Advances in subcutaneous immunotherapy.

PURPOSE OF REVIEW: Current limitations in subcutaneous immunotherapy (SCIT) include the length of time required to achieve tolerance as well as the potential for systemic side-effects. Advances in allergen immunotherapy include targeted therapies to B-cell and T-cell pathways that can lead to more rapid desensitization and potentially the prevention of allergic disease. RECENT FINDINGS: Novel molecularly engineered compounds and delivery vehicles allow for rapid and efficient desensitization. Combination with immune modifiers, treatment with epitope-based compounds, and hypoallergenic recombinant vaccines have the potential to improve immunogenicity while limiting systemic side-effects. SUMMARY: Advances in SCIT create new therapeutic opportunities for patients to improve safety, efficacy, and compliance. Concepts using epitope-based immunotherapy and carrier-fusion peptides have the potential to induce tolerance quickly via selective B-cell and T-cell pathways.

Handheld micromanipulator for robot-assisted stapes footplate surgery.

Stapes footplate surgery is complex and delicate. This surgery is carried out in the middle ear to improve hearing. High accuracy is required to avoid critical tissues and structures near the surgical worksite. By suppressing the surgeon's tremor during the operation, accuracy can be improved. In this paper, a fully handheld active micromanipulator known as Micron is evaluated for its feasibility for this delicate operation. An ergonomic handle, a custom tip, and a brace attachment were designed for stapes footplate surgery and tested in a fenestration task through a fixed speculum. Accuracy was measured during simulated surgery in two different scenarios: Micron off (unaided) and Micron on (aided), both with image guidance. Preliminary results show that Micron significantly reduces the mean position error and the mean duration of time spent in specified dangerous zones.

Identification of genetic and chemical modulators of zebrafish mechanosensory hair cell death.

Inner ear sensory hair cell death is observed in the majority of hearing and balance disorders, affecting the health of more than 600 million people worldwide. While normal aging is the single greatest contributor, exposure to environmental toxins and therapeutic drugs such as aminoglycoside antibiotics and antineoplastic agents are significant contributors. Genetic variation contributes markedly to differences in normal disease progression during aging and in susceptibility to ototoxic agents. Using the lateral line system of larval zebrafish, we developed an in vivo drug toxicity interaction screen to uncover genetic modulators of antibiotic-induced hair cell death and to identify compounds that confer protection. We have identified 5 mutations that modulate aminoglycoside susceptibility. Further characterization and identification of one protective mutant, sentinel (snl), revealed a novel conserved vertebrate gene. A similar screen identified a new class of drug-like small molecules, benzothiophene carboxamides, that prevent aminoglycoside-induced hair cell death in zebrafish and in mammals. Testing for interaction with the sentinel mutation suggests that the gene and compounds may operate in different pathways. The combination of chemical screening with traditional genetic approaches is a new strategy for identifying drugs and drug targets to attenuate hearing and balance disorders.