Quantitative evaluation of 99mTc-pyrophosphate muscle uptake in patients with inflammatory and noninflammatory muscle diseases.
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Biomedical subjects
Publications and source records attributed to S Bombardieri.
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The diagnostic approach to Sjögren's syndrome (SS) is devoted to the assessment of glandular and extraglandular features of the disorder. Although this syndrome has been attracting growing interest from many investigators in the last few decades, complete agreement on the diagnostic tools to be used for this syndrome has not yet been reached. Finding a rational diagnostic approach to Sjögren's syndrome is even further complicated by the fact that this disease may exist alone, or in association with a number of extraglandular systemic manifestations or a well-defined systemic autoimmune disease. In this paper the entire matter has been critically reviewed in order to evidentiate the differences among the various diagnostic procedures proposed by different authors and to underline the need for a uniform classification criteria for SS.
Blood, plasma and serum viscosity and blood filtration were investigated in 43 unselected mixed cryoglobulinemia patients. A hyperviscosity syndrome was present in only one patient, and rapidly improved after plasma exchange and cyclophosphamide therapy. A clear-cut increase in blood viscosity was infrequently observed in mixed cryoglobulinemia, although significant differences were present in the plasma and serum viscosity of patients and controls. In contrast, blood filtration was severely impaired in a high percentage of cases (51 and 72% of the values recorded at 37 degrees and 25 degrees C, respectively), and was on the average significantly higher in patients than in controls. Indirect evidence suggests that blood viscosity is at least in part related to cryoglobulins. In 19 patients studied before and after cryoglobulin removal, serum viscosity significantly decreased when the serum was deprived of cryoglobulins. In addition, the cryocrit correlated with all the hemorheological parameters with the exception of blood filtration. The hemorheological findings were compared with multisystemic features of the disease, i.e. liver, renal, lung, neurologic, vascular and funduscopic alterations. The potential clinical relevance of the hemorheological parameters was stressed by the close correlation between blood filtration parameters and serum creatinine. Furthermore, by discriminant analysis, viscosity and blood filtration changes were the serological parameters most significantly associated with the presence of renal, liver and neurological involvement. Thus, hemorheological parameters are frequently abnormal in mixed cryoglobulinemia patients, and seem to play a significant clinical role; they should therefore be included in the work-up of these patients.
The highly specific beta-adrenergic radioligand (-)[125I]iodocyanopindolol (ICYP) was used to characterize the beta-adrenergic receptor subtype present in human placenta. Binding of ICYP to membranes from human placenta was saturable with time and ligand concentration, of high affinity, and demonstrated appropriate stereoselectivity and agonist rank order of potency for binding to a beta-adrenergic receptor. From saturation binding curves, the KD and Bmax values for ICYP binding were 233 +/- 51 pM and 690 +/- 139 fmol/mg of proteins, respectively. Analysis of inhibition of ICYP binding by beta 1- and beta 2-selective adrenergic antagonists via Hofstee analysis resulted in linear plots, indicating the existence of a homogeneous population of beta-adrenergic receptors. From the resulting KI-values for the beta 1-selective drugs practolol (4.0 +/- 0.9 microM) and metoprolol (0.19 +/- 0.07 microM) and for the beta 2-selective drug ICI 118,551 (0.30 +/- 0.06 microM) it is concluded that the beta-adrenergic receptor in human placenta is of the beta 1-subtype. This is further supported by the fact that (-)-noradrenaline and (-)-adrenaline were equipotent in inhibiting ICYP binding.
It is well known that immune complex (ICs) diseases are caused by a number of factors which influence the localization, clearance and inflammatory potential of ICs. Several studies suggest that the Ag/Ab ratio is one of the most important of these. Previous studies have clarified that IC detection methods which differ, either in their recognition unit or in the phase used (solid or liquid), show a very poor correlation with each other. This study was developed in order to verify the hypothesis that different methods recognise different kinds of ICs on the basis of their Ag/Ab ratio. We used 3 homogeneous EIAs employing a probe complex enzyme--anti enzyme which competes with circulating ICs for the recognition unit (bovine conglutinin, C1q or monoclonal rheumatoid factor) to detect 10 unrelated in vitro-made ICs at different relative Ag/Ab concentrations (from 8 x Ag excess to 8 x Ab excess). We demonstrated that the 3 recognition units recognised the ICs principally on the basis of their Ag/Ab ratio. These results were then used to set up a mathematical model capable of retracing the Ag/Ab ratio of the ICs present in unknown samples. This was employed to test a panel of sera from patients with systemic lupus erythematosus, essential mixed cryoglobulinemia and rheumatoid arthritis; we obtained very suggestive results but they require further prospective studies to understand the full significance of this parameter.
