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Biomedical subjects

A J Bridges

Publications and source records attributed to A J Bridges.

At least 55 records · Page 3Linked to original sources
PubMed1993

A clinical and immunologic evaluation of women with silicone breast implants and symptoms of rheumatic disease.

OBJECTIVE: To describe the clinical and serologic features of women with silicone breast implants who were referred for symptoms of rheumatic disease. DESIGN: A case series. SETTING: University and private rheumatology practices. PATIENTS: A total of 156 women with silicone breast implants and rheumatic disease complaints. Controls for the serologic studies included women with silicone implants and no rheumatic symptoms (n = 12) and women with fibromyalgia without silicone implants (n = 174). MEASUREMENTS: Complete physical examination and testing for immunoglobulins; complement; C-reactive protein; rheumatoid factor; and autoantibodies by indirect immunofluorescence, immunodiffusion, and Western blot. RESULTS: Three subgroups of patients were defined based on clinical and laboratory findings: joint and muscle pain (n = 95), joint swelling (n = 32), and connective tissue disease (n = 29). Most women had normal immunologic studies. The patients with joint swelling had mild, asymmetric, rheumatoid-factor-negative synovitis that did not meet American College of Rheumatology criteria for rheumatoid arthritis. Fourteen patients had a scleroderma-like illness and anti-centromere or anti-PM-Sci antibodies by Western blot. Ten patients had a positive Western blot for BB' polypeptide, a small nuclear ribonucleoprotein (snRNP), but did not meet criteria for systemic lupus erythematosus. No autoantibodies to known disease-related polypeptides were detected on Western blot in the control groups. CONCLUSION: Most women with silicone implants and rheumatic complaints had normal results of serologic tests and nonspecific symptoms, suggesting no serious connective tissue disease. However, a subset of women had clinical signs and serologic tests that were unusual even for referred patients. These observations suggest, but cannot establish, that some women with silicone breast implants may develop atypical immunologic reactions.

Adult↗
PubMed1993

Inhibition of urokinase by 4-substituted benzo[b]thiophene-2-carboxamidines: an important new class of selective synthetic urokinase inhibitor.

Urokinase-type plasminogen activator (uPA) is an important mediator of cellular invasiveness. Specifically, cell surface receptor-bound uPA activates plasminogen to the potent general protease plasmin, which then degrades extracellular matrix or basement membrane either directly or via proteolytic activation of latent collagenases. Thus, cell surface uPA initiates an extracellular proteolytic cascade with which invasive cells eliminate barriers to movement. Since cellular invasiveness plays important roles in several disease states, including cancer metastasis and invasion, arthritis and inflammation, and diabetic retinal neovascularization, the development of synthetic uPA inhibitors is an attractive therapeutic goal. Here we show that 4-substituted benzo[b]thiophene-2-carboxamidines represent an important new class of potent and selective synthetic uPA inhibitor. Two compounds in this class, B428 and B623, inhibit human uPA in plasminogen-linked assays with median inhibition concentration (IC50) values of 0.32 and 0.07 microM, respectively. This level of inhibition represents 20- and 100-fold increases in potency, respectively, relative to the 6-7 microM potencies reported for amiloride and 4-chlorophenylguanidine, the two most potent selective synthetic uPA inhibitors previously described. Importantly, both compounds show > 300-fold selectivity for uPA relative to tissue-type plasminogen activator and > 1000-fold selectivity relative to plasmin. Lineweaver-Burk analyses show uPA inhibition by B428 and B623 to be competitive in nature with inhibition constants (Ki) of 0.53 and 0.16 microM, respectively. Since it is cell surface uPA and not free or secreted uPA that is primarily responsible for cellular invasiveness, biologically effective uPA inhibitors must be capable of inhibiting cell surface uPA. B428 and B623 meet this criterion by inhibiting cell surface uPA on HT1080 human fibrosarcoma cells with IC50 values of 0.54 and 0.20 microM, respectively. Moreover, degradation of [3H]fibronectin by HT1080 cells via cell surface uPA-mediated, plasminogen-dependent mechanisms is inhibited by B428 and B623, with IC50 values of 1.5 and 0.39 microM, respectively. In summary, 4-substituted benzo[b]thiophene-2-carboxamidines such as B428 and B623 represent the most potent class of competitive synthetic uPA inhibitors currently known. Their ability to selectively inhibit both free and cell surface uPA as well as cell surface uPA-mediated cellular degradative functions suggests that this class of compounds may hold significant promise for further development as antiinvasiveness drugs.

