Satellite imaging reveals increased proportion of population exposed to floods.

Flooding affects more people than any other environmental hazard and hinders sustainable development1,2. Investing in flood adaptation strategies may reduce the loss of life and livelihood caused by floods3. Where and how floods occur and who is exposed are changing as a result of rapid urbanization4, flood mitigation infrastructure5 and increasing settlements in floodplains6. Previous estimates of the global flood-exposed population have been limited by a lack of observational data, relying instead on models, which have high uncertainty3,7-11. Here we use daily satellite imagery at 250-metre resolution to estimate flood extent and population exposure for 913 large flood events from 2000 to 2018. We determine a total inundation area of 2.23 million square kilometres, with 255-290 million people directly affected by floods. We estimate that the total population in locations with satellite-observed inundation grew by 58-86 million from 2000 to 2015. This represents an increase of 20 to 24 per cent in the proportion of the global population exposed to floods, ten times higher than previous estimates7. Climate change projections for 2030 indicate that the proportion of the population exposed to floods will increase further. The high spatial and temporal resolution of the satellite observations will improve our understanding of where floods are changing and how best to adapt. The global flood database generated from these observations will help to improve vulnerability assessments, the accuracy of global and local flood models, the efficacy of adaptation interventions and our understanding of the interactions between landcover change, climate and floods.

Quantifying Sarcopenia Reference Values Using Lumbar and Thoracic Muscle Areas in a Healthy Population.

BACKGROUND: Sarcopenia is defined as the loss of skeletal muscle mass and function associated with aging. Muscle mass can be reliably and accurately quantified using clinical CT scans but reference measurements are lacking, particularly in healthy US populations. METHODS: Two-phase CT scans from healthy kidney donors (age 18-40) at the University of Michigan between 1999-2010 were utilized. Muscle mass was quantified using two thoracic and two lumbar muscle cross-sectional area (CSA) measures. Indexed measurements were computed as area divided by height-squared. Paired analyses of non-contrast and contrast phases and different Hounsfield Unit (HU) ranges for muscle were conducted to determine their effect on CSA muscle measures. We report the means, standard deviations, and 2SD sarcopenia cutoffs from this population. RESULTS: Healthy population CSA (cm2) cutoffs for N=604 males/females respectively were: 34.7/20.9 (T12 Dorsal Muscle), 91.5/55.9 (T12 Skeletal Muscle), 141.7/91.2 (L3 Skeletal Muscle), 23.5/14.3 (L4 Total Psoas Area), and 23.4/14.3 (L4 Psoas Muscle Area). Height-indexed CSA (cm2/m2) cutoffs for males/females respectively were: 10.9/7.8 (T12 Dorsal Muscle), 28.7/20.6 (T12 Skeletal Muscle), 44.6/34.0 (L3 Skeletal Muscle), 7.5/5.2 (L4 Total Psoas Area), and 7.4/5.2 (L4 Psoas Muscle Area). We confirmed that a mask of -29 to 150 HU is optimal and shows no significant difference between contrast-enhanced and non-contrast CT scan CSA measurements. CONCLUSIONS: We quantified reference values for lumbar and thoracic muscle CSA measures in a healthy US population. We defined the effect of IV contrast and different HU ranges for muscle. Combined, these results facilitate the extraction of clinically valuable data from the large numbers of existing scans performed for medical indications.

Th17 Responses to Collagen Type V, kα1-Tubulin, and Vimentin Are Present Early in Human Development and Persist Throughout Life.

T helper 17 (Th17)-dependent autoimmune responses can develop after heart or lung transplantation and are associated with fibro-obliterative forms of chronic rejection; however, the specific self-antigens involved are typically different from those associated with autoimmune disease. To investigate the basis of these responses, we investigated whether removal of regulatory T cells or blockade of function reveals a similar autoantigen bias. We found that Th17 cells specific for collagen type V (Col V), kα1-tubulin, and vimentin were present in healthy adult peripheral blood mononuclear cells, cord blood, and fetal thymus. Using synthetic peptides and recombinant fragments of the Col V triple helical region (α1[V]), we compared Th17 cells from healthy donors with Th17 cells from Col V-reactive heart and lung patients. Although the latter responded well to α1(V) fragments and peptides in an HLA-DR-restricted fashion, Th17 cells from healthy persons responded in an HLA-DR-restricted fashion to fragments but not to peptides. Col V, kα1-tubulin, and vimentin are preferred targets of a highly conserved, hitherto unknown, preexisting Th17 response that is MHC class II restricted. These data suggest that autoimmunity after heart and lung transplantation may result from dysregulation of an intrinsic mechanism controlling airway and vascular homeostasis.

