Left heart pressures can be the key to know the limitation of left ventricular assist device support against progression of aortic insufficiency

Aortic insufficiency (AI) is a worrisome complication under left ventricular assist device (LVAD) support. AI progression causes LVAD-left ventricular (LV) recirculation and can require surgical intervention to the aortic valve. However, the limitations of LVAD support are not well known. Using an animal model of LVAD with AI, the effect of AI progression on hemodynamics and myocardial oxygen metabolism were investigated. Five goats (Saanen 48?±?2 kg) underwent centrifugal type LVAD, EVAHEART, implantation. The AI model was established by placing a vena cava filter in the aortic valve. Cardiac dysfunction was induced by continuous beta-blockade (esmolol) infusion. Hemodynamic values and myocardial oxygen extraction ratio (O₂ER) were evaluated while changing the degree of AI which was expressed as the flow rate of LVAD-LV recirculation (recirculation rate). Diastolic aortic pressure was decreased with AI progression and correlated negatively with the recirculation rate (p?=?0.00055). Systolic left ventricular pressure (LVP) and mean left atrial pressure (LAP) were increased with AI progression and correlated positively with the recirculation rate (p?=?0.010, 0.023, respectively). LVP and LAP showed marked exponential increases when the recirculation rate surpassed 40%. O₂ER was also increased with AI progression and had a significant positive correlation with the recirculation rate (p?=?0.000043). O₂ER was increased linearly, with no exponential increase. AI progression made it difficult to reduce the cardiac pressure load, worsening myocardial oxygen metabolism. The exponential increase of left heart pressures could be the key to know the limitation of LVAD support against AI progression.     

Effects of leaflet geometry on the flow field in three bileaflet valves when installed in a pneumatic ventricular assist device

Our group is currently developing a pneumatic ventricular assist device (PVAD). In this study, in order to select the optimal bileaflet valve for our PVAD, three kinds of bileaflet valve were installed and the flow was visualized downstream of the outlet valve using the particle image velocimetry (PIV) method. To carry out flow visualization inside the blood pump and near the valve, we designed a model pump that had the same configuration as our PVAD. The three bileaflet valves tested were a 21-mm ATS valve, a 21-mm St. Jude valve, and a 21-mm Sorin Bicarbon valve. The mechanical heart valves were mounted at the aortic position of the model pump and the flow was visualized by using the PIV method. The maximum flow velocity was measured at three distances (0, 10, and 30 mm) from the valve plane. The maximum flow velocity of the Sorin Bicarbon valve was less than that of the other two valves; however, it decreased slightly with increasing distance it the X-Y plane in all three valves. Although different bileaflet valves are very similar in design, the geometry of the leaflet is an important factor when selecting a mechanical heart valve for use in an artificial heart.     

Prognostic significance of WNT signaling in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies and is associated with a variety of molecular abnormalities. Although WNT signaling through its canonical/non-canonical pathways is one of the major factors involved in oncogenesis or progression of PDA, the prognostic significance of WNT signaling still remains poorly investigated. In this study, the status of the WNT signaling pathways was immunohistochemically analyzed in 101 PDAs, and its potential association with patient postoperative survival was assessed. Nuclear expression of beta-catenin, a hallmark of the activated canonical pathway, was identified in 59 cases, and was associated with reduced survival compared to the patients lacking nuclear beta-catenin expression (P?=?0.002). In contrast, activation of the non-canonical pathway (25 cases), as indicated by co-expression of WNT2/5a and nuclear NFATc1, was not correlated with reduced survival (P?=?0.268). Co-activation of both pathways (16 cases) was associated with worse prognosis in comparison with cases with an activated non-canonical pathway (P?=?0.034). In addition, nuclear beta-catenin expression was an independent unfavorable prognostic factor (P?=?0.006). Our data indicate that activated WNT signaling through its canonical pathway has a significantly negative effect on the clinical course of PDA, and the canonical WNT pathway should be considered as a future therapeutic target for PDA.     

