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Biomedical subjects

M B Urowitz

Publications and source records attributed to M B Urowitz.

At least 19 recordsLinked to original sources
PubMed1992

Impairment of left ventricular diastolic function in systemic lupus erythematosus.

Left ventricular (LV) diastolic performance was evaluated with pulsed-wave Doppler echocardiography in a cross-sectional population of patients with systemic lupus erythematosus (SLE) in search of subclinical myocardial involvement. Such involvement is reported to occur infrequently, despite pathohistologic evidence of myocarditis in up to 70% of patients with SLE. Thirty-five consecutive patients with SLE were evaluated, 14 with active and 21 with inactive disease, and were compared with 30 age-matched healthy control subjects. Twenty-six patients were restudied at 7 months. All had normal LV systolic function, normal pericardial and valvular structures, and no significant valvular regurgitation on Doppler echocardiography. In SLE patients with active disease, indexes of LV diastolic function differed significantly from the inactive group and from control subjects, with marked prolongation of isovolumic relaxation time (104 +/- 18 vs 74 +/- 13 ms, p = 0.0001), as well as reduced peak early diastolic filling velocity (E) (0.69 +/- 0.19 vs 0.83 +/- 0.17 ms, p = 0.01), reduced ratio of early to late diastolic flow velocity (E/A) (1.15 +/- 0.53 vs 1.47 +/- 0.35, p = 0.02), and prolonged mitral pressure halftime (74 +/- 14 vs 65 +/- 8 ms p = 0.01). Similar significant differences were found between the active and inactive SLE patient groups. SLE patients with inactive disease differed from control subjects in only mild prolongation of mitral pressure halftime. Abnormal prolongation of isovolumic relaxation (greater than 100 ms) was found to be the most useful marker of diastolic impairment, being present in 64% of SLE patients with active disease and in 14% of patients with inactive disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE.

OBJECTIVE: To standardize outcome measures in systemic lupus erythematosus (SLE). Three indices were identified which could adequately describe outcome (disease activity, damage from disease, and health status); we describe here the development of the Disease Activity Index. METHODS: Twenty-four variables were identified as important factors in a disease activity index. These were used to generate 574 patient profiles, which were rated on a disease activity scale of 0-10 by 14 rheumatologists. A second rating of 10 of the profiles yielded scores that were not significantly different from the first, indicating that experienced clinicians can reliably make global estimates of disease activity. Multiple regression models were used to estimate the relative importance of the 24 clinical variables in the physicians' global rating of disease activity. These were estimated on a "training set" of 75% of physicians' ratings, and then validated on a "testing set," consisting of the remaining 25% of physicians' ratings. RESULTS: The explanatory power of the models in the training set was high (R2 = 0.93). The models' regression coefficients for the organ systems were simplified for easier use in clinical practice. This generated a "weighted" index of 9 organ systems for disease activity in SLE, the SLEDAI, as follows: 8 for central nervous system and vascular, 4 for renal and musculoskeletal, 2 for serosal, dermal, immunologic, and 1 for constitutional and hematologic. The maximum theoretical score is 105, but in practice, few patients have scores greater than 45. The SLEDAI predicted well the physicians' ratings in the testing set (Pearson's correlation coefficients = 0.64-0.79). CONCLUSION: The SLEDAI is a validated model of experienced clinicians' global assessments of disease activity in lupus. It represents the consensus of a group of experts in the field of lupus research.

Central Nervous System↗
PubMed1992

Comparison of azathioprine, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial.

OBJECTIVE: To compare the relative safety and efficacy of azathioprine (AZA), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). METHODS: Two hundred twelve patients with active RA were entered into a 24-week prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. RESULTS: One hundred fifty-eight patients finished 24 weeks of the study. There were no remissions seen but response rates were greater than 30% for all outcome measures. Combination therapy was not statistically superior to MTX therapy alone, but both combination therapy and MTX alone were superior to AZA alone when patients were analyzed by intent-to-treat and with withdrawals treated as therapy failures. If only patients who continued taking the therapy were analyzed, the mean improvement was greater for AZA therapy than for MTX, while the combination remained the most active. Adverse effects on the gastrointestinal tract and elevations of liver enzyme levels were the most frequent causes for discontinuations. CONCLUSION: Both combination therapy and MTX alone were superior to therapy with AZA alone for active RA but were not statistically different in their effect on outcome assessment.

