The effect of full-time faculty hospitalists on the efficiency of care at a community teaching hospital.

BACKGROUND: Hospitalists are increasingly being used for inpatient care. OBJECTIVE: To investigate whether the use of hospitalists is beneficial. DESIGN: Retrospective cohort study. SETTING: Inpatient medical service of a 500-bed community teaching hospital. PARTICIPANTS: 1620 patients in the study group, seen during the hospitalist year; 1679 patients from the same outpatient practice as the study group, seen during the previous year (prehospitalist year); an unselected comparison group of 3413 patients seen during the prehospitalist year and 3223 patients seen during the hospitalist year; and a subset of the unselected comparison group, cared for by outpatient practices, who had a prehospitalist length of stay similar to that of the study group (743 patients in the prehospitalist year and 786 in the hospitalist year). INTERVENTIONS: Full-time faculty hospitalists cared for the study group, were in the hospital during normal working hours, and made decisions throughout the day. In the prehospitalist year and in the comparison groups, primary care physicians managed their own hospitalized patients. MEASUREMENTS: Length of stay; cost of care; costs of hematology and chemistry evaluation, pharmacy, and radiology; and readmissions were determined for the prehospitalist and hospitalist years. RESULTS: In the study group, median length of stay decreased from 6.01 to 5.01 days (P < 0.001). Median cost of care decreased from $4139 to $3552 (P < 0.001), and the 14-day readmission rate decreased from 9.9 to 4.64 readmissions per 100 admissions (P < 0.001). In the comparison groups, length of stay decreased but both cost of care and readmission rates increased. CONCLUSION: Hospitalists may improve the efficiency of inpatient care. Further study in various settings is needed to verify these findings.

Interleukin-1beta-stimulated invasion of articular cartilage by rheumatoid synovial fibroblasts is inhibited by antibodies to specific integrin receptors and by collagenase inhibitors.

OBJECTIVE: To study the role of integrin receptors in the invasion of cartilage by rheumatoid synovial fibroblasts (RSF). METHODS: RSF were cocultured with cartilage slices alone or in the presence of various potential activators or inhibitors. The penetration of the cartilage surface by RSF was determined by live-cell imaging of fluorescent-labeled cells. RESULTS: Interleukin-1beta (IL-1beta) and IL-8 stimulated the RSF invasion of cartilage. Invasion was specific for RSF and required a concentration gradient of IL-1beta. The IL-1beta-activated invasion of cartilage was inhibited by anti-IL-1 antibodies, IL-1 receptor antagonist, and collagenase inhibitors. RSF invasion was also inhibited by antibodies to alpha4, alpha5, alphaV, and beta1 integrins. CONCLUSION: In this study, an IL-1beta concentration gradient was required for RSF invasion into cartilage, raising the possibility that in vivo invasion may be induced by IL-1beta released by chondrocytes. The IL-1beta activation of RSF assayed in vitro may contribute to the RSF invasion of cartilage in vivo. Cartilage invasion requires the availability of beta1 and alpha4, alpha5, and alphaV integrins and the presence of collagenase activity.

Fibronectin induces protease dependent focal matrix depletion and cell overlap in cultured rheumatoid synoviocytes.

OBJECTIVE: To characterize the effect of added fibronectin (Fn) on human rheumatoid synoviocytes (RAS). METHODS: Early passage cultured RAS were studied by fluorescent imaging microscopy with multiple parameter overlaying and confocal laser scanning microscopy. RESULTS: Added Fn induced a localized decrease in matrix Fn at sites of cell overlap. Similar matrix depletion could be induced by collagen VI, cell binding (120 k) and heparin binding (60 k) fragments of Fn, but not by gelatin binding fragment (45 k). CONCLUSION: The decrease in matrix Fn was associated with the induction of a transformation-like phenotype of overlapping cell growth. Both phenomena were inhibited by serine protease inhibitors.

Total quality management of a medical residency.

Although many hospitals have begun the long and difficult process of adapting to the concepts of total quality management, few have reported efforts to apply total quality management to a medical residency. We report here the initial results of the Western Pennsylvania Hospital's efforts, as part of the hospital's conversion of its management structure to total quality management.

Improved in vitro models for assay of rheumatoid synoviocyte chemotaxis.

