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Biomedical subjects

C A Gorman

Publications and source records attributed to C A Gorman.

At least 19 recordsLinked to original sources
PubMed1992

Torsional diplopia after transantral orbital decompression and extraocular muscle surgery associated with Graves' orbitopathy.

Graves' orbitopathy can be associated with horizontal, vertical, and torsional diplopia. Of 428 patients treated with transantral orbital decompression, 21 had incycloduction (mean, 12.8 degrees; range, 5 to 20 degrees) and five had excycloduction (mean, 12 degrees; range, 5 to 20 degrees). All 26 patients had had recessions of the medial or inferior rectus muscle (or both) before onset of torsional diplopia. Mean recession was 5.5 mm (range, 4 to 10 mm) and 5.3 mm (range, 2 to 10 mm) of medial rectus muscle and inferior rectus muscle, respectively. An A pattern was often associated with the condition. Superior oblique tenectomy and inferior oblique myectomy were performed most frequently for incycloduction and excycloduction, respectively. Superior oblique tenectomy induced a mean incycloduction decrease of 7.1 degrees (range, 0 to 12 degrees). Exotropia in downgaze was decreased, and a small ipsilateral hyperdeviation was induced. Bilateral inferior oblique myectomy in one patient decreased excycloduction 10 degrees without inducing new deviation. At follow-up (mean, 63.7 months) after last strabismus operation, 15 patients with incycloduction and two with excycloduction had no diplopia.

Adult↗
PubMed1992

Emergency treatment of Graves' ophthalmopathy.

The ocular emergencies encountered in Graves' ophthalmopathy, namely optic neuropathy, corneal ulceration, subluxation of the globe, and severe periorbital oedema with chemosis have been discussed. Evaluation of the clinical signs and symptoms of these conditions, as well as their treatment, have been outlined. Of particular concern is the complaint of 'blurry vision' that may indicate the presence of optic neuropathy. Early recognition of this entity, with prompt referral to an ophthalmologist is important because there is an inverse relationship between duration of visual loss and efficacy of treatment. The ophthalmological evaluation of a patient with optic neuropathy may demonstrate decreased visual acuity, impaired colour perception, or an afferent pupillary defect. In addition, a visual field examination may be a helpful adjunctive test. Available therapy for optic neuropathy includes high-dose corticosteroids, supervoltage X-irradiation and orbital decompressive surgery. We have reviewed the literature concerning these modalities and outlined our approach to the treatment of optic neuropathy. In general, we recommend orbital decompression at an early stage for this condition. Another worrisome complaint is of 'eye pain'. In this case, distinction must be made between the causes that include ocular inflammation, corneal keratitis and corneal ulceration. The corneal ulceration is characterized by extreme eye pain and erythema, and may require surgical intervention. Severe ocular inflammation may respond well to a course of high-dose steroids. A combination of these ocular emergencies in a patient with Graves' ophthalmology necessitates careful consideration of the available treatment options.

Acute Disease↗
PubMed1991

Clever is not enough: NOSPECS is form in search of function.

The NOSPECS mnemonic helps students to examine systematically the eyes and orbits of patients with Graves' ophthalmopathy. NOSPECS and related numerical indices are unsuited to recording the results of treatment for Graves' ophthalmopathy because they do not distinguish between primary causes and secondary events. They do not discriminate between what is important and what is not. They do not reflect the effectiveness of treatment directed toward only one component of the index. An alternative is proposed in which investigators conducting clinical trials are asked to specify the potential benefits of therapy. Specific measurements are suggested that may be used in support of each claim. These data should be provided separately, not lumped in an overall index.

Graves Disease↗
PubMed1991

Stimulation of glycosaminoglycan accumulation by interferon gamma in cultured human retroocular fibroblasts.

Fully expressed Graves' disease involves an accumulation of glycosaminoglycan (GAG) in the retroocular connective tissue which contributes to the pathogenesis of ophthalmopathy. We treated cultured retroocular and dermal fibroblasts with recombinant interferon gamma (100 U/ml) for 16-24h and measured [3H]GAG accumulation. The cytokine stimulated [3H]GAG accumulation in retroocular fibroblast cultures obtained from eight different donors by 36-124% above control values. In contrast, interferon gamma had no consistent effect on macromolecular accumulation in dermal fibroblast cultures derived from the pretibium or from areas ordinarily uninvolved in Graves' dermopathy. These results suggest that retroocular fibroblasts may be uniquely targeted for one action of interferon gamma which involves the modulation of GAG metabolism.

Cells, Cultured↗
PubMed1991

Increased induction of HLA-DR by interferon-gamma in cultured fibroblasts derived from patients with Graves' ophthalmopathy and pretibial dermopathy.

