Biomedical subjects
Publications and source records attributed to G F Ferraccioli.
Two patients who developed thrombocytopenia while on Tiopronin and gold salts respectively were HLA typed. Their common haplotype was A25(10), B8, DR3. A survey of the literature showed that the association between DR3 and the sudden onset form of thrombocytopenia is striking. A genetic predisposition, besides other unknown factors, seems to play a crucial role.
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Lymphocytotoxic activity is known to better occur at low temperatures and to be relatively enriched in cryoglobulins. As the cold insoluble globulin, Fibronectin, is a main component of cryoglobulins, experiments were carried out to find out whether Fibronectin was involved in the mechanism of cytotoxicity or not. No direct or indirect (complement-mediated) effects were seen. A significant association was observed between lymphocytotoxic activity and circulating immune complexes and between Fibronectin positivity and cytotoxicity in PEG-precipitates of sera from three groups of patients affected with SLE, RA and Ps.A. respectively. As Fibronectin is a cryoprecipitagogue protein, possible implications of these findings are discussed.
The clinical features, serology behaviour, scintiscan characteristics and the degree of X-ray progression according to the disease duration were compared in two RA groups with a disease onset after 65 years of age (LORA) and before 65 (EORA) respectively. No differences emerged in either the clinical findings or in the scintiscan picture. A sub-group of LORA showed acute flares of the illness presenting with very high ESR values and high fever. The erosive index (EI) evaluated in three areas (carpal-bone and wrist, MCP and PIP joints) revealed an undistinguishable degree of X-ray damage either in seropositive or seronegative patients, whereas seropositive EORA fared clearly worse than seronegative ones. A prospective study in two small sub-groups of LORA and EORA revealed a progression of X-ray erosions despite second line drug treatment in both groups, especially in LORA.
A follow-up of 15.4 months has been carried out in 50 patients suffering from classical or definite rheumatoid arthritis, treated with tiopronin, a new slow acting sulphydrylant agent. The attention was focused mainly on the frequency of the major side effects needing withdrawal of the drug in 20% of the patients; in other 20% of the cases we have observed the disappearance of the major side effects after reduction of the tiopronin dosage. The most important major side effect was renal toxicity. Five cases of proteinuria and among these four cases of nephrotic syndrome were recorded. These side effects disappeared 2-5 weeks after withdrawal of the tiopronin. From a clinical point of view a positive response was observed in 56% and a complete lack of efficacy in 22% of patients. The clinical benefit and a panel of side effects very close to those of D-penicillamine were confirmed.
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Hydroxyproline and zinc excretion was evaluated in 87 patients with neoplastic breast disease; 40 of these had carcinoma, without radiological and scintigraphy demonstration of bone metastases. In the group of patients with breast cancer, the mean values of hydroxyproline and zinc excretion were found to be significantly higher than in the group with benign breast disease; only 12 of the patients with histologically detected breast cancer had hydroxyprolinuria levels which were higher than the upper limit of the values obtained in the control group. The authors, therefore, conclude that the patients in this group must be considered as being at greater risk.
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Ninety-four rheumatoid patients were studied through laboratory, clinical, algometric, functional and psychological parameters (29 variables in all). Using factorial analysis, four factors emerged which explained 74% of the common variance. The four factors were: the disability factor (explaining 39% of the variance); the biology factor (explaining 21%); the algology factor (explaining 8%); and the clinical factor represented by the Ritchie Articular Index (RAI) (explaining 6%). The four items were used to construct a Chronic Arthritis Systemic Index (CASI) which correlated significantly with other indices, such as the Mallya-Mace, the Thompson and the limited Lansbury indices. CASI provided to be very useful in monitoring the disease course in a short term study of 22 patients undergoing DMARD treatment. Taking into account the parameters proposed as outcome measures by several workshops, CASI can monitor both the activity and severity of chronic arthritides through simple measures.
