Effects of Hatchery Rearing Density, Handling, and Nutrition on Renibacterium salmoninarum Infection Prevalence in Juvenile Chinook Salmon.

Bacterial kidney disease, caused by Renibacterium salmoninarum (RS), is a chronic and often fatal disease of salmonid species, and can be particularly harmful to hatchery-reared Chinook Salmon Oncorhynchus tshawytscha. A considerable amount of research has focused on the prevention of vertical and horizontal transmission; however, a comparatively little amount has investigated factors that increase the prevalence of RS infection in captive environments. We evaluated the effects of three common hatchery conditions (handling, nutrition level, and rearing density) on RS infection prevalence. Fish were sampled at 30-d and 60-d postexposure to RS. Of 577 juveniles examined, 65 (11.27%) had anterior kidneys infected with RS. Using a logistic mixed model analysis, we found effects of nutrition level (P = 0.018), handling (P = 0.010), and sampling period (P = 0.003) on the prevalence of RS. The interactions of nutrition and handling (P = 0.008) and nutrition and time (P < 0.001) were also significant. When fed a standard-nutrition diet, proportionately fewer fish were infected with RS when not handled (7.16% versus 0.04%; P = 0.003). Fish in the standard-nutrition group also had a lower prevalence of RS during the second sampling period (4.08% versus 0.08%, respectively; P < 0.001). When not handled, rearing with standard nutrition (11.50% versus 0.04%; P = 0.004) resulted in a reduction in prevalence of RS infection. Additionally, nonhandled fish had a much lower prevalence of RS infection during the second sampling period (2.66% versus 0.21%; P = 0.009). While density did not affect the prevalence of RS infection (P = 0.145), fish reared at a higher density had lower RS infection when not handled (16.48% versus 0.84%, P = 0.004). For fish at a higher density, the RS prevalence was lower during the second sampling period (10.57% versus 1.40%; P = 0.002). Our results suggest that hatchery managers can reduce RS infection prevalence by maintaining an adequate nutritional regime as recommended by the manufacturer. Additionally, the prevalence of RS may be reduced if managers decrease handling of hatchery-reared Chinook Salmon if exposed to RS.

Variability in Radiation Dose From Repeat Identical CT Examinations: Longitudinal Analysis of 2851 Patients Undergoing 12,635 Thoracoabdominal CT Scans in an Academic Health System.

OBJECTIVE: The purpose of this study was to conduct longitudinal analyses of radiation dose data from adult patients undergoing clinically indicated, repeat identical thoracoabdominal CT examinations. MATERIALS AND METHODS: Radiation dose data were electronically collected from 2851 subjects undergoing 12,635 repeat identical CT scans (mean number of scans per patient, 4.8; range, 2-33) in one health system. Included CT protocols were chest-abdomen-pelvis with contrast administration (n = 4621 CT studies of 1064 patients), abdomen-pelvis with contrast administration (n = 876 CT studies of 261 patients), renal stone (n = 1053 CT studies of 380 patients), and chest (n = 6085 CT studies of 1146 patients) without contrast administration. A radiation-tracking software infrastructure was adopted to extract data from DICOM headers in PACS. Size-specific dose estimate (SSDE) was calculated. RESULTS: A trend was observed toward global reduction in SSDE values with all protocols investigated (chest-abdomen-pelvis slope, -1.78; abdomen-pelvis slope, -0.82; renal stone slope, -0.83; chest slope, -0.47; p < 0.001 for all comparisons). The intraindividual analyses of radiation dose distribution showed widespread variability in SSDE values across the four protocols investigated (chest-abdomen-pelvis mean coefficient of variance, 14.02 mGy; abdomen-pelvis mean coefficient of variance, 10.26 mGy; renal stone mean coefficient of variance, 34.18 mGy; chest mean coefficient of variance, 6.74 mGy). CONCLUSION: Although there is a trend toward global reduction in radiation doses, this study showed widespread variability in the radiation dose that each patient undergoing identical repeat thoracoabdominal CT protocols absorbs. These data may provide a foundation for the future development of best-practice guidelines for patient-specific radiation dose monitoring.

