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Biomedical subjects

M B Urowitz

Publications and source records attributed to M B Urowitz.

At least 73 records · Page 4Linked to original sources
PubMed1995

Mortality studies in systemic lupus erythematosus. Results from a single center. I. Causes of death.

OBJECTIVE: To study the causes of death in patients with SLE, followed prospectively in a single center. METHODS: The study population comprised 665 patients with systemic lupus erythematosus (SLE). Causes of death were determined by review of hospital files, autopsy reports, and death certificates. Nonparametric lifetable models were used to calculate Kaplan-Meier estimates of survival probabilities. RESULTS: One hundred and twenty-four patients (18.6%) had died. The primary causes of death were active SLE in 20 (16%), infection in 40 (32%), acute vascular event in 19 (15.4%), sudden death in 10 (8.1%), organ failure in 6 (4.8%), malignancy in 8 (6.5%), others in 8 (6.5%), and unknown in 13 (10.5%). Death as a result of active SLE was more common in patients who died within 5 years of diagnosis compared to those dying after 5 years (p = 0.021), and deaths due to vascular events and end organ failure not related to active lupus were more frequent in the late death group (p = 0.028). The overall 5, 10, 15, and 20 year survival rates were 93, 85, 79, and 68%, respectively. Patients with SLE had a 4.92 fold increased risk for death compared with the general population. CONCLUSION: Survival rates continue to improve in SLE but causes of mortality vary at different stages.

Adolescent↗
PubMed1995

Mortality studies in systemic lupus erythematosus. Results from a single center. II. Predictor variables for mortality.

OBJECTIVE: To analyze the factors associated with mortality in patients with systemic lupus erythematosus (SLE), followed prospectively in a single center. METHODS: The study included 665 patients with SLE followed over a 20-year period according to a standard protocol. Clinical laboratory information has been entered into a database. Univariate analysis was carried out to identify prognostic factors of death. The Cox proportional hazard regression model was used to estimate risk ratio of death. RESULTS: Renal damage, thrombocytopenia, lung involvement, systemic lupus erythematosus disease activity index (SLEDAI) > or = 20 at presentation, and age > or = 50 at diagnosis were predictive factors for mortality in the univariate as well as in the multivariate analyses. Hypertension and ischemic heart disease were significantly associated with death only in the univariate analysis. CONCLUSION: Renal damage, thrombocytopenia, SLEDAI > or = 20 at presentation, lung involvement, and age > or = 50 at diagnosis are prognostic factors associated with mortality.

Adolescent↗
PubMed1995

Induction of TNF-alpha and proinflammatory secretory phospholipase A2 by intravenous administration of CAMPATH-1H in patients with rheumatoid arthritis.

OBJECTIVE: To test the effect of infusions of CAMPATH-1H on levels of proinflammatory secretory phospholipase A2 (sPLA2) and tumor necrosis factor alpha (TNF-alpha) in patients with rheumatoid arthritis (RA). METHODS: Two patients with RA were infused with CAMPATH-1H; extracellular nonpancreatic sPLA2 activity was tested using radiolabelled E. coli membrane phospholipid, and circulating TNF-alpha levels were tested by ultrasensitive immunoassay. RESULTS: Circulating TNF-alpha began to rise within the first 2 h after infusion, reaching > 1000-fold values compared to preinfusion levels. Circulating sPLA2 activity began to rise a few hours after the start of infusion and reached extremely high values in 12 h, concomitant with fever and hypotension. The activity of sPLA2 decreased to pretreatment values in 3-18 days after infusion. CONCLUSION: The mechanism leading to the increase of TNF-alpha and hyperphospholipasemia A2 has not been elucidated. It is possible that CAMPATH-1H activates cells that synthesize and release TNF-alpha and sPLA2, and/or that it induces interleukin 2 release, which in turn activates TNF-alpha, with subsequent release of sPLA2.

Adult↗
PubMed1994

Kidney biopsy in systemic lupus erythematosus. III. Survival analysis controlling for clinical and laboratory variables.

OBJECTIVE: To examine the importance of renal biopsy as a predictor of death due to any cause in patients with systemic lupus erythematosus (SLE). METHODS: The study included 123 SLE patients who had a renal biopsy between 1970 and 1984 and were followed up as part of a prospective study. Data were initially analyzed to identify clinical and laboratory features that were significantly associated with the risk of dying. Renal biopsy variables were then examined to determine whether they contributed additional information about prognosis. RESULTS: The clinical and laboratory factors most closely associated with the risk of dying in multivariate analyses were the serum creatinine level and the SLE Disease Activity Index score. The presence of chronic renal lesions on biopsy contributed significantly to the prognostic information offered by clinical and laboratory factors in the subset of patients who had normal serum creatinine levels--the majority (85%) of patients in this study. CONCLUSION: These results indicate that renal biopsy serves an important role in the assessment of prognosis in patients who do not have advanced renal disease.

