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J M Grossman

Publications and source records attributed to J M Grossman.

10 recordsLinked to original sources
PubMed2001

Genetics and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex, multifactorial autoimmune disease. Genetic factors are believed to contribute to its pathogenesis. There have been numerous recent advances in the study of murine and human lupus genetics. In well-defined, experimental, transgenic or gene-knockout mouse models, the development of lupus-like disease has implicated specific genes and pathways in the disease pathogenesis. Linkage analyses have mapped multiple susceptibility loci and disease suppressive loci using inbred strains of mice that spontaneously develop lupus-like disease. Elegant genetic dissection has demonstrated that a component phenotype of SLE is displayed by each congenic strain carrying a single susceptibility locus on a resistant genetic background, whereas polycongenic strains exhibit fatal lupus nephritis. These studies suggest that genes in separate pathways can interact to augment or suppress the initiation and progression of systemic autoimmunity. In association studies of human lupus, the contributions of the MHC loci, Fcg receptors, various cytokines, components of the complement cascade, and proteins involved in apoptosis have been explored. Most recently, linkage analyses have been performed and provide many chromosomal regions for further exploration for susceptibility genes. Studies to identify the genes in the susceptibility regions are underway. An understanding of the genes involved in the development of lupus should provide targets for more focused therapy in lupus.

Animals↗
PubMed2000

Genetics and systemic lupus erythematosus.

Systemic lupus erythematosus is a complex, multifactorial, autoimmune disease. Genetic factors are believed to contribute to its pathogenesis. There have been numerous recent advances in the study of both murine and human lupus genetics. In murine lupus, congenic strains of three susceptibility loci have been developed. Transgenic and knock-out mice models of candidate genes now exist. In association studies of human lupus, the contributions of the MHC loci, Fcgamma receptors, various cytokines, components of the complement cascade, and proteins involved in apoptosis have been explored. Most recently, linkage analyses have been performed and provide numerous regions for further exploration for susceptibility genes. Studies to identify the genes in the susceptibility regions are underway. An understanding of the genes involved in the development of lupus should provide targets for more focused therapy.

Animals↗
PubMed2000

Health plan competition in local markets.

OBJECTIVE: To examine the structure of local health insurance markets and the strategies health plans were using to respond to competitive pressures in local markets in 1996/1997. DATA SOURCES/STUDY SETTING: Community Tracking Study site visits conducted between May 1996 and April 1997 in 12 U.S. markets selected to be nationally representative. STUDY DESIGN: In each site, 36 to 60 interviews on local health system change were conducted with healthcare industry informants representing health plans, providers, and purchasers. DATA COLLECTION/EXTRACTION METHOD: Relevant data for this article were abstracted from standardized protocols administered to multiple respondents in each site. PRINCIPAL FINDINGS: Although the competitive threat from national plans was pervasive, local plans in most sites continued to retain strong, often dominant, positions in historically concentrated markets. In all sites, in response to purchaser pressures for stable premiums and provider choice, and the threat of entry and to plans were using three strategies to increase market share and market power: (1) consolidation/geographic expansion, (2) price competition, and (3) product line/segment diversification that focused on broad networks and open-access products. In most markets, in response to the demand for provider choice, the trend was away from ownership and exclusive arrangements with providers. CONCLUSIONS: Although local plans were moving to become full-service regional players, there was uncertainty about the abilities of all plans to sustain growth strategies at the expense of margins and organizational stability, and to effectively manage care with broad networks.

Community Health Services↗
PubMed1999

PARP alleles within the linked chromosomal region are associated with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by various autoantibodies that recognize autoantigens displayed on the surface of cells undergoing apoptosis. The genetic contribution to SLE susceptibility has been widely recognized. We previously reported evidence for linkage to SLE of the human chromosome 1q41-q42 region and have now narrowed it from 15 to 5 cM in an extended sample using multipoint linkage analysis. Candidate genes within this region include (a) PARP, poly(ADP-ribose) polymerase, encoding a zinc-finger DNA-binding protein that is involved in DNA repair and apoptosis; (b) TGFB2, encoding a transforming growth factor that regulates cellular interactions and responses; and (c) HLX1, encoding a homeobox protein that may regulate T-cell development. Using a multiallelic, transmission-disequilibrium test (TDT), we found overall skewing of transmission of PARP alleles to affected offspring in 124 families (P = 0.00008), preferential transmission of a PARP allele to affected offspring (P = 0.0003), and lack of transmission to unaffected offspring (P = 0.004). Similar TDT analyses of TGFB2 and HLX1 polymorphisms yielded no evidence for association with SLE. These results suggest that PARP may be (or is close to) the susceptibility gene within the chromosome 1q41-q42 region linked to SLE.

Alleles↗
PubMed1999

Validity and reliability of retrospective assessment of disease activity and flare in observational cohorts of lupus patients.