A Physical Heart Failure Simulation System Utilizing the Total Artificial Heart and Modified Donovan Mock Circulation.

With the growth and diversity of mechanical circulatory support (MCS) systems entering clinical use, a need exists for a robust mock circulation system capable of reliably emulating and reproducing physiologic as well as pathophysiologic states for use in MCS training and inter-device comparison. We report on the development of such a platform utilizing the SynCardia Total Artificial Heart and a modified Donovan Mock Circulation System, capable of being driven at normal and reduced output. With this platform, clinically relevant heart failure hemodynamics could be reliably reproduced as evidenced by elevated left atrial pressure (+112%), reduced aortic flow (-12.6%), blunted Starling-like behavior, and increased afterload sensitivity when compared with normal function. Similarly, pressure-volume relationships demonstrated enhanced sensitivity to afterload and decreased Starling-like behavior in the heart failure model. Lastly, the platform was configured to allow the easy addition of a left ventricular assist device (HeartMate II at 9600 RPM), which upon insertion resulted in improvement of hemodynamics. The present configuration has the potential to serve as a viable system for training and research, aimed at fostering safe and effective MCS device use.

Reliability of the Thoratec HeartMate II flow measurements and alarms in the presence of reduced or non-existent flow.

INTRODUCTION: The Thoratec Corporation has over 10,000 patients registered as recipients of the HeartMate II left ventricular assist device (LVAD) worldwide. Although it has undoubtedly prolonged the lifespan of heart failure patients, the most recognized risk associated with these devices is the development of thrombus. In the presence of a small or developing clot, the HeartMate II display module and system monitor indicate that there is a decrease in pump flow, adjusts its pump power and is accompanied by audible and visual alarms when flow rates drop below a fixed threshold established by Thoratec. In contrast, when thrombus completely inhibits flow through the device, the display module and system monitor have failed in previous case studies to indicate that flow has reduced to zero and do not produce any corresponding alarms. METHODS: To test the efficacy of the HeartMate II alarms, a cardiovascular simulation tank was used to reproduce the hemodynamics of a typical heart failure patient. The hemodynamics were then improved by the addition of the HeartMate II LVAD and different partial and complete occlusions were applied to the inlet and outlet of the HeartMate II pump. CONCLUSIONS: Partially occluding the inflow and/or outflow of the HeartMate II did display changes in flow and presented with alarms when flow was estimated to be below 2.5 L/min; however, complete occlusion of the inflow and/or outflow failed to produce any alarms or accurately measured changes in flow.

Respiratory motion artifact affecting hepatic arterial phase MR imaging with gadoxetate disodium is more common in patients with a prior episode of arterial phase motion associated with gadoxetate disodium.

PURPOSE: To determine, in a dual-center setting, whether patients who experience transient severe motion ( TSM transient severe motion ) in the arterial phase during gadoxetate disodium-enhanced magnetic resonance (MR) imaging are at higher risk for a subsequent episode of TSM transient severe motion than patients who do not have TSM transient severe motion during initial gadoxetate disodium administration. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective, multi-institutional HIPAA-compliant study. The requirement for informed consent was waived. One hundred seventy patients each underwent two MR imaging examinations with bolus injection of gadoxetate disodium at one of two sites. Three radiologists reviewed the examinations at each site for TSM transient severe motion , based on severe arterial phase motion, despite minimal motion in the other dynamic phases. The occurrence rate of TSM transient severe motion in the second examination was compared between patients who had TSM transient severe motion in their first examination and those who did not by using the χ(2) or Fisher exact test, as appropriate. Relative risks and 95% confidence intervals ( CI confidence interval s) were calculated. RESULTS: TSM transient severe motion rates in second examinations were significantly higher for patients who had TSM transient severe motion in their first examination: site 1, 67% (six of nine) vs 4% (three of 69) (P < .0001); site 2, 60% (three of five) vs 6% (five of 87) (P < .005); and both sites, 64% (nine of 14) vs 5% (eight of 156) (P < .0001). Relative risks were 15 for site 1 (95% CI confidence interval : 5, 51), 10 for site 2 (95% CI confidence interval : 3, 32), and 13 for both sites (95% CI confidence interval : 6, 27). CONCLUSION: Patients who experience TSM transient severe motion during gadoxetate disodium-enhanced MR imaging are at significantly and substantially higher risk for TSM transient severe motion in the next gadoxetate disodium-enhanced examination compared with patients who do not have TSM transient severe motion during their initial gadoxetate disodium administration.

