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M D Lockshin

Publications and source records attributed to M D Lockshin.

At least 19 recordsLinked to original sources
PubMed2006

International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).

New clinical, laboratory and experimental insights, since the 1999 publication of the Sapporo preliminary classification criteria for antiphospholipid syndrome (APS), had been addressed at a workshop in Sydney, Australia, before the Eleventh International Congress on antiphospholipid antibodies. In this document, we appraise the existing evidence on clinical and laboratory features of APS addressed during the forum. Based on this, we propose amendments to the Sapporo criteria. We also provide definitions on features of APS that were not included in the updated criteria.

Antibodies, Antiphospholipid↗
PubMed2006

Treating rheumatic diseases in pregnancy: dos and don'ts.

This paper presents a critical appraisal of the current evidence and recommendations regarding the use of pharmaceuticals and biologicals in pregnancy. Clinical experience is often at variance with published recommendations as studies have not taken into account the differences in physiology in the various stages of gestation and between animal and human pregnancies. Physicians should bear in mind that pregnancy causes disruption in several organ systems; the effects of an intervention may depend on the stage of gestation; and some effects of interventions in pregnancy may not manifest until adulthood.

Antirheumatic Agents↗
PubMed2006

Sex differences in autoimmune disease.

Female/male ratios of autoimmune diseases range from 10:1 to 1:3, with similar severity between the sexes. Men and women respond similarly to the infection and to vaccination, arguing against intrinsic sex differences in immune response. In autoimmune-like illnesses caused by environmental agents sex discrepancy is explained by differences in exposure. Endogenous hormones could cause sex discrepancy if their effect is a threshold off-on switch rather than quantitatively variable. X-inactivation and imprinting could cause sex discrepancy. Other possibilities include chronobiologic differences and pregnancy and menstruation biologies in which men differ from women.

Animals↗
PubMed2005

Real world experience with antiphospholipid antibody tests: how stable are results over time?

OBJECTIVE: To determine the stability and the degree of variation of antiphospholipid antibody (aPL) results over time in a large cohort of well evaluated aPL positive patients; and to analyse factors contributing to aPL variation and the validity of aPL in a real world setting in which aPL tests are done in multiple laboratories. METHODS: The clinical characteristics, drug treatment, and 1652 data points for lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-beta2 glycoprotein I antibodies (anti-beta2GPI) were examined in 204 aPL positive patients; 81 of these met the Sapporo criteria for antiphospholipid syndrome (APS) and 123 were asymptomatic bearers of aPL. RESULTS: 87% of initially positive LA results, 88% of initially negative to low positive aCL results, 75% of initially moderate to high positive aCL results, 96% of initially negative to low positive anti-beta2GPI results, and 76% of initially moderate to high positive anti-beta2GPI results subsequently remained in the same range regardless of the laboratory performing the test. Aspirin, warfarin, and hydroxychloroquine use did not differ among patients whose aCL titres significantly decreased or increased or remained stable. On same day specimens, the consistency of aCL results among suppliers ranged from 64% to 88% and the correlation ranged from 0.5 to 0.8. Agreement was moderate for aCL IgG and aCL IgM; however, for aCL IgA agreement was marginal. CONCLUSIONS: aPL results remained stable for at least three quarters of subsequent tests, regardless of the laboratory performing the test; the small amount of variation that occurred did not appear to be caused by aspirin, warfarin, or hydroxychloroquine use.

Adult↗
PubMed2005

Cardiac involvement in the antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease, associated with a hypercoagulable state and fetal loss and with other clinical manifestations including cardiac involvement. Cardiac manifestations of APS are valve abnormalities (valve thickening and vegetations), occlusive arterial disease (atherosclerosis and myocardial infarction), intracardiac emboli, ventricular dysfunction, and pulmonary hypertension. Antiphospholipid antibodies (aPLs) may have a role in the accelerated atherosclerotic arterial disease observed in APS, related to their ability to induce endothelial activation. aPLs have been incriminated in the pathogenesis of heart valve lesions in APS patients. Markers of endothelial cell activation are up-regulated with prominent deposition of aPL in heart valves, suggesting aPL deposition initiates an inflammatory process that recruits complement leading to the valve lesion. Autoantibody-mediated endothelial cell activation probably plays a role in sustaining a proadhesive, proinflammatory, and procoagulant phenotype. The heterogeneity of APS clinical manifestations is likely linked to the varied effects that aPL can induce on endothelial cells and to the different functions that endothelial cells display depending on the anatomic localization.

