Monorail™ Piccolino catheter: A new rapid exchagne/ultralow profile coronary angioplasty system

The Monorail^TM Piccolino coronary angioplasty balloon catheter (MBC) was evaluated on 118 patients at two centers. Technical success was achieved in 110 patients (93%). Time for catheter exchange and total fluoroscopy time were significantly lower for the Monorail catheter than with standard equipment (exchange time 97 vs. 170 seconds P <.05 and fluoroscopy time 17 vs. 88 seconds P < 0.001). The advantages of rapid exchange and the ability of utilize 2 Monorail balloon catheters through one 9F guiding catheter for simultaneous inflations allowed for maximal flexibility in treating patients with bifurcation lesions. The double wire approach utilizing one Monorail balloon catheter with a 7F guiding catheter was also technically successful. The Monorail^TM Piccolino balloon catheter has unique features that allow for greater ease of operator use, rapid catheter exchange, and optimal angiographic visualization. It is felt that this catheter design provides distinct advantages over standard angioplasty equipment.     

Glucose-6-phosphate dehydrogenase modulates cytosolic redox status and contractile phenotype in adult cardiomyocytes

Reactive oxygen species (ROS)-mediated cell injury contributes to the pathophysiology of cardiovascular disease and myocardial dysfunction. Protection against ROS requires maintenance of endogenous thiol pools, most importantly, reduced glutathione (GSH), by NADPH. In cardiomyocytes, GSH resides in two separate cellular compartments: the mitochondria and cytosol. Although mitochondrial GSH is maintained largely by transhydrogenase and isocitrate dehydrogenase, the mechanisms responsible for sustaining cytosolic GSH remain unclear. Glucose-6-phosphate dehydrogenase (G6PD) functions as the first and rate-limiting enzyme in the pentose phosphate pathway, responsible for the generation of NADPH in a reaction coupled to the de novo production of cellular ribose. We hypothesized that G6PD is required to maintain cytosolic GSH levels and protect against ROS injury in cardiomyocytes. We found that in adult cardiomyocytes, G6PD activity is rapidly increased in response to cellular oxidative stress, with translocation of G6PD to the cell membrane. Furthermore, inhibition of G6PD depletes cytosolic GSH levels and subsequently results in cardiomyocyte contractile dysfunction through dysregulation of calcium homeostasis. Cardiomyocyte dysfunction was reversed through treatment with either a thiol-repleting agent (L-2-oxothiazolidine-4-carboxylic acid) or antioxidant treatment (Eukarion-134), but not with exogenous ribose. Finally, in a murine model of G6PD deficiency, we demonstrate the development of in vivo adverse structural remodeling and impaired contractile function over time. We, therefore, conclude that G6PD is a critical cytosolic antioxidant enzyme, essential for maintenance of cytosolic redox status in adult cardiomyocytes. Deficiency of G6PD may contribute to cardiac dysfunction through increased susceptibility to free radical injury and impairment of intracellular calcium transport. The full text of this article is available online at http://www.circresaha.org.     

Breathing pattern and eye movement density during REM sleep in humans

Changes in the density of eye movement during rapid eye movement (REM) sleep are associated with changes in ventilation and ventilatory response in animals. Recent data in patients with chronic obstructive pulmonary disease suggest that periods of frequent eye movements may be associated with hypoxemia during REM sleep. We have therefore investigated the association between eye movements and ventilation and ventilatory pattern in 10 normal men. Expired ventilation was measured using a pneumotachograph attached to a valved face mask with a dead space of 50 ml and incorporating a peripheral CO2 leak detector. Ventilation was reduced (p less than 0.02) in all stages of sleep compared with that during wakefulness, with no difference between the level of ventilation in each sleep stage (awake, 7.18 +/- 0.43 SEM; Stage 2, 6.47 +/- 0.43; Stage 3/4, 6.45 +/- 0.52; REM sleep, 6.55 +/- 0.47 L/min). During REM sleep, eye movements (EMs) were associated with rapid shallow breathing. Dividing REM into 20-s epochs with or without EMs, EMs were associated with a raised breathing frequency (no EMs, 14.4 +/- 0.4 breaths/min; EMs, 15.8 +/- 0.5 breaths/min; p = 0.01), reduced tidal volume (0.49 +/- 0.03 L; 0.41 +/- 0.03 L; p less than 0.01), and reduced minute ventilation (6.87 +/- 0.45 L; 6.27 +/- 0.51 L; p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Detection of clonal platelet antibodies in immunologically-mediated thrombocytopenias: association with circulating clonal/oligoclonal B cells