Dodecafluoropentane emulsion elicits cardiac protection against myocardial infarction through an ATP-Sensitive K+ channel dependent mechanism.

PURPOSE: Dodecafluoropentane emulsion (DDFPe) is a perfluorocarbon with high oxygen dissolving, transport, and delivery capacity that may offer the potential to limit ischemic injury prior to clinical reperfusion. Here we investigated the cardiac protective potential of DDFPe in a mouse model of myocardial infarction. METHODS: Myocardial infarction was initiated by permanent ligation of the left anterior descending (LAD) coronary artery. Mice were administered vehicle or 5-hydroxydecanoate (5-HD) intravenously 10 min before LAD occlusion followed by a single intravenous administration of vehicle or DDFPe immediately after occlusion. Heart tissue and serum samples were collected 24 after LAD occlusion for measurement of infarct size and cardiac troponin I (cTnI) levels, respectively. RESULTS: DDFPe treatment reduced infarct size by approximately 72% (36.9 ± 4.2% for vehicle vs 10.4 ± 2.3% for DDFPe; p < 0.01; n = 6-8) at 24 h. Serum cTnI levels were similarly reduced by DDFPe (35.0 ± 4.6 ng/ml for vehicle vs 15.8 ± 1.6 ng/ml for DDFPe; p < 0.01; n = 6-8). Pretreatment with 5-HD, a mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) inhibitor, blocked the reduction in infarct size (29.2 ± 4.4% for 5-HD vs 35.4 ± 7.4% for 5-HD+DDFPe; p = 0.48; n = 6-8) and serum cTnI levels (27.4 ± 5.1 ng/ml for 5-HD vs 34.6 ± 5.3 ng/ml for 5-HD+DDFPe; p = 0.86; n = 6-8) by DDFPe. CONCLUSION: Our data indicate a cardiac protective role of DDFPe that persists beyond its retention time in the body and is dependent on mitoK(ATP), an important mediator of ischemic preconditioning induced cardiac protection.

Behavioral evidence of olfactory imprinting during embryonic and larval stages in lake sturgeon.

Many migratory fishes are thought to navigate to natal streams using olfactory cues learned during early life stages. However, direct evidence for early-life olfactory imprinting is largely limited to Pacific salmon, and other species suspected to imprint show life history traits and reproductive strategies that raise uncertainty about the generality of the salmonid-based conceptual model of olfactory imprinting in fishes. Here, we studied early-life olfactory imprinting in lake sturgeon (Acipenser fulvescens), which have a life cycle notably different from Pacific salmon, but are nonetheless hypothesized to home via similar mechanisms. We tested one critical prediction of the hypothesis that early-life olfactory imprinting guides natal homing in lake sturgeon: that exposure to odorants during early-life stages results in increased activity when exposed to those odorants later in life. Lake sturgeon were exposed to artificial odorants (phenethyl alcohol and morpholine) during specific developmental windows and durations (limited to the egg, free-embryo, exogenous feeding larvae and juvenile stages), and later tested as juveniles for behavioral responses to the odorants that were demonstrative of olfactory memory. Experiments revealed that lake sturgeon reared in stream water mixed with artificial odorants for as little as 7 days responded to the odorants in behavioral assays over 50 days after the initial exposure, specifically implicating the free-embryo and larval stages as critical imprinting periods. Our study provides evidence for olfactory imprinting in a non-salmonid fish species, and supports further consideration of conservation tactics such as stream-side rearing facilities that are designed to encourage olfactory imprinting to targeted streams during early life stages. Continued research on lake sturgeon can contribute to a model of olfactory imprinting that is more generalizable across diverse fish species and will inform conservation actions for one of the world's most imperiled fish taxonomic groups.

Aquatic insects differentially affect lake sturgeon larval phenotypes and egg surface microbial communities.

