Silicone breast implants: epidemiological evidence of sequelae.
Skeptics may certainly find fault with the third study (the only one to report a significant finding) or with all or any of the statistics described. But few could argue, after examining these studies, that the relative risk for a known and well-defined connective tissue disease is likely greater than 2. Another possibility has been raised, one that calls to mind other difficult-to-study syndromes linked to exposures. In a study addressing Gulf War syndrome, signs and symptoms were often mentioned that proved difficult to describe systematically and therefore difficult to study. What if a suspected silicone exposure syndrome were so mild and transient that it did not warrant a physician visit (as in the Mayo Clinic study). receive a diagnosis (as in the Nurses' Health Study), or require admission to a hospital (as in the Danish and Swedish studies)? And if such a disorder were, in fact, mild and transient, should it merit the concern that has been shown and the compensation that has been awarded in the silicone implant litigation cases to date? We suggest that neither a well-described disorder with a relative risk of less than 2 nor a transient and mild disorder seems compatible with the number of litigants over silicone implants and the apparent seriousness of their complaints. Some 400,000 women joined in one class action suit for damages, and 170,000 joined in another. Even if there had been 2 million implants undertaken in the United States over the 3 decades in which implant surgery has been practiced (and some estimates put the number closer to 1 million), there is no conceivable way in which a relative risk of 2 or 3 (or even 4) for each of the rare syndromes reported could explain so many exposed women being affected. At most, 2200 out of 2 million unexposed women would be expected to have had any one of the listed forms of connective tissue disorders, most of which are very rare. Doubling the risk among the exposed population yields 4400, and increasing the risk 20-fold produces 44,000. At this rate, there is no way in which 400,000 litigants could all be affected. Extensions of the already-completed studies are ongoing, at least 1 of which is government funded; apparently it is thought in the United States (though not in the United Kingdom or elsewhere) that there is still room for reasonable doubt as to the supposed causal relationships. But if epidemiology is invoked in the interest of public health to prevent the many uses of silicone, the weight of the evidence abstracted here supports the inference that silicone breast implants have not been proved guilty of causing connective tissue disorders. (+info)
Pulmonary artery pressure variation in patients with connective tissue disease: 24 hour ambulatory pulmonary artery pressure monitoring.
BACKGROUND: The specific contribution of secondary pulmonary hypertension to the morbidity and mortality of patients with underlying lung disease can be difficult to assess from single measurements of pulmonary artery pressure. We have studied patients with secondary pulmonary hypertension using an ambulatory system for measuring continuous pulmonary artery pressure (PAP). We chose to study patients with connective tissue disease because they represent a group at high risk of pulmonary vascular disease, but with little disturbance of lung function. METHODS: Six patients (five with progressive systemic sclerosis and one with systemic lupus erythematosis) were studied. They underwent preliminary cardiopulmonary investigations followed by Doppler echocardiography, right heart catheterisation, and ambulatory pulmonary artery pressure monitoring to measure changes in pressure over a 24 hour period including during a formal exercise test. RESULTS: All patients had pulmonary hypertension as measured by Doppler echocardiography with estimated pulmonary artery systolic pressures of 40-100 mm Hg. Pulmonary function testing revealed virtually normal spirometric values (mean FEV1 86.9% predicted) but marked reduction in CO gas transfer factor (KCO 57.8% predicted). Exercise responses were impaired with mean VO2max 50.6% predicted. Ambulatory PAP monitoring indicated significant changes in pressures with variation in posture and activity throughout 24 hours. Resting PAP did not predict the change in PAP seen on exercise. CONCLUSION: Conventional methods of assessment of the pulmonary circulation based on single measurements in the supine position may underestimate the stresses faced by the right side of the circulation. This ambulatory system allows monitoring of pulmonary haemodynamics continuously over 24 hours during normal activities of daily living. These measurements may increase our understanding of the contribution made by secondary pulmonary hypertension to the morbidity and mortality of the underlying lung disease. (+info)
Petroleum distillate solvents as risk factors for undifferentiated connective tissue disease (UCTD).
