Age-related changes in the elastic tissue of the human thoracic aorta.

Thirty human aortas with varying degrees of atheroma graded macroscopically according to the WHO classification were taken at autopsy from subjects of different ages (24-86 years). Study by light microscopy showed aortas with an intact wall (4 subjects, 25-46 years) with a thin intima and regular elastic layers, and aortas with varying degrees of modification of the wall, where the intima was of varying thickness and the elastic fibers showed varying degrees of damage (moderate lesions: 5 subjects, 35-52 yrs; severe lesions: 21 subjects, 26-86 yrs). From each aorta, a 4-cm segment from the tunica media, free of atheromatous lesions, was defatted and subjected to successive treatment with EDTA-Tris, 6 M guanidine-HCl-Tris, 6 M guanidine-HCl-Tris-DTE and collagenase. The residues (EP residues) were subjected to amino acid (AA) analysis and transmission electron microscopy (TEM) study. In the young subject, the AA composition was similar to that of elastin and the TEM images were characteristic of this substance. In the aging subject, an increase in polar AA and a parallel decrease in apolar AA and crosslinks was noted. By TEM, the elastin was seen to be associated with abundant fibrillar material. Trypsin treatment of EP residues gave E residues, whose composition and TEM appearance were similar in all samples, corresponding to the standard composition of elastin and its classic appearance by electron microscopy. We suggest that the fibrillar material removed by trypsin is the morphological reflection of the chemical variations observed in the EP residues. These correspond to contamination of the elastin by a polar protein fraction. This contamination is closely correlated with age but not with the degree of atheroma. Thus the age-related chemical changes in elastin appear to be independent of the onset and evolution of atheromatous lesions. The 10-15 nm diameter of the contaminating fibrillar material suggests that may be the microfibrillar fraction of elastic tissue.

Hypothesis on microangiopathy of cutaneous capillaries.

Microangiopathy is a more or less pronounced PAS deposit-located exterior to the endothelial cells of the lymphatics and the basal membrane of the capillaries. This lesion, found in various normal and pathological states, has generated numerous pathogenic hypotheses. The presence of microangiopathy in 5 groups of 50 subjects representing five different clinical conditions, subjects over 60 years old or less than 40, diabetics, latent diabetics or patients with severe coronary heart disease, together with microscopic and/or ultrastructural lesions of the connective tissue (fibroblasts, collagen and elastic fibers, ground substance) has enabled us to propose a pathogenic hypothesis applicable to any microangiopathy. The initial change, hereditary or acquired, would be fibroblastic or interstitial. It would be characterized by the accumulation of glycoproteins, proteoglyacans and soluble collagen in the interstitium. Incomplete drainage of these macromolecules would occur around the blood and lymphatic capillaries and manifest itself by a PAS deposit, the hallmark of the microangiopathy.

Is cutaneous apoprotein B a better discriminator than serum lipoproteins for atherosclerosis?

Serum lipids, skin apoprotein B (apo B) and skin cholesterol measurements have been investigated in 2 populations: one with normal coronarography, the other with pathological coronarography. Within these 2 populations there were highly significant differences in serum apo B (P less than 0.001), skin cholesterol (P less than 0.01) and skin apo B (P less than 0.001) levels. Skin apo B is a valuable test because its increase is closely related to the coronary heart disease. From these 2 populations, 2 groups with normal serum apo B (less than 1.3 g/l) were selected and compared. No significant differences in the various serum lipids were observed except for triglycerides (P less than 0.05) and serum apo B (P less than 0.05). However, a very significant difference was noticed in the skin apo B (P less than 0.001). With this cutaneous apo B determination it was possible to foresee coronary heart disease in 75% of patients. This test can be therefore considered useful to predict coronary status.

Collagen of the normal and the varicose human saphenous vein: a biochemical study.

Various types of collagen (I, III, IV, V) were identified in normal and varicose human saphenous veins using pepsin digestion and cyanogen bromide digestion followed by SDS-polyacrylamide gel electrophoresis. Varicose veins were found to have a higher collagen content than normal veins. This is consistent with the morphological fibrosis which has regularly been described. No essential differences were found in the collagen composition of dilated and apparently healthy portions of varicose veins.

[Cimetidine treatment of primary hyperparathyroidism]. / Traitement par la cimétidine de l'hyperparathyroidie primitive.

Since Sherwood's report in 1979, contradictory findings have been published with regarding the treatment of primary hyperparathyroidism with Cimetidine. We studied 16 patients with primary hyperparathyroidism treated with 1,200 mg of Cimetidine and followed-up clinically and biochemically. A decrease in serum calcium and urinary CAMP was observed after the fourth week of Cimetidine therapy with no significant change in parathormone levels. In none of the cases did Cimetidine seem to provide a treatment of hyperparathyroidism, a condition which remains curable with surgery.