Documentation of how interactions among members of different stream communities [e.g., microbial communities and aquatic insect taxa exhibiting different feeding strategies (FS)] collectively influence the growth, survival, and recruitment of stream fishes is limited. Considerable spatial overlap exists between early life stages of stream fishes, including species of conservation concern like lake sturgeon (Acipenser fulvescens), and aquatic insects and microbial taxa that abundantly occupy substrates on which spawning occurs. Habitat overlap suggests that species interactions across trophic levels may be common, but outcomes of these interactions are poorly understood. We conducted an experiment where lake sturgeon eggs were fertilized and incubated in the presence of individuals from one of four aquatic insect FS taxa including predators, facultative and obligate-scrapers, collector-filterers/facultative predators, and a control (no insects). We quantified and compared the effects of different insect taxa on the taxonomic composition and relative abundance of egg surface bacterial and lower eukaryotic communities, egg size, incubation time to hatch, free embryo body size (total length) at hatch, yolk-sac area, (a measure of resource utilization), and percent survival to hatch. Mean egg size varied significantly among insect treatments. Eggs exposed to predators had a lower mean percent survival to hatch. Eggs exposed to predators had significantly shorter incubation periods. At hatch, free embryos exposed to predators had significantly smaller yolk sacs and total length. Multivariate analyses revealed that egg bacterial and lower eukaryotic surface community composition varied significantly among insect treatments and between time periods (1 vs 4 days post-fertilization). Quantitative PCR documented significant differences in bacterial 16S copy number, and thus abundance on egg surfaces varied across insect treatments. Results indicate that lethal and non-lethal effects associated with interactions between lake sturgeon eggs and free embryos and aquatic insects, particularly predators, contributed to lake sturgeon trait variability that may affect population levels of recruitment.

First Isolation of a Herpesvirus (Family Alloherpesviridae) from Great Lakes Lake Sturgeon (Acipenser fulvescens).

The lake sturgeon (Acipenser fulvescens; LST) is the only native sturgeon species in the Great Lakes (GL), but due to multiple factors, their current populations are estimated to be <1% of historical abundances. Little is known about infectious diseases affecting GL-LST in hatchery and wild settings. Therefore, a two-year disease surveillance study was undertaken, resulting in the detection and first in vitro isolation of a herpesvirus from grossly apparent cutaneous lesions in wild adult LST inhabiting two GL watersheds (Erie and Huron). Histological and ultrastructural examination of lesions revealed proliferative epidermitis associated with herpesvirus-like virions. A virus with identical ultrastructural characteristics was recovered from cells inoculated with lesion tissues. Partial DNA polymerase gene sequencing placed the virus within the Family Alloherpesviridae, with high similarity to a lake sturgeon herpesvirus (LSHV) from Wisconsin, USA. Genomic comparisons revealed ~84% Average Nucleotide Identity between the two isolates, leading to the proposed classification of LSHV-1 (Wisconsin) and LSHV-2 (Michigan) for the two viruses. When naïve juvenile LST were immersion-exposed to LSHV-2, severe disease and ~33% mortality occurred, with virus re-isolated from representative skin lesions, fulfilling Rivers' postulates. Results collectively show LSHV-2 is associated with epithelial changes in wild adult LST, disease and mortality in juvenile LST, and is a potential threat to GL-LST conservation.

Truncation of titin's elastic PEVK region leads to cardiomyopathy with diastolic dysfunction.

