for grade ≥1 vertebral fracture was fair ( κ = 55%) for one reader and excellent for another reader ( κ = 77%), whereas intra-reader agreement for grade ≥2 vertebral fracture was excellent for both readers ( κ = 76% and 98%). Thoracic vertebrae were more difficult to evaluate than the lumbar region, and agreement was lowest (inter-reader κ = 43%) for fracture at the upper (T4-T9) thoracic levels and highest (inter-reader κ = 76-78%) for the lumbar spine (L1-L4). Conclusions: Based on a semi-quantitative method to classify vertebral fractures using CT scout views, agreement within and between readers was fair to good, with the greatest source of variation occurring for fractures of mild severity and for the upper thoracic region. Agreement was good to excellent for fractures of at least moderate severity. Lateral CT scout views can be useful in clinical research settings to assess vertebral fracture. [ABSTRACT FROM AUTHOR]

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Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Measures of left ventricular (LV) mass and dimensions are independent predictors of morbidity and mortality. We determined whether an axial area-based method by computed tomography (CT) provides an accurate estimate of LV mass and volume.Method: A total of 45 subjects (49% female, 56.0 +/- 12 years) with a wide range of LV geometry underwent contrast-enhanced 64-slice CT. LV mass and volume were derived from 3D data. 2D images were analysed to determine LV area, the direct transverse cardiac diameter (dTCD) and the cardiothoracic ratio (CTR). Furthermore, feasibility was confirmed in 100 Framingham Offspring Cohort subjects.Results: 2D measures of LV area, dTCD and CTR were 47.3 +/- 8 cm(2), 14.7 +/- 1.5 cm and 0.54 +/- 0.05, respectively. 3D-derived LV volume (end-diastolic) and mass were 148.9 +/- 45 cm(3) and 124.2 +/- 34 g, respectively. Excellent inter- and intra-observer agreement were shown for 2D LV area measurements (both intraclass correlation coefficients (ICC) = 0.99, p < 0.0001) and could be confirmed on non-contrast CT. The measured 2D LV area was highly correlated to LV volume, mass and size (r = 0.68; r = 0.73; r = 0.82; all p < 0.0001, respectively). On the other hand, CTR was not correlated to LV volume, mass, size or 2D LV area (all p > 0.27).Conclusion: Compared with traditionally used CTR, LV size can be accurately predicted based on a simple and highly reproducible axial LV area-based measurement. [ABSTRACT FROM AUTHOR]

