Coronary atherosclerosis in Mangalore--a random post mortem study

A study was undertaken in Mangalore, South Kanara District of Karnataka, India to evaluate the rising prevalence of coronary artery diseases in our country. Seventy hearts were analysed, at post-mortem, between December 1996 and December 1997. The coronary arteries and the myocardium were examined, both grossly and histologically, to relate them with regard to the age and gender of the deceased. Fifty five hearts were from males and 15 were from females. Forty eight (68.59%) hearts were proven to be afflicted with coronary atherosclerosis. Twenty seven of these had three or four vessel disease. A total of 192 sections from the four major epicardial arteries of the 48 hearts were examined. Of these, 124 showed atherosclerosis (with 37 in advanced stages), of which 103 were occlusive lesions while the remaining 21 were fatty streaks. Severe stenosis (grade III or IV) was commonest in the left anterior descending artery. Twenty one (30%) of the 70 hearts showed histological evidence of myocardial ischaemia. Of these 6 were from females and 15 were males. Myocardial ischaemia was found to have no correlation to the severity of stenosis.     

Myocardial ischemia due to vascular systemic amyloidosis: a quantitative analysis of autopsy findings on stenosis of the intramural coronary arteries

A case is reported of a 65 year old man who suffered myocardial ischemia resulting from extensive stenosis of the intramural coronary arteries secondary to systemic vascular involvement by primary amyloidosis. In the myocardium, there were multiple fibrotic foci scattered mainly in the subendocardial region of the ventricle. Intramural coronary arteries were stenotic or occlusive due to amyloid-induced luminal narrowing, but there was no significant stenosis of the epicardial coronary arteries. Quantitative analysis of amyloid deposits in the intramural coronary arteries demonstrated that occlusive arteries were predominant in the surrounding area of myocardial fibrosis, and the extent of coronary stenosis by amyloid deposition was significantly more severe than in hearts of the five control patients who had coronary amyloidosis without myocardial fibrosis. These results indicate that myocardial fibrosis originates from coronary ischemia due to vascular amyloid deposition. This is the first time that the relationship between myocardial lesions and coronary amyloid deposition has been elucidated using histopathologic quantitative analysis.     

Massive haemorrhagic necrosis of the liver after liver transplantation.

Six of the first 85 patients who received the first 100 liver transplantations carried out in Birmingham developed a syndrome of fulminant liver failure with distinctive clinical and pathological features. The typical clinical presentation was of an uneventual initial postoperative period, followed by a sudden deterioration in graft function, progressing rapidly to graft failure. All six patients died. The characteristic pathological changes were those of massive haemorrhage and hepatocyte necrosis with only mild inflammation and without occlusive lesions in large arteries or veins. These distinctive features differed from other recognised patterns of graft damage and seemed to comprise a specific post-transplant syndrome. The pathogenesis was not clear and in the absence of any definite aetiology it is suggested that the term "massive haemorrhagic necrosis" be used to describe these cases. Additional findings seen in five of the six cases were venoocclusive lesions (n = 4) and a combination of ductopenia and foam cell arteriopathy (n = 2). The presence of these associated lesions suggests that there may be an overlap with other types of graft damage.     

Pathology of the human heart in drowning

Examination of the hearts of ten human drowning victims revealed smooth-muscle contraction banding within the media of the major coronary arteries of eight patients (80%), focal ventricular myocyte hypereosinophilia in eight patients (80%), and ventricular myocyte contraction banding in five patients (50%). These lesions suggest that drowning is associated with a sympathetic storm, which produces both coronary arterial spasm and focal myocyte injury. The lesions may be the first-described positive morphologic markers of drowning in immersed subjects. This study provides further support for the concept that medial smooth-muscle contraction bands may be morphologic markers for antemortem coronary arterial spasm.     

Dilated cardiomyopathy in children with acquired immunodeficiency syndrome: a pathologic study of five cases

Clinicopathologic features with special reference to the heart are presented in five fatal cases of acquired immunodeficiency syndrome (AIDS) in children. Three children showed clinical evidence of cardiovascular compromise or congestive heart failure. Autopsy was performed in all cases. The enlarged heart showed biventricular dilatation with grossly unremarkable valves and coronary arteries and absence of mural thrombi. Microscopic examination of the heart revealed primarily myopathic abnormalities with hypertrophy of the myocardium and only rare foci of sparse inflammatory infiltrate. The pathogenesis of dilated cardiomyopathy in these children with AIDS is not known. Infection, immunologic factors, anemia, deficiency of nutritional factor(s), and longer survival may be related to the pathogenesis. Pediatricians should be alert to the possibility of cardiac involvement in pediatric AIDS.     

