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Biomedical subjects

J Graham

Publications and source records attributed to J Graham.

At least 307 records · Page 17Linked to original sources

Evaluation of patients for cochlear implant by promontory stimulation. Psychophysical responses and electrically evoked brainstem potentials.

The protocol for assessing patients for cochlear implantation at University College Hospital and the Royal National Institute for the Deaf, London, includes a session of electrophysiological tests and electrical stimulation of the cochlea. Electrocochleography is performed with the object of excluding non-organic hearing loss and of clarifying the site of deafness. Using the same transtympanic needle, AC and DC electrical stimulation is performed to establish whether patients perceive a sensation of sound, dynamic range and ability to detect frequency shifts. Tinnitus suppression was produced by AC and DC stimulation. It is likely that AC suppression of tinnitus occurs by a masking effect. Electrically evoked auditory brainstem potentials were recorded in one patient.

Brain Stem↗

Phase I and pharmacokinetic study of LM985 (flavone acetic acid ester).

We have conducted a Phase I and initial clinical pharmacological evaluation of LM985, the first of a series of compounds based on the flavone ring structure to be considered for clinical trial in malignant disease. The drug was administered i.v. to 26 patients with advanced cancer on an every-21-day schedule. Patients were treated at 14 dosage levels ranging from 10 to 1500 mg/m2. Dose limiting toxicity was identified as acute reversible hypotension occurring during drug infusion; no leukopenia, alopecia, hepatic toxicity, or renal toxicity was observed, but at the higher dose range, mild sedation was apparent. Twenty patients had measurable disease and were evaluable for response. One patient with colorectal carcinoma had stable disease after three courses of LM985; however, no other responses were seen. Pharmacokinetic and in vitro drug degradation studies imply that the ester LM985 is hydrolyzed to LM975 (flavone acetic acid) rapidly in vivo. LM975 is active in a variety of animal tumor models, but it does not have the cardiovascular side effects seen with LM985 (hypotension and bradycardia) in pithed or anesthetized rats. We would recommend that LM975 be considered for clinical trial, because it seems likely that substantially higher doses of LM975 than of LM985 can be given without dose limiting cardiovascular toxicity.

Adult↗