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Biomedical subjects

F C McDuffie

Publications and source records attributed to F C McDuffie.

At least 19 recordsLinked to original sources

The use of long-acting drugs in the treatment of rheumatoid arthritis.

Experience to date strongly indicates that long-acting drugs currently used in treatment of rheumatoid arthritis are very potent antiinflammatory agents which act in most cases by completely unknown mechanisms. All of them have built in but recognizable toxicity which can usually be prevented by appropriate monitoring. Although most of them offer relatively short term (up to 3 years) benefits, with the probable exception of methotrexate, nonetheless they can offer for a period of time improved function and relief of pain for many individuals. Thus, even though they do not dramatically affect the long-range outcome of the disease, they continue to offer useful benefit for patients with rheumatoid arthritis who are not responding to conservative therapy. Some of the long-acting agents are only slightly more toxic than the widely nonsteroidal antiinflammatory drugs which do have a definite risk of serious upper gastrointestinal bleeding. Currently the use of combinations as well as the continued introduction of new drugs in this class, offer hope that greater benefit than we can currently provide is within reach over the next few years.

Anti-Inflammatory Agents

Estimates of the prevalence of selected arthritic and musculoskeletal diseases in the United States.

The National Arthritis Data Workgroup focused its studies primarily on joint disease with the addition of osteoporosis which is a frequently occurring musculoskeletal condition and public health problem. We used national data sets as well as published studies to estimate prevalence in the United States. We report on prevalence rather than incidence because of the difficulty in defining the point of onset and because primary national data sources currently available are concerned with disease prevalence.

Adolescent

The role of the Arthritis Foundation in training of rehabilitation research manpower.

In 1973 the Arthritis Foundation established a research training program for nonphysician health professionals in fields related to nonmedicinal care such as physical therapy, occupational therapy, psychology and health education. This program is primarily designed for individuals performing the research involved in a predoctoral program. For trained investigators in this field the Foundation offers a research grants program as well.

Arthritis

Antigen detection in immune complexes by a modified staphylococci binding assay and Western blot analysis.

The combination of a modified Staphylococci binding assay for immune complexes and Western blot analysis is described for the isolation and detection of antigen in immune complexes from human sera. The strategy of the procedure is to preclear immune complexes from other serum components by sequential polyethylene glycol precipitation and incubation with insoluble protein A under conditions in which immune complexes are preferentially bound. Immune complexes are eluted from protein A in sodium dodecyl sulfate buffer and dissociated by acrylamide electrophoresis. Resolved proteins are then transblotted to nitrocellulose, and antigen is detected with specific antibody. Immune complexes were prepared in vitro with an antigen (keyhole limpet hemocyanin) that focuses well on electrophoresis and for which a potent immunologic probe (antibody) was available. In this system, antigen could be detected when immune complexes were present in sera in concentrations as low as 20 micrograms aggregated-IgG eq/ml, regardless of antigen-antibody ratio. We demonstrate the detection of horse globulin in immune complexes from a patient with acute serum sickness and hepatitis B virus antigen in complexes from a patient with vasculitis.

Adult

Morbidity impact of rheumatoid arthritis on society.

Classic and definite rheumatoid arthritis affects from 0.5 to 1 percent of the United States' population between the ages of 20 and 80. In the age group of 55 to 75 years, this figure increases to 4.5 percent. In addition to the pain and suffering produced by this disease, family structure is dramatically affected--the divorce rate for patients with rheumatoid arthritis is 70 percent above that for the general population. Rheumatoid arthritis also results in serious economic loss to society. In 1983, the direct cost (out-of-pocket expense for medical care) was $777 million, and the indirect cost (loss of productivity) was $215 million, with a total of approximately $1 billion. The average person with stage III rheumatoid arthritis suffers a 60 percent decline in earnings during the first six years after onset of the disease. Recent studies have indicated that the ability to remain employed depends at least as much on job-related factors as on the extent of disease or success of medical treatment. Job autonomy or the ability to control one's working conditions is the most important factor. Other important variables are education, seniority, and work that is not excessively physically demanding. Good transportation between home and job is also an essential requirement for remaining employed. There are few data available on the cost/benefit ratio of the treatment of rheumatoid arthritis. An 18-month study showed a trend toward greater improvement in patients given optimal care by a team of experts in a medical center as compared with average treatment provided in the community. A study in Scotland on cost of hospitalization of 366 patients (about one half underwent surgery) showed cost benefits of xi 14,000 to xi 131,000 over a five- to 10-year period for those who returned to work. Patients who did not return to work incurred medical costs of xi 100,000. There is little question that more effective medical treatment and better rehabilitation strategies for people with rheumatoid arthritis would provide significant benefits for patients, their families, and society.

Adolescent

Immunoassay for IgG rheumatoid factor with a murine monoclonal anti-Fd antibody.

