Biomedical subjects

J Kennerdell

Publications and source records attributed to J Kennerdell.

8 recordsLinked to original sources

PubMed1996

Serum antibodies reactive with eye muscle antigens and the TSH receptor in a euthyroid subject who developed ophthalmopathy and Graves' hyperthyroidism.

Serum antibodies reactive with eye muscle autoantigens, in particular a 64-kDa protein that is also expressed in the thyroid, and the TSH receptor, are associated with the ophthalmopathy that occurs in about 50% of patients with Graves' hyperthyroidism. We have had the opportunity to study a euthyroid, apparently normal, 35-year-old woman with a family history of thyroid autoimmunity and "colitis" but no clinical or biochemical evidence for thyroid disease or ophthalmopathy, who developed Graves' hyperthyroidism and ophthalmopathy together 18 months later. Serum taken when the patient was first seen was positive for antibodies reactive with (i) 9 different eye muscle proteins ranging in size from 15 to 130 kDa, notably those of 64, 55, and 50 kDa, by immunoblotting with eye muscle membranes, (ii) eye muscle and Müller's muscle cell membrane antigens in antibody-dependent cell-mediated cytotoxicity (ADCC), (iii) an eye muscle cytoplasmic antigen in indirect immunofluorescence, and (iv) the TSH receptor as measured in a radioreceptor binding inhibition assay. When she developed Graves' disease, serum concentration of antibodies to the 55-kDa protein had decreased from +2 to +/-, those reactive with other eye muscle antigens had not changed significantly, and TSH receptor antibodies had increased 3-fold. This case report suggests that antibodies reactive with eye muscle antigens and the TSH receptor are markers of the ophthalmopathy and able to predict its development in predisposed subjects. The significance of these findings needs to be confirmed in a prospective study of first-degree relatives of patients with thyroid-associated ophthalmopathy and patients with Graves' hyperthyroidism without eye signs.

Adult↗

PubMed1995

Upper eyelid retraction in the absence of other evidence for progressive ophthalmopathy is associated with eye muscle autoantibodies.

We have studied 25 clinically euthyroid patients with eyelid lag and retraction referred to thyroid/eye clinic for clinical and orbital imaging evidence of extraocular eye muscle (EM) involvement, evidence of progressive ophthalmopathy and serum antibodies reactive with EM membrane antigens in immunoblotting. Fourteen patients had Graves' hyperthyroidism, 5 had Hashimoto's thyroiditis, and 6 had euthyroid Graves' disease. By carrying out orbital imaging we showed EM abnormalities in 10 of 23 patients (43%). Serum antibodies reactive with EM membrane antigens were detected in 96% of patients. Antibodies reactive with a 64-kDa antigen were detected in 66% of patients, while those reactive with 35-, 55-, and 95-kDa antigens were found in 21, 33, and 25% of patients, respectively. Antibody prevalences compared to normals were significantly different (P < 0.005) only for the 64-kDa protein. The prevalence and the degree of reactivity of 64-kDa antibodies were significantly different in patients with abnormal EM compared to those with normal EM at orbital imaging (P < 0.04 and P < 0.01, respectively). The results of this work suggest that in some patients inflammation of the eyelid muscles may be an isolated feature of ophthalmopathy and remains as the only sign of a "subclinical" eye disease in patients with thyroid autoimmunity.

Adult↗

PubMed1994

Idiopathic sclerosing inflammation of the orbit. A distinct clinicopathologic entity.

BACKGROUND: Idiopathic sclerosing inflammation of the orbit is a poorly delineated, fibrosing, immune-mediated entity resulting in significant ocular disability. To characterize this process and propose more specific and effective therapy, clinical and pathologic findings in 16 cases are reviewed. METHODS: The clinical records of 16 patients with biopsy-proven disease were retrospectively reviewed to determine demographic and clinical features, radiologic features, course, management, and outcome. These findings were correlated with pathologic features to describe this unique entity. Immunohistologic characteristics were compared with those of a clinically and histopathologically similar process, retroperitoneal fibrosis. RESULTS: The study included 11 male and 5 female patients, ranging in age from 8 to 81 years. Disease onset was usually unilateral (14/16) and chronic (11/15), with two distinct anatomic presentations, lacrimal (11/16) and apical (3/16), characterized by infiltration (15/16), mass effect (12/16), and visual loss (3/16). The most common signs and symptoms were dull pain (13/16), proptosis (11/16), mild inflammation (11/16), restricted motility (9/16), swelling (9/16), and diplopia (8/16). Two features, a sparse, chronic inflammatory infiltrate, the immunopathologic characteristics of which suggested a cell-mediated process, and a desmoplastic stroma of early onset, dominated the pathologic picture. Treatment with corticosteroids (11/16), radiotherapy for steroid failures (8/11), and observation alone (3/16) was inadequate, resulting in blindness in 3/16 cases, restricted movement in 10/16, and complete resolution in only 2/16 patients. CONCLUSION: Idiopathic sclerosing inflammation of the orbit is a unique clinicopathologic entity, similar to retroperitoneal fibrosis, that is characterized by primary, chronic, and immunologically mediated fibrosis, poor response to corticosteroid treatment or radiotherapy, and frequent visual disability. Early and aggressive immunosuppressive therapy is recommended.