Features of the non-contact carotid pressure waveform: Cardiac and vascular dynamics during rebreathing.

This report amplifies and extends prior descriptions of the use of laser Doppler vibrometry (LDV) as a method for assessing cardiovascular activity, on a non-contact basis. A rebreathing task (n = 35 healthy individuals) was used to elicit multiple effects associated with changes in autonomic drive as well as blood gases including hypercapnia. The LDV pulse was obtained from two sites overlying the carotid artery, separated by 40 mm. A robust pulse signal was obtained from both sites, in accord with the well-described changes in carotid diameter over the blood pressure cycle. Emphasis was placed on extracting timing measures from the LDV pulse, which could serve as surrogate measures of pulse wave velocity (PWV) and the associated arterial stiffness. For validation purposes, a standard measure of pulse transit time (PTT) to the radial artery was obtained using a tonometric sensor. Two key measures of timing were extracted from the LDV pulse. One involved the transit time along the 40 mm distance separating the two LDV measurement sites. A second measure involved the timing of a late feature of the LDV pulse contour, which was interpreted as reflection wave latency and thus a measure of round-trip travel time. Both LDV measures agreed with the conventional PTT measure, in disclosing increased PWV during periods of active rebreathing. These results thus provide additional evidence that measures based on the non-contact LDV technique might provide surrogate measures for those obtained using conventional, more obtrusive assessment methods that require attached sensors.

Differential requirement for P2X7R function in IL-17 dependent vs. IL-17 independent cellular immune responses.

IL17-dependent autoimmunity to collagen type V (Col V) has been associated with lung transplant obliterative bronchiolitis. Unlike the T helper 1 (Th1)-dependent immune responses to Tetanus Toxoid (TT), the Th17 response to Col V in lung transplant patients and its Th1/17 variant observed in coronary artery disease patients requires IL-1ß, tumor necrosis factor α and CD14(+) cells. Given the involvement of the P2X7 receptor (P2X7R) in monocyte IL-1ß responses, we investigated its role in Th17-, Th1/17- and Th1-mediated proinflammatory responses. Transfer of antigen-pulsed peripheral blood mononucleated cells (PBMCs) from Col V-reactive patients into SCID mouse footpads along with P2X7R antagonists revealed a selective inhibition of Col V-, but not TT-specific swelling responses. P2X7R inhibitors blocked IL-1ß induction from monocytes, including both Col V-α1 peptide-induced (T-dependent), as well as native Col V-induced (T-independent) responses. Significantly higher P2X7R expression was found on CXCR3(neg) CCR4(+)/6(+) CD4(+) [Th17] versus CXCR3(+)CCR4/6(neg) CD4(+) [Th1] subsets in PBMCs, suggesting that the paradigm of selective dependence on P2X7R might extend beyond Col V autoimmunity. Indeed, P2X7R inhibitors suppressed not only anti-Col V, but also Th1/17-mediated alloimmunity, in a heart transplant patient without affecting anti-viral Epstein-Barr virus responses. These results suggest that agents targeting the P2X7R might effectively treat Th17-related transplant pathologies, while maintaining Th1-immunity to infection.

Responses of dietary ileal amino acid digestibility to consumption of different cultivars of potatoes and conventional fibers in grower pigs fed a high-fat basal diet.