Objective:Volumetric visceral abdominal adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAT) as measured by computed tomography (CT) are associated with metabolic risk factors. We sought to identify the correlations of VAT and SAT between area-based measures at different anatomic locations with volumetric measurements to identify the optimal anatomic site, and to relate measurements at this site with metabolic risk factors.Methods:We measured SAT and VAT volumes across the total imaging volume, whereas we measured SAT and VAT area at seven predefined anatomic landmarks in 200 participants from the Framingham Heart Study (mean age 54 years, 50% women) who underwent abdominal multi-detector CT. Correlation coefficients were used to assess the association between area measurements and volumes as well as metabolic risk factors stratified by gender.Results:Area-based measurements of SAT and VAT obtained at all anatomic landmarks were strongly associated with SAT and VAT volumes (all r>0.93, P<0.0001 and r>0.87, P<0.0001, for women and men; respectively). Consistently, area-based measurements of SAT and VAT obtained at L3/4 were most strongly associated with volumetric measured VAT and SAT independent of age (both r=0.99 in men, r=0.96 for SAT and r=0.99 for VAT in women, all P-value <0.0001) and were similarly correlated with risk factors compared with SAT and VAT volumes (all P<0.05 for fasting plasma glucose, triglycerides, high-density lipoprotein, systolic blood pressure).Conclusion:Among area-based measurements of SAT and VAT, those obtained at the level of L3/4 were strongly associated with SAT and VAT volumes and cardio-metabolic risk factors in both men and women. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the accuracy and reproducibility of non-calcified plaque quantification as simulated by a low-density stenosis in vessel phantoms using diameter and area measures, as well as the influence of vessel size and motion on quantification accuracy in dual-source computed tomography (DSCT).Methods: Four phantoms (2, 2.5, 3, and 4 mm in luminal diameter) made from a radiopaque Lucite (126 +/- 23 Hounsfield units, HU) simulating a fixed radiolucent concentric coronary stenosis (7 +/- 2 HU, 50% luminal narrowing) were connected to a cardiac motion simulator. Stenosis quantification was based on area and diameter measurements. All measurements were highly reproducible (all ICC > or =0.95, p < 0.001).Results: The mean measured degree of stenosis was 38.0 +/- 11.7% for a single diameter measurement, resulting in a mean relative error of 22.0 +/- 18.7%, decreasing with increasing phantom size (31.9 +/- 22.1%; 25.2 +/- 20.9%; 16.3 +/- 12.8%; 14.5 +/- 11.4%; for 2-, 2.5-, 3-, and 4-mm phantoms, respectively; p < 0.0001). Measurement accuracy significantly increased to 13.3 +/- 13.9% by using area measurement (p < 0.0001). The degree of stenosis was not significantly different when comparing a motioned image with an image at rest.Conclusion: DSCT enables highly reproducible quantification of low density stenosis, but underestimates the degree of stenosis, especially in small vessels. Area-based measurements reflect the true degree of stenosis with higher accuracy than diameter. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Schmerz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Coronary computed tomography angiography (CTA) may be helpful to manage patients with chronic coronary occlusions. The aim of this study was to determine the sensitivity and specificity of CTA to detect the presence and extent of coronary collaterals as compared to invasive coronary angiography (ICA). We retrospectively evaluated 26 patients who underwent both coronary CTA and ICA within 3 weeks and demonstrated a total coronary occlusion (TIMI grade 0) in one of the major coronary arteries. CTA was performed using a 64-slice multidetector CT. The presence, and extent of collateralization was assessed by two blinded observers using the Rentrop classification for ICA. CTA accurately identified the presence and location of all 26 total occlusions. The presence of any collaterals was accurately detected in 21/23 patients [sensitivity 91% (CI: 71-98%)] and the absence in three patients [specificity 100% (CI: 29%-100%)]. The sensitivity of coronary CTA to identify patients with collateralization increased from 91 to 94% (CI: 71-99%) and 100% (CI: 59-100%) for collaterals Rentrop grade 2 and 3 in ICA, respectively. Coronary CTA accurately detects the presence of any coronary collateralization in patients with total occlusions. Although CT technology is currently limited in the assessment of individual collaterals and smaller vessels, it may be helpful in the management of patients with total occlusions. [ABSTRACT FROM AUTHOR]

Background:Perivascular adipose tissue may be associated with the amount of local atherosclerosis. We developed a novel and reproducible method to standardize volumetric quantification of periaortic adipose tissue by computed tomography (CT) and determined the association with anthropometric measures of obesity, and abdominal adipose tissue.Methods:Measurements of adipose tissue were performed in a random subset of participants from the Framingham Heart Study (n=100) who underwent multidetector CT of the thorax (ECG triggering, 2.5 mm slice thickness) and the abdomen (helical CT acquisition, 2.5 mm slice thickness). Abdominal periaortic adipose tissue (AAT) was defined by a 5 mm cylindrical region of interest around the aortic wall; thoracic periaortic adipose tissue (TAT) was defined by anatomic landmarks. TAT and AAT were defined as any voxel between −195 and −45 HU and volumes were measured using dedicated semiautomatic software. Measurement reproducibility and association with anthropometric measures of obesity, and abdominal adipose tissue were determined.Results:The intra- and inter-observer reproducibility for both AAT and TAT was excellent (ICC: 0.97 and 0.97; 0.99 and 0.98, respectively). Similarly, the relative intra- and inter-observer difference was small for both AAT (−1.85±1.28% and 7.85±6.08%; respectively) and TAT (3.56±0.83% and −4.56±0.85%, respectively). Both AAT and TAT were highly correlated with visceral abdominal fat (r=0.65 and 0.77, P<0.0001 for both) and moderately correlated with subcutaneous abdominal fat (r=0.39 and 0.42, P<0.0001 and P=0.009), waist circumference (r=0.49 and 0.57, P<0.0001 for both) and body mass index (r=0.47 and 0.58, P<0.0001 for both).Conclusion:Standardized semiautomatic CT-based volumetric quantification of periaortic adipose tissue is feasible and highly reproducible. Further investigation is warranted regarding associations of periaortic adipose tissue with other body fat deposits, cardiovascular risk factors and clinical outcomes.International Journal of Obesity (2009) 33, 226–232; doi:10.1038/ijo.2008.267; published online 13 January 2009 [ABSTRACT FROM AUTHOR]

