Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)

Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO.National Institutes of Health (U.S.) (DC010998)National Institutes of Health (U.S.) (NIH DC010231)Harvard College (1780- )Sarah Fuller Foundation for Little Deaf Childre

The hospital admissions study in England: Are there alternatives to emergency hospital admission?

Study objective - To assess the potential for substituting alternative forms of care for admission to an acute hospital in particular groups of patients. Design - A screening tool, the intensity-severity-discharge review system with adult criteria (ISD-A), developed for hospital utilisation review in the USA, was used in a cohort of hospital admissions to identify a group of patients who could potentially have been treated outside the acute hospital. These patients were further assessed by a panel of general practitioners (GPs) to determine the most appropriate alternative form of care. A cost analysis was performed on the results obtained. Setting - General medicine and geriatric specialties in one acute hospital in the south western region. Patients - Patients comprised a sample of 701 admitted to general medical and geriatric specialties. Main results - The screening tool identified 19.7% of admissions for whom there was potential for treatment outside the acute hospital. Assessment by the GP panel reduced this potential to between 9.8% and 15.0% of emergency admissions. The alternatives most frequently identified as 'most appropriate' were the community hospital-GP bed and the urgent outpatient assessment (within either 24 or 48 hours). Potential resource savings based on the average cost were relatively small. This potential seemed to be greater for the alternative of the urgent outpatient assessment. Conclusions - Potential exists for treating a proportion of patients in lower intensity alternatives to the acute hospital. If this potential were exploited few resource savings would occur