Whereas dietary fibers are well recognized for nutritional management of human health issues, fiber is also known to be one of the dietary factors potentially affecting digestive use of dietary proteins. As a staple food, potato (Solanum tuberosum) may be a significant dietary fiber source. The objective of this study was to examine effects of dietary supplementation of six potato cultivar-genotype samples that differ in soluble fiber content and two conventional fiber components (i.e., cellulose and guar gum) on the apparent ileal AA digestibility in pigs fed a high-fat basal diet. The basal diet was formulated as a zero-fiber negative control (NC) to contain 41.5% poultry meal, 4% casein, 15% animal fat-oil blend, 2.8% sucrose, 31% corn (Zea mays) starch, 0.50% salt, and 0.40% trace mineral-vitamin supplement with fat contributing to 47% of the dietary GE. The two fiber diets were formulated by respectively diluting the basal diet with 10% guar gum and 10% cellulose at the expense of corn starch. Six other test diets were formulated by including 8.5% guar gum and further diluting the basal diet with 25.1% one of the six cultivar-genotype samples of dehydrated potato tuber powder to contain about 10% total dietary fiber at the expense of corn starch. Eighty-one 25-kg barrows were fitted with a simple T-cannula at the distal ileum and fed the diets according to a completely randomized block design with each block lasting 28 d. Compared with the NC, the ileal digestibility of Ala, Gly, and Pro were decreased (P < 0.05) by 10% guar gum whereas the digestibility of Gly was reduced (P < 0.05) by 10% cellulose. The ileal digestibility of several AA was decreased (P < 0.05) by the test potatoes plus 8.5% guar gum compared with the NC. Our results suggest that dietary inclusion of fiber at 10% from guar gum and cellulose and contributed by potatoes may adversely affect digestive use of dietary protein.

Composite arterial grafts versus conventional grafting for coronary artery bypass grafting.

OBJECTIVES: Composite arterial grafts for coronary artery bypass grafting surgery allow complete arterial revascularization but are limited by the inflow of a single internal thoracic artery supplying all the grafted vessels. We reviewed the safety of composite arterial grafts using either bilateral internal thoracic arteries or a single internal thoracic artery and radial artery. METHODS: From January 1999 to July 2002, 402 consecutive patients receiving composite grafts only were compared to a control group of patients (n = 542) undergoing coronary artery bypass grafting with internal thoracic artery and saphenous veins operated upon by the same surgeons. Two different statistical approaches were used to compare groups in this retrospective analysis. First, propensity score analysis with greedy matching technique was used to match patients from each group. Second, a multivariate analysis was performed looking at a combined patient outcome of death, intra-aortic balloon counterpulsation utilization, myocardial infarction, stroke, and prolonged ventilation on all patients in both groups. RESULTS: After matching by propensity score, the major clinical outcomes in composite arterial (n = 249) and control (n = 249) groups were found to be similar. The in-hospital mortality in the composite group was 1.2% as compared with 0.4% in matched patients (P =.62). However, patients in the composite group were found to have a significantly longer pump time (P <.0001), longer clamp time (P <.0001), increased incidence of prolonged mechanical ventilation (12.8% vs 4.8%; P =.002), and higher incidence of combined morbidity outcome (13.6% vs 6.4%; P =.007) as compared with matched patients. Multivariable analysis showed that composite arterial grafting was an independent predictor of the combined morbidity outcome with an odds ratio of 2.1 (1.2-3.7). CONCLUSIONS: These findings suggest that composite arterial grafting may be associated with an increase in risk-adjusted patient morbidity when compared with a conventional coronary artery bypass grafting group, although a mortality difference was not demonstrable.

Diagnostic and treatment challenges of neuronopathic Gaucher disease: two cases with an intermediate phenotype.

Gaucher disease (GD) is a lysosomal storage disorder with a broad, overlapping clinical spectrum. The presented two case reports highlight the clinical evaluation required in neuronopathic GD to assist with medical management and genetic counselling.

Use of autologous blood as part of the perfusate for cardiopulmonary bypass: a priming technique.

