Six-canal video head impulse test in patients with labyrinthine and retrolabyrinthine pathology: detecting vestibulo-ocular reflex deficits.

BACKGROUND: Abnormal gains in six-canal video head impulse test are attributed to semi-circular canal deficits. However, as video head impulse test responses are linked to the vestibulo-ocular reflex, it was hypothesised that abnormal gains can be caused by vestibulo-ocular reflex pathway deficits. METHODS: This study compared video head impulse test gains in 20 patients with superior semi-circular canal dehiscence (labyrinthine cause) and 20 side- and gender-matched patients with vestibular schwannomas (retrolabyrinthine cause), and investigated correlations between them (Mann-Kendall trend test). RESULTS: Vestibular schwannoma but not superior semi-circular canal dehiscence was significantly associated with abnormal lateral (odds ratio = 9.00 (95 per cent confidence interval = 1.638-49.44), p = 0.011) and posterior (odds ratio = 9.00 (95 per cent confidence interval = 2.151-37.659), p = 0.003) canal status. In vestibular schwannoma patients, there was a statistically significant degree of dependence between all ipsilesional canal video head impulse test gains; such dependence was not observed in superior semi-circular canal dehiscence. CONCLUSION: Vestibulo-ocular reflex gains differ in patients with labyrinthine and retrolabyrinthine disease; this suggests that abnormal gains can indicate deficits not only in the semi-circular canals but also elsewhere along the vestibulo-ocular reflex pathway.

Historical use of silver nitrate for the management of epistaxis - evidence-based practice?

OBJECTIVE: Epistaxis is one of the most common emergencies presenting to the ENT service, and silver nitrate cautery is the mainstay of epistaxis treatment in most centres worldwide. This review aimed to ascertain the historical evidence behind current common practice. METHOD: A review was conducted of historical published literature pertaining to epistaxis management. RESULTS: Silver in medicine dates back to 4000 BC, with silver nitrate first being used in 69 BC. Modern medical use for epistaxis is documented in case reports over the last 200 years. CONCLUSION: The precise origin and evidence-based practice of using silver nitrate for epistaxis is not well-established or understood. The mechanism of action is questionable; novel research of silver nitrate for this common ENT emergency presentation may be required.

Evaluation of the Sysmex XN-550, a Novel Compact Haematology analyser from the XN-L® series, compared to the XN-20 system.

INTRODUCTION: The XN-550 is a new, automated, compact, haematology analyser designed to generate a full blood count with a standard five-part white blood cell differential and an immature granulocyte count, as well as an optional reticulocyte and optical platelet (PLT) counts. The aim of the study was to evaluate the performance of the XN-550 and compare it to the established XN-20 system. METHODS: We evaluated the basic parameter and special measurement channels of the XN-550, using the XN-20 (which has a similar operating system), as a reference analyser. Precision, carry-over and throughput evaluations were performed. In addition, a total of 202 samples including normal controls and various pathological samples were studied for comparability. RESULTS: Good correlations with the reference analyser were obtained for all parameters except basophils. The XN-550 offers impedance and optical PLT counts and the latter showed a better correlation and less scatter than the impedance count and was comparable to the XN-20 fluorescent count at PLT counts ≤40×109 /L. Precision was good, and no significant carry-over was detected. CONCLUSIONS: The XN-550 was simple and easy to use, while maintaining the good diagnostic sensitivity seen with high-range systems such as the XN-20, making this compact device suitable for near-patient services and smaller satellite laboratories.

A placental phenotype for intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disease associated with significant risk of fetal complications. It is hypothesised that the risk of adverse fetal outcomes relates to the toxic effects of bile acids, the levels of which are increased in both maternal and fetal serum. Human and rodent studies have shown that transplacental transfer of bile acids is impaired in ICP. Furthermore, the morphology of placentas from the rodent model of ICP is markedly abnormal, and is associated with increased expression of apoptotic markers and oxidative stress. Using placental tissue from ICP cases and normal pregnancies and cultured placental explant fragments we investigated the histological and molecular effects of cholestasis. We also examined the influence of ursodeoxycholic acid (UDCA) administration on these parameters. Here we report that ICP is associated with several morphological abnormalities of the placenta, including an increase in the number of syncytial knots, and that these can be reproduced in an in vitro (explant) model exposed to the bile acids taurocholic acid and taurochenodoexycholic acid. Furthermore, we demonstrate that ursodeoxycholic acid, a drug commonly used in the management of ICP, has a protective effect on placental tissue both in vivo and in vitro.