Adult↗
PubMed1994

Serologically active clinically quiescent systemic lupus erythematosus--predictors of clinical flares.

OBJECTIVE: To identify the frequency of serologic activity in the face of clinical quiescence in a large cohort of patients with systemic lupus erythematosus (SLE) followed prospectively in a single center. METHODS: In a prospective cohort study, patients serologically active but clinically quiescent (SACQ) in 3 consecutive clinic visits were analyzed for the development of a clinical flare over the subsequent year and were evaluated for predictive factors for flare before and during their SACQ period. RESULTS: Forty-six episodes of SACQ went on to clinical flare within one year while 60 did not. No predictive factors for flare were found either during or before the SACQ period. CONCLUSIONS: A significant population of patients with SLE are SACQ and must be followed over time and treated only on the basis of clinical criteria.

Adult↗
PubMed1994

Prolactin in systemic lupus erythematosus.

OBJECTIVE: To estimate the prevalence and evaluate the clinical significance of hyperprolactinemia in a cohort of 82 consecutively reviewed patients with systemic lupus erythematosus (SLE). METHODS: Basal prolactin levels and clinical data were analyzed in 82 consecutive patients with SLE, and longitudinal studies were carried out in 30/82 patients. RESULTS: Hyperprolactinemia was not associated with active disease in the group as a whole (p = 0.145) or in longitudinal studies in 30 patients (p = 0.294). However, SLE was more often active in patients with hyperprolactinemia without any obvious causes (8/9 samples) compared with patients with known secondary causes for hyperprolactinemia (p = 0.088). CONCLUSION: Hyperprolactinemia is likely not associated with disease activity in SLE.

Adult↗
PubMed1994

Sensitivity to change of 3 Systemic Lupus Erythematosus Disease Activity Indices: international validation.

OBJECTIVE: Three indices, the SLE Disease Activity Index (SLEDAI), the Systemic Lupus Activity Measure (SLAM) and the British Isles Lupus Assessment Group (BILAG), have been found to be reliable and valid measures of disease activity in patients with systemic lupus erythematosus (SLE). Our aim was to investigate their use and comparative ability to assess change in disease activity over time. METHODS: Clinical and laboratory features of 8 patients with SLE on each of 3 consecutive visits were abstracted and sent in 3 separate packages to physicians from 8 centers. The order of the patient visit summaries was randomized, and the 3 indices rated in one of 6 specific sequences. RESULTS: The 3 indices were significantly (p < 0.01) correlated: SLEDAI/SLAM = 0.61, BILAG/SLAM = 0.55, SLEDAI/BILAG = 0.35. The sequence presented, the order of patients and order of index scoring did not contribute significantly (p > 0.05) to the variation of any of the 3 indices. All 3 indices detected differences among patients (p < 0.01). Differences between visits were detectable with SLEDAI (p = 0.04) but not with SLAM or BILAG: CONCLUSION: Our study confirms that the SLEDAI, SLAM and BILAG are comparable disease activity measures. SLEDAI appears to be sensitive to change in disease activity over time.

Computers↗
PubMed1994

Methotrexate in systemic lupus erythematosus.

OBJECTIVE: Methotrexate (MTX) has been used successfully in the treatment of rheumatoid arthritis, psoriatic arthritis, polymyositis, and Reiter's syndrome. Our objective was to determine the effectiveness of MTX in the treatment of systemic lupus erythematosus (SLE). METHODS: We reviewed retrospectively MTX therapy in 5 patients with SLE, 3 with renal disease and 2 with arthritis. RESULTS: MTX therapy was well tolerated and effective in all 5 patients. CONCLUSION: MTX appears to be both effective and well tolerated in patients with SLE.

Adolescent↗
PubMed1994

Accelerated nodulosis, pleural effusion, and pericardial tamponade during methotrexate therapy.

We describe a patient with seropositive erosive rheumatoid arthritis (RA) who developed accelerated nodulosis, pleural effusion, and pericardial tamponade during methotrexate (MTX) therapy while her arthritis remained inactive. MTX is an effective therapy for the articular manifestations of RA. However, on occasion it may result in triggering the development of extraarticular manifestations of RA.

Arthritis, Rheumatoid↗
PubMed1994

Circulating group II phospholipase A2 activity and antilipocortin antibodies in systemic lupus erythematosus. Correlative study with disease activity.