Amidines↗
PubMed1993

AI/LEARN/Rheumatology. A comparative study of computer-assisted instruction for rheumatology.

OBJECTIVE: To assess the effectiveness of AI/LEARN/Rheumatology, a computer-controlled interactive videodisc system for teaching. METHODS: We assessed improvement in knowledge about rheumatic diseases, using a pretest and posttest in a control year and a treatment year. The subjects were medical students and postgraduate trainees taking the rheumatology elective. The control year used traditional lectures and the standard rheumatology curriculum. The treatment year used AI/LEARN/Rheumatology in place of lectures on rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis. RESULTS: The trainees showed significant improvement in knowledge in both the control year and the treatment year (P < 0.0001 for both). The average time spent using AI/LEARN/Rheumatology was similar to the time spent in lectures (3 hours). The number of patient consultations in which trainees participated was lower in the treatment year than in the control year; however, the adjusted posttest scores using the pretest as a covariate tended to be higher in the treatment year (P = 0.10). Analysis of covariance of the adjusted posttest scores for the treatment year only showed that the trainees who spent more time using AI/LEARN/Rheumatology learned more (r = 0.57). Trainees felt that AI/LEARN/Rheumatology was the most helpful educational experience of the elective. CONCLUSION: AI/LEARN/Rheumatology is an effective means of teaching about the rheumatic diseases. It has many advantages: availability for independent study, effective use of trainee's time, and liberation of faculty time from lectures. Trainees enjoyed using AI/LEARN/Rheumatology.

Computer-Assisted Instruction↗
PubMed1993

The synthesis of three 4-substituted benzo[b]thiophene-2-carboxamidines as potent and selective inhibitors of urokinase.

Efficient synthesis of structurally novel 4-substituted benzo[b]thiophene-2-carboxamidines 1-3, which selectively inhibit urokinase-type plasminogen activator (uPA) with IC50 values of 70-320 nM, are described. The key intermediate, methyl 4-iodobenzo[b]thiophene-2-carboxylate (7), is prepared from 3-fluoroiodobenzene in two steps in 70% overall yield via fluorine-directed metalation/formylation and subsequent thiophene annulation. Amidination of ester 7 gives the 320 nM inhibitor 1. Palladium-catalyzed arylacetylene and vinyl stannane couplings with ester 7 or 4-iodobenzo[b]thiophene-2-carbonitrile (16, derived from 7), respectively, followed by amidination leads to the more potent inhibitors 2 (IC50 = 133 nM) and 3 (IC50 = 70 nM). These compounds represent an important new class of synthetic uPA inhibitors, with carboxamidine 3 being the most potent selective inhibitor currently described in the literature.

Amidines↗
PubMed1993

Tissue plasminogen activator treatment of digital thrombosis in severe Raynaud's phenomenon--a case report.

A thirty-one-year-old woman with long-standing mixed connective tissue disease and severe obliterative vasculopathy of the digits developed digital thrombosis of the first three digits of the left hand after using an electric blow dryer. The digits remained cool, cyanotic, and painful for thirty-six hours before medical evaluation. She was given 100 mg recombinant tissue plasminogen activator (TPA) intravenously. Within one hour the blood flow to the digits returned, accompanied by severe intermittent vasospasm of the digits. The thumb did not necrose; however, the second and third digits required amputation. No improvement was noted in the patient's baseline Raynaud's phenomenon or digital pressures of the uninvolved digits after TPA treatment. This case documents the usefulness of TPA for digital thrombosis in the setting of vasculopathy of connective tissue disease. However, it does not support the utility of a single dose of TPA for severe Raynaud's phenomenon and recurrent digital ischemia in patients with connective tissue disease.

