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Biomedical subjects

A Ruffatti

Publications and source records attributed to A Ruffatti.

At least 19 recordsLinked to original sources

[Relationship between late ventricular potentials and ventricular arrhythmias in patients in chronic dialysis treatment].

BACKGROUND: Arrhythmias are frequent pathology in patients with chronic hemodialysis. We evaluated whether a relatively new technique, signal averaging, could be useful in predicting the development of complex arrhythmias in these patients. METHODS: Thirty-three patients, 18 male and 15 female, subjected to thrice weekly chronic hemodialytic treatment with various dialysis techniques, were studied. Exclusion criteria were the presence of antiarrhythmic and inotropic treatment. The following examinations were carried out in all patients: a Holter dynamic electrocardiography for a duration of 24 hours, begun on the day of dialysis, high resolution ECG pre- and post-dialysis to find out if there were any ventricular late potential (VLP). Four hundred beats were examined in order to obtain a background noise of less than 0.7 microV and a better definition of the signal. The following parameters were considered significant for the presence of VLP: a) filtered QRS duration > 120 msec; b) the root mean square of the signal expressed in the terminal portion of QRS (RMS) < 25 microV) high frequency low amplitude signals duration (HFLA) > 40 msec. A positive value in two of these parameters was considered indicative of the presence of VLP. In addition various pre and post-dialysis indices of dialytic efficiency and a mono and two-dimensional echocardiogram with pulsed and color Doppler were carried out. Of the 33 patients studied, ten were excluded because they presented too high a background noise at the high resolution ECG. Of the remaining 23 patients, 13 (56%) presented VLP and nine of these (69%) presented complex arrhythmias. Of the ten patients without VLP, 5 (50%) presented complex arrhythmias. The incidence of arrhythmias was highest during the last two hours of dialysis and in the two hours following it. The patients were then divided into two groups (A and B) according to the ejection fraction (EF) found at the echocardiogram. Group A was composed of 17 patients of whom 8 (47%) presented complex arrhythmias; group B (EF < 45%) was composed of the remaining six patients, who all presented complex arrhythmias. In group A nine patients (53%) out of 17 had LVP, in group B four out of six (66%) had it. All the patients except one presented an increase in the thickness of the ventricular wall and alterations of Doppler transmitral filling rate. Left ventricular hypertrophy was diagnosed in 22 out of the 23 patients. Four patients also had chronic ischaemic heart disease; of these three had LVP. There was no correlation between the presence of LVP and the hemodialytic indices and between the latter and complex arrhythmias. CONCLUSIONS: Our study showed that arrhythmias are more frequent in patients with LVP before dialysis than in those without. The difference was statistically significant (p < 0.006); the incidence of arrhythmias was higher in patients with FE < 45% (p < 0.001). The majority of patients (95%) had left ventricular hypertrophy; only four (17%) had ischaemic heart disease too. It is highly probable that the presence of LVP in our patients can be attributed to hypertension and subsequent left ventricular hypertrophy. As patients with LVP at the end of dialysis had a greater incidence of arrhythmias than those without LVP, we suggest that this method could be useful as a first screening in dialysed patients.

Adult

Trends in immunoglobulin G anticardiolipin antibodies in ten successful heparin-treated pregnancies.

The pregnancies of ten women, all with histories of at least two spontaneous abortions of unknown cause, were followed. All patients were positive for immunoglobulin (Ig) G anticardiolipin antibodies (aCL) and one also for IgM aCL, while none had lupus anticoagulant activity. During pregnancy, the patients were treated with calcium heparin in doses varying between 15,000 and 30,000 IU daily. IgG aCL were assayed on average at the 9th, 17th, 24th and 29th weeks of pregnancy and at the moment of delivery. Mean values of IgG aCL levels during the 10 pregnancies steadily fell as the pregnancies progressed, and this decrease was significant (r = 0.985, P = 0.002). All pregnancies terminated favourably, although delivery was brought forward in eight patients and six of the nine placentas examined showed signs of thrombotic events. We assume that a steady fall in IgG aCL levels during pregnancy may be considered as indicative of a favourable outcome.

