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Biomedical subjects

G Valesini

Publications and source records attributed to G Valesini.

At least 91 records · Page 5Linked to original sources

Antiphospholipid antibodies and cerebral artery dissection: two frequent causes of brain ischemia in young adults.

As part of a multicenter study on ischemic stroke in the young, we report the occurrence of high antiphospholipid antibody (aPLs) levels and cerebral dissection in 75 patients. These represent the two most frequent non-thromboembolic causes of cerebral ischemia in our population. Increased aPL titres were found in nine cases (12%); cerebral artery dissection in eleven (14%). Our data stress the need to modify the classical diagnostic approach to cerebral ischemia by including hematological assessments and new neuroimaging techniques as screening tests.

Adult↗

Prevalence of lupus anticoagulant in patients with cirrhosis: relationship with beta-2-glycoprotein I plasma levels.

We have previously demonstrated that patients with cirrhosis may be positive for lupus anticoagulant and anticardiolipin antibodies. The prevalence and clinical value of antiphospholipid antibodies in cirrhosis have never been described. Besides, it has not yet been determined if serum levels of beta-2-glycoprotein I, which is synthesized by the liver and mediates the interaction between cardiolipin and anticardiolipin antibodies affects lupus anticoagulant detectability in cirrhosis. We evaluated the prevalence of lupus anticoagulant in 63 patients with cirrhosis and related it to beta-2-glycoprotein I serum levels. We also analyzed whether lupus anticoagulant and anticardiolipin antibodies were associated with previous thrombotic complications. Eleven patients (18%) were lupus anticoagulant positive; 14 (22%) had high values of anticardiolipin antibodies. Fourteen patients had a previous history of splanchnic venous thrombosis (n = 9) or thrombophlebitis (n = 5). A significant association between lupus anticoagulant (p = 0.0001), anticardiolipin antibodies (p = 0.0001) and venous thrombosis was found. Patients with severe liver failure had significantly lower beta-2-glycoprotein I levels than those with moderate (p < 0.01) or low (p < 0.001) hepatic insufficiency. Among 14 anticardiolipin antibodies positive patients, six with severe liver failure were lupus anticoagulant negative and had beta-2-glycoprotein I values below 100 micrograms/ml. In four of these, basal values of dilute activated partial thromboplastin time were not modified by the addition of 50 micrograms/ml of exogenous beta-2-glycoprotein I. This study shows that antiphospholipid antibodies are relatively frequent in cirrhosis and that beta-2-glycoprotein I levels are not so low as to affect lupus anticoagulant detectability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pathogenic natural anti-cardiolipin antibodies: the experience from monoclonal gammopathy.

Anti-cardiolipin antibodies (ACA) were detected in 19% of sera from patients with monoclonal gammopathies (MG). ACA were purified from the sera of patients with MG. One of the IgG-ACA was found to be monospecific with high affinity for cardiolipin, and to carry a pathogenic ACA Id (1.10). Active immunization of naive BALB/c mice with the purified IgG-ACA was followed by production in the mice of sustained high titres of ACA, associated with prolonged activated partial thromboplastin time (APTT) (61 +/- 14s versus 31 +/- 2s in control mice; P < 0.001) and thrombocytopenia (468,000 +/- 224,000/mm3 versus 994,000 +/- 92,000/mm3 in controls; P < 0.001). The titres of other autoantibodies (e.g. anti-DNA, anti-histones), although being high after immunization, decreased rapidly and were undetected after 1 month following the boost injection. The mice immunized with the IgG-ACA exhibited low fecundity (36% of mice became pregnant versus 62% observed in the group immunized with control IgG). The pregnant mice had increased resorption rate (the equivalent of fetal loss in the human) of 52 +/- 8% (versus 5 +/- 4% in the control group). The mean (+/- s.d.) embryo and placental weights in mice with anti-phospholipid syndrome (APLS) were significantly lower compared with the mice injected with control IgG (682 +/- 304 mg and 102 +/- 12 mg versus 1303 +/- 105 mg and 145 +/- 8 mg, respectively; P < 0.001). Serum monoclonal immunoglobulins having autoantibody activity may be regarded as an expansion of clones producing natural autoantibodies. Our results confirm the pathogenic role of natural ACA in the pathogenesis of the anti-phospholipid syndrome.

Adult↗

Sjögren's syndrome presenting as ischemic stroke.