Conventional radioimmunoassays for IgG rheumatoid factors (RF) detect the binding of IgG RF (or their F(ab')2 fragments) to solid-phase human IgG Fc fragments or rabbit IgG. Binding is detected with a radiolabeled antibody that is IgG-specific but is nonreactive with human Fc (i.e., an alpha-Fd reagent) or with rabbit IgG. Anti-Fd reagents are quite laborious to produce. We developed a murine monoclonal alpha-Fd antibody, confirmed its specificity, and compared it with conventional rabbit alpha-Fd in the IgG RF radioimmunoassay. We also adapted the assay to an enzyme-linked assay with both human Fc and rabbit IgG as antigen. We compared the four assay methods with each other and examined their relationship to certain clinical and laboratory features of rheumatoid arthritis.

Animals

The turnover in normal dogs of prothrombin and its fragments; effect of induced intravascular coagulation.

When 125I-labeled canine prothrombin was given to normal adult dogs intravenously, it was calculated that 240% of the plasma prothrombin crossed the capillary barrier per day, 410% of the interstitial prothrombin returned to the blood stream daily, and 79% of the plasmatic prothrombin was catabolized per day. These data are in close agreement with those observed for bovine prothrombin in calves by Takeda (1970). When derived from normal dog prothrombin, prethrombin-1 is a mixture of 2 polypeptides, one larger than the other, and both present in about equal amounts. The longer peptide, "prethrombin-1-long," was catabolized twice as fast as prothrombin, and the shorter, "prethrombin-1-short," 4 times faster. Prothrombin fragment-1 was catabolized by the normal dog still more rapidly. The catabolism of prothrombin was not accelerated in 3 dogs receiving continuous infusions of a thromboplastic emulsion of dog brain. Nor was the level of prothrombin in their plasma remarkably altered.

Afibrinogenemia

Comparison of three immunoassays for immune complexes in rheumatoid arthritis.

Three widely used radioassays that depend on different principles for the measurement of circulating immune complexes (CIC) in biologic fluids are the monoclonal rheumatoid factor (mRF), Raji cell, and C1q binding tests. A comparison of the ability of these methods to measure immune complex-like material in 71 sera and 30 synovial fluids of 91 patients with rheumatoid arthritis (RA) was carried out by a group working in adjacent laboratories in a single institution. The highest number of abnormal levels in the seropositive group was detected by the C1q binding assay (91%). Levels of CIC by the mRF and Raji cell tests were elevated in 81% and 76% of the patients, respectively. The closest correlation was between the Raji and mRF tests (r = 0.44 and P = 0.002) although one depends on complement fixation and one does not. Though significant correlations between the levels of CIC determined by the C1q test and either the mRF (P = 0.2) or Raji cell (P = 0.3) assay were not found in this group, 59% of the samples had elevated levels by all three tests. The frequency of CIC in the sera of patients with seronegative RA was much lower, with the C1q test again giving the highest number of abnormal results (29% versus 16% and 12% for the Raji and mRF tests). In view of the technical problems associated with these tests, particularly lack of a uniform reliable standard, it is likely that all three tests measure the same material in most RA sera and that some of the differences observed are related to inherent variability in the tests themselves rather than intrinsic differences among the CIC detected in these samples.

Adult

Cellular immunity in polymyalgia rheumatica and giant cell arteritis: lack of response to muscle or artery homogenates.

Peripheral blood lymphocyte functions were evaluated in 20 patients with active polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA) by determining the percent of E-rosette-forming cells and by measuring the uptake of tritiated thymidine by peripheral blood lymphocytes after exposure to common infectious antigens and to homogenates of homologous and heterologous artery, muscle, and elastin. Although lymphocytes from patients with PMR and/or GCA were stimulated slightly by artery and muscle homogenates, no differences in lymphocyte responses were found when the results were compared with 22 normal controls and 16 patients with rheumatoid arthritis. The hypothesis that GCA results from a cellular immune reaction to normal or diseased arterial wall antigens is not supported by these studies.

Aged

Measurement of immunoglobulin binding to synovial fibroblast monolayers: comparison of staphylococcal protein A binding to cytotoxic assay methods.

We have studied the binding of rabbit antibody to cultured synovial fibroblasts by 3 methods: complement mediated cell lysis, 125I-labeled staphylococcal protein A ([125I]PrA) and antibody dependent cell mediated cytotoxicity (ADCC). The relative sensitivities of these 3 methods is 1 : 33 : 3300 respectively. The [125I]PrA binding method is shown to quantitatively detect cell bound IgG with a molar stoichiometry of approximately 1 : 1, protein A (PrA) to IgG if PrA is present in excess.

Animals

Consumption of C3 via the classical and alternative complement pathways by sera and synovial fluids from patients with rheumatoid arthritis.

Five sera and four synovial fluids from patients with rheumatoid arthritis were found to contain substances which consumed hemolytic C3 in normal human serum (NHS) and in normal guinea pig serum (NGPS). These fluids were then tested for ability to activate the alternative pathway by incubating them with NHS containing MgEGTA and C4 deficient GPS. All sera and two synovial fluids depleted C3 in these reagents, indicating direct activation by the alternative pathway. Density gradient ultracentrifugation demonstrated C3 fixing activity in some specimens in the greater than 19s regions. These substances may also activate complement similarly in vivo and participate in the development of inflammatory processes associated with this disease.

Adult