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M N Sheppard

Publications and source records attributed to M N Sheppard.

At least 55 records · Page 3Linked to original sources
PubMed1998

Anatomy of the pig heart: comparisons with normal human cardiac structure.

Transgenic technology has potentially solved many of the immunological difficulties of using pig organs to support life in the human recipient. Nevertheless, other problems still remain. Knowledge of cardiac anatomy of the pig (Sus scrofa) is limited despite the general acceptance in the literature that it is similar to that of man. A qualitative analysis of porcine and human cardiac anatomy was achieved by gross examination and dissection of hearts with macrophotography. The porcine organ had a classic 'Valentine heart' shape, reflecting its location within the thorax and to the orientation of the pig's body (unguligrade stance). The human heart, in contrast, was trapezoidal in silhouette, reflecting man's orthograde posture. The morphologically right atrium of the pig was characterised by the tubular shape of its appendage (a feature observed on the left in the human heart). The porcine superior and inferior caval veins opened into the atrium at right angles to one another, whereas in man the orifices were directly in line. A prominent left azygous vein (comparable to the much reduced left superior caval or oblique vein in man) entered on the left side of the pig heart and drained via the coronary sinus. The porcine left atrium received only 2 pulmonary veins, whereas 4 orifices were generally observed in man. The sweep between the inlet and outlet components of the porcine right ventricle was less marked than in man, and a prominent muscular moderator band was situated in a much higher position within the porcine right ventricle compared with that of man. The apical components of both porcine ventricles possessed very coarse trabeculations, much broader than those observed in the human ventricles. In general, aortic-mitral fibrous continuity was reduced in the outlet component of the porcine left ventricle, with approximately two-thirds of the aortic valve being supported by left ventricular musculature. Several potentially significant differences exist between porcine and human hearts. It is important that these differences are considered as the arguments continue concerning the use of transgenic pig hearts for xenotransplantation.

Adult↗
PubMed1997

Location of the coronary arterial orifices in the normal heart.

We examined the coronary arterial orifices in relation to the aortic valve to determine the range of normality in 23 normal hearts from autopsied adults. We determined the position of the zones of apposition between leaflets, the size of the leaflets, the number, position, and shape of the coronary arterial orifices, and their relation to the sinutubular junction. The aortic valve had three leaflets in all specimens, nearly equally spaced around the aorta. The left coronary artery arose within the left posterior aortic sinus (of Valsalva) in 16 (69%) specimens, above the sinutubular junction in five (22%), and at the level of the junction in two (9%). The distance of the left orifice from the zone of apposition between the left posterior and anterior aortic leaflets was between 13% and 61% of the width of the aortic sinus at the sinutubular junction. The right coronary artery arose within the anterior aortic sinus in 18 (78%) specimens, above the junction in three (13%), and at the level of the junction in two (9%). The distance of the orifice from the zone of apposition between the leaflets hinged from the anterior and right posterior aortic sinuses was between 5% and 62% of the width of the aortic sinus at the sinutubular junction. An accessory coronary orifice was found in the anterior aortic sinus in 17 (74%) specimens, whereas a third orifice in this sinus was found in five hearts. The coronary arterial orifices are usually located within the aortic sinuses below the sinutubular junction, but are rarely centrally located. Accessory coronary arterial orifices are found in the majority of the anterior aortic sinuses.

Adult↗
PubMed1997

Primary epithelioid angiosarcoma of the lung presenting as pulmonary hemorrhage.

Pulmonary angiosarcomas are usually secondary tumors, and only a few primary cases have been described. We report a unique case of epithelioid angiosarcoma arising in the lungs as a bilateral multinodular infiltrate and presenting as pulmonary hemorrhage. Because of its epithelioid histology, this tumor may resemble a carcinoma, also staining positively for keratin markers. Therefore, unless the diagnosis of epithelioid angiosarcoma is considered and endothelial markers used, the diagnosis of epithelioid angiosarcoma may be overlooked at this site.