OBJECTIVES: (1) To define the optimal conditions for transwell assay of synoviocyte chemotaxis. (2) To develop a live cell imaging chemotaxis assay for synoviocytes. (3) To characterize the chemotaxis of rheumatoid synoviocytes (RAS). RESULTS: Optimal conditions for transwell assay of synoviocyte chemotaxis were 8 microns pore size filters coated with collagen I (C1), assayed for 24 hours. Without the C1 coating 2.9 x 10(3) RAS migrated to the lower chamber. This increased to 4.7 x 10(3) when 20 micrograms/ml fibronectin (Fn) was added. With the C1 coating 4.3 x 10(3) cells migrated through the filter without chemotactic stimulation compared to 12.8 x 10(3) with interleukin 1 beta (IL-1 beta) 5 ng/ml, 12.2 x 10(3) with granulocyte-macrophage colony stimulating factor (GM-CSF) 25 ng/ml, 11.7 x 10(3) with Fn 20 micrograms/ml, and 9.0 x 10(3) with transforming growth factor-beta 1 (TGF-beta 1) 20 ng/ml (all p < 0.01). In the imaging assay, 50.7% of the RAS migrated toward the C1 coating without bound chemoattract. The percentage of cells migrating toward each chemoattractant at its optimal concentration was 64.3% for IL-1 beta, 60.8% for IL-8, 64.7% for GM-CSF, 61.0% for Fn, 58.9% for IL-6, and 69.1% for TGF-beta 1 (all p < 0.01). All of these chemoattractants increased directed migration without changing the random migration. Indomethacin (100 ng/ml) and Dexamethasone (10 ng/ml) inhibited Fn-induced chemotaxis. CONCLUSION: We report two in vitro assays for synoviocyte chemotaxis adapted and optimized for the study of synoviocytes. The live cell imaging assay had the advantage that it could separate directed and random migration.

An analysis of the cost and revenue of an expanded medical residency.

OBJECTIVE: To analyze the additive costs and revenues resulting from expansion of a medical residency and associated subspecialty programs. METHODS: Direct and indirect costs of the residency program were analyzed as was reimbursement for the costs of the residency. To determine whether expansion of the residency affected cost of care, the authors compared the costs of care on the teaching service and nonteaching services. RESULTS: The number of residents increased from 18 medical resident and subspecialty fellows in the 1988 academic year to 36 medical residents and 12 subspecialty fellows in the 1991 academic year. Total measured costs increased by $2,036,570 to $3,911,196. Reimbursement increased to $5,319,117, of which $2,290,221 was attributed to the increase in the number of residents. Net income from the residency after subtracting costs increased by $815,714 to a total of $1,407,971, excluding any higher costs at the authors' hospital that were an indirect result of the teaching program. Costs for the same diagnosis-related groups (DRGs) were not significantly different on the teaching and nonteaching services. CONCLUSIONS: Expanding the medical residency increased the net income available to offset the higher costs per DRG at the hospital. These costs did not increase in proportion to the increase in resident numbers. Increased revenue came primarily from Medicare indirect cost reimbursement. A reduction in this rate from 7.7% to less than 4.1% would have resulted in a net loss for medical education costs. Present reimbursement policy is not aligned with actual costs or public policy goals. This may have undesired effects both now and in the future.

Successful treatment of T-gamma lymphoproliferative disease with human-recombinant granulocyte colony stimulating factor.

A trial of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was attempted in a male with agranulocytosis, infection, and T-gamma lymphoproliferative disease (T-gamma-LPD). During five days of rhG-CSF (960 micrograms/day), the absolute neutrophil count (ANC) increased from 0.0 to 4.5 K/microliters. There were no changes in eosinophil or lymphocyte counts. In addition, there was no toxicity. Bone marrow cytotoxic/suppressor cells (CD57+/CD8+) were elevated (21.9%) before and decreased to 10.6% (normal less than 12%) following rhG-CSF. By contrast, there was no change in activated T cells (CD3+DR+) or T cell gene rearrangements. These findings suggest rhG-CSF can improve granulopoiesis in T-gamma-LPD, possibly by altering T-cell mediated marrow suppression.

Control of crystal-induced arthropathies.

Present approaches to the treatment to crystal-induced arthropathies and indications for their use are reviewed. Successes and limitations of such therapy are discussed and potential new approaches to treatment are discussed. Treatment of gout hyperuricemia is generally effective if appropriately applied and is likely to be improved principally by better application of presently available drugs. New approaches to treatment may improve care for those patients in whom present approaches to management remain unsatisfactory.

Spectrum of diseases for resident education in internal medicine.

We examined the spectrum of diseases to which medical residents were exposed in a fully integrated residency program comprised of a voluntary and a municipal acute-care hospital. Although circulatory disorders and diseases of the respiratory and nervous systems accounted for the majority of cases, a broad spectrum of diseases was present for residents' training at both institutions. These observations must be considered within the context of the changing nature of medical practice in the United States, with a marked shift from inpatient to outpatient and office medical care.

