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S Visvanathan

Publications and source records attributed to S Visvanathan.

10 recordsLinked to original sources
PubMed2001

Identification of anti-thrombin antibodies in the antiphospholipid syndrome that interfere with the inactivation of thrombin by antithrombin.

The combined presence of anti-phospholipid (PL) Ab, including lupus anticoagulants (LAC) and/or anticardiolipin Ab (aCL), and thrombosis is recognized as the antiphospholipid syndrome (APS). LAC are detected as an inhibitory effect on PL-restricted in vitro blood coagulation tests, and are comprised mainly of Ab against beta(2) glycoprotein I and prothrombin (PT). Recently, anti-PT Ab (aPT) were found to be associated with thrombosis by some investigators, although this is not confirmed by others. Considering that aPT are heterogeneous in patients and that PT is converted into thrombin, we hypothesize that certain aPT in patients may bind to thrombin, and that some of such anti-thrombin Ab may interfere with thrombin-antithrombin (AT) interaction and thus reduce the AT inactivation of thrombin. To test this hypothesis, we searched for anti-thrombin Ab in APS patients and then studied those found for their effects on the AT inactivation of thrombin. The results revealed that most, but not all, aPT-positive patient plasma samples contained anti-thrombin Ab. To study the functional significance of these Ab, we identified six patient-derived mAb that bound to both PT and thrombin. Of these mAb, three could reduce the AT inactivation of thrombin, whereas others had minimal effect. These findings indicate that some aPT in patients react with thrombin, and that some of such anti-thrombin Ab could inhibit feedback regulation of thrombin. Because the latter anti-thrombin Ab are likely to promote clotting, it will be important to develop specific assays for such Ab and study their roles in thrombosis in APS patients.

Adolescent↗
PubMed2000

Monocyte tissue factor induction by activation of beta 2-glycoprotein-I-specific T lymphocytes is associated with thrombosis and fetal loss in patients with antiphospholipid antibodies.

Antiphospholipid (aPL) syndrome (APS) is characterized by thromboembolic events, thrombocytopenia, or recurrent miscarriage associated with aPL Abs with specificity for beta2-glycoprotein-I (beta2GPI). We recently reported that at least 44% of patients with the APS possess circulating type 1 (Th1) CD4+ T cells that proliferate and secrete IFN-gamma when stimulated with beta2GPI in vitro. In this study, we show that stimulation of PBMCs from 20 APS patients with beta2GPI induced substantial monocyte tissue factor (TF) (80 +/- 11 TF stimulation index (TF-SI)), whereas no induction was observed using PBMCs from 13 patients with aPL Abs without APS (6 +/- 1 TF-SI) or 7 normal and 7 autoimmune controls (5 +/- 1 and 3 +/- 1 TF-SI, respectively) (p < 0.0001). TF induction on monocytes by beta2GPI was dose dependent and required CD4+ T lymphocytes and class II MHC molecules. Because monocyte TF induction by beta2GPI was observed in all patients with APS, but not in any patient with aPL Abs without APS, this response is a potentially useful predictor for APS in patients with aPL Abs, as well as providing mechanistic insight into thrombosis and fetal loss in these patients.

Antibodies, Antiphospholipid↗
PubMed1999

Cellular immunity to beta 2-glycoprotein-1 in patients with the antiphospholipid syndrome.

Patients with antiphospholipid syndrome (APS) suffer recurrent thromboses, thrombocytopenia, and/or fetal loss in association with Abs that can be detected in phospholipid-dependent assays. Despite the name, the Igs associated with APS are predominantly directed against epitopes on phospholipid-binding plasma proteins, such as beta 2-glycoprotein-1 (beta 2GP1) and prothrombin. The aim of this study was to examine the cellular immune response to beta 2GP1 in patients with APS. Using a serum-free stimulation assay, PBMCs from 8 of 18 patients with APS proliferated to purified beta 2GP1 or to the beta 2GP1 present in serum, whereas no stimulation was observed by PBMCs from healthy individuals, patients with other autoimmune diseases, or anticardiolipin Ab-positive patients without histories of thromboses or fetal loss. The immune response was Ag-specific, requiring class II molecules, CD4+ T cells, and APCs, and was associated with a selective expansion of CD4+ but not CD8+ T cells. The proliferating T cells produced IFN-gamma but not IL-4, indicating a bias toward a type 1 immune response. Chronic low grade stimulation of autoreactive beta 2GP1-specific, IFN-gamma-producing Th1 CD4+ T cells may contribute to the high risk of thromboses and pregnancy failure in patients with APS.

Adult↗
PubMed1999

The symptomatic carpal boss. Is simple excision enough?

We reviewed 48 patients with symptomatic carpal boss seen during the 10 year period 1985-1994. Thirty-one patients had undergone either local excision of the boss or arthrodesis of the affected carpometacarpal joint. The mean follow-up was 3 years and nine cases have been revised. Twenty-four patients remained symptomatic and considered that surgery had failed to relieve their symptoms. These findings are in sharp contrast to previous reports that suggest simple excision of the carpal boss gives uniformly good results.

Adult↗
PubMed1999

Techniques for Vascularised Bone Grafting in Scaphoid Nonunion.

Nonunion of the scaphoid remains a significant problem in the management of scaphoid fractures. Recurrent persistent nonunion following attempts at internal fixation, and nonunions with sclerosis or avascular necrosis of the proximal pole of the scaphoid are particularly challenging. However, the aims of restoration of scaphoid anatomy and the achievement of union of the scaphoid remain the foundation pillars of scaphoid treatment. In recent years, several techniques for using vascularised bone grafts in the treatment of these difficult problems have been described. This article will review the currently described treatments, provide an overview of our unit experience with these techniques, and also describe a technique for in situ vascularisation of a conventional bone graft.

Journal Article↗