PubMed Health⌕ Search

Biomedical subjects

Graham R V Hughes

Publications and source records attributed to Graham R V Hughes.

At least 19 recordsLinked to original sources
PubMed2006

Factor XII autoantibodies as a novel marker for thrombosis and adverse obstetric history in patients with systemic lupus erythematosus.

AIM: To investigate the clinical significance of anti-factor XII (FXII) in a large cohort of patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: This study comprised 127 patients with SLE. IgG and IgM anti-FXII were tested by an in-house ELISA. 123 healthy donors comprised the control group. RESULTS: 51 (40%) patients with SLE and 9 (7%) healthy controls were positive for anti-FXII. IgG and IgM anti-FXII were frequently found in patients with thrombosis (28% and 13%, respectively). Levels of IgG and IgM anti-FXII were higher in patients with thrombosis than in the control group (p<0.001 and p=0.005, respectively). Anti-FXII was more frequent in patients with arterial thrombosis (31% vs 4% for IgG and 14% vs 3% for IgM, respectively) and venous thrombosis than in controls (37% vs 4% for IgG). IgG anti-FXII were more frequent in patients with miscarriages and fetal death (35% and 40% vs 4% for IgM). The prevalence of IgM anti-FXII was not different between groups. CONCLUSION: Anti-FXII are frequent in patients with SLE. Their presence is associated with thrombosis and adverse obstetric history, making these antibodies a novel marker for the antiphospholipid syndrome.

Abortion, Spontaneous↗
PubMed2006

Intravenous immunoglobulin in the treatment of resistant subacute cutaneous lupus erythematosus: a possible alternative.

Subacute cutaneous lupus erythematosus (SCLE) is a common manifestation of systemic lupus erythematosus. In many cases it appears to be resistant to various systemic or topical treatments. Three cases of resistant SCLE with good response to intravenous immunoglobulin (IVIG) are described here suggesting that IVIG could be an alternative treatment in these patients.

Adult↗
PubMed2006

Antiphospholipid antibody testing: which are most useful for diagnosis?

Laboratory diagnosis of APS relies on the demonstration of a positive test for aPL. In clinical practice, the gold standard tests are those that detect beta2GPI-dependent aCL or LA. The question on the use of anti-beta2GPI asa routine diagnostic test remains unanswered, and testing for these antibodies should be only performed in very selected cases and not as an alternative to aCL or LA testing. Clinical utility and standardization are still lacking for other aPL specificities; therefore, their application as routine diagnostic tools is not recommended.

Antibodies, Anticardiolipin↗
PubMed2005

[Neurological manifestations of the antiphospholipid syndrome].

Antiphospholipid syndrome can be associated with several neurological manifestations. The most common symptom is headache. It has also been associated with cognitive dysfunction, probably due to ischemia. A high prevalence of antiphospholipid antibodies has been found in patients with epilepsy and in transverse myelitis. The most common thrombotic manifestation is stroke. Venous thrombosis can also be found, yet it is less frequent. A stroke in a young person obliges to rule out the antiphospholipid syndrome. The neurological manifestations can mimic multiple sclerosis. Thus, determination of antiphospholipid antibodies is recommended in the study of patients with atypical manifestations of multiple sclerosis. Other manifestations associated with antiphospholipid antibodies include chorea, neurosensorial deafness, Guillain-Barre syndrome, and psychotic disorders.

Antiphospholipid Syndrome↗
PubMed2005

Electroencephalography in the assessment of neuropsychiatric manifestations in antiphospholipid syndrome and systemic lupus erythematosus.