In an attempt to replace the oncotic and protein coating capabilities of serum albumin in the perfusate, we established a priming protocol that used autologous blood as part of the perfusate solution. Prior to March 1, 1999, our standard priming protocol was 1650 ml of crystalloid with 250 ml of 5% serum albumin and 5,000 units of heparin. After removing albumin from our prime, our standard protocol was altered to include 40 ml of the patient's autologous blood in 1,800 ml of crystalloid and 10,000 units of heparin. To determine the intraoperative effects of using albumin/crystalloid primes (Group A), autologous blood/crystalloid primes (Group B) and crystalloid primes (Group C), a total of 178 patients were sequentially evaluated. Intraoperative parameters evaluated were total protein (TP), colloid osmotic pressure (COP), platelets (Plts) and fluid requirements during cardiopulmonary bypass (CPB). During an overlapping 12-month period of time, 1,092 consecutive cardiac surgical cases using CPB (584 albumin prime; 508 autologous blood prime) were evaluated for clinical outcomes in terms of mortality and length of hospitalization. In addition, over a period of 15 months, 1,458 patients in both the autologous blood/crystalloid group and the crystalloid only group were evaluated for the incidence of high-pressure excursions (HPE) after going on bypass. Comparative reviews of TP, COP and Plts demonstrated no significant difference 10 min after the start of bypass between Groups A and B. However, in Group C, there was a statistically significant increase in the intraoperative fluid requirements during CPB, compared to both of the other groups. There was no significant difference in the incidence of HPE, with an occurrence of 1.04% in the crystalloid only group and 1.11% in the autologous blood/crystalloid group. Autologous blood perfusates were identical to albumin perfusates in their platelet protection and reduction of fluid shifts during the intraoperative period.

Deblurring subject to nonnegativity constraints when known functions are present with application to object-constrained computerized tomography.

The reconstruction of tomographic images is often treated as a linear deblurring problem. When a high-density, man-made metal object is present somewhere in the image field, it is a deblurring problem in which the unknown function has a component that is known except for some location and orientation parameters. We first address general linear deblurring problems in which a known function having unknown parameters is present. We then show how the resulting iterative solution can be applied to tomographic imaging in the presence of man-made foreign objects, and we apply the result, in particular, to X-ray computed tomography imaging used in support of brachytherapy treatment of advanced cervical cancer.

A plastid envelope location of Arabidopsis ent-kaurene oxidase links the plastid and endoplasmic reticulum steps of the gibberellin biosynthesis pathway.

We have used fusions of gibberellin biosynthesis enzymes to green fluorescent protein (GFP) to determine the subcellular localization of the early steps of the pathway. Gibberellin biosynthesis from geranylgeranyl diphosphate is catalysed by enzymes of the terpene cyclase, cytochrome P450 mono-oxygenase and 2-oxoglutarate-dependent dioxygenase classes. We show that the N-terminal pre-sequences of the Arabidopsis thaliana terpene cyclases copalyl diphosphate synthase (AtCPS1) and ent-kaurene synthase (AtKS1) direct GFP to chloroplasts in transient assays following microprojectile bombardment of tobacco leaves. The AtKS1-GFP fusion is also imported by isolated pea chloroplasts. The N-terminal portion of the cytochrome P450 protein ent-kaurene oxidase (AtKO1) directs GFP to chloroplasts in tobacco leaf transient assays. Chloroplast import assays with 35S-labelled AtKO1 protein show that it is targeted to the outer face of the chloroplast envelope. The leader sequences of the two ent-kaurenoic acid oxidases (AtKAO1 and AtKAO2) from Arabidopsis direct GFP to the endoplasmic reticulum. These data suggest that the AtKO1 protein links the plastid- and endoplasmic reticulum-located steps of the gibberellin biosynthesis pathway by association with the outer envelope of the plastid.

Preoperative prediction of prolonged mechanical ventilation following coronary artery bypass grafting.

OBJECTIVE: Few studies have attempted to evaluate who would require prolonged mechanical ventilation following heart surgery. The objectives of this study were to identify predictors of prolonged ventilation in a large group of coronary artery bypass grafting (CABG) patients from a single institution. METHODS: One thousand, eight hundred and twenty-nine consecutive patients undergoing CABG were reviewed retrospectively and evaluated for preoperative predictors of prolonged ventilation which included: age, gender, ejection fraction (EF), renal function, diabetes, angina status, New York Heart Association Class, number of diseased vessels, urgency of the procedure, re-operation, chronic lung disease (COPD) and intraoperative variables such as IABP, inotropes, stroke and myocardial infarction. Prolonged ventilation was defined as > or = 24 h. Stepwise logistic regression analysis was performed. RESULTS: Patients were on average 65.4+/-10.6 years of age, 30% were diabetic, 80% had triple vessel disease and 93% were of functional class III/IV. The mean ejection fraction was 60+/-16 percent. Overall peri-operative mortality was 2.7%. There were 157 patients that required prolonged ventilation with a peri-operative mortality of 18.5% (P < 0.001). Preoperative independent predictors of prolonged ventilation were found to be: unstable angina (OR 5.6), EF < 50 (OR 2.3), COPD (OR 2.0), preop. renal failure (OR 1.9), female gender (OR 1.8) and age > 70 (OR 1.7). Based on these predictors, a model was created to estimate of the risk of prolonged ventilation in individual patients following CABG with results ranging from < or = 3% in patients without any risk factors to > or = 32% in patients with five or more independent risk factors. Certain intraoperative variables were strong predictors of prolonged ventilation and included: stroke (OR 12.3), re-operation for bleeding (OR 6.9) and perioperative MI (OR 5.8). CONCLUSION: We were able to create a stable model where several preoperative and intra-operative variables were shown to be predictive of prolonged ventilation after CABG surgery. The ability to identify patients at increased risk for prolonged ventilation may allow the development of pre-emptive strategies and more effective resource allocation.

