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Biomedical subjects

F Invernizzi

Publications and source records attributed to F Invernizzi.

At least 73 records · Page 4Linked to original sources
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The cryoglobulinemic syndrome.

The clinical and immunochemical classification of 376 patients with cryoglobulinemia is presented. In 141 cases (37.5%) the syndrome was considered idiopathic. Among the secondary forms, chronic liver diseases and connective tissue diseases shared most frequently mixed cryoglobulins (18.8 and 15.4% of cases, respectively). Another common association was that with Waldenström's macroglobulinemia: cryoglobulins were found in 20% of these patients. In 5 patients (2 with the essential form and 3 with cryoglobulinemia secondary to Waldenström's disease) a Cl-inhibitor deficiency was discovered; the complement profile was characteristic of the acquired type and episodes of angioedema occurred. Studying the clinical course of 71 cases of essential mixed cryoglobulinemia followed-up for 4-20 years we concluded that the evolution of type II and type III cryoglobulinemias is different because that of type II seems to have a more severe course and may differentiate in a lymphoproliferative disorder; the immunochemical type of cryoglobulins seems therefore to have a prognostic significance. Because of the considerable overlap in the distribution of immunochemical types among the clinical subsets, a mixed classification (both biochemical and clinical) is proposed.

Adult↗
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Immune complexes and IgG-Fc receptors on human platelets in essential mixed cryoglobulinemia.

An enzyme-linked immunosorbent assay (ELISA) using wells coated with normal platelets has been tested in order to quantitate cell-bound immune complexes (ICs) by measuring the uptake of alkaline phosphatase-conjugated antibodies to IgG in the immune complexes. All patients with essential mixed cryoglobulinemia had levels of serum IgG ICs above control values; a poor accordance was found between levels of ICs detected by this method and those obtained using the conglutinin method. The presence of these complexes was correlated with human platelet aggregation: platelets aggregated in vitro when cryoglobulins with higher IgG/IgM ratio were present. This type of ICs could be critical also for platelet activation and aggregation in vivo.

Antigen-Antibody Complex↗
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Cryoglobulins and infectious diseases.

The relationship between infectious diseases due to various pathogenetic factors and cryoglobulin production mechanisms has been investigated. Cryoglobulins have been evidenced in infections caused by very heterogeneous pathogens, i.e. leptospirosis, psittacosis, Mediterranean tick typhus, brucellosis, gram-negative bacterial septicemias, in which they had never been previously reported. In type A hepatitis a high cryoglobulin prevalence (91%) has been confirmed during the acute phase, with a rapid decrease both in prevalence and concentration in the subsequent stages of the disease. Cryoglobulins were all of type III and were mainly represented by IgM; anti-HAV-IgM antibodies have been evidenced in all but one cryoprecipitates. In non-A, non-B hepatitis a lower cryoglobulin prevalence (44.7%) was shown during the acute phase and the same fast decrease has been noted in the subsequent stages. Cryoglobulins were all of type III and in some cases polyclonal IgG was the only Ig class present in cryoprecipitates. The cryoglobulin prevalence in the acute phase of HBsAg-positive hepatitis amounted to 73.4%; all the cryoprecipitates were of type III. No correlation between the presence of cryoglobulins and HBeAg positivity or between cryoglobulins and delta agent infections was found. In all the cases studied the presence of cryoglobulins was related to the persistence of liver damage. Cryoglobulins were not found in HBsAg chronic carriers, while they have been evidenced, by a preliminary study, in 41.6% of HTLV-III antibody-positive subjects complaining of a persistent generalized lymphadenopathy without clinical or laboratory signs of liver impairment. No HTLV-III antibodies were found by ELISA method in the type III cryoprecipitates.

AIDS-Related Complex↗
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Fibronectin and cryoprecipitation.

Fourteen patients with essential mixed cryoglobulinemia were studied. The relevance of fibronectin (FN) in cryoprecipitation seems to be of relative importance since only two thirds of the cryoprecipitates have a higher cryocrit level when FN is present. On the other hand, the other samples show a lower precipitating activity after plasma heating at 60 degrees C. This reduction may reflect either a structural FN modification by heating or the denaturation of other cryoprecipitating molecules. It is possible, even if not necessary, that at least in vitro FN plays a role in the cryoprecipitate formation.

Antithrombin III↗
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Cryoglobulinemia and liver involvement.

Liver involvement during essential mixed cryoglobulinemia (EMC) and cryoglobulins secondary to acute and chronic liver diseases has often been reported. Cryoglobulins in the serum seem to depend on an abnormal balance between their production and clearance. In this paper, 58 cases of mixed, mainly polyclonal cryoglobulinemia secondary to chronic liver diseases, and 23 cases of EMC, mainly monoclonal, are described. Amongst the EMC, 15 cases have been histologically followed-up and we have shown different types of related pathological liver involvement: from 'pathosis torbida' and chronic persistent hepatitis to chronic active hepatitis and liver cirrhosis. Only a few hepatic lymphoid infiltrates were nodular. According to our data and to those in the literature, we can suggest the following correlations between mixed cryoglobulinemic states and liver diseases: transient polyclonal cryoglobulins are secondary to acute viral liver diseases; polyclonal cryoglobulins are related to chronic liver diseases, initially produced by a polyclonal stimulation; mainly monoclonal, but also polyclonal cryoglobulins in which there is not always liver damage, but nodular infiltrates can be seen at the hepatic site; monoclonal, but also polyclonal cryoglobulins, in which there are nodular lymphoid infiltrates and vasculitis, as in immune complex diseases.

Adult↗
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Hypergammaglobulinemic purpura of Waldenström. (A report of serologic and immunogenetic studies and long-term follow-up in 18 patients).

