Insight into the current practice of ototoxicity monitoring during cisplatin therapy.

BACKGROUND: The aim of this study is to evaluate the current state of ototoxicity monitoring for patients receiving cisplatin chemotherapy in an academic medical center with particular attention to how closely monitoring adheres to national ototoxicity guidelines. METHODS: Case series including retrospective medical records review of patients (age > 18) treated with cisplatin at University of California Davis Medical Center between January 2014 and August 2017. Patient and ototoxicity related variables were analyzed. Patients that underwent a transfer of care during treatment and with less than 3 months of follow-up were excluded. RESULTS: Three hundred seventy-nine patients met study criteria, of which 104 (27.4%) had a prior history of hearing loss. Prior to treatment, 196 (51.7%) patients were counseled regarding the ototoxic nature of cisplatin and 92 (24.3%) patients had a pretreatment audiogram. During treatment, 91 (24%) patients had documented otologic complaints. Only 17 patients (4.5%) patients had an audiogram ordered during their cisplatin treatment period. 130 (34.3%) patients had otologic complaints following cisplatin treatment. Audiograms were ordered for 20 (7.8%), 13 (5.1%), and 16 (6.2%) patients at 1-month, 3-month, and 6-month follow-ups, respectively. No patients in the study cohort received baseline, treatment, and post-treatment audiograms as recommended by national ototoxicity monitoring protocols. Patients with Head and Neck Cancer (HNC) represented the largest subgroup that received cisplatin (n = 122, 32.2%) and demonstrated higher rates of ototoxicity counseling (n = 103, 84.4%) and pretreatment audiograms (n = 70, 57.4%) compared to the non HNC group (n = 36, 36.2%, P < 0.0001 and n = 22, 8.5%, P < 0.0001). CONCLUSIONS: There is poor adherence to national ototoxicity monitoring guidelines at a large academic medical center. This is a missed opportunity for intervention and aural rehabilitation. Improved education and collaboration between otolaryngology, audiology, and medical oncology is needed to develop and promote an effective ototoxicity-monitoring program.

Novel approaches to the automated assay of ß-glucanase and lichenase activity.

We report herein the development of a novel assay procedure for the measurement of ß-glucanase and lichenase (EC 3.2.1.73) in crude enzyme extracts. Two assay formats based on a) a direct cleavage or b) an enzyme coupled substrate were initially investigated. The 'direct cleavage' substrate, namely 4,6-O-benzylidene-2-chloro-4-nitrophenyl-ß-31-cellotriosyl-ß-glucopyranoside (MBG4), was found to be the more generally applicable reagent. This substrate was fully characterised using a crude malt ß-glucanase extract, a bacterial lichenase (Bacillus sp.) and a non-specific endo-1,3(4)-ß-glucanase from Clostridium thermocellum (EC 3.2.1.6). Standard curves were derived that allow the assay absorbance response to be directly converted to ß-glucanase/lichenase activity on barley ß-glucan. The specificity of MBG4 was confirmed by analysing the action of competing glycosyl hydrolases that are typically found in malt on the substrate. Manual and automated assay formats were developed for the analysis of a) ß-glucanase in malt flour and b) lichenase enzyme extracts and the repeatability of these assays was fully investigated.

Quantitative fluorometric assay for the measurement of endo-1,4-ß-glucanase.

There is a growing demand for research tools to aid the scientific community in the search for improved cellulase enzymes for the biofuel industry. In this work, we describe a novel fluorometric assay for cellulase (endo-1,4-ß-glucanase) which is based on the use of 4,6-O-benzylidene-4-methylumbelliferyl-ß-cellotrioside (BzMUG3) in the presence of an ancillary ß-glucosidase. This assay can be used quantitatively over a reasonable linear range, or qualitatively as a solution screening tool which may find extensive use in the area of metagenomics.