Endothelial progenitor cells mobilization after maximal exercise according to heart failure severity

BACKGROUNDVascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium. They also have low levels of endothelial progenitor cells (EPCs). EPCs are bone marrow derived cells involved in endothelium regeneration, homeostasis, and neovascularization. Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities. However, the effects of exercise on EPCs in different stages of CHF remain under investigation.AIMTo evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing (CPET) on EPCs in CHF patients of different severity.METHODSForty-nine consecutive patients (41 males) with stable CHF [mean age (years): 56 ± 10, ejection fraction (EF, %): 32 ± 8, peak oxygen uptake (VO₂, mL/kg/min): 18.1 ± 4.4] underwent a CPET on a cycle ergometer. Venous blood was sampled before and after CPET. Five circulating endothelial populations were quantified by flow cytometry: Three subgroups of EPCs [CD34⁺/CD45^-/CD133⁺, CD34⁺/CD45^-/CD133⁺/VEGFR₂ and CD34⁺/CD133⁺/vascular endothelial growth factor receptor 2 (VEGFR₂)] and two subgroups of circulating endothelial cells (CD34⁺/CD45^-/CD133^- and CD34⁺/CD45^-/CD133^-/VEGFR₂). Patients were divided in two groups of severity according to the median value of peak VO₂ (18.0 mL/kg/min), predicted peak VO₂ (65.5%), ventilation/carbon dioxide output slope (32.5) and EF (reduced and mid-ranged EF). EPCs values are expressed as median (25th-75th percentiles) in cells/10⁶ enucleated cells.RESULTSPatients with lower peak VO₂ increased the mobilization of CD34⁺/CD45^-/CD133⁺ [pre CPET: 60 (25-76) vs post CPET: 90 (70-103) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133⁺/VEGFR₂ [pre CPET: 1 (1-4) vs post CPET: 5 (3-8) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133^- [pre CPET: 186 (141-361) vs post CPET: 488 (247-658) cells/10⁶ enucleated cells, P < 0.001] and CD34⁺/CD45^-/CD133^-/VEGFR₂ [pre CPET: 2 (1-2) vs post CPET: 3 (2-5) cells/10⁶ enucleated cells, P < 0.001], while patients with higher VO₂ increased the mobilization of CD34⁺/CD45^-/CD133⁺ [pre CPET: 42 (19-73) vs post CPET: 90 (39-118) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133⁺/VEGFR₂ [pre CPET: 2 (1-3) vs post CPET: 6 (3-9) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD133⁺/VEGFR₂ [pre CPET: 10 (7-18) vs post CPET: 14 (10-19) cells/10⁶ enucleated cells, P < 0.01], CD34⁺/CD45^-/CD133^- [pre CPET: 218 (158-247) vs post CPET: 311 (254-569) cells/10⁶ enucleated cells, P < 0.001] and CD34⁺/CD45^-/CD133^-/VEGFR₂ [pre CPET: 1 (1-2) vs post CPET: 4 (2-6) cells/10⁶ enucleated cells, P < 0.001]. A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak, ventilation/carbon dioxide output slope and EF as well (P < 0.05). However, there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison (P > 0.05).CONCLUSIONOur study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients, but this increase was not associated with syndrome severity. Further investigation, however, is needed.     

Specific measures of executive function predict cognitive decline in older adults

Decline in executive function has been noted in the prodromal stage of Alzheimer's disease (AD) and may presage more global cognitive declines. In this prospective longitudinal study, five measures of executive function were used to predict subsequent global cognitive decline in initially nondemented older adults. Of 71 participants, 15 demonstrated significant decline over a 1-year period on the Dementia Rating Scale (Mattis, 1988) and the remaining participants remained stable. In the year before decline, the decline group performed significantly worse than the no-decline group on two measures of executive function: the Color-Word Interference Test (CWIT; inhibition/switching condition) and Verbal Fluency (VF; switching condition). In contrast, decliners and non-decliners performed similarly on measures of spatial fluency (Design Fluency switching condition), spatial planning (Tower Test), and number-letter switching (Trail Making Test switching condition). Furthermore, the CWIT inhibition-switching measure significantly improved the prediction of decline and no-decline group classification beyond that of learning and memory measures. These findings suggest that some executive function measures requiring inhibition and switching provide predictive utility of subsequent global cognitive decline independent of episodic memory and may further facilitate early detection of dementia.     

