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Biomedical subjects

M Galeazzi

Publications and source records attributed to M Galeazzi.

At least 73 records · Page 4Linked to original sources

Synovial fluid lactic acid in septic and nonseptic arthritis.

We determined lactic acid levels by the lactic dehydrogenase method in synovial fluid of 41 patients with various rheumatic diseases, to test the concept that significantly elevated values were diagnostic of septic arthritis. Nine patients had septic arthritis, 15 rheumatoid arthritis (RA), and the remainder miscellaneous conditions. In another 9 patients with different rheumatic diseases, including 1 with septic arthritis, synovial fluid lactic acid was determined by both the lactic dehydrogenase and gas-liquid chromatography methods. There was a wide scatter of values among patients with septic and nonseptic inflammatory arthritis, and much overlap occurred. We could not differentiate septic arthritis from RA on the basis of synovial fluid lactic acid levels. Results were similar with both procedures for determining lactic acid levels.

Arthritis, Infectious↗

[Long-term treatment of arthrosis using Arumalon].

Cartilage and bone marrow extracts have been used to enhance cartilage mucopolysaccharide levels. The value of this form of treatment was appraised in 250 groups of 250 patients with well established arthrosis. Comparison was made between standard management with anti-inflammatory drugs, analgesics, anti-rheumatic compounds, physiotherapy and heat treatment, and management with the addition of cartilage and bone marrow extracts (Arumalon) over a period of 5 yr. Patients who received Arumalon had a lower frequency of painful exacerbations, a lower and more delayed frequency of functional incapacity, and a slower and less striking radiological progression. These results corroborate experimental and clinical data in the literature. They were particularly marked in 50 cases of gonarthrosis.

Analgesics↗

Serum tumor markers may precede instrumental response to chemotherapy in patients with metastatic cancer.

PURPOSE: Although serum tumor markers (STMs) are widely used in clinical practice, their predictive role for the response to anticancer treatment is still controversial. The correlation of CEA, CA 15.3, CA 19.9, CA 125 (only with peritoneal involvement) and NSE levels with imaging response and clinical benefit was investigated in 60 non-selected patients with metastatic epithelial cancers treated by single-agent docetaxel chemotherapy. METHODS: STM measurement was performed at baseline and subsequently every three to four weeks. We applied the WHO criteria to evaluate both STM and instrumental responses. Concordance analysis was performed by the Cohen Kw index, and the significance of the results was established using the Fleiss, Cohen & Everitt test. Qualitative interpretation of data was obtained with the Landis & Koch scale. Correlations of STM response with clinical benefit (PS or pain improvement) were evaluated by the chi-square test. RESULTS: The primary tumors included breast cancers (38 patients), gastrointestinal non-colorectal cancers (12 patients), and lung cancers (10 patients). An overall significant good degree of agreement was observed between STM and instrumental response (p < 0.0005). The degree of agreement for each marker was as follows: excellent for CEA (p < 0.0005) and CA 125 (p = 0.006), good for CA 15.3 (p < 0.0005) and CA 19.9 (p = 0.011). Restricted analysis for the correlation of each marker with primary tumor origin showed good prediction of radiological response for CA 15.3 and CEA in breast cancer patients (p<0.0005 for both), for CEA and CA 19.9 in gastrointestinal cancer patients (p = 0.01 and 0.04, respectively), and for CEA+NSE in lung cancer patients (p = 0.01). Conversely, STM response did not correlate significantly with the clinical benefit for the patients, both in terms of PS and pain improvement (p = 0.24 and p=0.42, respectively). CONCLUSION: This study showed STMs to be good predictors of tumor response. Although STMs cannot replace diagnostic imaging, in metastatic cancer they might be useful to optimize the timing of radiological re-evaluation in the palliative setting.

Adolescent↗

Comparison of different methods for the detection of anti-Ro/SSA antibodies in connective tissue diseases.

