Pathological features of temporal arteries in patients with giant cell arteritis presenting with permanent visual loss.

BACKGROUND: Permanent visual loss (PVL) is the most feared complication of giant cell arteritis (GCA), and its risk factors are still unclear. OBJECTIVES: The aim of our study was to assess the pathological features predictive of PVL on temporal artery biopsy (TAB) specimens in patients with GCA. METHODS: The slides of 391 TAB specimens from patients with GCA were reviewed by two pathologists without clinical information. RESULTS: A total of 29 patients (26 females and 3 males, mean age 78.3 years) presented with unilateral PVL at the onset of the disease, and 362 patients (258 females, 104 males, mean age 74.7 years), did not. The pathological features strongly predictive for PVL were the presence (p = 0.003), number (p = 0.001) and aggregates of giant cells (p = 0.001), presence of plasmocytes (p = 0.002), thickened intima (p = 0.007), neoangiogenesis (p = 0.001) and degree of arterial occlusion (p = 0.006). Presence of neutrophils, eosinophils, parietal necrosis, calcification in the arterial wall and disruption of the internal elastic membrane were similar in both groups. Total obstruction of the arterial lumen by a thrombus, intensity of the inflammatory cells infiltration and inflammation of small vessels, nerves and veins surrounding the temporal artery were not associated with blindness. In multivariate analysis, only giant cells remained significantly associated with PVL. CONCLUSION: Giant cells are strongly associated with PVL, with a significant gradient between great risk and large number of giant cells. However, PVL was neither associated with the intensity of the inflammatory infiltrate, nor with the presence of arterial thrombosis.

[Incidence of cardiovascular events in giant cell arteritis: preliminary results of a prospective double cohort study (GRACG)]. / Incidence des accidents cardiovasculaires au cours de la maladie de Horton: résultats préliminaires de l'étude prospective en double cohorte GRACG.

UNLABELLED: Giant cell arteritis is the most frequent vasculitis. Cardiovascular events such as cerebrovascular accident or ischemic heart disease may occur in patients with giant cell arteritis. However, their real incidence, as well as their relative risk compared to the general population, remains unknown. PURPOSE: To assess in a prospective, double cohort study, the incidence of cardiovascular events in giant cell arteritis patients compared to controls, after controlling for cardiovascular risk factors. PATIENTS AND METHODS: We included on predefined criteria 432 newly diagnosed patients with giant cell arteritis, each assigned to sex- and age-matched controls randomly selected from the general population. Cardiovascular risk factors (high-blood pressure, diabetes, smoking, hypercholesterolemia and preexisting peripheral vascular disease) were collected at inclusion. During the 24-month follow-up, all cardiovascular events were collected. After stratification for cardiovascular risk factors, a log-rank test was performed to compare cases and controls. A parametric survival model was used for multivariate analysis. RESULTS: Cardiovascular events all combined were significantly increased in patients with giant cell arteritis (RR = 2.15 [1.21-3.81], P = 0.009), and were mainly associated with age (P = 0.0001), past history of cardiovascular disease (P = 0.023) but also with giant cell arteritis (P = 0.009). However, each subset of cerebrovascular accident (RR = 2.42 [0.84-7]) or ischemic heart disease (RR = 1.67 [0.72-3.89]) increased but did not significantly. CONCLUSION: Cardiovascular events incidence is increased in patients with giant cell arteritis, and prescription of preventive antiagregant treatment may be discussed.

[Giant cell arteritis and polymyalgia rheumatica: influence of past pregnancies? The GRACG multicenter case control study]. / Maladie de Horton et pseudopolyarthrite rhizomélique: influence des antécédents de grossesse? Etude cas-témoins prospective GRACG.

BACKGROUND: The overprevalence of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) in women remains unexplained. Microchimerism pathogenicity has been discussed in some systemic diseases. We tested history of pregnancy as a risk factor for GCA. METHODS: Prospective, multicenter case-control study with multiple, age-matched, control groups. Patients have been included in 40 different centers. The first control group has been randomly selected in the general population, consecutive hospitalized patients in two geographically distant departments of internal medicine made up the second and third ones. RESULTS: Three hundred and fifteen patients (249 GCA and 66 PMR), 242 general population controls, 333 in the first hospitalized control group, and 355 in the second, have been included in the 1991-1998 period. Pregnancy has been constantly protective against GCA/PMR (Wilcoxon rank sum test: P = 0.0001, 0.0005, and 0.054, respectively, for the three control groups), more particularly for parity equal or greater than 4 (OR = 0.32, 95% CI: 0.18-0.57, P = 0.00003; OR = 0.44, 95% CI: 0.26-0.74; P = 0.0009, and OR = 0.42; 95% CI: 0.25-0.71, P = 0.0006, respectively). In multivariate analysis, risk for GCA on pre-existing degenerative, vascular disease is decreased by half for each pregnancy (OR = 0.49, 95% CI = 0.27-0.90, P = 0.022). CONCLUSION: Contrary to the initial hypothesis, multiparity is a protective factor against GCA. Mechanism is unknown.

