Role of osmolality in blood pressure stability after dialysis and ultrafiltration

Role of osmolality in blood pressure stability after dialysis and ultrafiltration. To clarify the mechanisms involved in the stability of blood pressure during ultrafiltration (UF) alone versus regular dialysis, this study systematically examined the importance of changes in serum potassium, osmolality, and plasma norepinephrine during several dialysis maneuvers. Six stable, normotensive chronic dialysis patients were subjected to a uniform 2 to 3% decrease in body weight during the 2 hours of each dialysis maneuver. Supine to upright mean blood pressure (MBP) decreased (90 to 75 mm Hg, P < 0.05), and three patients became symptomatic after weight loss during regular dialysis, but orthostatic blood pressure was stable (89 to 86 mm Hg, NS) and the patients were asymptomatic after UF and weight loss. Isokalemic regular dialysis did not afford hemodynamic stability, as orthostatic MBP declined (85 to 56 mm Hg, P < 0.02), and four of the patients again were symptomatic after standing. A continuous hypertonic mannitol (25%) infusion during the 2-hour dialysis, however, kept osmolality from decreasing and was associated with a stable orthostatic MBP (89 to 83 mm Hg, NS). A continuous infusion of isotonic mannitol (5%) given in a volume five times that of the hypertonic mannitol failed to prevent orthostatic hypotension (89 to 60 mm Hg, P < 0.005). Plasma norepinephrine concentrations were high in these patients and increased only modestly after weight loss. These results implicate constant plasma osmolality as a critical protective factor of blood pressure during UF and further demonstrate that changes in blood pressure may be dissociated from changes in both serum potassium and plasma norepinephrine concentration.Rôle de l'osmolalité dans la stabilité de la pression artérielle après dialyse et ultrafiltration. Afin de clarifier les mécanismes impliqués dans la stabilité de la pression artérielle au cours de l'ultrafiltration (UF) seule par comparaison avec la dialyse habituelle ce travail évalue systématiquement l'importance des modifications de la kaliémie, de l'osmolalité et de la norépinéphrine plasmatique au cours de plusieurs tactiques de dialyse. Six sujets stables, normotendus, en hémodialyse chronique ont subi une diminution de poids corporel de 2 à 3% au cours des 2 heures de chaque tactique de dialyse. La pression artérielle moyenne a diminué de la position couchée à la position debout (de 90 à 75 mm Hg, P < 0,05) et trois patients sont devenus symptomatiques après la perte de poids au cours de la dialyse habituelle. Par contre la pression artérielle orthostatique a été stable (89 à 86 mm Hg, NS) et les malades ont été asymptomatiques après UF. La dialyse habituelle isokaliémique n'a pas déterminé de stabilité hémodynamique, la pression artérielle moyenne orthostatique a diminué (85 à 56 mm Hg, P < 0,02) et quatre malades ont été à nouveau symptomatiques quand ils se sont levés. Cependant quand une perfusion continue de mannitol hypertonique (25%) pendant les deux heures de la dialyse a empêché la baisse de l'osmolalité la pression artérielle moyenne orthostatique a été stable (89 à 83 mm Hg, NS). Une perfusion continue de mannitol isotonique (5%) apportant un volume cinq fois celui du mannitol hypertonique n'a pas empêché l'hypotention orthostatique (89 à 60 mm Hg, P < 0,005). Les concentrations plasmatiques de norépinéphrine étaient élevées chez ces malades et n'ont que peu augmenté après la perte de poids. Ces résultats impliquent qu'une osmolalité plasmatique constante est un facteur protecteur critique pour la pression artérielle au cours de UF et ils démontrent, de plus, que les modifications de la pression artérielle peuvent être dissociées des modifications du potassium plasmatique et de la concentration de norépinéphrine

Improved left ventricular contractility with cool temperature hemodialysis

Improved left ventricular contractility with cool temperature hemodialysis. Cool temperature dialysis (CTD) has been shown to sharply decrease the frequency of intradialytic hemodialysis hypotension, but the mechanism of this hemodynamic protection is unknown. Therefore, we performed two-dimensional echocardiographic studies of left ventricular contractility in six stable hemodialysis patients before and after hemodialysis at 37°C (RTD) and 35°C (CTD). Left ventricular function was assessed by plotting the rate-corrected velocity of circumferential fiber shortening (Vcfc) against end-systolic wall stress (σes) at four different levels of afterload. Linear regression was used to calculate Vcfc at a common afterload of 50 g/cm2. Changes in weight and dialysis parameters were similar following RTD and CTD. Mean arterial pressure and heart rate did not change significantly following RTD or CTD. The Vcfc – σes relation was shifted upward in each patient after CTD, indicating increased contractility as compared to RTD or pre-dialysis baseline. Pre-dialysis Vcfc at an afterload of 50 g/cm2 was similar during RTD and CTD (0.94 ± 0.24 circ/sec vs. 0.92 ± 0.22 circ/sec). Post-dialysis Vcfc at an afterload of 50 g/cm2 was significantly higher for CTD than for RTD (1.13 ± 0.29 circ/sec vs. 0.98 ± 0.30 circ/sec, P = 0.0004). Thus, cool temperature dialysis increases left ventricular contractility in hemodialysis patients, which may be a potential mechanism whereby hemodynamic tolerance to the dialysis procedure is improved

Innovative Research Exploring the Effects of Physical Activity and Genetics on Cognitive Performance in Community-Based Older Adults

Physical activity is predictive of better cognitive performance and lower risk of Alzheimer’s disease (AD). The apolipoprotein E gene (APOE) is a susceptibility gene for AD with the e4 allele being associated with a greater risk of AD. Cross-sectional and prospective research shows that physical activity is predictive of better cognitive performance for those at greater genetic risk for AD. However, the moderating role of APOE on the effects of a physical activity intervention on cognitive performance has not been examined. The purpose of this manuscript is to justify the need for such research and to describe the design, methods, and recruitment tactics used in the conductance of a study designed to provide insight as to the extent to which cognitive benefits resulting from an 8-month physical activity program are differentiated by APOE e4 status. The effectiveness of the recruitment strategies and the feasibility of recruiting APOE e4 carriers are discussed

Prediction of cardiovascular outcomes with machine learning techniques: application to the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study.

