Lung cancer in 19 patients with HIV infection. The Italian Cooperative Study Group on AIDS and Tumors (GICAT)
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Biomedical subjects
Publications and source records attributed to M Spina.
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Since their introduction in clinical practice, antigliadin antibodies (AGA) have simplified the diagnostic iter of coeliac disease. In addition they have allowed us to recognize an even high number of new cases and also to identify new clinical forms. While AGA are widely used in the diagnostic phase, their determination during follow-up of the disease has been always limited. With the present work we observe the behaviour of AGA during the various phases of coeliac disease. The study was carried out on 288 coeliac children divided as follows: 96 at diagnosis, 136 on gluten-free-diet (75 diet adherent and 61 non adherent) and 56 on gluten-challenge. 145 healthy children were also studied as a control group. In all children AGA (IgA and IgG) were determined, with a micro-ELISA method, every two months in the children on gluten-free-diet and monthly in the children on gluten-challenge. Data obtained showed AGA behaviour strictly related to the diet. In fact while children with good compliance to the diet had AGA normalization within the 2nd and 6th month, respectively for IgA and IgG, children with poor adherence to diet had constantly positive AGA. Noteworthy was the AGA behaviour during challenge. Gluten introduction determined a rapid increase of IgA and a slow increase of IgG. Our results confirm the usefulness of AGA determination during the follow-up of coeliac children giving us the possibility to avoid one or more biopsies included in the ESPGAN protocol.
Recent antigliadin antibody (AGA) determination has become an important diagnostic tool in coeliac disease (CD). Although this test has high sensibility for the disease, it is less specific, especially for IgG class, because of its having been found in some acute and chronic common intestinal childhood diseases. We studied the behaviour of AGA, IgA and IgG, in 234 children affected by various gastrointestinal diseases, comparing the results with those obtained in 125 coeliac children and 788 normal children. The intestinal diseases were as follows: irritable bowel syndrome, cow's milk protein intolerance, acute infectious diarrhoea, parasitosis, lactase deficiency, recurrent abdominal pain, cystic fibrosis, chronic constipation, gastroesophageal reflux, intestinal lymphangiectasia, chronic intractable diarrhoea and nodular lymphoid hyperplasia. Our results showed that while AGA-IgA were absent in all children studied, with the exception of 3 cases of acute diarrhoea, a moderate percentage of AGA-IgG was observed in subjects with cow's milk protein intolerance, acute diarrhoea, irritable bowel syndrome, lactase deficiency, chronic intractable diarrhoea and in a low percentage of children with parasitosis, intestinal lymphangiectasia and nodular lymphoid hyperplasia. There was no antibody movement in subjects with cystic fibrosis, gastroesophageal reflux, recurrent abdominal pains and chronic constipation. The different behaviour of the two antibody classes could be explained by the fact that AGA-IgG were detected in diseases where scattered areas of mucosal damage could allow the permeability of the macromolecules inducing passage of gliadin through the mucosal barrier and immune system-induced antibody stimulation.
Ninety-two cases of Hodgkin's disease (HD) in patients with HIV infection have been collected by the Italian Cooperative Group on AIDS and Tumors (G.I.C.A.T.). In accordance with the epidemiology of HIV infection in Italy, 82% were intravenous drug users (IVDU), 8% homosexual men, 5% IVDU+homosexuals and 5% heterosexuals. At diagnosis of HD, 16% had AIDS, 20% AIDS related complex (ARC), 33% persistent generalized lymphadenopathy (PGL) and 31% were asymptomatic. Fifty-three percent of the patients had stage IV disease and 70% mixed cellularity and lymphocytic depletion. Forty-six patients were treated with MOPP or MOPP [symbol: see text] ABVD +/- radiotherapy (zidovudine was not given) with complete remission (CR) in 54% and partial remission (PR) in 46% of the patients. Fifty-six percent of these patients developed opportunistic infections (OI) during therapy or follow-up. Sixteen patients were treated with epirubicin, bleomycin and vinblastine (EBV) and concomitant zidovudine, with CR in 44% and PR in 38%. However, only one of these patients developed OI during therapy or follow-up. The clinico-pathological features and natural history of HD in HIV setting are peculiar and quite distinct from those observed in HD in the general population. Better combined chemotherapy and antiretroviral therapy is needed in order to ameliorate the CR rate and decrease the OI in patients with HIV infection and HD.