Adult↗
PubMed1992

Peripheral vascular disease in patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus may develop premature atherosclerosis, notably coronary artery disease. A group of 10 patients with peripheral vascular disease presenting with intermittent claudication or gangrene were studied from a group of 563 patients followed prospectively at the Wellesley Hospital Lupus Clinic. These 10 patients were compared with the next lupus clinic patient matched for age and sex, with respect to demographic characteristics and risk factors. The patients and controls did not differ significantly in lupus activity criteria count, partial thromboplastin time, the number with antibody to cardiolipin, number receiving steroids or mean steroid dose, family history of atherosclerosis, hyperlipidaemia, smoking, hypertension or use of oral contraceptives. The risk factors for developing peripheral vascular disease were a longer duration of systemic lupus erythematosus and a longer duration of use of steroids. Eight of the 10 patients had coexistent coronary artery disease or transient ischaemic attack.

Adult↗
PubMed1992

The "shrinking lungs syndrome" in systemic lupus erythematosus--improvement with corticosteroid therapy.

A 35-year-old woman had a 13-year history of systemic lupus erythematosus (SLE) with recurrent flares since 1972 responding to corticosteroid therapy. In August, 1990 she presented with a 2-month history of dyspnea at rest, 4-pillow orthopnea and paroxysmal nocturnal dyspnea. Respiratory rate was 32-36/min, chest expansion 2 cm and crackles were present at the lung bases. On chest radiograph diaphragms were elevated. Pulmonary function tests (PFT) showed further reduction in lung volumes, maximum inspiratory pressures, maximum expiratory pressures and arterial blood gases. Ventilation/perfusion and gallium lung scans were normal. A diagnosis of "shrinking lungs syndrome" was made. Treatment with 40 mg of prednisone resulted in resolution of the patient's shortness of breath. PFT showed improvement in all variables. Corticosteroid therapy for acute "shrinking lungs syndrome" in active SLE can improve symptoms and pulmonary function.

Adrenal Cortex Hormones↗
PubMed1992

A family study of the antiphospholipid syndrome associated with other autoimmune diseases.

Antiphospholipid syndrome (APS) is an entity characterized by recurrent thrombotic events and may occur spontaneously or in the context of systemic lupus erythematosus (SLE). We describe an English Canadian family in whom the propositus, a woman with Graves' disease and SLE, was found to have a lupus anticoagulant and anticardiolipin antibody (aCL). A brother with deep vein thrombosis, pulmonary emboli, bilateral adrenal hemorrhage and thrombocytopenia, circulating anticoagulant and aCL had a positive antinuclear antibody and Coombs' test, but no other features of SLE. Fourteen members of 3 generations of this family underwent clinical assessments, serological testing and HLA typing. The propositus' mother had a family history of autoimmune thyroid disease and the father had aCL, but was asymptomatic. The thyroid disease and the SLE were associated with HLA-B8, DR3 haplotype. The aCL and the anticoagulant were associated with HLA-B60, DR4 haplotype. Both these haplotypes were present in the propositus. Among the other 4 carriers of the haplotype B60, DR4, 3 demonstrated significant titers of aCL. Our findings support the reported association between APS and the HLA haplotype DR4 in patients of English descent with SLE.

Adolescent↗
PubMed1992

Crosscultural validation and reliability of 3 disease activity indices in systemic lupus erythematosus.

Rheumatologists from 4 countries, representing 8 rheumatology centers, tested 3 systemic lupus erythematosus (SLE) disease activity indices: the SLE Disease Activity Index (SLEDAI) from Toronto; the Systemic Lupus Activity Measure (SLAM) from Boston and the British Isles Lupus Assessment Group (BILAG) for their reproducibility and validity in the assessment of real patients. Seven patients representing a spectrum of disease manifestations and activity were each examined by 4 of 7 observers from all centers except Toronto, using a Youden square design. Each observer completed all 3 indices and a category rating scale for disease activity on each of the 4 patients seen. All 3 indices detected differences among patients. There was no detectable observer effect among the 7 observers with each of the 3 indices. There was a detectable order effect with the SLAM. The 3 indices are comparable and reproducible for evaluating disease activity in SLE.

Boston↗
PubMed1991

Kidney biopsy in systemic lupus erythematosus. II. Survival analyses according to biopsy results.

Renal biopsy specimens from 123 patients with systemic lupus erythematosus (SLE) seen between 1970 and 1984 were assessed according to the World Health Organization classification and according to the presence of proliferative, active, or chronic renal lesions. Survival analysis was used to study the determinants of mortality. Survival rates were higher for patients with minimal lesions, intermediate for patients with focal or diffuse proliferative nephritis, and low for patients with glomerular sclerosis. The presence of proliferative and chronic lesions was associated with a higher risk of dying. Renal biopsy results are helpful in predicting prognosis for all-cause mortality in patients with SLE.

