Our series of 100 consecutive patients operated on either electively or in emergency without clinical work, for abdominal aortic aneurysms, estblishes the post operative prognosis up to a ten year follow-up period. The operative mortality of 12% is mainly due to renal coronary complications. All survivors, except one, have been reviewed. 64% 5 year survival and 46% 8 year survival rates were found. These results emphasize the importance of early and systematic surgical management except when major contraindications, which we have outlined, are present. Echotomography appears to be the best method of following up small aneurysms (diameter less than 7 cms) in elderly patients.

Aged↗

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T cells, cytokines, IgE and allergic airways inflammation.

Great progress in the knowledge of the cellular and molecular signals involved in IgE antibody synthesis and in the induction of allergic inflammation has been achieved. A great deal of data support the view that Th-2-like cells are the main type of cells required for IgE production and are able to orchestrate allergic tissue inflammation. In particular, a reciprocal role for IL-4 (positive)- and IFN-gamma (negative)-producing CD4+ Th cells in the regulation of human IgE synthesis has been proven. However, a physical membrane interaction between T and B cells is required for IL-4-dependent IgE synthesis. The analysis of cytokine production by allergen-specific T cells has demonstrated that the great majority of these cells, derived from the peripheral blood of atopic patients, express a Th-2/Th-0 phenotype. Furthermore, in atopic subjects, aberrant in vitro production of IL-4 and IL-5, even in response to bacterial antigens, is displayed by CD4+ T cell clones. There is a general consensus on the accumulation of Th-2-like cells at the level of the target tissues of allergic inflammation such as the respiratory mucosa during allergic rhinitis and asthma, and at the level of the skin during atopic dermatitis. Even in other forms of bronchial asthma (intrinsic and occupational asthma), particular subsets of T cells, able to produce IL-2 and IL-5 but not IL-4, may play an important role. A great effort on the characterization of the factors that may favor the development in atopics of Th cells into Th-2-like cells has been made.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

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[Cellular and molecular mechanisms of allergic respiratory tract inflammation].

Knowledge of the cellular and molecular aspects of allergic airway inflammation has increased greatly. It is now clear that the type of specific immune response is determined by the preferential activation of CD4+ T cell subsets which secrete defined patterns of cytokines, and it has been suggested that Th2-like cells, able to produce IL-4 and IL-5, but not IFN-gamma, play an important role in the induction and maintenance of allergic airway inflammation. It has been demonstrated, moreover, that mast cells can secrete cytokines which are analogous to those produced by Th2-like cells. It is thus possible that both mast cells and Th2-like cells are involved in the induction and maintenance of allergic airway inflammation. We review here the genetic and environmental factors predisposing to allergic respiratory diseases, especially those potentially favoring the development of Th2-like cells. Particular attention is paid to the possible role of the antigen presenting cells, HLA class II molecules, T cell repertoire, and microenvironmental cytokines. We also discuss the crucial role that IL-4 plays in the development of Th2-like cells from their precursors as well as hypotheses concerning the possible molecular alterations responsible for the overexpression of the IL-4 gene in atopic subjects. This new information certainly facilitates the planning of preventive and treatment tactics for bronchial asthma.

Antigen-Presenting Cells↗

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Cellular and molecular basis of airway allergic inflammation.

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Animals↗

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[Current views on the etiopathogenesis of type-I diabetes mellitus].

In the last few years the improvement of our knowledge of the pathogenesis of type I diabetes mellitus has been possible mainly because of the development of studies of the role played by genetic factors and the better definition of lesion mechanisms. The availability of experimental models such as "non obese diabetic (NOD)" mice and "Bio-Breeding (BB)" rats, which develop a form of type I diabetes similar to that of humans, has provided many data regarding the relevance of T lymphocytes in the pathogenesis of the disease, and made it possible to anticipate the immunopathological steps leading to pre-insulitis, insulitis and, finally, to pancreatic beta-cell destruction. The analysis of sera of patients with type I diabetes has demonstrated the presence, also in the preclinical states, of several autoantibodies directed against specific autoantigenic structures of beta cells, which have come to be useful for early diagnosis and in the monitoring of the disease. However, hard evidence for a relevant role of these autoantibodies in the pathogenesis of the disease does not exist. At present, we can affirm that the expansion of autoreactive T lymphocytes specific for membrane antigens of beta cells is the most relevant immunological event for the induction and sustenance of insular lesions. Autoreactive T lymphocytes may be able to activate several effector systems of lesions through the production of multiple combinations of cytokines. The aetiology of the disease is certainly multifactorial and involves both genetic and environmental factors. With respect to the former, the most accurate studies have been performed on the HLA system. It has been clearly shown that type I diabetic patients more frequently display HLA DR3 and DR4 specificities. The results obtained by the application of molecular techniques have suggested considering as risk factors the occurrence of DQB1 0302 DQB1 0201 alleles, the presence of a neutral amino acid residue in position 57 of the DQ beta chain instead of aspartic acid, as well as an arginine residue in position 52 of the DQ alpha chain. With regard to acquired aetiological factors, the hypothesis that primary lesions of pancreatic islets could be due to some viral infections capable of triggering, through several undefined mechanisms, persistent and self-sustaining autoimmune reactions, has gained some credit.