Adolescent↗

PubMed1993

Pathogenesis of thyroid-associated ophthalmopathy: an autoimmune disorder of the eye muscle associated with Graves' hyperthyroidism and Hashimoto's thyroiditis.

Thyroid-associated ophthalmopathy, the progressive eye disorder which occurs frequently in patients with Graves' hyperthyroidism and, occasionally, in those with Hashimoto's thyroiditis, may be a two-stage disorder of the eye muscle. In the first stage, which may occur in the great majority of patients with Graves' hyperthyroidism and in an unknown, but probably small, proportion of those with Hashimoto's thyroiditis, antibodies and CD4+ (helper) T lymphocytes reactive with eye muscle and thyroid shared antigens, of which 64-kDa membrane proteins are good candidates, may initiate a mild eye muscle inflammation, manifested as eye muscle swelling on orbital imaging. The second stage, which occurs in about 25% of patients with Graves' hyperthyroidism and in 2% of those with Hashimoto's thyroiditis, may be due to reactivity of cytotoxic antibodies against eye muscle-specific membrane antigens, one of which at approximately 35 kDa appears a likely candidate, and, possibly, cytotoxic T cells in the context of the appropriate class I MHC molecule. Orbital connective tissue inflammation, which plays an important role in the development of progressive orbital inflammation, is likely to be secondary to the eye muscle reaction. The recent cloning of a 64-kDa thyroid and eye muscle antigen which shares significant homology with the muscle protein tropomodulin and mapping of its antibody-reactive epitopes provide structural information about one candidate eye muscle autoantigen and promise for a more rational approach to the diagnosis and management of this common, progressive eye disorder.

Graves Disease↗

PubMed1993

Idiopathic sclerosing inflammation of the orbit: immunohistologic analysis and comparison with retroperitoneal fibrosis.

Idiopathic sclerosing inflammation of the orbit is clinically characterized by an insidious, chronic and progressive fibrosing process damaging orbital structures through entrapment and mass effect. Histologically, desmoplasia and a sparse infiltrate of lymphocytes, histiocytes, plasma cells, and occasional neutrophils and eosinophils are seen. An immune pathogenesis is suspected but presently poorly understood. To characterize the inflammatory infiltrate and to compare orbital and other inflammatory fibrosing lesions, immunoperoxidase studies using the streptavidin method were performed on 16 formalin or Bouins' fixed, paraffin-embedded orbital biopsy specimens and six specimens of retroperitoneal fibrosis. Positive staining of orbital tissue occurred as follows: T-cells (UCHL-1) 94% of cases, B-cells (L26) 40%, tissue macrophages (KP-1) 56%, HLA Dr positive antigen presenting cells and activated T-cells (LN3) 44%, and immunoglobulins (kappa, 80%; lambda, 63%, IgG, 73%, IgA, 44% and IgM, 31%). Results were strikingly similar for retroperitoneal fibrosis. These findings imply a cell mediated pathogenesis in idiopathic sclerosing inflammation of the orbit that is similar to retroperitoneal fibrosis and suggest therapeutic potential for agents modifying this facet of the immune system.

Humans↗

PubMed1986

Paraocular lymphoid tumors.

Forty-two patients with paraocular lymphoid tumors were treated with radiation. Histologically, 20 tumors were classified as benign lymphoid hyperplasia (BLH), ten as indeterminate histology (IH), and 12 as malignant lymphoma (ML). Of the patients with an initial diagnosis of BLH or IH, disseminated ML developed in 23%. Cytologic and histologic studies were not helpful in predicting the malignant potential in some of these tumors. The possibility that BLH represents a premalignant condition with subsequent transformation into ML is discussed. A total of 45 eyes were irradiated in these 42 patients. Initial local control rate was 93%, with ultimate control rate of 100% after retreatment with radiation or surgery. Radiation therapy is the treatment of choice for these tumors; local control rates are high, and morbidity is minimal with proper radiation treatment planning.

Aged↗

PubMed1985

Mucocele of the pterygoid recess treated by laser surgery. Case report.

Mucoceles arising from accessory paranasal sinuses about the orbit are quite rare. A case is reported of a retro-orbital mucocele arising from the pterygoid recess of the sphenoid sinus. The clinical and anatomical presentations, computerized tomographic and magnetic resonance imaging characteristics, and laser surgical management of such lesions are described.

Adult↗

PubMed1979

Diagnostic approaches to pituitary adenomas.

The utility of diagnostic tests for pituitary adenoma was compared in 12 patients. Endocrine and radiologic studies were always abnormal, even when neuro-ophthalmologic tests were normal. In most cases, both tomography of the sella turcica and CT scan revealed a mass in the region of the sella turcica. For more precise definition of suprasellar extension of the mass, metrizamide CT cisternography or tomographic pneumoencephalography with metrizamide provided similar details, although CT cisternography was much more easily done. Angiography provides a means to exclude an aneurysm or vascular malformation, a vascular tumor, or an aberrant course of the internal carotid artery.

Adenoma↗