Antibodies, Antiphospholipid↗
PubMed2004

Measuring systemic lupus erythematosus activity during pregnancy: validation of the lupus activity index in pregnancy scale.

OBJECTIVE: To validate the Lupus Activity Index in Pregnancy (LAI-P) scale as a diagnostic tool for lupus flares during pregnancy and the puerperium. METHODS: The LAI-P is a modified activity scale specific for pregnancy. Thirty-eight pregnant women with systemic lupus erythematosus (SLE) were prospectively followed in 3 clinics specific for lupus in pregnancy. On each visit, LAI-P was calculated. A modified physician global assessment (m-PGA) scale was used as gold standard (0 = no activity, 1 = mild-moderate activity, 2 = severe activity). A change > or = 0.25 in LAI-P was predefined as a flare according to previous studies in nonpregnant patients. For the purposes of the study, each visit was considered as an independent case. RESULTS: During the study period, 158 visits took place for a total 621 patient-weeks. Sensitivity to change was high (standardized response mean for LAI-P = 1.6). We found a significant association between LAI-P and m-PGA (P < 0.002 in all regression models performed). Sensitivity, specificity, and positive and negative predictive values were 0.93, 0.98, 0.88, and 0.99. Positive and negative likelihood ratios were 49 and 0.07, respectively. CONCLUSIONS: LAI-P has a high sensitivity to changes in lupus activity, a significant correlation with m-PGA, and high sensitivity, specificity, predictive values, and likelihood ratios for diagnosing SLE flares during pregnancy and the puerperium.

Adult↗
PubMed2004

Autoimmunity, infertility and assisted reproductive technologies.

Despite strongly held opinions, a trustworthy scientific basis for most statements about autoimmunity, autoimmune diseases and assisted reproductive technologies (ART) does not exist. It is not likely that autoimmunity causes infertility, nor that patients with autoimmune diseases are unusually infertile. When carefully monitored in selected patients, ART does not appear to harm patients who have pre-existing autoimmune diseases, but the ovarian hyperstimulation syndrome and multiple gestation pregnancies impart independent risks. Stable autoimmune diseases without major organ damage probably do not affect the outcomes of ART pregnancies. Children born of ART pregnancies are apparently normal at birth, whether or not the genetic or birth mother has autoimmune disease, but long-term follow-up is not available. Male fertility is probably not altered by autoimmune disease. Fiscal, ethical and moral issues related to ART in patients with autoimmune diseases are beyond the scope of this discussion but remain important.

Autoimmune Diseases↗
PubMed2003

Long term outcome of catastrophic antiphospholipid syndrome survivors.

BACKGROUND: Catastrophic antiphospholipid syndrome (APS) is defined as life threatening multiple organ thromboses developing simultaneously or over a short period. The survival rate of catastrophic APS is about 50%, but the long term outcome of patients who survive is unknown. OBJECTIVE: To determine the long term outcome of patients with catastrophic APS and provide further information on patients who survived. PATIENTS AND METHODS: The clinical characteristics and outcomes of 130 patients with catastrophic APS have been reported previously. Six new cases were recently added to this series. Based on these publications, the authors who reported patients who had survived were contacted. Each author was asked (a) what treatment they gave their patients after the catastrophic APS; (b) if their patients had any further thrombosis. RESULTS: 63/136 (46%) patients died at the initial event. Of the remaining 73 patients, information was available for 58 (79%). Thirty eight (66%) patients did not develop further APS related events during an average follow up of 67.2 months. Eleven (19%) patients developed further APS related events but were still alive. No patients developed further catastrophic APS. Nine (16%) patients died: due to multiple organ failure (three patients); myelofibrosis (one); pneumonia (one); and APS related events (four). CONCLUSION: Sixty six per cent of patients who survive an initial catastrophic APS event remained symptom free with anticoagulation during an average follow up of 67.2 months. Twenty six per cent of the survivors developed further APS related events and the mortality rate of these patients was about 25%.

