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Munther Khamashta

Publications and source records attributed to Munther Khamashta.

6 recordsLinked to original sources
PubMed2006

Anti-inflammatory and immunosuppressive drugs and reproduction.

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.

Adult↗
PubMed2006

Antiphospholipid antibodies from patients with the antiphospholipid syndrome induce monocyte tissue factor expression through the simultaneous activation of NF-kappaB/Rel proteins via the p38 mitogen-activated protein kinase pathway, and of the MEK-1/ERK pathway.

OBJECTIVE: Antiphospholipid syndrome (APS) is characterized by thrombosis and the presence of antiphospholipid antibodies (aPL). In patients with primary APS, expression of tissue factor (TF) on the surface of monocytes is increased, which may contribute to thrombosis in these patients. However, the intracellular mechanisms involved in aPL-mediated up-regulation of TF on monocytic cells are not understood. This study was undertaken to investigate the intracellular signals induced by aPL that mediate TF activation in monocytes from APS patients. METHODS: We analyzed, both in vivo and in vitro, aPL interactions with proteins that have signaling functions, including mitogen-activated protein kinases (MAP kinases) and NF-kappaB/Rel proteins. RESULTS: In vivo studies demonstrated significantly higher levels of both TF messenger RNA and TF protein in monocytes from APS patients compared with controls. At the molecular level, increased proteolysis of IkappaBalpha and activation of NF-kappaB were observed. Constitutive activation of both p38 and ERK-1 MAP kinases was also found. Treatment of normal monocytes with aPL activated ERK-1 and p38 MAP kinases, as well as the IkappaB/NF-kappaB pathway, in a dose-dependent manner. NF-kappaB activation and IkappaBalpha degradation induced by aPL were inhibited by the NF-kappaB inhibitor SN50 and the p38 MAP kinase inhibitor SB203580, thus suggesting crosstalk between these pathways. However, the MEK-1/ERK inhibitor PD98059 did not affect aPL-induced NF-kappaB binding activity. TF expression induced by aPL was significantly inhibited by combined treatment with the 3 inhibitors. CONCLUSION: Our results suggest that aPL induces TF expression in monocytes from APS patients by activating, simultaneously and independently, the phosphorylation of MEK-1/ERK proteins, and the p38 MAP kinase-dependent nuclear translocation and activation of NF-kappaB/Rel proteins.

Adult↗
PubMed2006

Antiphospholipid syndrome and the kidneys.

OBJECTIVES: To study the relationship between antiphospholipid antibodies and kidney diseases. METHODS: We reviewed the medical literature from 1968 to 2005 using MEDLINE and the keywords antiphospholipid syndrome, anticardiolipin antibodies, lupus anticoagulant, hypertension, renal artery stenosis, renal vascular thrombosis, thrombotic microangiopathy, and glomerulonephritis. RESULTS: The renal manifestations of the antiphospholipid syndrome may result from thrombosis occurring at any location within the renal vasculature, that is, in the renal artery trunk or branches, intraparenchymal arteries and arterioles, glomerular capillaries, and the renal veins. The spectrum of these manifestations includes renal artery stenosis and/or malignant hypertension, renal infarction, renal vein thrombosis, thrombotic microangiopathy, increased allograft vascular thrombosis, and reduced survival of renal allografts. More recently nonthrombotic conditions like glomerulonephritis have also been reported. CONCLUSION: The kidney appears to be a major target organ in both primary and secondary APS. Early detection of renal involvement may improve the prognosis of these patients.

Antibodies, Antiphospholipid↗
PubMed2003

Thromboprophylaxis with unmonitored intermediate-dose low molecular weight heparin in pregnancies with a previous arterial or venous thrombotic event.

The comparatively high rate of complications, both to the mother and foetus, of warfarin and unfractionated heparin have led to an increased use of low molecular weight heparins (LMWH) in pregnant women at risk of thrombosis. However, despite reliable pharmacokinetics of LMWH, current practice is that anti-activated factor X levels are monitored in this group of patients. We report the use of unmonitored dalteparin in 27 pregnancies of 25 women who had previous thrombotic events. All women had normal renal function and weighed less than 85 kg prior to conceiving. The regimen consisted of 5000 IU dalteparin once daily started at the time of a positive pregnancy test, and increased to twice daily at 16-20 weeks gestation. In this cohort of patients there was a low complication rate. None of the women developed recurrent venous thromboses during these pregnancies but two women with known cerebral antiphospholipid syndrome developed recurrent cerebral ischaemia, which responded to an increase in dose. In our small group of patients, we have found that the use of intermediate-dose LMWH in pregnant women does not need to be monitored, and that it is safe and probably effective in preventing recurrent venous but not arterial thromboembolic events in high-risk pregnancies.

Adult↗