Focal histopathological progression of porcine experimental abdominal aortic aneurysm is mitigated by atorvastatin.

AIM: Observational studies in human patients and animal experiments suggested that statins have a potential in slowing the growth of small abdominal aortic aneurysms (AAA). Our aim was to quantify histological postoperative changes of AAA in porcine experimental model of AAA with and without administration of atorvastatin. METHODS: The AAA was induced by intraaortic infusion of porcine pancreatic elastase and subrenal application of plastic cuff. The AAA statin group (N.=14) received atorvastatin 1 mg/kg daily for 28 days, the other AAA group (N.=13) did not. The aortic diameter was measured by ultrasonography. Aortic samples were described using eleven quantitative histological parameters and compared with healthy aortae. RESULTS: There was no difference in aortic diameter between the AAA with statin when compared to AAA without statin. Administration of atorvastatin led to a better postoperative histological condition of the aortic elastin network, preservation of contractile phenotype of vascular smooth muscle, a higher density of vasa vasorum, it prevented thickening of intima and media. The increase in wall thickness in AAA without atorvastatin has not been accompanied by a proportional increase in number of vasa vasorum. CONCLUSION: The effects of atorvastatin seem to prevent the histopathological progression of AAA.

[Plasmatic levels of proinflammatory cytokines in abdominal aortic aneurysms]. / Plazmatické hladiny prozánetlivých cytokinu u aneuryzmatu abdominální aorty.

INTRODUCTION: Inflammation within the abdominal aortic wall is generally considered a very significant ethiopathogenic factor in the development of abdominal aortic aneurysms. Proinflammatory cytokines are important mediators of inflammation within the abdominal aortic wall. AIM: The aim of the study was to research, whether plasmatic levels of certain proinflammatory cytokines, which can commonly be evaluated (TNFalpha, IL-1, -2, -6 a -8), play a significant role in the development of AAA. METHOD: The prospective non-randomized study included 345 patients with AAAs. The patients were assigned to 5 subgroups based on their symptoms and AAA diameters. The first subgroup included patients with symptomatic AAAs, including AAA ruptures (N = 69), the second subgroup included subjects with asymptomatic AAAs (N = 276) with AAA diameters up to 5 cm (N = 72), the third subgroup included 5 cm (N = 72), the fourth included 5-8 cm (N = 192) and the fifth subgroup included subjects with AAA diameters of more than 8 cm (N = 81). The mean age of patients was 74.1 +/- 7.8 years (56-84 y.o.a.). The male to female ratio was 5:1. The control group included 30 healthy volunteer subjects of similar age and male to female rates, who had no clinical signs of arterial disorders. Plasmatic levels of cytokines were evaluated from venous blood samples using ELISA (Bender, Austria) testing. Statistical assessment of the results was performed using ANOVA and Wilcoxon tests with Spearman's correlation. P values < 0.05 were considered significant. RESULTS: Plasmatic concentrations of proinflammatory cytokines were found to be statistically significantly higher in patients with AAAs compared to those in healthy volunteers. Plasmatic IL8 levels were significantly decreasing proportionally to decreasing AAA diameters (p < 0.05). TNFalpha levels were found to be significantly low in symptomatic patients with AAA ruptures (p < 0.05). CONCLUSION: The study confirmed the significance of proinflammatory cytokines levels monitoring in AAA patients. The authors showed that, for instance IL8 activity and to a certain extent TNFalpha activity, is the highest in small and developing AAAs. These findings would be significant for customized medication therapy aimed at blocking the effects of these factors on the inflammatory process within the AAA wall.

Signaling molecules for early detection of adverse interactions during mechanical ventilation in animal models.

AIM: The early identification of adverse interactions during mechanical ventilation, investigated by multiplexed immunoanalysis. MATERIALS AND METHODS: Twenty piglets (average age 7 weeks, weight 23 kg) were intubated and divided into groups: A, spontaneously breathing; B, protectively ventilated; C, ventilated with injurious strategy; D, ventilated with lung disability. At the 1st hour (time-1) and 12th hour (time-2) of the study, brain natriuretic peptide (BNP), intercellular cell adhesion molecules (ICAM-1), vascular cell adhesion molecules (VCAM-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (Il-6) were analyzed in the blood. RESULTS: The injurious ventilated group C exhibited an increase in both cell adhesion molecules (p<0.01), TNF-alpha and BNP (p<0.05) at time-1, and at time-2 further increases (p<0.05). In group D, an increase in ICAM-1 and BNP (p<0.05) at time-1, and increases in Il-6 and ICAM-1 (p<0.05) at time-2, with notable decreases in urine output were observed. Overall, the lung damage correlated with TNF-alpha (r=0.904), Il-6 (r=0.740), and ICAM-1 (r=0.756) levels. CONCLUSION: All five monitored molecules quickly and reliably signaled adverse interactions.