Waiting for cardiac surgery: results of a risk-stratified queuing process.

BACKGROUND: The Queen Elizabeth II Health Sciences Centre uses a weekly peer-review conference of cardiovascular experts to prioritize each surgical case to 1 of 4 queues with the use of standardized criteria of coronary anatomy, stress test result, and symptoms. We examined the hazard of waiting as well as the impact of waiting on surgical outcomes. METHODS AND RESULTS: Analysis was performed for 2102 consecutive patients queued for CABG, aortic valve replacement, or CABG+aortic valve replacement between January 1, 1998, and December 31, 1999. Among 1854 patients undergoing surgery, median waiting times on the respective queues were as follows: in-house urgent group, 8 days; semiurgent A group, 37 days; semiurgent B group, 64 days; and elective group, 113 days. There were 13 deaths (12 cardiac) that occurred during the waiting period (0.7% of the patients). Of the 8.7% patients upgraded to a more urgent queue, 86.1% required hospitalization before surgery. Although female sex was not associated with prolonged waiting time, it was predictive of urgent status (P=0.001). The incidence of postoperative complications was 25.0%, and operative mortality was 2.86%. Both were more frequent among patients undergoing surgery early (P=0.01); however, this difference was attributable to the in-house urgent queue. The median length of stay was 7 days for all patients and was not affected by waiting time. CONCLUSIONS: Death and upgrades while the patients were waiting tended to occur early in the queuing process, and prolonged waiting was not associated with worse surgical outcomes. The cost of reducing waiting times could in part be offset by prevention of hospital admissions among upgraded patients.

Fas ligand/Fas-mediated apoptosis in human coronary artery smooth muscle cells: therapeutic implications of fratricidal mode of action.

OBJECTIVE: This study aimed to determine the mode of action of Fas ligand (FasL)/Fas at mediating apoptosis so as to evaluate the potential of FasL in gene therapy for restenosis. METHODS: Passaged human coronary artery smooth muscle (HCASM) cells were infected with recombinant adenoviral vectors expressing murine FasL. Various parameters of FasL expression and apoptosis were measured using FACS, immunofluorescence, calorimetric, and cytotoxicity assays. RESULTS: Most HCASM cells under normal growth conditions expressed Fas and were shown to be susceptible to membrane bound but not soluble FasL. However, some FasL expressing cells survived for up to 7 days. These surviving cells were observed to be spatially distributed and were not in direct physical contact with each other. Upon examination, it was determined that although the majority of the surviving cells expressed FasL, only 30% expressed both Fas and FasL. These cells were capable of inducing apoptosis of target cells and some were also susceptible to FasL expressing cells, provided that the effector and target cells were in close physical contact. FasL/Fas-mediated apoptosis was inhibited by p35, a baculovirus gene that inhibits caspases. Additionally, in contrast to HCASM cells, neither membrane-bound nor soluble FasL induced apoptosis in coronary artery endothelial cells. CONCLUSIONS: FasL expressing HCASM cells do not undergo FasL/Fas mediated "suicide" but kill neighboring cells bearing Fas in a "fratricidal" manner. A small population of HCASM cells expresses no surface Fas. These results imply that HCASM cells transduced in vivo with FasL may serve as "scavengers" and exert a bystander effect on surrounding cells that may be enhanced by co-expression of p35. As FasL-mediated apoptosis occurs in coronary arterial smooth muscle but not endothelial cells, FasL may also offer an advantage over other genes for use in restenosis since the latter may indiscriminately delay re-endothelialization at the sites of gene.

