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Biomedical subjects

M Khamashta

Publications and source records attributed to M Khamashta.

At least 37 records · Page 2Linked to original sources
PubMed1997

Thromboprophylaxis with low molecular weight heparin (Fragmin) in high risk pregnancies.

Venous thromboembolic disease remains the commonest cause of maternal death. The management of thromboprophylaxis in high risk women during pregnancy is contentious. Low molecular weight heparins (LMW) have theoretical advantages compared with unfractionated heparin and warfarin but have been poorly studied in pregnancy. We report on the use of LMW heparin (Fragmin) as thromboprophylaxis in thirty four high risk pregnancies. All the women had a previous thrombosis or a thrombosis in their current pregnancy +/- a recognised thrombophilic state (eleven had the antiphospholipid syndrome). Fragmin was given subcutaneously to maintain trough anti-Xa activity of 0.15-0.2 U/ml and 2 h post injection levels of 0.4-0.6 U/ml. The levels were checked monthly during pregnancy. Most women required 5,000U Fragmin once daily during the first trimester unless they were greater than 100 kg at the start of pregnancy. The mean time for dosage increase was 20.5 week (S.D. 8.2). 26/34 pregnancies (76%) required 5,000 twice daily at the end of pregnancy. Epidural anaesthesia was managed by omitting Fragmin dose or inserting the needle 6 hours after the previous Fragmin injection. There were no thromboembolic events thrombocytopenias or excessive haemorrhage. One woman had osteoporotic vertebral collapse post partum, she had no other risk factors for osteoporosis. LWM heparin (Fragmin) appears to be efficacious in preventing recurrent thromboembolic disease in pregnant women at high risk, but it is notable that osteoporotic fractures occurred post partum in one woman. Further trials are required to determine optimal dosage and safety.

Adult↗
PubMed1996

Antibodies against endothelial cells in patients with multiple sclerosis.

OBJECTIVES: The humoral immune response seems to play a role in the pathogenesis of multiple sclerosis (MS). The blood-brain-barrier (BBB) and particularly the endothelial cell may be a possible target for this immune response. MATERIAL & METHODS: using an ELISA technique, we have investigated the prevalence of antibodies directed against human vein endothelial cells in the sera of 84 patients with MS, 35 stroke patients, 50 systemic lupus erythematosus (SLE) and 76 normal controls. The measurements in MS patients were tested a second time after cytokine stimulation with gamma and beta-interferon at different doses. Seven MS patients (two positive and five negative) had three or more clinical assessments including the Expanded Disability Status Scale (EDSS) over a three-month period, and at least three AECA determinations were carried out. Gadolinium MRI examinations were performed monthly during these three months. RESULTS: Anti-endothelial cell antibodies (AECA) have been identified in 9 of 84 patients suffering from MS (10.71%), in 3 of 35 stroke patients (8.57%) and in 20 of 50 SLE patients (40%). None of 76 normal controls had a positive titre of AECA. Cytokine stimulations did not modify the detection of these antibodies. No correlation between AECA and different clinical parameters such as onset age, clinical symptoms at onset and at sampling, clinical course and score measured by the EDSS was found in MS patients. No relationship was found between MRI activity and the presence of AECA. CONCLUSION: AECA do not seem to be a marker for a specific subset of MS patients.

Adolescent↗
PubMed1996

Interethnic differences in the association of tumor necrosis factor promoter polymorphisms with systemic lupus erythematosus.

OBJECTIVE: To assess the role of polymorphisms in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene in susceptibility to systemic lupus erythematosus (SLE). METHODS: Two ethnically different populations of patients with SLE (49 white from the UK and 49 black from South Africa) were genotyped for TNF-238 and TNF-308 polymorphisms using amplification refractory mutation system-polymerase chain reaction (PCR). HLA-DR genotypes were assigned to the patients and controls either serologically or by PCR and sequence specific oligonucleotides. The frequencies of the respective variants were compared between patients and ethnically matched controls. RESULTS: No significant differences were found in the frequency of the TNF-238 variants in either ethnic group. At TNF-308, the TNF2 variant was significantly increased (p = 0.04) in white patients with SLE compared to controls. However, TNF2 was strongly associated with HLA-DR3 (p = 0.00002), which also showed a strong trend of increase in the white patients (p = 0.06). In contrast, in the black patients with SLE in whom DR2 but not DR3 was increased, the frequency of TNF2 was actually reduced rather than increased. CONCLUSIONS: The increase of TNF2 in Caucasians with SLE is most likely due to linkage disequilibrium between TNF2 and DR3. Furthermore, the observation that TNF2 seems to be reduced in blacks with SLE strongly suggests this polymorphism is not an independent risk factor for SLE. Overall, our data indicate that the TNF-238 and TNF-308 promoter polymorphisms do not confer susceptibility to SLE.