BACKGROUND: We describe a young woman who presented with minor stroke as a first clinical symptom of Sjögren's syndrome (SS) in the absence of well-known risk factors for cerebrovascular disease. CASE DESCRIPTION: The medical history included recurrent miscarriages and sun rashes, which directed the diagnosis toward immunologic disorders such as systemic lupus erythematosus and antiphospholipid antibody syndrome, which are often associated with stroke. Only complete laboratory testing, including SSB antibody studies, and ophthalmologic and salivary gland evaluation revealed the correct diagnosis. CONCLUSIONS: Sjögren's syndrome should be considered among the causes of stroke, especially in a young female patient.

Adult↗

Magnetic resonance imaging of the parotid glands and lip biopsy in the evaluation of xerostomia in Sjögren's syndrome.

Magnetic Resonance Imaging (MRI) of the parotid glands was performed in 23 patients with dry mouth. Each patient underwent lip salivary gland (LSG) biopsy and complete clinical and immunological assessment. MRI showed a quite specific nodular pattern in the parotid glands of patients with Sjögren's syndrome (SS), especially those with severe histologic abnormalities in LSG. However no significant correlation could be detected between MRI score and both LSG biopsy class and immunological abnormalities. MRI of the parotid glands can be regarded as a useful noninvasive procedure with high positive predictive value for the evaluation of the salivary component in SS.

Adult↗

Pathogenic serum IgG anticardiolipin antibodies and the idiotypic network.

OBJECTIVES: To determine whether active immunisation of mice with pathogenic anticardiolipin antibodies (IgG and IgM), derived from the serum of a patient with the antiphospholipid syndrome, could dysregulate the idiotypic cascade and induce the production of anti-anti-anti-cardiolipin (Ab3) with anticardiolipin activity by the mice with the association of overt antiphospholipid syndrome. METHODS: Anticardiolipin antibodies were purified from the serum of a patient with the antiphospholipid syndrome. The purified anticardiolipin antibodies were used to immunise mice at the footpads and the mice were then followed up for serological and clinical manifestations of the antiphospholipid syndrome. RESULTS: The IgG anticardiolipin antibody was found to be monospecific and to bind cardiolipin with high affinity. Immunisation of naive BALB/c mice with the purified IgG anticardiolipin antibody was followed by production in the mice of sustained high titres of IgG anticardiolipin antibody, associated with a prolonged activated partial thromboplastin time (64.5 (9.7) v 30.1 (1.7) seconds in control mice) and thrombocytopenia (0.4 (0.06) x 10(9) v 1.0 (0.09) x 10(9)/l platelets in controls). The titres of other autoantibodies (for example, antibodies to DNA, histone), though high after the immunisation, decreased rapidly and were almost undetected one month after the boost injection. The mice immunised with the IgG anticardiolipin antibody showed low fecundity (36% of mice became pregnant v 62% in the group immunised with control IgG). The pregnant mice had an increased resorption rate (the equivalent of fetal loss in the human) of 61 (9)% v 5 (4)% in the control group. The mean (SD) embryo and placental weights in mice with the antiphospholipid syndrome were significantly lower than in the mice injected with control IgG (641 (210) and 103 (14) mg v 1303 (105) and 145 (8) mg respectively. The IgM anticardiolipin antibodies purified from the same patient were found to be polyspecific, binding with low affinity to anticardiolipin antibodies and double stranded DNA, and carried the anti-DNA idiotype 16/6. Mice immunised with the purified IgM anticardiolipin antibodies, though showing reduced fecundity (30%), had only a slightly increased resorption rate (12 (9) v 3 (5)% in controls) and only a slight and statistically non-significant decrease in mean (SD) embryo and placental weights (1134 (188) and 136 (11) mg respectively). CONCLUSIONS: The results confirm the induction of pathogenic anticardiolipin antibodies by immunisation with serum anticardiolipin, dysregulating the idiotypic network, and point to the higher pathogenic potential of serum IgG v IgM anticardiolipin antibodies.

Adult↗

Reflex seizures as initial manifestations of systemic lupus erythematosus in childhood.

We report a 10-year-old girl with reflex seizures characterized by visual and acoustic hallucinations, induced by visual and acoustic stimulations. The EEG showed atypical spike-wave discharges on the left temporo-occipital area, markedly activated by visual and acoustic stimuli (intermittent light, pattern-reversal stimulation and monoaural right pure tone). The patient was treated with carbamazepine and seizure stopped within 7 months. After 10 months from the start of the therapy she developed signs of systemic lupus erythematosus.

Acoustic Stimulation↗

Detection of anti-phospholipid and anti-DNA antibodies and their idiotypes in newborns of mothers with anti-phospholipid syndrome and SLE.