In order to evaluate their sensitivity and specificity, parotid sialography (PS) and labial salivary gland biopsy were performed in 150 putative patients with Sjögren's syndrome (SS) (74 with SS alone and 76 with SS associated with other well-defined disorders). Although PS and LSGB strongly correlated to each other (Kendall's Tau 0.47, z = 7.78, p less than 0.0001), PS confirmed the diagnosis of SS in a significantly higher prevalence of patients with respect to LSGB (63% vs 37%, chi 2 = 18.25, p less than 0.001). When the sensitivity and specificity of PS and LSGB were calculated, PS showed a better sensitivity, and an only slightly lower specificity than LSGB (86% vs 70% and 78% vs 86% respectively). In conclusion, our study indicates that PS has been unduly overlooked in the past decades as a diagnostic tool for the salivary component of SS, and should be reconsidered as a potentially useful and relatively non-invasive procedure in the approach of patients with this disease.
The potential value for the diagnosis of Sjögren's syndrome (SS) of 28 clinical and 18 serological parameters was evaluated in 38 patients with primary (1 degree) SS, 29 with rheumatoid arthritis (RA), 30 with systemic lupus erythematosus (SLE), and 22 with mixed cryoglobulinemia (MC), by means of a stepwise discriminant analysis. Twelve patients with RA, 11 with SLE, and 8 with MC had evidence of sicca syndrome and were then classified as having a secondary (2 degree) SS. When comparing the various disease groups to each other, it was always possible to select different combinations of clinical and serological variables which defined highly significant discriminant functions. In addition, some parameters appeared to have a stronger discriminant power between different disease groups. For instance, 1 degree SS was well discriminated from RA by anti-Ro antibodies (Ab) and normal C-reactive protein (CRP) levels, from SLE by normal complement levels and the positivity of rheumatoid factor, from MC by the absence of liver involvement and normal complement levels. While anti-La Ab had the highest value in differentiating patients with 1 degree from those with 2 degrees SS, anti-Ro Ab and recurrent parotid swelling seem to be typical features of patients with SS with respect to those with other connective tissue disease but without sicca syndrome.
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In order to evidentiate whether a circadian rhythm of the myoglobin serum concentration is present in humans, we measured serially the myoglobin levels in blood samples of 21 healthy subjects (10 females and 11 males), at bed rest, by means of a sensitive and accurate radioimmunological method. The data obtained were then evaluated according to the single and mean cosinor analysis, to assess the presence of a significant circadian rhythm. Eighteen of the 21 subjects showed a significant circadian rhythm. The calculated equation for the mean cosinor was: Y = 19.12 + 4.09 cos (15t-128.24) and the F-value for the zero amplitude test was 19.9 (p less than 0.001). Our data demonstrate that circadian variations of myoglobin serum concentration are likely to occur in humans. These findings strongly emphasize the need to take the time of sample collection into account when employing serum myoglobin as a marker for muscle damage.
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Several clinical indices have been proposed to measure disease activity in systemic lupus erythematosus (SLE), a disorder characterised by alternate phases of flare and remission. Over the last 5 years a European multicenter study was carried out in order to reach a consensus on the definition of SLE activity. A new index, ECLAM (European Consensus Lupus Activity Measurement), was created and then validated in the first and in the second parts of the study, respectively. In addition, a comparison between ECLAM and the other most commonly used lupus activity indices was performed. ECLAM appeared to be the best activity index for classifying lupus patients, whether used as a single state index (i.e., to measure activity at a given moment in time) or as a transition index. (i.e., to measure variations in activity over time).
