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The results of this study suggest that incidentally found thyroid lesions by FDG-PET/CT, especially a focal FDG uptake and a high SUV, have a high risk of thyroid malignancy. Further diagnostic work-up is needed in these cases.

Our results identified this sonographic classification as a useful tool in the differentiation of malignant nodules from benign nodules. In view of the high negative predictive value of sonographic classification, a more aggressive approach is recommended only for category 3 nodules.

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Amino acid Asp-351 in the ligand binding domain of estrogen receptor ␣ (ER␣) plays an important role in regulating the estrogen-like activity of selective estrogen receptor modulator-ER␣ complexes. 4-Hydroxytamoxifen is a full agonist at a transforming growth factor ␣ target gene in situ in MDA-MB-231 human breast cancer cells stably transfected with the wild-type ER␣. In contrast, raloxifene (Ral), which is also a selective estrogen receptor modulator, is a complete antiestrogen in this system. Because D351G ER␣ allosterically silences activation function-1 activity in the 4-hydroxytamoxifen-ER␣ complex with the complete loss of estrogenlike activity, we examined the converse interaction of amino acid 351 and the piperidine ring of the antiestrogen side chain of raloxifene to enhance estrogen-like action. MDA-MB-231 cells were either transiently or stably transfected with Asp-351 (the wild type), D351E, D351Y, or D351F ER␣ expression vectors. Profound differences in the agonist and antagonist actions of Ral⅐ER␣ complexes were noted only in stable transfectants. The agonist activity of the Ral⅐ER␣ complex was enhanced with D351E and D351Y ER␣, but raloxifene lost its agonist activity with D351F ER␣. The distance between the piperidine nitrogen of raloxifene and the negative charge of amino acid 351 was critical for estrogen-like actions. The role of the piperidine ring in neutralizing Asp-351 was addressed using compound R1h, a raloxifene derivative replacing the nitrogen on its piperidine ring with a carbon to form cyclohexane. The derivative was a potent agonist with wild type ER␣. These results support the concept that the side chain of raloxifene shields and neutralizes the Asp-351 to produce an antiestrogenic ER␣ complex. Alteration of either the side chain or its relationship with the negative charge at amino acid 351 controls the estrogen-like action at activating function 2b of the selective estrogen receptor modulator ER␣ complex.Raloxifene (Ral) 1 (see Fig. 1) is a polyhydroxyphenyl benzothiophene antiestrogen that has low estrogen agonist activity in the rodent uterus (1). The compound originally referred to as Ly156758 or keoxifene was abandoned for development as a treatment for breast cancer (2), because its bioavailability was less than 2% administered dose (3). However, the recognition that raloxifene maintains bone density (4, 5) and inhibits mammary carcinogenesis in the rat (6, 7) illustrates the concept of selective estrogen receptor modulation. Raloxifene is used for the prevention of osteoporosis in postmenopausal women (8), and treatment is associated with a reduced incidence of breast cancer (9).Tamoxifen is the prototype selective estrogen receptor modulator (SERM) that is used clinically for the treatment and prevention of breast cancer (10, 11) with the ability to maintain bone density in postmenopausal women (12). However, tamoxifen therapy is also associated with estrogen-like effects in the uterus with an increased incidence of endometrial cancer (13). Raloxifene is currently being ...

Amniotic membrane matrix introduced at an early stage of the corneal wound healing process effectively reduced corneal haze induced by excimer laser photoablation in rabbits. Studies linking suppression of apoptosis in the acute wound-healing process with reduction of subsequent corneal scarring may have useful clinical applications.

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OBJECTIVEWe aimed to determine the effects of thyroid hormone on A1C and glycated albumin (GA) in nondiabetic patients with overt hypothyroidism.RESEARCH DESIGN AND METHODSA1C levels were measured in 45 nondiabetic patients with overt hypothyroidism and 180 euthyroid control subjects. A1C, GA, fasting blood glucose (FBG), 1,5-anhydroglucitol, and erythrocyte indexes were determined in 30 nondiabetic patients with overt hypothyroidism before and after thyroid hormone replacement.RESULTSA1C levels were higher in patients with hypothyroidism compared with control subjects. A1C levels were decreased by thyroid hormone replacement. Thyroid hormone replacement increased serum erythropoietin, reticulocyte count, and mean corpuscular hemoglobin (MCH). The change in A1C level was significantly correlated with the change in reticulocyte count or MCH. Thyroid hormone replacement decreased serum levels of albumin and GA. However, FBG and 1,5-anhydroglucitol levels were not altered.CONCLUSIONSLevels of A1C and GA are spuriously high in nondiabetic patients with overt hypothyroidism.