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Biomedical subjects

M D Lockshin

Publications and source records attributed to M D Lockshin.

At least 109 records · Page 6Linked to original sources

Antibody to cardiolipin as a predictor of fetal distress or death in pregnant patients with systemic lupus erythematosus.

During a prospective study of pregnancies in women with systemic lupus erythematosus, we examined the relation between antibody to cardiolipin, measured by the enzyme-linked immunosorbent assay, and midpregnancy fetal distress, identified by abnormal results of antepartum fetal heart-rate testing or by fetal death. All of nine patients with lupus and this complication had abnormally high antibody levels (mean, 212.3 +/- 55.3 units), as compared with values in normal nonpregnant women (28.2 +/- 10.1 units). None of 12 pregnant patients with lupus but without this complication had antibody levels above 50 units (mean, 27.5 +/- 3.4 units; P less than 0.005 vs. women with lupus and fetal distress); 4 of 12 pregnant subjects without lupus had antibody levels above 50 units (mean, 42.5 +/- 11.0), and fetal death occurred in the subject with the highest level. The mean antibody level in 12 nonpregnant patients with lupus was 117.4 +/- 35.0 units. Two patients who had lupus anticoagulant but not clinical lupus, both with histories of prior fetal death, also had high antibody levels; fetal death occurred in one, and spontaneous fetal bradycardia in the other. Antibody to cardiolipin was loosely linked to a history, but not the simultaneous presence, of demonstrable lupus anticoagulant or thrombocytopenia, and could be detected as early in pregnancy as either anticoagulant or thrombocytopenia. We conclude that measurement of antibody to cardiolipin is the most sensitive assay to predict fetal distress or death in patients with systemic lupus erythematosus and may be of pathogenetic importance in this syndrome.

Autoantibodies↗

Lupus pregnancy. II. Unusual pattern of hypocomplementemia and thrombocytopenia in the pregnant patient.

To explore the causes of complications in pregnant women with systemic lupus erythematosus (SLE), we prospectively evaluated 34 pregnancies in 28 SLE patients, and 2 additional pregnancies in patients with lupus anticoagulant and positive antinuclear antibody, but no other manifestations of SLE. Nineteen pregnancies (55%) were complicated by marked proteinuria, thrombocytopenia, and/or lupus anticoagulant. Hypocomplementemia occurred in 18 pregnancies (52%). Neither thrombocytopenia-anticoagulant nor proteinuria was accompanied by an increase in antibody to double-stranded DNA or by clinical signs of active SLE. Antibody to Ro antigen did not predict fetal death. Both thrombocytopenia and proteinuria appeared abruptly during pregnancy and disappeared quickly after delivery. Fetal death was the result in 7 of 9 (77%) pregnancies in patients with anticoagulant, 6 of 10 (60%) in patients with thrombocytopenia, 6 of 18 (33%) in patients with hypocomplementemia, and 3 of 11 (27%) in patients with proteinuria. Twenty of 29 (68%) children were identified as male. The pathogenesis of hypocomplementemia was evaluated by a new assay, C1s-C1 inhibitor complex, which is thought to measure rate of complement activation by the classical pathway. Most pregnant patients with low CH50 levels and proteinuria had normal levels of C1s-C1 inhibitor complex, whereas nonpregnant patients with equivalent proteinuria and hypocomplementemia had high levels, as did pregnant patients with hypocomplementemia who did not have SLE. Pregnant and nonpregnant hypocomplementemic patients with proteinuria had similar levels of C3 and C4. In pregnant patients with SLE, C1s-C1 inhibitor complex was independent of CH50; in nonpregnant patients a linear relationship between C1s-C1 inhibitor complex and CH50 was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antinuclear↗

Lupus pregnancy.

It should be obvious that our understanding of the problems of SLE pregnancy is just beginning, but that individual problems can be isolated, studied, and controlled. It should also be obvious that casual reassurance about pregnancy is never indicated; even very well patients can have major complications. All patients need to be closely monitored by both primary physician and obstetrician. Under these circumstances healthy, living babies and mothers are possible even in severely adverse circumstances.

Adrenal Cortex Hormones↗

Lupus pregnancy. Case-control prospective study demonstrating absence of lupus exacerbation during or after pregnancy.

To assess whether pregnancy is associated with exacerbation of systemic lupus erythematosus (SLE), a variety of clinical markers of disease activity in 28 pregnant patients with SLE (33 pregnancies) were compared with the same markers in age-, race-, organ system-, and disease severity-matched nonpregnant women with SLE. Both groups were followed up for periods of up to one year after delivery. Eight patients elected abortion for nonmedical reasons. In all patient groups, there were no differences between pregnant and nonpregnant patient groups in frequency of any disease activity marker studied including therapy. However, new proteinuria occurred in four pregnant patients compared with one nonpregnant patient, and thrombocytopenia attributable to SLE occurred in five pregnant patients and one nonpregnant patient. Renal disease, when it occurred, more closely resembled pregnancy-induced hypertension than lupus nephritis. It is concluded that pregnancy complications are frequent, but the assertion that pregnancy causes exacerbation of SLE remains unproved.

Abortion, Spontaneous↗

Reversible "end-stage" lupus nephritis. Analysis of patients able to discontinue dialysis.

