Project description:Progressive stenosis is one of the main factors that limit the lifetime of bioprosthetic valved conduits. To improve long-term performance we aimed to identify targets that inhibit pannus formation on conduit walls. From 11 explanted, obstructed, RNAlater presevered pulmonary valved conduits, we dissected the thickened conduit wall and the thin leaflet to determine gene expression-profiles using ultra deep sequencing. Differential gene expression between pannus and leaflet provided the dataset that was screened for potential targets. Promising target candidates were immunohistologically stained to see protein abundance and the expressing cell type(s). While immunostainings for DDR2 and FGFR2 remained inconclusive, EGFR, ErbB4 and FLT4 were specifically expressed in a subset of tissue macrophages, a cell type known to regulate the initiation, maintenance, and resolution of tissue repair. Taken toghether, our data suggest EGFR, ErbB4 and FLT4 as potential target candidates to limit pannus formation in bioprosthestic replacement valves.
Project description:Prototheca wickerhamii is ubiquitous, saprophytic achlorophyllous algae that cause opportunistic infections in the dog and cat and disseminated disease usually in immunocompromised animals. In this report an uncommon case of canine cutaneous protothecosis is presented. A 6-year-old female boxer was brought in with skin lesions that consisted of nodules and generalized footpad hyperkeratosis, depigmentation, and erosion. Cytology and histopathology showed pyogranulomatous inflammation along with organisms containing round sporangia with spherical sporangiospores. PCR and sequencing identified the causal organism as Prototheca wickerhamii. Therapy applied in this patient with either fluconazole alone or combination of amphotericin B and itraconazole proved effective only for footpad lesions but not for skin nodules. Systemic therapy seems to be ineffective for skin nodules, at least in chronic cases of canine cutaneous protothecosis. Although canine protothecosis usually presents with the disseminated form, cutaneous disease as sole clinical manifestation of the infection may also be witnessed.
Project description:Carcinoid heart disease is a rare condition that occurs in less than half of patients with carcinoid syndrome. The disease mainly affects right-sided heart valves; however, in 5%-10%, it can also involve left-sided valves. This case illustrates the most complicated form of the disease involving four heart valves.
Project description:The Ehlers-Danlos Syndrome (EDS) is part of a group of connective tissue diseases that affect the synthesis and processing of collagen leading to alterations in the structure of many tissues and organs. Herein, we reported a case of a patient with prolapse of the four cardiac valves. Non-significant regurgitation of the mitral, aortic, and tricuspid valves was observed. The pulmonary regurgitation (PR) was considered significant. Dilatation of the right ventricle with preserved systolic function was also noted. A cardiac magnetic resonance confirmed the findings of the echocardiogram and determined a severe PR (regurgitant fraction of 41%). The physical examination revealed hyperlaxity of the joints, skin hyperelasticity, defects in wound healing, and abdominal hernias suggesting EDS. The stress test did not develop any symptoms or complex arrhythmias. In this patient, the heart team initially decided medical treatment and evolutionary control. At the moment, he remains asymptomatic. Valvular involvement in EDS is an infrequent event and the compromise of the four cardiac valves is exceptional. The existence of severe PR with a marked increase in ventricular volumes, even in the absence of symptoms, in most cases requires an intervention on the valve. However, in patients with EDS, there are a high rate of complications and interventions should be avoided as much as possible.
Project description:Canine tachycardia-induced cardiomyopathy caused by several weeks of rapid ventricular pacing is a well-established animal model of congestive heart failure. However, little is known about the underlying changes in gene expression that occur in the canine myocardium after the induction of heart failure. This project aims to compare expression profiles in left ventricular free wall samples from control dogs and dogs with pacing-induced heart failure on the custom MuscleChip. Keywords: other
Project description:Extensive biaxial mechanical testing of the atrioventricular heart valve leaflets can be utilized to derive optimal parameters used in constitutive models, which provide a mathematical representation of the mechanical function of those structures. This presented biaxial mechanical testing protocol involves (i) tissue acquisition, (ii) the preparation of tissue specimens, (iii) biaxial mechanical testing, and (iv) postprocessing of the acquired data. First, tissue acquisition requires obtaining porcine or ovine hearts from a local Food and Drug Administration-approved abattoir for later dissection to retrieve the valve leaflets. Second, tissue preparation requires using tissue specimen cutters on the leaflet tissue to extract a clear zone for testing. Third, biaxial mechanical testing of the leaflet specimen requires the use of a commercial biaxial mechanical tester, which consists of force-controlled, displacement-controlled, and stress-relaxation testing protocols to characterize the leaflet tissue's mechanical properties. Finally, post-processing requires the use of data image correlation techniques and force and displacement readings to summarize the tissue's mechanical behaviors in response to external loading. In general, results from biaxial testing demonstrate that the leaflet tissues yield a nonlinear, anisotropic mechanical response. The presented biaxial testing procedure is advantageous to other methods since the method presented here allows for a more comprehensive characterization of the valve leaflet tissue under one unified testing scheme, as opposed to separate testing protocols on different tissue specimens. The proposed testing method has its limitations in that shear stress is potentially present in the tissue sample. However, any potential shear is presumed negligible.
Project description:The aim of this study was to reveal the pathogenesis of aortic stenosis (AS) and regurgitation (AR) by comparing differences in mechanical and biochemical alterations. We applied scanning acoustic microscopy (SAM) to measure the speed of sound (SOS) through valves to estimate the elasticity and monitor sensitivity to protease treatment, as the SOS is correlated with the stiffness of materials, which is reduced after digestion by proteases. The fibrosa of both the AS and AR groups were stiffer than the fibrosa of the normal group. The AR group displayed significantly stiffer fibrosa than the AS group, with the exception of calcified areas. The AS group showed significantly decreased SOS values following protease digestion, whereas the AR showed little reduction. The AS group presented type III collagen in the fibrosa and the ventricularis. In the AR group, both type I collagen and type III collagen coexisted in the fibrosa and the ventricularis. Upon immunostaining for advanced glycation end-products, the AS group showed sparse, weak staining, whereas the AR group presented a strong, band-like positive reaction in the fibrosa. In conclusion, tissue remodelling associated with damage and repair is associated with AS pathogenesis, whereas static chemical alterations with slow collagen turnover induce AR.
Project description:This report presents a novel style of placing nasal stents. Patients undergoing surgical procedures in the region of nasal vestibule and nasal valves are at risk of developing vestibular stenosis and lifelong problems with the external and internal nasal valves; sequels of the repair. The objective of the report is to demonstrate a simple and successful method of an inverted V- Stent placement to prevent potential complication of vestibular stenosis and nasal valve compromise later in life. Following a fall on a sharp edge of a metallic bed, a sixteen month old child with a deep lacerated nasal wound extending from the collumellar base toward the tip of the nose underwent surgical exploration and repair of the nasal vestibule and nasal cavity. A soft silicone stent fashioned as inverted V was placed bilaterally. The child made a remarkable recovery with no evidence of vestibular stenosis or nasal valve abnormalities. In patients with nasal trauma involving the nasal vestibule and internal and external nasal valves stent placement avoids sequels, adhesions, contractures, synechia vestibular stenosis and fibrosis involving these anatomical structures. The advantages of the described V- stents over the traditional readymade ridged nasal stents, tubing's and composite aural grafts are: a) technical simplicity of use, b) safety, c) less morbidity, d) more comfortable, and e) economical. To our knowledge, this is the first report of such a stent for prevention of vestibular stenosis and preserving nasal valves.