Adult

Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies.

Anti-phospholipid (aPL) antibodies are defined as antibodies detected in systems employing phospholipids (PL). This general definition is misleading as it comprises a large group of autoimmune phospholipid-reactive antibodies that are directed against specific phospholipid-binding plasma proteins, such as beta 2-glycoprotein I (beta 2GPI) and prothrombin. Definition of phospholipid-reacting antibodies according to the plasma protein against which they are directed appears more appropriate and could be useful in understanding clinical events and pathogenic mechanisms. Using ELISA systems we have studied the presence of antibodies directed against specific phospholipid-binding proteins in a series of 22 patients with thrombosis and phospholipid-reactive antibodies of the IgG isotype. High levels of anti-beta 2 GPI IgG were detected in all 22 patients. Normal values were calculated on the basis of OD values at 405 nm (OD405) obtained for 22 age- and sex-matched healthy subjects (cut off value = 0.401). Levels of anti-beta 2 GPI antibodies were linearly correlated with those of cardiolipin-reactive (aCL) antibodies. Eleven out of 22 patients (50%) had values of anti-prothrombin antibodies exceeding the cut-off value of 0.250. No relationship was found between the levels of anti-beta 2GPI and anti-prothrombin antibodies. Tests for antibodies against two natural inhibitors of blood coagulation, protein C and protein S, revealed elevated levels of anti-protein C IgG and anti-protein S IgG in 4 and 12 patients, respectively. A highly significant correlation between anti-protein C IgG and anti-protein S IgG values as well as between antibody titers against the two studied natural coagulation inhibitors and anti-prothrombin IgG was found. When comparing patients positive for aCL and presence or absence of a previous thrombotic episode (aCL+/T+ vs aCL+/T-), the positivity of anti-beta 2GPI IgG was found to be statistically associated with thrombosis. Conversely, among patients with previous thromboembolism with or without aCL (aCL+/T+ vs aCL-/T+ vs aCL-/T+) the positivity of anti-beta 2GPI IgG was strictly associated with the positivity of aCL, thus identifying the aPL antibody syndrome. These data demonstrate that anti-beta 2GPI antibodies are a marker of "autoimmune" thrombosis. Anti-prothrombin antibodies are not a marker of thrombosis and are closely associated with antibodies to protein C and protein S.

Antibodies, Antiphospholipid

Anticardiolipin antibodies and antiphospholipid syndrome in chronic discoid lupus erythematosus.

Anticardiolipin antibodies (aCL) of immunoglobulin (Ig) G and M classes were determined in 28 patients affected with chronic discoid lupus erythematosus (CDLE), comparing their prevalence and levels to those in 60 healthy subjects matched for age and sex. A high and significant frequency of IgG (67.8%) and IgM (50.0%) aCL together with prevalence of high antibody levels was found in CDLE patients, while healthy controls had IgG and IgM aCL in 1.6% and 3.3% of cases respectively. Clinical features in keeping with the diagnosis of antiphospholipid syndrome were found in one patient (3.5%), which, as the first manifestation of the syndrome, showed a pulmonary thromboembolism which appeared some days after prolonged exposure to the sun. These results provide additional data on autoimmune phenomena in CDLE and suggest that aCL test should be considered as useful aids in immunological diagnosis of CDLE.

Adult

Anti beta 2-glycoprotein I antibodies in a patient with catastrophic antiphospholipid syndrome.

Autoimmune antiphospholipid antibodies are a hallmark of patients with antiphospholipid syndrome, and require a protein cofactor, beta 2-glycoprotein I, to bind anionic phospholipids. In these same patients, moreover, IgG directly binding beta 2-glycoprotein I are described. We found high plasma titres of both IgM and IgG anti beta 2-glycoprotein I antibodies in a patient with catastrophic antiphospholipid syndrome. After passing plasma through a Sephacryl S-300 column, an identical distribution pattern between anti beta 2- glycoprotein I and anticardiolipin antibodies was observed. Moreover, when IgG immunocomplexes were isolated from a high molecular fraction, IgM anti- beta 2-glycoprotein I and anticardiolipin antibodies were detected. Thus IgG, IgM ad IgG-IgM complexes of anti-beta 2-glycoprotein I antibodies are present at the same time in a patient with antiphospholipid syndrome.

