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Mary Sheppard

Publications and source records attributed to Mary Sheppard.

10 recordsLinked to original sources
PubMed2006

Comparison of two gene transfer models for the attenuation of myocardial ischemia-reperfusion injury following preservation for cardiac transplantation.

OBJECTIVE: Two models of ex vivo gene transfer were compared by examining the protective effect of adenovirus-mediated transfection of a free radical scavenger superoxide dismutase (SOD) during experimental ischemia-reperfusion mimicking preservation for cardiac transplantation. METHODS: Donor rat hearts (n=6 per group) were infused (subgroups IA and IB) or continually perfused (subgroups IIA and IIB) with solution containing adenoviral vector carrying beta-galactosidase (subgroups IA and IIA) or Mn-SOD (subgroups IB and IIB) over 5s with 1h storage and 15 min, at 4 degrees C, respectively. Hearts were then implanted heterotopically into the abdomen of recipient rats. Four days later, transplanted hearts were collected, connected to Langendorff perfusion apparatus and subjected to 6h of ischemia followed by 1h of reperfusion. Cardiac function was evaluated using intraventricular balloon at the beginning of Langendorff perfusion and following ischemia-reperfusion. RESULTS: Blue staining from hydrolyses of X-gal by beta-galactosidase was confirmed in AdLacZ transduced hearts. Immunoreactivity with anti-human Mn-SOD antibody then staining was positive in AdMnSOD-transduced hearts. Percent recovery of preischemic left ventricular developed pressure (LVDP) increased from 55.9+/-3.1% to 67.3+/-6.2% (P=0.048) and from 58.0+/-8.0% to 78.9+/-6.0% (P<0.001) in subgroups IA, IB, IIA and IIB, respectively. The difference in LVDP recovery between treatment groups of the two transfection methods (IB vs IIB) was significant (P=0.044). CONCLUSION: Adenoviral Mn-SOD ex vivo delivery using continuous myocardial perfusion is superior to bolus infusion in the attenuation of myocardial ischemia-reperfusion injury.

Adenoviridae↗
PubMed2006

The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease.

Anderson-Fabry Disease (AFD) is a storage disease that mimics hypertrophic cardiomyopathy. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance occurs in approximately 50% of patients in the basal inferolateral LV wall, but how an intracellular storage disease causes focal LGE is unknown. We present a whole-heart histological validation that LGE is caused by focal myocardial collagen scarring. This scarring may be the substrate for electrical re-entry and sudden arrhythmic death. The reasons for this distribution of fibrosis are unclear, but may reflect inhomogeneous left ventricular wall stress.

Analysis of Variance↗
PubMed2005

The coronary sinus conduit function: anatomical study (relationship to adjacent structures).

BACKGROUND: The mitral valve annulus (MVA) is anchored antero-medially to the aorta. Dilatation of the MVA primarily affects its postero-lateral aspect, which is related to the coronary sinus (CS). The CS and its tributaries have been used for pacing the left ventricle in patients with intractable heart failure. The aim of this study was to determine anatomical relations between the CS and its adjacent structures in 40 adult normal cadaveric heart specimens. METHODS: In 32 specimens, longitudinal sections were made along the free circumference of the MVA in 6 separate regions, 36 degrees between each, with the 0 degree marked by a line joining the centre of the CS ostium and that of the MV. In each section, the relations of the CS to the circumflex artery and the MVA were determined. CS diameter and its distance from the endocardium, just below the MVA, were also measured by a digital calliper. RESULTS: The great cardiac vein (GCV) diameter is 5.6 +/- 1.6 mm. As it leaves the interventricular groove, it curves to the left forming the base of the triangle of "Brocq and Mouchet" with the two branches of the left coronary artery, having a triple relationship with the circumflex artery. It then continues as the CS (diameter 9.3 +/- 5.3 mm) in the inferior atrioventricular groove. The end part of the GCV crosses superficial to the left circumflex artery at the level of the left marginal vein. The shortest distance between the wall of the CS and the endocardium adjacent to the MVA at the level of the anterolateral commissure is 5.2 +/- 1.6 mm, i.e. beyond the Vieussens valve. Thus, together with the CS the great cardiac vein, form a semicircular venous channel at the postero-lateral aspect of the MVA. In 37/40 hearts, this venous channel arches upwards in its middle part to be in direct contact with the left atrium. CONCLUSION: This study demonstrates an intimate proximity between the coronary sinus, at its beginning and end, and the mitral valve annulus. It also highlights the close relationship between the great cardiac vein, the annulus and the left ventricular free wall. Assessing the same relationship using the currently available imaging techniques should aid in the successful cannulation of the coronary sinus for various cardiological interventions.

Adult↗
PubMed2003

Detection of enterovirus capsid protein VP1 in myocardium from cases of myocarditis or dilated cardiomyopathy by immunohistochemistry: further evidence of enterovirus persistence in myocytes.

