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Biomedical subjects

E N Harris

Publications and source records attributed to E N Harris.

At least 91 records · Page 5Linked to original sources
PubMed1990

Recurrent adverse pregnancy outcome and antiphospholipid antibodies.

Antiphospholipid antibodies, which include lupus-like anticoagulant and anticardiolipin antibody, have been linked to a number of adverse pregnancy outcomes, although their exact pathogenic mechanisms remain poorly defined. The relative risk of complications such as intrauterine growth retardation, spontaneous abortions, and stillbirth in patients with antiphospholipid antibodies also remains undetermined. Heightened attention has been focused on the association, leading to investigations into the pathogenesis. Uncontrolled studies have also explored therapeutic regimens such as aspirin, steroids, and heparin, and clinical trials have used various treatment protocols. Although knowledge into the association of antiphospholipid antibodies and recurrent adverse pregnancy outcome is limited and continues to evolve, this association provides new insights into the disease and offers promise for pharmacologic prophylaxis. In this article, current concepts on pathogenesis, diagnosis, and therapy are reviewed and recommendations are made for clinical care of these patients.

Adrenal Cortex Hormones↗
PubMed1990

Maternal autoantibodies and pregnancy--I: The antiphospholipid antibody syndrome.

Despite the considerable interest in antiphospholipid antibodies during the last 10 years, the clinical disorders with which they are associated are still not well understood (Love and Santoro, 1990). The concept of the antiphospholipid syndrome (APS) and a means by which this can be defined (Harris, 1987) may aid us in better classifying these patients, evaluating their clinical features, and in conducting prospective studies. Standard methods for measurement of anticardiolipin antibodies (Harris et al, 1987b; Harris and the Kingston Anticardiolipin Standardization Group, 1990) and more attention to measurement of the lupus anticoagulant (Triplett and Brandt, 1988) will ultimately play an important role in improving the diagnosis of these patients. The initiation of the Kingston AntiPhospholipid Study (KAPS) group in January 1988 paves the way for future multicentre treatment trials of these patients (Harris, 1988; Triplett, 1989; Recker and Leff, 1989). For the practising physician managing a pregnant woman with the APS, there are few clear guidelines for treatment. An appropriate approach would be to assemble a multidisciplinary team for pregnancy management, exclude other causes of pregnancy loss and select the drug regimen which will cause the least harm and has some reported efficacy. Most importantly, the patient should be followed carefully throughout her pregnancy.

Abortion, Spontaneous↗
PubMed1990

Special report. The Second International Anti-cardiolipin Standardization Workshop/the Kingston Anti-Phospholipid Antibody Study (KAPS) group.

Forty-three laboratories in 13 countries participated in a workshop to determine the degree of agreement between laboratories performing anticardiolipin tests. Each laboratory received freeze-dried aliquots of three samples labeled G1 (107 GPL units), G2 (20 GPL units), and G3 (6 GPL units) to be used as reference standards in the IgG assay, and three samples labeled M1 (106 MPL units), M2 (21 MPL units), and M3 (5 MPL units) as references for the IgM assay. Participating laboratories were divided into 8 groups and serum samples were exchanged between laboratories in each group. For IgG anticardiolipin, results were reported as: high, IgG positive for samples with optical absorbance readings exceeding G1; medium, IgG positive for samples with readings between G1 and G2; low, IgG positive between G2 and G3, and negative, if less than G3. In like manner, samples were defined as high-, medium-, or low-IgM positive, with reference to standards M1, M2, and M3. An index of agreement was computed to determine the degree of agreement between laboratories in each group. Interlaboratory agreement was excellent in each category assessed. For high positive and negative IgG and IgM results, the index of agreement exceeded 90%, and for medium and low positive results, agreement exceeded 75%. The overall index of agreement between laboratories exceeded 90%. The researchers conclude that the use of these six standards to obtain a semiquantitative measure of anticardiolipin positivity will enable good interlaboratory agreement in reporting anticardiolipin results.

Antibodies↗
PubMed1989

Mortality of Jamaican patients with systemic lupus erythematosus.

A retrospective study of all patients with systemic lupus erythematosus (SLE) who died at the University Hospital of the West Indies over a 14-year period is presented. The major cause of death was infection followed by renal failure. Gram-negative organisms were the major microbiological agents causing infections. Side-effects of therapy were common, in particular bone marrow depression and haemorrhage related to anticoagulants. It appears that controlling severe lupus activity without increasing the risk of lifethreatening complications remains an important goal in the treatment of SLE.