Background: Data derived from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study were analyzed in an effort to employ machine learning methods to predict the composite endpoint described in the original study. Methods: We identified 573 CORAL subjects with complete baseline data and the presence or absence of a composite endpoint for the study. These data were subjected to several models including a generalized linear (logistic-linear) model, support vector machine, decision tree, feed-forward neural network, and random forest, in an effort to attempt to predict the composite endpoint. The subjects were arbitrarily divided into training and testing subsets according to an 80%:20% distribution with various seeds. Prediction models were optimized within the CARET package of R. Results: The best performance of the different machine learning techniques was that of the random forest method which yielded a receiver operator curve (ROC) area of 68.1%±4.2% (mean ± SD) on the testing subset with ten different seed values used to separate training and testing subsets. The four most important variables in the random forest method were SBP, serum creatinine, glycosylated hemoglobin, and DBP. Each of these variables was also important in at least some of the other methods. The treatment assignment group was not consistently an important determinant in any of the models. Conclusion: Prediction of a composite cardiovascular outcome was difficult in the CORAL population, even when employing machine learning methods. Assignment to either the stenting or best medical therapy group did not serve as an important predictor of composite outcome. Clinical Trial Registration: ClinicalTrials.gov, NCT00081731

Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related viruses

In 2009, a newly discovered human retrovirus, xenotropic murine leukemia virus (MuLV)-related virus (XMRV), was reported by Lombardi et al. in 67% of persons from the US with chronic fatigue syndrome (CFS) by PCR detection of gag sequences. Although six subsequent studies have been negative for XMRV, CFS was defined more broadly using only the CDC or Oxford criteria and samples from the US were limited in geographic diversity, both potentially reducing the chances of identifying XMRV positive CFS cases. A seventh study recently found polytropic MuLV sequences, but not XMRV, in a high proportion of persons with CFS. Here we tested blood specimens from 45 CFS cases and 42 persons without CFS from over 20 states in the United States for both XMRV and MuLV. The CFS patients all had a minimum of 6 months of post-exertional malaise and a high degree of disability, the same key symptoms described in the Lombardi et al. study. Using highly sensitive and generic DNA and RNA PCR tests, and a new Western blot assay employing purified whole XMRV as antigen, we found no evidence of XMRV or MuLV in all 45 CFS cases and in the 42 persons without CFS. Our findings, together with previous negative reports, do not suggest an association of XMRV or MuLV in the majority of CFS cases

Detection of Murine Leukemia Virus or Mouse DNA in Commercial RT-PCR Reagents and Human DNAs

The xenotropic murine leukemia virus (MLV)-related viruses (XMRV) have been reported in persons with prostate cancer, chronic fatigue syndrome, and less frequently in blood donors. Polytropic MLVs have also been described in persons with CFS and blood donors. However, many studies have failed to confirm these findings, raising the possibility of contamination as a source of the positive results. One PCR reagent, Platinum Taq polymerase (pol) has been reported to contain mouse DNA that produces false-positive MLV PCR results. We report here the finding of a large number of PCR reagents that have low levels of MLV sequences. We found that recombinant reverse-transcriptase (RT) enzymes from six companies derived from either MLV or avian myeloblastosis virus contained MLV pol DNA sequences but not gag or mouse DNA sequences. Sequence and phylogenetic analysis showed high relatedness to Moloney MLV, suggesting residual contamination with an RT-containing plasmid. In addition, we identified contamination with mouse DNA and a variety of MLV sequences in commercially available human DNAs from leukocytes, brain tissues, and cell lines. These results identify new sources of MLV contamination and highlight the importance of careful pre-screening of commercial specimens and diagnostic reagents to avoid false-positive MLV PCR results

Culture and Hallucinations: Overview and Future Directions

A number of studies have explored hallucinations as complex experiences involving interactions between psychological, biological, and environmental factors and mechanisms. Nevertheless, relatively little attention has focused on the role of culture in shaping hallucinations. This article reviews the published research, drawing on the expertise of both anthropologists and psychologists. We argue that the extant body of work suggests that culture does indeed have a significant impact on the experience, understanding, and labeling of hallucinations and that there may be important theoretical and clinical consequences of that observation. We find that culture can affect what is identified as a hallucination, that there are different patterns of hallucination among the clinical and nonclinical populations, that hallucinations are often culturally meaningful, that hallucinations occur at different rates in different settings; that culture affects the meaning and characteristics of hallucinations associated with psychosis, and that the cultural variations of psychotic hallucinations may have implications for the clinical outcome of those who struggle with psychosis. We conclude that a clinician should never assume that the mere report of what seems to be a hallucination is necessarily a symptom of pathology and that the patient’s cultural background needs to be taken into account when assessing and treating hallucinations