Occupational solvent exposure may increase the risk of connective tissue disease (CTD). The objective of this case-control study was to investigate the relation between undifferentiated connective tissue disease (UCTD) and solvent exposure in Michigan and Ohio. Women were considered to have UCTD if they did not meet the American College of Rheumatology classification criteria for any CTD but had at least two documented signs, symptoms, or laboratory abnormalities suggestive of a CTD. Detailed information on solvent exposure was ascertained from 205 cases, diagnosed between 1980 and 1992, and 2,095 population-based controls. Age-adjusted odds ratios (OR) and 95 percent confidence intervals (CI) were calculated for all exposures. Among 16 self-reported occupational activities with potential solvent exposure, furniture refinishing (OR = 9.73, 95 percent CI 1.48-63.90), perfume, cosmetic, or drug manufacturing (OR = 7.71, 95 percent CI 2.24-26.56), rubber product manufacturing (OR = 4.70, 95 percent CI 1.75-12.61), work in a medical diagnostic or pathology laboratory (OR = 4.52, 95 percent CI 2.27-8.97), and painting or paint manufacturing (OR = 2.87, 95 percent CI 1.06-7.76) were significantly associated with UCTD. After expert review of self-reported exposure to ten specific solvents, paint thinners or removers (OR = 2.73, 95 percent CI 1.80-4.16) and mineral spirits (OR = 1.81, 95 percent CI 1.09-3.02) were associated with UCTD. These results suggest that exposure to petroleum distillates increases the risk of developing UCTD. (+info)
Up-regulation of intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and class II MHC molecules on pulmonary artery endothelial cells by antibodies against U1-ribonucleoprotein.
In order to elucidate the pathogenic role(s) of autoantibodies in connective tissue disease (CTD), we examined whether autoantibodies against U1-ribonucleoprotein (RNP) and double-stranded (ds) DNA can up-regulate ICAM-1, ELAM-1 and class I and II MHC molecule expression on pulmonary artery endothelial cells (HPAEC). ICAM-1, ELAM-1 and class II MHC molecule expression on HPAEC cultured in the presence of anti-U1-RNP-containing and anti-dsDNA-containing IgG from CTD patients was up-regulated significantly in comparison with that on HPAEC cultured with IgG from normal healthy volunteers. Affinity chromatographic enrichment and depletion of the anti-U1-RNP antibody content of anti-U1-RNP-containing IgG confirmed that the anti-U1-RNP antibody did up-regulate ICAM-1, ELAM-1 and class II MHC molecule expression. The finding that an IgG F(ab')2-purified anti-U1-RNP antibody also up-regulated expression of these molecules may indicate that mechanisms other than Fc receptor-mediated stimulation are involved. These in vitro findings suggest that autoantibodies against U1-RNP and dsDNA play important roles in the immunopathological processes leading to the proliferative pulmonary arterial vasculopathy observed in CTD patients with pulmonary hypertension by up-regulating adhesion and class II MHC molecule expression on endothelial cells. (+info)
T cell receptor beta-chain third complementarity-determining region gene usage is highly restricted among Sm-B autoantigen-specific human T cell clones derived from patients with connective tissue disease.
OBJECTIVE: To determine the structure of T cell receptors (TCR) used by Sm-B-reactive human T cell clones, to map T cell epitopes on the Sm-B autoantigen, and to determine the HLA restriction element used in the recognition of Sm-B by T cells. METHODS: Sm-B-reactive T cell clones were generated from patients with connective tissue disease by using either a recombinant fusion protein or synthetic peptides. The TCR structure was defined with the use of polymerase chain reaction and DNA sequencing. Synthetic peptides were used to map T cell epitopes on Sm-B. HLA restriction element usage was defined by using monoclonal antibody blocking. RESULTS: Usage of the TCR third complementarity-determining region (CDR3) was highly restricted among Sm-B autoantigen-specific human T cell clones. Only amino acids 48-96 of the Sm-B2 autoantigen were recognized by T cells, and this occurred in the context of HLA-DR. CONCLUSION: TCR CDR3 gene usage is highly conserved by Sm-B autoantigen-specific T cell clones, and this appears to be related to the recognition of a limited number of T cell epitopes on the Sm-B autoantigen presented in the context of HLA-DR. (+info)
Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality.