Is there a "subcortical" profile of attentional dysfunction? A comparison of patients with Huntington's and Parkinson's diseases on a global-local focused attention task.

This study investigated focused attention in two subcortical degenerative disorders by examining the performance of patients with Huntington's disease (HD) and Parkinson's disease (PD) on a task utilizing global-local stimuli. Participants were presented with global-local figures and were instructed to focus their attention on either the global or local level. Stimuli were either "consistent", with the same form at the global and local levels, or "inconsistent", with different forms at the global and local levels. It was found that response times (RTs) of patients with PD were comparable to those of similarly-aged controls regardless of stimulus consistency. In contrast, patients with HD demonstrated disproportionately longer RTs to inconsistent stimuli relative to their age-matched control group. Difference scores between RTs for inconsistent versus consistent stimuli were not correlated with overall level of dementia or disease severity for either the HD or PD group. These results provide further evidence for the heterogeneity of attentional dysfunction among subcortical degenerative illnesses.     

Cogniform Disorder and Cogniform Condition: proposed diagnoses for excessive cognitive symptoms.

In neuropsychological practice, individuals often present with evidence of excessive cognitive complaints or invalid test performances indicative of symptom exaggeration; however, clinicians often struggle with how to diagnose these cases once they have been identified. Difficulties in subsuming these individuals within existing DSM-IV diagnoses such as Malingering, Factitious Disorder, and Conversion Disorder are discussed, including: (a) lack of a diagnostic category that adequately targets the specific features of this relatively common condition and (b) the use of criteria that require the clinician to make judgments about internal states that are difficult to evaluate in an objective manner (e.g., intentional versus unintentional production of exaggerated symptoms). Two diagnostic categories--Cogniform Disorder and Cogniform Condition--are proposed as new subtypes of the Somatoform Disorders to encompass cases of excessive cognitive complaints and inadequate test-taking effort in the absence of sufficient evidence to diagnose Malingering. Of the two new categories, Cogniform Disorder is defined as a more pervasive form in which the individual tends to exhibit the excessive cognitive symptoms in widespread areas of his or her life, thereby suggesting a conversion-like adoption of the sick role manifested primarily as cognitive dysfunction. Guidelines for improving the evidence-based diagnosis of these cases, particularly with regards to criteria related to intentionality, secondary gain, and sick role factors, are also discussed.     

Global-local processing in schizophrenia: hemispheric asymmetry and symptom-specific interference.

The hypothesis of atypical functional hemispheric asymmetry in schizophrenia is tested using the directed global-local paradigm, a lateralizing measure of visual perception. Results indicate low error rates (< 2%) for schizophrenia and normal control groups, but longer response times for the schizophrenia group. In the normal group, detection speed of global and local forms did not differ. In contrast, the schizophrenia group responded significantly faster to local relative to global forms, which supports the asymmetry hypotheses of left hemisphere overactivity-right hemisphere underactivity in schizophrenia. The normal group exhibited a global interference effect (slowed response latency to the local target in the presence of a dissimilar global distractor). When the schizophrenia group was examined according to symptom type and severity, high positive symptom severity was associated with local interference (slowed response latency to the global target in the presence of dissimilar local distractors). Negative symptoms were not associated with interference from the competing local or global forms. Patients with a combination of high positive and low negative symptoms showed significantly greater local interference than patients with high negative and low positive symptoms. Interconnected temporal and frontal systems are postulated to contribute to this pattern of perceptual processing efficiency and distractibility in schizophrenia.     

Effect of intermittent pneumatic foot compression on popliteal artery haemodynamics.

