Search PubMed⌕ Search

Biomedical subjects

T N James

Publications and source records attributed to T N James.

At least 19 recordsLinked to original sources
PubMed1992

Ultrastructural alterations of the conduction system in mice exhibiting sinus arrest or heart block during Coxsackievirus B3 acute myocarditis.

By light and electron microscopy we studied the sinus nodes and atrioventricular (AV) conducting tissue of six C3H/He mice having coxsackievirus B3 acute myocarditis. Sinus arrest was documented in all six mice, and second- or third-degree AV block was documented in three of the six mice. Although myocarditic changes in the conduction system, especially in the sinus node, were less than those in atrial and ventricular working myocardium, there were distinct abnormalities within both the sinus node and AV conducting tissue in all six hearts. Important ultrastructural alterations were inflammatory cell infiltrates and significant injury of specialized cells and of neural tissue. Specialized cells showed various features of degeneration and necrosis. Neural tissue damage included degeneration of axons and Schwann cells and disorganization of the neuromuscular junctions. Inflammatory cells, particularly macrophages, were often in intimate contact with injured specialized cells and neural tissue. Interstitial edema and bleeding and lymphatic vessel dilatation were also observed. These pathologic changes are considered to play an important role in the development of the documented disturbances of rhythm and conduction.

Animals↗
PubMed1992

Comparative ultrastructure of the tip of ventricular papillary muscle.

Electron microscopic studies of the tips of left ventricular papillary muscles from seven human, two monkey, three sheep, and two chicken hearts were done to elucidate the fine structure of myotendinous junctions. The human specimens were from normal hearts obtained 3 to 9 hours postmortem from persons aged 7 months to 30 years (mean, 13.3 years). We found no significant ultrastructural differences between the human hearts and those of monkey, sheep, and chicken. Myocardial fibers were elongated and thinner (tapered) in the tips of papillary muscles. In addition to usual working myocardial cells, the distal end of narrowing muscle fibers also contained small pale cardiocytes containing fewer myofibrils and smaller mitochondria. These cells were similar to P cells or transitional cells in the conduction system. Nerve axons and Schwann cells were commonly seen in the interstitium, usually in association with capillaries. Fibroblasts and axon varicosities were occasionally seen extremely close to the cardiocytes. These specialized myocardial cells associated with rich neural tissue in the papillary muscle tip possibly function as foci of local automaticity. This histologic organization may also represent neurosensory function responding to and monitoring local pressure changes, efferent adrenergic or cholinergic neural activity, or both.

Adolescent↗
PubMed1991

Clinical and pathologic manifestations of pulmonary vascular disease in the toxic oil syndrome.

The toxic oil syndrome in Spain affected greater than 20,000 people. In the initial stages, it was characterized by a respiratory distress syndrome with myalgias and eosinophilia. Pulmonary hypertension developed in 20% of the patients and in many, it has spontaneously regressed. Nevertheless, in a small subgroup, it has progressed to a malignant course of cor pulmonale, leading rapidly to death. Clinical and pathologic features of 40 patients with severe pulmonary hypertension due to the toxic oil syndrome are presented (32 female and 8 male patients; mean age 26 +/- 13 years). The study began in June 1981, which was near the onset of the toxic oil epidemic, and ended in December 1987, greater than 6 years later. The pulmonary hypertension is clinically and pathologically indistinguishable from primary pulmonary hypertension. Direct endothelial injury by the toxic agent is proposed as the initial trigger of this type of pulmonary hypertension, but an interaction between the toxic agent and specific individual susceptibility is probably required in its pathogenesis.

Adolescent↗
PubMed1991

Cardiac abnormalities in the toxic oil syndrome, with comparative observations on the eosinophilia-myalgia syndrome.