The titers, isotypes and idiotypes of antiphospholipid and anti-dsDNA antibodies were determined in seven pairs of mothers with antiphospholipid syndrome (APLS) and their offspring, in 11 pairs of SLE mothers and their matched infants and in seven respective pairs of healthy subjects. In addition, maternal as well as fetal sera were evaluated for the presence of anti-SSA (Ro), anti-SSB (La) and anti-70 kd RNP autoantibodies. In the sera from APLS patients, as well as in the sera from their offspring, the mean antibody titer of IgG aCL was found to be significantly higher then the corresponding value in the control group (P < 0.01). Highly significant increased titers of IgG anti-DNA antibodies were found in the sera of SLE mothers and their matched offspring (P < 0.0008). The prevalence of anti-SSA, anti-SSA, and anti-70Kd RNP antibodies was lower then that of antiphospholipid and anti-dsDNA antibodies. Only one of the respective offspring had increased levels of these antibodies. The quantity of maternal antibodies transferred to the fetus was depended on their concentration in the maternal circulation, as well as on their type and specificity. Follow-up of newborn sera showed a progressive decrease in the antiphospholipid antibody titers during 3 months. After 6 months it was undetected. Our results point to a transplacental transfer of aCL and anti-DNA antibodies, a phenomenon which is not necessarily associated with respective clinical manifestations, in contrast to the classical humoral mediated autoimmune diseases (e.g. myasthenia gravis).

Adult↗

Pulmonary arterial hypertension responsive to immunosuppressive therapy in systemic lupus erythematosus.

Two female patients with recent diagnosis of systemic lupus erythematosus (SLE) are reported. Pulmonary arterial hypertension was diagnosed by Doppler echocardiography. Immunosuppressive therapy was started at the time of diagnosis of SLE. After 2 months of therapy, Doppler echocardiography was repeated and the estimated pulmonary artery systolic pressure was substantially decreased from 78 to 42 mmHg and from 67 to 42 mmHg, respectively, along with significant improvement of the clinical conditions.

Adult↗

[Pulmonary hypertension and systemic sclerosis].

BACKGROUND: Pulmonary involvement in systemic sclerosis (SS) is a frequent complication and is associated with a poor prognosis. Pulmonary hypertension may or may not develop, however, its recognition is usually possible only in advanced stages. METHODS: In this study we noninvasively evaluated the pulmonary artery systolic pressure in 31 patients with SS using Doppler echocardiography. Pulmonary hypertension was detected in 48.4% of the patients. RESULTS: The prevalence of pulmonary hypertension was similar in patients with limited SS and diffuse SS (42.9% and 52.9%, respectively; p = NS). No differences were observed in pulmonary artery systolic pressure between patients with limited or diffuse SS and pulmonary hypertension. Pulmonary hypertension was usually mild, and only in two cases was pulmonary systolic pressure higher than 50 mmHg (63 and 107 mmHg, respectively). CONCLUSIONS: Pulmonary hypertension is frequently observed in patients with SS. The patients with diffuse or limited SS are equally affected by this complication. Doppler echocardiography has proved to be the technique of choice for the evaluation of pulmonary involvement in patients with SS because it is noninvasive, inexpensive and allows serial examinations. Early recognition of pulmonary hypertension may favor the use of therapeutical strategies to prevent the progression to advanced forms.

Adult↗

Pregnancy outcome in relation to uterine artery flow velocity waveforms and clinical characteristics in women with antiphospholipid syndrome.

OBJECTIVE: To determine whether uterine artery velocimetry is a useful tool for identifying pregnancies with antiphospholipid syndrome at risk for adverse outcome. METHODS: Twenty-four women with antiphospholipid syndrome, who had experienced 56 fetal losses in 63 previous pregnancies (88.9%), were treated with prednisone (40 mg/day) and aspirin (100 mg/day) during 28 pregnancies. Color Doppler ultrasound was performed at 18-24 weeks' gestation to investigate the resistance index of the uterine arteries. RESULTS: Treated women delivered 23 live infants in the 28 pregnancies (82.1%). Three infants weighed less than the tenth percentile (13%). Five pregnancies were complicated by preeclampsia and ten by nonproteinuric gestational hypertension. Positive results for all three assays for antiphospholipid antibodies (anticardiolipin antibodies, lupus anti-coagulant, VDRL) at conception identified pregnancies destined to have poor fetal outcome and a significantly lower birth weight compared to pregnancies not having all three assays positive. An abnormal resistance index of the uterine arteries predicted pregnancies with poor fetal outcome in terms of week of delivery, birth weight, and birth percentile, as well as four of five cases of preeclampsia. CONCLUSIONS: Three assays positive for antiphospholipid antibodies at conception and an abnormal resistance index of the uterine arteries at 18-24 weeks' gestation predicted pregnancies at major risk for obstetric complications. Future studies should determine whether treatment can be modulated based on the Doppler findings.