Circumstances of death and gross and microscopic observations in a series of 200 cases of sudden death associated with arrhythmogenic right ventricular cardiomyopathy and/or dysplasia.

BACKGROUND: Sudden death is a possible consequence of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). Prevalence of ARVC/D in unexpected sudden cardiac death (USCD), however, remains imprecise, as do circumstances of death and ARVC/D-associated gross and microscopic findings, especially His bundle anomalies. METHODS AND RESULTS: We reviewed 14 000 forensic autopsies required by judicial authorities from January 1980 to January 1999 in a 2 000 000-resident area. Age, gender, and circumstances of death were recorded. Hearts were examined macroscopically and microscopically. In this series, the ARVC/D group accounted for 200 consecutive cases (10.4%) of USCD, including 108 males and 92 females (average age 32.5 and 34.5 years, respectively). Nearly one third of deaths occurred during the fourth decade of life. Circumstances of death were various, but 75.6% occurred during everyday life events (at home, 63.1%; in the street, 6.6%; or at work, 6.1%); only 7 cases (3.5%) occurred during sports activity. Nineteen cases (9.5%) happened during the perioperative period. Adipose infiltration of the right ventricle was either isolated (20%) or associated with fibrosis (74.5%) and lymphocytes (5.5%). A total of 14.5% of cases had cardiac hypertrophy, assessed by an increase in heart weight and/or left ventricular wall thickness. In most cases, the His bundle and its branches were abnormal either because of infiltration of adipose tissue (8.1%), fibrosis (54.3%), or both (5.6%). CONCLUSIONS: In ARVC/D, both sexes are equally affected, and there is a peak of risk during the fourth decade. Death most frequently occurs during sedentary activity. His abnormalities and left ventricular hypertrophy may be associated with ARVC/D.

Constrictive bronchiolitis obliterans. Characterisation of fibrogenesis and lysyl oxidase expression patterns.

The process leading to irreversible fibrotic constriction of the bronchioles was studied in two cases of bronchiolitis obliterans (BO) after bone marrow transplantation. Because lysyl oxidase (LOX) is the main collagen cross-linking enzyme that might account for irreversible fibrosis, its expression was studied together with expression of extracellular matrix (ECM) proteins. Characteristic types of lesions could be distinguished on the basis of histological and immunohistological criteria. An inflammatory stage was characterised by infiltration restricted to the bronchioles by lymphocytes and dendritic cells. A fibro-inflammatory stage was characterised by the coexistence of a persistent immune cellular lesion pattern with further focal modelling of a sub-epithelial neo-synthesised connective matrix. LOX expression was observed at the tips of intra-luminal fibrotic protrusions, together with tenascin and cellular fibronectin. A fibrotic stage was characterised by dense ECM deposits spreading throughout the peri-bronchiolar connective tissue, resulting in bronchiole obliteration and final disappearance. In contrast to reversible cases of fibrosis, persistence of long-term LOX expression reflecting continuing fibrosing activity might account for the irreversible status of BO. Our two cases illustrated that, at inflammatory and fibro-inflammatory stages, BO may be stabilised by immunosuppressive treatment, while the persistence of LOX expression in the fibrotic stage might correspond to a disease that becomes irreversible and fatal.

Clinical presentation of left atrial cardiac myxoma. A series of 112 consecutive cases.

We analyzed a series of 112 consecutive cases of left atrial myxoma diagnosed in a single French hospital (72 women and 40 men; age range, 5-84 yr) over 40 years, from 1959 to 1998. Symptoms of mitral valve obstruction, the first arm of the classic triad of myxoma presentation, were present in 75 patients (67%), with mostly cardiac failure or malaise. Symptoms of embolism, the second frequent presentation in the classic triad, were observed in 33 cases (29%) with 1 or several locations, essentially cerebral emboli with stroke. Males are statistically at greater risk than females of developing embolic complications. The third arm of the classic triad consists of constitutional symptoms (34%) with fever, weight loss, or symptoms resembling connective tissue disease, due to cytokine (interleukin-6) secretion. Younger and male patients have more neurologic symptoms, and female patients have more systemic symptoms. Seventy-two patients (64%) had cardiac auscultation abnormalities, essentially pseudo-mitral valve disease (53.5%) and more rarely the suggestive tumor plop (15%). The most frequent electrocardiographic sign was left atrial hypertrophy (35%), whereas arrhythmias were uncommon. The greater number of myxoma patients (98) diagnosed preoperatively after 1977 reflects the introduction of echocardiography as a noninvasive diagnostic procedure. However, there was no significant reduction in the average time from onset of symptoms to operation between patients seen in the periods before and after 1977. The tumor diameter ranged from 1 to 15 cm with a weight of between 15 and 180 g (mean, 37 g). The myxoma surface was friable or villous in 35% of the cases, and smooth in the other 65% cases. Myxomas in patients presenting with embolism have a friable surface; those in patients with cardiac symptoms, pseudo-mitral auscultation signs, tumor plop, and electrocardiogram or radiologic signs of left atrium hypertrophy and dilatation are significantly the larger tumors. The long-term prognosis is excellent, and only 4 deaths occurred among our 112 cases over a median follow-up of 3 years. The recurrence rate is low (5%), but long-term follow-up and serial echocardiography are advisable especially for young patients.