Interaction between fibronectin and C1q in rheumatoid synovial fluid and normal plasma.

The interaction between fibronectin and C1q was studied in the presence of normal human plasma and rheumatoid synovial fluid by solid phase binding assay. Fibronectin-C1q binding occurred in the presence of rheumatoid synovial fluid but not in the presence of normal plasma. Binding was strongest at 4 degrees C and in the presence of EDTA. Fibronectin-C1q binding could be induced in the presence of normal plasma by hypotonicity, augmentation of the concentration of solution-phase fibronectin or by the addition of heat-aggregated IgG. The C1q present in rheumatoid synovial fluid bound to both aminoterminal collagen-binding and carboxyterminal noncollagen binding fibronectin fragments although binding to the aminoterminal fragment was stronger. The interaction between fibronectin and C1q in rheumatoid synovial fluid may modulate immune-complex deposition and complement activation in the inflamed joint.

Carbohydrate heterogeneity of fibronectins. Synovial fluid fibronectin resembles the form secreted by cultured synoviocytes but differs from the plasma form.

Large quantities of fibronectin (Fn) are present in inflammatory synovial fluid. Inflammatory synovial fluid Fn, while indistinguishable from plasma Fn on the basis of reactivity to polyclonal antibodies, displays alterations in molecular size and charge. Since biochemical differences between plasma and synovial fluid fibronectins might be in part due to differences in glycosylation we have compared the carbohydrate composition of plasma Fn, synovial fluid Fn, and Fn from synoviocyte conditioned medium by biochemical assay, glycopeptide analysis, and binding to a series of lectins. Synovial fluid Fn has a greater carbohydrate content but contains less sialic acid when compared with plasma Fn. Glycopeptides formed from synovial fluid Fn are smaller than plasma Fn glycopeptides. These data suggest the presence of an additional N-linked oligosaccharide chain on synovial fluid Fn. In addition, synovial fluid Fn contains N-acetyl galactosamine indicating the presence of O-linked oligosaccharides. Synovial fluid Fn and Fn isolated from rheumatoid synoviocyte-conditioned medium display strong reactivity with the lectins wheat germ agglutinin (WGA) and peanut agglutinin (PNA), whereas normal and rheumatoid plasma Fn react weakly. The PNA reactivity of synovial fluid Fn is mediated by terminal beta-galactose residues on the gelatin-binding domain, whereas the enhanced WGA reactivity of synovial Fn is mediated by a sialic acid containing oligosaccharide located on a 27-kD C-terminal fragment. These data demonstrate domain-specific biochemical differences between plasma and synovial fluid fibronectins. These differences suggest a local origin for synovial fluid Fn and may contribute to functional differences between these forms of the protein.

Plasma fibronectin in systemic lupus erythematosus: relationship to clinical activity, DNA binding and acute phase proteins.

Plasma fibronectin was measured by ELISA in 25 samples from 22 patients with systemic lupus erythematosus (SLE). The mean fibronectin level for the entire patient group (654 micrograms/ml) was greater than that of normal controls (450 micrograms/ml), with highest levels observed in the subgroup of patients with severe disease activity (838 micrograms/ml) followed by those with moderate disease activity (732 micrograms/ml) (p = .04). Fourteen patients with other rheumatic disease had a mean fibronectin level of 407 micrograms/ml. Decreases in fibronectin levels corresponded to clinical improvement and reductions in DNA binding. Although elevated fibronectin levels did not correspond to any specific pattern of organ system involvement, fibronectin levels seem to parallel disease activity in certain patients. Future longitudinal studies of plasma fibronectin in SLE may further define its role as an indicator of disease activity.

Synthesis, secretion, and deposition of fibronectin in cultured human synovium.

We examined fibronectin synthesis, secretion, and deposition in vitro by primary explants of rheumatoid synovium. Primary cultures initiated from tissue with monocytic infiltrates had higher levels of fibronectin synthesis; addition of dexamethasone at concentrations known to stimulate other tissue fibroblasts increased fibronectin synthesis and secretion. Newly synthesized fibronectin recovered from primary rheumatoid culture medium had a higher apparent molecular weight (240-245 kd), on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, compared with fibronectin recovered from passaged normal and rheumatoid cultures (230 kd). Primary rheumatoid explant cultures had a characteristic morphology which correlated with fibronectin deposition. Dense deposits of fibronectin extracellular matrix covered overlapping synoviocytes adjacent to esterase-positive mononuclear cells. Dexamethasone-treated cultures showed little fibronectin deposited as extracellular matrix and did not develop overlapping cellular networks. Characteristic patterns of fibronectin synthesis and deposition in primary rheumatoid cultures appear to result from interaction between fibroblastic and monocytic cells. This culture system may provide a model by which to study interactions between cells and extracellular matrix components that regulate synovial cell function.

