Keratins and skin disease.

Mutations in keratin genes cause a diverse spectrum of skin, hair and mucosal disorders. Cutaneous disorders include epidermolysis bullosa simplex, palmoplantar keratoderma, epidermolytic ichthyosis and pachyonychia congenita. Both clinical and laboratory observations confirm a major role for keratins in maintaining epidermal cell-cell adhesion. When normal tissue homeostasis is disturbed, for example, during wound healing and cancer, keratins play an important non-mechanical role. Post-translational modifications including glycosylation and phosphorylation of keratins play an important role in protection of epithelial cells from injury. Keratins also play a role in modulation of the immune response. A current focus in the area of keratins and disease is the development of new treatments including small inhibitory RNA (siRNA) to mutant keratins and small molecules to modulate keratin expression.

Can spiral analysis predict the FP-CIT SPECT scan result in tremulous patients?

BACKGROUND: Previous studies have compared the accuracy of spiral analysis in distinguishing essential tremor (ET) from PD. In this study, we have used this technique to distinguish cases of tremulous PD (TDPD) (N = 24) from tremulous parkinsonian subjects without evidence of dopaminergic deficit (N = 41). METHODS: All patients were characterized on clinical and (123)I-N-ω-fluoro-propyl-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane ([(123)I] FP-CIT) SPECT scan data, which were concordant in every case. All analyses were carried out by observers blinded to the clinical details and supplied with just the spiral drawings, from which tremor severity (TS), 3-turn spiral diameter (3TD), and spiral density (SD) were measured. RESULTS: The spirals drawn by TDPD cases had significantly smaller 3TD (P = 0.029) and greater SD (P = 0.0082) than those with normal FP-CIT scans. There was no significant difference in the TS between the two groups (P = 0.11). The sensitivity and specificity of TS were 62.5% and 65.0%, 3TD were 75% and 56.7%, and SD were 30.4% and 82.5%, respectively, in predicting the correct classification. Further analyses combining these factors into pairs, showed that the respective sensitivities and specificities of (1) TS × 3TD were 75.0% and 40.0%, (2) TS/SD were 56% and 70.0%, and (3) 3TD/SD were 87.0% and 40.0%. DISCUSSION: There are significant differences in the 3TD and SD of spirals drawn by tremulous patients with normal versus abnormal FP-CIT scans. Spiral analysis may have some clinical value in helping to distinguish tremulous parkinsonian patients with normal presynaptic dopaminergic imaging from tremulous PD patients, providing results similar to those reported for expert movement disorder neurologists using standardized videotaped examinations.