Adult↗
PubMed1992

New 8-(trifluoromethyl)-substituted quinolones. The benefits of the 8-fluoro group with reduced phototoxic risk.

A series of 8-(trifluoromethyl)-substituted quinolones has been prepared and evaluated for in vitro and in vivo antibacterial activity, and phototolerance in a mouse phototolerance assay. These analogues were compared to the corresponding series of 6,8-difluoro- and 6-fluoro-8H-quinolones (ciprofloxacin type). Although their in vitro antibacterial activities are less than the 6,8-difluoro analogues, the 8-(trifluoromethyl)quinolones are generally equivalent to their 8H analogues. In vivo, they are comparable to the 6,8-difluoro series and show up to 10-fold improvement in efficacy when compared to their ciprofloxacin counterparts vs Streptococcus pyogenes and Streptococcus pneumonia. In the phototolerance model, the 8-(trifluoromethyl)quinolones are comparable to the 8H-quinolones. Both of these series display much higher no effect doses (greater tolerance) than the corresponding 6,8-difluoroquinolones.

4-Quinolones↗
PubMed1992

Acute iritis associated with primary Sjögren's syndrome and high-titer anti-SS-A/Ro and anti-SS-B/La antibodies. Treatment with combination immunosuppressive therapy.

OBJECTIVE: We describe a patient with primary Sjögren's syndrome who developed severe, acute, anterior uveitis (iritis), an uncommon complication in this setting. METHODS: We present the case report of the clinical findings, course, treatment, and resolution of the acute uveitis. Titers of anti-SS-A/Ro and anti-SS-B/La antibodies were assessed (by immunodiffusion), as were fluorescent antinuclear antibodies (on HEp-2 cells) and cryoglobulins. RESULTS: Initial treatment with topical steroids, oral prednisone (20 mg/day), and oral methotrexate was unsuccessful. The iritis resolved after combined treatment with intravenous cyclophosphamide (1,500 mg/month), high-dose prednisone (60 mg/day), and cyclosporine (5 mg/kg/day). CONCLUSION: An uncommon, severe complication of primary Sjögren's syndrome is acute uveitis. Combination immunosuppressive therapy may be needed to control this condition.

Antibodies, Antinuclear↗
PubMed1992

AI/Learn/Rheumatology. A computer-assisted educational system for teaching about rheumatic diseases.

Education of health professionals about the rheumatic diseases is in need of improvement. The computer is an instrument that can be used efficiently to educate large numbers of users. With specific educational principles in mind, we developed AI/Learn/Rheumatology, a computer-assisted interactive videodisc system for teaching the rheumatic diseases. While interacting with the user, it conveys knowledge using visual and problem-solving techniques. The system is efficient, enjoyable to use, and useful for small groups and independent study. It is applicable for teaching medical and allied health professional students, postgraduate trainees, and primary care physicians.

Computer-Assisted Instruction↗
PubMed1992

Psychological factors, immunologic activation, and disease activity in rheumatoid arthritis.

The purpose of this study was to use structural equation modeling techniques to examine potential interrelationships among psychological factors, immunologic activation, and disease activity in rheumatoid arthritis (RA). The subjects were 80 male patients with a diagnosis of classic or definite RA. Measures included the Beck Depression Inventory, the Arthritis Helplessness Index, and the Arthritis Impact Measurement Scales (AIMS) pain score. Joint counts and immunophenotypic analyses of peripheral blood lymphocytes also were collected. Path analysis showed that percentage of HLA-DR+ cells in the peripheral blood and helplessness were related to join count. In addition, joint count had an effect upon depression. Depression had an effect upon pain, but there was no reciprocal effect of pain upon depression. This study describes a preliminary path model of interrelationships among psychological factors, immunologic activation, and disease activity in RA.