Myocardial scintigraphy correlates poorly with coronary angiography in the screening of transplant arteriosclerosis.

BACKGROUND: Coronary angiography remains an important screening tool for transplant coronary arteriosclerosis (TxCAD) after heart transplantation despite criticism that it underestimates the incidence of TxCAD. In an effort to improve TxCAD incidence estimation, several methods of screening have been proposed. In the present study, the incidence of TxCAD assessed by both yearly coronary angiography and stress myocardial scintigraphy imaging was reviewed. PATIENTS AND METHODS: Ninety-nine consecutive primary heart transplantations were performed from 1988 to 1999. The standard immunosuppression protocol consisted of the introduction of antilymphocyte globulin and steroids, while maintenance therapy was with cyclosporine, imuran and steroids. Coronary angiography and a stress 2-methoxyisobutyl-isonitrile perfusion scan were performed yearly. TxCAD was defined by angiographic evidence of luminal abnormality by catheterization, or a perfusion abnormality at rest or after stress on myocardial scintigraphy. RESULTS: The mean recipient age was 49+/-12 years and the mean donor age was 33+/-13 years. The etiology of heart failure was ischemic cardiomyopathy (50%), dilated cardiomyopathy (41%) and congenital heart disease (9%). The freedom from angiographic TxCAD was 92% at one year, 64% at five years and 35% at eight years. The freedom from nuclear imaging TxCAD was 92% at one year, 69% at five years and 44% at eight years. However, a diagnosis of TxCAD by angiography only correlated with a diagnosis of TxCAD by nuclear imaging 52.8% of the time in the same patient, with a median time between studies of one month. CONCLUSION: The overall incidence of TxCAD diagnosed by angiography and nuclear imaging appears similar but correlates poorly in patients, casting doubt on the routine use of myocardial scintigraphy for screening TxCAD.

Longitudinal study of the carrier testing process for fragile X syndrome: perceptions and coping.

This paper reports the results of a longitudinal study of women at-risk to inherit the fragile X mutation. It addresses 1) how upsetting the women perceived their carrier information to be, 2) how serious a problem they perceive fragile X syndrome to be, and 3) descriptions of feelings about the carrier testing process. The study sample consisted of 42 women (20 carriers and 22 noncarriers). There were two measurement times (just prior to carrier testing and after learning actual carrier status). The measures used were a Fragile X Visual Analog Scale and a structured interview. At time 1, being at-risk was reported to be upsetting and fragile X syndrome was perceived to be a serious problem. For the women found to be carriers there was no change from time 1 to time 2 on any of the items. Significant change occurred in the non-carriers. They were significantly less upset at time 2 after receiving the results of their carrier test than at time 1. They also perceived fragile X syndrome to be a more serious problem than they did at time 1 and a more serious problem than the carriers at time 2. Themes found included concerns that carrier status for fragile X syndrome presented a barrier for having healthy biological children and concern for children's and grandchildren's adaptation to their own carrier status. Coping behaviors were activated to manage the emotions related to these concerns. The coping behaviors identified were minimization, acceptance of the possibility of being a carrier, a sense of being able to deal with the outcome of the carrier test, positive comparison, problem solving, and positive interpretation.

Medtronic Mosaic porcine bioprosthesis: midterm investigational trial results.

BACKGROUND: The midterm clinical and hemodynamic performance of the Medtronic Mosaic porcine bioprosthesis was evaluated in a regulatory trial. METHODS: In nine Canadian centers, 802 bioprostheses (560 aortic and 242 mitral) were implanted between September 1994 and April 1999 in patients with a mean age of 70 years. RESULTS: Survival for aortic valve replacement at 4 years was 84.4%+/-3.1%. Freedom from valve-related or unexplained death was 95.6%+/-1.9%; structural valve deterioration, 100.0%; reoperation, 96.2%+/-1.7%; major thromboembolism, 96.1%+/-1.8%; and major antithrombotic-related hemorrhage, 96.4%+/-1.7%. Echocardiographic derived mean systolic gradient was 13.4 mm Hg at 4 years with an indexed effective orifice area of 0.7 to 0.8 cm2/m2. A significant decrease in left ventricular mass was shown over time in all valve sizes. Survival for mitral valve replacement at 4 years was 79.2%+/-6.8%. Freedom from valve-related or unexplained death was 96.5%+/-3.4%; structural valve deterioration, 100%; reoperation, 97.0%+/-3.2%; major thromboembolism, 95.7%+/-3.8%; and major antithrombotic-related hemorrhage, 95.0%+/-4.2%. Echocardiographically measured averaged mean diastolic gradient was 4.5 mm Hg. CONCLUSIONS: The Medtronic Mosaic bioprosthesis is safe and effective in both the aortic and mitral positions. The valve has low gradients in both positions and excellent left ventricular mass regression in the patients with aortic valve replacement.

