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Biomedical subjects

M A Fazekas-May

Publications and source records attributed to M A Fazekas-May.

4 recordsLinked to original sources

Utility of helical computed tomography in the study of arytenoid dislocation and arytenoid subluxation.

Conventional computed tomography (CT) has been considered a mainstay in the evaluation of the larynx. A major difficulty with utilizing this modality, especially in the study of the arytenoid, is the time necessary to perform a thin-slice examination through a structure that has a propensity to move with respiration and swallowing. Helical CT not only significantly reduces the time necessary to study the larynx, but enables one to perform multiple high-resolution multiplanar reconstructions. Eleven patients with arytenoid abnormalities documented by strobovideolaryngoscopy or direct laryngoscopy were imaged with helical CT. A comprehensive radiographic examination illustrating the cricoarytenoid relationship in all of the subjects was completed in less than 20 seconds by using axial reconstructions in 2-mm-thick slices at 1-mm intervals, with subsequently derived sagittal and coronal reconstructions. Helical CT may be a useful adjunct in the diagnosis of arytenoid subluxation or dislocation.

Adult↗

Nephrotoxic and ototoxic agents.

It is well established that many drugs, such as the aminoglycoside antibiotics and the chemotherapeutic drug cisplatin, are capable of inducing both nephrotoxicity and ototoxicity. The factors that selectively predispose the kidney and inner ear to the toxic effects of these agents as well as the mechanism by which damage is produced are not well defined. The two organs differ greatly in their exposure to these toxic agents. The kidney has an abundant vascular supply and tends to selectively concentrate a number of drugs within the renal cortex or medulla, often to toxic levels. The vascular supply of the inner ear is not as extensive. In addition, the stria vascularis of the cochlea may act as a functional regulator of drug entry into inner ear fluids. The absorption of drugs into perilymph and endolymph is poorly understood. Selective accumulation theories of drug accumulation in the inner ear must be questioned because of the results of recent pharmacokinetic studies, which give contrary data. Drug-induced ototoxicity and nephrotoxicity can be explained on a cellular level. Studies using radiolabeled gentamicin suggest that binding mechanisms of the drug to the plasma membrane of the outer hair cells of the cochlea and vestibular apparatus and to the brush border receptors of the renal proximal convoluted tubules are similar. This suggests the same receptor sites for aminoglycosides occur in otic and renal organs. Calcium channels are implicated because of the reversibility of aminoglycoside-induced changes in the cochlear microphonic by calcium and other divalent cations. Calcium channel blockers, such as verapamil, reduce the nephrotoxicity of a number of drugs that are also ototoxic. Studies are needed to assess potential prevention of ototoxicity by use of these same calcium channel blocking agents. Aminoglycosides concentrate within the lysosomes of renal proximal tubular cells. Possibly, they also may concentrate in lysosomes within the cells of cochlear and vestibular structures. Nephrotoxic heavy metals concentrate within proximal tubular cells and, some, such as lead or bismuth, specifically concentrate within intracytoplasmic or intranuclear inclusion bodies. Studies are necessary to determine if the same metals accumulate within the cochlear and vestibular cells, inclusion bodies, or both. These questions and others must be answered before it can be determined why many nephrotoxic drugs and agents are also ototoxic.

Adolescent↗

Prevention of cisplatin-induced toxicity by selected dithiocarbamates.

Cisplatin (CDDP) is a widely used antineoplastic agent, the administration of which is associated with dose-related toxicities. Currently, ototoxicity is the dose-limiting toxicity of cisplatin and difficult to prevent. The purpose of this study was to determine the ability of two substituted dithiocarbamates, diethyldithiocarbamate (DDTC) and N-methyl-D-glucaminedithiocarbamate (NMGDTC) to abrogate cisplatin-induced toxicity in young female Hartley albino guinea pigs. The animals were divided into saline controls, CDDP only, NMGDTC only, and CDDP-DDTC or CDDP-NMGDTC combinations with DDTC or NMGDTC given 30 minutes before or 30 minutes after CDDP. Auditory brainstem responses (ABR) were recorded periodically in sound-attenuated rooms to assess hearing thresholds. Representative cochleas were harvested at autopsy, processed, and examined by scanning electron microscopy (SEM). The NMGDTC produced marked reduction of CDDP-induced ototoxicity and weight loss. No significant ABR shift was found regardless of the order of CDDP and NMGDTC administration, but the derivative was more effective in preventing anorexia and weight loss when given prior to CDDP. Specifically, groups of guinea pigs given NMGDTC prior to CDDP showed the only weight gain among the treatment groups. Diethyldithiocarbamate, the other dithiocarbamate evaluated in this study, did not provide protection from cisplatin ototoxicity regardless of the order of administration. A CDDP-induced weight loss was reduced when DDTC was administered prior to CDDP. In summary, NMGDTC given prior to CDDP offers remarkable protection against cisplatin-induced ototoxicity and weight loss. It may help eliminate dose-limiting cisplatin-induced toxicity and allow the use of cisplatin at higher doses in cancer chemotherapy.

Animals↗