Base Sequence↗
PubMed1995

Detection of brain-reactive autoantibodies in the sera of patients with systemic lupus erythematosus and cerebral involvement.

We modified, and applied to man, an ELISA established for the detection of brain-reactive autoantibodies in a murine model of SLE. We found brain-reactive antibody levels to be significantly higher in lupus patients than in healthy subjects. The antibody levels were significantly higher in lupus patients with central nervous system involvement than in those without.

Adult↗
PubMed1995

Epitope specificity of monoclonal anti-beta 2-glycoprotein I antibodies derived from patients with the antiphospholipid syndrome.

beta 2-Glycoprotein I (beta 2GPI) has been identified as a cofactor in the recognition of the phospholipid Ag cardiolipin (CL) by anticardiolipin Ab (aCL) purified from patients with autoimmune diseases. However, there is considerable controversy as to the exact nature of the epitopes to which these Abs are directed. mAb derived from patients with the antiphospholipid syndrome bound to CL only in the presence of beta 2GPI. Synthetic peptides that span the fifth C-terminal domain of beta 2GPI supported the binding of one of the mAbs to CL in a beta 2GPI-free system. These peptides possessed the phospholipid binding sequence Cys281-Lys-Asn-Lys-Glu-Lys-Lys-Cys288. Three of the mAbs bound to beta 2GPI that had been adsorbed on gamma-irradiated microtiter plates. Binding to beta 2GPI was inhibited in a dose-dependent manner by the peptides from the carboxyl-terminal end of beta 2GPI and soluble beta 2GPI, indicating that the mAb bound to peptides and beta 2GPI in free solution. Thus, mAbs derived from patients with the antiphospholipid syndrome have specificity for epitopes on the fifth domain of beta 2GPI. Our results support the idea that beta 2GPI acts as a primary Ag for these Abs.

Adult↗
PubMed1995

Appearance of systemic lupus erythematosus after thymectomy: four case reports and review of the literature.

The appearance of systemic lupus erythematosus (SLE) after thymectomy (or thymomectomy) is presented in four patients together with a comparative review of additional reports found in a Medline search for the years 1966-94 in the English and French literature. Fourteen women and two men of average age of 39 years (range 11-66 years) at presentation, developed SLE after thymectomy (11 patients) or thymomectomy (five patients). Half developed SLE within 3 years after surgery (range 3 months to 18 years). The most common SLE manifestation was polyarthritis occurring in 15 of 16 patients either at presentation or during the first year. Other frequent manifestations included skin rashes, fever, cytopenias and pleuritis. Two rare manifestations of SLE, optic neuritis and transverse myelitis, were reported in two patients. Thymic hormone activity was measured in one patient and was undetectable compared with normal controls. HLA studies in eight patients showed the combination of A1, B8 in four. In conclusion, the appearance of SLE after thymectomy or thymomectomy appears to be more than a coincidence. It may provide insights into the pathogenesis of SLE.

Adolescent↗
PubMed1994

Characterization of the endothelial surface proteins recognized by anti-endothelial antibodies in primary and secondary autoimmune vasculitis.

The antigenic structures recognized by anti-endothelial cell antibodies (AECA) in sera from 10 Wegener's granulomatosis (WG) and 12 systemic lupus erythematosus (SLE) patients with signs of vasculitis were characterized by immunoprecipitation of selectively radiolabeled surface membrane proteins from human umbilical vein endothelial cells. Electrophoretic analysis of the immunoprecipitated proteins revealed reactivities against endothelial antigens ranging in size from 200 to 25 kDa. AECA antigens were not cell specific, since the same sera also reacted, at least in part, with radiolabeled human fibroblast surface proteins. The majority of WG patients displayed a constant precipitation pattern of five proteins (180, 155, 125, 68, and 25 kDa). On the contrary, AECA from SLE sera reacted with a more heterogeneous series of endothelial proteins. A group of four proteins, however, was also found in the majority of SLE sera: 200, 180, 155, and 25 kDa. In addition, some endothelial antigens were immunoprecipitated only by WG (125 kDa) or by SLE sera (200 kDa), suggesting a different endothelial reactivity in different vasculitic processes. The reaction did not involve intracellular proteins as demonstrated by the lack of reactivity of SLE sera negative for AECA but positive for anti-cytoplasmic or anti-nuclear antibodies. These data confirming that AECA recognize surface endothelial determinants further support a potential pathogenetic role for these antibodies in autoimmune vasculitis.

Antibodies↗
PubMed1994

Antibodies against platelet-activating factor in patients with antiphospholipid antibodies.