[Nonspecific interstitial pneumonitis: a new anatomoclinical entity among idiopathic diffuse interstitial pneumonias]. / Pneumopathie interstitielle non spécifique: une nouvelle entité anatomoclinique au sein des pneumopathies interstitielles diffuses idiopathiques.

Nonspecific interstitial pneumonitis with fibrosis has been individualized within the group of idiopathic diffuse interstitial pneumonias by pathological criteria. It is differentiated from usual interstitial pneumonitis by the temporal uniformity of the lesions, a prominent inflammatory interstitial infiltration, and the absence of honeycombing. Clinical and functional symptoms are those of diffuse interstitial pneumonitis. An etiology may be found in about half the cases, including connective tissue disease, exposure to organic antigens, or recent acute lung injury. Computed tomography of the chest shows bilateral ground glass opacities, and alveolar opacities with a peribronchiolar or patchy distribution. Prognosis is rather good, since a majority of patients improve when treated with corticosteroids or with an association of corticosteroids and immunosuppressive drugs. These etiologic and prognostic features justify the individualization of nonspecific interstitial pneumonitis with fibrosis as a distinct clinicopathological entity.

[Malignant mesothelioma with osteoblastic heterologous elements]. / Mésothéliome malin avec éléments hétérologues ostéoblastiques.

A 59 year-old man with a history of asbestos exposure presented with a right pleural effusion and a diffuse pleural thickening with focal calcifications on chest X-ray. Cytological examination of pleural fluid indicated malignant mesothelioma. A biopsy specimen showed malignant mesothelioma surrounding a fragment of mature bone. The patient was treated with intrapleural interferon, but relapsed 3 years later. A fresh biopsy specimen showed round tumor cells surrounding osteoid substance. Only ten cases of this rare variant of malignant mesothelioma with osteoblastic heterologous elements have been reported in the literature. The most difficult differential diagnosis is primary pleural osteosarcoma.

[Sudden death during anesthesia: human error, drug related or cardiac death?]. / Morts subites en cours d'anesthésie: erreur humaine, cause médicamenteuse, ou anomalie cardiaque occulte?

We carried out a retrospective analysis of 1500 forensic autopsies following sudden unexpected cardiac death. This analysis showed a group of 43 cases that could have been related to surgery and/or anaesthesia. Pathological examination revealed the existence of cardiac lesions in 40 cases: arrhythmogenic right ventricular cardiomyopathy (14 cases), coronary artery disease (9 cases), cardiomyopathy (8 cases), structural abnormalities of the His bundle (7 cases), mitral valve prolapse (1 case) and acute myocarditis (1 case). These disorders are compatible with a paroxysmal (rhythmic) phenomenon at the origin of the cardiac arrest. Identification of the cause of death in a patient who was presumed to be at low risk may provide major relief to the patient's family and the medical staff.

Unsuspected cardiac lesions associated with sudden unexpected perioperative death.

The retrospective analysis of 1700 forensic autopsies over 17 years (1981-97) following unexpected sudden cardiac death revealed a group of 50 cases that could have been related to surgery and/or anaesthesia. Patients were young with no history of cardiac disease. Surgery was performed for uncomplicated disorders, all classified as ASA 1. Cardiac arrest took place at induction of anaesthesia in 16% of cases, during surgery in 64% and at the end of surgery in 20%. Investigation and expertise reports ordered by the public prosecutor revealed none of the typical causes of death usually associated with surgery or anaesthesia. Pathological examination showed cardiac lesions in 47 cases: arrhythmogenic right ventricular cardiomyopathy in 18 cases, coronary artery disease in 10 cases, cardiomyopathy in eight cases, structural abnormalities of the His bundle in nine cases, mitral valve prolapse in one case, and acute myocarditis in one case. Identification of the cause of death of patients at low risk may provide major relief to the family of the patient and the medical staff.