Adult↗
PubMed1991

Pregnancy outcome following first trimester exposure to chloroquine.

Although the use of chloroquine (C) and hydroxychloroquine (HC) in the treatment of malaria prophylaxis during pregnancy is probably safe, the use of much higher doses for treatment of systemic lupus erythematosus (SLE) and rheumatoid arthritis during pregnancy has been controversial. We analyzed the cases of 24 pregnant women with a total of 27 pregnancies who had taken these drugs during their first trimester of pregnancy. C and HC were given in 11 patients with SLE, three with rheumatoid arthritis, and four for malaria prophylaxis. Most of these women had already been on antimalarial drugs for 1 to 172 months prior to pregnancy (mean, 32.2 months). Of the 27 pregnancies, 14 resulted in normal full-term deliveries, six were aborted due to severe disease activity or social conditions, three were stillbirths, and four pregnancies resulted in spontaneous abortions. No congenital abnormalities were detected in the 14 live births at ages between 9 months and 19 years (mean, 5.3 years). All these children are physically and developmentally normal with no clinical evidence of eye or hearing defects. The seven pregnancies that were associated with fetal loss occurred particularly in patients who had active SLE, although stillbirth and spontaneous abortion occurred also in patients with rheumatoid arthritis and in two of the three patients who had been treated prophylactically for malaria. Although of the 215 reported pregnancies with C and HC exposure, including our study, only seven (3.3%) had congenital abnormalities, the risk associated with antimalarials may be cumulative and further studies are needed to elucidate the safety of this drug later in pregnancy.

Abnormalities, Drug-Induced↗
PubMed1991

Glucocorticoid receptors in systemic lupus erythematosus.

Glucocorticosteroids remain the major treatment modality for systemic lupus erythematosus (SLE), but their mechanism of action is unclear. Over the past decade it has become clear that glucocorticosteroid receptors play a significant role in the mechanism of glucocorticosteroid action. We studied glucocorticosteroid receptor density and affinity on peripheral blood mononuclear cells by the glucocorticosteroid binding assay in 33 patients with SLE who had taken no glucocorticosteroid for the previous 6 months and in 32 healthy controls. Patients' disease activity was measured by the SLE Disease Activity Index (SLEDAI). Glucocorticosteroid receptors on leukocytes of patients with SLE were significantly higher than in healthy controls (4419 +/- 306 vs 3369 +/- 196, p less than 0.005). The binding affinity was not different between patients and controls. There was no correlation between glucocorticosteroid receptor number and SLE disease activity.

Adult↗
PubMed1991

Occurrence of neoplasia in patients with rheumatoid arthritis enrolled in a DMARD Registry. Rheumatoid Arthritis Azathioprine Registry Steering Committee.

The Rheumatoid Arthritis Azathioprine Registry (RAAR) was established in 1982 to examine the safety of azathioprine (AZA) and other disease modifying agents (DMARD) in the treatment of RA. In yearly followup over the past 7 years, 20 malignant conditions have been reported in 530 DMARD treated adult patients with RA. Incidence density ratios (IDR) and standardized morbidity ratios (SMR) were calculated to assess cancer risk. For all cancers the SMR was 1.52 (95% CI 0.90-2.60). For men the SMR was 1.71 (95% CI 0.84-3.52); for women the SMR was 1.52 (95% CI 0.89-2.60). Adjusted for age, the IDR was highest in the 70-79-year-old study population (3.41). The age and sex adjusted SMR for lymphoproliferative disorders and myeloma was 8.05 (95% CI 3.30-20.81). The SMR for lung cancer (n = 6) was also increased (3.37; 95% CI 1.58-7.34). Compared with the general population, patients with RA requiring DMARD therapy may be at increased risk of malignancy, particularly lymphoproliferative disorders. The RAAR is an important prospective technique which will ultimately permit assessment of neoplasia risk by type and duration of DMARD therapy.

Adult↗
PubMed1989

Treatment of refractory ischemic skin ulcers in patients with Raynaud's phenomenon with PGE1 infusions.