OBJECTIVE: To compare the performance characteristics of various tests commonly used to detect anti-SSA/Ro autoantibodies in the sera of patients affected by connective tissue diseases (CTD). METHODS: Indirect immunofluorescence (IIF) with HEp-2000 as substrate (ImmunoConcepts, USA), Ouchterlony's double immunodiffusion (ID) (home made), commercial Varelisa ReCombi anti-Ro kit (Pharmacia & Upjohn, Germany), research kits (60 kDa and 52 kDa) with human recombinant antigens (Pharmacia & Upjohn, Germany) and a commercial western blot (WB) kit (MarDx, USA) were evaluated in our study. Sixty-four sera from patients affected by CTD were tested: 15 had primary Sjögren's syndrome (SS), 34 only had sicca syndrome, and 15 had systemic lupus erythematosus (SLE). Thirty sera from healthy subjects were selected as controls. RESULTS: 54 sera were positive by at least one method. The specificity of all tests was good. The prevalence of anti-SSA antibodies on 54 positive sera was 76% (ID), 89% (IIF), 89% (Varelisa), 89% (ELISA Ro-60 kDa), 67% (ELISA Ro-52 kDa) and 85% (WB). Some differences were found between WB and ELISA in the detection of anti-60 kDa SSA and anti-52 kDa SSA; in 3 SS sera only anti-52 kDa protein was found by WB. CONCLUSION: Our data confirm that, although IIF HEp 2000 (Immuno Concepts) and Varelisa anti-Ro (Pharmacia & Upjohn) both performed well, a combination of 2 or more methods must still be recommended for anti-SSA antibody detection.

Antibodies, Antinuclear↗

Modification of DNA patterns in plasma and nucleated blood cells from systemic sclerosis patients.

OBJECTIVE: To analyze the DNA patterns extracted from plasma and nucleated blood cells (lymphocytes) in systemic sclerosis (SSc) with a new MFC DNA extracting kit. METHODS: Ten SSc patients and 9 healthy controls were studied. Heparin containing blood samples were separated into plasma and buffy coat fractions and subjected to DNA extraction. The DNA pattern was revealed by 0.4% agarose electrophoresis and analyzed in a Gelblot Programme file (UVP Product). RESULTS: In control samples the DNA pattern observed in plasma extract was different from that of the buffy coat. For the plasma a series of peaks ranging from 2-23 Kb were present, and for the buffy coat we usually observed 2 to 3 principle bands, respectively, at around 33 Kb and 0.5 Kb. For SSc patients the DNA patterns that resulted from the plasma and buffy coat were totally different from the control samples, with some exceptions. CONCLUSION: We observed that SSc samples contain a distinctively different DNA pattern compared to healthy controls. Further studies are needed to establish whether or not this DNA pattern might be considered peculiar to SSc, and whether or not the method is a useful tool for pathogenic studies of the disease and for diagnostic purposes.

Adult↗

Clinical determinants of bone mass and bone ultrasonometry in patients with systemic sclerosis.

OBJECTIVE: The aim of this study was to evaluate bone mass and bone ultrasonometry in patients affected with systemic sclerosis (SSc). METHODS: Fifty-five patients (mean age 54.1 +/- 14.1 years; 25 premenopausal, and 30 postmenopausal women) affected with SSc (in a limited, intermediate or diffused form) and 60 age-matched healthy controls (30 premenopausal, and 30 postmenopausal women) were studied for Bone Mineral Density (BMD) measured by fan-beam x-ray densitometry, Stiffness Index (SI) measured by ultrasonometry of the heel, inflammation indices (erithrocyte sedimentation rate, C-reactive protein), and autoantibodies (ANA, ENA). Examinations were also carried out in order to determine any internal organ involvement. None of the patients had previously received steroid treatment. RESULTS: BMD was significantly lower in the SSc group than in the control group, whether it was expressed in g/cm2 (lumbar spine: 0.980 vs 1.241, p < 0.01; femoral neck: 0.832 vs 0.955, p < 0.05; total body 1.050 vs 1.168, p < 0.01) or by T- and Z-score (lumbar spine: T = -2.48; Z = -1.10; femoral neck: T = -1.69; Z = -0.55; total body: T = -1.11; Z = -0.48). SI was also altered (75.8 vs 96.2, p < 0.01; T = -2.10, Z = -1.12). BMD and SI were lower in women with the diffuse form of skin involvement. BMD and SI were lower in women in whom one or more internal organs were involved. CONCLUSION: SSc patients had reduced BMD and SI that was more marked in the diffuse form and in those with internal organ involvement and that became more marked with age and estrogen deficiency. This demineralisation was not related to the inflammation indices, disease duration, or to the immunological pattern.