Diffuse alveolar damage due to inappropriate strategy of mechanical ventilation in an experimental porcine model.

BACKGROUND: The aim of the study was to determine how tidal volumes may affect the lung and haemodynamics during mechanical ventilation. MATERIALS AND METHODS: With the approval of the Ethics Committee, the study included a total of 24 healthy piglets, average weight 30 kg (range 28-33 kg). The animals were ventilated for 90 minutes under general anaesthesia with two different tidal volume strategies and allocated into three groups. Group A, animals were healthy controls, Group B, animals comprised 8 piglets with an abdominal aortic aneurysm and ventilated with a low tidal volume strategy (VT(exp) 7 ml/kg). Group C comprised 8 animals seven days after kidney transplantation, ventilated with a high tidal volume strategy (VT(exp) 12 ml/kg). Changes in lung mechanics and hemodynamics were assessed at 30th and 90th minutes. Lung tissue samples were examined histologically. RESULTS: Protective ventilation in Group A and B did not confer any haemodynamic and lung mechanic differences. Significant differences were only found in Group C at 90 minutes for increased preload of both heart ventricles (CVP; t-test 4.07, p<0.01 and PAoP; t-test 8.43, p<0.01), pulmonary vascular resistance (t-test 3.11, p<0.05), and decreased expiratory tidal volume (t-test 6.07, p<0.01), dynamic lung compliance (t-test 3.83, p<0.01) and cardiac output (t-test 2.07, p<0.01). Diffuse alveolar damage was detected histologically. CONCLUSION: Mechanical ventilation at high tidal volumes reaching 12 ml/kg caused functional changes in the lungs, diffuse alveolar damage and reduction of cardiac output within 90 minutes.

Quantification of plasminogen activator inhibitor type 1 in the aortic wall.

AIM: Plasminogen activator inhibitor type 1 (PAI-1) plays a key role in regulation of fibrinolytic system, cell-associated proteolysis and migration of smooth muscle cells (SMC). This study is focused on the types of PAI-1 expressing cells, quantification of PAI-1 expression in the walls of aneurysmatic abdominal aortas (AAA) and correlation between histological and clinical findings. METHODS: A group of nine patients who underwent surgery for AAA: asymptomatic (aAAA), symptomatic (sAAA) and ruptured (rAAA) and one control specimen (CA) were included in the study. Samples underwent histological processing and immunohistochemistry in comparison with in situ hybridisation. In order to assess the PAI-1 area fraction in histological sections through the aortic wall the Line System module of Ellipse software was used. PAI-1 expressing cells were measured in CA and AAA: endothelium, SMC, and foam cells. Photomicrographs with a total area of 0.7 mm(2) for each specimen were analysed by two independent observers. Mean values of PAI-1 positive components per section area were calculated as average values. RESULTS: The results of both observers are as follows: 28.6% in CA; 18.1% in aAAA; 10.9% in sAAA; 11.0% in rAAA. During the progression of AAA, the SMC (PAI-1 expression was found mainly in them) became less abundant in agreement with the values of PAI-1 area fraction. In rAAA immunohistochemistry detected PAI-1 in necrotic centres of atheromathous plaques. CONCLUSIONS: AAA may be evaluated as the result of gradual changes in regulation of fibrinolysis that is observed as redistribution of cells expressing PAI-1. The area fraction of PAI-1 positive components correlates with clinical classification of AAA.

Adverse effects of the high tidal volume during mechanical ventilation of normal lung in pigs.

INTRODUCTION: The "open lung concept" theory of mechanical ventilation is correct, but an unsuitable setting of the machine is not appropriate in children. TYPE OF STUDY: This experimental study is a comparative, closed, randomized, double-blind study. The aim of the study was to verify the hypothesis that even a short-term high tidal volume during the course of mechanical ventilation damages the lung parenchyma as well as extra-pulmonary organs. MATERIAL AND METHODS: The inappropriate strategy of mechanical lung ventilation was simulated on an animal model. The study was performed on 30 healthy white domestic piglets (25 kg). Using a random selection, the piglets with healthy lungs were ventilated for 120 minutes under general anaesthesia with two different strategies of mechanical ventilation, i.e. 15 animals achieving alveolar hyperinflation with a high tidal volume (14 ml.kg(-1)), and 15 animals according to the "lung protective strategy" principle. Lung tissue samples were examined morphologically using the blind test method, and the proinflammatory cytokines levels were assessed in the piglets' serum. RESULTS: The study demonstrated that a high tidal volume during mechanical lung ventilation with permanent positive pressure after 120 minutes induced very important morphological and functional lung changes that unfavourably influenced blood circulation, reduced cardiac output and induced a systemic inflammatory reaction (Fig. 9, Ref. 11).

[Splenosis in the abdominal wall subcutis]. / Splenóza v podkozí brisni steny.