The red-cell mass is continuously adjusted to the optimal size for its function as an oxygen carrier by messages transmitted to the bone marrow from an oxygen sensor in the kidney. These messages are mediated by the hormone erythropoietin. Erythropoietin is a glycoprotein growth factor synthesized by cells adjacent to the proximal renal tubule in response to signals from a renal oxygen-sensing device, probably a heme protein (1). In the bone marrow, erythropoietin binds to and activates specific receptors on the erythroid progenitor cells (2). In the presence of this erythropoietin-receptor complex the progenitor cells continue their predestined development into mature erythrocytes. Erythropoietin was the first hemopoietic growth factor to be molecularly cloned in 1985 (3). Our understanding of the biology and physiology of erythropoietin has been considerably improved with the advent of recombinant human erythropoietin (rHuEpo). During the past 7 years, rHuEpo has undergone extensive testing in clinical trials. It has been approved for treatment of the anemia of chronic renal failure, both in progressive renal failure and endstage renal failure (ESRD). In these instances, the administration of rHuEpo has been used in effect as a substitutive therapy, since patients' erythropoietin levels are very low despite severe anemia, due to the failure of affected kidneys to produce adequate amounts of the hormone. However, the application of rHuEpo has now moved largely from the primitive indication of renal diseases, and the hormone is currently under study in a number of anemic states of different etiologies, even with relatively high serum erythropoietin levels. Among these, some of the best documented indications are the anemia associated with malignancies, either due to neoplastic bone marrow infiltration or to chemotherapy-related myelosuppression, the anemia of myelodysplastic syndromes and AIDS, the anemia of chronic inflammatory diseases, prematurity, and bone marrow transplantation (4). The purpose of this review is to provide a summary of our present knowledge regarding rHuEpo therapy for the anemia of renal failure. We provide some clues for the correct use of rHuEpo in the treatment of the anemia of chronic inflammatory diseases. In addition, we address a series of new issues in the attempt to better understand the relationship between erythropoietin and liver disease.
While the simple detection of B-cell clonality does not imply B-cell malignancy, comprehensive analyses of B-cell clonality are crucial to investigate the pathobiology of B-cell lymphoproliferative disorders. Our recent studies in patients with Sjögren's syndrome have highlighted how multiple molecular analyses of B-cell clonality (Southern blot, polymerase chain reaction, single strand conformation polymorphism, and DNA sequence analysis) in prelymphomatous lesions may be of great value in helping to define the stages of progression towards low-grade malignancy. The study of T-cell expansion may also be important in investigations of the pathobiology of the different stages of B-cell lymphoproliferation (fully benign, pseudolymphomatous, or definitely malignant), which may still be T-cell-and antigen/ autoantigen-dependent.
MALT, or mucosa associated lymphoid tissue, is normally not present in gastric tissue. Its presence is often associated with persistent antigenic stimulation. MALT is a precursor of gastric MALT lymphoma, a low-grade lymphoma whose incidence recently appears to have increased. Although much epidemiologic and clinical evidence has linked both MALT and MALT lymphoma to Helicobacter pylori infection, it is not known whether other agents and or mechanisms may also play a role and whether there is a clearly defined pre-neoplastic lesion. In particular, the clinical significance of B-cell clonality remains unknown. In a recent study we attempted to define the role of H. pylori and MALT in the genesis of B-cell clonality in a northern Italian patient population referred to us for simple dyspepsia. The results show that B-cell clonality is unexpectedly frequent in these patients regardless of the presence of H. pylori infection. These observations raise the possibility that agents and mechanisms other than H. pylori may be involved in the genesis of MALT lymphoma. Indeed, other studies conducted by our group in patients with Sjögren's syndrome indicate that genetic/immunologic factors and possibly viruses may play a role. The high prevalence of B-cell clonality in an otherwise healthy population suggests either that most of these patients are at risk of developing MALT lymphoma (in which case this condition at the moment may be greatly underdiagnosed) or that B-cell clonality is a very early step in the development of neoplasia, which requires several other factors and which will occur only in a restricted fraction of these patients. Careful follow-up studies will provide an answer to this question.