RATIONALE: The giant protein titin plays key roles in myofilament assembly and determines the passive mechanical properties of the sarcomere. The cardiac titin molecule has 2 mayor elastic elements, the N2B and the PEVK region. Both have been suggested to determine the elastic properties of the heart with loss of function data only available for the N2B region. OBJECTIVE: The purpose of this study was to investigate the contribution of titin's proline-glutamate-valine-lysine (PEVK) region to biomechanics and growth of the heart. METHODS AND RESULTS: We removed a portion of the PEVK segment (exons 219 to 225; 282 aa) that corresponds to the PEVK element of N2B titin, the main cardiac titin isoform. Adult homozygous PEVK knockout (KO) mice developed diastolic dysfunction, as determined by pressure-volume loops, echocardiography, isolated heart experiments, and muscle mechanics. Immunoelectron microscopy revealed increased strain of the N2B element, a spring region retained in the PEVK-KO. Interestingly, the PEVK-KO mice had hypertrophied hearts with an induction of the hypertrophy and fetal gene response that includes upregulation of FHL proteins. This contrasts the cardiac atrophy phenotype with decreased FHL2 levels that result from the deletion of the N2B element. CONCLUSIONS: Titin's PEVK region contributes to the elastic properties of the cardiac ventricle. Our findings are consistent with a model in which strain of the N2B spring element and expression of FHL proteins trigger cardiac hypertrophy. These novel findings provide a molecular basis for the future differential therapy of isolated diastolic dysfunction versus more complex cardiomyopathies.

Natural analogues of degraded ecosystems enhance conservation and reconstruction in extreme environments.

Ecosystem rehabilitation strategies are grounded in the concept that coexisting species fit their environments as an outcome of natural selection operating over ecological and evolutionary timescales. From this perspective, re-creation of historical environmental filters on community assembly is a necessary first step to recovering biodiversity within degraded ecosystems; however, this approach is often not feasible in severely damaged environments where extensive physiochemical changes cannot be reversed. Under such circumstances management goals may shift from restoring historical conditions to reconstructing entirely new ecosystems or replicating natural ecosystems that may be locally novel but of regional conservation importance. This latter goal may be achieved by introducing to damaged sites species already adapted to filters maintaining the degraded state, through targeting assemblages from natural ecosystems biophysically analogous to the degraded state, here termed "degraded-state analogue" (DSA) ecosystems. This hypothesis predicts that, in high-stress sites where recruitment of previous inhabitants is strongly microsite-limited, DSA species will be primarily propagule-limited; furthermore, communities invaded by DSA species should shift in structure to reflect properties associated with high-value DSA target ecosystems. We tested these predictions by experimentally sowing long-abandoned limestone quarry floors with 18 perennial grass and forb species characteristic of rare natural limestone pavements called "alvars." Alvar species established successfully under a range of microsite conditions manipulated to alter suspected constraints on colonization, including nitrogen deficiency, excessive CaCO3, and competition with weeds. Alvar species performed equivalently to seeded weed species known to thrive on quarry floors. Resident communities doubled in species richness following alvar species addition, supporting 17-20 species/0.18 m2 (95% confidence interval) and providing refuge to regionally restricted or threatened species including Iris lacustris, Solidago ptarmicoides, and Liatris cylindracea. In contrast, maximum-diversity reference plots on a pristine alvar supported 20-23 species/0.18 m2. Strong propagule limitation but weak microsite constraints on quarry colonization by alvar species combined with establishment of species-rich communities comparable to natural alvar biodiversity hot spots confirms that targeting DSA assemblages in ecosystem reconstruction can promote both efficient site colonization and ex situ biodiversity conservation within difficult-to-restore anthropogenic wastelands.

IL-18 induction of osteopontin mediates cardiac fibrosis and diastolic dysfunction in mice.

Osteopontin (OPN), a key component of the extracellular matrix, is associated with the fibrotic process during tissue remodeling. OPN and the cytokine interleukin (IL)-18 have been shown to be overexpressed in an array of human cardiac pathologies. In the present study, we determined the role of IL-18 in the regulation of cardiac OPN expression and the subsequent interstitial fibrosis and diastolic dysfunction. We demonstrated parallel increases in IL-18, OPN expression, and interstitial fibrosis in murine models of left ventricular pressure and volume overload. Exogenous recombinant (r)IL-18 administered for 2 wk increased cardiac OPN expression, interstitial fibrosis, and diastolic dysfunction. Stimulation of the T helper (Th)1 lymphocyte phenotype with a selective toll-like receptor (TLR)9 agonist induced cardiac IL-18 and OPN expression, which was associated with increased cardiac fibrillar collagen concentrations and interstitial fibrosis resulting in diastolic dysfunction. rIL-18 induced OPN expression and protein levels in primary of cardiac fibroblast cultures. Conditioned media from TLR9-stimulated T lymphocyte cultures induced IL-18 and OPN expression in cardiac fibroblasts, while blockade of the IL-18 receptor with a neutralizing antibody abolished the increase in OPN expression. Furthermore, a mutation in the transcriptional factor interferon regulatory factor (IRF)1 or IRF1 small interfering RNA (siRNA) resulted in the decreased expression of IL-18 and OPN in cardiac fibroblasts. With pressure overload, IRF1-mutant mice showed downregulation of IL-18 and OPN expression in cardiac tissue, reduced cardiac fibrotic development, and increased left ventricular function compared with wild type. These results provide direct evidence that the induction of IL-18 regulates OPN-mediated cardiac fibrosis and diastolic dysfunction.