The immunoreactivity, ligand, and cell binding characteristics of rheumatoid synovial fluid fibronectin.

Fibronectin promotes macrophage adherence and expression of Fc receptors, is chemotactic for fibroblasts, and is an opsonin for fibrin and denatured collagen. These properties suggest a role for fibronectin in the modulation of joint inflammation. Since structural modification of the fibronectin molecule has been shown to result in loss or de novo acquisition of opsonic and chemotactic activity, we determined the functional and immunochemical properties of fibronectin isolated from the inflamed joint. Eighty-six percent of synovial fluids obtained from patients with active rheumatoid arthritis (RA) contained fibronectin fragments, and 39% of the fluids no longer displayed the dimeric form. Compared with native fibronectin, RA peptides were as active in promoting synoviocyte chemotaxis and in glycosaminoglycan binding, but displayed lower affinity for fibrin and gelatin. Although comparable with intact protein in augmenting monocyte attachment to gelatin, the RA synovial fluid peptides did not augment monocyte attachment to fibrin. Analysis of whole synovial fluid and isolated fibronectins by enzyme immunoassay showed that the increased fibronectin immunoreactivity, previously reported in RA synovial fluid, measures intact and nearly intact protein and does not measure extensively degraded fragments.

Factors influencing the incorporation of fibronectin into synovial fluid cryoprotein.

Methods of synovial fluid collection and processing known to affect cryoprotein formation were examined to investigate the proposed role of fibronectin in synovial fluid cryoprecipitation. Fibronectin, a nonimmunoglobulin, noncomplement synovial fluid protein was present in all resolubilized synovial fluid cryoproteins studied. Radiolabeled fibronectin was precipitated from rheumatoid synovial fluid to a significantly greater extent (10%) than from noninflammatory (osteoarthritic) synovial fluid (2.8%), normal plasma (1.3%), or normal serum (0.5%) (p less than 0.01). Clotting of synovial fluid reduced fibronectin concentration 44% and resulted in a reduction in the amount and percent incorporation of fibronectin into cryoprotein, whereas heparinization and hyaluronidase treatment increased cryoprecipitable fibronectin. Affinity depletion of synovial fluid fibronectin resulted in loss of C1q and reduction in IgG in the cryoprotein; however, fibronectin, C1q, and IgG could not be co-eluted from affinity matrices of gelatin and protein A-Sepharose. Cryoprotein formation from pathologic synovial fluid depends in part on fibronectin and appears to involve interactions between fibronectin and fibrinogen as well as immunoglobulin complexes and complement components.

A multicenter study of outcome in systemic lupus erythematosus. I. Entry variables as predictors of prognosis.

A retrospective study of factors influencing survival in 1,103 patients with systemic lupus erythematosus (SLE) was carried out at 9 university centers diverse in geographic, socioeconomic, and racial characteristics. The mortality and disease characteristics of the patients at study entry varied widely among centers. The survival rates from the time patients with a diagnosis of SLE were first evaluated at the participating center was 90% at 1 year, 77% at 5 years, and 71% at 10 years. Patients with a serum creatinine greater than 3 mg/dl at study entry had the lowest survival rates: 48%, 29%, and 12% at 1, 5, and 10 years, respectively. Survival rate also correlated independently with the entry hematocrit, degree of proteinuria, number of preliminary American Rheumatism Association criteria for SLE satisfied, and source of funding of medical care. When data were corrected for socioeconomic status, race/ethnic origin did not significantly influence survival. Survival rates varied widely at different participating institutions, generally due to differences in disease severity. Place of treatment was independently associated with survival only in the second year after study entry. Disease duration before study entry did not account for the differences in disease severity.

A multicenter study of outcome in systemic lupus erythematosus. II. Causes of death.

Causes of death were examined for 1,103 systemic lupus erythematosus patients who were followed from 1965 to 1978 at 9 centers that participated in the Lupus Survival Study Group. A total of 222 patients (20%) died. Lupus-related organ system involvement (mainly active nephritis) and infection were the most frequent primary causes of death. Causes of death were similar throughout the followup period. Hemodialysis had little impact on the length of survival for patients with nephritis. Active central nervous system disease and myocardial infarction were infrequent causes of death. There were no deaths from malignancy.