Adult↗

Methods for detecting lupus anticoagulants and their relation to thrombosis and miscarriage in patients with systemic lupus erythematosus.

AIMS: To examine the sensitivity and specificity to past thrombotic events of four different coagulation tests, which screen for lupus anticoagulant (LA), and of anticardiolipin antibodies in patients with systemic lupus erythematosus. METHODS: Fifty three consecutive patients with systemic lupus erythematosus were studied of whom three males and 21 females, aged 21-60 years, had a history of venous and arterial thrombosis, or miscarriage, or both. Activated partial thromboplastin time (aPTT), dilute Russell's viper venom time (dRVVT), kaolin clotting time (KCT), dilute aPTT and the circulating titre of anticardiolipin antibodies were investigated in the two groups of patients and in 20 healthy control subjects. RESULTS: The prolonged dilute aPTT was more sensitive to thromboses or miscarriages, or both than dRVVT (p less than 0.05), KCT (p less than 0.01), and aPTT (p less than 0.001). No significant differences in specificity were found among aPTT (100%), dRVVT (93%), KCT (93%) and dilute aPTT (86.2%); but aPTT and dRVVT were significantly more specific (p less than 0.01, p less than 0.05, respectively) than anticardiolipin antibodies. CONCLUSIONS: The study shows a strong association between lupus anticoagulant and thrombosis when a very sensitive test such as the dilute aPTT is used. The combination of this assay with a very specific test such as dRVVT might enable patients with SLE at high risk of thrombosis to be identified.

Abortion, Spontaneous↗

Distribution of two common idiotypes of anticardiolipin antibodies in sera of patients with primary antiphospholipid syndrome, systemic lupus erythematosus and monoclonal gammopathies.

The frequency of two common idiotypes of anticardiolipin antibodies (aCL) was determined in sera from three groups of subjects, patients with systemic lupus erythematosus (SLE), with primary antiphospholipid syndrome (PAPS) and with monoclonal gammopathies (MG), as compared to normal population. The idiotype 1.10, which was derived from a patient with active SLE and antiphospholipid syndrome, was found more frequently among patients with PAPS (10.5%, 10.5% and 22.2% in MG, SLE and PAPS, respectively) than the idiotype H3, which was derived from a human hybridoma monoclonal aCL generated from a healthy subject immunized with tetanus and diphtheria. The latter idiotype was detected in 8.7%, 6.5% and 11.7% of patients with MG, SLE and PAPS, respectively. Incidental findings in this study include a high prevalence of aCL among patients with MG (23%) and a high prevalence of anti-dsDNA antibodies, detected only by a sensitive enzyme-linked immunosorbent assay, among patients with PAPS. Our results indicate that idiotypic diversity exists among aCL derived from different sources. Some of these cross-reactive idiotypes may be more pathogenic than others.

Adult↗

A new player in the antiphospholipid syndrome: the beta 2 glycoprotein I cofactor.

The study of antiphospholipid (aPL) antibodies has been greatly developed in recent years and conclusive evidence now exists concerning the correlation between aPL and clinical signs such as thrombosis, thrombocytopenia, abortion, and fetal loss. Several hypotheses have been put forward concerning the pathogenic mechanism of aPL, but none has received final confirmation from experimental data. Many studies have been devoted to characterizing the antigens recognized by the different aPL autoantibodies and to a cofactor involved in the binding of autoantibodies and phospholipids; this cofactor has been identified as an apolipoprotein, the beta 2 glycoprotein I (beta 2GPI) or APO-H. Direct evidence now exists which suggests that both the beta 2GPI and the phospholipid comprise the epitope to which aPL are directed. On the other hand anti-beta 2GPI antibodies have been identified in sera of patients suffering from SLE and primary Antiphospholipid Syndrome. beta 2GPI is normally present in human plasma/serum and possesses numerous inhibitory functions in multiple coagulation pathways. The amino acid sequence of beta 2GPI has been identified and found to consist of five repeating units that belong to the complement control protein (CCP) superfamily. This development of knowledge related to aPL has followed three steps respectively: 1. the standardization of the techniques of detection: 2. identification of the clinical signs related to the autoantibodies: and finally 3. the discovery of a new player, the beta 2GPI cofactor.

Animals↗