Acute Disease

Fibrinolytic pattern in recurrent spontaneous abortions: no relationship between hypofibrinolysis and anti-phospholipid antibodies.

Patients with antiphospholipid antibodies may suffer from thrombotic events and recurrent spontaneous abortions. A defective fibrinolytic potential has been described in women with recurrent fetal losses. We investigated the prevalence of anticardiolipin antibodies and of various fibrinolytic abnormalities in 64 females with a history of at least two abortions of unknown origin. Anticardiolipin antibodies were present in the serum of 31 patients (48.4%). The overall prevalence of fibrinolytic disorders was 67.2% (43 cases) and resulted significantly higher than that of aCL positivity (P = 0.03). In most of cases the impaired fibrinolytic potential after venous occlusion test was due to increased PAI-1 levels; only in a few instances a defective fibrinolytic response was due to reduced t-PA release, a combined defect or an intrinsic fibrinolytic deficiency. After division of patients in two groups on the basis of the aCL presence, the distribution of different fibrinolytic defects was similar in aCL positive and negative women, suggesting the lack of correlation between hypofibrinolysis and aCL antibodies. Plasminogen abnormalities resulted compatible with congenital hypoplasminogenemia in two aCL negative women, whereas in four aCL positive patients they were suggestive for acquired dysplasminogenemia. Our results indicate that patients with recurrent spontaneous abortions may present fibrinolytic disorders, which occur independently and more often than aCL positivity. An accurate investigation of the fibrinolytic potential, and, namely, of PAI-1 levels, should be included in the study of females suffering from repeated fetal losses.

Abortion, Habitual

Cerebrovascular and neurological disorders associated with antiphospholipid antibodies in CSF and serum.

Paired serum and cerebrospinal fluid (CSF) samples from 70 patients with inflammatory and non-inflammatory neurological diseases, as well as 10 sera from patients with primary antiphospholipid syndrome (PAS), six of which presented with cerebrovascular ischemic syndromes, were studied for the presence of anticardiolipin antibodies (ACA) of the G and M classes. PAS sera and some selected paired CSF and serum specimens, were also analyzed for the presence of anti-phosphatidylserine (PS) and anti-phosphatidylethanolamine (PE) antibodies. High levels of IgG and IgM ACA were synthesized intrathecally only in patients with neurosyphilis. Patients with other infectious or inflammatory neurological diseases very rarely showed detectable levels of ACA in serum and/or CSF. ACA were found not only in patients with untreated PAS but also in the serum of 3/7 patients with migraine, thus confirming a relationship between ACA and vascular disorders. The search for PS and PE antibodies disclosed that in PAS patients the serum titers of these antibodies mirrored ACA IgG and IgM titers, while they were never found in the CSF.

Adolescent

A catastrophic antiphospholipid syndrome: the importance of high levels of warfarin anticoagulation.

We report the clinical observation of a 23-year-old woman affected by the so-called 'catastrophic antiphospholipid syndrome'. Within a 3-month period she suffered a number of thrombotic events and haemolytic anaemia with thrombocytopenia and had high levels of immunoglobulins G and M and anticardiolipin antibodies associated with lupus anticoagulant activity. The severity of the clinical and laboratory changes is described and diagnostic and therapeutic difficulties are discussed. The apparent control of thrombotic events only with high levels of warfarin anticoagulation is stressed.

Adult

Antiphospholipid antibodies (aPL) in systemic lupus erythematosus. Are they specific tools for the diagnosis of aPL syndrome?