Instability of lymphocyte chromosomes in a girl with Rothmund-Thomson syndrome.

Rothmund-Thomson syndrome is a rare autosomal recessive syndrome characterised by poikiloderma of the face and extremities, alopecia, short stature, and skeletal defects. We report a patient with the characteristic features of Rothmund-Thomson syndrome who also had lymphocyte chromosome abnormalities. She has a small flat face with short palpebral fissures and micrognathia together with severe skeletal abnormalities of the upper extremities with absence of both radii, short dysmorphic ulnae, a rudimentary right thumb, and aplasia of the left thumb. She also has anal atresia with a rectovaginal fistula. From the age of 3 months she developed poikiloderma skin changes on the face and extensor surfaces of the extremities. Mental development seems to be normal. Lymphocyte chromosomes in the neonatal period showed an unidentified marker chromosome in eight of a total of 32 cells. A repeat analysis at the age of 10 months showed three abnormal cells out of 100 analysed: 47,XX,-7,+i(7q),+7p, 46,XX,t(3;18)(p14.2;q22), and 49,XX,+del(3)(p11.2),+mar,+mar. A skin biopsy from an affected area showed poor growth and five of 48 cells analysed had structural abnormalities. The father had one of 48 cells with an additional marker chromosome and two cells with different 7;14 translocations. The abnormal chromosome complements in lymphocytes indicate that there may be in vivo chromosome instability in Rothmund-Thomson syndrome.     

Occlusive versus nonocclusive calcipotriol ointment treatment for palmoplantar psoriasis.

Thirty-nine patients with a clinical diagnosis of palmoplantar psoriasis [23 (58%) males and 16 (42%) females] were included in this study with the aim of evaluating the efficacy of occlusive calcipotriol 50 micrograms/mg ointment vs. nonocclusive therapy. Patients were randomized to either twice-weekly overnight calcipotriol ointment under occlusion or twice-daily topical nonocclusive application of the same ointment for 6 weeks. The effect of treatment was assessed on the basis of a psoriasis signs score for erythema, thickness and scaliness, which was graded from 0 (absent) to 4 (most severe) at the first visit, after 2 weeks and at the end of treatment. Analysis of our results showed that twice-weekly occlusive calcipotriol ointment was as effective as the twice-daily application. The mean total score at baseline was 6 for the occlusive group and 6.1 for the nonocclusive group. The score decreased to 1.5 in both groups at the end of treatment. No significant adverse effects were reported by patients or investigators. We conclude that occlusive calcipotriol ointment is effective in the treatment of palmoplantar psoriasis and may produce even better results with more frequent use, such as application on alternate days.     

A review on the vascular features of the hyperimmunoglobulin E syndrome

Autosomal recessive, autosomal dominant and the sporadic forms of hyperimmunoglobulin E syndrome (HIES) are multi‐system disorders. Although HIES patients may present with cold abscesses, the vascular features of HIES are not well recognized. The objective of this review is to characterize the nature and spectrum of vascular abnormalities in HIES patients. Vascular abnormalities in HIES patients were reviewed with Medline and Google Scholar‐based searches. In brief, the searches combined terms related to HIES with the terms related to vasculature. Furthermore, reference lists from the original studies and review papers identified were screened. There were vascular abnormalities in 25 patients with HIES. These abnormalities were identified as aneurysms (coronary, aortic, carotid and cerebral), pseudoaneurysms, congenital patent ductus venosus, superior vena cava syndrome, vasculitides, vascular ectasia, thrombosis and others. They may be congenital or acquired, in the veins and arteries, affecting both sexes. These abnormalities can be seen in all subtypes of HIES. They could be also fatal in children and adults. Limited pathological investigations revealed the presence of vasculitis. Three of the patients were found to have overlap diseases. In this review, the spectrum of vascular abnormalities in HIES are documented and discussed in detail for the first time. They highlight a previously under‐recognized and potentially devastating complication of these disorders. These vascular abnormalities constitute one of the major clinical characteristics in HIES. The presence of hypereosinophilia, vasculitis and defective angiogenesis in HIES may contribute to the formation of vascular abnormalities in HIES.     

