Kocová J

Inflammation in the wall of abdominal aortic aneurysm and its role in the symptomatology of aneurysm.

Cytosol levels of cytokines [interleukins 1b, 6, 8 (IL-1b, 6, 8), tumor necrosis factor-alpha (TNF-alpha)] in aneurysm walls were evaluated in a prospective non-randomized study of 57 patients. The group was divided into two subgroups: Subgroup I (ruptured aneurysms, n=11) and Subgroup II (asymptomatic aneurysms, n=32). A control group consisted of 14 kidney donors. Aortic walls were examined by immunohistochemistry and microscopy to detect inflammatory cells. More pronounced inflammatory changes and higher cytosol cytokine levels [IL6 (p<0.001), IL8 (p<0.0003) and TNFalpha (p<0.002)] were found in the walls of ruptured aneurysms than in the asymptomatic aneurysms. Immunohistochemically, most cells within the inflammatory infiltrates stained positively with the monoclonal antibody to the leucocyte common antigen (CD 45). The majority were of B-cell origin, which was demonstrated by positive staining with the monoclonal antibody L26 directed against the CD 20 antigen. These results show that an inflammatory process plays a significant role in patients with ruptured abdominal aortic aneurysms (AAA). A means of modifying the inflammatory process in the wall of AAAs might play an important role in preventing aneurysm rupture.

Asymptomatic Abdominal Aortic Aneurysms Show Histological Signs of Progression: A Quantitative Histochemical Analysis

Objective: Abdominal aortic aneurysm (AAA) is a serious disease due to its covert nature, relatively high prevalence and fatal prognosis in the case of rupture. To obtain new insights into AAA pathogenesis, we examined the relationships between histopathology, multiplex in vitro immunoassay data, diameter and symptomatology. Methods: In a prospective, non-randomised study, we evaluated samples from 6 normal infrarenal aortae and 65 AAA patients (65 walls, 55 thrombi). The AAA patients were either asymptomatic (n = 44), symptomatic (n = 7) or with ruptured AAA (n = 14). The AAA diameter was classified as small (<5 cm, n = 18), medium (5–7 cm, n = 26) and large (>7 cm, n = 21). We quantified the histopathology of the AAA wall and the adjacent thrombus. We assessed the expression of proteins in the same samples. Results: Asymptomatic AAAs had walls with more abundant inflammatory infiltrates, lower amounts of PAI-1, a higher number of tPA-positive elements, a tendency towards decreased collagen content, whereas the adjacent thrombi had a greater concentration of VCAM-1 and MMP-2 when compared with symptomatic AAAs. Compared with the aneurysmatic aorta, the normal aorta contained less collagen and more elastin, actin, desmin and PAI-1-positive elements; in addition, it was more vascular. Medium-sized AAAs were the most actin and vimentin rich, and large AAAs were the most vascular. Conclusion: Our results show that asymptomatic AAA walls often have more potentially deleterious histopathological alterations than symptomatic AAA walls. This result indicates that a progression from an asymptomatic AAA to rupture can be expected and screening patients who are at risk of rupture could be beneficial.

Subcutaneous splenosis of the abdominal wall

We report a case of subcutaneous splenosis in the abdominal wall of a 23-year-old oligophrenic man. It presented as a well-demarcated 8 x 7 x 5-cm subcutaneous tumor in the left inguinal area closely above the scar after a previous operation for hernia. The lesion simulated clinically a hernia or a tumor due to its large size and location and, additionally, no history could be taken from the patient due to his mental handicap.

A case study on peritoneal dialysis with biocompatible peritoneal dialysis fluid: increase in submesothelial compact zone thickness but not vessel density.