Animals↗

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[Current advances in various aspects of chronic obstructive bronchopneumopathy and in the pathogenesis of bronchial asthma].

The continuing interest of researchers in chronic obstructive pulmonary disease (COPD) is due not only to its increasing socio-economic impact, but also to the rapid advances made in the comprehension of various mechanisms of this disease, advances made feasible chiefly by a broader interdisciplinary approach to the subject. The most significant progress has been made through the study of bronchial asthma: researchers have confirmed that a particular inflammation of the bronchial mucosa is the common feature of all asthmatic syndromes. IgE antibodies specific for allergens as well as Th2 type T cells seem to play a central role in allergic bronchial asthma. Other types of T cells producing different combinations of cytokines, chiefly IL-5, may be involved in the pathogenesis of intrinsic and professional asthma. It is hoped that this recently gained knowledge will enable improvement in the prevention and therapy of asthma and other COPD syndromes.

Asthma↗

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[Cortisone-resistant bronchial asthma].

There is general agreement on the inflammatory pathogenesis of bronchial asthma: an accumulation of activated eosinophils, degranulated mast cells, T lymphocytes and in very severe forms, granulocytes has constantly been found in the bronchial mucosa. In allergic bronchial asthma, inflammation seems to be orchestrated predominantly by a subset of T lymphocytes, with a phenotype similar to the Th2 subset able to produce IL-4 and IL-5. Although corticosteroids are the most potent therapeutic agents used for this disease, their anti-inflammatory effect differs from patient to patient. Some criteria which can be used to define steroid-resistant bronchial asthma are listed here. This review analyzes various molecular alterations responsible for the deficient response to corticosteroid treatment observed in steroid-resistant bronchial asthmatic subjects. New knowledge on the mechanism of steroid resistance may have important implications for the treatment of chronic asthma and other diseases.

Adrenal Cortex Hormones↗

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IL-4 as a key factor influencing the development of allergen-specific Th2-like cells in atopic individuals.

In the last years Th2-like cells, able to produce IL-4, IL-5, IL-6 and IL-10, have been shown to play an important role in the pathogenesis of allergic diseases. They are absolutely required for IgE production by B-cells and are expanded at the level of target tissues of atopic patients. Very recently, much attention has been focused on the genetic and environmental factors responsible for the differentiation and ongoing expansion of allergen-specific Th2-like cells in atopic subjects. In this review possible cellular sources of IL-4 in the primary, secondary and ongoing responses to allergens are discussed. In atopics, Th cell precursors themselves could be proposed as a main source of IL-4 in the primary responses to allergens. However, there is extensive evidence for the role of other cells such as mast cells, basophils and eosinophils as important sources of IL-4 the secondary and ongoing responses to allergens.

Allergens↗

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New advances in the pathogenesis and therapy of bronchial asthma.

At present, general consensus exits on the inflammatory nature of bronchial asthma. Advances in the knowledge of pathogenetic mechanisms of bronchial asthma are certainly to be ascribed to the use of immunobiological, molecular and genetic approaches for studying experimental models and human bronchial asthma. The histopathological hallmark of bronchial asthma consists in the constant presence, at the level of bronchial mucosa, even in the mild and intermittent syndromes, of epithelial lesions, thickening of basement membrane, and inflammatory infiltration consisting of activated eosinophils, Th2 lymphocytes and degranulated mast cells. Cellular and molecular alterations responsible for this typical bronchial inflammation and the subsequent patho-physiological and clinical characteristics of bronchial asthma have been identified. It has been shown that interleukin-4 is the principal cytokine necessary for Th2 lymphocyte differentiation and expansion and IgE production. Interleukin-5 acts specifically on eosinophil activation, terminal differentiation, and survival. As only eosinophils primed by interleukin-5 as well as by interleukin-3 and granulocyte macrophage-colony stimulating factor can express all the membrane receptors and integrins, they become able to bind to adhesion molecules overexpressed on the mucosal microvascular endothelial cells and of being selectively chemoattracted by a particular subgroup of beta-chemokines, which bind to their membrane CC-receptor-3. The amplification and maintenance of airway inflammation and the clinical exacerbations and chronicity of bronchial asthma depend on complex mechanisms. Tumor necrosis factor-alpha and interleukin-1 beta play a fundamental role in the induction of multiple cellular and molecular interactions. Molecular approaches are now being used to define genetic predisposition. Candidate genes have been located on different chromosomes. In addition to bronchodilator medication to relieve symptoms, the most important purpose of asthma therapy must be based on anti-inflammatory agents to reduce airway inflammation and airway hyperreactivity. Corticosteroids appear able to interfere with almost all components of inflammation. New inhaled steroids have radically modified therapeutic principles of bronchial asthma. Even cromones and anti-leukotrienes have been recommended as anti-inflammatory agents. Some developing therapeutic strategies involve use of anti-IgE antibodies, interleukin-4 and interleukin-5 inhibitors and chemokine receptor antagonists.

Animals↗