Dengue virus type 2 vaccine: reactogenicity and immunogenicity in soldiers

A live dengue virus type 2 (dengue-2) vaccine (PR-159/S-1) was tested for reactogenicity and immunogenicity in a placebo-controlled, double-blind clinical trial involving 98 soldiers. Seroconversion rates based on the development of neutralizing antibody to dengue-2 were 90% in 70 recipients with immunity to yellow fever and 61% in 28 vaccinees without such immunity (P less than .01). Peak titers of neutralizing antibody were three times higher in recipients with antibody to yellow fever virus and persisted in most for at least 18 months. Individuals seroconverting to the vaccine virus more frequently experienced systemic symptoms than those who received placebo (P less than .02). Future users of this dengue-2 vaccine may wish to employ immunization schedules that include preliminary immunization against yellow fever and must be prepared to accept mild vaccine-related symptoms in some recipients.     

A Novel Rodent Orthotopic Forelimb Transplantation Model That Allows for Reliable Assessment of Functional Recovery Resulting From Nerve Regeneration

Improved nerve regeneration and functional outcomes would greatly enhance the utility of vascularized composite allotransplantation (VCA) such as hand and upper extremity transplantation. However, research aimed at achieving this goal has been limited by the lack of a functional VCA animal model. We have developed a novel rat midhumeral forelimb transplant model that allows for the characterization of upper extremity functional recovery following transplantation. At the final end point of 12 weeks, we found that animals with forelimb transplantation including median, ulnar and radial nerve coaptation demonstrated significantly improved grip strength and forelimb function as compared to forelimb transplantation without nerve approximation (grip strength: 1.71N ± 0.57 vs. no appreciable recovery; IBB scale: 2.6 ± 0.7? vs. 0.8 ± 0.40; p = 0.0005), and similar recovery to nerve transection‐and‐repair only (grip strength: 1.71N ± 0.57 vs. 2.03 ± 0.42.6; IBB scale: 2.6 ± 0.7 vs. 2.8 ± 0.8; p = ns). Moreover, all forelimb transplant animals with nerve coaptation displayed robust axonal regeneration with myelination and reduced flexor muscle atrophy when compared to forelimb transplant animals without nerve coaptation. In conclusion, this is the first VCA small‐animal model that allows for reliable and reproducible measurement of behavioral functional recovery in addition to histologic evaluation of nerve regeneration and graft reinnervation.     

Identification of fluocinolone acetonide to prevent paclitaxel‐induced peripheral neuropathy

Paclitaxel (PTX) is among the most commonly used cancer drugs that cause chemotherapy‐induced peripheral neuropathy (CIPN), a debilitating and serious dose‐limiting side effect. Currently, no drugs exist to prevent CIPN, and symptomatic therapy is often ineffective. In order to identify therapeutic candidates to prevent axonal degeneration induced by PTX, we carried out a phenotypic drug screening using primary rodent dorsal root ganglion sensory neurons. We identified fluocinolone acetonide as a neuroprotective compound and verified it through secondary screens. Furthermore, we showed its efficacy in a mouse model of PTX‐induced peripheral neuropathy and confirmed with four different cancer cell lines that fluocinolone acetonide does not interfere with PTX's antitumor activity. Our study identifies fluocinolone acetonide as a potential therapy to prevent CIPN caused by PTX.     

Tierexperimenteller Nachweis der Intermodulationswanderwelle

Ohne Zusammenfassung Mit Unterstützung durch den Bundesminister für Jugend, Familie und Gesundheit, und durch die Stiftung Volkswagenwerk.     

Bedeutung der Informationsrückgewinnung aus Summenaktionspotentialen für die klinische Elektrocochleographie

Summary Basing on model investigations as well as on theoretical considerations, a method for the processing of frequency-specific information contained in compound action potentials has been developed. This approach consists in doint the reserve process of the physiological formation of compound action potentials. Result of this method is the neural excitation pattern (in the location domain, i.e., as a function of frequency) at the level of primary auditory neurons. Processing originally recorded human compound APs as well, as derived APs could prove the outlined approach. Significance and limits of the method and its impact for clinical application are discussed.     

Elektrophysiologischer Nachweis des quadratischen Differenztons am Menschen

Ohne Zusammenfassung     

Effect of intranasal histamine challenge on Eustachian tube function

OBJECTIVE: To show a relationship between intranasal histamine challenge, the development of middle ear effusion and Eustachian tube (ET) dysfunction in a rat model. METHODS: Non-allergic Sprague-Dawley rats weighing between 450-600 g were randomly assigned to receive an intranasal infusion of 16 microl of 10% histamine or normal saline. ET function was assessed by using the forced-response test to measure passive and active opening and closing pressures at time intervals of 6, 10, 14, 18, 22, and 26 min and 24 h post-infusion. Mucociliary clearance times (MCCTs) of the tubotympanum at 18 min post-infusion were measured by timing the transit of dye from the middle ear to the nasopharynx. Outcome measures were ET dysfunction and evidence of clinical effusion. RESULTS: Intranasal histamine caused acute ET dysfunction when introduced into the nasopharynx demonstrated by significant elevations in passive and active opening and closing pressures (P < or = 0.001) compared to controls. The largest difference was seen at 26 min post-infusion. Furthermore, MCCTs were 2.4 times longer after infusing intranasal histamine than after saline infusion. No clinically significant effusions were evident in either group at any time interval. CONCLUSION: These data demonstrate a successful development of an intranasal histamine rat model, in addition to a relationship between intranasal histamine challenge and development of acute ET dysfunction.