Adolescent↗
PubMed2002

A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome.

OBJECTIVE: Antiphospholipid antibodies (aPL) are major risk factors for thrombosis. Other clinical factors exist in antiphospholipid syndrome (APS) patients which may have an additive or preventive effect on thrombosis. We therefore performed a cross-sectional study to analyse additive clinical thrombotic risk factors and possible preventive treatments in APS patients, and to compare the results with those obtained in asymptomatic aPL-positive (no history of vascular thrombosis or pregnancy morbidity) patients. METHODS: We identified 77 APS patients with non-gravid thrombotic events (group A) and 56 asymptomatic aPL-positive patients (group B). The study periods were defined as 6 months prior to the time of first vascular event in group A and 6 months prior to the patient's last visit in group B. Medical records were reviewed to evaluate the incidence of hypertension, diabetes mellitus, hypercholesterolaemia, regular cigarette smoking, oral contraceptive use or hormone replacement therapy, surgical procedures, pregnancy with or without an APS-related event, malignancy and infections. In addition, any history of thrombocytopenia or the use of aspirin, hydroxychloroquine, corticosteroids or immunosuppressives during the study periods was recorded. Bivariate statistical analysis and logistic regression tests were performed to compare groups. RESULTS: In group A, 75% (n=58) of patients and in group B 48% (n=27) of patients had at least one of the additional risk factors during the study periods. In the bivariate analysis, pregnancy (P=0.005) and surgical procedures (P=0.04) were significantly more frequent in group A, while aspirin (P<0.001), hydroxychloroquine (P<0.001) and corticosteroids (P=0.002) were used significantly more frequently in group B. In logistic regression, the probability of an event was decreased by taking aspirin and/or hydroxychloroquine. In women only, the probability of an event was increased with thrombocytopenia and pregnancy or surgical procedures. The incidences of hypertension and smoking and the presence of more than one risk factor were significantly associated with arterial thrombosis but not venous thrombosis. CONCLUSION: While traditional risk factors were similar between groups, pregnancy and surgical procedures increased the risk of thrombosis. Hypertension and smoking were associated with arterial events. Possessing a combination of risk factors may increase the occurrence of arterial thrombosis but not venous thrombosis. Use of aspirin and/or hydroxychloroquine may be protective against thrombosis in asymptomatic aPL-positive individuals.

Antiphospholipid Syndrome↗
PubMed2002

Sex ratio and rheumatic disease: excerpts from an Institute of Medicine report.

Some autoimmune diseases have high female/male (F/M) ratios. Definitions and classifications of autoimmune diseases differ, as do the F/M ratios themselves. The sex ratio of lupus is the single most prominent, little explored clinical fact that may lead to understanding of how lupus and other autoimmune diseases occur. The objective of this study was to evaluate evidence for causes of high F/M ratios of autoimmune and non-immunologic diseases. This was done by a literature review. Some thyroid, rheumatic and hepatic diseases consistently have high F/M ratios; other autoimmune diseases have low ratios. Because F/M ratios reflect disease incidence, not disease severity, an intrinsic biologic cause for the F/M ratios (such as estrogen) would be likely to act through a threshold or permissive mechanism rather than through quantitative immunomodulation. Sex differences related to environmental exposure, X-inactivation, imprinting, X or Y chromosome genes and intrauterine influences are other possible explanations for sex differences of incidence. The epidemiology of the sex discrepant autoimmune diseases, young, female, suggests that an explanation for sex discrepancy lies in differential exposure, vulnerable periods or thresholds, rather than in quantitative aspects of immunomodulation.

Behavior↗
PubMed2001

Prevalence and relation to risk factors of carotid atherosclerosis and left ventricular hypertrophy in systemic lupus erythematosus and antiphospholipid antibody syndrome.

The prevalence of preclinical cardiovascular disease was determined in women with systemic lupus erythematosus (SLE) and control subjects matched for traditional risk factors. Compared with control subjects, patients with SLE had a higher prevalence of carotid atherosclerosis (41% vs 9%, p < 0.005) and left ventricular hypertrophy (32% vs 5%, p < 0.005), supporting the possibility that chronic inflammation predisposes to premature cardiovascular disease in SLE.