Skin cholesterol and skin apoprotein B in atherosclerosis.

In order to quantify the accumulation of apoprotein B in skin we determined the amount of apo B in the skin of atherosclerotic patients using a modified Hoff's method with extraction and electroimmunoassay. Skin biopsies were taken from the lower limbs of nineteen male patients with arteriosclerosis obliterans during revascularization and from the thoracic region of thirty male patients with ischemic heart disease during coronary bypass graft surgery and thirty one male patients with abnormalities of cardiac valves during valvuloplasty. A significant positive correlation between skin apo B and skin cholesterol was found in three groups. Our data support the hypothesis that cholesterol deposit in the skin of patients with atherosclerosis is derived from plasma lipoprotein B and that the content of skin lipids parallels with the development of atherosclerosis in man.

Dermis ageing.

On ageing major changes within connective components of the dermis can be seen: collagen looses its regular and fascicular appearance, while ground substance increases, elastic material decreases and the fibroblast cell population becomes "at rest". The resulting dermal ageing is different according to individuals and is related to genetic back ground and exposition to multiple aggressions. This review presents these changes of the superficial dermis and the role of fibroblasts in the conservation of the connective tissue integrity.

What's new in cerebral pathology in acquired immune deficiencies?

Over the last few decades, a new pathology has appeared, directly related to the modified immune status of the hosts. It presents several distinctive points. The central nervous system is particularly affected. The opportunistic pathogenic agents do not usually injure the brain parenchyma and are not known for their aggressiveness in normal adults (papovavirus). Diagnosis of these different diseases is often difficult, some biological tests being irrelevant because of alterations of the immune system (toxoplasmosis). The lesions may be exclusively located in the brain (tuberculosis, lymphomas) which is not usually affected by these agents. Response to therapy is frequently poor, the clinical course being rapid and fatal. However, therapy may be successful in some cases, justifying the use of somewhat aggressive procedures (biopsy) in order to obtain an accurate diagnosis. It is important to be aware of these data, and an understanding of them may help in managing these already difficult patients. They also make possible some interesting pathogenic hypotheses.

Diffuse storage of vegetal wax hydrocarbons of dietary origin. Pathologic and chemical findings in a case.

A 55-year-old man died suddenly, after presenting with unstable angina and an asymptomatic micronodular pulmonary pattern. Autopsy revealed storage of a crystallized fatty substance in the lymph nodes, liver, spleen, adrenal glands, and lungs. In the latter organ, the deposition formed foreign body granulomas, accounting for the radiographic appearance. Mass spectrometry identified the fatty substance as straight-chain saturated hydrocarbons (n-alkanes) of carbon-29 and carbon-31 atoms, which are naturally present in the cuticular wax of many vegetals. The case history and the elimination as causal agent of products manipulated in the patient's work led to the conclusion that the storage was due to excessive consumption of apples, and to a lesser degree of Brussels sprouts. We present the light-microscopic findings and the principal biochemical results. Pathogenic mechanisms are described. As far as we are aware, this is the only observation of vegetal alkane storage to be described to date.

An unusual dermal collagen disorder in a dog.

An adult dog developed a connective tissue disorder characterized by hyperextensibility of the skin on the head, neck and shoulders. Under light microscopy, the thickness of the dermis was reduced and the collagen bundles were fragmented. Hypodermic lesions appeared as fat necrosis and swelling of the wall of the blood vessels. Electron microscopically, the packing of collagen bundles and fibres in the dermis was highly disorganized and the rough endoplasmic reticulum of fibroblasts showed dilatation of the cisternae. Whereas the dermal lesions were non-specific, this case differed fundamentally from canine inherited collagen diseases in that the clinical features appeared in an old dog and the dermal lesions were only localized and were associated with hypodermal atrophy.

An atypical aortic atherosclerotic lesion in cynomolgus monkeys during hypercholesterolemia: a protection by smooth muscle cells against advanced lesions?

This study focuses on the fortuitous discovery of an atypical atherosclerotic lesion in four of 49 male adult cynomolgus monkeys (macacus fascicularis) which were maintained for a long time at a high level of hypercholesterolemia, and in seven of 19 female cynomolgus monkeys examined from the second to the 24th week of hypercholesterolemic diet: this lesion was in formation or already mature during this period of diet. This atypical lesion was formed by a collagen and elastic network surrounding synthetic smooth muscle cells without fibrofatty or fibrous plaques. Lipids were occasionally seen in the inner intima. The lesion appeared early (from the third week of diet). Once established, its morphology did not change. It became more extensive, but was not complicated by lipid overload in spite of prolonged, permanent hypercholesterolemia. This response to hypercholesterolemia is interesting because the activity of the smooth muscle cells differs from that observed in the classic lesion: they intervene earlier, their replication is very marked and rapid, their elastin secretion is greater and remains constant over time, and their phagocytic properties are reduced. This experimental study examines the installation and the maintenance of this lesion and raises the problem of its origin.