Effects of 2 prevention programs on high-risk behaviors among African American youth: a randomized trial

OBJECTIVE: To test the efficacy of 2 programs designed to reduce high-risk behaviors among inner-city African American youth. DESIGN: Cluster randomized trial. SETTING: Twelve metropolitan Chicago, Ill, schools and the communities they serve, 1994 through 1998. PARTICIPANTS: Students in grades 5 through 8 and their parents and teachers. INTERVENTIONS: The social development curriculum (SDC) consisted of 16 to 21 lessons per year focusing on social competence skills necessary to manage situations in which high-risk behaviors occur. The school/community intervention (SCI) consisted of SDC and school-wide climate and parent and community components. The control group received an attention-placebo health enhancement curriculum (HEC) of equal intensity to the SDC focusing on nutrition, physical activity, and general health care. MAIN OUTCOME MEASURES: Student self-reports of violence, provocative behavior, school delinquency, substance use, and sexual behaviors (intercourse and condom use). RESULTS: For boys, the SDC and SCI significantly reduced the rate of increase in violent behavior (by 35% and 47% compared with HEC, respectively), provoking behavior (41% and 59%), school delinquency (31% and 66%), drug use (32% and 34%), and recent sexual intercourse (44% and 65%), and improved the rate of increase in condom use (95% and 165%). The SCI was significantly more effective than the SDC for a combined behavioral measure (79% improvement vs 51%). There were no significant effects for girls. CONCLUSIONS: Theoretically derived social-emotional programs that are culturally sensitive, developmentally appropriate, and offered in multiple grades can reduce multiple risk behaviors for inner-city African American boys in grades 5 through 8. The lack of effects for girls deserves further research.     

Three-dimensional sonographic volume measurement of the fetal spleen

AIM: The objective of this longitudinal study was to evaluate the growth of the fetal spleen in normal pregnancies, using three-dimensional ultrasound. METHODS: Three-dimensional sonographic examinations were performed on 14 appropriate-for-gestational-age fetuses. Fetal splenic volume was measured every 2-3 weeks after 20 weeks of gestational age until delivery. RESULTS: Curvilinear relationships were found between the gestational age and splenic volume (R(2) = 80.2%, P < 0.0001), and normal ranges of splenic volume measurements for estimating the growth of the fetal spleen during normal pregnancy were generated. We found that the splenic volume calculation based on the equation for the volume of the ellipsoid by conventional two-dimensional ultrasound in previous investigations is about twice as large as that using three-dimensional ultrasound in our study, whereas the present data described in this study is quite comparable with previous data from an autopsy series. CONCLUSION: Our findings suggest that the standard curve for the fetal splenic volume using three-dimensional ultrasound provides a superior means for evaluating the normal splenic growth in the fetus and for identifying splenic abnormalities in utero. However, the data and its interpretation in our study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size would be needed to confirm these findings.     

Hepatic changes in the acute phase of streptozotocin (SZ)-induced diabetes in mice

We have reported the streptozotocin (SZ)-induced hepatic lesions in the subacute phase (4 to 12 weeks after the treatment), which are characterized by appearance of oncocytic hepatocytes, cytomegalic hepatocytes and bile duct hyperplasia. In this study, we focused on the acute phase (6 to 48 hours after the treatment) of the SZ-induced hepatic lesions of mice to clarify the onset of the hepatic alterations, especially before the induction of hyperglycemia. Livers were taken from 8-week-old Crj:CD-1 (ICR) male mice at 6,12, 24, 36 and 48 hours after the 200 mg/kg b.w. of SZ-injection. SZ-induced hyperglycemia was noted at 36 and 48 hours after the treatment, but the hepatic changes including lipid peroxidation, mitochondrial swelling, peroxisome proliferation and inhibition of hepatocyte proliferation occurred before the elevation of the serum glucose levels. The present findings indicate the direct effects of SZ on hepatocytes rather than the secondary effects of diabetes, and certain correlations between the hepatocytic changes in the acute phase and those in the subacute one. In addition, ulcer and submucosal edema of the gallbladder were observed at 36 or 48 hours after the SZ-treatment, which can be a novel finding in SZ-treated animal.