Deletion of exon CD44v7 abrogates experimental colitis by apoptosis induction in intestinal mononuclear cells. Here we show that CD44v7 expression was upregulated upon CD40 ligation in human mononuclear cells, and examined whether ligation of CD44v7 also affects activation and apoptosis in lamina propria mononuclear cells (LPMC) from Crohn's disease (CD) patients. Thirty five patients with chronic inflammatory bowel disease (IBD), fourteen controls and four patients with diverticulitis were evaluated. CD44v7 was upregulated predominantly in the inflamed mucosa of CD patients. Furthermore, incubation with an anti-CD44v7 antibody induced apoptosis in LPMC isolated from inflamed mucosa of CD patients, but not from non-inflamed mucosa, from patients with ulcerative colitis (UC) or from normal controls. CD40 ligation and simultaneous incubation with anti-CD44v7 significantly downregulated CD80 in dendritic cells, thus inhibiting a critical second signal for naive T-cell activation. The apoptotic signal was mediated via the intrinsic mitochondrial pathway with decreased Bcl-2 and increased 7A6 (a mitochondrial membrane protein) expression. It was Fas independent and required caspases-3 and -9 activation. The process is highly specific for macrophage activation via CD40. These findings point to a novel mechanism of apoptosis induction in CD patients mediated by CD44v7 ligation.Cell Death and Differentiation (2007) 14, 1542–1551; doi:10.1038/sj.cdd.4402153; published online 4 May 2007 [ABSTRACT FROM AUTHOR]

Purpose:Cross-sectional imaging may enable accurate localization and quantification of subcutaneous and visceral adipose tissue. The reproducibility of multi-detector computed tomography (MDCT)-based volumetric quantification of abdominal adipose tissue and the ability to depict age- and gender-related characteristics of adipose tissue deposition have not been reported.Methods:We evaluated a random subset of 100 Caucasian subjects (age range: 37–83 years; 49% women) of the Framingham Heart Study offspring cohort who underwent MDCT scanning. Two readers measured subcutaneous and visceral adipose tissue volumes (SAV and VAV; cm3) and areas (SAA and VAA; cm2) as well as abdominal sagital diameter (SD) and waist circumference (WC).Results:Inter-reader reproducibility was excellent (relative difference: −0.34±0.52% for SAV and 0.59±0.93% for VAV, intra-class correlation (ICC)=0.99 each). The mean SAA/VAA ratio was significantly different from the mean SAV/VAV ratio (2.0±1.2 vs 1.7±0.9; P<0.001). The ratio of SAV/VAV was only weakly inversely associated with SD (ICC=−0.32, P=0.01) and not significantly associated with WC (ICC=−0.14, P=0.14) or body mass index (ICC=−0.17, P=0.09). The mean SAV/VAV ratio was significantly different between participants <60 vs >60 years (1.9±1.0 vs 1.5±0.7; P<0.001) and between men and women (1.2±0.5 vs 2.2±0.9; P<0.001).Conclusion:This study demonstrates that MDCT-based volumetric quantification of abdominal adipose tissue is highly reproducible. In addition, our results suggest that volumetric measurements can depict age- and gender-related differences of visceral and subcutaneous abdominal adipose tissue deposition. Further research is warranted to assess whether volumetric measurements may substantially improve the predictive value of obesity measures for insulin resistance, type 2 diabetes mellitus and other diseases.International Journal of Obesity (2007) 31, 500–506. doi:10.1038/sj.ijo.0803454; published online 5 September 2006 [ABSTRACT FROM AUTHOR]

The development of functional blood and lymphatic vessels requires spatio-temporal coordination of the production and release of growth factors such as vascular endothelial growth factors (VEGFs). VEGF family proteins are produced in multiple isoforms with distinct biological properties and bind to three types of VEGF receptors. A VEGF-A splice variant, VEGF-A165b, has recently been isolated from kidney epithelial cells. This variant is identical to VEGF-A165 except for the last six amino acids encoded by an alternative exon. VEGF-A165b and VEGF-A165 bind VEGF receptors 1 and 2 with similar affinity. VEGF-A165b elicits drastically reduced activity in angiogenesis assays and even counteracts signaling by VEGF-A165. VEGF-A165b weakly binds to heparan sulfate and does not interact with neuropilin-1, a coreceptor for VEGF receptor 2. To determine the molecular basis for altered signaling by VEGF-A165b we measured VEGF receptor 2 and ERK kinase activity in endothelial cells in culture. VEGF-A165 induced strong and sustained activation of VEGF receptor 2 and ERK-1 and −2, while activation by VEGF-A165b was only weak and transient. Taken together these data show that VEGF-A165b has attenuated signaling potential through VEGF receptor 2 defining this new member of the VEGF family as a partial receptor agonist. [ABSTRACT FROM AUTHOR]