OBJECTIVE: Pneumonia due to Pneumocystis carinii has been increasingly reported in patients with connective tissue diseases, but the frequency of this complication is not known. We sought to determine the frequency of P carinii pneumonia (PCP) in patients with connective tissue diseases, and to determine the role that a hospital's acquired immunodeficiency syndrome (AIDS)-related experience may have in the diagnosis of PCP in these patients. METHODS: We used a state hospitalization registry to identify all patients with PCP and either rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis, polymyositis, dermatomyositis, polyarteritis nodosa, or scleroderma who had an emergent or urgent hospitalization in California from 1983 to 1994. We compared patient and hospital characteristics between these patients and patients with connective tissue diseases hospitalized with other types of pneumonia. RESULTS: Two hundred twenty-three patients with connective tissue diseases were diagnosed with PCP in the 12-year study period. The frequency of PCP ranged from 89 cases/10,000 hospitalizations/year in patients with Wegener's granulomatosis to 2 cases/10,000 hospitalizations/year in patients with rheumatoid arthritis. Compared with 5,457 patients with connective tissue diseases and pneumonia due to other organisms, patients with PCP were more likely to be younger, to be male, to have private medical insurance, and to have systemic lupus erythematosus, Wegener's granulomatosis, inflammatory myopathy, or polyarteritis nodosa rather than rheumatoid arthritis, and were less likely to be African American. Hospital size, teaching status, urban/rural location, proportion of admissions due to AIDS or PCP, and proportion of patients with pneumonia undergoing bronchoscopy were each associated with the likelihood of diagnosis of PCP in univariate analyses, but only the number of patients with PCP being treated at a hospital (odds ratio [OR] 1.03 for each additional 10 cases/year, 95% confidence interval [95% CI] 1.01-1.05) was associated with the likelihood of diagnosis of PCP in multivariate analyses. Patients were also somewhat more likely to be diagnosed with PCP if there had previously been a case of PCP in a patient with a connective tissue disease at the same hospital (OR 135, 95% CI 0.98-1.85). In-hospital mortality was 45.7%, and was unrelated to hospital characteristics. CONCLUSION: PCP is an uncommon, but often fatal, occurrence in patients with connective tissue disease. A hospital's prior experience with patients with PCP is associated with the likelihood that this condition is diagnosed in patients with connective tissue diseases who present with pneumonia, suggesting that diagnostic suspicion is an important factor in the correct identification of affected patients. (+info)
Joint hypermobility and genetic collagen disorders: are they related?
The HDCTs constitute a heterogeneous group of rare genetically determined diseases, the best known of which are Ehlers-Danlos and Marfan syndromes and osteogenesis imperfecta. Hypermobility is a feature common to them all, but it is also a feature that is highly prevalent in the population at large. Symptomatic hypermobile subjects (whose symptoms are attributable to their hypermobility) are said to be suffering from the benign joint hypermobility syndrome, which has many features that overlap with the HDCTs. It is not yet known whether there is a variety of hypermobility (symptomatic or otherwise) that is not part of a connective tissue disorder. (+info)
111Indium antimyosin antibody imaging of primary myocardial involvement in systemic diseases.
OBJECTIVE: The diagnosis of primary myocardial involvement in systemic diseases is clinically relevant but difficult in the absence of specific criteria. Whatever the underlying disease, myocytes degeneration is observed during the active phase of myocardial damage. The aim of this study was to assess the diagnostic value of scintigraphic imaging with 111Indium antimyosin antibody (AM), a specific marker of the damaged myocyte, for ongoing myocardial damage related to systemic diseases. METHODS: 40 patients with histologically confirmed systemic diseases were studied. They were classified into two groups according to the presence (group 1, n = 30), or the absence (group 2, n = 10) of clinical, electrocardiographic (ECG) or echocardiographic signs suggestive of myocardial involvement. Planar and tomographic acquisitions were obtained 48 hours after injection of AM (90 MBq). Rest 201thallium (T1) scintigraphy was also performed to assess myocardial perfusion and scarring. Clinical, ECG, and echocardiographic +/- scintigraphic evaluations were repeated during follow up (17 +/- 19 months) in 36 of 40 patients. RESULTS: In group 1, 13 of 30 patients (43%) showed diffuse significant AM uptake throughout the left ventricle (LV), and no or mild T1 abnormality. Two of these were asymptomatic, four had normal ECG, and two had no clinical or echographic LV dysfunction. All patients in group 2 had negative AMA scintigraphy and normal T1 scintigraphy. During follow up of 12 AM positive patients, cardiac status improved after immunosuppressive treatment was intensified in nine cases, worsened in two cases, and remained stable in one. During follow up of 24 AM negative patients, cardiac status remained stable in 23 cases despite treatment not being increased in 20, including two patients with sequellary myocardial involvement. The last patient developed mild LV dysfunction after 36 months. CONCLUSION: AM scintigraphy allows detection of active myocardial damage related to systemic diseases, with increased specificity compared with conventional methods, and increased sensitivity in some cases. Further studies are needed to assess the potential value of AM scintigraphy as a therapeutic guide. (+info)