Aged↗
PubMed1997

Nuclear pleomorphism in typical carcinoid tumours of the lung: problems in frozen section interpretation.

Pulmonary typical carcinoid tumours are generally easy to diagnose with their uniform cells, carcinoid growth pattern and lack of mitoses. However, nuclear pleomorphism, which is common in other neuroendocrine tumours, is not emphasized in pulmonary carcinoid tumours. Three cases of typical carcinoid tumours, because of marked nuclear pleomorphism on frozen section, were misdiagnosed as non-small cell carcinomas.

Adult↗
PubMed1997

Localisation of a gene causing endocrine neoplasia to a 4 cM region on chromosome 1p35-p36.

The development of some endocrine tumours, such as medullary thyroid carcinomas, phaeochromocytomas, anterior pituitary adenomas, and parathyroid adenomas involve a putative tumour suppressor gene located on chromosome 1p32-pter, a region that represents 111 cM. In order to refine the location of this gene, 93 endocrine tumours (39 parathyroid adenomas, 40 anterior pituitary adenomas, seven pancreatic islet cell adenomas, and seven carcinoids) were investigated for loss of tumour heterozygosity (LOH) using the seven polymorphic loci 1pter-D1S228-D1S507-D1S234-D1S476-D1S22 0-D1S207-D1S206-1cen. LOH was detected in 27% of the parathyroid tumours and in 7.5% of the pituitary tumours, but in none of the pancreatic islet cell or carcinoid tumours. In addition, seven of the 10 parathyroid tumours that showed LOH of chromosome 1p facilitated a more precise mapping of this putative tumour suppressor gene; five tumours involved a loss only of the telomeric locus D1S228, whereas two other tumours showed LOH at the centromeric loci D1S507, D1S234, D1S476, and D1S220, but not D1S228. Thus, our results have mapped this tumour suppressor gene implicated in endocrine tumours to a 4 cM region flanked by D1S228 and D1S507 on chromosome 1p35-p36.

Alleles↗
PubMed1996

Innervation of human atrioventricular and arterial valves.

BACKGROUND: Limited information exists on the innervation of human cardiac valves and the relationship of nerve fibers and terminals with functional elements within leaflets. METHODS AND RESULTS: We examined human AV and arterial valves, obtained postmortem and at surgery, using quantitative immunohistochemical, histochemical, and confocal microscopic techniques. Significant differences in nerve density and distribution were found both between and within cardiac valves. Nerve density within the anterior leaflet of the mitral valve, for example, was twofold greater than that in the posterior leaflet (P < .001). Nerves within the AV valves were situated in the atrial layer and extended over the proximal and medial portions of the leaflets, whereas those in the arterial valves were situated in the ventricular layer. No nerves reached either the free edge or the fibrous core of the leaflets. The arterial valves displayed a similar density of innervation, except for the noncoronary leaflet of the aortic valve in which the innervation was attenuated (P < .01). The innervation of aortic valvar leaflets was age dependent. Nerve terminal arborizations, arising from myelinated nerves and exhibiting variable morphology, were detected in all four cardiac valves and in some tendinous cords. Nerve terminals exhibited either acetylcholinesterase activity or tyrosine hydroxylase and neuropeptide Y immunoreactivity. Varicose nerve fibers occurred in close physical proximity to valvar endothelial, smooth muscle, and fibroblast cells. CONCLUSIONS: Human cardiac valves have distinct patterns of innervation that comprise both primary sensory and autonomic components. The presence of distinct nerve terminals and the close association of varicose nerve fibers with endothelial, smooth muscle, and fibroblast cells suggest a possible neural involvement in the control of valvar function.

Acetylcholinesterase↗
PubMed1996

A quantitative assessment of innervation in the conduction system of the calf heart.