OBJECTIVE: To describe the prevalence and clinical associations of abnormalities on electroencephalography (EEG) in patients with antiphospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE) who have neuropsychiatric symptoms. METHODS: The study group comprised 57 patients (age </=50 years) with manifestations of neuropsychiatric illness. Patients with stroke, epilepsy, or other encephalopathies were excluded. Fourteen patients had APS, 24 patients were positive for antiphospholipid antibodies (aPL), and 19 patients had SLE without aPL. All patients underwent EEG and brain magnetic resonance imaging (MRI) while they were awake. RESULTS: Abnormal EEG findings (showing mainly bitemporal slow activity) were recorded in 37 of 57 patients (65%). Abnormal EEG findings were observed in all patients with APS and in 17 of 24 aPL-positive patients (71%), compared with 6 of 19 patients with SLE (32%) (P < 0.001 and P < 0.05, respectively). There was an association between abnormal EEG findings and the frequency of aPL positivity (at least 2 positive results) (P = 0.002). Three EEG recordings showed potentially epileptiform activity. Results of brain MRI were abnormal in 18 (31.6%) of 57 patients: 8 in the APS group (57.1%), 7 in the aPL-positive group (29.2%), and 3 in the SLE group (15.8%). None of the patients with normal EEG findings had abnormal MRI results. Thus, brain MRI findings were normal in the majority of patients. Patients with abnormal EEG results were more likely to report memory problems (P < 0.001). CONCLUSION: Our findings suggest that EEG abnormalities are common and correlate with the presence of aPL even in the absence of brain abnormalities on MRI. EEG should be considered in aPL-positive patients with neuropsychiatric symptoms, because use of antiaggregants or anticoagulation may need to be considered.

Adult↗
PubMed2005

Thalidomide for the treatment of resistant cutaneous lupus: efficacy and safety of different therapeutic regimens.

PURPOSE: Thalidomide is effective for the treatment of severe cutaneous lupus. Our aim was to study the safety and efficacy of different doses of thalidomide in this condition. METHODS: We studied patients with severe cutaneous lupus that was unresponsive to antimalarials, prednisolone, methotrexate, azathioprine, and cyclosporin A. Starting doses of 100 mg daily (n = 16 patients), 50 mg daily (n = 17), or 50 mg on alternate days (n = 15) were compared. The response to thalidomide was categorized as complete remission, partial remission, or no visible improvement. All patients received a baseline electromyogram (EMG) followed by repeat EMG every 3 to 6 months, or sooner if neuropathic symptoms developed. RESULTS: Forty-eight patients (46 female; mean [+/- SD] age, 44 +/- 12 years; range, 22 to 71 years) with discoid lupus (n = 18), subacute cutaneous lupus (n = 6), or systemic lupus erythematosus with skin involvement (n = 24) were included. The response rate was 81%, including 29 patients (60%) in complete remission and 10 (21%) in partial remission. Nine patients (19%) failed to respond. Thirteen patients (27%) developed peripheral neuropathy, which was EMG-proven in 11, including 4 patients in the 50-mg alternate-day group. Other side effects included drowsiness, constipation or abdominal pain, and amenorrhea. The relapse rate after stopping thalidomide was 67% (26/39). There was no association between a positive response to the drug and either starting doses or cumulative dose. Similarly, no association was found between peripheral neuropathy and the starting or cumulative dose. CONCLUSION: Thalidomide is effective for the treatment of severe cutaneous lupus. There were no clear dose-dependent effects. However, the high incidence of neurotoxicity, even at low doses, suggests that it may be most useful as a remission-inducing drug.

Adult↗
PubMed2005

Diagnosis of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent vascular thrombosis and pregnancy losses. Laboratory diagnosis of APS relies on the demonstration of a positive anticardiolipin antibody test by an in-house or commercially available enzyme-linked immunosorbent assay, or on the presence of lupus anticoagulant by a coagulation-based test. Persistence of the positive results must be demonstrated, and other causes and underlying factors considered. Although it is universally recognized that the routine screening tests (anticardiolipin antibody or lupus anticoagulant) might miss some cases of APS, careful differential diagnosis and repeat testing are mandatory before the diagnosis of 'seronegative APS' can be made. Correct identification of patients with APS is important because prophylactic anticoagulant therapy can prevent thrombosis from recurring and treatment of affected women during pregnancy can improve fetal and maternal outcome.

Animals↗
PubMed2005

Long-term follow-up in 128 patients with primary antiphospholipid syndrome: do they develop lupus?

We retrospectively studied a large cohort of patients with primary antiphospholipid syndrome (APS) from 4 different referral centers to analyze the clinical and serologic features and, specifically, to determine the number of patients going on to develop systemic lupus erythematosus (SLE) or other autoimmune disease after long-term follow-up. The study included 128 unselected patients with primary APS who fulfilled the Sapporo International Criteria from 4 different tertiary hospitals in the United Kingdom, Mexico, and Spain. The patients had attended the referral centers between January 1987 and July 2001. We reviewed clinical and serologic characteristics according to a pre-established protocol. We used univariate analysis with the chi-squared or Fisher exact test and logistic regression to analyze possible factors related to the coexistence of SLE and APS. Ninety-seven female and 31 male patients fulfilled the criteria, with a median age of 42 +/- 12 years (range, 16-79 yr), and with a mean follow-up of 9 +/- 3 years (range, 2-15 yr). The main manifestations included deep vein thrombosis in 62 patients (48%), arterial thrombosis in 63 (49%) patients, pregnancy loss in 177/320 (55%) cases, and pulmonary embolism in 37 (30%) patients. Other clinical manifestations were migraine in 51 (40%) patients, thrombocytopenia in 48 (38%), livedo reticularis in 47 (37%), and valvular disease in 27 (21%). Serologic findings were anticardiolipin antibodies (aCL) IgG positive in 110 (86%) patients, aCL IgM in 36 (39%), lupus anticoagulant in 71 (65%), antinuclear antibodies in 47 (37%), and positive Coombs test in 5 (4%) patients. During the follow-up and after a median disease duration of 8.2 years (range, 1-14 yr), 11 (8%) patients developed SLE, 6 (5%) developed lupus-like disease, and 1 (1%) developed myasthenia gravis. The remaining 110 patients (86%) continued to have primary APS. After the univariate analysis, a family history of lupus, the presence of Raynaud phenomenon, migraine, psychiatric features, multiple sclerosis-like features, hemolytic anemia, low C3 and C4, and Coombs positivity conferred a statistically significant risk for the subsequent development of SLE (p < 0.05). Only the presence of Coombs positivity had statistical significance (odds ratio, 66.4; 95% confidence interval, 1.6-2714; p = 0.027) after the logistic regression evaluation. The current study confirms that progression from primary APS to SLE or lupus-like disease is unusual, even after a long follow-up. Only 3 patients developed anti-dsDNA antibodies. The presence of a positive Coombs test might be a marker for the development of SLE in patients with primary APS.

Abortion, Spontaneous↗
PubMed2005

Antiprothrombin antibodies detected in two different assay systems. Prevalence and clinical significance in systemic lupus erythematosus.

We evaluated the clinical significance of aPT and aPS-PT by testing for the presence of these antibodies in 212 SLE patients and in 100 healthy individuals. Results show that anti-prothrombin antibodies were found in 47% of the patients (aPT in 31% and aPS-PT in 31%). Their presence did not correlate with that of aCL, anti-beta2GPI, LA and/or anti-protein S. IgG but not IgM aPT were more frequently found in patients with thrombosis than in those without. IgG and IgM aPS-PT were also more frequent in patients with thrombosis (venous and/or arterial) than in those without. Levels of IgG aPT and IgG and IgM aPS-PT were higher in patients with thrombosis than in those without. Although aPT and aPS-PT were more frequently found in women with adverse obstetric history than in those without, the differences were not statistically significant. More significantly, 48% of the patients with aPL-related clinical features who were negative for standard tests had antiprothrombin antibodies. We can conclude that aPT and aPS-PT are frequently found in SLE. Their presence is associated with thrombosis, making these antibodies potential markers for the APS. Testing for these antibodies could be of clinical benefit in patients who are negative for the routinely used tests.

Adult↗
PubMed2005

Hughes syndrome, the antiphospholipid syndrome: a new chapter in neurology.

The importance of cerebral disease in patients with the antiphospholipid (Hughes) syndrome (APS) is now becoming more widely recognized. The range of neuropsychiatric manifestations of APS is comprehensive and includes focal symptoms attributable to lesions in a specific area of the brain as well as diffuse or global dysfunction. Patients with APS frequently present with strokes and transient ischemic attacks, but a wide spectrum of other neurologic features, also including nonthrombotic neurological syndromes, has been described in association with the presence of antiphospholipid antibodies. In this review, we attempt to highlight the large variety of the neurological features of APS.

Antiphospholipid Syndrome↗
PubMed2005

Mycophenolate mofetil in systemic lupus erythematosus: efficacy and tolerability in 86 patients.

OBJECTIVE: To assess the indications, efficacy, and tolerability of mycophenolate mofetil (MMF) in patients with systemic lupus erythematosus (SLE) resistant to other immunosuppressive therapy. METHODS: Records of 93 patients with SLE were retrospectively reviewed. Seven patients were excluded. The remaining 86 patients received other immunosuppressive drugs before MMF. Efficacy was measured by changes in daily oral prednisolone dose, European Consensus Lupus Activity Measurement Index (ECLAM), erythrocyte sedimentation rate (ESR), C-reactive protein, and dsDNA antibody titer. In renal patients, changes in serum creatinine, creatinine clearance, chromium-51 EDTA glomerular filtration rate (EDTA-GFR), and 24 hour urine protein excretion were also evaluated. RESULTS: Indications for MMF were mainly renal involvement (59% of patients), uncontrolled disease activity (14%), and other SLE related manifestations (13%). Overall, we found a significant reduction in the steroid dosage, ECLAM, ESR, and anti-dsDNA antibody titer. Renal patients (n = 35) showed a significant reduction in urinary 24 hour protein excretion. Levels of serum creatinine, creatinine clearance, and EDTA-GFR showed no significant change during treatment. Thirty-seven patients (42.8%) developed adverse events. Gastrointestinal intolerance in 25 (29%) and infections in 20 (23.2%) were the most frequent. The drug was discontinued in 14 (16.3%) patients due to side effects and 6 patients discontinued MMF because they achieved disease remission and were trying to conceive. MMF was stopped due to lack of efficacy in 12 patients. CONCLUSION: Our data suggest that MMF is a good therapeutic alternative for patients with SLE and renal involvement or refractory disease activity.

Adult↗
PubMed2004

Transverse myelitis as the first manifestation of systemic lupus erythematosus or lupus-like disease: good functional outcome and relevance of antiphospholipid antibodies.

OBJECTIVE: Transverse myelitis (TM) is a rare complication of systemic lupus erythematosus (SLE). Although usually a late manifestation of SLE, it can occur at presentation. We investigated the clinical presentation, treatment and outcome of 15 patients with TM as the presenting manifestation of SLE or lupus-like disease. METHODS: All patients received corticosteroids, while 13 also received immunosuppressive therapy. Five patients were fully anticoagulated with warfarin. RESULTS: A sensory level with spastic lower limb weakness and sphincter disturbance was the most common presentation: 14/15 patients had a thoracic or cervical sensory level. Cerebrospinal fluid examination showed high protein concentrations in 3 patients and oligoclonal bands in 8. Eleven of the 15 (73%) had antiphospholipid antibodies (aPL). Of the 15 patients, 3 had complete resolution of the symptoms, 6 had good functional improvements, 5 had good to fair outcome with some functional deficit, and one patient who received corticosteroids alone later died from pneumonia. CONCLUSION: We describe 15 patients with TM as the presenting manifestation of SLE or lupus-like disease with a high prevalence of aPL. Our data support the view that early diagnosis and immunosuppressive therapy may be superior to corticosteroids alone in improving functional outcome. In those patients with aPL, antiplatelet agents and/or warfarin should also be considered.

Adult↗
PubMed2004

Features associated with epilepsy in the antiphospholipid syndrome.

OBJECTIVE: To assess the frequency of epilepsy in primary and secondary antiphospholipid syndrome (APS); to analyze the clinical and laboratory features characterizing those with epilepsy in a cohort of 538 patients with APS; and to find associated features that would suggest risk factors for epilepsy in APS. METHODS: We analyzed the clinical features of patients with APS who had epilepsy and compared them to the clinical features of non-epileptic APS patients. RESULTS: Of 538 APS patients, 46 (8.6%) had epilepsy. Epilepsy was more prevalent among APS secondary to systemic lupus erythematosus (SLE) compared to primary APS (13.7% vs 6%; p < 0.05). The patients with epilepsy had a higher prevalence of central nervous system (CNS) manifestations including focal ischemic events (strokes or transient ischemic events, 54.3% vs 24.6%; p < 0.0001) and amaurosis fugax (15.2% vs 4.9%; p < 0.05). APS patients with epilepsy had a higher frequency of valvular pathology (30.4% vs 14.6%; p < 0.01), thrombocytopenia (43.5% vs 25%; p < 0.05), and livedo reticularis (26.1% vs 11.5%; p < 0.01). The multivariate logistic regression analysis found CNS thromboembolic events as the most significant factor associated with epilepsy, with an odds ratio (OR) of 4.05 (95% confidence interval, CI: 2.05-8), followed by SLE (OR 1.4, 95% CI 1.2-4.7), and valvular vegetations (OR 2.87, 95% CI 1-8.27). CONCLUSION: Epilepsy is common in APS and most of the risk seems to be linked to vascular disease as manifested by extensive CNS involvement, valvulopathy, and livedo reticularis and to the presence of SLE. These factors, however, explain only part of the increased occurrence of epilepsy in APS and other causes such as direct immune interaction in the brain should be investigated.

