Franklin Kozin

The Quality of Well-being Scale. Applications in AIDS, cystic fibrosis, and arthritis.

The Quality of Well-being (QWB) Scale combines preference-weighted measures of symptoms and functioning to provide a numerical point in-time expression of well-being that ranges from zero (0) for death to 1.0 for asymptomatic optimum functioning. The QWB includes three scales of function: mobility, physical activity, and social activity. Each step of these scales is associated with preference weights. Preference adjustments for symptoms are also included. This paper describes how this general system was used to evaluate outcomes in three different clinical conditions: acquired immune deficiency syndrome (AIDS), cystic fibrosis, and arthritis. In one study, the QWB was administered to 31 patients participating in evaluation of azidothymidine (AZT) treatment for AIDS. The QWB system demonstrated substantial benefits of AZT treatment in comparison to placebo. In a second study, the QWB and a series of pulmonary function measures were administered to 44 patients with cystic fibrosis. The QWB was demonstrated to be significantly correlated with measures of pulmonary function, including FEV1 and maximal midexpiratory flow rate (MMEFR). In addition, there were significant associations between the QWB and measures of exercise tolerance. In the third study, the QWB and an arthritis-specific measure were administered to 83 arthritis patients before and after their treatment. The QWB was at least as capable of detecting clinical change in this population as was the disease-specific measure. For all three conditions, the QWB considered side effects and benefits of treatment in a common unit. Clinical trial data are cited to suggest that the QWB is a valuable outcome measure in arthritis treatment evaluation. We conclude that the QWB has substantial validity as a general health outcome measure and that the system can be used with different populations.

Molecular basis of an autoantibody-associated restriction fragment length polymorphism that confers susceptibility to autoimmune diseases.

Recently, combined serological and molecular studies of autoantibodies have revealed that these antibodies play an important role in the normal function of the immune system and in the development of the B cell repertoire. Accordingly, we hypothesized that a homozygous deletion of a critical autoantibody-associated Ig variable (V) gene may alter the immune system and thus predispose the host to autoimmune disorders. Initial experiments revealed several restriction fragment length polymorphisms (RFLP) of the Humhv3005 gene, that is likely to encode heavy chains of rheumatoid factors, and the closely related 1.9III gene. By probing EcoR1-digested DNA with the Humhv3005/P1 probe, we found that one of the four major hybridizing bands was missing in approximately 20% of patients with either rheumatoid arthritis or systemic lupus erythematosus, but only 2% of normal subjects. To delineate the genetic basis of this polymorphism, we have now employed the PCR to amplify and analyze hv3005, 1.9III, and homologous genes in individuals with characteristic RFLP genotypes. Our results indicate that the human Vh gene repertoire contains several hv3005- and 1.9III-like genes, and that a complete deletion of the hv3005-like genes is relatively restricted to a subset of autoimmune patients. These findings provide initial evidence for deletion of developmentally regulated autoreactive V genes in autoimmune diseases.