BACKGROUND: The aim of the present investigation was to determine the relative distribution of autonomic and sensory nerves in the cardiac conduction tissues of calves. METHODS: A quantitative immunohistochemical and histochemical technique was adopted. RESULTS: Immunoreactivity to the general neuronal marker protein gene product 9.5 (PGP 9.5) demonstrated that all regions of the conduction system possessed a higher relative density of total nerves when compared with the surrounding myocardial tissues. Unlike myocardial innervation, the conduction system did not display an atrial-to-ventricular gradient in nerve density. PGP 9.5-immunoreactive nerve trunks and varicose nerve fibres were more numerous in the transitional atrioventricular node and the penetrating atrioventricular bundle than in either the sinus node, compact atrioventricular node, or bundle branches. The Purkinje network of the ventricular conduction tissues possessed a rich supply of PGP 9.5-immunoreactive nerve trunks and varicose nerve fibres. Acetylcholinesterase (AChE)-positive nerves were the main subtype identified in the sinus and atrioventricular nodes and in the ventricular conduction tissues, representing 50-80% of the area occupied by PGP 9.5-immunoreactive nerves. The compact atrioventricular node possessed AChE-positive and tyrosine hydroxylase (TH)-immunoreactive nerves in similar proportions (45%), although, in general, TH-immunoreactive nerves had a lower relative nerve density than AChE-positive nerves. Neuropeptide Y (NPY)-immunoreactive nerves represented the main peptide-containing subpopulation and occurred throughout the conduction system, displaying a similar pattern of distribution and relative density to those demonstrating TH immunoreactivity. Nerve fibres immunoreactive for somatostatin, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide formed relatively minor subpopulations. CONCLUSIONS: The general innervation of the bovine conduction tissues exhibits significant regional variation. Throughout all regions of the conduction system, AChE-positive nerve represented the dominant subtype when compared with TH- and NPY-immunoreactive nerves. The distribution and relative density of nerve subtypes in the tissues of the bovine conduction system are similar to those observed in man, whereas differences were observed in other regions, such as the atrioventricular bundle and bundle branches. This finding must be considered by those making interspecies comparisons.

Acetylcholinesterase↗
PubMed1996

Loss of heterozygosity studies at the retinoblastoma and breast cancer susceptibility (BRCA2) loci in pituitary, parathyroid, pancreatic and carcinoid tumours.

OBJECTIVE: Allelic deletion of the retinoblastoma (Rb) gene on chromosome 13 has been reported in both pituitary and parathyroid tumours. We have investigated the roles of the Rb and the hereditary breast cancer susceptibility gene (BRCA2), which lie within 25 cM of each other on chromosome 13q12-14, in the multi-step aetiology of endocrine tumours. PATIENTS AND MEASUREMENTS: Seventy-seven endocrine tumours (43 anterior pituitary, 22 parathyroid, 7 carcinoid, and 5 pancreatic islet cell tumours) with paired leucocytes have been examined for loss of heterozygosity (LOH) at the Rb and BRCA2 loci by using specific oligonucleotide primers for the PCR amplification of microsatellite polymorphisms at three intragenic Rb markers, Rb1.20, Rbi4 and D13S153, and D13S260 which is linked to the BRCA2 locus. RESULTS: Seventy-five of the 77 tumour-leucocyte pairs were informative and LOH was detected in 1 of 16 non-functioning pituitary tumours, 1 of 8 prolactinomas, 3 of 19 parathyroid adenomas and 1 of 1 parathyroid carcinoma. All the 3 parathyroid adenomas with LOH were associated with aggressive clinical and histopathological features. Allele loss was not detected in any of the 16 somatotrophinomas, 2 corticotrophinomas, 1 gonadotrophinoma, 7 carcinoid tumours (6 bronchial, 1 metastatic intestinal) or 5 pancreatic islet cell tumours that were informative. CONCLUSIONS: These results demonstrate that allelic deletions of the 13q12-14 region occur in some pituitary adenomas and 16% of parathyroid adenomas. The extensive loss, which involves both the Rb gene and the BRCA2 locus, suggests that tumour suppressor genes in this region other than Rb or BRCA2 may be involved in the development and progression of some endocrine tumours.

BRCA2 Protein↗
PubMed1996

Fatal giant cell myocarditis after resection of thymoma.

A case of fulminant, fatal myocarditis occurring 10 days after resection of a benign medullary thymoma is described. A rare association between thymoma and giant cell myocarditis is recognised, but fulminant presentation so soon after removal of thymoma has not previously been reported.

Fatal Outcome↗
PubMed1996

Value and impact of necropsy in paediatric cardiology.

OBJECTIVE: To assess the current value of necropsy in paediatric cardiology and cardiothoracic surgery and determine its potential impact on clinical practice. DESIGN AND SETTING: Descriptive study of all paediatric cardiac deaths occurring over four years in a tertiary referral centre. Data were obtained from reviewing the hospital files, available necropsy records and specimens, and audit reports. PATIENTS: Paediatric patients with congenital or acquired heart disease, who died of a cardiac cause between January 1992 and July 1995. Inclusion criteria were that the diagnosis of heart disease was made before death, and that patients were managed thereafter medically and/or surgically at the referral centre. The value of necropsy was assessed according to its contribution in establishing the cause of death (confirmed, clarified, precise cause of death uncertain) and the anatomy (simple confirmation or additional information provided). For cases not submitted to necropsy the clinical information relating to the cause of death was assessed and the case assigned as cause of death firm, uncertain, or unknown. RESULTS: One hundred and six deaths were identified (61 males, age at death: one day to 20 years). Seventy occurred early (a month or less) after surgery and were graded as postoperative deaths. The rest were considered to be either medical or late surgical deaths. Necropsy was performed in 59 (55.6%). The precise cause of death was confirmed in 33 (55.9%), clarified in 22 (37.3%), and remained uncertain in four (7.8%). Additional information regarding the anatomy was found in eight (13.6%) cases. In five cases (8.5%) the necropsy detected findings which, if known before death, would probably have improved outcome. For the patients dying without a necropsy, the cause of death remained uncertain in 10 (21.3%) and unknown in seven (14.9%). In 36% of cases, therefore, a firm cause of death that might have been provided by a necropsy was missing. CONCLUSION: In paediatric cardiology necropsy continues to provide clinically relevant information at a high level. It remains vital for ensuring quality of medical care, in instigating improvements in future management, and increasing understanding of congenital heart disease. The procedure should therefore be sought actively in all cases.

Adolescent↗
PubMed1996

Pulmonary B-cell non-Hodgkin's lymphoma associated with autoimmune disorders: a clinicopathological review of six cases.

Because pulmonary B-cell non-Hodgkin's lymphomas are now thought to arise in bronchial mucosa-associated lymphoid tissue (MALT), 45 patients with pulmonary B-cell lymphomas were reviewed to look for aetiological factors in the lung. It was found that six of the 45 lymphomas arose in patients with systemic autoimmune disease, which in three patients involved the lung. These three patients all had cryptogenic fibrosing alveolitis treated with long-term immunosuppressive therapy. Five of the six lymphomas were high grade and one was low grade. The association of pulmonary lymphomas with autoimmune interstitial lung disease is consistent with associations between autoimmune diseases and lymphomas presenting at other mucosal sites, and lends weight to the hypothesis that formation of bronchial mucosa-associated lymphoid tissue precedes the development of lymphoma.

Adult↗
PubMed1996

A quantitative study of nerve distribution in the conduction system of the guinea pig heart.

Quantitative measurements of relative nerve density were achieved using computer-assisted image analysis of immunohistochemically and histochemically defined nerves in the conduction system of the guinea pig heart. All regions of the conduction system possessed a similar density of nerve fibres and fascicles displaying immunoreactivity for the general neuronal marker protein gene product 9.5 (PGP 9.5), and this was 3 to 4-fold higher than in the adjacent myocardium. Acetylcholinesterase (AChE) positive and tyrosine hydroxylase (TH)-immunoreactive nerves were the main subtypes identified in the sinus and atrioventricular nodes, representing 40-45% of the stained area occupied by PGP 9.5-immunoreactive nerves. AChE-positive nerves were the dominant subtype identified in the left and right bundle branches, but were equal in proportion to TH-immunoreactive nerves in the penetrating bundle. Neuropeptide Y-immunoreactive nerves represented the main peptide-containing subpopulation in the nodal tissues, displaying a similar pattern of distribution and relative density to those nerves demonstrating TH immunoreactivity. Substance P and calcitonin gene-related polypeptide immunoreactive nerves were present throughout the conduction system and represented the main peptide-containing subpopulation in the ventricular conduction tissues. Nerve fibres showing immunoreactivity for either somatostatin or vasoactive intestinal polypeptide exhibited distinct patterns of distribution and comprised a relatively minor component of the innervation. The innervation of the guinea pig conduction tissues thus exhibits a uniform distribution and it comprises putative parasympathetic nerves and intrinsic neurons (AChE positive), sympathetic efferent nerves (NPY and TH-immunoreactive nerves) as well as other peptide-containing nerves, some of which (substance P and calcitonin gene-related polypeptide) are considered to represent afferent nerves. The distribution and density of nerve subpopulations in the guinea pig conduction system differ from those observed in the human conduction system, which suggests that the guinea pig may be an inappropriate model for comparative functional studies.

Animals↗
PubMed1995

Distribution, morphology, and neurochemistry of endocardial and epicardial nerve terminal arborizations in the human heart.

BACKGROUND: The heart contains a variety of morphologically distinct nerve terminals known to influence cardiac function. Little is known about the distribution, morphology, and neurochemistry of these terminals in the human heart. METHODS AND RESULTS: We examined the entire endocardial and epicardial surfaces of infant and adult hearts obtained postmortem and at transplantation using immunohistochemical and histochemical staining of whole-mount preparations in conjunction with confocal and fluorescence microscopy. Terminals arising from nerve fibers (diameter, 6 to 10 microns) immunoreactive for myelin basic protein were identified in the atrial endocardium, epicardium, and coronary sinus, and four types were distinguished by differences in immunostained nerve area (range, 358 to 797 microns 2) and dispersion (range, 620 to 4684 microns 2). These terminals displayed immunoreactivity for tyrosine hydroxylase, neuropeptide Y, and the general neural marker protein gene product 9.5. Acetylcholinesterase (AChE) activity was detected in < 5% of endocardial terminals and in no epicardial terminals arising from myelinated fibers. The latter were observed in close proximity to mesothelial cells, and nerve fibers supplying these terminals were found to be associated with local ganglia. A distinct population of terminals (mean stained area, 35 microns 2; 18 to 53 microns 2, 95% CI; and mean dispersion, 59 microns 2; 38 to 80 microns 2, 95% CI) was demonstrated to arise from nonmyelinated fibers (mean diameter, 2.5 microns; 2.2 to 2.8 microns, 95% CI) in the endocardial plexus of the atria and left ventricle and were predominantly AChE-positive. CONCLUSIONS: Specialized nerve terminals are distributed more widely in the human heart than has been described in experimental animals. These terminals express either AChE activity or tyrosine hydroxylase and neuropeptide Y immunoreactivity, suggesting that acetylcholine, catecholamines, and neuropeptide Y may be present in sensory and autonomic nerves in the human heart.

Acetylcholinesterase↗
PubMed1995

Pulmonary B-cell non-Hodgkin's lymphomas. The value of immunohistochemistry and gene analysis in diagnosis.

