Atheroembolism in HIV-positive individuals.
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Biomedical subjects
Publications and source records attributed to P Bruneval.
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A model of arterial graft arteriosclerosis is described in which arterial wall immune injury was induced by grafting segments of abdominal aorta between two histologically incompatible strains of rats. The effect of hypertension and its treatment with the angiotensin-converting enzyme (ACE) inhibitor perindopril was tested using inbred spontaneously hypertensive rats (SHR) and their normotensive controls (Wistar-Kyoto [WKY]). Each of the grafted hypertensive and normotensive rats was randomly allocated to placebo treatment (10 SHR, 10 WKY) and perindopril treatment (2 mg/kg/day) (10 SHR, 10 WKY). The immune injury and the arterial wall response were quantified morphometrically 2 months after the grafting using specific stains for collagen, elastin, and nuclei. Hypertension was associated with a significant increase in intimal thickness. Treatment with perindopril greatly reduced intimal proliferation, decreasing the intimal thickness and the collagen content within the intimal layer. In contrast, hypertension and ACE inhibition had little effect on the arterial wall injury. We conclude that hypertension and its treatment with perindopril significantly affect graft arteriosclerosis. These effects seem to be independent of their effects on arterial wall injury, but not independent of blood pressure.
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Reports concerning unruptured, isolated aneurysms of one sinus of Valsalva are rare. These aneurysms usually protrude inside the heart and are very rarely extracardiac. We report 4 cases of isolated, unruptured extracardiac aneurysms of the noncoronary sinus of Valsalva. Clinical symptoms were nonspecific. Operation was performed by patch reconstruction of the dilated aortic sinus without replacement of the ascending aorta. Microscopic examination of the diseased aortic wall revealed absence of medial elastic fibers. Late follow-up in all 4 cases revealed a normal ascending aorta with no dilatation of the aortic root and no aortic regurgitation.
To investigate the sites of renin gene expression and localization of renin in primate ovaries, five cynomolgus (Macaca fascicularis) and one rhesus (Macaca mulatta) monkey were treated with gonadotropins to induce multiple follicle development. One ovary was removed before hCG injection (1200 IU) from three monkeys and one ovary was removed 36 h after hCG administration from three monkeys. In three monkeys, the remaining ovary was removed 3, 5, and 7 days after injection of hCG. To detect and localize renin messenger RNA, 35S-radiolabelled 1.1 kb length complementary DNA and RNA probes of human renin were used for in situ hybridization. To compare the synthesis with the presence and the storage of renin or prorenin, renin antigen was assessed by immunohistochemistry in the same tissues using a polyclonal antibody against human renin (R15). Renin mRNA was detected by in situ hybridization only in ovaries collected within 5 days of exposure to hCG. All such ovaries exhibited a positive signal. Renin mRNA was localized to the theca interna and theca lutein cells. Positive cells were observed in a few growing antral follicles, in occasional mature preovulatory follicles, in corpus luteum, and most strikingly in atretic follicles. No signal was detected in primordial, primary, or in small antral follicles of ovaries exposed to hCG. In contrast with the in situ hybridization data, no signal was detected by immunohistochemistry using antirenin antibodies which exhibited a positive signal in monkey kidney. These results indicate that hCG turns on renin gene expression. Renin is synthesized without significant intracellular storage in monkey ovarian theca interna cells and in corpus luteum. The absence of storage of renin is consistent with the high concentrations of prorenin found in ovarian follicular fluid of hCG stimulated primates and with our knowledge of cellular renin processing which indicate that prorenin is secreted constitutively as it is synthesized.
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The aetiologies of mitral regurgitation were reviewed in 336 patients operated on between 1970 and 1990. The relative frequency of rheumatic fever has decreased and the most common cause is now primary mitral valve prolapse (PMVP) which accounts for 60% of all patients. The increasing age of the surgical population seems to be one of the main factors of this change. Conservative surgical repair according to Carpentier's technique is now performed in 60% of all patients with mitral regurgitation and 80% of cases of PMVP. The aetiology of PMVP is still under discussion. Surgical description seems to indicate the existence of two different morphological aspects with significantly different rates and localizations of chordae ruptures, but our study failed to demonstrate any other anatomical, clinical or histological differences between the two groups.
We have studied the effect of ramipril (10 mg/kg daily by gastric gavage) on the development of neointima 2 and 14 days after injury to rat aorta with a balloon catheter. In treated animals, there was no significant inhibition of the early mitotic reaction after injury (synthesis of DNA, as reflected by aortic thymidine incorporation on the second day): the mean (95% confidence interval) was 3,553 (892) in the control group vs. 2,853 disintegrations/min/micrograms of DNA (555) in the treated group, 2 p greater than 0.15. However, ramipril decreased the amount of neointima formed 14 days after injury, as characterized by (a) a highly significant decrease of the intima to intima + media areas ratio [21.1 (2.4) vs. 13.7% (2.2), 2 p less than 10(-4]); (b) a significant decrease of intima-media wet weight [35.4 (1.0) vs. 30.9 mg (0.9), 2p less than 0.005]; and (c) without any significant effect on intima-media DNA content [96.3 (7.9) vs. 91.7 micrograms (5.7), 2p greater than 0.3]. These observations suggest that angiotensin converting enzyme inhibitors may not act mainly through an inhibition of smooth muscle cell proliferation. Other effects, such as inhibition of migration, hypertrophy, and matrix synthesis, should also be considered.
