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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↗
PubMed1979

Comparative effectiveness of dextrothyroxine and levothyroxine in correcting hypothyroidism and lowering blood lipid levels in hypothyroid patients.

Data reported here establish that treatment regimens of 4 mg dextrothyroxine and 0.15 mg levothyroxine in hypothyroid subjects produce similar degrees of lowering of serum TSH, cholesterol, triglycerides, and phospholipid levels and equal stimulation of metabolic rate. The Murphy-Pattee total T4 determination applied to blood samples drawn 24 h after the last dose of dextrothyroxine can be used to assess adequacy of treatment. Correction of hypothyroidism requires high serum levels of dextrothyroxine than of levothyroxine. Serum T3 levels increase in patients treated with dextrothyroxine. In the treatment of hypothyroidism, the cholesterol-lowering and metabolic rate-stimulating effects of dextrothyroxine do not appear to be dissociated. Further studies are needed to determine whether such an effect can be demonstrated in euthyroid hypercholesterolemic subjects with doses established herein as equivalent in terms of the stimulating effect on metabolic rate.

Basal Metabolism↗
PubMed1978

Thyrotropin receptors in normal and pathological human thyroid tissues.

The properties of TSH receptors in normal and pathological human thyroid tissues were studied. Highly purified bovine TSH after lactoperoxidase iodination retained full biological activity, as assessed by radioreceptor assay. Binding of bovine [125I]TSH to 1000 x g pellets of human thyroid homogenate was specific with respect to hormone and tissue. Total binding amounted to 50-60% of total radioactivity using 10 mg (wet weight) normal thyroid tissue. Nonspecific binding was only 6% of total radioactivity. Normal thyroid tissue contained two orders of binding sites, which were shown to be independent of each other by Hill plot analysis. The high affinity sites [equilibrium dissociation constant (Kd), 0.015-0.16 x 10-9 M] were present in concentrations of 1.05-9.30 pmol/mg protein and concentrations of low affinity sites (Kd, 1.2-2.4 x 10-9 M) were 35.9-213 pmol/mg. In all pathological thyroid tissue studied, two orders of binding sites were found with dissociation constants similar to those of normal tissues, but the number of binding sites was markedly reduced. Both orders of binding sites in solitary "cold" adenomas and only the low affinity sites in thyroid tissue from patients with Graves' disease were significantly reduced in number (P less than 0.01). There was a questionable decrease in high affinity sites in the Graves' tissue (P = 0.05). We have found the definite presence but a decreased number of binding sites in both orders of receptors in papillary and follicular carcinomas. There were few or no binding sites in medullary carcinoma.

Adenocarcinoma↗
PubMed1978

Rectilinear thyroid scanning as a predictor of malignancy.

Rectilinear scan findings were correlated with the surgically documented size, location, and histology of thyroid carcinoma in 67 patients. At the site of the carcinoma, 36 (54%) had hypofunction, associated with a palpable abnormality in all but one patient; 16 (24%) had an abnormality on palpation but not on scanning; 11 (16%) had both a normal clinical examination and a normal scan, associated with a benign abnormality in another part of the thyroid; and four (6%) had a patchy uptake. A literature review established that use of the gamma camera with pinhole collimator does not increase the specificity of carcinoma predictability, despite the enhanced sensitivity. The scan may still be used in evaluating the clinically solitary nodule that is not obviously malignant. However, unless that module is hyperfunctioning, clinical criteria rather than appearance of the scan should contribute most to the decision of whether to treat surgically.

Diagnostic Errors↗
PubMed1978

Radiation dose in the selection of 131I or surgical treatment for toxic thyroid adenoma.

Clinicians, by their patterns of referral to colleagues in nuclear medicine or surgery, may strongly influence the selection of 131I versus surgical treatment for patients with toxic thyroid adenoma. The information presented here is intended to aid them in making an informed choice. As nodule size of an adenoma increases from 2 cm to 6 cm, the amount of radioiodine administered to the patient to deliver the same dose (30 000 rads to the nodule center, assuming a 30% uptake) increases from 5.6 mCi to 135 mCi. Concurrently, the suppressed thyroid tissue receives a radiation dose as high as 2300 rads. Despite these potentially carcinogenic doses, few patients with radioiodine-induced thyroid tumors have been reported; we discuss possible reasons for this. For young patients with large nodules, surgery is preferred.

Adenoma↗