Acute Kidney Injury↗
PubMed1989

Antibody to phosphatidylethanolamine in a patient with lupus anticoagulant and thrombosis.

Most patients with lupus anticoagulant (LA) activity have coincident antibodies to a group of negatively charged phospholipids, and its is suggested that LA and anticardiolipin tests detect antibodies with overlapping specificities. Some discordance between the two assays has been described, however. One patient presenting with severe thrombotic disease (recurrent deep vein thrombosis, pulmonary embolism, inferior venocaval obstruction, myocardial infarction, and digital gangrene) showed strong LA activity in February 1987. An enzyme linked immunosorbent assay (ELISA) showed no binding to the negatively charged phospholipids cardiolipin, phosphatidylserine, and phosphatidic acid, but binding to zwitterionic phosphatidylethanolamine (PE) was demonstrated. Inhibition studies and affinity purification confirmed this finding. Interestingly, the serum did not bind to the kaolin cephalin clotting time reagent when used as antigen in an ELISA. The pathogenic significance of anti-PE antibodies and their relation to LA remains to be clarified. Further studies of the occurrence of anti-PE antibodies in patients with LA activity who have negative anticardiolipin tests are suggested.

Autoantibodies↗
PubMed1989

Antiphospholipid antibodies: a risk factor for occlusive ocular vascular disease in systemic lupus erythematosus and the 'primary' antiphospholipid syndrome.

Seven cases of occlusive ocular vascular disease affecting retinal and choroidal vessels were found among 84 consecutive patients with raised levels of anticardiolipin antibodies attending the lupus arthritis clinic at St Thomas's Hospital from 1985 to 1987. Six patients with systemic lupus erythematosus (SLE) and one with a 'primary antiphospholipid syndrome' had occlusive ocular vascular disease affecting a variety of vessels. This gives a prevalence of occlusive ocular vascular disease of 8% in this subgroup of patients, significantly higher than the 0.5-2.0% previously reported in patients with SLE. Four of these patients also suffered from cerebrovascular disease, supporting the previously documented association between occlusive ocular vascular disease and central nervous system disease in SLE. Additionally, other features of the antiphospholipid syndrome were frequently present. These findings suggest that patients with SLE and raised anticardiolipin antibodies have a higher risk of developing occlusive ocular vascular disease than has been previously reported.

Adult↗
PubMed1989

Anticardiolipin antibody levels in diabetic subjects with and without coronary artery disease.

Moderate (greater than 20 units) and high (greater than 80 units) IgG anticardiolipin antibody (aCL) titres are strongly predictive for recurrent thrombosis and early myocardial infarction in non-diabetic subjects. We have tested the hypothesis that the excess risk of myocardial infarction in diabetic subjects relates to the presence of aCL by measuring the frequency and titre of aCL in two groups of diabetic subjects and in 2500 healthy controls. One non-diabetic subject (0.04%) had low (5-20 units) IgG aCL titres. Seven out of 126 diabetics without cardiovascular disease (5.6%) and 9 out of 79 diabetics who were either myocardial infarction survivors or who had angiographically-proven coronary artery disease (11.4%) had low aCL titres (P less than 0.01 for comparison of either diabetic group with controls, and P less than 0.1 for comparison between diabetic groups). One subject in each diabetic group, but no non-diabetics, had moderate IgM aCL titres. No subjects had high aCL titres. Diabetics have an increased frequency of low aCL titres which may relate to macrovascular disease. Macrovascular disease in diabetics is not associated with moderate or high aCL titres.

Cardiolipins↗
PubMed1989

The "primary" antiphospholipid syndrome: major clinical and serological features.

The antiphospholipid syndrome--the association of venous and/or arterial thromboses, often accompanied by thrombocytopenia in the presence of the antiphospholipid antibodies ("lupus anticoagulant" antibodies to cardiolipin)--is seen mainly in patients with systemic lupus erythematosus (SLE) and the closely related "lupus-like" disease, i.e., lupus patients not conforming to the 1982 revised American Rheumatism Association classification for SLE. It is also seen in a group of patients who do not manifest any of the major clinical or serologic features of SLE, the majority of whom do not appear to progress to classical lupus. A multicenter study of 70 of these patients is documented and their major clinical and serologic characteristics examined: They have been characterized as suffering from a "primary" antiphospholipid syndrome and present typically with a history of deep vein thromboses, often accompanied by pulmonary thromboembolism, which in a few is complicated by thromboembolic pulmonary hypertension, arterial occlusions (most commonly strokes), or fetal loss. The events are often recurrent and may be accompanied by hemocytopenias (thrombocytopenia and less frequently Coombs positivity and/or hemolytic anemia). They are often antinuclear antibody-negative and are always negative for antibodies to dsDNA and to ENA, typical serologic features of SLE. There may be a family history of SLE or a familial clotting tendency in a minority. The group of patients presented appears to be closely related, but distinctly separate from SLE.