Several autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), are characterized by B cell hyperactivity, polyclonal activation, and autoantibody synthesis. Overt B cell clonal expansion occurs in a minority of the patients, while at the tissue level clonotypic B cells may be more easily detected in the majority of patients. The data available suggests that antigen-driven B cell expansion, eventually leading to somatic mutation and transformation, is the main event. Immunosuppressive drugs known to increase chromosomal damage and to lead to earlier transformation should therefore be avoided, unless strictly necessary to preserve vital organ functioning. New immunosuppressive drugs such as methotrexate, cyclosporine A, and Rapamycin are promising for they seem to offer effective control of disease-related organ damage with acceptable side effects. The B cell lymphoproliferative diseases occurring under treatment seem to remit spontaneously after prompt drug withdrawal. Close surveillance, employing new techniques capable of detecting early B or T cell clonal expansion, may allow better monitoring of possible complications. Biological agents such as alpha-interferon and monoclonal antibodies (which are directed against specific immunological mediators and thus target-selected steps of the immune-inflammatory process) have opened promising new research topics in all these diseases.
OBJECTIVES: To define whether Sjögren's syndrome (SS) patients have lymphocytopenia compared to healthy controls, and to assess which lymphocyte subset might be involved. The presence of any concurrent infection was recorded. METHODS: A cohort of ten consecutive patients with SS was studied, and the results were compared with ten sex- and age-matched controls (C). RESULTS: In SS, a significant cytopenia of CD4+ (679 +/- 339 vs 1110 +/- 222 cells/mm3, p < 0.005) and an even more impressive decrease in the CD4+CD45 RA+ (242 +/- 154 vs 491 +/- 190 cells/mm3, p < 0.005) subset was observed. An absolute CD4 lymphocytopenia (CD4+ < 300 cells/mm3) was seen in two patients. In one patient an unusual finding was the expansion of a double positive population of CD4+CD8+ lymphocytes. No striking relationship with any particular infection was shown. A retrospective review of the absolute CD4+ cytopenia in 54 consecutive SS cases revealed a prevalence of 5.5%. CONCLUSION: Some SS patients have T lymphocytopenia which mainly affects the CD4+CD45 RA+ subset. Occasional cases with absolute CD4 lymphocytopenia may also be observed. These patients show some evidence of mild recurrent or chronic, but never severe, opportunistic infections.
The actual efficacy and applicability of high dose intravenous immunoglobulin (IVIG) therapy in the rheumatic disorders is still being debated. In the last few years clinical results have become available on a large number of patients, and efforts have been devoted to experimental studies of the mechanism of action of IVIG. However, the results of controlled clinical trials will be crucial to indicate stricter guidelines and directions for future clinical and experimental research. IVIG is of major value in Kawasaki disease and in severe lupus-associated thrombocytopenia. Its possible benefits are also remarkable in refractory dermatomyositis and probably in some patients with the antiphospholipid syndrome and recurrent miscarriages despite standard treatment. At present, the role of IVIG therapy remains controversial in lupus nephritis and in systemic vasculitis, while it does not seem to be effective in rheumatoid arthritis.
OBJECTIVE: The effect of recombinant interferon alpha-2 (IFN alpha 2) therapy in Sjögren's syndrome (SS) was studied. METHODS: An open study was performed in which 20 SS patients were given IFN alpha 2 3.10(6) MU/3 times/week or OH-chloroquine (OH-C) 6 mg/kg/daily, for a mean period of 11 months. RESULTS: Gland assessment showed that lacrimal and salivary function improved by 67% and 61% versus 15% and 18% respectively (p < 0.01) in the patients treated with IFN alpha 2 compared to those treated with OH-C. Immunological parameters did not change over time in either group. In 3 patients a decrease in the tissue score was observed in the IFN alpha 2 group, while no changes were seen in the control group. Tolerability was acceptable. CONCLUSION: This study shows that IFN can improve tear function and dry mouth in SS, without causing significant side effects.
According to the most recent literature, few antirheumatic drugs can claim disease-controlling properties over the anatomical joint damage in rheumatoid arthritis (RA). A small number of studies have favored one or another of the available agents, in particular parenteral gold salts, sulphasalazine and methotrexate, but the evidence regarding their efficacy is not convincing when analysed using methodological criteria known to be important in evaluating radiologic evidence of joint damage. The radiologic results in long-standing RA patients have shown that CsA may be of benefit in reducing disease progression. Data from the second year of a clinical trial designed to compare the disease-controlling, anti-rheumatic properties of CsA with those of conventional disease-modifying anti-rheumatic drugs (DMARDs) in early RA support the hypothesis that CsA may be useful in delaying the appearance of new joint erosion.