Epidemiology of hepatitis C virus infection in dialysis units: first-versus second-generation assays.
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Biomedical subjects
Publications and source records attributed to A Tricerri.
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Circulating immune complexes (CIC) have been detected in several autoimmune diseases, and studies have also suggested that CIC provide a useful tool as tumor markers. In order to identify differences or similarities in antigenic composition, CIC from 23 patients with gastrointestinal (GI) tumors, from 20 patients with stage III and IV melanoma and from 6 patients with inflammatory bowel disease (IBD) were studied. Serum from all GI, melanoma and IBD patients showed higher levels of CIC than controls. SDS/PAGE electrophoresis under reducing conditions revealed some differences between cancer and IBD patients as far as the CIC protein composition was concerned. In melanoma patients, two fast-migrating bands, in the regions of 71-74 and 30-49 kD, were found, consistent with previously isolated and characterized antigens described in the literature.
Sixty patients with Echinococcus granulosus infection of the liver, lungs, bone and/or soft tissues were treated for several months with oral mebendazole (50-60 mg kg-1 day-1), in divided doses after fat-rich meals, either without surgery (WS), post-surgery (PS) or pre- and post-surgery (PPS). Long-term follow-up, possible for 52 of the patients, showed that WS, PS and PPS patients have so far remained disease-free following treatment for (means +/- standard deviations) 65.5 +/- 37.7, 82.5 +/- 37.0 and 84.1 +/- 28.3 months, respectively. Ultrasound and computed tomography scans were similar in WS and PPS patients post-treatment. Blood eosinophil levels, which were sometimes elevated initially, returned to normal in all patients and this decrease indicated cyst degeneration before this was evident on the scans. Treatment of patients with cystic echinococcosis may no longer require surgery.
Coagulation disorders are frequently detected in patients affected by different tumours even though clinical symptoms occur in a very small percentage of such subjects. Coagulation processes are probably involved in the mechanism of metastatic spread. We assayed the plasma levels of thrombin-antithrombin III (TAT) complexes in a group of 276 patients with several tumours in different stages in order to achieve a better understanding of the complex interactions between coagulation disorders and either tumour growth or metastatic spread. High levels of TAT complexes were found in 51% of localized, 66.3% of metastatic and 58.3% of patients with no evidence of disease; a statistically significant difference was observed comparing metastatic cancer either with localized (p < 0.00015) or with free-of-disease (p < 0.004) groups. Gastrointestinal tract neoplasms showed higher levels of TAT complexes in the metastatic than in the localized group. No difference was seen between small-cell and non-small-cell lung-localized cancer. Our results confirm the frequent coexistence of cancer and subclinical blood coagulation disorders. The evidence of higher levels of TAT complexes in metastatic cancer than in the other groups could be related to the mechanisms involved in tumour spread.
The relationship between cancer and coagulation disorders is widely accepted. Such disorders can contribute to the metastatic spreading of the primary tumor. Aim of our study was to evaluate the alterations of thrombin-antithrombin III complex (TAT) measured by an ELISA plasma assay in a population of 78 patients suffering from various gastrointestinal tumors. We found high levels of TAT in 68.6% of the patients. Our data show that assay of TAT plasma levels may be a useful test in detecting early coagulation disorders in cancer patients.
To investigate the presence of reduced bone mineral density (BMD) and to assess determinants of bone loss in rheumatoid arthritis, 45 female patients suffering from non-steroid treated rheumatoid arthritis were submitted to dual photon absorptiometry of the lumbar spine and to laboratory tests for calcium metabolism. The rheumatoid arthritis patients were divided into two groups according to anatomic grade and functional class; no abnormalities in calcium metabolism were detected whereas BMD was significantly lower in the third and fourth grade and in the third and fourth class patients (P less than 0.005 versus controls, versus grades I and II and versus classes 1 and 2). BMD was significantly correlated with age (P less than 0.001) and years postmenopausal (P less than 0.01), but not with duration of disease. By multiple linear regression we derived an equation predictive of BMD. Osteoporosis in rheumatoid arthritis is observed even in non-corticosteroid treated patients; articular lesions with subsequent reduction in physical activity appear to play an important role in axial bone loss in rheumatoid arthritis.