Human atheromatous aorta segments as well as presumably disease-free control aorta were obtained at autopsy. They were incubated with solutions of various purified dicarboxylic porphyrins including hematoporphyrin (HP) and hydroxyethylvinyldeuteroporphyrin (HVD), and with solutions of Photofrin. Selective labelling of the atheroma was shown by macroscopic and microscopic observations of the characteristic porphyrin fluorescence associated with the atheromatous plaques. The time dependence of the uptake, monitored by absorption spectrophotometry or by high performance liquid chromatography, was inferred from the disappearance of the porphyrins in the incubation medium. Significant binding was observed in the absence of albumin or serum proteins. The uptake of HP was less than that of the more hydrophobic compounds HVD or Photofrin when these porphyrins were used alone. The presence of albumin or serum drastically reduces atheroma labelling. Some competition between HP and HVD for binding sites is also seen. The present results do indicate that hydrophobic porphyrins have an intrinsic affinity for atheroma and that they can be taken up through passive processes. Taking into account previous data on animal models (Photochem. Photobiol. (1989), 731-737), it appears however that, in vivo, interactions with proteins and pharmacokinetics will primarily determine plaque labelling.
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Whipple's disease and pulmonary and lymph node tuberculosis have been diagnosed in a 70 year-old man hospitalized for weight loss and fever. The tuberculous or Whipple's disease-related nature of associated non-necrotizing epithelioid hepatic granulomas could not be determined. The existence of cellular immune defects in Whipple's disease could explain the association with tuberculosis, which has not been previously reported in the literature.
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Erythropoietin (Epo) is a glycoprotein that promotes the proliferation and differentiation of erythrocyte precursors. The major site of Epo production is the kidney, while the liver is the main extrarenal site of Epo production. Within these organs, the cells synthesizing Epo were identified by using in situ hybridization in hypoxic animals with an increased Epo mRNA expression. Epo-producing cells in the kidney were peritubular cells, most likely endothelial cells of the cortex and outer medulla. Glomerular and tubular cells were not labeled. In three patients with renal adenocarcinomas associated with polycythemia, in situ hybridization showed a strong labeling of the tumor cells. Epo secretion is stimulated by hypoxia, which is detected by an oxygen sensor located in the kidney. This oxygen sensor has been recently shown to be an heme protein. At the Epo gene level, studies to identify cis-acting DNA sequences, and trans-activation factors for inducible kidney and liver Epo expression are being pursued.
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One to five percent of human renal cell carcinomas are associated with polycythemia. It is generally assumed that polycythemia results from the secretion of erythropoietin (Epo) by the malignant cells. However, there is no direct proof supporting this hypothesis. Three patients with typical renal adenocarcinoma and polycythemia were studied. All three exhibited high Epo serum levels as measured by radioimmunoassay (RIA). A strong Epo signal was observed on Northern blot analysis of total RNA extracted from the renal tumors. The Epo message seemed to be of normal size and no Epo gene rearrangement was observed with the restriction enzymes tested. Using the in situ hybridization technique, a significant labeling was constantly observed on the tumor cells. Immunohistochemical studies showed that these tumor cells, known to be of tubular origin, were labeled by an anti-cytokeratin antibody and therefore were of epithelial nature. Thus, this study demonstrated that malignant cells of tubular origin were able to produce Epo constitutively, whereas in the mouse hypoxic kidney, peritubular cells (probably capillary endothelial cells) were the major site of Epo synthesis.
Seventeen surgical biopsy specimens of the axillary or subclavian artery were obtained from patients who had inflammatory, nonatherosclerotic arterial lesions and were studied retrospectively. Initial roentgenologic clinical, and histologic findings were evaluated and compared with final diagnosis. Histological examination suggested Takayasu's disease in 11 patients whereas the roentgenologic and clinical signs led us to suspect Takayasu's disease in only eight instances. Takayasu's disease was confirmed in these eight cases later in the course of the disease. In six patients subclavian artery biopsy specimens showed lesions consistent with Horton's disease in contrast to roentgenologic and clinical signs which suggested Takayasu's disease. In five patients, the final diagnosis was Horton's disease and in one, the diagnosis remained unknown. Of 13 patients who had revascularization procedures, bypasses remained patent in patients followed from nine months to 16 years (mean: 68 months). Histopathologic criteria are more reliable than roentgenologic or clinical signs in the diagnosis of Takayasu's disease. The subclavian artery is frequently involved in Takayasu's disease and is a desirable site for retrieval of diagnostic specimen when a revascularization procedure is entertained.