Epidemiology versus outcome. The silicone breast implant controversy.
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Biomedical subjects
Publications and source records attributed to F B Vasey.
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OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis (AS) that is not controlled with nonsteroidal antiinflammatory drug therapy. METHODS: Two hundred sixty-four patients with AS were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on morning stiffness, back pain, and physician and patient global assessments. RESULTS: While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment, no difference was seen at the end of treatment. Response rates were 38.2% for SSZ and 36.1% for placebo (P = 0.73). The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). AS patients with associated peripheral arthritis showed improvement that favored SSZ (P = 0.02). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic, longstanding disease. SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement. This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients.
OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy. METHODS: Two hundred twenty-one patients with PsA were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint pain/ tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA.
OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective in the treatment of reactive arthritis (ReA) that has been unresponsive to nonsteroidal antiinflammatory drug (NSAID) therapy. METHODS: One hundred thirty-four patients with ReA who had failed to respond to NSAIDs were recruited from 19 clinics, randomized (double-blind) to receive either SSZ or placebo, and followed up for 36 weeks. The definition of treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed improvement in the patients taking SSZ compared with those taking placebo, which appeared at 4 weeks and continued through the trial (P = 0.02). At the end of treatment, response rates were 62.3% for SSZ treatment compared with 47.7% for placebo treatment. The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and effective in patients with chronically active ReA.
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The controversy over silicone breast implants continues. This review considers evidence on both sides of the issue. Clinical observations suggests consistent chronic fatigue, muscle pain, joint pain, lymphadenopathy, peripheral neuritis and bladder dysfunction syndrome. Epidemiologic studies of defined connective tissue diseases do not show an association, but some studies show a statistical increase in prevalence of symptoms. The author believes symptomatic women should consider having the breast implants removed and not replaced.
We report the clinical findings in a series of women with silicone breast implants (SBI) and rheumatic disease. These findings represent the first 50 patients seen at the University of South Florida Medical Clinic between March 1977 and January 1991. The average age was 44 years with a range of 30 to 66 years. The most common clinical findings included chronic fatigue, muscle pain, joint pain, joint swelling, and lymphadenopathy. Seventeen women with an average Steinbrocker functional class of 1.8 decided not to remove the implants. An average of 14 months later, follow-up showed no change in their condition. Thirty-three women, with an average functional class of 2.5 underwent implant removal. Twelve of the 33 had documented implant rupture. During an average follow-up of 22 months after implant removal, 24 women improved clinically, 8 did not change, and 1 worsened. We believe this series supports a relationship between silicone breast implants and rheumatic disease signs and symptoms. Although this report is not a definitive epidemiological study, findings suggest that physicians should inform women about the possible benefit of implant removal.
A retrospective study was performed to determine the frequency of new symptoms and diseases after silicone breast implantation. Questionnaires were mailed to 826 women who made up a breast implant group (n = 516) and a control group who had undergone blepharoplasty (n = 124), liposuction (n = 111), or rhinoplasty (n = 75). Responses were obtained from 370 women (45 percent); however, 68 of these patients (18 percent) were considered ineligible. The overall response rate was 59 percent for the breast implant group and 46 percent for controls. The 302 eligible women included patients with silicone breast implants (n = 222) and controls (n = 80). Women with implants were significantly younger than controls, the median age of women with breast implants being 37 years compared with 46.5 years for controls (p < 0.0001). We compared the incidence of 23 symptoms and 4 connective-tissue diseases after cosmetic surgery in the two groups. The symptoms of swollen glands under arms (p < 0.05) and tender glands under arms (p < 0.01) were statistically more frequent in the breast implant group. The symptom change in skin color was more common in the controls (p < 0.001). The Bonferroni correction for multiple (27) endpoints adjusts the 5 and 1 percent significance cutoff points to 0.00185 and 0.00037, respectively, leaving only change of skin color significant at the 5 percent level on the adjusted data. No cases of scleroderma or lupus were found, and the incidence of arthritis was not significantly different between the implant and control groups.
The purpose of this study is to review the background, safety, and potential complications of silicone breast implants. Relevant studies were identified using a MEDLINE search of the English-language literature, followed by a manual search of the references of all identified articles and a review of abstracts from the 1992 American College of Rheumatology meeting. Review of the literature suggests that silicone does not appear to fulfill the characteristics of an ideal synthetic soft-tissue substitute, although it may be the best substitute available. Silicone breast implants are associated with local inflammation and tissue fibrosis with breast fibrous capsule contracture developing in 10% to 40% of the patients. There are no epidemiologic data that establish a direct link between silicone and cancer or rheumatic disease. However, scleroderma appears to be overrepresented among the published articles on patients with silicone breast implants and rheumatic disease. Autoantibodies of unclear significance may be found in 5% to 30% of women with silicone breast implants. Large, longitudinal, population-based studies that include patients who have had implants for 5 to 15 years may be necessary to fully understand the relationship of silicone implants and immune dysfunction.
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.