PURPOSE: the aim was to investigate the effect of intermittent pneumatic foot compression (IPC(foot)) on popliteal artery haemodynamics in normal individuals and in patients with intermittent claudication due to peripheral vascular disease (PVD) (Fontaine stage II). MATERIAL AND METHODS: popliteal artery volume flow [vFl], pulsatility index [PI], mean velocity [mV], peak systolic [PSV] and end diastolic velocity [EDV], in 25 limbs of 20 normal subjects and 40 limbs of 32 stable claudicants were obtained in the sitting position before, during and within 30 seconds after the application of IPC(foot)(applied pressure: 120 mmHg; inflation time: 3 seconds; deflation time: 17 seconds) using colour-flow duplex imaging (CFDI). The reproducibility of flow velocity estimations using CFDI in the horizontal [hor] (recovery) and sitting [sit] positions was evaluated in 20 limbs of normal controls and 20 limbs of claudicants. RESULTS: popliteal artery vFl, mV, PSV and PI measurements were performed with a coefficient of variation (CV) of less than 14.6% among claudicants and of less than 13.3% in normal subjects. EDV is the least reproducible parameter with an overall CV range of 10.2-21.5% in normal controls and 9.1-18.6% in arteriopaths. On application of IPC(foot)popliteal artery vFl increased by 111% in the control group (p<0.001) and by 51% in the claudicants (p<0.001). Within 30 seconds of the cessation of pump action flow decreased significantly in both groups (p<0.001), but maintained a significantly higher level than that at baseline (p<0. 001, in both groups). The mV, PSV and EDV showed a similar pattern of significant changes. Both in normals and claudicants, the PI decreased with IPC(foot)(p<0.001) and increased post-compression; however, it was significantly lower than baseline (p<0.005) within 30 seconds of impulse delivery. CONCLUSIONS: current CFDI technology enables a reproducible estimation of popliteal artery flow velocities. IPC(foot)can significantly augment arterial calf inflow on an acute basis both in normals and claudicants. The increase of EDV and decrease of PI indicate that attenuation of peripheral resistance to flow is the main mechanism underlying the popliteal artery vFl enhancement on application of IPC(foot). Prospective trials on the long-term effect of IPC(foot)in the management of patients with PVD are indicated from the results of this study.     

Can electronic zoom replace magnification in mammography? A comparative Monte Carlo study