[Cutaneous apoprotein B and coronary atherosclerosis]. / Apoprotéine B cutanée et athérosclérose coronarienne.

Cutaneous and plasma lipids (cholesterol and Apoprotein B) were studied in 2 populations (average age 57.5 years), one with pathological and the other with normal coronary angiography. Skin biopsy was performed during the incision of thoracotomy. The concentrations of Apo B and cholesterol in the skin were compared to those of plasma lipids, lipoproteins and apoprotein B for the diagnosis of atherosclerosis. This study showed that skin Apo B was the best marker of coronary atherosclerosis in patients with plasma Apo B concentrations of less than 1.3 g/l. The skin Apo B concentration was closely correlated to the presence but not to the severity of this arterial pathology. The cardiovascular risk factors of this population, studied separately and in a cumulative manner, confirmed the results of previously published reports.

[Cutaneous cholesterol in the young and aged coronary patient]. / Le cholestérol cutané du coronarien jeune et âgé.

Serum cholesterol (ch), its lipoprotein fractions and triglycerides were measured in three populations of proven coronary patients (less than 50 years, n = 56; between 50 and 65 years, n = 56; greater than 65 years, n = 23); the risk factor total ch/HDL ch was calculated. The level of skin cholesterol was also estimated by skin biopsy in each patient and compared to that of three control populations of the same age. The results indicated that 1) there was no significant difference in skin cholesterol of patients with myocardial infarction whatever their age, 2) there was a significant difference (p less than 0,001) with control subjects of the same age except in the over 65 population, 3) the total cholesterol was normal in all three groups, 4) the HDL cholesterol of coronary patients over 50 year old was normal and slightly reduced in younger coronary patients, 5) the ratio total ch/HDL ch was increased in coronary patients under 50, but normal after this age, 6) the triglyceride level was higher in the young coronary patients than in those over 50 years old. Four conclusions are drawn: 1) the total Ch/HDL ch ratio is a good indicator of coronary risk in patients under 50 years old but shows less sensitive variations than the level of skin cholesterol, 2) the ch/HDL ch in coronary patients between 50 and 65 years old is normal; the only laboratory finding which correlates with the coronary event is skin cholesterol; after 65 years of age the skin cholesterol stabilises to the same levels as found in control subjects; 3) from the outset, at whatever age infarction occurs, skin cholesterol is increased (about 0,45 mumol/100 ngr of fresh skin), whilst the risk factor is higher in the younger population; 4) skin cholesterol shows less variation in the three coronary groups than the other blood parameters measured. It would therefore appear to be a very discriminating index of coronary atherosclerosis.

Experimental lathyrism: exostoses and aneurysmal-like bone cysts of the mandible in the rat.

The effect of chronic lathyrism on the mandible of the rat was studied. Exostoses, thinning and discoloration of the cortical plates, intraosseous bleeding and hemorrhagic cyst were observed after six weeks of administration of beta-aminoproprionitrile fumarate. The exostoses consisted of homogeneous cellular fibrous tissue containing osteoid, hyalin-like material and abundant ground substance. The cysts were filled with erythrocytes and lined by spindle-shaped fibroblasts, collagen fibers or osteoblast-like cells. Between the cysts, bands and sheets of dense and cellular connective tissue presenting foci of hemorrhage, osteoid and metaplastic cartilage were found. Numerous mast cells were demonstrated with alcian and toluidine blue in the hematopoietic bone marrow, cancellous bone and around the capillary network surrounding the exostoses and cysts. Exostoses have already been studied and explained by the action of BAPN (lysyl oxidase). Hemorrhagic cysts could be explained by histamine release from the mast cells (hypervascularity, hyperemia, increased permeability, rupture and progressive confluence of these small hemorrhagic cysts). Histopathology of the experimental cysts had some points in common with the human aneurysmal bone cyst. Could the pathogenic mechanisms be similar for both lesions?

[Association of an adenoid cystic epithelioma with a clear cell carcinoma of the palate]. / Association d'un épithélioma adénoïde kystique et d'un carcinome à cellules claires du palais.

An infrequent polymorphous minor salivary gland tumor is described. It involved the palate and later invaded the upper jaw. The morphologic features are those of both adenoid cystic carcinoma and clear cell carcinoma. The clinical course, the cellular admixture of tumour components, and the immunohistologic results allow us to propose that clear cell carcinoma originating from adenoid cystic carcinoma offers the worst prognosis.

[Human aorta: endothelium and atheroma (author's transl)]. / Aorte Humaine: endothélium et athérome.