Seventeen of 41 patients with lupus nephritis who underwent dialysis for renal failure recovered renal function and discontinued dialysis. Two of these 17 had confounding factors unrelated to lupus that contributed to renal dysfunction (one meningococcemia, one vigorous diuresis). Indications for dialysis were identical both in patients who discontinued dialysis (short-term) and in those who did not (long-term). The rate of progression to dialysis, measured as the slope of the reciprocal of the serum creatinine level versus time, was significantly more rapid in the short-term group (p less than 0.001). Patients who underwent short-term dialysis were more likely to have had lupus for less than two years (p = 0.015). Anti-DNA antibody binding values, total hemolytic complement levels, extent of extrarenal disease, and hypertension did not differentiate the short-term from long-term dialysis groups. Renal biopsy performed within three months of first dialysis did not demonstrate a consistent picture in the short-term dialysis group. Dialysis is not equivalent to irrevocable end-stage renal disease in patients with lupus nephritis. Thirteen of 22 patients (59 percent) with a 10 percent reduction time for renal function of less than three weeks were able to discontinue dialysis. Ten of these 13 were alive without need for dialysis six months later, with a mean follow-up serum creatinine level of 2.9 +/- 1.9 mg/dl.

Adolescent↗

Monocyte-induced inhibition of lymphocyte response to phytohaemagglutinin in progressive systemic sclerosis.

In patients with progressive systemic sclerosis (PSS) lymphocyte responses to phytohaemagglutinin (PHA) are abnormal (27.2 +/- 3.5 X 10(-3) counts per minute (cpm) versus 69.8 +/- 4.4 X 10(-3) for normal persons, p less than 0.005). Removal of adherent peripheral blood mononuclear cells improves the response of PSS lymphocytes (42.3 +/- 3.4 X 10(-3) cpm, 155% of control) but diminishes the response of normal lymphocytes (60.3 +/- 5.9 +/- 10(-3), 86% of control). Supernatant fluids from cultures of PSS unfractionated and adherent cells depress normal T cell response to PHA (64% and 55% of control respectively), but supernatant fluids from normal unfractionated and adherent cells do not (104% and 101% of control). Supernatant fluids of PSS and normal adherent cells, cultured in the presence of indomethacin, are not inhibitory to normal T cells (109 +/- 15% and 124 +/- 14% of control respectively). Supernatant fluids from PSS patients are more inhibitory than comparable fluids from patients with systemic lupus erythematosus (60 +/- 8% of control versus 80 +/- 5% of control). These data support the hypothesis that cellular immunity is abnormal in patients with PSS and indicate that adherent mononuclear cells mediate at least one component of the abnormality via an indomethacin-sensitive mechanism.

Dinoprostone↗

Systemic lupus erythematosus: problems in management.

The management of the SLE patient is never routine. Each patient presents a complex set of biochemical, pathophysiological, emotional, and sociological problems that undulate in unpredictable ways, and challenge every physician.

Adolescent↗

Systemic lupus erythematosus in men. Genetic and endocrine features.

Sixteen men with systemic lupus erythematosus (SLE) were examined to assess their genetic and hormonal status. The results of buccal smears in 13 patients examined were normal. Hormonal profiling was done in eight patients receiving no steroid therapy. Four patients had elevated plasma estradiol levels (30, 35, 55, and 103 pg/mL; normal, 12 to 23 pg/mL) and elevated plasma estrone levels (115, 150, 155, and 160 pg/mL; normal, 48 to 100 pg/mL). One patient had a decreased serum testosterone level (134 ng/dL; normal, 300 to 1,000 ng/dL), with an elevated luteinizing hormone (LH) level (4.2 ng/mL; normal, 1.6 to 4.0 ng/mL). One patient had an elevation in both levels of serum follicle-stimulating hormone (17.6 ng/mL; normal, 1 to 5 ng/mL) and LH (10.0 ng/mL). Two patients given infusions of 3H-androstenedione and 14C-testosterone had normal findings from kinetic studies of these hormones. Hyperestrogenemia and hypoandrogenemia observed in some men with SLE suggest that female sex hormones may create an immunologic milieu that facilitates the autoimmune phenomena.

Adolescent↗

Rheumatology education in United States medical school.

Although rheumatology manpower in United States medical schools has dramatically increased in the past decade, 13% of medical schools did not have a full-time staff rheumatologist in 1980. Thirty-eight percent of medical schools had 2 or less full-time rheumatologists. Staff rheumatologists and rheumatology fellows provided the majority of medical student education in the clinical aspects of rheumatic disease; however, rheumatologists in less than 50% of medical schools taught in the basic science curriculum or in related fields such as collagen biochemistry, metabolic bone disease, and orthopedic intervention in arthritis. The staff rheumatologists' time commitment to medical student education was inversely proportional to the rheumatology faculty size. At medical schools with no rheumatologists, however, there was little, if any, formal education in the rheumatic diseases. Most subjects are taught in systems-oriented lectures. Education is currently limited to the common rheumatic conditions such as bursitis and back pain. Only 62% of medical schools provide a structured course on the musculoskeletal examination. Elective rotations in rheumatology, usually offered in the third or fourth year, are currently being provided to only 15% of U.S. medical students.

Curriculum↗

High-dose intravenous methylprednisolone pulse therapy in systemic lupus erythematosus.

To determine guidelines for treatment with high-dose intravenous methylprednisolone in lupus nephritis, we prospectively assessed the response to pulse therapy in 34 patients. In 12 of them, serum creatinine decreased by at least 20 percent within two months of treatment whereas in the remaining 22 there was no such response. Patients who responded were characterized by recent deterioration in function whereas nonresponders had had a more stable antecedent course (p = 0.003). Responders also had more diffuse lesions on renal biopsy (p = 0.028), had higher levels of anti-DNA antibodies (p less than 0.05), and tended to have higher titers of immune complexes and lower total hemolytic complement. High-dose intravenous methylprednisolone therapy may lead to striking improvement in renal function in lupus nephritis, especially in the subset of patients with recent antecedent functional deterioration. This improvement was maintained in 60 percent of the patients who responded for at least six months.

Adolescent↗