Noninvasive measurements of intracardiac blood flow velocities with Doppler ultrasound

The response to prolonged hyperventilation (HVT) was evaluated by electrocardiography (HVT-ECG) and thallium-201 myocardial scintigraphy (HVT-Tl-Sc) in 40 patients suspected of vasospastic angina. Both tests showed ischaemic changes in 16 patients and no changes in 20 patients. Two patients had abnormal HVT-ECG and normal HVT-Tl-Sc, and the reverse combination was found in two patients. Prolonged HVT was performed in 14 patients during coronary angiography (CAG). Nine developed transient total or subtotal occlusion in one of the major coronary arteries, all of whom had ischaemic HVT-ECG and eight had abnormal HVT-Tl-Sc. In the five patients without spasm at CAG four had normal HVT-ECG and all five normal HVT-Tl-Sc. Our data suggest that HVT-ECG and HVT-Tl-Sc have essentially the same sensitivity and specificity in detecting vasospastic angina.     

Systemic occlusive arteriopathy with sudden death in a 10-year-old boy

A 10-year-old boy died suddenly while playing. Autopsy examination disclosed an extensive occlusive arteriopathy involving all major epicardial coronary arteries, with associated remote myocardial infarct. Also affected were the renal arteries and a branch of a pulmonary artery. The process was characterized by concentric intimal hyperplasia, focally replacing the media, with disruption of elastic laminae in more advanced lesions. The proliferating cells had ultrastructural features of smooth muscle cells. There was no evidence of atherosclerosis or vasculitis. While the case shares some features with known arteriopathies, this constellation of clinical and pathologic findings appears to be unique.     

Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries

Acetylcholine is believed to dilate normal blood vessels by promoting the release of a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). By contrast, if the endothelium is removed experimentally, acetylcholine constricts blood vessels. We tested the hypothesis that muscarinic cholinergic vasodilation is impaired in coronary atherosclerosis. Graded concentrations of acetylcholine and, for comparison, the nonendothelial-dependent vasodilator nitroglycerin were infused into the left anterior descending artery of eight patients with advanced coronary stenoses (greater than 50 percent narrowing), four subjects with angiographically normal coronary arteries, and six patients with mild coronary atherosclerosis (less than 20 percent narrowing). Vascular responses were evaluated by quantitative angiography. In several segments each of four normal coronary arteries, acetylcholine caused a dose-dependent dilation from a control diameter of 1.94 +/- 0.16 mm to 2.16 +/- 0.15 mm with the maximal acetylcholine dose (P less than 0.01). In contrast, all eight of the arteries with advanced stenoses showed dose-dependent constriction, from 1.05 +/- 0.05 to 0.32 +/- 0.16 mm at the highest concentration of acetylcholine (P less than 0.01), with temporary occlusion in five. Five of six vessels with minimal disease also constricted in response to acetylcholine. All vessels dilated in response to nitroglycerin, however. We conclude that paradoxical vasoconstriction induced by acetylcholine occurs early as well as late in the course of coronary atherosclerosis. Our preliminary findings suggest that the abnormal vascular response to acetylcholine may represent a defect in endothelial vasodilator function, and may be important in the pathogenesis of coronary vasospasm.     

Early vulvar squamous neoplasia: advances in classification, diagnosis, and differential diagnosis

The recognition and classification of preinvasive vulvar neoplasia are complicated by the facts that (a) their respective carcinomas have a diverse (human papillomavirus [HPV]- and non-HPV-related) pathogenesis; (b) not all vulvar squamous carcinomas are associated with precursors with strictly defined morphologic features; (c) many carcinomas have epithelial changes that are abnormal but lack sufficient nuclear atypia to warrant classification as an intraepithelial neoplasm; and (d) even lesions associated with a common etiologic agent (HPV) present a diverse morphologic spectrum. In this review, five categories of early vulvar neoplasia are defined, based on the available literature, into (a) low-grade lesions with minimal cancer risk, (b) high-grade lesions associated with HPV, (c) high-grade lesions associated with other etiologies, (d) squamous atypias defined by abnormalities in differentiation rather than abnormalities in nuclear morphology, and (d) early carcinomas that do not exhibit conspicuous stromal invasion. The first three groups are arranged into low- and high-grade intraepithelial lesions, the fourth into intraepithelial atypias that bear careful follow-up and attention to the co-existing squamous mucosa, and the fifth into a category that, depending on the degree of cell differentiation, may warrant local excision or lymph node dissection. Recognition of these five categories is germane to proper management of women with squamous lesions of the vulva.     

