Alfred D. Steinberg

Bio: Alfred D. Steinberg is an academic researcher from Mitre Corporation. The author has contributed to research in topics: Antibody & Antigen. The author has an hindex of 74, co-authored 295 publications receiving 20974 citations. Previous affiliations of Alfred D. Steinberg include National Institutes of Health & University of California, Berkeley.

The Fatigue Severity Scale: Application to Patients With Multiple Sclerosis and Systemic Lupus Erythematosus

Abstract: • Fatigue is a prominent disabling symptom in a variety of medical and neurologic disorders. To facilitate research in this area, we developed a fatigue severity scale, subjected it to tests of internal consistency and validity, and used it to compare fatigue in two chronic conditions: systemic lupus erythematosus and multiple sclerosis. Administration of the fatigue severity scale to 25 patients with multiple sclerosis, 29 patients with systemic lupus erythematosus, and 20 healthy adults revealed that the fatigue severity scale was internally consistent, correlated well with visual analogue measures, clearly differentiated controls from patients, and could detect clinically predicted changes in fatigue over time. Fatigue had a greater deleterious impact on daily living in patients with multiple sclerosis and systemic lupus erythematosus compared with controls. The results further showed that fatigue was largely independent of self-reported depressive symptoms and that several characteristics could differentiate fatigue that accompanies multiple sclerosis from fatigue that accompanies systemic lupus erythematosus. This study demonstrates (1) the clinical and research applications of a scale that measures fatigue severity and (2) helps to identify features that distinguish fatigue between two chronic medical disorders.

Methylprednisolone and Cyclophosphamide, Alone or in Combination, in Patients with Lupus Nephritis

Abstract: Background: Uncertainty exists about the efficacy and toxicity of bolus therapy with methylprednisolone or of the combination of methylprednisolone and cyclophosphamide in the treatment of lupus ne...

Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis : A randomized, controlled trial

Abstract: Background : Uncertainty exists about the efficacy and toxicity of bolus therapy with methylprednisolone or of the combination of methylprednisolone and cyclophosphamide in the treatment of lupus nephritis. Objective : To determine 1) whether intensive bolus therapy with methylprednisolone is an adequate substitute for bolus therapy with cyclophosphamide and 2) whether the combination of methylprednisolone and cyclophosphamide is superior to bolus therapy with methylprednisolone or cyclophosphamide alone. Design : Randomized, controlled trial with at least 5 years of follow-up. Setting : Government referral-based research hospital. Patients : 82 patients with lupus nephritis who had 10 or more erythrocytes per high-power field, cellular casts, proteinuria (>1 g of protein per day), and a renal biopsy specimen that showed proliferative nephritis. Interventions : Bolus therapy with methylprednisolone (1 g/m 2 body surface area), given monthly for at least 1 year ; bolus therapy with cyclophosphamide (0.5 to 1.0 g/m 2 body surface area), given monthly for 6 months and then quarterly ; or bolus therapy with both methylprednisolone and cyclophosphamide. Measurements : 1) Renal remission (defined as <10 dysmorphic erythrocytes per high-power field, the absence of cellular casts, and excretion of <1 g of protein per day without doubling of the serum creatinine level), 2) prevention of doubling of the serum creatinine level, and 3) prevention of renal failure requiring dialysis. Results : Renal remission occurred in 17 of 20 patients in the combination therapy group (85%), 13 of 21 patients in the cyclophosphamide group (62%), and 7 of 24 patients in the methylprednisolone group (29%) (P < 0.001). Twenty-eight patients (43%) did not achieve renal remission. By life-table analysis, the likelihood of remission during the study period was greater in the combination therapy group than in the methylprednisolone group (P = 0.028). Combination therapy and cyclophosphamide therapy were not statistically different. Adverse events were amenorrhea (seen in 41% of the cyclophosphamide group, 43% of the combination therapy group, and 7.4% of the methylprednisolone group), cervical dysplasia (seen in 11% of the cyclophosphamide group, 7.1% of the combination therapy group, and 0% of the methylprednisolone group), avascular necrosis (seen in 11% of the cyclophosphamide group, 18% of the combination therapy group, and 22% of the methylprednisolone group), herpes zoster (seen in 15% of the cyclophosphamide group, 21% of the combination therapy group, and 3.7% of the methylprednisolone group) and at least one infection (seen in 26% of the cyclophosphamide group, 32% of the combination therapy group, and 7.4% of the methylprednisolone group). Conclusions : Monthly bolus therapy with methylprednisolone was less effective than monthly bolus therapy with cyclophosphamide. A trend toward greater efficacy with combination therapy was seen.

Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis.

Abstract: With extended follow-up, pulse cyclophosphamide continued to show superior efficacy over pulse methylprednisolone alone for treatment of lupus nephritis. The combination of pulse cyclophosphamide a...

Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only.

Abstract: The purpose of this study was to assess long-term preservation of renal function in 111 patients with systemic lupus erythematosus and active glomerulonephritis who participated in a randomized treatment trial. Four different drug treatment programs, each of which allowed the use of low-dose oral prednisone in addition to the study drug(s), were compared with a regimen consisting solely of high-dose oral prednisone. Patients randomized to receive intravenous cyclophosphamide, oral cyclophosphamide, or oral azathioprine plus cyclophosphamide had significantly better preservation of renal function than did patients who were randomized to receive prednisone only. Results in the azathioprine group did not differ from those in the prednisone-only group. Cyclophosphamide appears to have long-term benefit in the delay or prevention of end-stage renal disease in patients with lupus nephritis.

Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.

Abstract: Approximately 10% of peripheral CD4+ cells and less than 1% of CD8+ cells in normal unimmunized adult mice express the IL-2 receptor alpha-chain (CD25) molecules. When CD4+ cell suspensions prepared from BALB/c nu/+ mice lymph nodes and spleens were depleted of CD25+ cells by specific mAb and C, and then inoculated into BALB/c athymic nude (nu/nu) mice, all recipients spontaneously developed histologically and serologically evident autoimmune diseases (such as thyroiditis, gastritis, insulitis, sialoadenitis, adrenalitis, oophoritis, glomerulonephritis, and polyarthritis); some mice also developed graft-vs-host-like wasting disease. Reconstitution of CD4+CD25+ cells within a limited period after transfer of CD4+CD25- cells prevented these autoimmune developments in a dose-dependent fashion, whereas the reconstitution several days later, or inoculation of an equivalent dose of CD8+ cells, was far less efficient for the prevention. When nu/nu mice were transplanted with allogeneic skins or immunized with xenogeneic proteins at the time of CD25- cell inoculation, they showed significantly heightened immune responses to the skins or proteins, and reconstitution of CD4+CD25+ cells normalized the responses. Taken together, these results indicate that CD4+CD25+ cells contribute to maintaining self-tolerance by down-regulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage; elimination/reduction of CD4+CD25+ cells relieves this general suppression, thereby not only enhancing immune responses to non-self Ags, but also eliciting autoimmune responses to certain self-Ags. Abnormality of this T cell-mediated mechanism of peripheral tolerance can be a possible cause of various autoimmune diseases.

The Chronic Fatigue Syndrome: A Comprehensive Approach to Its Definition and Study

Abstract: The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations.

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

Abstract: 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.

The Fas Death Factor

Abstract: Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells. Various cells express Fas, whereas FasL is expressed predominantly in activated T cells. In the immune system, Fas and FasL are involved in down-regulation of immune reactions as well as in T cell-mediated cytotoxicity. Malfunction of the Fas system causes lymphoproliferative disorders and accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction.

Systemic Lupus Erythematosus

Abstract: In sharp distinction to organ-specific autoimmune diseases such as thyroiditis, diabetes, or myasthenia gravis, systemic lupus erythematosus (SLE) is a constellation of signs and symptoms classified as one nosologic entity. Indeed, it is the diversity of presentation, accumulation of manifestations over time, and undulating disease course that challenge the most astute of clinicians. With rare exception, the unifying laboratory abnormality is the presence of circulating antinuclear antibodies (ANA). Acknowledging the complexity of this disease, its broad differential diagnosis, and the need to develop better and more specific therapies, the American College of Rheumatology (ACR) has designated 11 diagnostic criteria (presented in Table 15A-1) (1,2). These criteria reflect the major clinical features of the disease (mucocutaneous, articular, serosal, renal, neurologic) and incorporate the associated laboratory findings (hematologic and immunologic). The presence of four or more criteria is required for diagnosis. They need not necessarily present simultaneously: a single criterion such as arthritis or thrombocytopenia may recur over months or years before the diagnosis can be confirmed by the appearance of additional features. While there is incomplete agreement among rheumatologists as to whether these criteria need to be strictly applied in a practice setting, or reserved only for formal academic studies, they do facilitate a methodologic approach to evaluate a patient.