We investigated the effects of several cytokines on HLA-DR expression in cultured fibroblasts derived from retroocular connective tissue and pretibial and abdominal skin of patients with Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD), as well as from normal individuals. We hypothesized that differences in response to cytokines between fibroblasts from various anatomical areas might play a role in the site-selective involvement of the extrathyroidal manifestations of Graves' disease. HLA-DR expression in fibroblasts was quantitated by scanning densitometry of whole cell lysates subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Direct immunofluorescence of cell monolayers was also performed. We hypothesize that unique characteristics of these fibroblasts may play a role in GO and PTD. Cultured retroocular, pretibial, and abdominal fibroblasts from patients with Graves' disease as well as from normal individuals did not express HLA-DR spontaneously. Treatment in vitro with interferon-gamma (IFN gamma; 100 U/mL) for 5 days induced HLA-DR by 50- to 80-fold (P less than 0.0001) in fibroblasts from all sites and subjects studied. However, IFN gamma-induced HLA-DR expression was significantly greater in retroocular (P less than 0.005) and pretibial (P less than 0.0005) fibroblasts from patients with GO and PTD than in fibroblasts obtained from the same anatomical sites of normal individuals. Further, retroocular and pretibial fibroblasts from patients with GO and PTD responded to IFN gamma more vigorously than did abdominal fibroblasts from these same patients (P less than 0.0001). IFN gamma-induced HLA-DR expression was enhanced by concomitant treatment with tumor necrosis factor-alpha (100 U/mL). In contrast, treatment of retroocular fibroblasts with transforming growth factor-beta (10 ng/mL), epidermal growth factor (1 ng/mL), or interleukin-6 (IL-6; 100 U/mL) significantly attenuated IFN gamma-induced HLA-DR reactivity by 40-59% (P less than 0.05). Incubation of retroocular fibroblasts with tumor necrosis factor-alpha, IL-1 alpha (10 U/mL), IL-2 (10 U/mL), IL-6, granulocyte-macrophage colony-stimulating factor (100 U/mL), epidermal growth factor, and transforming growth factor-beta alone did not affect HLA-DR expression. These results indicate that several cytokines can influence HLA-DR expression in cultured fibroblasts. The enhanced induction of HLA-DR by IFN gamma in retroocular and pretibial fibroblasts compared with that in abdominal fibroblasts may partially explain the selective involvement of the retroocular connective tissue and pretibial skin in fully expressed Graves disease.

Cell Line↗
PubMed1991

Detection, cellular localization, and modulation of heat shock proteins in cultured fibroblasts from patients with extrathyroidal manifestations of Graves' disease.

We hypothesize that fibroblasts obtained from the retroocular space and the pretibial skin, sites affected by the peripheral manifestations of Graves' disease, share unique characteristics that may in part explain the site specificity of Graves' ophthalmopathy (GO) and pretibial myxedema (PTM). Heat shock proteins (HSPs), synthesized by cells undergoing stress, function to maintain cellular homeostasis and are probably involved in the intracellular processing and cell surface presentation of antigens. We investigated possible differences in the expression of 70-kDa HSPs between cultured fibroblasts obtained from patients with severe GO and normal individuals. In addition, we compared HSP expression in fibroblasts derived from tissues involved in the extrathyroidal manifestation of Graves' disease (GO and PTM) with that in fibroblasts from uninvolved tissues. HSPs were detected by both immunoblotting and indirect immunofluorescence, using monoclonal antibodies that are directed against HSP72, HSP72/73 (termed HSP70), and HSP90. HSP expression at baseline and after treatment with various cytokines and heat stress was examined. At baseline, HSP72 reactivity was exclusively detected in retroocular and pretibial fibroblasts from patients with severe GO and PTM, but was not observed in abdominal fibroblasts from these patients and was not detectable in fibroblasts from any anatomical site of normal individuals. The abundance of HSP70 expression at baseline and after treatment with certain cytokines was significantly greater in retroocular and pretibial fibroblasts from patients with GO than in normal individuals. In addition, characteristic changes in the cellular localization of HSPs before and after exposure to heat stress and cytokines were observed; cell surface expression of HSP70 was detected at baseline in fibroblasts from patients, but not in normal fibroblasts. These data provide the first evidence that HSPs are differentially expressed by fibroblasts derived from tissues affected by the extrathyroidal manifestations of GD. These proteins may have a role in localized immune processes, leading to the development of GO and PTM.

Biopsy↗
PubMed1990

Clinical review 13: Diagnosis and management of Graves' ophthalmopathy.