A case of subcutaneous splenosis in the abdominal wall of a 23-year-old oligophrenic man is reported. Further, the most important features of splenosis in various localisations are provided. The patient presented with a well-demarcated 8x7x5 cm subcutaneous tumour in the left inguinal area closely above the scar after a previous operation for hernia. The lesion simulated clinically a hernia or a tumour due to its large size and location. Additionally, no history could be taken from the patient due to his mental handicap. The diagnosis of splenosis was established histologically.

[Treatment of Hodgkin's disease using the German Study Group protocol. Personal experience and results]. / Lécba Hodgkinovy choroby podle protokolu Nemecké studijní skupiny. Nase zkusenosti a výsledky.

The article present an evaluation (02/1999) of the study of primary treatment of Hodgkin's disease (HD) according to the third generation of the German Hodgkin's Disease Study Group (GHSG), and our experience with this treatment strategy. HD7 study of early stages HD showed better results (fewer relapses) for combined chemo and radiotherapy than for radiotherapy alone (2x ABVD + extended field radiotherapy compared to extended field radiotherapy alone). HD8 study of intermediate stage HD did not show any difference between chemotherapy 2x (COPP + ABVD) combined with radiotherapy extended field, or involved field. Due to the long-term consequences (especially secondary neoplasm), in the current (fourth) generation protocol extended field radiotherapy in early and intermediate stage HD has been replaced by a combination of lesser toxic chemotherapy and involved field radiotherapy. HD9 study of advanced HD. The standard treatment at present of COPP/ABVD (A) was compared with the new chemotherapeutic regimen, BEACOPP baseline (B) and escalated (C). The first evaluation of this study (1996) showed better results in the case of BEACOPP. The latest evaluation showed significantly better results for the escalated version. This is best illustrated by the low percentage of disease progression (C 2%, B 8%, A 12%, p < 0.05). Therefore, DHSG is considered to be the new standard for treatment of advanced stage HD. OUR RESULTS: Between 1995-1998, 54 patients with primary HD were treated at the FN Královaké Vinohrady, Prague according to the third generation GHSG protocol. Of these, 5 patients (9%) according to HD7, 14 (26%) according to HD8 and 35 patients (65%) according to HD9. Our results correspond to those of the whole GHSG, but they can not be statistically evaluated because of the small number of patients involved.

[Type I and III procollagen in patients with abdominal aorta aneurysms]. / Prokolagen typu I a III u nemocných s aneuryzmaty brisní aorty.

BACKGROUND: Collagen and elastin are the basic building stones of the aortal wall. During the process of development of an aneurysm of the abdominal aorta (AAA) degradation and remodelling of elastin and collagen in the intercellular matrix of its wall occurs. The two main types of collagen in the aorta are collagens type I and III. During type I collagen synthesis the carboxyterminal propeptide of procollagen (PICP) is released and during synthesis and degradation of collagen type III the aminoterminal propeptide collagen III (PIIINP). The objective of the present work was to assess to what extent the two factors can be used to follow up metabolic processes in the AAA wal and in plasma in relation to the extent and symptomatology of AAA. METHODS AND RESULTS: Samples of venous blood and the AAA wall were examined using radioimmunoanalytical methods. PIIINP levels in venous blood were significantly higher (wall p < 0.01) in patients with AAA (n = 78) as compared with the control group (n = 15). The authors did not reveal a statistically significant difference between the levels of the two factors in the blood of patients with AAA of different extent and symptomatology. The PIIINP concentration in the AAA wal correlated significantly with its extent and symptomatology (wall p < 0.01). CONCLUSIONS: Evidence was provided of an enhanced metabolism of collagen type III in the AAA wal with predominant degradation in growing and symptomatic AAA. For complete evaluation of the importance of PICP and PIIINP plasma levels it will be necessary to follow up their dynamics in subjects with growing, small (< 5 cm) AAA.

[Cytokine metabolism in aneurysms of the abdominal aorta]. / Metabolismus cytokinu u aneuryzmatu brisní aorty.

The main cytokines which participate in the etiopathogenesis of aneurysms of the abdominal aorta (AAA) are: tumour necrotizing factor (TNF), interleukins 1b, 2, 6 and 8 (IL 1b, 2, 6, 8), platelet growth factor (PDGF) and endothelin 1, 2 (ET 1, 2). The objective of the presented work was to assess whether plasma levels of these cytokines can be used as endogenous markers of the size and symptomatology of AAA and also to what extent they correlated with hypertension which is a serious risk factor of AAA. During the three-year period (1995-1997) 86 patients with AAA were examined. The control group (n = 30) was formed by patients admitted for planned cholecystectomy. Plasma levels of all investigated cytokines with the exception of IL 8 in AAA differed markedly from the levels in the control group (p < 0.05-p < 0.0001). Changes in levels of IL8 and ET 1, 2 were significant in relation to the size of AAA (p < 0.05 and p < 0.01 resp.). The IL8 levels together with TNF in hypertonic patients correlated with the size of the AAA (p < 0.05 and p < 0.01 resp.), in normotonic subjects with the levels of IL 1b and IL2 (p < 0.05). The TNF levels were significant in symptomatic AAA (p < 0.05). The rising or declining levels of some plasma cytokines can serve as plasma markers of the growth and symptomatology of AAA.