Recombinant galectin-1 and its genetic delivery suppress collagen-induced arthritis via T cell apoptosis.

Galectin-1 (GAL-1), a member of a family of conserved beta-galactoside-binding proteins, has been shown to induce in vitro apoptosis of activated T cells and immature thymocytes. We assessed the therapeutic effects and mechanisms of action of delivery of GAL-1 in a collagen-induced arthritis model. A single injection of syngeneic DBA/1 fibroblasts engineered to secrete GAL-1 at the day of disease onset was able to abrogate clinical and histopathological manifestations of arthritis. This effect was reproduced by daily administration of recombinant GAL-1. GAL-1 treatment resulted in reduction in anticollagen immunoglobulin (Ig)G levels. The cytokine profile in draining lymph node cells and the anticollagen IgG isotypes in mice sera at the end of the treatment clearly showed inhibition of the proinflammatory response and skewing towards a type 2-polarized immune reaction. Lymph node cells from mice engaged in the gene therapy protocol increased their susceptibility to antigen-induced apoptosis. Moreover, GAL-1-expressing fibroblasts and recombinant GAL-1 revealed a specific dose-dependent inhibitory effect in vitro in antigen-dependent interleukin 2 production to an A(q)-restricted, collagen type 2-specific T cell hybridoma clone. Thus, a correlation between the apoptotic properties of GAL-1 in vitro and its immunomodulatory properties in vivo supports its therapeutic potential in the treatment of T helper cell type 1-mediated autoimmune disorders.

Amelioration of collagen-induced arthritis and suppression of interferon-gamma, interleukin-12, and tumor necrosis factor alpha production by interferon-beta gene therapy.

OBJECTIVE: To investigate the therapeutic effects and possible mechanisms of action of constitutive expression of interferon-beta (IFNbeta) by syngeneic fibroblasts from DBA/1 mice in the collagen-induced arthritis (CIA) model. METHODS: Immortalized embryonic DBA/1 fibroblasts were infected with a retrovirus expressing murine IFNbeta. IFNbeta-expressing fibroblasts were then implanted intraperitoneally into mice immunized with bovine type II collagen. The effect of IFNbeta on paw swelling, anticollagen antibody levels, IgG1/IgG2a isotype profiles, arthritis score, histologic joint damage, and cytokine secretion from lymph node cells and from bone marrow-derived macrophages was assessed. RESULTS: A single injection of IFNbeta-secreting fibroblasts was sufficient to prevent arthritis or to ameliorate existing disease. Thus, IFNbeta reduced the clinical score and paw swelling irrespective of whether the injection was administered before or after disease onset in treated mice, compared with that in the untreated control group (P < 0.05). Histologic findings in the IFNbeta-treated mice were markedly less severe than in the control group (P < 0.001). This effect was accompanied by a decrease in total anticollagen IgG levels, a decrease in anticollagen IgG2a, and an increase in IgG1. In vitro, supernatants from these engineered fibroblasts inhibited collagen-induced interferon-gamma secretion from lymph node cells, and reduced the levels of tumor necrosis factor alpha and interleukin-12 produced by lipopolysaccharide/IFNgamma-treated bone marrow-derived macrophages. This effect was specific, since it was reversed with anti-IFNbeta polyclonal antibodies. CONCLUSION: These results indicate that IFNbeta, which is currently used as a treatment for relapsing, remitting multiple sclerosis, is a potent immunomodulatory and antiinflammatory cytokine in CIA and should be considered for the treatment of rheumatoid arthritis.