Report of the American College of Rheumatology Pain Management Task Force

Pain is the most common symptom of patients with rheumatic disorders and can occur in both inflammatory and noninflammatory conditions. As a complex phenomenon with a strong subjective component, pain can be influenced by the nature of the underlying disease, personal predisposition (biologic and psychological), as well as environmental and psychosocial factors that impact the pain experience. In the management of patients with musculoskeletal disease, therefore, the characterization of pain (e.g., its onset, duration periodicity, and impact on functioning) is important in establishing the diagnosis and developing a comprehensive treatment plan to reduce pain and to improve quality of life. Although rheumatologists diagnose and treat pain, they do not characterize themselves as “pain physicians.” Rather, in their professional identity, many rheumatologists consider themselves more narrowly as subspecialists who treat musculoskeletal disorders that have a component of acute and chronic nonmalignant pain. Furthermore, rheumatologists have traditionally approached pain from the perspective of the proximal causes of pain such as tissue injury and inflammation, and have concentrated therapy on reducing inflammation either locally or systemically. The therapies used have been predominantly pharmacologic and include nonsteroidal antiinflammatory drugs (NSAIDs), disease-modifying agents including biologics, and corticosteroids. Although commonly recommended, nonpharmacologic psychosocial interventions such as cognitive–behavioral therapy or body-based therapies including exercise are generally considered less effective by rheumatologists despite evidence that such approaches can be highly efficacious depending on the setting or disease (1–3). For most conditions treated by rheumatologists, the etiology of pain has been conceptualized primarily in the context of events in peripheral tissue. As a result, rheumatologists have relied heavily on pharmacologic therapies directed at the immune system to control symptoms, especially in inflammatory disease. Correspondingly, for patients with major or irreversible tissue damage, whether arising in inflammatory or noninflammatory disease, surgery has been the mainstay of treatment, with pharmacologic therapy used as a transition until a definitive operation is performed. Given this approach, events in the central nervous systems contributing to the experience of pain have received less attention in treatment, with additional analgesic, psychosocial, or interventional therapies receiving neither extensive investigation nor widespread or appropriate use. This approach may limit the utilization of newer and multidisciplinary approaches to pain manMembers of the American College of Rheumatology Pain Management Task Force are as follows: David Borenstein, MD: Arthritis & Rheumatism Associates, Washington, DC; Roy Altman, MD: University of California, Los Angeles; Alfonso Bello, MD, MHS: Illinois Bone & Joint Institute, Glenview; Winn Chatham, MD: University of Alabama, Birmingham; Daniel Clauw, MD: University of Michigan, Ann Arbor; Leslie Crofford, MD: University of Kentucky, Lexington; Joseph Croft, MD: Bethesda, Maryland; Afton Hassett, PsyD: Robert Wood Johnson Medical School, New Brunswick, New Jersey; Franklin Kozin, MD: Scripps Clinic Medical Group, La Jolla, California; David Pisetsky, MD, PhD: Durham VA Hospital, Durham, North Carolina; Jan Richardson, PT, PhD, Laura Schanberg, MD: Duke University, Durham, North Carolina; Terence Starz, MD: Arthritis & Internal Medical Associates, Pittsburgh, Pennsylvania; James Witter, MD, PhD: NIH, Bethesda, Maryland. The American College of Rheumatology is an independent, professional, medical and scientific society which does not guarantee, warrant, or endorse any commercial product or service. Dr. Borenstein has received consultant fees, speaking fees, and/or honoraria (less than

The incidence of a new human cross-reactive idiotype linked to subgroup VHIII heavy chains

10,000 each) from Pfizer and King, and (more than

Genetic studies of four highly homologous rheumatoid factor-associated Vk genes in rheumatoid arthritis patients and normal individuals

10,000) from Cephalon. Dr. Altman has received consultant fees, speaking fees, and/or honoraria (less than

Sjögren's syndrome. Proposed criteria for classification

10,000 each) from Nutramax, McKinsey, Endo, Cypress, Theralogix, Forest Laboratories, and NicOx, and (more than

Prevalence of the use of unconventional remedies for arthritis in a metropolitan community

10,000 each) from Ferring and Smith & Nephew. Dr. Bello has received consultant fees, speaking fees, and/or honoraria (less than

Autoantibody production by severe combined immunodeficient mice reconstituted with synovial cells from rheumatoid arthritis patients

10,000 each) from Abbott, BMS, Amgen, Lilly, and UCB, and (more than

Plasma Protein Binding by Monosodium Urate Crystals

10,000 each) from Pfizer and Horizon Therapeutics. Dr. Hassett has received consultant fees, speaking fees, and/or honoraria (less than

Possible deletion of a developmentally regulated heavy-chain variable region gene in autoimmune diseases

10,000 each) from Forest Pharmaceuticals and Jazz Pharmaceuticals. Dr. Kozin has received speaking fees (less than