Although Graves ophthalmopathy is a potentially sight threatening and disfiguring condition that can be frightening for the patient to experience, there are effective means of management. At the present time, treatment is based on the relief of excessive intraorbital pressures and is accomplished either by shrinking the orbital contents or by expanding the orbital volume. The most effective treatment modality or combination of modalities is an area of controversy. However, it must be remembered that the approach to management undertaken should be finely tuned to the needs of the particular individual afflicted with the condition. Perhaps with a greater understanding of pathophysiology, more reliable and effective treatments, based on specific pathophysiological mechanisms, may be developed. In addition, tests to reliably predict those patients most likely to progress in their disease might be developed, allowing preventive measures to be taken.

Female↗
PubMed1990

Iodine-131 treatment of Graves' disease using modified early iodine-131 uptake measurements in therapy dose calculations.

We hypothesized that early uptake of iodine-131 (131I) at 3-6 hr (EU) by the thyroid could be used to calculate 131I therapy with results comparable to those obtained using late uptake of 131I at 20-28 hr (LU) results. A retrospective study was undertaken. Twenty-seven patients with untreated thyrotoxic Graves' disease were given 3-5 microCi of 131I and EU and LU were determined with an uptake probe. We derived a "best fit" curve on plots of EU (X-axis) and LU (Y-axis). The equation for the curve (LU = -55.7 + 73.2 log EU) was used to predict late uptake (PU) from EU results on a second group of 24 similarly defined Graves' patients. PU and measured LU were then applied to 131I treatment calculations in these 24 patients. PU correlated closely with LU (r = 0.94). Dose calculations based on PU and LU gave very similar results (r = 0.97). Using this method, same day diagnosis and treatment of Graves' is achievable.

Female↗
PubMed1989

Presence of antibodies in the sera of patients with Graves' disease recognizing a 23 kilodalton fibroblast protein.

We examined whether antibodies (present in sera from patients with Graves' disease) might be directed against a connective tissue cellular component of the anatomical regions affected in the peripheral manifestations of that disease. Accordingly, we performed immunoblot analyses of cultured retroocular and pretibial fibroblasts. Retroocular connective tissue was obtained during orbital decompression surgery (n = 7) and at autopsy from normal individuals (n = 2). Pretibial skin biopsies were obtained from patients with pretibial dermopathy (n = 3) and at autopsy (n = 2). In addition, biopsies from other regions [extraocular muscle (n = 6), thyroid (n = 2), and abdominal skin (n = 3)] were also collected at surgery or autopsy. Serum samples were obtained from patients with severe Graves' ophthalmopathy (n = 31), hyperthyroid Graves' disease without overt ophthalmopathy (n = 13), nodular thyroid disease (n = 7), Hashimoto's thyroiditis (n = 7), rheumatoid arthritis (n = 5), and systemic lupus erythematosus (n = 3) and from normal individuals (n = 33). Electrophoresed fibroblast proteins were immunoblotted with 1:100 dilutions of sera using an antihuman immunoglobulin G-alkaline phosphatase conjugate. Antibodies against a 23kDa fibroblast protein were present in the sera from 24 of 44 (56%) of patients with Graves' disease with or without ophthalmopathy, 0 of 7 nodular thyroid disease, 0 of 7 Hashimoto's thyroiditis, 0 of 5 rheumatoid arthritis, 0 of 3 systemic lupus erythematosus, and 5 of 33 (15%) normal subjects. Significant differences in the observed frequency of antibodies existed between the Graves' disease group and the normal control group (P less than 0.01) or those patients with the other conditions (P less than 0.01). This 23kDa antigen was apparent in fibroblasts derived from individuals with Graves' disease as well as normal individuals and was present in fibroblasts from all anatomical sites studied. It was the sole protein uniquely recognized by sera from patients with Graves' disease. However, this serum reactivity did not appear to be related to the presence of clinically overt ophthalmopathy or pretibial dermopathy. Subcellular localization studies disclosed that the antigen was present in the supernatant but not the pellet resulting from a 100,000 x g centrifugation of whole cell sonicates. Antibodies against a 23kDa fibroblast protein are present in the majority of sera from patients with Graves' disease and rarely in sera from either normal individuals or those with other thyroid disorders or autoimmune diseases. Our results suggest the possibility that antibodies directed against this fibroblast antigen may be related to the developm

Antibodies↗
PubMed1989

Hormonal regulation of hyaluronate synthesis in cultured human fibroblasts: evidence for differences between retroocular and dermal fibroblasts.

