The aim of this work was to evaluate the diagnostic performance of grey-scale, color Doppler, and dynamic ultrasound (US) for diagnosing carpal tunnel syndrome (CTS) using the medical diagnostic test called nerve conduction study (NCS) as the reference standard, and to correlate the increase in median nerve (MN) cross-sectional area (CSA) with severity of CTS. Fifty-one patients (95 wrists) with clinical symptoms of idiopathic CTS were recruited. The CSA and flattening ratio of the MN were measured at the distal radio-ulnar joint, pisiform, and hamate levels; bowing of the flexor retinaculum was determined at the hamate level. The hypervascularity of the MN was evaluated. The transverse sliding of the MN was observed dynamically and recorded as being either normal or restricted/absent. Another 15 healthy volunteers (30 wrists) were recruited as controls. Interoperator reliability was established for all criteria. CTS was confirmed in 75 wrists (75/95: 79%; 14 minimal, 21 mild, 23 moderate, 17 severe). CSA at the pisiform level was found to be the most reliable and accurate grey-scale criterion to diagnose CTS (optimum threshold: 9.8 mm(2)). There was a good correlation between the severity of NCS and CSA (r = 0.78, p < 0.001). The sensitivity and specificity of color-Doppler and dynamic US in detecting CTS was 69, 95, 58, and 86%, respectively. Combination of these subjective criteria with CSA increases the sensitivity to 98.3%. US measurement of CSA provides additional information about the severity of MN involvement. Color-Doppler and dynamic US are useful supporting criteria that may expand the utility of US as a screening tool for CTS.

Thyrotropin (TSH) receptor (TSHr) mutations have been investigated in relation to Graves' disease (GD) genetic susceptibility under the hypothesis that a modified antigen may have novel immunogenic properties. The prevalence of three germline polymorphisms--D36H, P52T, and D727E--were studied in a cohort of multiracial GD patients together with their associations with disease state, Graves' ophthalmopathy, and thyroid autoantibodies titers. Polymerase chain reaction products of exon 1 and 10e of the TSHr were generated from 164 GD patients (109 Chinese, 34 Malays, and 21 Indians) and 240 individuals with no thyroid illnesses (74 Chinese, 84 Malays, and 82 Indians). Mutations were detected by single-strand conformational polymorphism and confirmed with direct sequencing. The D36H mutation was absent, while significant ethnic differences in the distribution of the P52T and D727E mutations were found. The levels of thyroid autoantibodies also differed significantly amongst the three ethnic groups, with the Indian cohort having the lowest titer. Both the P52T and D727E mutations were not associated with GD. An intron mutation, C/G+63IVS1, was detected and showed significant association with GD. Overall, it conferred a twofold increase risk of GD, while subgroup analysis showed increased odds ratios of 2.4 for Chinese (p = 0.008) and 2.8 for Indian (p = 0.049) but not for the Malay ethnic group. Together with recent identification of disease susceptibility markers in the region of the TSHr gene, these results are supportive of genetic factors existing in this region that may be in linkage disequilibrium with the inheritance of various TSHr polymorphisms.

The study demonstrates markedly different thyroid autoantibody profiles in newly diagnosed GD patients with ophthalmic dominant as opposed to thyroid dominant features. It suggests differing antibody patterns are associated with predisposition to hyperthyroidism and orbitopathy. In addition, an association between smoking and low TPOAb levels was noted.

The study demonstrated that these parameters can supplement the evaluation of liver cirrhosis and will be able to distinguish the different grades of liver cirrhosis using Doppler ultrasound.

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Animal models of Graves' disease have been generated in recent years with various vaccination protocols using wild-type TSH receptor. In this study, we report the findings of genetic immunization of Swiss outbred mice with three different mutated human TSH receptor plasmids, each containing one constitutive activating mutation located at the ectodomain (S281N), exoloop (I486F), and transmembrane segment (D633H) respectively. Although the overall rate of thyrotoxicosis in the mice was !10%, anti-TSH receptor antibodies could be detected in many animals by flow cytometry, radioreceptor assay, and functional bioassays using recombinant human TSH receptor. Mice injected with plasmids harboring activated mutants (S281N and D633H) showed production of predominantly stimulating antibodies, whilst those treated with wild-type receptor plasmids generated mainly blocking sera. Most of these antibodies displaced radiolabeled bovine TSH, and their epitopes, independent of functional characteristics, were mapped to the first 271 amino acids of the TSH receptor. This supports recent findings that binding of stimulatory or blocking antibodies lie in close proximity within the leucine-rich repeat region.

From these data, we proposed Cys 398 as a stable disulfide bond partner of Cys 283, corroborating with a model based on evolutionary history of TSHR across species. This pairing of Cys 283 and Cys 398 also provides an objective alternative to conventional hypotheses on Cys coupling based on other predictive models.

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