Aged↗
PubMed1992

GALE: a graphics assisted learning environment for computer-based interactive videodisc education.

GALE, a Graphics Assisted Learning Environment, is a computer-based interactive videodisc authoring tool. GALE was created as the authoring package for AI/LEARN/Rheumatology, an independent study system for teaching rheumatology to medical trainees. GALE has potential widespread application beyond rheumatology. Interactive videodisc technology is a prime feature of GALE. Other highlights are: WordPerfect macros which simplify programming, graphics-based large text characters, tracking of user responses, hypertext-like definition capabilities, color coded screens to distinguish between hypertext branches and the mainstream of the course content and ability to overlay text on the video image. GALE runs on a PC-compatible computer with selected Pioneer LaserDisc players. GALE uses WordPerfect 5.1 for text editing and has been designed for use by non-programmers.

Computer Graphics↗
PubMed1992

A controlled study of lymphocyte subsets in rheumatoid arthritis.

The purpose of this study was to determine if patients with rheumatoid arthritis (RA) exhibited unique patterns of peripheral blood lymphocyte (PBL) subsets in comparison to patients with osteoarthritis (OA) and, further, if such differences related to disease activity or nondisease factors. Data from 63 RA patients and 47 OA patients revealed that the RA patients had lower absolute numbers of CD2+ and CD4+ lymphocytes. Small differences also were found in selected B-cell subsets and subsets of lymphocytes expressing CD16 and/or CD57 antigens. Further analysis revealed that these differences were due primarily to the effects of cytotoxic medications in the RA group. However, there were also alterations in some subsets independent of medication groups. PBL subsets in RA patients did not relate to chronic low-dose prednisone or measures of disease activity. This study demonstrated the need to control carefully for variables such as age and medication in immunophenotypic investigations of RA.

Aging↗
PubMed1992

Joint hypermobility in adults referred to rheumatology clinics.

Joint hypermobility is a rarely recognised aetiology for focal or diffuse musculoskeletal symptoms. To assess the occurrence and importance of joint hypermobility in adult patients referred to a rheumatologist, we prospectively evaluated 130 consecutive new patients for joint hypermobility. Twenty women (15%) had joint hypermobility at three or more locations (greater than or equal to 5 points on a 9 point scale). Most patients with joint hypermobility had common musculoskeletal problems as the reason for referral. Two patients referred with a diagnosis of rheumatoid arthritis were correctly reassigned a diagnosis of hypermobility syndrome. Three patients with systemic lupus erythematosus had diffuse joint hypermobility. There was a statistically significant association between diffuse joint hypermobility and osteoarthritis. Most patients (65%) had first degree family members with a history of joint hypermobility. These results show that joint hypermobility is common, familial, found in association with common rheumatic disorders, and statistically associated with osteoarthritis. The findings support the hypothesis that joint hypermobility predisposes to musculoskeletal disorders, especially osteoarthritis.

Adolescent↗
PubMed1992

Preliminary evaluation of learning via the AI/LEARN/Rheumatology interactive videodisc system.

