Restricted and shared patterns of TCR beta-chain gene expression in silicone breast implant capsules and remote sites of tissue inflammation.

Silicone breast implants (SBI) induce formation of a periprosthetic, often inflammatory, fibrovascular neo-tissue called a capsule. Histopathology of explanted capsules varies from densely fibrotic, acellular specimens to those showing intense inflammation with activated macrophages, multinucleated giant cells, and lymphocytic infiltrates. It has been proposed that capsule-infiltrating lymphocytes comprise a secondary, bystander component of an otherwise benign foreign body response in women with SBIs. In symptomatic women with SBIs, however, the relationship of capsular inflammation to inflammation in other remote tissues remains unclear. In the present study, we utilized a combination of TCR beta-chain CDR3 spectratyping and DNA sequence analysis to assess the clonal heterogeneity of T cells infiltrating SBI capsules and remote, inflammatory tissues. TCR CDR3 fragment analysis of 22 distinct beta variable (BV) gene families revealed heterogeneous patterns of T cell infiltration in patients' capsules. In some cases, however, TCR BV transcripts exhibiting restricted clonality with shared CDR3 lengths were detected in left and right SBI capsules and other inflammatory tissues. DNA sequence analysis of shared, size-restricted CDR3 fragments confirmed that certain TCR BV transcripts isolated from left and right SBI capsules and multiple, extracapsular tissues had identical amino acid sequences within the CDR3 antigen binding domain. These data suggest that shared, antigen-driven T cell responses may contribute to chronic inflammation in SBI capsules as well as systemic sites of tissue injury.

Elevated concentrations of interleukin-1 beta and interleukin-1 receptor antagonist in plasma of women with silicone breast implants.

Plasma from 27 women with silicone breast implants (SBIs) and 50 age-matched control women without SBIs were examined by enzyme immunoassay for the presence of interleukin-1 beta (IL-1 beta) and its naturally occurring receptor antagonist, IL-1ra. The results show that 74% (20 of 27) of women with SBIs had elevated concentrations of IL-1ra, whereas only 2% (1 of 50) of controls without SBIs had elevated concentrations of IL-1ra. In contrast to the IL-1ra results, the frequency of elevated IL-1 beta concentrations among women with SBIs was only 40% (11 of 27), but this was significantly higher than the 0% (0 of 50) in control women without SBIs. These findings suggest that there is a chronic ongoing inflammatory process in some women with SBIs, the implications of which are discussed in the context of silicone as an antigenic stimulant of the immune system.

Cardiac abnormalities in mixed connective tissue disease.

Sixteen patients with mixed connective tissue disease (MCTD) were studied using noninvasive cardiovascular techniques. Cardiovascular abnormalities including pericarditis, asymmetric septal hypertrophy, and LV dilatation were found in 38 percent of the study group. Borderline ECG and echocardiographic abnormalities were present in 31 percent of the study group, and the remaining 31 percent were normal by all study techniques. MCTD patients have a high prevalence of cardiovascular abnormalities when studied noninvasively. The most common clinical abnormality is a steroid-responsive pericarditis, present in 25 percent of our series.

Systemic lupus erythematosus with myocarditis complicating pregnancy.

We report a patient with systemic lupus erythematosus and myocarditis complicating pregnancy. Cardiomegaly and compensated congestive heart failure persisted postpartum and we had the therapeutic dilemma of a pregnancy six months later. The defined maternal prognosis of a similar disease, peripartum cardiomyopathy, suggested the need for termination of pregnancy.

Computerized tomography in evaluation of atlantoaxial subluxation in rheumatoid arthritis.

Nineteen patients with rheumatoid C1-C2 subluxation of greater than or equal to 5mm were studied by computerized tomography (CT). CT demonstration of spinal cord compression as defined by loss of posterior subarachnoid space was present in 11/19 (CT+) and absent in 8/19 (CT-). Fourteen patients were examined by a blinded neurologist. Cord compression by CT correlated better with clinical neurologic status than did routine radiographic studies. Absent superficial abdominal reflexes and history of bladder dysfunction correlated highly with cord compression by CT. Two CT+ patients developed neurologic deterioration requiring spinal fusion. Our data suggest that CT is a useful, noninvasive adjunct in management of patients with rheumatoid C1-C2 subluxation.

