Gregory J. Matz

Comparative study of ototoxicity and nephrotoxicity in patients randomly assigned to treatment with amikacin or gentamicin

Fifty-four patients treated with gentamicin and 52 patients treated with amikacin were evaluated for nephrotoxicity and ototoxicity in a prospective, randomized, blinded comparative trail. According to our definition of nephrotoxicity (an increase in serum creatinine levels to at least 50 percent and 0.5 mg/dl above the baseline value), nephrotoxicity occurred in eight (15 percent) of the patients who were treated with gentamicin and none of the patients who were treated with amikacin (p = 0.006). Using several other definitions of nephrotoxicity, the differences in incidence between the treatment arms were not significant. Nephrotoxicity appeared to be associated with impaired baseline renal function, greater age, and the presence of bacteremia. Ototoxicity occurred in six (11 percent) of the 54 gentamicin-treated patients; auditory toxicity occurred in three patients, and toxic changes were observed in three of the 33 patients who could also be evaluated for vestibular toxicity. Similarly, ototoxicity was observed in seven (13 percent) of the 52 amikacin-treated patients; auditory toxicity occurred in four patients, and of the 34 patients who could also be evaluated for vestibular toxicity, three exhibited vestibular toxicity without auditory toxicity are one experienced vestibular effects in addition to those affecting the cochlea. We observed a modest association of ototoxicity with nephrotoxicity and with an elevated mean trough aminoglycoside serum level. The results of this study indicate that amikacin may be less nephrotoxic than gentamicin in humans; however, the broad applicability of this finding to other patient populations is uncertain.

Comparative clinical studies of ototoxicity and nephrotoxicity of amikacin and gentamicin

A comparative study of the oto- and nephrotoxicity of amikacin and gentamicin was carried out prospectively. Twenty-six gentamicin-treated patients and 27 amikacin-treated patients were monitored for changes in auditory and renal function during and after therapy. Thirteen of those treated with gentamicin and 20 of those treated with amikacin underwent vestibular caloric testing which could be evaluated for evidence of toxicity. In four (15.4%) of the gentamicin-treated patients, nephrotoxicity developed; no such toxicity was seen in the amikacin-treated patients. This difference may have been due to a fortuitously higher incidence of pretreatment renal impairment in the gentamicin-treated group. In two gentamicin-treated patients (7.7%), ototoxicity developed (one auditory, one vestibular), and in two amikacin-treated patients (7.4%), auditory toxicity developed. Statistical analysis of oto- and nephrotoxicity and their risk factors was not attempted because of the small numbers of patients who could be evaluated. Additional patients are being studied.

The ototoxic effects of ethacrynic acid in man and animals

A review of the literature was carried out to summarize the ototoxic effects of ethacrynic acid on man and animal. The effects of this drug on the electrolytes of the endolymphatic and perilymphatic systems, on the cochlear potentials and the auditory cortical-evoked responses, were reviewed. Histological animal studies determined by light and electron microscopy were described. Potentiation of this drug with previous aminoglycoside therapy was discussed. In this paper, a human case report with temporal bone findings was present in addition to the histopathological effects of this drug which were shown in a series of animals receiving this drug over a period of time. Edematous and cellular changes in the stria vascularis, especially with animals receiving large doses of the drug, were described. No permanent alterations in the cochlear potentials resulted from the long-term therapy with ethacrynic acid.A review of the literature was carried out to summarize the ototoxic effects of ethacrynic acid on man and animal. The effects of this drug on the electrolytes of the endolymphatic and perilymphatic systems, on the cochlear potentials and the auditory cortical‐evoked responses, were reviewed. Histological animal studies determined by light and electron microscopy were described. Potentiation of this drug with previous aminoglycoside therapy was discussed. In this paper, a human case report with temporal bone findings was presented in addition to the histopathological effects of this drug which were shown in a series of animals receiving this drug over a period of time. Edematous and cellular changes in the stria vascularis, especially with animals receiving large doses of the drug, were described. No permanent alterations in the cochlear potentials resulted from the long‐term therapy with ethacrynic acid.

Temporal Bone Pathology in Herpes Oticus

The etiology of hcrpes oticus was first postulated by Hunt1 after reviewing the excellent pathological work of Head and Campbell on spinal herpes zoster.2 Hunt attributed the pathology of herpes oticus to the geniculate ganglion. In his specimen the pars intermedius was degenerated and by the proximity of the geniculate ganglion to this sensory root, he concluded that the geniculate ganglion was the site of the pathology although this structure was avulsed at the time of the dissection.

Acute vestibular paralysis in herpes zoster oticus.

A case of herpes zoster oticus is presented in which the lateral and superior semicircular canals of the labyrinth were affected unilaterally. The results of several electronystagmographic examinations are described and correlated with the patients description of symptoms. This case study indicates that disease affecting the lateral semicircular canal is reliably detected by the conventional caloric test. However, the fact that the posterior semicircular canal remained intact could not be inferred from the results of the caloric test in this case. Also, the appearance of nystagmus upon eye closure appears to have been a more sensitive index of the state of the disease process than was the caloric test.

Indirect Videolaryngoscopy versus Direct Endoscopy for Larynx and Pharynx Cancer Staging Toward Elimination of Preliminary Direct Laryngoscopy

Thirty-nine patients with cancer of the larynx and pharynx (33 untreated and six previously treated patients) underwent tumor mapping by both direct laryngoscopy (DL) and indirect videolaryngoscopy (IVL). The examiner in each case was unaware of the findings of the other evaluation method. After definitive treatment had been carried out so that pathologic and operative information was also available, comparisons of the accuracies of the two methods of staging were made. In 32 cases, IVL provided information equal to or better than that provided by DL, and a tissue sample also could be obtained during IVL. On the basis of these findings, we conclude that aggressive, office-based IVL can guide initial treatment planning (partial or total laryngectomy versus irradiation) and patient counseling. A confirmatory DL can be performed without surprises at the time of definitive surgery, rather than as a separate procedure — A cost-effective modification of standard practice.

Oat cell carcinoma of the larynx. Response to combined modality therapy

A patient with oat cell carcinoma of the larynx with metastasis to cervical lymph nodes is presented. Treatment with radiation and chemotherapy has achieved a sustained remission. Pretherapy staging and combined modality therapy are discussed.

Carcinoma of the Tonsil

This disease is often thought to be primarily a surgical lesion, which carries the suggestion that radiation be reserved for surgical failures or for very early lesions. Other opinions name radiation as the primary mode of treatment. In an effort to improve the cure rate, combination therapy such as preoperative radiation followed by surgery is here suggested.

Late onset chronic mucocutaneous candidiasis with lymphoma and specific serum inhibitory factor.

A patient with late onset chronic mucocutaneous candidiasis developed lymphocytic lymphoma. A specific inhibitor of in vitro lymphoproliferative responses to candidal antigen was detected in her serum which persisted following clinical remission of candidiasis after combined amphotericin‐B and 5‐Fluorocystosine therapy. It is unclear whether the combined therapy was exclusively anticandidal, nonspecific immunostimulant or cytotoxic affecting the underlying incipient lymphoma.

Ototoxic effects of ethacrynic acid.

Hearing loss from the diuretic ethacrynic acid was initially described by Maher and Schreiner, I and laterby other investigators.v? According to these reports the ototoxicity occurred in patients with renal failure, and was characterized by a temporary or permanent neurosensory deafness. In many cases the deafness appeared during or immediately after treatment with the diuretic, but because of liver andl heart failure, shock, and the use of other drugs, it was often difficult to evaluate the effects of ethacrynic acid alone.