Hypericin and pulsed laser therapy of squamous cell cancer in vitro.

OBJECTIVE: This in vitro study compares continuous wave and pulsed laser light at longer wavelengths for activation of the phototoxic drug hypericin in human cancer cells. BACKGROUND DATA: Two-photon pulsed laser light now allows high-resolution fluorescent imaging of cancer cells and should provide deeper tissue penetration with near infrared light for improved detection as well as phototoxicity in human tumors. METHODS: Cultured Seoul National University (SNU)-1 tumor cells from a squamous cell carcinoma (SCC) were incubated with hypericin before photoirradiation at four laser wavelengths. Phototoxicity of hypericin sensitized SCC cells was measured by dimethyl thiazoldiphenyl (MTT) tetrazolium bromide cell viability assays and by confocal fluorescence microscopy via 532-nm and infrared two-photon pulsed laser light. RESULTS: Phototoxic response increased linearly with hypericin dose of 0.1-2 microM, light exposure time of 5-120 sec, and pulsed dye laser wavelengths of 514-593 nm. Light energy delivery for 50% cell phototoxicity (LD50) response was 9 joules at 514 nm, 3 joules at 550 nm, and less than 1 joule at the 593 nm hypericin light absorption maxima. Fluorescence confocal microscopy revealed membrane and perinuclear localization of hypericin in the SNU cells with membrane damage seen after excitation with visible 532 nm continuous wave light or two-photon 700-950 nm picosecond pulsed laser irradiation. CONCLUSIONS: Hypericin may be a powerful tumor targetting drug when combined with pulsed laser light in patients with recurrent head and neck SCC.

Etiologic diagnosis of sensorineural hearing loss in adults.

OBJECTIVE: To determine the etiology of adult-onset sensorineural hearing loss. STUDY DESIGN AND SETTING: This is a prospective cohort study of 60 adult subjects with bilateral sensorineural hearing loss of no obvious etiology by medical history and physical examination. These patients were evaluated at an academic medical center and underwent evaluation by high-resolution computed tomography of the temporal bone, autoimmune panel, and DNA testing for mutations of both the GJB2 gene and the mitochondrial DNA (1555A>G and 7445A>G). RESULTS: An etiologic diagnosis was achieved in 6 patients: cochlear otosclerosis, 1 case; dilated vestibular aqueduct, 1 case; a mitochondrial DNA 7445A>G mutation, 3 cases; and a mitochondrial DNA 1555A>G mutation, 1 case. CONCLUSION: This result underscores the importance of a search for the etiology of a hearing deficit in adult patients. There are specific interventions now available for the management of hearing-impaired patients with cochlear otosclerosis and mitochondrial DNA mutations.