The association of enteroviruses with myocardial disease has been investigated extensively by molecular biological techniques to detect viral RNA, but remains controversial. This retrospective study investigated the involvement of enterovirus in myocarditis or dilated cardiomyopathy (DCM) by detection of viral antigens in myocardial samples from a new patient series using an optimized immunohistochemical technique. Formalin-fixed, paraffin-embedded biopsy, autopsy or explanted myocardial tissue samples were obtained from 136 subjects. These comprised histologically proven cases of acute fatal myocarditis (n=10), DCM (n=89, including 10 patients with healing/borderline myocarditis) and a comparison group of samples from 37 unused donor hearts and cases with other conditions. A monoclonal antibody 5-D8/1 directed against a conserved, non-conformational epitope in capsid protein VP1 was employed for broad detection of different enterovirus serotypes. Investigations were performed blindly. Histological sections from 7 of 10 fatal myocarditis cases, 47 of 89 patients (52.8%) with DCM were positive for the viral capsid protein VP1 by immunohistochemical staining. Consecutive sections of positive samples were negative when the antibody was omitted or replaced with subclass- and concentration-matched normal mouse IgG. In contrast, only 3 of 37 samples (8.1%) in the comparison group were positive (Yates corrected chi(2)=19.99, P<0.001: odds ratio =12.68). VP1 staining was distributed in individual or grouped myofibers and localized in the cytoplasm of myocytes. In some cases, VP1 was detected in only a few myofibers within an entire section. These results provide further evidence of enterovirus involvement in a high proportion of DCM cases and demonstrate that VP1 is present in disease stages from acute myocarditis, healing myocarditis to end-stage DCM requiring cardiac transplantation, indicating translation of viral protein during persistent enterovirus infection.

Animals↗
PubMed2003

Herpes simplex virus type 1 infection associated with atrial myxoma.

Some findings suggest an infectious factor in cardiac myxoma and certain histopathological features indicate herpes simplex virus type 1 (HSV-1) infection. We hypothesized that HSV-1 may be involved in the pathogenesis of cardiac myxoma. Paraffin-embedded tissue samples from 17 patients with atrial myxoma were investigated for HSV-1 antigen by immunohistochemistry and viral genomic DNA by nested polymerase chain reaction. The histogenesis and oncogenesis of atrial myxoma were assessed by the expression of calretinin, Ki67, and p53 protein, respectively. Autopsy myocardial samples, including endocardium from 12 patients who died by accident or other conditions, were used for comparison. HSV-1 antigen was detected in atrial myxoma from 12 of 17 patients: 8 of these 12 samples were positive also for HSV-1 DNA. No HSV-1 antigen or DNA was found in tissue from the comparison group. Antigens of HSV-2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus were not found in atrial myxoma. Calretinin was found in myxoma cells of all 17 cases but Ki67 was present only in smooth muscle cells or infiltrating cells in some cases. p53 was not detectable in any myxoma. Most infiltrating cells were cytotoxic T lymphocytes. These data suggest that HSV-1 infection is associated with some cases of sporadic atrial myxoma and that these may result from a chronic inflammatory lesion of endocardium.

Adolescent↗
PubMed2003

Multigene adenoviral therapy for the attenuation of ischemia-reperfusion injury after preservation for cardiac transplantation.

OBJECTIVE: The protective effect of adenovirus-mediated ex vivo multigene transfer with superoxide dismutase, a free radical scavenger, and nitric oxide, a vasodilator with anti-inflammatory properties, was examined in the rat heart during experimental ischemia-reperfusion mimicking preservation for cardiac transplantation. METHODS: Donor rat hearts (n = 6 per group) were perfused with solution containing adenoviral vector carrying genes for beta-galactosidase (group A), endothelial nitric oxide synthase (group B), manganese superoxide dismutase (group C), or both endothelial nitric oxide synthase and manganese superoxide dismutase (group D). Hearts were then implanted heterotopically into the abdomens of recipient rats. Four days later, transplanted hearts were collected, connected to a Langendorff perfusion apparatus, and subjected to 6 hours of ischemia followed by 1 hour of reperfusion. Cardiac function was evaluated with an intraventricular balloon at the beginning of Langendorff perfusion and after ischemia-reperfusion. RESULTS: Effective gene transfection was confirmed with X-gal staining in group A hearts. Positive immunoreactivity for endothelial nitric oxide synthase, manganese superoxide dismutase, or both was present predominantly in cardiomyocytes in group B, C, and D hearts. Percentage recovery of preischemic left ventricular developed pressure was 62.1% +/- 7.36% in group A; recoveries were increased to 79.6% +/- 6.4%, 86.8% +/- 9.1%, and 79.4% +/- 6.2% in groups B, C, and D, respectively. CONCLUSION: These results indicate that adenoviral gene transfer of manganese superoxide dismutase and endothelial nitric oxide synthase can attenuate myocardial ischemia-reperfusion injury, with the former providing the most significant protection. Combined overexpression of manganese superoxide dismutase and endothelial nitric oxide synthase did not enhance myocardial recovery any further.

