The questionnaire may be a useful in-practice screening tool in chronic canine otitis for moderate to severe bilateral hearing deficits (MHT ≥41 dB NHL). The hearing loss grading system may help clinicians make therapeutic decisions. Chronic otitis media may be associated with higher grades of hearing loss.

Ear cleaners with activity against Malassezia may help to reduce the unnecessary use of antibiotic-containing polypharmaceutical ear medications. This study shows that the use of a large number of isolates may provide a more accurate account of the in vitro activity of a product.

We compared the in vitro activity of a new triazole, D0870, with those of fluconazole, itraconazole, and ketoconazole against 41 clinical isolates of fluconazole-resistant Candida belonging to nine different species. The 50% inhibitory concentrations (IC 50 s) were determined by a microdilution method with morpholinopropanesulfonic acid (MOPS)-buffered RPMI medium and an inoculum of Ϸ10 4 yeasts per ml. After incubation for 48 h at 37؇C the optical density at 550 nm was measured. The IC 50 was the lowest drug concentration which reduced the optical density at 550 nm by Ն50% compared with that for a drug-free control. D0870 had significant activity against many of the isolates. Its activity was comparable to that of ketoconazole, slightly superior to that of itraconazole, and markedly superior to that of fluconazole against Candida albicans. Against Candida glabrata, Candida krusei, and Candida inconspicua, it had activity similar to those of itraconazole and ketoconazole but had activity superior to that of fluconazole. D0870 IC 50 s for some isolates were increased. This may be due to cross-resistance mechanisms because the IC 50 s of both itraconazole and ketoconazole for these isolates were often high. When IC 50 s and IC 80 s were compared there was a marked organism and drug variation. With C. glabrata much higher endpoints for itraconazole were observed when an IC 80 endpoint was used. For C. albicans there was also a significant shift upward in endpoints for itraconazole and ketoconazole. Values were changed little when IC 50 and IC 80 endpoints of D0870 were compared. For 35 of 41 isolates tested the D0870 IC 50 was less than the 2.5-mg/liter breakpoint threshold proposed previously. Therefore, D0870 may be a useful agent for the therapy of infections caused by fluconazole-resistant Candida spp.Serious infections caused by yeasts, particularly Candida albicans, are an increasing problem because of factors such as intensive care practices, the use of indwelling catheters, human immunodeficiency virus infection, organ transplantation, and other immunosuppressive conditions. Such infections require prompt and appropriate therapy; however, the choice of drugs is limited and the first-choice drug for the treatment of systemic infections, amphotericin B, is associated with numerous toxic side effects. Imidazole and triazole antifungal drugs, such as itraconazole (ITZ) and ketoconazole (KTZ), have been developed and are among the most useful drugs for the treatment of human candidoses. The triazole drug fluconazole (FLU) has low toxicity, is well tolerated and absorbed, and has been used successfully in the treatment of both mucosal and invasive candidoses (9).A disturbing consequence of the long-term use of FLU is the increase in the number of patients, particularly AIDS patients, failing treatment because of infection with FLU-resistant Candida spp. (1, 2, 4-6, 13, 15, 16, 20, 21, 26, 27, 29). Treatment failure may be attributable to the development of azole resistance, infection with a species intrinsically ...

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Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer.