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Biomedical subjects

R L Brey

Publications and source records attributed to R L Brey.

At least 19 recordsLinked to original sources
PubMed1996

Neurological aspects of antiphospholipid antibody syndrome.

Antiphospholipid antibodies (aPL) have been associated with a variety of neurological disorders, mostly linked to focal neuroparenchymal ischemia or infarction. Cerebral ischemia associated with the antiphospholipid syndrome (APS) occurs at a younger age than typical atherothrombotic cerebrovascular disease, is often recurrent, and high positive GPL values are usually linked to the presence of a lupus anticoagulant. When other features of the syndrome are not present and cerebral ischemia occurs only associated with anticardiolipin immunoreactivity, there appears to be no discerning features of these patients unless GPL > 40 for which recurrent thrombo-occlusive events appear to occur more frequently. Other neurological manifestations associated with aPL include cerebral venous sinus thrombosis, ocular ischemia, dementia, including ischemic encephalopathy, and chorea. The role of aPL in migrainous events is controversial and may not play a role in recent, large case-controlled studies. Most seizures in patients harboring aPL are associated with focal brain infarction.

Antiphospholipid Syndrome↗
PubMed1996

Treatment of neurologic complications of antiphospholipid antibody syndrome.

Thrombosis associated with antiphospholipid antibodies (aPL) occurs in both venous and the arterial circulation. The most common arterial thrombo-occlusive event is cerebral infarction. We briefly review treatment strategies aimed at patients with cerebrovascular disease and aPL. Besides general treatment issues, we discuss primary prevention and secondary prevention. Most regimens include antithrombotics or immune modulation. Prospective studies (currently underway) are required to better estimate the rate of recurrent thrombo-occlusive events on standardized therapy before one therapy can be recommended over another with reasonable evidence.

Antiphospholipid Syndrome↗
PubMed1995

Recurrent stroke and thrombo-occlusive events in the antiphospholipid syndrome.

We prospectively studied 81 consecutively identified patients with antiphospholipid antibodies (aPLs) who developed focal cerebral ischemia over a 7-year period. The mean age of this cohort was approximately a decade younger than the average atherothromboembolic stroke victim and women were more commonly involved than men. The frequency of conventional stroke risk factors was lowest in the group of stroke patients with the highest levels of IgG cardiolipin immunoreactivity. Other serological abnormalities associated with aPL (false-positive Venereal Disease Research Laboratory test, thrombocytopenia, prolonged activated partial thromboplastin time [aPTT]) were more common in the group with over 100 GPL units (high positive). Patients with the highest IgG anticardiolipin titers had the shortest times to subsequent thrombo-occlusive events. The most common recurrent event was cerebral infarction, often occurring within the first year of follow-up during a mean prospective follow-up of 3 years. Over one-half of the cohort had at least one recurrent thrombo-occlusive event during follow-up. This distinct syndrome of cerebral ischemia should be recognized for its younger age at onset, predominance of women, high risk of recurrent thrombo-occlusive events, and the possible use of the IgG anticardiolipin antibody titer for prognosis.

Adult↗
PubMed1995

Accuracy of anticardiolipin antibodies in identifying a history of thrombosis among patients with systemic lupus erythematosus.

OBJECTIVE: To measure the accuracy of anticardiolipin antibodies (aCL) in identifying a history of thrombosis among patients with systemic lupus erythematosus (SLE) or the primary antiphospholipid syndrome (PAPS). PATIENTS AND METHODS: Patients with SLE or PAPS who attended our rheumatology clinic between April 1992 and March 1994 were included in a retrospective analysis of the relationship between thrombotic events and aCL. All aCL measurements were performed in the same laboratory by enzyme-linked immunosorbent assay, blinded as to the presence or absence of thrombosis. The diagnostic accuracy of IgG, IgM, and IgA aCL was quantified by means of the receiver operating characteristic area under the curve (ROC AUC) for each isotype. Stratum-specific likelihood ratios and their 95% confidence intervals were calculated to define strata with optimal discriminant power. RESULTS: During the period of study, aCL was measured in 117 patients (113 SLE and 4 PAPS), of whom 24 (20.5%) had experienced thrombotic events. The ROC AUC +/- the standard error for IgG aCL was 0.81 +/- 0.05, signifying an 81% accuracy in the identification of a history of thrombosis. In contrast, the accuracy of the IgM and IgA aCL was significantly lower (0.60 +/- 0.08 and 0.54 +/- 0.07, respectively, P < 0.05). Using stratum-specific likelihood ratios, we defined three strata in the IgG aCL scale that discriminate between patients with low, indeterminate, and high probabilities of thrombosis. For IgG aCL levels below 21.4 IgG phospholipid (GPL) U/mL, the posttest probability of thrombosis was 0.07, whereas for IgG aCL levels > or = 65.1 GPL U/mL, the posttest probability of thrombosis was 0.75. For IgG aCL values between 21.4 and 65.0 GPL U/mL, the probability of thrombosis was 0.20, equivalent to the entire cohort. CONCLUSIONS: The IgG aCL determinations perform well in the identification of thrombosis in SLE or PAPS, while the IgM and IgA aCL have poor diagnostic accuracy. These findings may have implications for management of these patients.

Adolescent↗
PubMed1995

Early onset of autoimmunity in MRL/++ mice following immunization with beta 2 glycoprotein I.

Antiphospholipid antibodies (aPL) are associated with thrombosis, thrombocytopenia and recurrent fetal loss in humans and in some animal models. Immunization with beta 2 glycoprotein I (beta 2GPI) induced aPL production in normal rabbits and mice. However, the association of these antibodies with disease manifestations remains controversial. To determine whether induction of aPL by beta 2GPI immunization in an autoimmune strain of mice (MRL/++) would result in acceleration of clinical and serological autoimmune disease manifestations, three groups of 8-week-old female mice were studied. One group was immunized with beta 2GPI, and one with ovalbumin (OVA); the third was not immunized. After two booster injections, sera were analysed for the presence of anticardiolipin (aCL) and anti-DNA by ELISA and anti-nuclear antibody (ANA) by immunofluorescence. Mice were studied for thrombocytopenia, proteinuria, fecundity rates, litter sizes and the development of central nervous system dysfunction. Elevated levels of aCL, anti-DNA and ANA were detected in all beta 2GPI-immunized, in three OVA-immunized, and in none of the unimmunized mice. The anti-DNA antibodies were inhibited by CL micelles, suggesting cross-reactivity between aCL and anti-DNA. Platelet counts, fecundity rates and litter size were reduced in beta 2GPI-immunized but not in OVA-immunized or unimmunized mice. None of the mice developed neurological dysfunction or significant proteinuria over a 10-week period post-immunization. These findings suggest that beta 2GPI immunization induces aPL in MRL/++ mice associated with accelerated autoimmune manifestations resembling the antiphospholipid syndrome.

Animals↗
PubMed1995

Model for the neuromuscular complications of systemic lupus erythematosus.

The purpose of this study is to evaluate nerve and muscle physiology and histopathology in a murine lupus model. Muscle strength, compound muscle action potentials (distal latency and amplitude), proximal limb muscle, sciatic nerve and joint specimens were studied in MRL/lpr (lupus model) and MRL/++ (control) mice. MRL/lpr mice showed decreased muscle strength (P < 10(-6, Wilcoxon rank sum), lower compound muscle action potential mean amplitude and prolonged distal latency (P = 0.005 and 0.042. Mann-Whitney U-test), and muscle and nerve inflammation (P = 0.002 and P = 0.037, Fisher's exact test) compared with MRL/++ mice. The MRL/lpr strain evaluated in this study demonstrated muscle weakness, abnormal motor nerve conduction studies and inflammation of both muscle and nerve. These features make it an excellent model for studying the neuromuscular complications of lupus.

Action Potentials↗
PubMed1994

Effects of repeated freeze-thaw cycles on anticardiolipin antibody immunoreactivity.

The effect of repeated freeze-thaw cycles on anticardiolipin antibody levels was evaluated using an enzyme-linked immunosorbent assay. Normal human serum was spiked with known quantities of freeze-dried human polyclonal anticardiolipin antibody IgG and IgM (19 samples each) or IgA (11 samples). Each spiked sample was split into four identical aliquots; one aliquot was never frozen, and the remaining three were taken through successive freeze-thaw cycles. All aliquots from each sample were evaluated on the same day using the same plate and reagents. A significant decline in mean anticardiolipin IgG levels occurred between the aliquot which had never been frozen and the one which had been through three freeze-thaw cycles (Student's t-test, P = .04). Although mean IgM and IgA values declined as well, the differences were not significant. When individual samples were evaluated the decline appeared to occur most often between the second and third freeze-thaw cycle. Eight anticardiolipin IgG and three IgM-containing samples which had been positive initially became negative by the third freeze-thaw cycle. These data show that handling and storage of serum used to perform anticardiolipin antibody assays are important potential sources of assay variability.

Antibodies, Anticardiolipin↗
PubMed1993

Soluble terminal complement components in human myasthenia gravis.

The loss of membrane acetylcholine receptor (AChR) leading to muscle weakness and impaired neuromuscular junction (NMJ) transmission in human myasthenia gravis (MG) is in part due to complement mediated muscle membrane damage. This has been supported by the histologic finding of C9 at the NMJ in human MG. We evaluated for evidence of terminal complement components in plasma by using an ELISA for SC5b-9 in 42 separate plasma samples from 31 patients with MG and from healthy controls. Abnormal elevations of SC5b-9 was found in 18 of 31 patients (58%) at one or more time points when plotted on a standard positive dilution curve. Multiple samples were available from 8 patients over time. Clinical deterioration in some, but not all, was accompanied by an increase in SC5b-9 values. There was no clear distinction in the group as a whole between MG severity or AChR antibody levels and SC5b-9 values. This supports the potential role of complement-mediated muscle membrane damage in the pathogenesis of human MG, but also demonstrates that plasma levels as measured by ELISA do not always correlate with disease activity.

Adolescent↗
PubMed1993

Neurologic complications of antiphospholipid antibodies.

Antibodies directed against phospholipids are highly associated with venous and arterial thrombotic episodes, which are often recurrent. There seems to be a skewed frequency of cerebral and ocular events when the arterial circulation is affected. Other neurologic syndromes, including dementia, migraine, chorea, transverse myelopathy, Guillain Barré syndrome, transient global amnesia, seizures, motor neuron disease, myasthenia gravis, and depression, have also been described in association with aPL. Although some of them (for example, dementia, chorea, seizures, and transient global amnesia) could well be the result of aPL-related cerebrovascular disease, the relationship of aPL to the underlying pathophysiology of these syndromes is less clear. Clues that should lead one to consider evaluating for these antibodies include recurrent thrombosis (especially in young people), recurrent fetal loss, and thrombocytopenia. Associated laboratory abnormalities may include a biologically false-positive VDRL test, abnormal ANA or anti-DNA titers, and a high ESR. If the APTT is positive on routine screening and does not correct with mixing studies, a LA should be highly suspected. More sensitive and specific tests are usually necessary to detect aPL, however. Many in vitro and, more recently, in vivo systems strongly suggest that aPL may be directly implicated in the pathogenesis of thrombosis, as opposed to being markers of a procoagulant state. The management of patients with aPL-associated thrombosis can be difficult. Prospective studies are needed to determine the optimal treatment strategies for this group of patients.

Antibodies, Antiphospholipid↗
PubMed1992

The role of antiphospholipid antibodies in stroke.

Antiphospholipid antibodies may be found in about 10% of all subjects with acute stroke but probably are present in as many as 50% of young persons with stroke and perhaps even in high prevalence in persons who have coexisting rheumatologic diseases such as SLE. In these latter groups, the association may be as high as 50%. Probably the best related syndrome is Sneddon's syndrome, which has a high prediction to dementia. Furthermore, vascular dementia may be a prominent feature of the aPL syndrome in subjects under age 55. The cause and mechanism by which aPL are related to stroke remain unknown. Likewise, there is a dearth of information about prognosis, morbidity, and stroke recurrence in subjects who have these immunoglobulin markers. Thus therapy remains very problematic, but current strategies include the use of antiaggregate therapy, warfarin, and limited implementation with prednisone and plasmaphoresis. Data that demonstrate clear cut benefit of any of these therapies are lacking. Ultimately, unraveling these crucial problems concerning the aPL syndrome may provide great insight into certain stroke mechanisms.

Autoantibodies↗
PubMed1992

Antiphospholipid antibodies: origin, specificity, and mechanism of action.

Antiphospholipid antibodies provide a model for immune-mediated thrombosis. Study of the pathophysiological effects of antiphospholipid antibodies has revealed several potential thrombotic mechanisms. Experiments designed to elucidate these mechanisms have used both in vitro and in vivo techniques. Results implicate endothelial anticoagulant dysfunction, abnormalities of prostacyclin, antithrombin III, placental anticoagulant protein, proteins C and S, and complement activation, any of which could lead to thrombosis. In an individual patient, thrombosis may result from a combination of these abnormalities or it may require the presence of other nonimmune-mediated perturbations of the coagulation system.

Animals↗