Early in the course of studies of the Spanish toxic oil syndrome it was recognized that vascular lesions were a major problem, most logically attributable to endothelial damage by the toxic oil. However, most clinical attention has been directed to the pulmonary complications and the evolution into a scleroderma-like illness later. In this study of 11 victims of the toxic oil syndrome careful postmortem studies of the coronary arteries and conduction system and neural structures of the heart demonstrated major injury to all those components of the heart. Obliterative fibrosis of the sinus node in four cases resembled findings in fatal scleroderma heart disease, and in eight the cardiac lesions resembled those of lupus erythematosus. The more impressive pathologic features involved the coronary arteries and neural structures, which were abnormal in every heart. The arterial disease included widespread focal fibromuscular dysplasia, but there was also an unusual myointimal proliferative degeneration of both small and large coronary arteries in five patients, four of whom were young women. In two hearts, portions of the inner wall of the sinus node artery had actually detached and embolized downstream. Coronary arteritis was rarely found. Inflammatory and noninflammatory degeneration of cardiac nerves was widespread. Fatty infiltration, fibrosis and degeneration were present in the coronary chemoreceptor. In most respects these cardiac abnormalities resemble those described in the eosinophilia-myalgia syndrome caused by an altered form of L-tryptophan. In both diseases there is good reason to anticipate more clinical cardiac difficulties than have so far been reported, and even more basis for future concern, especially relative to coronary disease and cardiac electrical instability.

Adult↗
PubMed1991

Postmortem studies of the heart in three fatal cases of the eosinophilia-myalgia syndrome.

OBJECTIVE: To examine the hearts of individuals who died from the eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan, with particular attention paid to the coronary arteries, the neural structures, and the conduction system of the heart because of reported terminal disturbances of cardiac rhythm and conduction. STUDY MATERIAL: Three hearts fixed in neutral formalin and well preserved with all the relevant areas of conduction system intact. METHODS: Light microscopic examination of subserial sections of the sinus node, atrioventricular node and His bundle, coronary chemoreceptor and regional nerves, ganglia, and small coronary arteries. Routine stains used were Goldner trichrome and Verhoeff-van Gieson. RESULTS: Arterial abnormalities were numerous and primarily of two types: focal fibromuscular dysplasia causing moderate to severe narrowing, as well as endarteritis and panarteritis. Extensive examples of neuritis and ganglionitis were present throughout the heart, including the conduction system, where arterial abnormalities were also abundant. In the coronary chemoreceptor there were both old and new lesions comprising focal inflammation with degeneration as well as older areas of fibrotic destruction. Within the sinus node, areas of dense fibrosis replaced all nodal tissue. These abnormalities were similar in nature and extent in all three hearts. CONCLUSIONS: The pathologic lesions present in the coronary arteries, neural structures, and conduction system of the heart in patients who died from the eosinophilia-myalgia syndrome provide a suitable anatomic substrate for substantial cardiac electrical instability, including the occurrence of sudden death. In cases of unexplained cardiac electrical instability or sudden unexpected death an inquiry should be made about previous use of L-tryptophan. In patients with the eosinophilia-myalgia syndrome, the possibility of cardiac electrical instability should be considered as part of long-range clinical management.

Aged↗
PubMed1991

Histologic abnormalities of large and small coronary arteries, neural structures, and the conduction system of the heart found in postmortem studies of individuals dying from the toxic oil syndrome.

Hundreds died and thousands were poisoned by rapeseed oil adulterated with aniline and sold illegally in Spain in 1981. The clinical manifestations, now known as the toxic oil syndrome, include pulmonary hypertension and right ventricular hypertrophy plus widespread vascular and neural lesions in other organs. Many of the late deaths ended with a scleroderma-like illness. Because scleroderma involves the heart, in this study we examined the small and large coronary arteries, neural structures, and conduction system from eight victims dying with the toxic oil syndrome. Dense fibrosis of the sinus node in two hearts resembled changes found in scleroderma. Atrionodal junctional hemorrhages and cystic degeneration of the sinus node present in the other six hearts resembled changes found in lupus erythematosus. Small and large coronary arteries exhibited focal fibromuscular dysplasia and a proliferative cystic myointimal degeneration. This latter abnormality was associated with sloughing of the inner wall and embolization of the detached fragment downstream in the same coronary artery. Every heart had many degenerative lesions within nerves, ganglia, and the coronary chemoreceptor. Both the arterial and neural abnormalities prominently involved the conduction system. Based upon observations by others with experimental feeding of rapeseed oil containing either high or low erucic acid, we suggest that this oil must remain a major suspected cause of the toxic oil syndrome, particularly in conjunction with some as yet unexplained facilitative influence by oleoanilids. If this is so, it is important to reconsider the widely recommended use of any rapeseed oil product as a suitable food for man or other animals.

Adolescent↗
PubMed1991

Adenylate cyclase activity in various components of the sarcoplasmic reticulum: a cytochemical study of ventricular biopsies from diseased human hearts.