We reviewed 45 pulmonary B-cell non-Hodgkin's lymphomas to determine whether their morphology and immunohistochemical features were those of lymphomas arising from mucosa-associated lymphoid tissue (MALT), as described in other sites. The polymerase chain reaction was used to provide further information on clonality. We found that these lymphomas infiltrate the pulmonary interstitium along bronchovascular bundles and interlobular septa, subsequently spilling out into airspaces and finally destroying the alveolar architecture of the lung. Central hyaline sclerosis and vascular infiltration were common features. All lymphomas stained CD20 positive and were accompanied by variable numbers of reactive CD3 positive T-cells. Cytokeratin staining with CAM 5.2 was useful in identifying lymphoepithelial lesions. CD21 staining of follicular dendritic cells revealed germinal centres where they were not recognizable on H & E staining. The polymerase chain reaction was performed on paraffin tissue from 28 patients. Twenty were low grade, of which 12 showed a clonal band and eight showed a polyclonal smear pattern. Eight were high grade, of which one revealed a clonal band. Three produced polyclonal smear patterns and four cases were inadequate samples. In one patient who had lymphoma at a second extranodal site, identical bands were identified, evidence for 'homing' of lymphoid cells towards mucosal epithelium.

Base Sequence↗
PubMed1995

Reactive pulmonary lymphoid disorders.

The two main reactive pulmonary lymphoid disorders are lymphoid interstitial pneumonia and follicular bronchitis/bronchiolitis, both pathological entities with a variety of aetiologies. We reviewed the morphological and immunohistochemical features of 26 cases with one or other of these two diagnoses, to explore the possibility that they represented overlapping patterns of hyperplasia of the bronchopulmonary immune system. The polymerase chain reaction was used to determine the clonality of the infiltrates. Histologically, there was a spectrum of changes with two main components. An interstitial infiltrate of mainly T lymphocytes, plasma cells and histiocytes predominated in lymphoid interstitial pneumonia, whilst lymphoid follicles predominated around airways in follicular bronchitis/bronchiolitis. Classification of the disorder rested on which component the pathologists believed to be dominant. In two cases, histology and immunohistochemistry suggested lymphoma, and in one of these cases this diagnosis was confirmed by the polymerase chain reaction. One case of lymphoid interstitial pneumonia produced three bands. The remainder produced polyclonal patterns when samples were adequate. Clinically, there was no clear difference between patients with the two disorders, or patients with pathological features of both.

Adolescent↗
PubMed1995

The value of PE-10, a monoclonal antibody against pulmonary surfactant, in distinguishing primary and metastatic lung tumours.

A new monoclonal antibody (PE-10) raised against components of pulmonary surfactant has been assessed for its ability to distinguish primary from secondary carcinomas in the lung. We applied this antibody to a series of 107 primary lung carcinomas, 40 adenocarcinomas of other sites, and 26 cases of adenocarcinoma metastatic to lung and pleura. Of the primary lung carcinomas, all the non-mucinous bronchiolo-alveolar carcinomas were positive whereas all the mucinous cases were negative; 60% of other types of adenocarcinoma were positive and 10% of large cell undifferentiated carcinomas, 20% of small cell carcinomas and 40% of atypical carcinoids also showed focal positivity. Squamous cell carcinomas were all negative. Adenocarcinomas of the breast, kidney, large bowel and ovaries were all negative, as were all 26 cases of adenocarcinoma metastatic to the lung and pleura. We conclude that this antibody is highly specific and moderately sensitive for primary tumours of the lung.

Adenocarcinoma↗
PubMed1995

Symptomatic cardiomyopathy as a presentation in Whipple's disease.

A patient presenting with congestive cardiac failure and anaemia underwent investigation which led to the diagnosis of Whipple's disease, associated with dilated cardiomyopathy. Conventional antibiotic therapy for Whipple's disease resulted in resolution of the traditional features of Whipple's disease and a marked improvement in the patient's heart failure.

Aged↗