OBJECTIVE: Antiphospholipid antibody (aPL) specificity for aPL-related events was evaluated in systemic lupus erythematosus (SLE). METHODS: A study was carried out on 105 patients affected with SLE comparing the prevalence of lupus anticoagulant (LA) and IgG and IgM anticardiolipin antibodies (aCL) between patients with and without features of antiphospholipid syndrome (APS). Antiphospholipid antibody profile was subsequently evaluated in the aPL positive patients with and without aPL-related events, thus excluding the patients with complications of APS possibly due to factors other than aPL. RESULTS: LA showed a strong association with thrombosis and livedo reticularis, and IgG aCL with thrombosis and neurological disorders, while no clinical features were associated with IgM aCL. A considerable number of aPL positive patients with no aPL-related manifestations was also observed, suggesting the low specificity of aPL assays (54.4%). When studying the 60 aPL positive patients, LA was specific (91.3%) for the diagnosis of aPL-related thrombosis, whereas aCL were not specific, although IgG aCL mean levels were higher in patients with arterial thrombosis than in those without APS features. CONCLUSIONS: LA but not aCL positivity is a specific tool for the diagnosis of thrombotic complications due to aPL in SLE.

Adolescent

Antiphospholipid antibody syndrome associated with ovarian cancer. A new paraneoplastic syndrome?

We describe a 41-year-old woman, in whom antiphospholipid antibody syndrome (APS) occurred at presentation, before the detection of an ovarian endometrial adenocarcinoma. This syndrome was characterized by widespread and worsening thromboembolism and it did not respond to conventional anticoagulant treatment. The paraneoplastic nature of this APS was strongly suggested by the disappearance of both thromboembolism and antiphospholipid antibodies only after surgical removal of the cancer.

Adenocarcinoma

Early phenotypic activation of circulating helper memory T cells in scleroderma: correlation with disease activity.

OBJECTIVES: The differential expression of several accessory/activation molecules (CD26, CD29, CD45RA, CD25, MLR4, HLA-DR) on peripheral blood CD4+ and CD8+ T lymphocytes in patients with scleroderma was compared with that in controls and patients with other connective systemic diseases to look for evidence of the involvement of T cells in the disease process of scleroderma. METHODS: The two colour expression of surface molecules by circulating T cells was analysed with a panel of monoclonal antibodies and flow cytometry in 17 patients with scleroderma, 10 patients with systemic lupus erythematosus, and five patients with rheumatoid arthritis, and the results compared with those for 10 normal controls. The two colour T CD4+ phenotype was further compared between patients with active and quiescent disease in these patients with scleroderma. The coexpression of surface molecules by CD4+ T cells was also analysed by three colour flow cytometry in eight patients with scleroderma. RESULTS: Patients with scleroderma showed increased CD4+CD26+ and CD4+CD25+ percentages and absolute numbers and decreased CD8+CD29+ percentages compared with controls. Moreover, a significant correlation between the higher CD4+CD26+ T cell percentage and absolute cell numbers with disease activity was observed. Most of the CD4+ peripheral blood T cells from patients with scleroderma showed the CD26+CD45RA- phenotype by three colour flow cytometry analysis. CONCLUSIONS: The distinctive pattern of early helper memory T cell activation in these patients with rapidly evolving scleroderma supports the role of a T cell mediated mechanism in the progression of scleroderma.

Adult

Antiphospholipid antibodies in mixed connective tissue disease.

We studied the prevalence and clinical significance of antiphospholipid antibodies (ab) in 28 patients affected with well-defined mixed connective tissue disease (MCTD). Forty-two patients affected with systemic lupus erythematosus (SLE) and 60 healthy subjects were also evaluated, as controls. In MCTD the prevalence of anticardiolipin (aCL) ab was: IgG high level 17.8% (p less than 0.01 versus healthy controls), IgG low level 7.1% and IgM high level 7.1%. No patients had low level of aCL IgM, lupus anticoagulant or false positive VDRL. The aCL profile was similar to that found in SLE patients, but in SLE all prevalences were higher than in MCTD. Furthermore, in MCTD patients the aCL ab were correlated with thrombocytopenia but not with recurrent thrombosis and/or abortions.