Localization of adenylate cyclase (ACLase) activity was studied in biopsies of diseased human myocardium by means of electron microscopic cytochemistry. Five right and seven left ventricular biopsy specimens were obtained from patients with idiopathic dilated (3 cases) and hypertrophic (3 cases) cardiomyopathies, various acquired (3 cases) and congenital (1 case) heart diseases, and other heart diseases (2 cases). Catecholamine-stimulated ACLase activity was assessed relative to the fine structure of cardiocytes. The most intense ACLase activity was found in the sarcoplasmic reticulum (SR), but activity was also present in the sarcolemma. The enzyme activity was present in a wide morphologic spectrum of components of the SR, including junctional SR of internal and peripheral coupling (12 cases), free SR in association with myofibrils (6 cases), and free SR in association with mitochondria (5 cases). ACLase activity in junctional SR in the human myocardium resembles the findings in hearts of other mammalian species. The enzyme activity in human myocardial SR may represent a local regulatory function of the ACLase-cyclic AMP-phosphodiestrerase system in the SR components.

Adenylyl Cyclases↗
PubMed1990

Morphologic characteristics and functional significance of focal fibromuscular dysplasia of small coronary arteries.

Focal fibromuscular dysplasia of small coronary arteries is not so rare as it is unrecognized. Although sometimes occurring as an isolated abnormality, it more often accompanies a variety of other lesions including inflammation or infiltration. In this review based on personal study of over 1,000 human hearts, the 3 topics include a description of the morphologic characteristics of the lesion, a discussion of its functional consequences affecting coronary flow, and an iteration of theoretical explanations for its development. The typical lesion is focal in distribution, is comprised of both fibrous and smooth muscle elements, and the histologic organization is one of dysplastic array. Included among the subjects discussed in functional consequences are coronary spasm, coronary reserve, chest pain, electrical instability of the heart, and comments on the role of focal fibromuscular dysplasia of small coronary arteries in hypertension, myocardial hypertrophy and heart failure. Theories as to its development include primary faults of smooth muscle or collagen, and focal abnormalities of clotting or neurovascular relation, but it is likely that the cause is multifactorial.

Aged↗
PubMed1990

The spectrum of diseases of small coronary arteries and their physiologic consequences.

There is a wide spectrum of abnormalities in the structure of small coronary arteries, with regard both to the portion of the arterial wall involved and to the histologic nature of the disease. A fuller understanding of this spectrum permits more useful interpretation of the pathophysiologic basis for the functional consequences of small coronary artery disease. In this review based on personal observations during examination of more than 1,000 human hearts postmortem there is initially a description of the wide variety of structural abnormalities, then a discussion of the functional consequences of these abnormalities and finally a section of general comments to weave together the structural and functional discussion in the context of clinical evaluation of patients who have small coronary artery disease. Future studies should apply fractal analysis and quantitative topology, methods that lend themselves particularly well to an investigation of the progressively smaller branching of the human coronary tree.

Coronary Circulation↗
PubMed1990

Cardiac abnormalities demonstrated postmortem in four cases of accidental electrocution and their potential significance relative to nonfatal electrical injuries of the heart.

Death from accidental electrocution is generally thought to be due to an arrhythmia, but little is known of the anatomic changes in the heart and almost nothing is known about the conduction system itself. We have studied the hearts of four men who died from electrical accidents and directed particular attention to the coronary arteries, conduction system, and neural structures of the heart. In every heart there was widespread focal necrosis involving all the myocardium and including the specialized tissue of the sinus and atrioventricular nodes. In all four hearts there was contraction band necrosis of smooth muscle cells in the tunica media of the coronary arteries. Cells in the His bundle and bundle branches were less affected. Neural structures of the heart were minimally involved. We also sought any cardiac changes of a chronic nature that may have predisposed to a fatal arrhythmia. Two of the four hearts were slightly enlarged, and increased myocardial mass predisposes to ventricular fibrillation and makes it more difficult to revert. One heart exhibited focal fibromuscular dysplastic narrowing of small coronary arteries, including that artery supplying the coronary chemoreceptor. Another heart had fatty deposition extensively present within and around the sinus and atrioventricular nodes. Thus numerous abnormalities specifically attributable to the electrocution help explain the pathogenesis of the electrical instability known to occur. But in three of the four hearts there were also chronic abnormalities favoring electrical instability but predating the electrocution.