Reproducibility studies for anti-DNA antibody detection in systemic lupus erythematosus and related diseases. FIAX fluorometric immunoassay and Farr radioimmunoassay.

We compared the FIAX fluorometric immunoassay for antiDNA antibodies with a Farr radio-immunoassay. Neither was precise; coefficients of variation usually exceeded 10%. The 2 assays correlated well (r = 0.87). Both were almost completely specific for numbers of sera with elevated antiDNA preferable to the Farr assay and probably to all other antiDNA assays currently used in clinical situations, although its reproducibility needs improvement.

Articular and soft tissue abnormalities in a "normal" population.

One hundred twenty-three medical students underwent comprehensive locomotor physical examinations as part of their sophomore physical diagnosis course. Sixty-nine point one per cent of subjects were found to have between 1 and 7 separate congenital, developmental, post-traumatic, inflammatory or idiopathic abnormalities. More than 30 different types of abnormalities were noted. The data presented suggest a high prevalence of locomotor abnormalities in a "normal" population, and supports the need for history and physical examinations in the selection of control subjects for clinical studies.

Hypokalemic periodic paralysis in Sjögren's syndrome.

A 30-year-old woman had scleroderma, Sjögren's syndrome, deforming polyarthritis, distal renal tubular acidosis, hypokalemic periodic paralysis, and persistent mild myopathy. During a five-year period the patient's otherwise mild course of disease was complicated by the occurrence of five episodes of severe flaccid muscle paralysis involving both proximal and distal muscle groups. Between the paralytic episodes the patient functioned well without replacement therapy, and had normal potassium levels. The sicca component was mild and went unrecognized for several years. There was no family history of muscle disease. The data presented in this report support the view that the paralytic episodes were due to hypokalemia secondary to renal tubular acidosis associated with Sjögren's syndrome. Hypokalemic periodic paralysis may occur as a rare complication of Sjögren's syndrome and renal tubular acidosis.

Association of myositis and myocarditis in progressive systemic sclerosis.

A retrospective review of 47 patients with progressive systemic sclerosis revealed a highly significant (P less than 0.001) association between myositis and myocarditis. Three patients developed clinically overt myocarditis as an early feature of their disease. These patients had an inflammatory myopathy indistinguishable from polymyositis. Despite an excellent clinical response to steroids, the late occurrence of life-threatening conduction system defects appeared while they were receiving therapy. Consequently, patients with progressive systemic sclerosis and myositis should be evaluated for a coexisting myocarditis. The findings in these patients lend further support to the concept of a generalized myopathic process among the connective tissue diseases.

Mixed connective tissue disease in children and adolescents.

Since the recognition of mixed connective tissue disease in 1972, a small number of pediatric and adolescent patients with this disorder have been described in detail. Four additional patients, two male and two female, are reported in this study. Age range at onset of symptoms was 11 to 18 years. All had arthritis or arthralgia, cervical lymphadenopathy, and hypergammaglobulinemia. Skin rashes and restrictive pulmonary disease were present in three; Raynaud phenomenon, skeletal myopathy, elevation of serum IgE, and neurologic abnormalities were present in two of the four patients. One patient had cardiomyopathy which was progressive over three years. Renal function was normal in all four patients. Most manifestations of the disease in these patients appeared to respond to variable doses of corticosteroids. A review of 234 reported patients with mixed connective tissue disease, including 50 pediatric patients, suggests a higher prevalence of renal and cardiac disease in affected children and adolescents. A multicenter cooperative study of patients with mixed connective tissue disease is strongly recommended to determine the natural history and the effects of therapeutic interventions in this disease.

Systemic vasculitis with coexistent large and small vessel involvement. A classification dilemma.

A patient with systemic vasculitis had the palpable purpuric lower extremity lesions of leukocytoclastic vasculitis and the renal aneurysms of polyarteritis nodosa, features thought to clearly separate these two syndromes. Questions are raised pertinent to the classification, diagnosis, treatment, and prognosis of systemic vasculitis.

Brown's syndrome. An unusual manifestation of rheumatoid arthritis.

Two patients presented with an ocular complication of rheumatoid arthritis that was extraocular in location. Clinical manifestations include vertical diplopia, an intermittent nature, a clicking sensation, and apparent inferior oblique palsy. A stenosing tenovaginitis of the superior oblique tendon and its sheath is the probable underlying pathologic mechanism.