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Sjögren's syndrome (SS) represents a pathological model of the evolution from polyclonal B lymphocyte activation to oligo-monoclonal B cell expansion, which may culminate in the development of a true lymphoproliferative disease. The different phases of this process are usually marked by the appearance of type II mixed cryoglobulins in which the monoclonal component is commonly represented by an IgM with rheumatoid factor activity. A similar mechanism exists in mixed cryoglobulinaemia (MC), a different pathological entity in which hepatitis C virus infection has been demonstrated to play an important etiopathogenetic role. Although there are significant differences between SS and MC, they also share many clinical and immunological characteristics, which suggest that common pathogenetic mechanisms may underlie both disorders.
Hepatitis C virus has been proven to be the major cause of NANB hepatitis, cirrhosis and hepatocellular carcinoma worldwide. Based on the genome similarities between HCV and flavivirus or pestivirus, this agent has been included within the family Flaviviridae as a separate genus. Among the analogies between HCV and the other members of the same family there is the possibility of infecting blood cells. In particular, significant evidence obtained through studies performed in vivo and in vitro support the concept that HCV is not only a hepatotropic but also a lymphotropic virus. This suggests that, in addition to playing a role in inducing hepatic diseases (both of a non-tumoral and a neoplastic nature), HCV infection may also play a role in extrahepatic pathologies. The striking association observed between HCV infection and some autoimmune-lymphoproliferative disorders of either benign or neoplastic nature is consistent with this hypothesis. However, in analogy with what has been observed in the case of liver disease, the mechanisms involved in the pathogenesis of HCV-related extra-hepatic manifestations have to be more deeply analysed and clarified.
Hepatitis C virus (HCV) infection has been found in the majority of patients with mixed cryoglobulinemia (MC) in studies conducted in different countries. In our series of 110 MC patients the frequency of HCV markers was significantly high (91%) compared with other rheumatic diseases (6.4%) and with healthy Italian controls (1.2%). Moreover, HCV RNA was detected in 81% of the peripheral lymphocytes from MC patients. Comparable percentages of HCV infection were detectable in other disorders, i.e. porphyria cutanea tarda (77%) and autoimmune hepatitis type 1 (77%). The HCV infection of peripheral lymphocytes suggests that this virus could be the triggering factor for the lymphoproliferation underlying MC. In a number of patients with MC the evolution from a benign lymphoproliferation to frank B-cell lymphoma was observed. In these subjects HCV RNA in the sera and in fresh and cultured peripheral lymphocytes was constantly detected. The same phenomenon has been observed in patients with long-lasting type C chronic hepatitis. Interestingly, HCV infection has also been recorded in 32% of idiopathic B-cell non-Hodgkin's lymphomas. Taken together, the above findings suggest that HCV can cause benign B-cell proliferation with the consequent production of various autoantibodies, including rheumatoid factor and mixed cryoglobulins. These serological abnormalities characterise different clinical disorders, including the appearance of lymphoma in a not negligible number of individuals.
The principal therapeutic procedures and when they are clinically indicated in the management of essential mixed cryoglobulinemia (EMC) have been the subject of much debate. This paper reviews current knowledge and our experience in the treatment of this complex disease. It is generally agreed that patients with purpura, the primary symptom of EMC, should avoid long periods of sitting or standing in the same position. Non-steroidal antiinflammatory drugs can be used for the management of arthralgias and/ or arthritis. Low dose steroids (0.5-0.3 mg/kg/die) are usually sufficient to control the purpura, arthralgias, arthritis and weakness, while larger doses (0.5-1.5 mg/kg/die) are needed to treat the renal involvement, peripheral neuropathy and serositis. Since the discovery of the association between EMC and viral infections, the appropriateness of cytotoxic drugs has been re-evaluated and they are no longer used. With the low antigen content diet, a regimen designed to restore a saturated mononuclear phagocytic system, good results have been obtained in the treatment of purpura, arthralgias, weakness and peripheral neuropathy. Furthermore, this dietary regimen may play a steroid sparing role. Plasma exchange is widely used in the management of severe renal involvement, hyperviscosity syndrome, sensory motor neuropathy and liver involvement in EMC.