Medtronic Intact porcine bioprosthesis experience to twelve years.

BACKGROUND: The Medtronic Intact porcine bioprosthesis was further evaluated to determine the influence of zero-pressure glutaraldehyde fixation on structural valve deterioration (SVD). METHODS: From 1986 through 1996, at three Canadian centers, 1,272 patients had 1,296 procedures: 836 aortic valve replacement (AVR), 332 mitral valve replacement (MVR), 14 tricuspid valve replacement, 3 pulmonary valve replacement, and 111 multiple valve replacements. The mean age of the patient population was 67 years (range 9 to 91 years). The total follow-up was 8,011 patient-years (mean 6.2 years). RESULTS: The late mortality (overall) was 4.8% and 6.7% per patient-year for AVR with or without concomitant procedures, respectively; and 4.7% and 10.4% per patient-year for MVR, respectively. There were 51 cases of SVD (AVR 22 of 836; MVR 23 of 332; pulmonary valve replacement 1 of 3; and multiple valve replacement 5 of 111). The actuarial freedom from SVD at 12 years for AVR was 94.3%+/-3.3% for patients aged 61 to 70 years and 97.7%+/-1.1% for those more than 70 years; for MVR actuarial freedom from SVD at 12 years was 93.7%+/-3.9% for patients more than 70 years. The actual freedom at 12 years from SVD for AVR was 92.4%+/-3.1% for patients aged 51 to 60 years, 96.1%+/-2.1% for those 61 to 70 years, and 98.4%+/-0.7% for those older than 70 years; for MVR actual freedom from SVD at 12 years was 89.6%+/-3.2% for patients 61 to 70 years and 96.6%+/-3.4% for those more than 70 years. CONCLUSIONS: The Medtronic Intact porcine bioprosthesis, formulated with tissue preservation at zero-pressure fixation, has encouraging freedom from structural failure.

Pregnancy-specific enhancement of agonist-stimulated ERK-1/2 signaling in uterine artery endothelial cells increases Ca(2+) sensitivity of endothelial nitric oxide synthase as well as cytosolic phospholipase A(2).

Uterine artery endothelial cells (UAEC) from pregnant ewes (P-UAEC) demonstrate generally enhanced ability to couple growth factor and G protein-coupled receptors to the ERK-1/2 signaling pathway and stimulate NO production independently of elevated [Ca(2+)]. Herein we investigate the signaling and vasodilator responses to ATP, an agonist that also elevates [Ca(2+)](i) in both NP and P-UAEC, to determine the relative importance of Ca(2+) vs. ERK-1/2 in the activation of eNOS. We observed in both NP-UAEC and P-UAEC that ATP acts through G protein-coupled P(2Y) receptors to activate phospholipase C and dose-dependently elevate [Ca(2+)](i) independently of extracellular Ca(2+). The small reduction in the [Ca(2+)](i) response in NP vs. P-UAEC did not, however, account for the difference in NO production by P-UAEC>>NP-UAEC. ATP had no stimulatory effect on Akt phosphorylation but rapidly stimulated ERK-1/2 phosphorylation in P-UAEC>>NP-UAEC in a manner that correlated with NO production. In both NP- and P-UAEC, both ERK-1/2 and Ca(2+) were absolutely required for eNOS as well as cPLA(2) activation and the Ca(2+) sensitivity of eNOS was enhanced through the cytosolic [Ca(2+)](i) range in P-UAEC>>NP-UAEC. Thus ERK-1/2 may regulate the Ca(2+) sensitivity of eNOS to an even greater extent than is known to occur for cPLA(2).