AI/LEARN/Rheumatology is a level three videodisc system to teach clinical observational skills in three important diseases: rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. The AI/LEARN software was developed on an independent authoring system called GALE designed for MS-DOS based computers. The purpose of this paper is to present preliminary data about the efficacy of teaching by the use of an interactive videodisc system as evaluated by examinations centered upon disease-oriented learning objectives and by attitude questionnaires. We tested the efficacy of the AI/LEARN/Rheumatology system using both medical students and residents taking the rheumatology elective. Data collected were on learning, attitudes, and ranking of curricular elements of the rotation. We kept records on the student time and search path through the interactive videodisc system. Control data were collected during 1990, before the AI/LEARN/Rheumatology program was available. Data for the treatment groups were collected during 1991 and 1992, while the trainees used the AI/LEARN/Rheumatology system. The basic difference between the control year and the treatment year curricula was the substitution of AI/LEARN/Rheumatology for three hours of lecture covering the three target diseases. AI/LEARN/Rheumatology was as effective as traditional methods of instruction as measured by scores on a multiple choice test. Student and resident learning was related to the time spent on the system. Students and residents ranked the AI/LEARN/Rheumatology system as the single most helpful learning tool in their 8 week rheumatology block, ranking it above the examination of patients.

Arthritis, Rheumatoid↗
PubMed1992

Bronchiolitis obliterans organizing pneumonia and scleroderma.

Pulmonary involvement in scleroderma is characterized by interstitial fibrosis and pulmonary hypertension. Although bronchiolitis obliterans organizing pneumonia (BOOP) may be associated with a variety of connective tissue diseases and their treatment, there are only rare reports of bronchiolitis associated with scleroderma. We describe 2 patients with scleroderma and rapidly evolving pulmonary infiltrates, which upon biopsy showed histologic findings of BOOP. Each patient had severe restrictive lung disease and markedly diminished diffusion capacity. Treatment with high dose prednisone showed a good response in one patient. The rapid course of pulmonary findings in these patients differs from the usual course of pulmonary fibrosis in scleroderma. Although BOOP is a rare finding in scleroderma, our findings suggest that rapid pulmonary decompensation or atypical findings for pulmonary fibrosis should prompt consideration for an open lung biopsy. Finding a potentially steroid responsive disorder in an otherwise steroid unresponsive disorder has important clinical implications.

Adult↗
PubMed1991

Human synovial mast cell involvement in rheumatoid arthritis and osteoarthritis. Relationship to disease type, clinical activity, and antirheumatic therapy.

Mast cells were isolated by enzymatic digestion of synovium obtained from 48 patients with rheumatoid arthritis (RA) and 42 patients with osteoarthritis (OA). A significantly lower percentage of stainable synovial mast cells was obtained by tissue digestion from patients with clinically active RA compared with those with less active disease. The 54 patients treated with nonsteroidal antiinflammatory drugs had a significantly lower percentage of stainable synovial mast cells in cell suspension than did the other 36 patients. When anti-IgE antibody was used as a secretagogue in vitro, significantly greater histamine release was observed from synovial mast cells of RA patients compared with OA patients. Greater histamine release in response to anti-IgE was observed in the RA patients with more clinically active disease and those who were treated with prednisone, compared with RA patients without these features. Synovial mast cells of RA patients treated with a disease-modifying antirheumatic drug had a significantly lower mean histamine content than did cells from patients not receiving such treatment. Our data suggest that there are differences between synovial mast cells from tissues of patients with RA and OA and suggest that synovial mast cells may be activated in clinically active RA. In addition, the data indicate an effect of systemic antirheumatic therapy on mast cells isolated from synovium of patients with arthritis.

Adult↗
PubMed1991

Biopsychosocial parameters of disease activity in rheumatoid arthritis.

The purpose of this study was to examine the applicability of a biopsychosocial model for estimating disease activity in rheumatoid arthritis (RA). Sixty-three patients with RA were evaluated at baseline, 3 months, and 6 months. Joint counts were collected as the measure of disease activity. Peripheral blood immunophenotypic subsets, demographic characteristics, and psychological measures were obtained and entered into hierarchical regression analyses, with the joint count as the dependent variable. Immunophenotypic subsets (that is, CD57+/CD16-, HLA-DR+) were predictive of disease activity at all three time intervals. At baseline and 3 months, psychological variables (that is, helplessness and depression) were significantly related to joint counts, and the full model was highly significant. The conclusion was that the biopsychosocial perspective is useful for estimating RA disease activity.

Aged↗