Absorptiometry, Photon↗

Association of extrahepatic manifestations with HLA class II alleles and with virus genotype in HCV infected patients.

It has been postulated that host factors, such as the human leucocyte antigen (HLA) system, may play a predominant role in the pathogenesis of HCV-related extra-hepatic manifestations. This study was performed to investigate the role of HLA- DR and DQ alleles in a group of Italian patients, with HCV infection and associated extrahepatic manifestations and to test whether an association between HCV genotype, HLA locus and clinical or serological manifestations can be demonstrated. Thirty unrelated patients affected by HCV infection with extra-hepatic manifestations were consecutively included in the study. One hundred and sixty-three HCV patients without extrahepatic manifestations were tested as controls for the prevalence of HCV genotypes, and 283 healthy donors were used as controls for HLA class II alleles distribution. HCV-RNA was quantified by an reverse transcription-PCR. HLA class II alleles typing was performed using a standard microlymphocytotoxicity assay on B lymphocyte purified. HCV 2c genotype was found in 53.3% compared to 18.4% of controls (p=0.00001; OR=5.1). Cryoglobulins were detected in 72.7% DR6+ patients and in 31.6% DR6- patients (p=0.05; OR=3.21). Rheumatoid factor was found in 90.9% of DR6+ patients and in 42.1% DR6- patients (p=0.018; OR 13.7). Only two DR5+ patients (20%) had cryoglobulinemia, while 6 patients (30%) in the DR5- group had cryoglobulinemia (p=0.02; OR=0.07). Associations were found between DR7 and ANA (OR=1.74) and between DQ2 and ANA (OR=1.97). According to our findings HLA-DR6 might play an important role in developing extra-hepatic manifestations and genotype 2c could be considered as a risk factor for their onset.

Aged↗

Autoinflammatory syndromes.

The autoinflammatory disorders are a new and expanding classification of inflammatory diseases characterized by recurrent episodes of systemic inflammation in the absence of pathogens, autoantibodies or antigen specific T cells. These disorders are caused by primary dysfunction of the innate immune system, without evidence of adaptive immune dysregulation. Innate immune abnormalities include aberrant responses to pathogen associated molecular patterns (PAMPs) like lipopolysaccharide and peptidoglycan, prominent neutrophilia in blood and tissues, and dysregulation of inflammatory cytokines (IL-1beta, TNF-alpha) or their receptors. The autoinflammatory diseases comprise both hereditary (Familial Mediterranean Fever, FMF; Mevalonate Kinase Deficiency, MKD; TNF Receptor Associated Periodic Syndrome, TRAPS; Cryopyrin Associated Periodic Syndrome, CAPS; Blau syndrome; Pyogenic sterile Arthritis, Pyoderma gangrenosum and Acne syndrome, PAPA; Chronic Recurrent Multifocal Osteomyelitis, CRMO) and multifactorial (Crohn's and Behçet's diseases) disorders. Mutations responsible for FMF, TRAPS, CAPS, PAPA are in proteins involved in modulation of inflammation and apoptosis.

Autoimmune Diseases↗

Homocysteine enhances cytokine production in cultured synoviocytes from rheumatoid arthritis patients.

OBJECTIVE: Hyperhomocysteinemia is commonly observed in Rheumatoid Arthritis (RA) patients, thus putatively accounting in part for the high rate of cardiovascular events in these subjects. Homocysteine (Hcy) is known to exert a pro-inflammatory effect putatively contributing to the progression of atherosclerotic lesions by cytokine production from several vascular cell-types. In order to evaluate the possibility that Hcy may play a direct pro-inflammatory activity also in the joints of RA patients, we investigated: (i) the joint concentration of Hcy, and (ii) the effect of Hcy on cytokine production by unstimulated and IL-1beta-stimulated human RA cultured synoviocytes. METHODS: In 5 RA and 5 controls subjects, Hcy was measured in the blood and knee synovial fluid, and specimens of synovial tissue were taken to obtain cell cultures. Cultures were incubated with Hcy (10-100 micromol/l) +/- IL-1beta, and IL-6 and IL-8 concentrations were evaluated in the supernatants (ELISA) together with the activation of nuclear factor-kB (NF-kB) (immunocytochemistry). RESULTS: Hcy was present in synovial fluids, with a mean concentration significantly higher in RA patients than in controls (9.0 +/- 1.1 vs 5.9 +/- 1.2 micromol/l). Hcy enhanced IL-6 and IL-8 production in RA synoviocytes only (up to 35%). Moreover, Hcy produced a clear-cut activation of NF-kB in rheumatoid cells only. CONCLUSION: Hcy enhances IL-1-dependent cytokine production by rheumatoid synoviocytes at a concentration measurable in RA joints in vivo. Thus, in RA patients, Hcy may not only represent an important risk factor for the progression of cardiovascular diseases, but it may also contribute to the joint damage.