Prostaglandin E1 (PGE1) is a potent vasodilator and inhibitor of platelet aggregation. We administered 20 PGE1 infusions to 12 patients with severe Raynaud's phenomenon, associated with refractory ischemic skin ulcers. There was symptomatic improvement following 17 of the 20 infusions, while 35 of the 65 ischemic ulcers healed between 2-6 weeks following treatment. The beneficial effects persisted for between 1-18 months. While the treatment was well-tolerated in most patients, the procedure is not without risks. On the basis of this retrospective study, a trial of PGE1 infusion is recommended in the treatment of patients with ischemic skin ulcers, which have been refractory to other treatment modalities.

Adult↗
PubMed1989

Kidney biopsy in SLE. I. A clinical-morphologic evaluation.

The relationship between renal morphology and clinical disease was analysed in 148 patients with SLE attending a lupus clinic. Patients were not selected for renal disease. Renal tissue was assessed according to the World Health Organization classification of lupus nephritis, the presence of active and chronic lesions was recorded and disease activity was measured according to a standard protocol. All sections of the classification were represented in this group of patients. Active and chronic lesions were more likely to occur among patients with Class III/IV (proliferative glomerulonephritis), than in any other category. Patients with Class III/IV biopsy were more likely to have evidence of clinical renal disease than patients in Class II (mesangial). However, almost half of the Class II patients had some evidence of renal disease, including elevated serum creatinine, as well as important non-glomerular lesions. Without biopsy they might have been thought to have proliferative lesions and been treated more aggressively. Two patients with proliferative glomerulonephritis had no clinical evidence of renal disease. Thus, at the time of biopsy results renal histological examination did not uniformly correlate with clinical renal disease.

Adolescent↗
PubMed1989

"Latent lupus".

Twenty-two patients with constellation of features suggestive of systemic lupus erythematosus (SLE), but who did not qualify by "criteria" or a rheumatologist's intuition as having SLE, have been followed prospectively for at least 5 years, and have been labeled latent lupus. These patients presented with at least one of the 1971 or 1982 classification criteria, plus any of a constellation of minor criteria. They differed from patients with SLE in the absence of renal and central nervous system disease, and the lower frequency of DNA antibodies and depressed complement. They had a similar distribution of HLA antigens. Seven of the 22 patients evolved into SLE during the period of followup. There were no clinical or laboratory features which distinguished these patients from the remaining 15 with persistent latent lupus. Patients with latent lupus may represent a mild spectrum of SLE, and evolutionary phase of classic SLE, or a diathesis awaiting other provoking factors.

Adult↗
PubMed1988

Lupus pregnancy. A prospective study of placental changes.

Eleven patients with systemic lupus erythematosus (SLE) were monitored prospectively during pregnancy. Clinical and serologic features of disease activity were recorded, and after delivery, a careful search for pathologic changes in the placenta was carried out. Seven patients delivered live infants, and 4 patients had unsuccessful pregnancies, with fetal loss occurring between 12 and 27 weeks of gestation. One of these 4 patients had active SLE at delivery, and all had circulating lupus anticoagulant and thrombocytopenia. Other serologic abnormalities, including anticardiolipin and anti-Ro antibodies, were not associated with fetal loss. The overall placental size was reduced in SLE patients compared with that in healthy controls and in diabetic controls. A variety of pathologic changes were noted, including placental infarction, intraplacental hematoma, deposition of immunoglobulin and complement, and thickening of the trophoblast basement membrane. The reduction in placental size appeared to enhance the clinical significance of these pathologic changes.

Antibodies↗
PubMed1988

Lupus retinopathy. Patterns, associations, and prognosis.

In a prospective study of 550 patients with systemic lupus erythematosus (SLE), 41 were found to have retinopathy. Lupus retinopathy in the majority of cases consisted of a microangiopathy, with an excellent prognosis for vision. Five patients developed other complications that resulted in loss of visual acuity. Lupus retinopathy was associated with active SLE in 88% of patients and with lupus cerebritis in 73% of cases. Retinopathy in SLE was a marker of poor prognosis for survival.

Adult↗
PubMed1988

Successful pregnancy in systemic lupus erythematosus with an untreated lupus anticoagulant.

A lupus anticoagulant in pregnancy has almost always been associated with an adverse outcome. In previous reports of successful pregnancy in patients with a lupus anticoagulant, whether treated or untreated, all were complicated by premature delivery, and many were complicated by preeclampsia or placental insufficiency. Four patients with systemic lupus erythematosus and an untreated lupus anticoagulant, had an uncomplicated pregnancy that resulted in a live birth at term. The circulating anticoagulant persisted throughout the pregnancy in three patients, and disappeared spontaneously during pregnancy in the fourth patient. As pregnancy outcome is unpredictable, the best treatment of these patients remains to be determined by controlled studies.

Adult↗