BACKGROUND: The use of validated retrospective tools to assess disease activity in an observational cohort of patients would allow researchers the flexibility to analyze unique exploratory questions. Valid, reliable tools exist for assessing disease activity and flare for Systemic Lupus Erythematosus (SLE) patients. However, these tools have been designed for use in structured settings. Many of these populations under study are subject to strict inclusion, exclusion criteria and disease management protocols. The ability to apply these tools to populations not subject to such control would allow researchers to explore questions about unique populations, new treatment applications or predictors of clinical outcomes. This study sought to establish the reliability and validity of retrospective medical record abstraction of SLE disease activity and flare instruments by two rheumatologists. METHODS: From university rheumatology outpatient clinics, 22 patients were randomly selected to establish intra-rater reliability and 26 patients were selected to establish inter-rater reliability. Two rheumatologists using a Physician Global Assessment (PGA), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Safety of Estrogens in Lupus Erythematosus-National Assessment (SELENA) flare tool retrospectively abstracted patient charts. Agreement between the tools was evaluated to assess validity. RESULTS: The mean patient age was 39 y; 96% were female, 54% Caucasian, 27% Hispanic, 19% Asian; median PGA was 1.4 (on a 0-3 scale) and median SLEDAI score was 4 (range 0-27). Intra-rater reliability for PGA, SLEDAI and the SELENA flare tool was 0.88, 0.87 and 0.52, respectively. Inter-rater reliability for PGA, SLEDAI, and SELENA flare was 0.79, 0.75, and 0. 50, respectively. To assess validity, the tools were compared against each other to assess agreement. From the parent study sample (n=54 patients), the disease activity measures, PGA and SLEDAI demonstrated adequate agreement (r=0.60). However, the SELENA flare tool demonstrated poor agreement with either PGA-defined flare or SLEDAI-defined flare (weighted kappa, 0.29 and 0.40 respectively). PGA-defined and SLEDAI-defined flare also demonstrated poor agreement (weighted kappa, 0.35). CONCLUSIONS: These data suggest that investigators can reliably reproduce patient disease activity through retrospective chart abstraction using PGA and SLEDAI. Assessing flare is a more difficult concept. The validity of assessing flare at a specific patient-visit is poor. Retrospective assessment of patient flare risk over a specified time period is conceptually more valid and avoids difficulties assessing timing and duration of flare. As there have been no similar published prospective analyses of validity using the SELENA flare tool, it is not clear if this problem was unique to the method of retrospective chart abstraction, the nature of non-protocol study patient visits, the tool itself or a combination of all three aspects.

Adult↗
PubMed1997

Rheumatoid arthritis: current clinical and research directions.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis and joint erosions. It affects approximately 1% of the adult population in a female/male ratio ranging from 2:1 to 4:1. RA is an insidious disease, typically having an onset of symmetric joint swelling and reaching a peak incidence in the fourth and fifth decades. Extraarticular manifestations include pulmonary, ocular, and vascular disease. The etiology of RA remains unknown. Attempts to discover infectious causes have proven unsuccessful, although environmental influences may trigger a response leading to the development of this autoimmune disease. Genetic associations have been identified, particularly with the major histocompatibility complex class II antigens. Furthermore, twin studies have shown a 30%-50% concordance rate for monozygotic twins. Approximately 70%-80% of patients with RA have rheumatoid factor present in the blood, although its role remains unclear. Hormonal status may influence RA. The majority of RA patients are women, and in 75% of them, the disease improves during pregnancy. RA has significant financial and social implications associated with treatment costs, lost wages, disability, and increased mortality. Mainstays of medical therapy have included nonsteroidal anti-inflammatory and immunosuppressive agents, such as prednisone and methotrexate. Recent advances in the treatment of RA include specific inhibitors of cyclooxygenase II, T cells, blood vessels, cytokines (such as tumor necrosis factor-alpha [TNF-alpha] or interleukin-1 [IL-1]), and adhesion molecules. Additional studies are ongoing with combination interventions. It is anticipated that a better understanding of the basic pathophysiologic mechanisms critical in RA pathogenesis will provide more precise and efficacious therapy.

Adult↗
PubMedDate not supplied

Managed care and physicians' provision of charity care.

CONTEXT: Health system changes may be affecting the ability of physicians to provide care with little or no compensation from patients who are uninsured and under-insured and may result in decreased access to physicians for uninsured persons. OBJECTIVE: To examine the association between managed care and physicians' provision of charity care. DESIGN: The 1996-1997 Community Tracking Study physician survey. SETTING AND PARTICIPANTS: A nationally representative sample of 10881 physicians from 60 randomly selected communities. MAIN OUTCOME MEASURE: The number of hours in the month prior to the interview that the physician provided care for free or at reduced fees because of the financial need of the patient. RESULTS: Overall, 77.3% of respondents provided an average of 10.3 hours of charity care per month [corrected]. Physicians who derive at least 85% of their practice revenue from managed care plans were considerably less likely to provide charity care and spend fewer hours providing charity care than physicians with little involvement in managed care plans (P = .01). In addition, physicians who practice in areas with high managed care penetration provided fewer hours of charity care than physicians in other areas, regardless of their own level of involvement with managed care (P<.01). Differences in charity care provision were also shown for other important factors, including ownership of the practice and practice arrangements (more charity care occurred in solo and 2-physician practices; P<.01). CONCLUSION: Physicians involved with managed care plans and those who practice in areas with high managed care penetration tend to provide less charity care.

Charities↗