Off-pump coronary artery bypass grafting in moyamoya disease

Moyamoya disease is an occlusive intracranial arteriopathy owing to intimal hyperplasia with formation of abnormal cerebrovascular collateral networks; however, the etiology remains unclear. Although this disease is known to be associated with renovascular hypertension, it is extremely rare for it to be associated with stenoses of the coronary arteries. We herein described a case of a 56-year-old female with angina and asymptomatic moyamoya disease. We performed off-pump coronary artery bypass grafting (OPCAB) to avoid cardiopulmonary bypass and the risk of intraoperative hypotension. Conventional coronary artery bypass grafting has a potential risk of brain ischemia in moyamoya patients, but OPCAB may avoid this perioperative cerebral ischemic complication.     

Fibromuscular dysplasia of coronary arteries resulting in myocardial infarction associated with hypertrophic cardiomyopathy in Noonan's syndrome

The first autopsy case of fibromuscular dysplasia in the coronary arteries associated with hypertrophic cardiomyopathy in Noonan's syndrome is reported. A 16-month-old female infant with no significant family history was diagnosed with Noonan's syndrome and subsequently died of cardiac and respiratory failure. Autopsy revealed cardiac hypertrophy, atrial septal defect, and scar lesions in the left ventricle and ventricular septum. Histologically, the myocardium exhibited myocardial fiber disarray, which was indicative of hypertrophic cardiomyopathy. The main trunks of the coronary arteries showed protuberant intimal thickening with interruption of the internal elastic lamina. Intramyocardial coronary arteries also exhibited various degrees of irregular intimal proliferation and diffuse fibrous thickening of the adventitia. These arterial lesions were consistent with fibromuscular dysplasia. Small arteries around the scar showed remarkable stenoses, which probably led to myocardial ischemia. The fibromuscular dysplasia in this case was considered to arise as a cardiovascular disorder in conjunction with Noonan's syndrome.     

IDIOPATHIC ARTERIAL CALCIFICATION IN A 3-MONTH-OLD CHILD, ASSOCIATED WITH MYOCARDIAL INFARCTION

Idiopathic arterial calcification, which is characterized by intimal fibroblastic proliferation in arteries with mural calcification, may be a cause of sudden death in children. We presented here a three-month-old male infant terminating in sudden death, whose postmortem examination revealed characteristic occlusive disorder of the coronary arteries, associated with secondary myocardial infarction. Histologic study of the coronary arteries demonstrated fibrous intimal proliferation and numerous calcified foci in the internal elastic lamina or in the intima, causing luminal occlusion of the arteries. Similar morphologic changes were found in medium-sized elastic or muscular arteries of other organs. These light microscopic features are consistent with that of so-called idiopathic arterial calcification. Electron microscopic examination of the coronary arteries revealed foamy degeneration of the internal elastic lamina, with focal aggregates of granular high density material. It is suggested that these light and electron microscopic changes of the internal elastic lamina may disclose the fundamental process resulting in mineralization of the lamina, with secondary fibroblastic hyperplasia in the intima.     

Pulmonary vascular disease in systemic lupus erythematosus.

The pulmonary vascular changes in systemic lupus erythematosus (SLE) have been investigated from 20 autopsies performed at the Mount Sinai Hospiral from 1964 to 1973. Acute lesions included fibrinoid necrosis and vasculitis. Chronic lesions consisted of intimal fibrosis, medial hypertrophy, alteration of elastic laminae, periadventitial fibrosis, and, in one case, aneruysmal dilatation. These changes were found variously in arterioles, arteries and veins. The fibrotic and occlusive vascular lesions may account for the syndrome of "unexplained breathlessness" that occurs in SLE. These lesions may progress in certain individuals to overt pulmonary hypertension; the concept of coexisting primary pulmonary hypertension and SLE should be re-examined.     

Congenital coronary arteries anomalies: review of the literature and multidetector computed tomography (MDCT)-appearance

The prevalence of coronary arteries congenital anomalies is 1 to 2% in the general population. Although the spectrum of their clinical manifestations is very broad from total inocuity to lethal, anomalies of coronary arteries need to be recognized by clinicians in certain circumstances: they are the first cause of death in young adults under physical exercise and an abnormal course of a coronary artery can complicate a cardiac surgery. Therefore, a non-invasive test is highly suitable for detecting anomalies of coronary arteries and multidetector computed tomography (MDCT) is likely to be the best one. To understand how anomalies of coronary arteries may occur, we have reviewed the recent literature about their development. Then, the main types of anomalies are presented with their clinical context, and representative MDCT images from our personal database are used for illustration.     