To the Editor: For patients undergoing peritoneal dialysis (PD), changes in the number and structure of blood vessels and thickening of the submesothelial compact connective tissue could lead to impairment and/or loss of peritoneal function and, eventually, to PD treatment failure (1). Peritoneal thickening appears to be a universal response to uremia, bioincompatible PD fluid, inflammation, infection, and other stimuli, including diabetes (2–5). Histological PD findings have been comprehensively systematized (6). Other studies have also focused on quantitative assessments of submesothelial blood vessels (3,7), as induction of angiogenesis is likely to be related to increased solute transport and peritoneal membrane ultrafiltration failure (2,8). It is believed that some long-term peritoneal membrane changes could be prevented or even reversed with the use of more biocompatible fluids, for example, fluids with fewer glucose degradation products (GDP) (1,9,10). Although data from in vitro and animal experiments almost universally show more favorable profiles with new biocompatible fluids (10–13), human studies regarding peritoneal morphology and function with biocompatible PD fluids are scant (14). Recent experimental evidence has suggested that increased angiogenesis, once triggered by glucose and GDP, becomes a key feature in ultrafiltration failure (15). PD solutions rich in glucose induce apoptosis of endothelial cells, which is followed by remodeling of the submesothelial vascular network (16). Angiogenesis increases high transport rates of low molecular weight solutes, which leads to a rapid dissipation of the osmotic gradient, causing peritoneal transport abnormalities (17). Experiments in rats have shown that pyruvatebuffered solutions induce less peritoneal angiogenesis than conventional solutions (18). To our knowledge, no quantitative histological evidence has been published yet regarding the prevention of angiogenesis in human patients who are treated with low-GDP solutions. We designed a study to evaluate the effect of biocompatible PD fluid on peritoneal morphology (the density of microvessel profiles in and the thickness of submesothelial connective tissue), as determined from biopsy specimens obtained while inserting and removing peritoneal catheters upon PD termination. The study was approved by the local ethics committee, and all participating patients gave their informed consent. For the purpose of this case study, we present a report of the first patient for whom both biopsy specimens are available. For this patient, PD was undertaken uneventfully for a six-month period, after which time PD was terminated because of resumed residual renal function (RRF).

Tissue levels of interleukins 6, 8 and of tumor necrosis factor alpha in the wall of ruptured and asymptomatic abdominal aortic aneurysms

ZusammenfassungGRUNDLAGEN: Entzündliche Veränderungen der atherosklerotischen Plaques spielen eine wichtige Rolle in der Ätiologie des abdominellen Aortenaneurysmas (AAA), wobei dafür proinflammatorische Zytokine bedeutsam sind. Das Ziel unserer Studie war, die Wichtigkeit der Entzündung für die Entstehung der Aneurysmen zu untersuchen. METHODIK: Cytosolspiegel der Interleukine 6 und 8 (IL 6, IL 8), Tumor-Nekrose-Faktor-α (TNF-α) in der Wand des Aortenaneurysm wurden in einer prospektiv-nicht- randomisierten Studie mit 110 Patienten beurteilt. Gruppe I (Aneurysmenruptur, N = 41), Gruppe II (asymptomatische Aneurysmen, N = 54), Gruppe III (Kontrollgruppe: 15 Nierenspendern). Zur Feststellung der entzündlichen Zellen in der Aorta-Wand dienten die immunohistochemische Untersuchung, sowie Licht- und Elektronenmikroskopie. ERGEBNISSE: In Aneurysmenrupturen fanden sich entzündliche Veränderungen, und wir haben in der Wand erhöhte IL 6 (P < 0,001), IL 8 (P < 0,0003) und TNF-α- Spiegel (P < 0,002) gefunden. Die meisten Zellen in den entzündlichen Infiltraten waren Stammzellen-B (CD 45 und CD 20 Antigen). SCHLUSSFOLGERUNGEN: Die Entzündung spielt eine wichtige Rolle in der Pathogenese des abdominellen Aortenaneurysmas, vorzugsweise bei rupturierten Aneurysmen. Diese Erkenntnisse müssen durch größere klinische Studien bestätigt werden. Möglicherweise können Medikamente, die gegen Zytokine wirksam sind, eine Hemmung der Entzündung im Aneurysma bewirken.SummaryBACKGROUND: Inflammation of abdominal aortic aneurysm (AAA) wall plays an important role in the etiopathogenesis of AAA. Proinflammatory cytokines are probably the key factors in this process. The aim of this study was to evaluate the significance of inflammation for AAA rupture. METHODS: Cytosol levels of interleukin 6, 8 (IL 6, 8), tumor necrosis factor-α (TNF-α) in the AAA walls were evaluated in a prospective non-randomised study including 110 patients: Group I (ruptured aneurysms, N = 41), group II (asymptomatic aneurysms, N = 54), group III (control group) consisted of 15 kidney donors. Aortic walls were examined using immunohistochemistry, light and electron microscopy to detect inflammatory cells. RESULTS: The significant inflammatory changes were found in the walls of the ruptured aneurysms with increased levels of IL 6 (P < 0.001), IL 8 (P < 0.0003) and TNF-α (P < 0.002). The majority of cells within the inflammatory infiltrates was of B-cell origin (CD 45 and CD 20 antigen). CONCLUSIONS: Inflammation plays an important role in the pathogenesis of abdominal aortic aneurysm especially in ruptured aneurysms. Additional clinical studies are needed to support this observation and test if anti-cytokine-drugs may play a role in the prevention of aneurysm rupture.