The French-Italian Cooperative Study Group included patients with poor-prognosis AIDS-related non-Hodgkin's lymphoma (NHL), defined as those with performance status (PS) > or = 3 and/or opportunistic infections (OI), in a prospective study with a 50% reduced-dose combination chemotherapy regimen: CHVmP-Vincristine-bleo (cyclophosphamide 300 mg/m2 i.v. day 1, doxorubicin 25 mg/m2 i.v. day 1, teniposide 30 mg/m2 i.v. day 1, prednisone 20 mg/m2 per os days 1-5, vincristine 2 mg i.v. day 15, and bleomycin 10 mg i.v. day 15), given every 21 days for eight cycles, and concomitant zidovudine 500 mg per os per day. The aims of this combined treatment were to reduce bone marrow toxicity and infectious complications related to chemotherapy (with a low-dose chemotherapy regimen), and to control the HIV and related infectious complications (with zidovudine therapy). Thirty-seven patients entered this prospective study. At the time of the NHL diagnosis, 41% of the patients had asymptomatic HIV infection, 27% had ARC and 32% had already had CDC-defined diagnoses of AIDS. The median CD4+ cell count was 35 mm3. Only 29 patients are evaluable for response, since 8 received only one cycle of chemotherapy. Fifteen of 29 (52%) patients obtained objective responses, with only 4 (14%) achieving complete remissions (CR) of 1, 4, 14 and 29+ months. Three (16%) CRs were achieved in 19 evaluable patients included in the study because of poor PS, and only one CR was observed in 10 evaluable patients with histories of OI, either alone or with poor PS. The most common side effect was bone marrow toxicity with 2 related toxic deaths.(ABSTRACT TRUNCATED AT 250 WORDS)
The association of malignancies, such as non-Hodgkin's lymphoma and Kaposi's sarcoma, with human immunodeficiency virus infection has been recognized since the beginning of the epidemic. However, an increasing number of tumors not diagnostic of acquired immunodeficiency syndrome has been described in this setting. Taking into consideration that survival of patients with human immunodeficiency virus infection is increasing because of improvement of supportive care and better control of human immunodeficiency virus and related opportunistic infections, oncogenic viruses such as human papillomavirus, hepatitis B virus, Epstein-Barr virus, in a setting of prolonged immunosuppression could increase the risk of a variety of malignant tumors.
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The Italian Cooperative Group on AIDS & Tumors (GICAT) is collecting data on the epidemiological and clinical features of Kaposi's sarcoma (KS) in Italy, a country where intravenous drug users (IVDUs) comprise the largest group affected by AIDS. As of December 31st 1989, among 5317 cases of CDC-defined AIDS reported to the National Registry of AIDS, there were 419 (8%) cases of KS. Twenty-five percent of all of the homosexual men with CDC-defined AIDS had KS, while only 3% of the IVDU patients with CDC-defined AIDS had KS. The first case of KS was observed in 1982, 2 cases in 1983, 7 cases in 1984, 17 cases in 1985, 55 cases in 1986, 89 cases in 1987, 120 cases in 1988 and 128 cases in 1989. Of the 226 cases of KS reported to GICAT, 60% were in homosexual men, 21% in IVDUs, and 9% in heterosexuals. An increased number of KS has been observed since 1982, although the number of new cases in the past year seems to have been stable, possibly due to the usual delay in notification. There is, however, an actual decrease of the percentage of KS among AIDS patients, from 18% in 1984 to 6% in 1989. Almost half of the patients had had a diagnosis of AIDS prior to the appearance of KS, but in 25% of the patients KS was the first AIDS manifestation. Almost all patients had skin involvement either alone or in association with other sites, whereas very few patients had only lymph node involvement. Only treatment with alpha-2 interferon was able to obtain complete remission in 9% of evaluable patients.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of this study was to evaluate whether left ventricular hypertrophy in spontaneously hypertensive rats (SHR) is accompanied by myocardial collagen quantitative and/or qualitative changes. 15 SHR and 20 control normotensive rats (WKR) of three months of age were used. At this age, hypertension has already caused a significant increase in the ratio of the ventricular mass to body weight (mg/g) in hypertensive animals (SHR: 5.11 +/- 0.21; WKR: 3.40 +/- 0.22; p less than 0.001). With respect to body mass, the amount of collagen elicited from the hydroxyproline concentration increases in SHR but remains percentually the same with respect to the biventricular mass. In SHR, changes in the amount of type-1 alpha chains and type-V alpha chains, and the presence of a low molecular weight collagenous fraction have been observed. Moreover, we have found an increase in the ratio of type-1 alpha 1 chains to type-1 alpha 2 chains. This change might be related to the appearance of a type-1 alpha 1 trymer. The presence of such a type-1 alpha trymer and of low molecular weight collagenous fractions may suggest the appearance of fetal collagenous isoforms in ventricular myocardium, due to the increased pressure load as well as to the increased turnover (an index of a remodelling activity of cardiac stroma). These changes might play a role in the transformation of myocardial viscoelastic properties in SHR with a progressive diastolic stiffness of the ventricular wall.
