A randomized, double-blind comparison of the total dose of 1.0% lidocaine with 1:100,000 epinephrine versus 0.5% lidocaine with 1:200,000 epinephrine required for effective local anesthesia during Mohs micrographic surgery for skin cancers.

OBJECTIVE: We sought to compare total lidocaine dose and patient comfort when using 1.0% lidocaine with 1:100,000 epinephrine versus 0.5% lidocaine with 1:200,000 epinephrine during Mohs micrographic surgery. METHODS: In all, 149 patients were randomized to receive 1.0% lidocaine with 1:100,000 epinephrine or 0.5% lidocaine with 1:200,000 epinephrine during Mohs micrographic surgery. The total dose of lidocaine and measures of patient comfort were recorded. RESULTS: Compared with the 1.0% lidocaine group, there was a 52% reduction in lidocaine dose in the 0.5% group (mean difference, 147.85 mg; 95% confidence interval, 108.15-187.55; P < .001). Patient comfort was equivalent in both groups, as evidenced by the similar mean visual analog scale scores (P = .48) and mean volumes of rescue lidocaine administered (P = .18). LIMITATIONS: No lidocaine blood levels were measured, and one Mohs surgeon performed all surgeries. CONCLUSION: The dose of 0.5% lidocaine with 1:200,000 epinephrine provides pain control equivalent to 1.0% lidocaine with 1:100,000 epinephrine at approximately half the total lidocaine dose.

Roles of Src and epidermal growth factor receptor transactivation in transient and sustained ERK1/2 responses to gonadotropin-releasing hormone receptor activation.

The duration as well as the magnitude of mitogen-activated protein kinase activation has been proposed to regulate gene expression and other specific intracellular responses in individual cell types. Activation of ERK1/2 by the hypothalamic neuropeptide gonadotropin-releasing hormone (GnRH) is relatively sustained in alpha T3-1 pituitary gonadotropes and HEK293 cells but is transient in immortalized GT1-7 neurons. Each of these cell types expresses the epidermal growth factor receptor (EGFR) and responds to EGF stimulation with significant but transient ERK1/2 phosphorylation. However, GnRH-induced ERK1/2 phosphorylation caused by EGFR transactivation was confined to GT1-7 cells and was attenuated by EGFR kinase inhibition. Neither EGF nor GnRH receptor activation caused translocation of phospho-ERK1/2 into the nucleus in GT1-7 cells. In contrast, agonist stimulation of GnRH receptors expressed in HEK293 cells caused sustained phosphorylation and nuclear translocation of ERK1/2 by a protein kinase C-dependent but EGFR-independent pathway. GnRH-induced activation of ERK1/2 was attenuated by the selective Src kinase inhibitor PP2 and the negative regulatory C-terminal Src kinase in GT1-7 cells but not in HEK293 cells. In GT1-7 cells, GnRH stimulated phosphorylation and nuclear translocation of the ERK1/2-dependent protein, p90RSK-1 (RSK-1). These results indicate that the duration of ERK1/2 activation depends on the signaling pathways utilized by GnRH in specific target cells. Whereas activation of the Gq/protein kinase C pathway in HEK293 cells causes sustained phosphorylation and translocation of ERK1/2 to the nucleus, transactivation of the EGFR by GnRH in GT1-7 cells elicits transient ERK1/2 signals without nuclear accumulation. These findings suggest that transactivation of the tightly regulated EGFR can account for the transient ERK1/2 responses that are elicited by stimulation of certain G protein-coupled receptors.