OBJECTIVE: Lipocortin (LC) and phospholipase A2 (PLA2) are involved in phospholipid metabolism, and on the cellular level LC seems to be an antagonist of PLA2. Since anti-LC1 autoantibodies were found in systemic lupus erythematosus (SLE), we undertook a study of the relationship between PLA2, anti-LC1, and disease activity in a large group of patients with SLE. METHODS: Sera from 81 patients with SLE were tested for the activity of extracellular PLA2 and the presence and level of antilipocortin 1 [anti-LC1 (IgM) and anti-LC1 (IgG)] antibodies. Both were compared to SLE activity. RESULTS: Mean PLA2 activity was 4.6-fold higher in patients with SLE than in healthy controls (707 +/- 219 vs 154 +/- 6 u/ml, p < 0.01). PLA2 activity correlated significantly with PLA2 immunoreactivity as estimated by an ELISA method using monoclonal antibodies against "synovial type" PLA2 (n = 21, r = 0.984, p < 0.001). Anti-LC1 IgM and IgG antibody levels were significantly higher in SLE than in healthy individuals [anti-LC1 (IgM) 54.5 +/- 4.6 vs 22.6 +/- 2.3 EU/ml, p < 0.001 and anti-LC1 (IgG) 54.3 +/- 3.4 vs 22.9 +/- 2.3 EU/ml, p < 0.001]. There was no correlation between PLA2 activity and anti-LC1 antibody titers. Elevated levels of PLA2 [> normal mean + 2 SD (i.e., > 300 u/ml)] were found in 41/81 patients with SLE. Anti-LC1 antibody titers were high (> 64 EU/ml) in 23/41 patients; 14/40 patients with SLE with normal PLA2 (< 300 u/ml) also had higher titers of anti-LC1 antibodies. PLA2 activity was significantly associated with the presence of synovitis, being markedly increased in 11/12 patients. Mean PLA2 in this group of patients (1593 +/- 957 u/ml) was significantly higher (p < 0.001) than that (553 +/- 188 u/ml) in the group of 69 patients with SLE without synovitis. CONCLUSIONS: There was no correlation of PLA2 activity with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) or the Lupus Activity Criteria Count (LACC). Circulating PLA2 activity in SLE correlated only with active synovitis. There was no correlation of anti-LC1 titers with duration of the disease, age, steroid dosage, SLEDAI, or LACC or any individual clinical or laboratory variable included in the assessment of SLEDAI and LACC.

Adult↗
PubMed1993

Lupus and pregnancy studies.

OBJECTIVE: To examine factors prior to pregnancy in patients with systemic lupus erythematosus (SLE) that are prognostic for the occurrence of active disease during and shortly after pregnancy. METHODS: Case-control study of pregnant SLE patients and nonpregnant SLE controls, using logistic regression analyses to assess the role of prepregnancy disease activity as a prognostic factor for flare during pregnancy or the postpartum followup period. RESULTS: Lupus flares occurred frequently and in similar percentages of pregnant SLE patients and control SLE patients. Active lupus at study entry, both in control and in pregnant patients, was not predictive of flare. Inactive lupus at onset was not protective against flare in controls but was protective in pregnant lupus patients. CONCLUSION: Inactive disease at the onset of pregnancy in SLE provides optimum protection against the occurrence of flare during pregnancy.

Adrenal Cortex Hormones↗
PubMed1993

Dilemmas in neuropsychiatric lupus.

It is estimated that two thirds of neuropsychiatric (NP) manifestations in lupus are not directly related to active NP lupus but instead are a consequence of secondary causes such as drugs, infections, and hypertensive and metabolic complications in the setting of systemic lupus erythematosus (SLE). It is often difficult to distinguish clinically between primary central nervous system lupus and secondary causes of NP manifestations. In general, NPSLE has been reported to be a prognostic factor for a poor long-term outcome in lupus. Despite early recognition of the disease and aggressive therapeutic interventions, it is still frequently associated with increased mortality.

Central Nervous System Diseases↗
PubMed1993

Is "aggressive" therapy necessary for systemic lupus erythematosus?

Much of the initial attention in therapeutic studies for systemic lupus erythematosus (SLE) has justifiably been focused on the severe forms of the disease such as diffuse proliferative glomerulonephritis or central nervous system manifestations. Unfortunately, to all forms of SLE, thereby submitting patients with more benign variants of lupus have been submitted to aggressive, toxic, and probably unnecessary treatments. The thesis of this article is that aggressive therapy is not always necessary for SLE.

Cyclophosphamide↗
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↗