[Severe hypoxemia with orthodeoxia due to right to left shunt in idiopathic bronchiolitis obliterans organizing pneumonia]. / Hypoxémie sévère avec orthodéoxie par shunt droit-gauche au cours d'une bronchiolite oblitérante avec organisation pneumonique idiopathique.

We report a case of BOOP with severe hypoxemia and orthodeoxia. Chest X-ray showed bilateral infiltrative pneumonia and computed tomography scan revealed consolidations on lower lobes. Diagnosis of right-to-left shunt was made on the increase of alveolar-arterial oxygen difference under FIO2 100%, accented in standing position. Contrast-enhanced echocardiography and technetium-99 macroaggregated albumin body scanning did not show anatomical right-to-left shunt and permitted the diagnosis of intrapulmonary shunt at the capillary level because of intra-alveolar organisation. Treatment with corticosteroids and cyclophosphamide led to clinical, and radiological improvement with correction of the hypoxemia and the shunt.

Accelerated coronary atherosclerosis and arteriosclerosis in young human-immunodeficiency-virus-positive patients.

OBJECTIVE: To determine the type of lesions observed in young patients infected with human immunodeficiency virus-1 (HIV-1). DESIGN: Examination of coronary networks in corpses of 13 men and two women who had died aged 23-32 years after having been infected with HIV-1 virus, having been seropositive for 2-5 years. Causes of death were infectious complications (five cases), infection with cytomegalovirus leading to gastro-intestinal haemorrhaging (one case), infection with cytomegalovirus and Kaposi's sarcoma (one case), overdoses of drugs (five cases) and sudden death (three cases). METHODS: The pathological analysis was carried out on the proximal and distal coronary networks. In order to characterize the lesions better, the cells and the cytokines involved were characterized by immunohistochemistry. RESULTS: In all 15 cases we observed thickening of intima in the proximal network at least as great as that of the media, caused by a proliferation of secreting cells, phenotypically identified as smooth muscle cells, with exaggerated production of elastic fibres and in association with an increase in the expression of tumor necrosis factor-alpha and interleukin-1 alpha. In nine cases, atherosclerosis had developed from and on the surface of this proliferation and in four cases arteriosclerosis had an unusual appearance, in the form of mamillated vegetations with endoluminal protrusions. A similar proliferation was found in the distal network in four cases, but with a significantly smaller proportion of elastic fibres. CONCLUSIONS: The lesions we examined in these young HIV-1-infected patients presented particular features and were intermediate between the lesions observed during common coronary atherosclerosis and atherosclerosis associated with chronic rejection of cardiac transplants.

[Transthoracic aspiration. Evaluation of cytologic and histologic diagnosis in a pulmonary nodule by retrospective comparison of 2 series of 267 cytoaspirations and 292 coaxial needle aspirations]. / La ponction trans-thoracique. Evaluation du diagnostic cytologique et histologique d'un nodule pulmonaire par comparaison rétrospective de 2 séries de 267 cytoponctions et de 292 ponctions à l'aiguille coaxiale.

Percutaneous fine-needle aspiration is a well established method for the diagnosis of peripheral lung lesion. In order to compare different methods of aspiration, we analyze retrospectively two different series: 267 fine needle aspirations (FNA) compared with the histological diagnosis on surgical specimens and 292 lung biopsies using a coaxial technique with comparison between cytological diagnosis--smears and imprints--and histological diagnosis simultaneously obtained on the same specimen. The sensitivity (91%), the specificity (90%) and the overall typing accuracy related to the histological types obtained by FNAB are equivalent to those of the literature. The low rate of pneumothorax in the series (6%) is related to the use of immediate interpretation of the specimen. Automated biopsy with a coaxial cutting needle provide cytological specimens--smears and imprint--with a high rate of sensibility (95.3%) and of sensibility (98%). The overall sensitivity of the cytological methods alone is better than biopsy (95.3% vs. 92.9%), but the typing accuracy is not as good as biopsy alone (98% vs. 100%). False-positive and false-negative diagnoses are the same in both series. In conclusion the percutaneous aspiration method choose to establish a morphological diagnosis in lung lesion depends now on the habits of the radiologist and the pathologist.

[Primary sarcoma of the pulmonary artery. Case report]. / Sarcome primitif de l'artère pulmonaire. A propos d'une observation.

INTRODUCTION: Sarcoma of the common pulmonary artery is a rare malignant tumor that can mimic pulmonary embolism. EXEGESIS: We report a case of a pulmonary artery sarcoma that occurred in a 60-year-old woman and had an unusual (4-year duration) evolution. CONCLUSION: Early diagnosis with adequate surgical procedures (complete resection) leads to better prognosis.