Myocardial lysyl oxidase regulation of cardiac remodeling in a murine model of diet-induced metabolic syndrome.

Metabolic syndrome (MetS) represents an increased risk of cardiovascular disease. Although its individual components adversely affect cardiac structure and function, the extent to which multiple components of MetS affect the cardiac extracellular matrix (ECM) has not been well characterized. Lysyl oxidase (LOX) is one of the cardiac ECM-modifying enzymes that catalyze the formation of collagen cross-linking. Our objective was to define the effect of diet-induced MetS on the LOX enzyme. MetS was induced in male C57BL/6 mice by administrating a high-fat, high-simple carbohydrate diet for 6 mo. Gene expression was determined by real-time PCR. The cardiac protein expression and enzymatic activity of LOX were measured. The severity of fibrosis was assessed by histology and hydroxylproline assay. Cardiac diastolic function was assessed by in vivo analysis of the pressure-volume relationship. LOX, matrix metalloproteinases, and their tissue inhibitors were analyzed, and of these three, LOX was most significantly changed in the MetS mice. Despite the blunted gene expression of LOX isoforms, MetS mice demonstrated a significant upregulation of bone morphogenetic protein-1. Correspondingly, there was an increase in the ratio of protein expression of mature to proenzyme LOX by 25.9%, enhanced LOX activity by 50.0%, and increased cardiac cross-linked collagen compared with the controls. This fibrotic response coincided with a marked increase in end-diastolic pressure, increased left ventricular stiffness, and impaired diastolic filling pattern. Our data signify that diet-induced MetS alters the remodeling enzymes, mainly LOX, thereby altering ECM structure by increasing the amount of cross-linking and inducing diastolic dysfunction.

Effect of eicosapentaenoic and docosahexaenoic acid on resting and exercise-induced inflammatory and oxidative stress biomarkers: a randomized, placebo controlled, cross-over study.

BACKGROUND: The purpose of the present investigation was to determine the effects of EPA/DHA supplementation on resting and exercise-induced inflammation and oxidative stress in exercise-trained men. Fourteen men supplemented with 2224 mg EPA+2208 mg DHA and a placebo for 6 weeks in a random order, double blind cross-over design (with an 8 week washout) prior to performing a 60 minute treadmill climb using a weighted pack. Blood was collected pre and post exercise and analyzed for a variety of oxidative stress and inflammatory biomarkers. Blood lactate, muscle soreness, and creatine kinase activity were also measured. RESULTS: Treatment with EPA/DHA resulted in a significant increase in blood levels of both EPA (18 +/- 2 micromol x L(-1) vs. 143 +/- 23 micromol x L(-1); p < 0.0001) and DHA (67 +/- 4 micromol x L(-1) vs. 157 +/- 13 micromol x L(-1); p < 0.0001), while no differences were noted for placebo. Resting levels of CRP and TNF-alpha were lower with EPA/DHA compared to placebo (p < 0.05). Resting oxidative stress markers were not different (p > 0.05). There was a mild increase in oxidative stress in response to exercise (XO and H2O2) (p < 0.05). No interaction effects were noted. However, a condition effect was noted for CRP and TNF-alpha, with lower values with the EPA/DHA condition. CONCLUSION: EPA/DHA supplementation increases blood levels of these fatty acids and results in decreased resting levels of inflammatory biomarkers in exercise-trained men, but does not appear necessary for exercise-induced attenuation in either inflammation or oxidative stress. This may be due to the finding that trained men exhibit a minimal increase in both inflammation and oxidative stress in response to moderate duration (60 minute) aerobic exercise.