Magnification, which is considered to be a relatively high "dose cost" mammographic technique, is a complementary examination performed on women exhibiting breast complaints or abnormalities. Particular attention is given to the imaging procedure as the primary aim is to confirm the existence of suspected abnormalities, despite the additional dose. The introduction of post-processing capabilities and the widespread use of digital mammography promoted some controversy in the last decades on whether electronic zoom performed on the derived initial screening mammogram can effectively replace this technique. This study used Monte Carlo simulation methods to derive simulated screening mammograms produced under several exposure conditions, aiming to electronically magnify and compare them to the corresponding magnification mammograms. Comparison was based on quantitative measurements of image quality, namely contrast to noise ratio (CNR) and spatial resolution. Results demonstrated that CNR was higher for geometric magnification compared to the case of electronic zooming. The percentage difference was higher for lesions of smaller radius and achieved 29% for 0.10 mm details. Although spatial resolution is maintained high in the zoomed images, when investigating microcalcifications of 0.05 mm radius or less, only with geometric magnification can they be visualised.The carcinogenic risk associated with the delivery of high radiation doses such as those related to magnification views in mammography, in addition to the requirements for high image quality, have made it essential to optimise this technique. Although this radiation risk is considered to be relatively insignificant in the context of accurate diagnosis, work-up and treatment, an investigation has started for alternative techniques that could provide equivalent or improved characterisation of lesions and improved diagnostic information compared with that obtained from magnification views. The psychological “cost” of a woman being recalled for a second mammographic examination, the discomfort from the breast compression and the economic impact of an additional examination are also factors that have promoted research into alternative procedures that complement the information provided by standard mammography.For many decades, magnification mammographic images of selected breast regions have been considered the most effective diagnostic tool for enhancing the visibility of subtle suspicious breast lesions and microcalcifications, thus providing improved diagnostic sensitivity and specificity. To this end, screen-film radiography was the gold standard for many decades and has now been replaced with digital radiography, which can also be combined with digital post-processing methods. The enhancement of visibility in magnification views is attributed to the increase in contrast to noise ratio (CNR) caused by the increased fluence per irradiated area. The CNR increases with the degree of magnification, particularly for low degrees (increase of 75% between degrees 1.0 and 1.4) [5]. By contrast, a major disadvantage of magnification is the additional and significantly high dose of radiation delivered to the breast compared with the contact case. Owing to the fact that the breast is placed closer to the X-ray focal spot, both the entrance dose at the skin surface and the mean glandular dose (MGD) to the irradiated part of the breast are considerably higher than for the corresponding contact view. Typically, MGD is doubled at 1.5× magnification compared with a standard mammogram. Thus, there is an increased radiation risk [6, 7]. Regarding spatial resolution, this is significantly degraded as magnification increases owing to the finite dimensions of the focal spot and the detrimental penumbra effects [8, 9]. At the same time, however, spatial resolution is improved due to the effective detector resolution, which depends on the irradiated object''s size on the detector plane [9]. For the low degrees of magnification usually applied in clinical practice, the overall system resolution is improved with magnification. However, for higher degrees it is degraded owing to the dominant effect of the focal spot dimensions [9, 10].Among the new techniques introduced in the effort to replace magnification views, image post-processing, often facilitated by digital mammography, has become very popular [11–13]. Electronic magnification (zoom) of digital (or digitised) screening mammograms has recently come to the foreground of this research area and many authors are addressing this alternative. A question that arises is whether the image quality provided by electronic zoom is comparable to that provided by the (original) geometric magnification views. If not, another question arises – whether the dose-saving provided by electronic zooming can compensate for a potential detriment in image quality.Several studies have been performed, most involving observers, to evaluate the image quality provided by the two techniques. Perisinakis et al [4] demonstrated that the enhancement of image features through post-processing (zooming) of both digitised contact images and geometric magnification mammograms equally improved the visualisation of subtle microcalcifications that are only rarely identified in standard full-field screen-film mammograms. Similar results have been reported by Vyborny et al [11], Smathers et al [14] and Powell et al [15]. These authors also showed that lesion visualisation achieved with geometric magnification mammograms (without the application of further post-processing) was similar to that achieved by electronic magnification and processing of the contact full-field image. Chan et al [16] showed that geometric magnification combined with stereotactic imaging in mammography provides better results than electronic display zooming of the contact stereotactic images.Smith et al [17] included the radiologist''s experience in their study; the authors demonstrated that, when evaluating microcalcifications, radiologists less experienced in mammography should not replace digitised and enhanced contact mammograms for microfocal-spot magnified mammograms. Other studies in this area have been reported in recent years [18–23] and, despite the fact that their conclusions vary, most exhibit a common characteristic: they are based on subjective human perception and decision criteria, known to vary significantly, rather than on objective metrics of image quality such as CNR and spatial resolution. Moreover, to our knowledge, to date no studies have been published comparing the primary image for both techniques without the application of additional post-processing methods (e.g. denoising or enhancement), based only on objective metrics of image quality.In this study, a validated Monte Carlo model developed for producing simulated mammographic images under exposure conditions representative of clinical mammography was used. Sets of standard contact and geometrically magnified mammograms were produced using the same output. The contact mammograms were then electronically magnified (zoomed) and compared with the corresponding images produced with the geometric magnification with no further post-processing undertaken. The comparison was based on CNR (derived from signal and noise measured in the images and their background) and spatial resolution.     