Summary Aware that T and B cells in autoimmune thrombocytopenia are abnormal, including the existence of clonal B cell populations, we sought to characterize this clonal phenomenon in various immunological thrombocytopenias using platelet antibody light chain analysis, flow cytometry, Southern blot analysis, and PCR. Using a monoclonal antibody-antigen capture ELISA, we analysed sera from 21 of 26 patients with autoimmune, alloimmune. or drug-induced immunological thrombocytopenia for the light chain phenotypes of their platelet antibodies. Alloantibodies and drug-dependent antibodies from four and 14 patients, respectively, were found that expressed a predominant type of light chain, suggesting that these platelet-reactive antibodies were monoclonal or oligoclonal in nature. 14 of the 26 patients were available for light chain B cell phenotyping studies. Of these 14 patients, thrombocytopenia was due to autoimmunity in two, drug-induced immunity in four, and alloimmunity in eight. We detected clonal populations of B cells in all 14 patients by flow cytometry. Although six of these latter patients possessed platelet antibodies with clonal characteristics, light chain phenotypes of antibodies in five patients were opposite to those of their B cells. Eight of these patients were further examined for immunoglobulin gene rearrangement using Southern and/or polymerase chain reaction analysis. In all eight patients we detected clonal or oligoclonal B cell populations. Only two of these patients had malignancies (chronic lymphocytic leukaemia) that would be expected to have detectable clonal B cells, and thus the mechanism for clonal expansion in the other six patients did not appear to he related to an obvious neoplastic process. Prior to these studies, detection of clonal B cells in thrombocytopenic patients without known malignancies was limited to individuals with autoimmune thrombocytopenia, prompting the speculation that this particular autoimmune disorder arises from B cell dysregulation, rather than from expansion of specific autoantibody producing B cell clones. In contrast, the current studies provide evidence that clonal B cells are common to patients with any form of immunologically-mediated thrombocytopenia. Moreover, the majority of the platelet antibodies (86%) present in these disorders exhibited monoclonal characteristics in that there was an apparent restriction in light chain usage.     

Constraining eye movement when redirecting walking trajectories alters turning control in healthy young adults

Humans use a specific steering synergy, where the eyes and head lead rotation to the new direction, when executing a turn or change in direction. Increasing evidence suggests that eye movement is critical for turning control and that when the eyes are constrained, or participants have difficulties making eye movements, steering control is disrupted. The purpose of the current study was to extend previous research regarding eye movements and steering control to a functional walking and turning task. This study investigated eye, head, trunk, and pelvis kinematics of healthy young adults during a 90° redirection of walking trajectory under two visual conditions: Free Gaze (the eyes were allowed to move naturally in the environment), and Fixed Gaze (participants were required to fixate the eyes on a target in front). Results revealed significant differences in eye, head, and trunk coordination between Free Gaze and Fixed Gaze conditions (p < 0.001). During Free Gaze, the eyes led reorientation followed by the head and trunk. Intersegment timings between the eyes, head, and trunk were significantly different (p < 0.05). In contrast, during Fixed Gaze, the segments moved together with no significant differences between segment onset times. In addition, the sequence of segment rotation during Fixed Gaze suggested a bottom-up postural perturbation control strategy in place of top-down steering control seen in Free Gaze. The results of this study support the hypothesis that eye movement is critical for the release of the steering synergy for turning control.     

Adapting to inversion of the visual field: a new twist on an old problem

While sensorimotor adaptation to prisms that displace the visual field takes minutes, adapting to an inversion of the visual field takes weeks. In spite of a long history of the study, the basis of this profound difference remains poorly understood. Here, we describe the computational issue that underpins this phenomenon and presents experiments designed to explore the mechanisms involved. We show that displacements can be mastered without altering the updated rule used to adjust the motor commands. In contrast, inversions flip the sign of crucial variables called sensitivity derivatives—variables that capture how changes in motor commands affect task error and therefore require an update of the feedback learning rule itself. Models of sensorimotor learning that assume internal estimates of these variables are known and fixed predicted that when the sign of a sensitivity derivative is flipped, adaptations should become increasingly counterproductive. In contrast, models that relearn these derivatives predict that performance should initially worsen, but then improve smoothly and remain stable once the estimate of the new sensitivity derivative has been corrected. Here, we evaluated these predictions by looking at human performance on a set of pointing tasks with vision perturbed by displacing and inverting prisms. Our experimental data corroborate the classic observation that subjects reduce their motor errors under inverted vision. Subjects’ accuracy initially worsened and then improved. However, improvement was jagged rather than smooth and performance remained unstable even after 8 days of continually inverted vision, suggesting that subjects improve via an unknown mechanism, perhaps a combination of cognitive and implicit strategies. These results offer a new perspective on classic work with inverted vision.