CardioWest temporary total artificial heart.

BACKGROUND: The CardioWest temporary total artificial heart (TAH-t) replaces both native ventricles of the heart and is more beneficial for a select group of patients than most other typical ventricular assist devices (VADs). This review will expand on the current literature and highlight the chronology of this device. The CardioWest TAH-t has been implanted in over 715 patients at 30 multiple institutional centers worldwide as a bridge-to-transplant (BTT) since 1993. The mechanical flow dynamics of the device are manufactured and designed differently from other traditional VADs, allowing increased outputs and normal filling pressures, allowing for sufficient organ and tissue perfusion and dramatic recoveries, allowing patients to return to an almost normal quality of life. RESULTS: There was a 79% survival to transplant achievement in the protocol group who received the TAH-t versus a 46% in the control group (P < 0.001). Furthermore, there was a 70% survival rate at one year in the protocol group versus 31% in the control group (P < 0.001). The one- and five-year survival rates after transplantation were 69% and 34%, respectively, in the control group and 86% and 64%, respectively, in the protocol group. CONCLUSION: It is evident that the advancement of modern engineering and medicine has made way for a reliable and durable device that provides a promising future in the field of end-stage heart failure.

Formal psychological testing in patients with paradoxical vocal fold dysfunction.

OBJECTIVE: The etiology of paradoxical vocal fold dysfunction (PVFD) has been unclear, but it has long been hypothesized that there is a significant psychological component. The purpose of this study was to elucidate the psychological profiles of patients newly diagnosed with PVFD using psychometrically-sound psychological assessment instruments. STUDY DESIGN: Prospective cohort study of 45 adults newly diagnosed with PVFD at a tertiary university referral center. METHODS: The Minnesota Multiphasic Personality Inventory (MMPI-2) was administered to test for psychopathology. The Life Experiences Survey (LES) was administered to investigate levels of stress. Demographic, medical, and social histories were reviewed. MMPI-2 and LES scores for the PVFD cohort were compared with scores previously established for normative populations. RESULTS: The study population included 81% female and 60% who were age 50 or older. Compared to the normative population for the MMPI-2, significant differences were noted for both male and female PVFD patients; on average, scores were highly elevated on the hypochondriasis scale and hysteria scale and less elevated on the depression scale. This pattern was consistent with conversion disorder (P < .01). In MMPI-2 subset analysis, 18 patients had a classic conversion profile while 13 others had elevated scores in the three scales of interest, but not in the classic conversion disorder pattern. Also, 11 patients had normal scores, suggesting no psychopathology. PVFD patients with a psychological history scored significantly higher on the depression and anxiety scales than PVFD patients without a psychological history. Patients with a history of asthma or gastroesophageal reflux disease (GERD) achieved significantly higher scores on the hypochondriasis scale than those without that medical history. On the LES assessment, female PVFD patients had significantly lower levels of positive stress and higher levels of negative stress than the general population; total levels of stress were not significantly different, however. Male PVFD patients had significantly lower levels of positive, negative, and total stress. For the entire cohort, asthma (65%), GERD (51%), and a history of abuse (38%) were common comorbidities. CONCLUSIONS: On average, in both male and female adults, PVFD is associated with conversion disorder, representing a physical manifestation of underlying psychological difficulty. There also appears to be a subset of PVFD that is not associated with psychopathology. PVFD patients with a previous psychological history are prone to more depressive and anxious symptomatology. Patients with PVFD and a history of asthma or GERD are more likely to excessively complain about physical symptoms. Overall levels of stress are not higher in PVFD patients compared to a general population. However, females report more negative stress, and both males and females may have trouble coping with the amount of stress that they do have. PVFD is more common among women, more prevalent among older individuals, and can be comorbid with asthma, GERD, and previous abuse. These results have implications for treatment- psychotherapy directed for somatoform and conversion disorders may be added to traditional speech therapy for increased efficacy.

Lusitropic effects of dobutamine in young and aged mice in vivo.