BACKGROUND:Coronary artery disease continues to be one of the leading causes of death and disability around the globe, challenging the efficacy of currently applied schemes to predict the risk for future coronary events. In fact, algorithms such as the Framingham risk score that are based on traditional risk factors like hypertension and dyslipidemia are not very sensitive, leaving a majority of the population at intermediate risk.METHODS:Advances in multidetector computed tomography (MDCT) technology with submillimeter slice collimation (∼0.6 mm) and high temporal resolution now permit contrast-enhanced imaging of the coronary artery lumen and wall in a single breath hold. The current generation of MDCT provided in-plane resolution of 0.5 mm and a temporal resolution of 210 ms. The simultaneous acquisition of 16/64 parallel cross-sections reduces image acquisition time to about 10–20 s using 60–80 ml of contrast agents to opacify the coronary artery lumen. CT imaging for coronary calcification is an established method with low radiation exposure. The amount of calcification is expressed as an Agatston Score (AS).RESULTS:The presence and amount of coronary calcification significantly increases the relative risk for future coronary events, independent from traditional risk factors (risk ratio 8.7 [95% CI, 2.7–28.1]). Especially, individuals with a high AS (>400) who are at intermediate 10-y Framingham event risk may benefit from this additional risk stratification. However, calcification is rarely present in children and adolescents. However, there is a growing body of evidence suggesting that contrast-enhanced MDCT can detect both calcified and noncalcified plaques with high sensitivity and specificity for the detection of plaques >0.5 mm when compared to intravascular ultrasound. Moreover, initial data suggest that plaque characteristics such as plaque area, volume, quantify and coronary plaque remodeling index can be quantified in good agreement with IVUS. The composition of noncalcified plaque may be further stratified into predominantly fibrous or lipid-rich plaque. Noncalcified plaque may be present already in children and adolescents with multiple risk factors.CONCLUSION:The available data indicate that high resolution MDCT can reliably detect, quantify and characterize calcified and noncalcified coronary atherosclerotic plaque. With MDCT, we now have a unique opportunity to study the natural history and response to therapy of noncalcified coronary plaques, which may be already present in obese children or children with multiple risk factors.International Journal of Obesity (2005) 29, S46–S53. doi:10.1038/sj.ijo.0803083 [ABSTRACT FROM AUTHOR]

Prolactin (PRL) has been reported to inhibit apoptosis in various cell types and to serve as a cofactor in the upregulation of CD25 on T cells during activation. We investigated a possible relation between prolactin receptor (PRL-R) or IL-2 receptor alpha (IL-2Ralpha, CD25) expression on circulating T lymphocytes and their apoptosis in patients with breast cancer. Peripheral blood mononuclear cells obtained from 25 patients, 25 normal controls (NC) and three cord blood samples were evaluated for Annexin V binding and expression of CD95, CD25, and PRL-R on CD3(+) T cells by multicolour flow cytometry. Plasma levels of PRL, sCD95L, and sIL-2R were determined in patients and controls and related to T-cell apoptosis. The ability of PRL to protect T cells from apoptosis induced by various agents was also studied. Expression of PRL-R on the surface of T cells was comparable in patients with breast cancer and NC, but PRL plasma levels in patients were significantly lower (P<0.05). In patients, 18+/-11% (mean+/-s.d.) of CD3(+) cells bound Annexin V, compared to 9+/-6% in NC (P<0.0004). Percentages of CD3(+)Fas(+) and CD3(+)CD25(+) cells were higher in the peripheral circulation of patients than NC (P<0.0001 and <0.04, respectively). Levels of sFasL were lowest in plasma of the patients with the highest proportions of CD3(+)Fas(+) T cells. Most T cells undergoing apoptosis were CD3(+)CD25(-) in patients, and the proportion of CD3(+)CD25(-) Annexin V(+) cells was significantly increased in patients compared to NC (P<0.006). Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis. These results indicate that expression of CD25 but not of PRL-R on the surface of activated T lymphocytes appears to be involved in modulating Fas/Fas - ligand interactions, which are, in part, responsible for apoptosis of T lymphocytes and excessive turnover of immune cells in the circulation of patients with breast cancer. [ABSTRACT FROM AUTHOR]