An electron microscopic study of aortic endothelium obtained from necropsy and biopsy material shows pathological changes corresponding the severity of the atheromatous state, but unrelated to age. All stage I aortas show the same type of endothelial changes. So do stage II aortas. The pathological structural changes in the endothelial cells corresponding to aortas of stage I, II-III involve the microfilaments, vesicles, intercellular junctions and basement membrane. The microfilaments are more numerous and better defined in atheromatous aortas. Also rare bundles of microfilaments with electron-dense centers are seen. The intra-cytoplasmic vesicles increase presently deeper invaginations (pseudo-channels) in the stages II and III aortas. In these stages the intercellular junctions are open involving all or part of the junctions. All three described ultra-structural changes increase the permeability of the endothelium to lipids and plasma glycoproteins. The thickening of the sub-endothelial basement membrane résults from the increase of type IV collagen synthesized by the endothelial cells. Lysis of endothelial cells and platelet agregation are related to the stage of atheromatosis. The number of Weibel Palade bodies increase in stade II and III aortas. These organelles play a role in blood coagulation and accelerate atheromatosis. In conclusion, the aortic endothelium constitutes an active barrier. The pathological atheromatosis process involves the endothelium. The endothelial cells play a normal role in the passage of molecules from blood plasma into the aortic wall. That explains intimal formation and intimal fibrosis. The endothelium also participates in the initial pathogenic mechanism of atheroma formation (fatty dot and streak, gray gelatinous elevation and mural thrombus).

[Primary bilateral tubular adenocarcinoma with antecedents of invasive galactophoric carcinoma of the breast. Apropos of a case; review of the literature]. / Adéno-carcinome tubaire primitif bilatéral avec antécédents de carcinome galactophorique invasif du sein. A propos d'une observation, revue de la littérature.

The authors report a case of primary bilateral adenocarcinoma of the fallopian tube in a woman with invasive ductal carcinoma of the breast in her antecedents. The tubal carcinoma was in situ or invasive and appeared as a bilateral hydrosalpinx, fact which often happens in the literature. Gross examination showed a tumoral mass of about 2 cm diameter at the fimbriated end of the right tube, the diagnostic of bilaterality requiring serial cuts on the left tube. The electron microscopic study showed ciliated differentiation in the neoplastic cells, bearing out the primitive nature of the proliferation.

[Adeno-myoepithelial proliferation in the breast]. / Les proliférations adéno-myoépithéliales du sein.

The authors report 13 cases of myoepithelial cell proliferation in the breast. One of them is a neoplasm with a predominant myoepithelial component. These proliferations in mastopathies or neoplasms raise important questions concerning differential diagnosis with invasive adenocarcinoma and prognosis.

[The place of type I familial amyloid neuropathy in amylosis. Anatomo-clinical study of a case in France]. / Place de la neuropathie amyloïde familiale de type I dans l'amylose. Etude anatomo-clinique d'un cas français.

The clinical and pathologic findings of a case of amyloidogenic heredo familial neuropathy type I is presented. The patient is a man, died at 46 years. The examination of a nerve biopsy, the clinical evolution and the family history are representative of the condition. The study of autopsy material revealed amyloïd deposits within vessels walls, autonomic nerves of almost all viscera but liver, muscle and skin, around myofibers in the heart. Kidney glomeruli were markedly involved and numerous obsolescent glomeruli were seen. Lesions of central nervous system were of interest: enlargement of meningeal vessels walls due to amyloïd deposits as subpial deposition band were observed. The pattern of amyloïd deposits within peripherical nerves was quite different according to their proximal or distal ends. While distal amyloïd deposits were scant, nerve damages were striking. In proximal portions, amyloïdosis could be found in all layers of nerve structures including the walls of endoneural small vessels. Semi-thin sections allowed to observe rare myelinated fibers entrapped by aggregates of a microfibrillary material. While there was absence of a patent axonal lesion, clusters of regenerating fibers were not infrequent. Ultrastructural study confirmed the close relationship between amyloïd fibrils, Schwann cell basal laminae and collagen fibers. An immunopathological study using immunserums raised against the AA composant of amyloïdosis, K and lambda light chains, and prealbumin were negative. Our results are in agreement with descriptions already reported in the medical literature. Therefore, they allow to discuss already known pathogenic mechanisms for this rare affection transmitted by a dominant autosomic gene.

Staining of elastic tissue by Verhoeff's iron hematoxylin.

The elastic system of normal human skin was studied by light and immunofluorescence. Oxytalan, elaunin et elastic fibers were stained by weigert, orcein, gomori and Verhoeff. By Verhoeff's method all elastic system of dermis is shown, with other three stains, only elaunic and elastic fibers are well visualized. These results are confirmed by immunofluorescence studies.