Fibroblasts derived from retroocular connective tissue and skin were propagated in culture in an effort to identify structural and functional differences in connective tissue which might explain the apparent region-specific involvement in Graves' disease. Striking morphological differences existed between cultured cells from the two anatomical sites. Inhibition of glycosaminoglycan (GAG) accumulation by T3 and dexamethasone in these cultures was compared. Confluent cultures were labeled with [3H]acetate, and total [3H]GAG was quantitated. Fibroblasts from the skin responded to T3 (100 nmol/L) and dexamethasone (100 nmol/L) with 27% and 55% inhibition of [3H]GAG accumulation, respectively (n = 12). In contrast, retroocular fibroblasts responded with 12% and 8% inhibition (n = 6) to the two hormones. When cultures from abdominal skin and retroocular tissue were treated with n-butyrate (10 mM), a compound known to inhibit hyaluronate specifically, they responded similarly with 78% and 83% inhibition, respectively. A pulse-chase study was performed using fibroblasts from both sites, and no [3H]GAG degradation could be detected for the duration of the chase period (up to 72 h). These results suggest that retroocular fibroblasts, likely participants in the pathogenesis of Graves' ophthalmopathy, do not respond vigorously to T3 or glucocorticoids in terms of inhibition of [3H]GAG synthesis as do their dermal counterparts.

Cells, Cultured↗
PubMed1988

Triiodothyronine: a substrate for the thermostable and thermolabile forms of human phenol sulfotransferase.

The enzyme(s) responsible for the sulfate conjugation of L-T3 in man has not been characterized. T3 sulfotransferase (T3-ST) activity was characterized in normal human liver tissue obtained during clinically indicated surgical resection. Subcellular distribution studies showed that the T3-ST activity was localized to the cytoplasmic fraction. This finding raised the possibility that T3-ST activity might be similar to the 2 previously identified forms of cytoplasmic phenol sulfotransferase (PST) found in human tissue. A thermostable (TS) form of PST catalyzes the sulfate conjugation of micromolar concentrations of p-nitrophenol, and a thermolabile (TL) form catalyzes the sulfate conjugation of dopamine and other monoamines. Thermal stability and enzyme inhibitor experiments showed that T3-ST activity in pooled liver homogenates was very similar to the TS form of PST. The apparent similarity of T3-ST to TS PST was studied further by measuring T3-ST, TS PST, and TL PST activities in 20 individual liver samples. T3-ST activities correlated significantly with TS PST activities (r = 0.939; P less than 0.001) measured with p-nitrophenol, but not with TL PST activities (r = -0.118; P greater than 0.6) measured with dopamine. However, sulfation of T3 by the TL form of the enzyme might have been masked by the 18-fold higher specific activity of TS than TL PST in human liver homogenates. When the two forms of PST were separated by ion exchange chromatography, T3 was found to be a substrate for both the TS and TL forms of PST. "True" Km values for T3 were similar for TS and TL PST (81 and 127 microM, respectively).

Adult↗
PubMed1988

Distant metastases in differentiated thyroid carcinoma: a multivariate analysis of prognostic variables.

From a cohort of 988 patients with differentiated thyroid carcinoma receiving primary surgical treatment between 1946 and 1970, we studied the 85 (9%) patients who had distant metastases diagnosed during life. Clinically detected metastases were found in 7% of the 859 patients with papillary cancers, 19% of the 100 patients with follicular cancers, and 34% of the 29 patients with Hürthle cell cancers. The total experience amounted to 607 patient-years of observation after the diagnosis of metastases, with a median follow-up in the 12 survivors of 23 yr (range, 13-32 yr). At the time of first diagnosis of metastases, the lungs only were involved in 53%, and bones only in 20%; 16% had multiple organ involvement. The overall mortality rates 5 and 10 yr after the diagnosis of metastases were 65% and 75%, respectively. Seventy-eight percent of all deaths were directly attributable to thyroid cancer; 82% of cancer deaths occurred within 5 yr. By univariate analysis, patient age, tumor extent, pattern of lung involvement, radioiodine uptake of the metastases, and radioiodine treatment were significant prognostic factors. By multivariate analysis, only age (as a continuous variable) at the time of first diagnosis of distant metastases (P less than 0.0001) and involvement of multiple organ sites (P = 0.0003) were independently associated with cancer mortality. The survival at 5 yr in 12 patients aged less than 40 yr with only a single organ involved was 92%. Older patients (aged greater than or equal to 40 yr) with a single metastasis (n = 59) had a lower survival (38% at 5 yr). The highest risk of cancer death (92% at 5 yr) was found in the 14 patients (any age) who at the time of first diagnosis of metastases had multiple organ involvement. The Cox regression model suggested that radioiodine therapy did not have a significant influence on survival, after adjusting for age and extent of metastatic involvement.

Adolescent↗