A new, sensitive assay based on the enzyme-linked immunosorbent assay has been developed for measuring elastolytic activity produced by invasive and/or metastatic tumor cells in culture. Elastin peptides, obtained by treating the insoluble protein with either oxalic acid, KOH, or chymotrypsin, are adsorbed onto the surface of cell culture microtiter plastic wells, and incubated with dilution of standard proteinases or viable normal or tumor cells. The total amount of immobilized elastin peptides is revealed by the mean of specific antibodies, and detected by a microplate reader, while dose- and time-dependent reduction of bound antibodies after incubation with proteases or cells is taken as a measure of elastin degradation. Adsorbed elastin has been found to be available as a substrate for purified enzymes, as well as for living melanoma cells (A2058 and B16-BL6), c-Ha-ras transformed rat embryo fibroblasts, and human pulmonary macrophages, as demonstrated by the release into the culture medium of lower molecular weight digestion products. No degradation was achieved by BALB/3T3 and rat embryo control fibroblasts, and no inhibition was produced by the presence of fetal calf serum which, on the contrary, potentiated the degradation by active cells. This new method, revealing degradation of only a few nanograms of soluble elastin peptides, can be used for studying the importance in tissue invasion and metastasis of elastolytic proteinases produced by cells in culture.
The modifications of the extracellular matrix (ExM) components in the alveolar parenchyma of elderly subjects were investigated using a panel of polyclonal antibodies. The elastic fibers showed a notable decrease along the alveolar walls while type III collagen increased when compared with that of non-elderly controls. No variations of these components were detectable in the alveolar ducts or in the respiratory bronchioli. An increase in the thickness of the alveolar basement membranes was detected in some of the subjects when antibodies against type IV collagen and laminin were used, while antibodies to fibronectin and type V collagen did not reveal any modifications compared with the controls. The modifications revealed in the lungs of the elderly can be related to the alterations of the elastic recoil and pulmonary compliance observed in these subjects.
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A rapid and accurate reverse-phase high-performance liquid chromatography procedure for amino acid analysis of connective tissue proteins has been optimized. The method is based on quantitative dansyl chloride precolumn derivatization of protein hydrolyzates and chromatographic separation of the dansyl derivatives on Ultrasphere ODS C18 column. High molar uv absorption of Pro and Hyp derivatives, quantitation of low Des and Ide amounts (60 pmol), and good separation of all the amino acid derivatives (CV mostly less than 0.1%) including Hyl overcome the difficulties of other methods in producing reliable single run amino acid analysis of collagen and elastin. The use of fluorescence detector and the possibility of concentrating derivatized samples would give even higher sensitivity to the system. The procedure appeared to be suitable for single run analysis of other proteins, particularly those having an unbalanced amino acid composition.
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Impaired platelet aggregation, normal shape change, and agglutination and normal ATP secretion and thromboxane synthesis in response to high concentrations of thrombin or arachidonic acid were found in a patient with multiple myeloma and hemorrhagic tendency. The purified IgG1 kappa or its F(ab1)2 fragments induced similar changes when added in vitro to platelet-rich plasma from normal subjects. In addition, the paraprotein inhibited adhesion to glass microbeads, fibrin clot retraction, and binding of radiolabeled fibrinogen or von Willebrand factor to platelets exposed to thrombin or arachidonic acid without affecting intraplatelet levels of cAMP. The radiolabeled para-protein bound to an average of 35,000 sites on normal platelets but it bound to less than 2,000 sites on the platelets from a patient with Glanzmann's thrombasthenia. Immunoprecipitation studies showed that the platelet antigen identified by the paraprotein was the glycoprotein IIIa. Furthermore, binding of radiolabeled prostaglandin E1 (PGE1) to resting platelets as well as binding of von Willebrand factor to platelets stimulated with ristocetin were entirely normal in the presence of patient's inhibitor. These studies indicate that bleeding occurring in dysproteinemia may be the result of a specific interaction of monoclonal paraproteins with platelets. In addition, our data support the concept that the interaction of fibrinogen and/or von Willebrand factor with the platelet glycoprotein IIb-IIIa complex is essential for effective hemostasis.
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