Adult↗
PubMed2001

Invited review: sex ratio and rheumatic disease.

Human illnesses affect men and women differently. In some cases (diseases of sex organs, diseases resulting from X or Y chromosome mutations), reasons for sex discrepancy are obvious, but in other cases no reason is apparent. Explanations for sex discrepancy of illness occur at different biological levels: molecular (e.g., imprinting, X-inactivation), cellular (sex-specific receptor activity), organ (endocrine influences), whole organism (size, age), and environmental-behavioral, including intrauterine influences. Autoimmunity represents a prototypical class of illness that has high female-to-male (F/M) ratios. Although the F/M ratios in autoimmune diseases are usually attributed to the influence of estrogenic hormones, evidence demonstrates that the attributed ratios are imprecise and that definitions and classifications of autoimmune diseases vary, rendering at least part of the counting imprecise. In addition, many studies on sex discrepancy of human disease fail to distinguish between disease incidence and disease severity. In April 2001, the Institute of Medicine of the National Academy of Sciences published Exploring the Biological Contributions to Human Health: Does Sex Matter? (Wizemann T and Pardue M-L, editors). This minireview summarizes the section of that report that concerns autoimmune and infectious disease. Some thyroid, rheumatic, and hepatic autoimmune diseases have high F/M ratios, whereas others have low. Those that have high ratios occur primarily in young adulthood. Gonadal hormones, if they play a role, likely do so through a threshold or permissive mechanism. Examples of sex differences that could be caused by environmental exposure, X inactivation, imprinting, X or Y chromosome genetic modulators, and intrauterine influences are presented as alternate, theoretical, and largely unexplored explanations for sex differences of incidence. The epidemiology of autoimmune diseases (young, female) suggests that an explanation for sex discrepancy of these illnesses lies in differential exposure, vulnerable periods, or thresholds. Biologists have an opportunity to inform medical scientists about sex differences that explain different attack rates in specific diseases, and physicians offer biologists experiments of nature to test theories of sex.

Animals↗
PubMed2001

Sex ratio and rheumatic disease.

Autoimmune diseases are said to have high female/male (F/M) ratios, but these ratios are imprecise. Published definitions and classifications of autoimmune diseases differ substantially, as do the F/M ratios themselves. Imputed causality of autoimmune diseases requires better precision. Some thyroid, rheumatic and hepatic diseases consistently have high F/M ratios, but marked differences exist in the reported quantity of the ratios. Other autoimmune diseases have low F/M ratios. Because F/M ratios reflect incidence and not severity of disease, gonadal hormones, if they play a role, must do so through a threshold or permissive mechanism. Sex differences related to environmental exposure, X-inactivation, imprinting, X or Y chromosome genetic modulators, and intrauterine influences remain as alternate, theoretical, explanations for sex differences of incidence. The epidemiology of the sex-discrepant autoimmune diseases--young, female--suggests that an explanation for sex discrepancy lies in differential exposure, vulnerable periods, or thresholds, rather than in quantitative aspects of immunomodulation.

Age Factors↗
PubMed2000

Validation of the Sapporo criteria for antiphospholipid syndrome.

OBJECTIVE: To test the Sapporo criteria for the classification of the antiphospholipid syndrome (APS). METHODS: We classified 243 consecutive patients who had clinical diagnoses of primary APS (n = 49), secondary APS (n = 26), systemic lupus erythematosus (SLE) without clinical APS (n = 131), and lupus-like disease without clinical APS (n = 37). RESULTS: Sensitivity, specificity, positive predictive value, and negative predictive value were 0.71, 0.98, 0.95, and 0.88, respectively. False-negative findings were the result of patients being classified on the basis of minor criteria that were not included in the Sapporo criteria, such as livedo reticularis, thrombocytopenia, low-titer IgG or IgM anticardiolipin antibody, IgA anticardiolipin antibody, and anti-beta2-glycoprotein I antibody. Some patients with false-negative results were true seronegative cases. CONCLUSION: The Sapporo criteria for APS compare favorably with the American College of Rheumatology criteria for SLE and are usable for clinical studies.

Adult↗