Pentoxifylline inhibits Vgamma9/Vdelta2 T lymphocyte activation of patients with active Behçets disease in vitro.

The aim of this study is to evaluate the in vitro effect of pentoxifylline (PTX) on T Vgamma9/Vdelta2 lymphocyte function in Behçets disease (BD). We investigated the effect of PTX on Vgamma9/Vdelta2 T cell expansion and expression of TNFRII receptor and perforin content before and after PTX addition by means of FACS analysis lymphocyte cultures from patients with active and inactive BD and healthy subjects. The addition of PTX at a concentration of 1 mg/ml determined a significant inhibition of cell expansion, a down regulation of TNF receptor expression and inhibited the PMA-induced degranulation of perforin. Taken together these data indicate that PTX is capable of interfering with Vgamma9/Vdelta2 T cell function in BD, and although cell culture models cannot reliably predict all of the potential effects of the drug in vivo, our results encourage the possibility that this drug may find use in a range of immunological disorder characterized by dysregulated cell-mediated immunity.

The level of soluble Granzyme A is elevated in the plasma and in the Vgamma9/Vdelta2 T cell culture supernatants of patients with active Behçet's disease.

OBJECTIVE: Gramzyme A (GrA) is a serine proteinase with trypsin-like activity that is released extracellularly during the degranulation of cytotoxic cells. Among the cytotoxic cells, gamma/delta T cells participate in the early phases of the immune response and are known to express perforin and granzymes constitutively in agreement with their cytolytic pontential. METHODS: GrA activity was detected using the synthetic substrate N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester in the plasma and supernatants of peripheral blood mononuclear cell cultured in the presence of Dimethylallyl pyrophosphate to obtain Vgamma9/Vdelta2 T cell expansion. RESULTS: Significantly high levels of GrA were found in the serum and supernatants of lymphocytes from patients with active Behçet's disease cultured in the presence of DMAPP. Levels were found to be significantly lower after remission. A positive correlation was observed between GrA levels in the supernatants and the Vgamma9/Vdelta2 T cell expansion factor. CONCLUSION: These results strongly suggest that Vgamma9/Vdelta2 T cells are active participants in the pathogenesis of the disease through their degranulation and granzyme release.

Lower cranial nerve palsy due to dissection of the internal carotid artery: CT and MR imaging.

Three patients with unilateral lower cranial nerve palsy underwent contrast enhanced CT and magnetic resonance (MR) imaging for the investigation of possible compressive pathology in the region of the jugular foramen. Computed tomography revealed a mural crescentic hypodensity of the corresponding internal carotid artery (ICA) in two patients and a faulty visualization of the vessel in one. Magnetic resonance revealed a corresponding hyperintense lesion expanding the wall and narrowing the lumen of the cervical ICA on both T1- and T2-weighted images. Dissection of the ICA was confirmed by angiography in all three patients. Among the possible etiologies of lower cranial nerve palsy, a dissecting hematoma of the cervical ICA must be considered, which can be diagnosed by CT and MR.

Vascular deaths in elderly neurological patients with leukoaraiosis.

OBJECTIVES: The prognostic significance of leukoaraiosis is still not completely elucidated. The objective was to examine survival and causes of death among elderly neurological patients with leukoaraiosis. METHODS: From 1 January 1994, vital status and causes of death were drawn from municipality lists and death certificates of 216 patients (mean age (SD) 70.6 (8.3) years) admitted to a geriatric unit who underwent cranial CT between 1 January 1984 and 31 December 1986 (mean observation period (SD) 8.4 (0.8) years). These patients had been enrolled for a study of clinical predictors of leukoaraiosis. Based on the presence of leukoaraiosis on CT, this group had been divided into two subgroups of patients, with and without leukoaraiosis. The difference in survival and causes of death between these groups formed the objective of the study. RESULTS: Survival time was shorter among the 90 patients with leukoaraiosis than among the 126 patients without (median survival time 4.07 v 7.78 years, log rank test P < 0.001). After controlling for age and other major death predictors, the risk of death remained significantly increased (relative risk (RR) = 1.64, 95% confidence interval (95% CI) 1.15-2.34) among patients with leukoaraiosis. Moreover, patients with leukoaraiosis had an almost threefold higher risk of dying from vascular causes than patients without (RR = 2.81, 95% CI 1.74-4.53). CONCLUSION: Leukoaraiosis is a predictor of vascular deaths in elderly neurological patients. Careful diagnostic evaluation and attention to preventive measures are required in patients with leukoaraiosis.

IVIG in APS pregnancy.

For more than two decades, the intravenous administration of high doses of IgG pooled from the plasma of healthy donors (immune globulin therapy, also known as 'IVIG') has benefited patients with a variety of autoimmune disorders. A potential therapeutic role of IVIG in the prevention of thrombosis and of miscarriages in antiphospholipid syndrome (APS) has been postulated. Multicenter randomized controlled trials attempted to define the role of IVIG in preventing pregnancy complications in APS indicate that simple anticoagulation could not be completely satisfactory, and certain patient subgroups might take advantage of IVIG therapy alone or in combination with heparin.