The expression pattern and inhibitory influence of Tenascin-C on the growth of spiral ganglion neurons suggest a regulatory role as boundary formation molecule in the postnatal mouse inner ear.

Sensorineural hearing loss, as a consequence of acoustic trauma, aging, genetic defects or ototoxic drugs, is highly associated with irreversible damage of cochlear hair cells (HCs) and secondary degeneration of spiral ganglion (SG) cells. Cochlear implants (CIs), which bypass the lost HC function by direct electrical stimulation of the remaining auditory neurons, offer an effective therapy option. Several studies imply that components of the extracellular matrix (ECM) have a great impact on the adhesion and growth of spiral ganglion neurons (SGNs) during development. Based on these findings, ECM proteins might act as bioactive CI substrates to optimize the electrode-nerve interface and to improve efficacy of these implants. In the present study, we focused on the ECM glycoproteins Tenascin-C (TN-C), Laminin (LN), and Fibronectin (FN), which show a prominent expression along the growth route of SGNs and the niche around HCs during murine postnatal development in vivo. We compared their influence on adhesion, neurite length, and neurite number of SGNs in vitro. Moreover, we studied the expression of the chondroitin sulfate proteoglycan (CSPG) dermatan sulfate-dependent proteoglycan-1 (DSD-1-PG), an interaction partner of TN-C. In sum, our in vitro data suggest that TN-C acts as an anti-adhesive and inhibitory factor for the growth of SGNs. The DSD-1 carbohydrate epitope is specifically localized to HC stereocilia and SG fibers. Interestingly, TN-C and the DSD-1-PG exhibit a mutually exclusive expression pattern, with the exception of a very restricted region beneath the habenula perforata, where SG neurites grow through the basilar membrane (BM) toward the HCs. The complementary expression of TN-C, LN, FN, and the DSD-1 epitope suggests that TN-C may act as an important boundary formation molecule in the developing postnatal mouse inner ear, which makes it a promising candidate to regulate neurite outgrowth in the light of CIs.

Adjuvant therapy in patients with pancreatic cancer.

The prognosis for patients with pancreatic cancer is still very poor. A complete (R0) surgical resection of the tumor poses the only chance of cure. At the moment only postoperative chemotherapy with gemcitabine has significantly delayed the development of recurrent disease and showed an improvement in long-term survival compared to observation alone. It is essential to develop more effective adjuvant therapy strategies with involvement of all therapeutic options to change the disappointing situation.

Directly observed isoniazid preventive therapy for released jail inmates.

This study was designed to determine whether an integrated screening program could be implemented that identified persons with latent tuberculosis infection among jail inmates and produced a high rate of completion of isoniazid preventive therapy (IPT) in those persons after their discharge from short-term detention, by means of community-based directly observed preventive therapy (DOPT). From June 1, 1992 through December 31, 1994 inmates in the King County Jail who were from populations at high risk of tuberculosis were screened by means of the tuberculin skin test and those with latent tuberculosis infection were offered IPT. Among 262 inmates receiving IPT upon release from jail, 105 (40%) could not be located after release. Among another 105 enrolled on DOPT, 63 (60%) completed therapy. Among 52 who chose self-supervised isoniazid therapy after release, 15 (29%) completed therapy (chi-square = 13.50, p = 0.0002). Among persons with latent tuberculosis infection detected during screening at a county jail, a postrelease DOPT program resulted in a high rate of immediate loss to follow-up and a low rate of completion of therapy. Based on these results, we suggest that funds for TB control, if limited, should not be diverted to jail-based screening and postrelease DOPT.