Arthritis, Rheumatoid↗

Immune imbalance in the synovial fluid of rheumatoid arthritis patients: effects of intra-articular injection of thymopentin.

T cell subsets in the synovial fluid (SF) and peripheral blood (PB) of RA patients and controls suffering from different forms of chronic synovitis have been investigated. The immunological evaluation showed a reduction of CD4 subsets in RA-SF compared to RA-PB (p less than 0.001), and an almost complete absence of the suppressor-inducer/naive T cells in RA-SF compared to RA-PB and SF from patients with other forms of chronic synovitis. The CD8 subpopulation showed an increased proportion of cytotoxic cells only in RA-SF. On the basis of these results, an intra-articular immunomodulating treatment with thymopentin has been performed: its effects were characterized by an increase of CD8+CD11b+ T cells in the CD8 subset parallel to the enhancement of the suppressor-inducer/naive T cells in the CD4 subset with a statistically significant correlation. The enhanced levels of soluble CD8 decreased after treatment in RA-SF, whereas the soluble IL-2R levels were not significantly modified. Clinical evaluation showed a significative amelioration in all considered parameters.

Adult↗

HLA antigens in Italian patients with systemic lupus erythematosus: evidence for the association of DQw2 with the autoantibody response to extractable nuclear antigens.

In order to verify the hypothesis that Italian patients with systemic lupus erythematosus (SLE) may be immunogenetically distinct from SLE patients born in other regions, we investigated the HLA class I and II antigens and their relation with the various autoantibodies characteristic of the disease in an Italian SLE population. Forty-four SLE patients were typed for HLA-A, -B, -C, -DR and -DQ antigens; sera from the same patients were tested for the presence of antibodies to the nuclear or cytoplasmic antigens Ro/SSA, La/SSB, Sm and RNP (ENA). Results of HLA typing showed that the frequencies of DR3 and DQw2 were increased in patients compared with controls. Analysis of the correlations between HLA antigens and anti-ENA antibodies showed that both DQw2 and DR3 were increased in patients with anti-Ro and/or antiLa antibodies, while in patients with anti-Sm and/or antiRNP antibodies the DQw2 and DR4 were found to be increased. Only DQw2 was found to be significantly increased in anti-ENA positive patients. These results might suggest that Italian patients with SLE are, at least in part, different from lupus patients living in other geographical areas and suggest the association of DQw2 with the autoantibody response to ENA in SLE.

Adult↗

[Clinical manifestations correlated with anticardiolipin antibodies in systemic lupus erythematosus: preliminary results of a prospective study].

Antiphospholipid antibodies (aPL) have been linked to various clinical manifestations in systemic lupus erythematosus (SLE), mainly thrombosis, repeated abortions and thrombocytopenia. Despite the large number of studies which have been published in the recent years, there is still some debate on this matter, and no firm conclusion has been reached as yet. Among the various aPL, anticardiolipin antibodies (aCL) have received more attention, mostly because they can be easily detected by means of immunoenzymatic assays. The main objective of the present study was to determine the prevalence of IgG and IgM aCL isotypes in SLE in order to compare their possible association with the clinical manifestations of the disease. Clinical features of 40 consecutive and unselected SLE patients (35 female and 5 male) were prospectively studied. Sera from the same patients were tested for the presence of aCL, using a standardised ELISA assay, and the presence of aCL was correlated with the various clinical events. Results showed that the prevalence of aCL was 42.5% for the IgG isotype and 10% for the IgM isotype. Regarding the clinical associations of aCL, we found a strong linkage between the presence of these antibodies and the occurrence of both thrombosis and abortions; a weaker association with neurological events was also demonstrated. These results, if confirmed on larger series, suggest that aCL should be searched in patients with SLE in order to identify those who are at greater risk of developing some severe clinical problems and could benefit by prophylactic treatment.

Adult↗