Adult↗
PubMed1988

Anticardiolipin antibodies in Lyme disease.

Sera from 28 patients with Lyme disease were tested for the presence of anticardiolipin antibodies (ACLA). Seven serum samples had elevated levels of IgM ACLA, and 4 had elevated levels of IgG ACLA. Higher IgM ACLA positivity tended to be associated with neurologic disease, and IgM ACLA levels correlated with the specific IgM response to the infecting spirochete (P less than 0.01). Absorption experiments indicated that ACLA and antispirochete antibodies are largely separate populations. Thus, ACLA may occur in patients with Lyme disease, particularly in those with neurologic abnormalities, and the production of these antibodies seems to be linked to the specific IgM response.

Adult↗
PubMed1988

Use of an enzyme-linked immunosorbent assay and of inhibition studies to distinguish between antibodies to cardiolipin from patients with syphilis or autoimmune disorders.

We report a VDRL-enzyme-linked immunosorbent assay (ELISA) that enabled us to distinguish between the antibodies to cardiolipin from patients with autoimmune disorders and those from patients with syphilis. Additional studies using inhibition experiments with phospholipid liposomes, as well as ELISAs with a variety of phospholipid antigens, showed that antibodies to phospholipids from patients with syphilis bind cardiolipin (best when presented as the VDRL antigen) but exhibited little cross-reactivity with negatively charged phospholipids. On the other hand, antibodies to phospholipids from patients with autoimmune disorders exhibited little or no binding to the VDRL antigen but cross-reacted with both cardiolipin and negatively charged phospholipids. These findings may explain why antibodies to phospholipids only from patients with autoimmune disorders may have lupus anticoagulant activity and why they are associated with thrombosis, fetal loss, and thrombocytopenia.

Antibodies↗
PubMed1988

Immune mediated mechanism for thrombosis: antiphospholipid antibody binding to platelet membranes.

Because thrombocytopenia occurs frequently in patients with anticardiolipin (aCL) antibodies and thrombosis, some investigators have proposed that aCL antibodies may play a direct part in thrombosis by binding and activating platelets. To test this proposal experiments were performed to determine whether aCL antibodies can bind platelets. Preincubation of aCL positive sera with freeze-thawed platelets caused significant inhibition of aCL activity in four serum samples tested. Antibodies with cardiolipin binding activity were subsequently eluted from these platelets. Total phospholipids extracted from platelets inhibited aCL activity, and the specific phospholipids bound were shown to be phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. It is concluded that aCL antibodies can bind phospholipids in platelet membranes but pertubation of the membrane must first occur.

Antibodies↗
PubMed1988

IgG subclass and light chain distribution of anticardiolipin and anti-DNA antibodies in systemic lupus erythematosus.

The IgG subclass and light chain distribution of anticardiolipin and anti-DNA antibodies were determined in serum samples from patients with systemic lupus erythematosus. With an enzyme linked immunosorbent assay (ELISA) and mouse monoclonal antibodies to individual subclasses, significant differences in the distributions of IgG2, IgG3, and IgG4 subclasses were observed between anticardiolipin and anti-DNA antibodies. Whereas anti-DNA antibodies were predominantly IgG1 and IgG3, all subclasses of anticardiolipin were detected with a prevalence ranging from 34% (IgG3) to 57% (IgG1). Clinical complications were found slightly more frequently (83%) in patients with sera containing the non or weak complement fixing subclasses (IgG2 and IgG4) than in patients with sera containing complement fixing (IgG1 and IgG3) subclasses (62%). Light chain analysis by ELISA showed a trend towards use of kappa chains for anti-DNA and lambda chains for anticardiolipin antibodies. These findings further emphasise the differences between anti-DNA and anticardiolipin antibodies in terms of their origins and potential mechanisms for producing tissue injury.

Antibodies, Antinuclear↗