Aged individuals have impaired diastolic relaxation-lusitropic function. Dobutamine, a selective B1-adrenergic agonist, is used to augment systolic cardiac function at the termination of cardiopulmonary bypass (CPB). However, our question is whether dobutamine will also enhance the lusitropic function in the aged individual. The myocyte mechanism for the rate of ventricular relaxation is dependent on the velocity of calcium removal from the myocyte contractile elements by sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), which is regulated by an inhibitory protein, phospholamban (PLB). Ventricular tissues harvested from young (4 month) and aged (20 months) mice were analyzed to compare the protein levels of SERCA2a and PLB with immunoblot and gene expression for PLB with reverse-transcriptase-polymerase chain reaction. The molecular analyses were compared with in vivo left ventricular function in the young and old mice before and during an intravenous infusion of dobutamine (5 microg/kg/min). The SERCA2a levels were not different between the groups; however, there was a 2-fold increase in PLB in the aged group compared with the young group (p < .05). The gene expression for PLB was increased by 5-fold in the aged group compared with the young group (p < .01). There were significant differences between the young and aged groups related to the lusitropic parameters, tau and dP/dt(min), and dobutamine infusion increased these parameters in the aged group to that of the young group. This report supports the concept that altered PLB levels correspond with the respective lusitropic function and that dobutamine administration in the aged group increased lusitropic function that was comparable with the young group. Because the patient population requiring CPB is aging, these data suggest that the use of dobutamine at the terminal phase of CPB is warranted to increase systolic and diastolic function.

Impact of Pycnogenol on cardiac extracellular matrix remodeling induced by L-NAME administration to old mice.

Cardiac remodeling is a determinant of the clinical progression of heart failure and now slowing or reversing remodeling is considered as a potential therapeutic target in heart failure. Pycnogenol has been reported to mediate a number of beneficial effects in the cardiovascular system but its effects on hemodynamic and functional cardiovascular changes following cardiac remodeling have not been elucidated. Therefore, we investigated the influence of Pycnogenol supplementation (30 mg/kg) on left ventricular function and myocardial extracellular matrix composition in old C57BL/6N mice following induction of cardiac remodeling by chronic nitric oxide synthase blockade by NG-nitro-L-arginine methyl ester (L-NAME) administration. L-NAME-treated mice demonstrated dilated cardiomyopathy at compensated state, associated with a significant increase of pro-matrix metalloproteinase (MMP)-9 gene expression and activity, a marked decrease in pro-collagen IIIalpha1 gene expression, and a subsequent reduction in cardiac total and cross-linked collagen content. Upon supplementation with Pycnogenol in L-NAME-exposed mice, cardiac gene expression patterns for pro-MMP-2, -9, and -13, and MMP-9 activity were significantly decreased, associated with a significant increase in cardiac tissue inhibitor of metalloproteinase (TIMP)-4 expression. These findings were coincided with a marked increase in myocardial total and cross-linked collagen content, compared with L-NAME-only-treated mice. Moreover, Pycnogenol treatment was associated with reversal of L-NAME-induced alternations in hemodynamic parameters. These data indicate that Pycnogenol can prevent adverse myocardial remodeling induced by L-NAME, through modulating TIMP and MMPs gene expression, MMPs activity, and further reduction in myocardial collagen degradation rate.

Macrophage migration inhibitory factor: controller of systemic inflammation.

Macrophage migration inhibitory factor (MIF) is a cytokine that is secreted by the anterior pituitary and immune cells in response to surgical stress, injury, and sepsis. This cytokine appears to be a critical regulator of the inflammatory pathways, leading to systemic inflammatory response syndrome and subsequent multiple organ dysfunction syndrome. This report provides an integrated scheme describing the manner by which MIF controls the neurohormonal response and the adaptive immune system, namely the T-helper (Th)1 and Th2 lymphocytes, which results in the release of pro-inflammatory cytokines and the anti-inflammatory cytokine interleukin-10. The development of systemic inflammatory response syndrome and subsequent development of multiple organ dysfunction syndrome appear to be related to MIF levels and the balance of Th1 and Th2 function.