[Segmental mediolytic arteriopathy]. / Segmentální mediolytická arteriopatie.

Three cases of segmental mediolytic arteriopathy occurring in abdominal muscular arteries are presented. This unusual arterial lesion is noted for cytoplasmic vacuolar degeneration of the arterial smooth muscle cells, intercellular vacuoles of various sizes, and focal arterial wall defects designated "arterial gaps". This spectrum of histologic changes can progress to formation of aneurysms with rupture of the vascular wall. The extensive intraabdominal haemorrhage led to the death of all our patients. Pathogenesis and differential diagnosis of this lesion is discussed.

[Radiodiagnostic methods in the postmortem study of a dicephalus masculinus]. / Radiodiagnostische Methoden in der postmortalen Untersuchung eines Dicephalus masculinus.

With conventional radiography and with CT several malformations were detected in a dicephalus masculinus. The most important were: 2 spinal medullas in a common spinal canal (TH1 to L4), hydrocephalus of both lateral ventricles and of the third ventricle, prolaps of the left hepatic lobe into the left thoracic cavity, two aortic arcs, one large internal jugular vein, and twin bases of the vertebrae TH1 to L5. The dicephalus had not only a double head, but also two cervices connected by a falx.

[Sudden death in venous diseases]. / Mort subite dans les maladies veineuses.

We have studied 286 cases of sudden death due to massive pulmonary embolism. In 155 women and 131 men, we made a statistical analysis of the average age, the presence of thrombosis, varices, atherosclerosis, and other complications, and also dietary considerations. We present a detailed observation of a thirty-two year old woman, who died following massive pulmonary embolism, the source of which was thrombosis of the ovarian and pelvic veins. We learned that this woman, who did not smoke, and whose liver was slightly affected, had, for three years, been taking an uninterrupted course of the contraceptive pill Non-Ovlon.

PIP: Between 1963-82, 286 deaths were diagnosed after autopsy as due to pulmonary embolism at the Medico-Legal Institute of Plzen, Czechoslovakia. In almost 95% of cases, there was a massive and acute embolism of the pulmonary artery. 155 women and 131 men were involved. The average age of victims was 70 years for women and 66 for men. A thrombosis of the deep veins of the legs was found in 95% of the men and women. Unilateral or bilateral varices or their trophic complications were observed in 30% of women and 27% of men. Almost all patients were affected by arteriosclerosis, with the most serious sclerosis occurring in 32% of the women and 27% of the men. 32% of the men and 53% of the women were obese. The pulmonary embolism coexisted with another serious illness or a trauma in over 90% of cases. The deaths of 12 men and 13 women under 50 years old were studied in greater detail. In this group the cause of death was massive embolism of the pulmonary artery accompanied by deep thrombosis of the legs. The greatest differences were found in the degree of sclerosis of the arteries. Trauma preceded death in 30% of these patients. 50% of the women and 30% of the men were obese. A 32-year-old obese, nonsmoking woman originally consulted for intolerable back pains. About 8 days later she was hospitalized and died. The autopsy revealed a massive and acute pulmonary embolism with vast hemorrhagic infarcts. Thrombosis of the veins was discovered to be the source of the embolism. Microscopic examination also disclosed a venous thrombosis in the ovaries. A proliferation of elastic tissue and a visible thickening of the intima were seen in the arteries, as well as a dilatation of the lymphatic vessels. There was no indication of thrombophlebitis in the leg veins. The medical history showed that the woman had been taking an oral contraceptive (OC) for the past 3 years and continued doing so until the day before her death. The woman's gynecologist stated that 4 months before her death a routine liver examination was slightly positive and the patient was advised to discontinue her combined OC (Non-Ovlon) for 3 months. The woman felt well and disregarded the advice. Non-Ovlon contains 1 mg of norethisterone acetate and .5 mg of ethinyl estradiol.

The development of the vascular system in man.

On the basis of material comprising 10 developmental stages of man in 35 embryonic series, the authors tried to determine the critical developmental period of the blood vessel wall. This period falls between the 5th and 16th weeks of intrauterine life, that is in the period of the formation of the basic wall structure characteristic of the particular vessel type (i. e. the elastic and muscular arteries, large veins, limb veins, and lymphatics). In limbs the differences between the superficial and deep veins as regards the vessel wall development, were disclosed.