Adenoviridae↗
PubMed2003

Evidence for rheumatic valve disease in patients with severe tricuspid regurgitation long after mitral valve surgery: the role of 3D echo reconstruction.

BACKGROUND AND AIM OF THE STUDY: Although severe tricuspid regurgitation (TR) is a well-recognized, long-term complication of rheumatic mitral valve replacement that impairs the functional results of surgery, its exact basis remains unclear and its management is unsatisfactory. The study aim was to obtain a detailed assessment of tricuspid valve morphology and function using 2D transesophageal echocardiography (TEE) with 3D reconstruction, and to determine long-term clinical outcome in patients after surgery for rheumatic mitral valve disease. METHODS: A total of 42 patients (mean age 50 +/- 10 years) was followed up; 39 patients had mitral replacement and three had valvotomy. Thirty patients had developed impaired exercise tolerance, fluid retention and echocardiographic evidence of severe TR at 8.2 +/- 2.6 years after surgery; the remainder had mild regurgitation. RESULTS: Follow up showed greater mortality in the severe TR group, with approximately 50% survival at 60 months after diagnosis compared with mild TR. None of the patients with severe TR had a dysfunctional mitral prosthesis. In these patients, transthoracic echo-Doppler showed enlarged right atrium and right ventricle, a mean transtricuspid retrograde pressure drop of 15 +/- 4 mmHg and apparently normal leaflet anatomy. Twenty patients (15 with severe TR) underwent a TEE and 3D reconstruction study for further evaluation. Abnormal leaflet anatomy was demonstrated in all patients with severe TR, with restricted leaflet motion in 10, leaflet shortening and thickening in the remainder, and dilatation of tricuspid valve annular insertion suggestive of rheumatic involvement. Although diastolic transtricuspid velocities were increased (peak flow 0.8 +/- 0.1 m/s) in these patients due to increased stroke volume, significant tricuspid stenosis was present in only two cases (mean gradient 4 and 3 mmHg respectively). Histopathology confirmed the presence of leaflet vascularization and extensive fibrosis in two patients who underwent tricuspid valve replacement. CONCLUSION: Rheumatic leaflet involvement contributes to severe TR occurring long after mitral valve replacement, though overt stenosis is uncommon. Knowledge of the structural basis of this condition may thus improve its long-term management, possibly with early tricuspid valve repair.

Adult↗
PubMed2002

Intravascular inflammatory myofibroblastic tumors in infancy.

Inflammatory myofibroblastic tumor (IMT), previously described as inflammatory pseudotumor, can occur at any age but is a recognized soft tissue tumor of childhood. Less than 10 previous cases have been described of IMT affecting the heart, in patients ranging from 5 months to 17 years of age. We present three unusual, but similar, cases of IMT in infants, which were all predominantly intravascular in location, one of which was associated with death due to angiodestructive lesions of the coronary and cerebral arteries. These cases demonstrate an apparently distinct phenotype, with a predominant intravascular location of the tumor. Furthermore, this series highlights the difficulty in categorizing such lesions as benign versus malignant on histological grounds alone. IMT should be considered in the differential diagnosis of unusual pediatric intravascular spindle cell lesions.

Biomarkers, Tumor↗
PubMedDate not supplied

Left ventricular aneurysm, aortic valve disease and coronary narrowing in a patient with Hunter's syndrome.

Hunter's syndrome (mucopolysaccharidosis type 2, MPS 2) is an inherited disorder of glycosaminoglycan degradation commonly associated with cardiac disease. We present the case of a young man with unusual cardiac manifestations of this syndrome. When mixed aortic valve disease was noted in childhood, other classical features of the milder form of Hunter's syndrome were present. There was no symptomatic or echocardiographic cardiovascular deterioration until age 27 when the patient presented in severe biventricular failure. Investigations demonstrated cardiomegaly and a large apical left ventricular aneurysm. The patient died suddenly soon after this diagnosis. Post mortem examination demonstrated a hypertrophied left ventricle with a 6-cm apical aneurysm. Coronary arterial walls were diffusely thickened but with only mild lumenal stenosis. Mitral and aortic valve disease was also present. There is one previous report of ventricular aneurysm in Hunter's syndrome. Pathophysiological contributions to aneurysm formation may include abnormal coronary flow, the presence of aortic stenosis and abnormal myocardium. This patient's sudden deterioration after a long period of clinical stability reinforces the need for careful follow-up of patients with cardiac manifestations of Hunter's disease.

Adult↗