Data from a study carried out on a group of 18 patients with hypergammaglobulinemic purpura of Waldenström (HPW) followed-up for 3-14 years are reported in this paper. In 11 patients the syndrome was considered to be idiopathic, while in the remaining 7 it was associated with Sjögren's syndrome (SS). A marked (17/1) female prevalence was observed. Purpura was the presenting clinical manifestation in 9 patients, but it occurred at different points during the course of the disease; Raynaud's phenomenon was present in one third of patients. Serum gammaglobulin levels were higher than 2.2 g/dl in all the cases and higher than 3 g/dl in 9 cases. Immune complexes were detected in all patients. A significant serologic finding in our case series was represented by the frequency of anti-Ro (16/16) and anti-La (14/15) antibodies, clearly higher than that reported in SS patients. HLA typing showed a marked increase of B8 and DR3 antigens as well as A1,B8,DR3 haplotype, never reported in other autoimmune diseases. On the basis of serologic and immunogenetic features, HPW seems a clearly distinguishable entity among autoimmune vasculitis.

Adult↗
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Five-year follow-up of 165 Italian patients with undifferentiated connective tissue diseases.

OBJECTIVE: To study those conditions with a proven or hypothesised immunologic pathogenesis and denominated under a working definition of undifferentiated connective tissue diseases (UCTD). METHODS: A multicentre prospective study was organised involving 10 tertiary referral centers of internal medicine in Italy, with the aim of describing the natural history of UCTD and the prevalence of its different clinical and immunological manifestations. RESULTS: After a five-year follow-up period, data on 165 patients were available for analysis. UCTDs occur mainly in females in their fourth decade of life. Articular and mucocutaneous features and Raynaud's phenomenon represent the most common findings. Nevertheless, we also detected a relatively high incidence of permanent major organ damage. Regarding the immunologic parameters, we documented some conflicting results in the correlation between serologic abnormalities and clinical features. In 10 patients UCTD evolved to a major disease, generally systemic lupus erythematosus or Sjögren's syndrome. CONCLUSION: A low rate of evolution to a defined autoimmune disease, the limited use of steroid or immunosuppressive therapy, and a favourable course in the majority of cases are the main characteristics of patients with UCTDs.

Adolescent↗
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Hepatitis B virus-related markers in secondary and in essential mixed cryoglobulinemias: a multicentric study of 596 cases. The Italian Group for the Study of Cryoglobulinemias (GISC).

The aim of this study was to assess the prevalence of HBV-related markers in cryoglobulinemias and the possible association between hepatitis B virus (HBV) and essential mixed cryoglobulinemia (EMC). A retrospective survey of the prevalence of HBV infection in cryoglobulinemic patients was carried out in 596 cases of cryoglobulinemia. On the basis of clinical and laboratory criteria the cases were grouped as secondary to connective tissue disease, to lymphoproliferative disorders, to chronic liver diseases or to chronic infectious diseases. The cases in which an associated disease was not evidenced were considered as essential mixed cryogobulinemias. Subjects in which liver dysfunction was first diagnosed simultaneously with cryoglobulinemia, were considered as a separate group. A greater prevalence of HBsAg and anti-HBc antibodies was found in cryoglobulinemias secondary to chronic liver disease (p < 0.0001) and in those associated with liver involvement at diagnosis (p < 0.05) than that found in EMCs. The prevalence of anti-HBs antibodies did not differ significantly among the groups. Proven contact with the virus, documented by at least one positive marker, was evidenced more frequently in cryoglobulinemias secondary to liver disease than in the other groups (p < 0.01). The prevalence of HBV related markers in EMCs and in hospitalized patients not suffering from diseases associated with cryoglobulin production were similar, and seems to reflect the epidemiological situation of HBV infection in Italy. In conclusion, our findings do not support an association of HBV with EMC.

Biomarkers↗
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[Chronic eosinophilic pulmonitis with eosinophilic pleurisy. A report on 2 clinical cases seen by the authors].

We discuss the cases of two patients affected with chronic eosinophilic pneumonia (CEP) pleurisy and eosinophilia in pleural effusion, not previously mentioned in the literature, to point out their peculiarity, to consider differential diagnosis and the effect of steroid therapy. Both patients, a 57-year-old man and a 55-year-old woman, were atopic: they had been suffering from allergic rhinitis and asthma for several years when they suffered sudden onset of cough, dyspnea and thoracic pain. This symptomatology persisted for more than 6 weeks. Chest radiography highlighted pulmonary infiltrates, not fixed in the first case, fixed in the second. The laboratory features revealed eosinophilia in peripheral blood and in pleural effusion. These data conformed to the criteria suggested by Jederlinic et al. for the diagnosis of chronic eosinophilic pneumonia. Tuberculosis had been present in the remote history of the second case; the repeated research for mycobacteria was negative, and no improvement was seen after antitubercular chemotherapy for one month. We excluded the diagnosis of allergic bronchopulmonary aspergillosis because of the absence of both precipitating antibodies against Aspergillus fumigatus and bronchiectasis. Neither vasculitis nor autoantibodies were found; possible drug-related correlations were excluded; culture data and serological researches for infections were negative in both cases; no involvement of other districts correlated to hypereosinophilia was evidenced. Clinical and radiological remission was obtained in both cases after steroid therapy for a month at the dosage of 1-2 mg/kg daily. No clinical recurrence was seen during a follow-up period of 6 months. Pleural effusion has already been reported in patients with CEP, while we have not found any references to pleural fluid eosinophilia in this disease; this finding has instead been already reported in patients affected with acute eosinophilic pneumonia or hypereosinophilic syndrome.

Chronic Disease↗