Background We have previously shown that treatment with streptokinase induces abrupt complement activation and transient neutropenia in patients with acute myocardial infarction (AMI). The purpose of this study was to compare the effects of two different thrombolytic agents -streptokinase (SK) and recombinant tissue-type plasminogen activator (rTPA) -on activation of the complement and kinin systems in plasma of patients with AMI.Methods and Results Forty-one patients with AMI who were eligible for thrombolytic therapy were studied. Twentythree patients were treated with streptokinase (1.5 million IU IV over 60 minutes) and 18 were treated with rTPA (8 with

Complement activation is necessary for an adequate immune and inflammatory response to infections. Activation releases anaphylatoxins that cause vasodilation, increase vascular permeability, and trigger release of polymorphonuclear neutrophil leukocyte (PMN) lysosomal enzyme and oxygen radicals. Under normal circumstances, an orderly progression of such events has a beneficial antimicrobial effect. The same mechanism, however, when uncontrolled, may damage host tissues. To provide information about the clinical importance of such events in sepsis, different complement parameters (C3, C4, and the desarginated forms of C3a [C3a(des)-Arg] and C5a [C5a(des)-Arg]), PMN elastase, and malondialdehyde (a by-product of membrane peroxidation by oxygen radicals) were measured daily in 26 septic patients and correlated with two objectively assessed and previously validated severity scores (acute physiology and chronic health evaluation [APACHE II] and Sepsis Severity Score [SSS]). Nonsurvivors (n = 12) had significantly greater and longer lasting complement activation than that in survivors, as reflected by higher levels of catabolic peptides (C3a(des)-Arg) and lower levels of native proteins (C3 and C4). C3a(des)-Arg, C3, C4, and the C3a(des)-Arg-C3 ratio were correlated with Sepsis Severity Scores. Polymorphonuclear neutrophil leukocyte elastase levels were higher in nonsurvivors and were correlated with C3a(des)-Arg and the C3a(des)-Arg-C3 ratio. Malondialdehyde levels were significantly higher in all patients than in controls, without, however, any relationship to severity of disease or clinical outcome. Since the higher and more persistent the complement activation and polymorphonuclear neutrophil leukocyte stimulation, the worse the patient's prognosis, we conclude that these mechanisms may be important in the clinical development of sepsis.

To review recent advances and current controversies on the association between systemic sclerosis (SSc) and cancer, PUBMED was searched from 1966 to the present using the terms: systemic sclerosis, cancer, morphoea, sclerotic diseases. Malignancies, mainly in lung and breast, coexist with idiopathic SSc or with SSc-like disorders, but not with localized forms of scleroderma (morphoea), with the exception of squamous cell carcinoma in patients with pansclerotic morphoea and skin ulcers. The mechanisms connecting SSc and malignancies are unknown. The occurrence of different cancer types with SSc or SSc-like disorders suggest different underlying mechanisms, including altered immune response, common genetic and environmental links, disease-dependent factors, tumor-derived biologic substances and therapies. The process of sclerosis itself may favour cancer in certain sites, and a reaction between T cells and neoantigens formed during irradiation has been suggested to explain the frequent development of morphoea after breast irradiation. Radiotherapy, especially when used for breast cancer, may trigger idiopathic SSc or morphoea and influence the severity of preexisting SSc, with the consequence that SSc is considered a relative contraindication to breast radiotherapy. In conclusion, cancer and SSc may be associated, but it is still controversial as to whether there is a causal relationship. Continuing interest in these associations, in particular in the different modalities of associations, may help to understand the underlying biological mechanisms and to identify patients at risk.