The occurrence of chronic renal insufficiency was investigated in 171 patients with severe idiopathic calcium stone disease. Ninety healthy subjects matched for age and sex were used as controls. The patients were thereafter subclassified into two subgroups, assuming a GFR of 80 ml/min/1.73 m2 body surface area as a cut-off value: the normal GFR, 141 patients, and the impaired GFR, 30 patients. The normal GFR group included more males and the patients were younger both at onset and at presentation. In the impaired GFR group the disease lasted longer, but the overall stones and the stone recurrence rate were as high as those of the normal GFR patients. The single stone episodes were more severe in the former group as suggested by the occurrence of more surgery and complications. The GFR level was in part predicted by the age of patients; however, stone disease was shown to induce a clear-cut influence in accelerating the natural worsening of GFR with age. The onset of renal insufficiency causes multiple changes in renal pathophysiology, which result in a sharp decrease in the urine saturation with respect to calcium salts. These changes account for the decrease in the stone recurrence rate in the impaired GFR group. Thus, unless factors independent of or complicating the calcium stone disease supervene, the renal insufficiency of treated patients remains mild and relently progressive.
Circulating immune complexes (CIC) were previously reported to be higher in extended cancer rather than in localized one, by a few groups of investigators as well as by ourselves. The techniques employed were quite different in each study. We described a "direct" laser nephelometric assay. At the same time we determined the serum levels of 4 acute phase proteins (AFP)--alpha 2 macroglobulin, C reactive protein, haptoglobin, alpha 1 acid glycoprotein--by conventional light scattering method, in order to investigate on other possible "immune-modulating" factors. The possible correlations either with prognosis or clinical stage are looked for; the hypothetical behaviour of CIC as one of the serum "blocking factors" and of acute phase reactant as "immune modulating" proteins are discussed. The data concerning the techniques able to remove CIC from the blood stream of the cancer patients were also showed (plasmapheresis and immunoadsorption).
Juxtaarticular osteoporosis is a recognized clinical feature in both rheumatoid arthritis (RA) and psoriatic arthritis (PA), while generalised osteopenia seems to be characteristic of RA only. To assess differences in bone turnover in the two forms of disease, we measured serum osteocalcin levels and other parameters of bone metabolism in two groups of female, ambulant, age-matched patients suffering from active RA or active PA and never treated with steroid therapy. Serum osteocalcin levels were significantly higher in RA patients than in PA patients (13.05 +/- 1.27 ng/ml vs 4.83 +/- 0.88 ng/ml; p less than 0.001), with a significant positive correlation between osteocalcin and serum alkaline phosphatase in both groups. These data suggest that bone turnover is higher in active RA than in active PA. Juxtaarticular osteoporosis could be mediated by local disease mechanisms both in RA and in PA, while factors specifically related to active RA seem to determine a more generalized impairment of bone turnover.
Some nonspecific components (IgG, C3c, C4,) of circulating immune complexes (IC) precipitable by 3.5% PEG were assayed by laser nephelometry in the sera of 71 patients with solid tumours, and of 39 patients with autoimmune diseases. PEG-IgG, PEG-C3c, and PEG-C4 were higher in cancer and in autoimmune diseases than in controls. In cancer patients, PEG-C4 levels and PEG-C4 positivity rate correlated well with tumour burden. PEG-C3c and PEG-IgG were present at higher levels and PEG-C4 was present at lower concentration in cancer than in autoimmune diseases. The results of the present study, performed on a large population of patients with cancer and autoimmune diseases, indicate a different composition of circulating IC in these diseases. Particularly, these data suggest a preferential involvement of the alternative pathway of complement activation in cancer, as already described by other authors. The aggregation of C3c to IC, mediated by the alternative pathway, seems to be the "key" event in the process of IC solubilization. In cancer patients' sera, the presence of "solubilized" IC could partly explain their peculiar biological behaviour as well as the disagreement observed among the different assay methods based upon the binding with complement factors.
C-reactive protein and rheumatoid factor assays are relevant laboratory parameters, among the most used in the clinical practice, being very useful in diagnosing and "monitoring" rheumatic diseases. A quantitative test to detect these two serum proteins is an important, more specific, new tool for clinical medicine. In our study we evaluated two new laser nephelometric assays, both quantitative, based on the agglutination of polystyrene latex particles, able to show serum concentration of CRP and RF. With a similar technique we tested the presence of circulating immune complexes. We performed our tests in a group of patients with rheumatoid arthritis, other autoimmune diseases, and healthy blood bank donors assaying simultaneously, whenever possible, the "classic" Rose-Waaler and RA tests. We found both methods easy to perform, well correlating with the semi-quantitative techniques and highly reproducible.
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The results are presented of the dietary management, alone or in association with thiazides and/or allopurinol, evaluated in 143 idiopathic calcium stone formers after a mean follow-up of 18 months. Diet alone proved to be effective in the prevention of stone relapses. The addition of thiazide and/or allopurinol provided mild improvements of urine environment but seemed to give no further clinical benefits irrespective of underlying metabolic abnormalities.