Adult

Hepatitis C virus infection in hemodialyzed patients detected by first and second generation assays.

A prospective study of liver disease has been conducted among patients entering our Dialysis Unit between 1987 and 1990. On entry, 7 patients had a history of blood transfusions but none had clinical or biochemical features of liver disease. During follow-up, 13 further patients were transfused; 1 case developed acute resolving hepatitis B and another acute non-A, non-B hepatitis progressing to chronicity. Eleven other cases showed transient or fluctuating ALT abnormalities. On entry, anti-HCV was negative by both 1st and 2nd generation ELISA assays (Ortho-Diagnostic Systems) in all cases. During follow-up, a positive reaction was detected in 17 cases: 4 patients were positive by both assays and 13 only by 2nd generation test (p less than 0.01). HCV was implicated in 66% of cases with liver disease of the non-A, non-B type and in 50% of transfused as compared to 23% of nontransfused cases (p = n.s.). These findings suggest that HCV could play a major etiological role in liver disease of hemodialysis patients and that anti-C100 reactivity is more affected by immunosuppression associated with chronic uremia.

Adult

Japanese diagnostic criteria for mixed connective tissue disease in Caucasian patients.

Preliminary Japanese diagnostic criteria for the classification of mixed connective tissue disease (MCTD) were tested in a group of 32 Caucasian patients with this disease. Many clinical and laboratory similarities were found between Caucasian and Japanese patients. However, polyarthritis was more frequent in the Caucasians, while finger and hand swelling, DLCO reduction and muscle involvement were more frequent in the Japanese. In Caucasians the sensitivity of this criteria set was 87%, very similar to that found in the Japanese group (88%), and the specificity was 94%, higher than that of Japanese (87%). The difference resulted from the higher specificity of anti-nRNP antibody positivity in the Caucasian patients, probably due to the use of counterimmunoelectrophoresis in the detection of this antibody. The Japanese criteria seem more useful than others because they allow the use of techniques other than passive hemagglutination in detecting the anti-nRNP antibody. In our experience, such criteria also contribute to a better definition of MCTD in Caucasian patients.

Adult

Anti-thyroid microsomal antibody in synovial fluid as a revealing feature of seronegative autoimmune thyroiditis.

Two cases of recurrent monoarthritis are described in which antithyroid microsomal (antiMi) autoantibody (Ab) was found in synovial fluid (SF) before any clinical or serological evidence of thyroid disease. Subsequently, the follow-up of the two patients showed the appearance of thyroiditis within 2-5 years. The presence of anti-Mi Ab in SF might anticipate the appearance of autoimmune thyroiditis even in the absence of serum detectable antithyroid Ab, as was later observed in these two cases.

Adult

Prevalence and characteristics of anti-single-stranded DNA antibodies in localized scleroderma. Comparison with systemic lupus erythematosus.

Prevalence, levels, and immunoglobulin classes of anti-single-stranded DNA antibodies were determined by an enzyme-linked immunosorbent assay in 52 patients with localized scleroderma (33 with morphea, four with generalized morphea, and 15 with linear scleroderma), in 60 healthy controls, and, for comparison, in 31 patients with systemic lupus erythematosus. Localized scleroderma revealed a significant prevalence of anti-single-stranded DNA antibodies, mainly characterized by high levels and IgM and IgA isotypes. Comparison of antibody characteristics in different clinical forms of localized scleroderma showed some significant differences (levels and immunoglobulin isotypes). Comparison with systemic lupus erythematosus showed that frequency, high levels, and IgG isotype of anti-single-stranded DNA antibodies significantly prevailed in systemic lupus erythematosus, while the IgM isotype significantly prevailed in localized scleroderma. However, generalized morphea and linear scleroderma did not significantly differ from systemic lupus erythematosus as regards antibody frequency and prevalence of high antibody levels.

Adult