We have studied the specificity of antiphospholipid antibodies in 148 patients with autoimmune diseases, 120 patients with systemic lupus erythematosus and 28 with the primary antiphospholipid syndrome. In addition, 20 patients suffering from syphilis were studied. As a control group, 64 healthy volunteers were investigated. Patient and control serum samples were tested for binding to seven different phospholipid antigens by ELISA. Interestingly, 90% of the sera from syphilis patients and 6% of the autoimmune patients exhibited a significant binding to platelet-activating factor (PAF), a molecule similar to the structure of phosphatidylcholine. In addition, the IgG fraction from one of the lupus patients, which showed a high binding activity to PAF, was further affinity-purified using both liposomes and an affinity chromatography column. Preincubation of these antibodies with PAF inhibited subsequent binding to immobilized PAF. These observations might suggest a putative interaction of antiphospholipid autoantibodies with PAF 'in vivo', which may have, in some patients, important pathophysiological consequences.

Antibodies, Antiphospholipid↗
PubMed1993

Calprotectin in patients with systemic lupus erythematosus: relation to clinical and laboratory parameters of disease activity.

Calprotectin (L1) is a granulocyte and monocyte cytosolic protein released during activation of these cells. The plasma level of L1 has been shown to be a good marker of disease activity in rheumatoid arthritis. In this cross-sectional study of 100 patients with systemic lupus erythematosus (SLE), the serum level of L1 was found to be higher in patients than in matched controls (3661 micrograms/l versus 1051 micrograms/l; P < 0.001). The serum level of L1 was the only laboratory parameter with significant association to the disease activity index SLEDAI (r = 0.28; P < 0.01). Furthermore, the serum level of L1 was significantly higher in SLE patients with anti-DNA antibodies compared to patients without anti-DNA antibodies (4501 micrograms/l versus 3279 micrograms/l; P = 0.01). SLE patients with arthritis had higher serum levels of L1 than patients without arthritis (7652 micrograms/l versus 2811 micrograms/l; P < 0.01), indicating that the serum level of L1 also reflects arthritis activity in SLE.

Adult↗
PubMed1993

Malignancy in systemic lupus erythematosus: a report of five cases in a series of 96 patients.

The association of systemic lupus erythematosus (SLE) and malignancy has been reported previously and suggests an increased risk of cancer in this disease. Lymphomas are the most frequent neoplasias reported in these patients and carcinoma of the cervix and breast are also seen. Several factors probably play a role in the aetiology of malignancies associated with SLE including intrinsic disturbances of immunity and concomitant immunosuppressive therapy. We report five solid tumors (one breast carcinoma, one squamous cell carcinoma of the anus, one adenocarcinoma of the rectum, one carcinoma of the cervix and one carcinoma of the gallbladder) among 96 patients with SLE. The most striking finding in this study was the absence of haematological malignancies. The incidence of malignancy in the series, the age of diagnosis of SLE and neoplasia and the time delay between SLE and malignancy diagnosis was similar to other series. We did not find any clinical or immunological feature that predicted the development of neoplasia. In conclusion, patients with SLE may have the same malignancies as the general population after adjustment for age and sex. There are no predictive indicators for malignancy and immunosuppressive therapy may be a contributing factor.

Adenocarcinoma↗
PubMed1992

[Treatment of esophageal candidiasis with fluconazole in acquired immunodeficiency syndrome. Comparative study of 2 therapeutic schemes].

BACKGROUND: To evaluate the efficacy and pharmacological safety of 2 therapeutic trials with fluconazole in candida esophagitis in AIDS patients. METHODS: A total of 75 episodes of candida esophagitis in 70 AIDS patients were included in an open prospective study. In group I 36 patients were included who received 200 mg of fluconazole orally the first day followed by 100 mg daily for 4 weeks. In group II (34 patients) the length of treatment was reduced to 10 days with the same daily doses. Therapeutic response was evaluated by esophagoscopy, biopsy and fungal culture. RESULTS: The protocol was completed at 68 episodes with a cure being obtained in all but 2 patients in group II. No significant differences in clinical response were found between the 2 groups. The incidence of oropharyngeal colonization at the end of treatment was greater in patients from group I than from group II (43% vs 11%). Fluconazole was well tolerated in all the patients. A slight alteration of the hepatic enzymes was observed in 29 cases (40%) with a lower incidence in the shorter time group (p less than 0.001), however, treatment was discontinued only in 1 patient because of severe asymptomatic hepatic dysfunction to which a relation with the drug is unclear. CONCLUSIONS: Fluconazole in an efficient and safe agent in the treatment of candida esophagitis in AIDS patients. A 10 day treatment is a useful as longer treatment and has a lower risk of adverse effects.

Acquired Immunodeficiency Syndrome↗