In patients affected with different tumours, disorders concerning clotting are frequently observed. The biological processes leading to coagulation are probably involved in the mechanisms of metastasis. We studied plasma levels of thrombin-antithrombin III complexes (TAT) in 90 patients affected with lung tumours subgrouped in small cell and non-small cell (NSC) lung cancer: 17 patients had no evidence of disease after surgery (NE); the remaining 73 patients were divided according to the absence (LOC) or the presence (META) of metastases. All the patients were followed up for several months. In all the lung cancer patient groups, at the beginning of the study we detected TAT levels that were higher than in controls. During the follow-up period, the NSC-NE patients with no recurrence of the disease as well as the NSC-LOC patients responding to the treatment had a decrease in TAT levels (p < 0.01 and p < 0.05, respectively). The NSC-META patients with progression of their disease had, in contrast, an increase in TAT levels (p < 0.01). Our data reveal the presence of 'latent coagulation disorders' as assessed by the presence of high TAT levels in the majority of lung cancer patients. The follow-up study indicates that in the NSC group, a relation exists between coagulation activation and rate of tumour progression and/or response to treatment. In cancer patients the early detection of coagulation disorders could also allow, therefore, the prevention of thromboembolism and/or haemorrhage by administration of appropriate treatment.
The treatment with infliximab is employed successfully in Crohn's disease (CD) but predictors of efficacy are lacking. Activation of the transcription factor NF-kB has been demonstrated in CD and its inhibition is one of the mechanisms by which anti-inflammatory agents exert their effects. We evaluated the production of TNFalpha by peripheral blood mononuclear cells (PBMC) and the levels of NF-kappaB family molecules in the intestinal mucosa during infliximab therapy in 12 patients. TNFalpha was assayed on supernatants of PBMC culture stimulated with PHA or LPS. Immunohistochemistry was also done on intestinal biopsies. In six patients, Western blot analysis of the NF-kappaB subunit Rel-A, and its inhibitors IkappaBalpha and IkappaBgamma was performed on intestinal biopsies and PBMC. The TNFalpha production by LPS stimulated PBMC showed mild changes, while it was increased by PHA-stimulated PBMC after treatment. The number of inflammatory cells in the intestinal mucosa was reduced (p<0.002) by the treatment. In five out of six cases we detected an increase of the IkappaBalpha and IkappaBgamma)inhibitor levels in intestinal biopsies after treatment. An increase of IkappaB inhibitors levels could be one of the mechanisms by which infliximab decreases NF-kappaB activity and exerts its anti-inflammatory effects.
In the elderly, an impairment of the immune system could lead to increased incidence of infectious, neoplastic and autoimmune diseases; on the other hand, depression, which is the most common psychiatric problem in aged people, seems to be linked with alterations in immunological function. Thirteen institutionalized elderly subjects were studied to investigate the relationship between depression and immunological parameters. These subjects were selected as "healthy" according to the SENIEUR-EURAGE protocol and they belonged to a population already evaluated by our group--one year before--for psychological, endocrinological and immunological parameters. The lymphocyte mitotic response to PHA was greatly diminished in aged subjects, when compared to the adult controls. Depressed elderly showed impaired immunological function as compared with nondepressed ones, either "in vitro" or "in vivo". Lymphocyte stimulation with phytohemagglutinin (PHA), T cell growth factor (TCGF) production (induced by stimulation with PHA) and cutaneous delayed hypersensitivity (CDH) were reduced in depressed aged subjects. As far as lymphocyte proliferation with PHA in the whole group were concerned, no differences were found comparing the present results with those obtained in a former study. Although it is difficult to understand the significance of the immune imbalance associated with depression in the elderly, our results suggest that psychological status could influence the immunological functions in old people.
Keeping calcium (Ca) balance in equilibrium is one of the main goals in dialysis patients, and the dialysis schedule by itself can affect mineral metabolism. The aim of this paper is to evaluate Ca and magnesium (Mg) balances on different Quf in patients on RDT. Twenty-one patients [7 on hemodialysis (HD), 14 on hemodiafiltration (HDF)] were studied. Ca and Mg balances were assessed by measuring Ca and Mg in whole dialysis fluid. One patients on HDF was observed for three dialysis sessions, on different Quf, and negative values were observed for Quf above 70 ml/min. Mg balance was always negative. We conclude that an accurate survey of Ca balance is mandatory in high-efficiency dialysis, when high fluxes may produce adverse effects on mineral metabolism.