Transarterial Chemoembolization of Unresectable Hepatocellular Carcinoma with Drug Eluting Beads: Results of an Open-Label Study of 62 Patients

The purpose of this study was to assess the safety and efficacy of doxorubicin-loaded beads (DC Beads) delivered by transarterial embolization for the treatment of unresectable hepatocellular carcinoma (HCC). This open-label, single-center, single-arm study included 62 cirrhotic patients with documented single unresectable HCC. Mean tumor diameter was 5.6 cm (range, 3–9 cm) classified as Okuda stages 1 (n = 53) and 2 (n = 9). Patients received repeat embolizations with doxorubicin-loaded beads every 3 months (maximum of three). The maximum doxorubicin dose was 150 mg per embolization, loaded in DC Beads of 100–300 or 300–500 μm. Regarding efficacy, overall, an objective response according to the European Association for the Study of the Liver criteria was observed in 59.6%, 81.8%, and 70.8% across three treatments. A complete response was observed in 4.8% after the first procedure and 3.6% and 8.3% after the second and third procedures, respectively. At 9 months a complete response was seen in 12.2%, an objective response in 80.7%, progressive disease in 6.8%, and 12.2% showed stable disease. Mean tumor necrosis ranged from 77.4% to 83.9% (range, 28.6%–100%) across three treatments. α-Fetoprotein levels showed a mean decrease of 1123 ng/ml (95% CI = 846–1399; p = 3 × 10^–11) after the first session and remained stable after the second and third embolizations (42 and 70 ng/ml decrease, respectively). Regarding safety, bilirubin, γ-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase showed only transient increases during the study period. Severe procedure-related complications were seen in 3.2% (cholecystitis, n = 1; liver abscess, n = 1). Postembolization syndrome was observed in all patients. We conclude that hemoembolization using doxorubicin-loaded DC Beads is a safe and effective treatment of HCC as demonstrated by the low complication rate, increased tumor response, and sustained reduction of α-fetoprotein levels.     

Norms for depressed patients for the California verbal learning test: associations with depression severity and self-report of cognitive difficulties.

This study provides norms for depressed subjects for a widely used test of verbal memory, the California Verbal Learning Test (CVLT). Subjects were 156 outpatients with major depression tested during a drug washout period. Mean CVLT memory scores for these patients were generally between one-half and one standard deviation below age- and sex-corrected norms for nondepressed populations. Severity of depression in the patients was not associated with memory performance, but was associated with self-report of cognitive difficulties. A table of age-, sex-, and education-specific norms for the CVLT is provided.     

Discriminant validity and neuroanatomical correlates of rule monitoring in frontotemporal dementia and Alzheimer's disease

Despite the predominant frontal neuropathology of frontotemporal dementia (FTD), traditional measures of executive functioning do not reliably distinguish FTD from Alzheimer's disease (AD). Performance monitoring is an executive function that is associated with frontal lobe integrity and may be disrupted in FTD. The current study adopted a component process approach to evaluate the discriminant validity and neuroanatomical correlates of performance monitoring (i.e., rule monitoring) during an executive spatial planning task. Forty-four participants with FTD, 30 with AD, and 27 healthy comparison (HC) subjects completed the Delis-Kaplan Executive Function System (D-KEFS) Tower task. A subset of patients underwent structural magnetic resonance imaging to obtain regional measures of cortical volumes. FTD and AD groups demonstrated significantly poorer overall achievement scores on the Tower test relative to the HC sample, but did not differ from one another. In contrast, the FTD group committed significantly more rule violation errors than both HC and AD groups, indicating poorer performance monitoring. In addition, poorer overall achievement correlated with smaller brain volumes in several regions, including bilateral frontal and parietal regions, whereas an increased number of rule violations correlated specifically with decreased bilateral frontal volume. Both left and right frontal volumes remained significant predictors of rule violation errors after controlling for the contribution of overall achievement on the task and all other brain regions. Findings are consistent with literature implicating the frontal lobes in performance monitoring and highlight the importance of characterizing the component processes of performance failures in the cognitive assessment of FTD and AD.