Adult↗
PubMed1990

Sudden death due to isolated acute infarction of the His bundle.

A 29 year old black man considered to be in good health died suddenly and unexpectedly. At postmortem examination there were no significant gross abnormalities, all drug screens were normal and sicklemia was not present. Special studies of the cardiac conduction system demonstrated isolated acute infarction of the His bundle, with no similar evidence of myocardial infarction anywhere else in the heart. The atrioventricular (AV) node artery was moderately narrowed, but its branch supplying the His bundle was occluded greater than 95% by focal fibromuscular dysplasia. There were no other significant coronary lesions or other abnormalities in the heart.

Adult↗
PubMed1990

Tumor of the atrioventricular nodal region. A clinical and immunohistochemical study.

Autopsy specimens of 17 tumors of the atrioventricular nodal region were studied. Sudden death occurred in 14 children and adults; seven of these patients had a history of atrioventricular block or syncope. Three tumors were incidental findings in infants with other congenital anomalies; diaphragmatic agenesis, pulmonary hypoplasia, and Meckel's diverticulum in one patient; mitral atresia in one; and congenital hydrocephalus, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, and patent omphalovitelline duct in the third. Immunohistochemical stains demonstrated strong positivity for carcinoembryonic antigen in 13 of 13 cases, B72.3 antigen in 5 of 7 cases, and cytokeratin in 11 of 11 cases. Twenty control cases of mesothelioma and mesothelial hyperplasia were all negative for B72.3; one showed focal carcinoembryonic antigen staining. Ultrastructural analysis of one case demonstrated short rudimentary microvilli not characteristic of mesothelial cells. We conclude that so-called mesotheliomas of the atrioventricular nodal region are not of mesothelial origin, because of strong carcinoembryonic antigen positivity and occasional positivity with B72.3, as these antibodies react with glycoproteins found in endodermally derived tissue and generally not with mesothelial tissue. Conduction system tumors are most likely congenital rests of endodermal origin, can be associated with other congenital anomalies, and often cause symptoms of heart block and sudden death.

Adolescent↗
PubMed1989

A cardiogenic hypertensive chemoreflex.

A cardiogenic hypertensive chemoreflex is elicited by serotonin administered experimentally in the dog. The reflex nearly doubles aortic pressure within 4-6 sec and is associated with powerful inotropic, chronotropic, and dromotropic responses. The afferent pathway is via intrathoracic vagal branches, whereas the efferent paths engage not only the vagal and sympathetic routes but also the phrenic nerve. The reflex can be abolished by vagotomy or with cyproheptadine, and can be attenuated by local anesthesia of the intertruncal space. Small chemoreceptors lying between the aorta and pulmonary artery are the source of the reflex, and they receive their blood supply from the proximal left coronary artery. Human counterparts of the reflex may include new hypertension during angina pectoris or acute myocardial infarction, new postoperative hypertension after coronary bypass grafting, and hypertensive patients with carcinoid syndrome. Many unresolved problems include the precise mechanism of chemoreception, whether the chemoreflex has any tonic influence, and mechanisms of integration of the reflex with other events peripherally and centrally. Answers to these questions could be of great clinical value.

Animals↗
PubMed1989

On the pathogenesis of angina pectoris and its silence.

Recent interest in silent angina deals in a sense with a double unknown since the pathogenesis of angina pectoris remains unexplained. In this report, we present evidence from two human postmortem studies and from experiments conducted in eleven awake dogs which supports a hypothesis that angina pectoris may be mediated by an intracardiac chemoreceptor receiving its primary blood supply from the proximal coronary circulation. The clinical events and the postmortem findings in both human subjects supported the hypothesis. The somatic responses observed in the awake dogs resembled those of humans with angina pectoris. Because the cardiogenic hypertensive chemoreflex in dogs is maximally elicited by serotonin normally carried by the platelets and released during their aggregation, angina pectoris as well as numerous other clinical events observed during acute myocardial ischemic episodes could be similarly explained as consequences of the activation of a coronary chemoreceptor in man. Thus, at least some and possibly most examples of angina pectoris may be mediated via the coronary chemoreceptor and vagal afferents to the brain, and injury or destruction of this chemoreceptor could interdict the perception of anginal pain.

Adult↗