Adult↗
PubMed2004

Anti-52 kDa Ro, anti-60 kDa Ro, and anti-La antibody profiles in neonatal lupus.

OBJECTIVE: Studies suggest that anti-52 kDa Ro antibodies are more sensitive and specific than anti-60 kDa Ro antibodies for neonatal lupus. However, these studies mainly used immunoblot or ELISA using recombinant protein, which have poor sensitivity for anti-60 kDa Ro antibodies. In addition, the control patients were not disease matched. We reassessed the sensitivity and specificity of anti-52 kDa Ro, anti-60 kDa Ro, and anti-La, addressing these limitations. METHODS AND RESULTS: To assess sensitivity, 125 mothers of children with neonatal lupus (NLM) were recruited. All maternal sera were assessed using a commercial line immunoassay that uses natural 60 kDa Ro protein (Inno-Lia ANA Update, Innogenetics NV, Gent, Belgium). By this method, 96% of the sera had antibodies to 60 kDa Ro, 86% to 52 kDa Ro, and 78% to 48 kDa La. Immunoblot of 65 NLM showed significantly fewer positive results for anti-60 kDa Ro (p < 0.001) and anti-52 kDa Ro (p < 0.05). Sensitivity of the 3 antibodies was assessed in the symptomatic mothers of children with congenital heart block (CHB) (78 women) and disease matched controls with unaffected children (65 women) using Inno-Lia ANA Update. The sensitivity of each antibody was compared by multiple logistic regression to adjust for maternal disease. There was no significant difference between the groups for 60 kDa Ro or for anti-52 kDa Ro antibody. However, there was a significant difference for the anti-La antibody (p = 0.001), with an odds ratio of 3.59. This translates to an increase in risk from a published 2% for CHB in an anti-Ro-positive mother to 3.1% if the woman is also anti-La antibody-positive, and to a decrease in risk to 0.9% if anti-La-negative. CONCLUSION: Contrary to previous reports, 52 kDa Ro as detected by Inno-Lia ANA Update is not more specific for or frequent in CHB than 60 kDa Ro. However, the presence of anti-La antibodies significantly increases the risk for CHB.

Antibodies, Antinuclear↗
PubMed2003

Circulating oxidized LDL forms complexes with beta2-glycoprotein I: implication as an atherogenic autoantigen.

Beta2-glycoprotein I (beta2-GPI) is a major antigen for antiphospholipid antibodies (Abs, aPL) present in patients with antiphospholipid syndrome (APS). We recently reported (J. Lipid Res., 42: 697, 2001; J. Lipid Res., 43: 1486, 2002) that beta2-GPI specifically binds to Cu2+-oxidized LDL (oxLDL) and that the beta2-GPI ligands are omega-carboxylated 7-ketocholesteryl esters. In the present study, we demonstrate that oxLDL forms stable and nondissociable complexes with beta2-GPI in serum, and that high serum levels of the complexes are associated with arterial thrombosis in APS. A conjugated ketone function at the 7-position of cholesterol as well as the omega-carboxyl function of the beta2-GPI ligands was necessary for beta2-GPI binding. The ligand-mediated noncovalent interaction of beta2-GPI and oxLDL undergoes a temperature- and time-dependent conversion to much more stable but readily dissociable complexes in vitro at neutral pH. In contrast, stable and nondissociable beta2-GPI-oxLDL complexes were frequently detected in sera from patients with APS and/or systemic lupus erythematodes. Both the presence of beta2-GPI-oxLDL complexes and IgG Abs recognizing these complexes were strongly associated with arterial thrombosis. Further, these same Abs correlated with IgG immune complexes containing beta2-GPI or LDL. Thus, the beta2-GPI-oxLDL complexes acting as an autoantigen are closely associated with autoimmune-mediated atherogenesis.

Adolescent↗