A novel biallelic CRIPT variant in a patient with short stature,microcephaly, and distinctive facial features

Primordial dwarfism (PD) is one of a highly heterogeneous group of disorders characterized by severe prenatal/postnatal growth restriction. Defects in various pathways such as DNA repair mechanism, impaired centrioles, abnormal IGF expression, and spliceosomal machinery may cause PD including Seckel syndrome, Silver–Russell syndrome. Microcephalic osteodysplastic primordial dwarfism (MOPD) types I/III, II, and Meier–Gorlin syndrome. In recent years with the wide application of exome sequencing (ES) in the field of PD, new genes involved in novel pathways causing new phenotypes have been identified. Pathogenic variants in CRIPT (MIM# 604594) encoding cysteine-rich PDZ domain-binding protein have recently been described in patients with PD with a unique phenotype. This phenotype is characterized by prenatal/postnatal growth restriction, facial dysmorphism, ocular abnormalities, and ectodermal findings such as skin lesions with hyper/hypopigmented patchy areas and hair abnormalities. To our knowledge, only three patients with homozygous or compound heterozygous variants in CRIPT have been reported so far. Here, we report on a male patient who presented with profound prenatal/postnatal growth restriction, developmental delay, dysmorphic facial features, and skin lesions along with the findings of bicytopenia and extensive retinal pigmentation defect. A novel truncating homozygous variant c.7_8delTG; p.(Cys3Argfs*4) was detected in CRIPT with the aid of ES. With this report, we further expand the mutational and clinical spectrum of this rare entity.     

Morphology of graft arteriosclerosis in cardiac transplant recipients.

The morphologic features of graft arteriosclerosis (GA) and other vascular lesions were semiquantitatively evaluated. Five failed cardiac allografts attributable to GA and five other allografts were obtained from nine autopsies and one surgical explanation. The subjects, aged 4.5 to 67 years, had a mean allograft survival of 735 +/- 184 days. A total of 1,174 arterial and 754 venous cross-sections were reviewed. Intimal fibrosis (nine cases, 254 arteries, and 118 veins), fibrofatty plaques (eight cases and 35 arteries), and cellular intima thickening and concentric foam cell lesions (eight cases, 326 arteries, and 20 veins) were seen. Cellular lesions contained T lymphocytes, monocytes, and cells of smooth muscle cell origin detected by staining using the immunoperoxidase technique. Allografts with severe GA had a greater luminal stenosis in epicardial arteries (P less than .05), greater cellular proliferation in large mural arterial lesions (P less than .004), and more foam cell lesions in both arteries (P less than .06) and veins (P less than .03) than other allografts. Medical fibrosis and thinning were present in six allografts. Severity of acute rejection (P less than .01) was correlated with the presence of GA. The morphology and distribution of GA is heterogeneous, with evidence supporting an immune-mediated pathogenesis.     

Endothelial expression of endothelial nitric oxide synthase and endothelin-1 in human coronary artery disease. Specific reference to underlying lesion.

Nitric oxide and endothelin-1 (ET-1) are two major endothelium-derived factors with opposing effects on the function and structure of the vessel wall. We investigated the endothelial expression of endothelial nitric oxide synthase (eNOS) and ET-1 in coronary artery disease (CAD) with special reference to the types of underlying lesions. Immunohistochemistry and in situ hybridization were performed in coronary arteries of heart transplant recipients with (n = 16) and without (n = 11) CAD. All coronary arteries from patients with CAD (n = 23) had concentric fibrous or advanced lesions, whereas most of the arteries (25 of 31) from patients with non-CAD showed normal appearance (myointimal thickening only) or eccentric lesions alone. Normal coronary segments consistently showed apparent endothelial immunoreactivity and mRNA signals for both eNOS and ET-1. In atherosclerotic coronary segments, endothelial expression of eNOS and ET-1 was reduced in most lesion sites, particularly in severe subendothelial lesions with dense fibrosis or macrophage accumulation, but not with smooth muscle cells only. Conversely apparent ET-1, compared with weak or focal eNOS signals, were more frequently seen in coronary segments with concentric severe lesions from CAD but not non-CAD patients. Immunoreactivity and mRNA signals for ET-1 were co-localized with those for ET converting enzyme-1 in the endothelium, as well as in the underlying macrophages and smooth muscle cells. These results indicate the presence of differential endothelial expression of eNOS and ET-1 in diseased human coronary arteries with severe concentric atherosclerotic lesions, a finding that was rare in atherosclerotic lesions of coronary arteries of non-CAD patients. Altered expression of endothelium-derived factors may contribute to abnormality of coronary vasomotor tone and the formation of subendothelial lesions in CAD.