Don L. Burgio

The comparative effects of sodium thiosulfate, diethyldithiocarbamate, fosfomycin and WR-2721 on ameliorating cisplatin-induced ototoxicity

The efficacies of four agents in ameliorating cisplatin-induced ototoxicity were investigated. Hamsters were given a series of 5 cisplatin injections (3 mg/kg/injection once every other day, i.p.) either alone or in combination with 1600 mg/kg/injection sodium thiosulfate (STS), 300 mg/kg/injection diethyldithiocarbamate (DDTC), 18 mg/kg/injection WR-2721, or 300 mg/kg/injection fosfomycin (n = 10/group). Ototoxicity was assessed electrophysiologically by auditory brainstem responses (ABRs) and anatomically by cochlear histology. The greatest auditory protection was given by STS, followed by DDTC. WR-2721 and fosfomycin did not provide any protection. All of the animals in the STS and DDTC groups survived, while some fatalities occurred in the fosfomycin, WR-2721, and cisplatin-only groups. Thus, the agents that were protective against ototoxicity were also protective against mortality. The ABRs also provided evidence of cisplatin-induced neuropathy. In summary, STS and DDTC hold promise for ameliorating the ototoxic effects of cisplatin chemotherapy and the hamster proved to be an excellent model of cisplatin ototoxicity.

Comparison of five agents in protecting the cochlea against the ototoxic effects of cisplatin in the hamster

The purpose of this investigation was to study the ameliorating effects of four agents on cisplatin-induced ototoxicity. Hamsters were given a series of five cisplatin injections either alone or in combination with sodium thiosulfate (STS), diethyldihydrothiocarbamate (DDTC), and S-2(3-aminopropylamino) ethylphosphorothioic acid (WR-2721), or fosfomycin. Ototoxicity was assessed anatomically by quantifying the extent of cochlear damage with the scanning electron microscope and physiologically with measures of the auditory brain stem response. When administered alone, cisplatin induced widespread loss of outer hair cells (OHCs) along much of the cochlea in the hamster, especially in the basal and middle turns, with an average survival of only 56% of the OHC population. In contrast, inner hair cells resisted cisplatin ototoxicity in the hamster. Thus the ameliorative effects of the different test agents were assessed by counting the number of surviving OHCs in each treatment group and comparing with cisplatin-treated controls. STS provided the most effective protection against the ototoxic effects of cisplatin, yielding 91% survival of OHCs. DDTC also reduced the ototoxic effects of cisplatin, yielding 68% survival of OHCs. Cotreatment with WR-2721 and fosfomycin yielded 45% and 52% OHC survival, respectively, and thus did not provide any chemoprotection. The results closely paralleled those based on auditory brain stem response recordings in that the magnitude of threshold shift was proportional to the amount of OHC loss; also, the amount of threshold shift at each frequency was in good agreement with the pattern of hair cell loss along the cochlear spiral. Thus both histologic and physiologic results suggest that STS and DDTC hold promise for ameliorating the ototoxic effects of cisplatin chemotherapy.

Nasal alar reconstruction: A critical analysis using melolabial island and paramedian forehead flaps

Objectives: To qualitatively and quantitatively describe aesthetic and functional outcomes following Mohs ablative surgery involving the alar subunit, using a paramedian or subcutaneous melolabial island flap. Study Design: Retrospective review. Methods: A single surgeons results in 38 consecutive patients were analyzed. Objective measures (alar rim thickness, donor scar width and length), subjective assessment (seven aesthetic parameters) by three academic otolaryngologists, and patient satisfaction questionnaires were evaluated. Student t test was used to ascertain statistically significant differences between reconstructive groups. Results: Questionnaire results demonstrate a significant (P = .026) difference in donor site rating favoring melolabial group responses. Objective scar measurements and subjective ratings of textural quality and alar notching also favored melolabial reconstructions. Conclusions: More favorable aesthetic and functional outcomes are seen with single subunit cutaneous alar defects reconstructed with the melolabial island flap than with deep composite or extensive unilateral nasal defects reconstructed with the paramedian forehead flap.

Bone autografting of the craniofacial skeleton: Clinical and biological considerations

Bone grafting in the craniofacial region is an important reconstructive technique and has become widely used in otolaryngology-head and neck surgery. The success of bone grafting has greatly improved since the first recorded transplantation of a piece of dog skull to repair a defect in a Russian soldier’s skull by Van Meek’ren in 1682.’ The patient was excommunicated as a result of the procedure, and 2 years later Van Meek’ren removed the graft so the patient could return to his church. In 1820, Von Walther performed the first recorded human autologous bone graft.’ Interest in bone grafting was increased in 1867 by the publication of the experimental work of Ollier,3 which stressed the role of periosteum in the regeneration of bone. In 1878, Macewen4 reported a successful transplant of human bone allograft, and in 1912 he published a report of the repair of a mandibular defect with an autogenous rib graft.’ By 1923, bone grafting had become more widely used, and Albee’ published his experiences with over 3,000 bone graft operations. Since that time, many methods of bone transfer and aspects of bone grafting physiology have been studied and characterized, but still many more questions remain unanswered. Today, bone is a frequently transplanted tissue, with over 100,000 bone graft or bone implant procedures being performed each year in the United States alone.7 Autologous bone transplants are preferable to allografts (homologous bone) in their ability to be recognized as self, and thus avoid the

An Evaluation of the Head-Shaking Nystagmus Test

Head-shaking nystagmus can be observed in some patients with vestibular lesions. This nystagmus is transient and appears after 15 to 20 cycles of rapid head-shaking. Horizontal head-shaking may be associated with a low-amplitude reversal phase, which follows the primary response. Several previous studies using active head movement have indicated that head-shaking nystagmus is a sensitive indicator of vestibular loss. In this study, the head-shaking nystagmus test using passive head movement was evaluated in 115 patients and 17 control subjects, using three examiners. The data indicate that using passive head movement, the head-shaking nystagmus test is neither sensitive nor specific enough for use as a screening test for vestibular loss.

Mucosal injuries of the upper aerodigestive tract after smoking crack or freebase cocaine

The introduction of “crack” and “freebase” cocaine to the United States has resulted in an increased number of patients presenting to emergency rooms with cocaine‐related burns of the upper aerodigestive tract. Because symptoms are nonspecific and histories often unreliable, the emergency room physician must keep a high index of suspicion for cocaine use when confronted with these types of patients. We present seven patients who had burns to the upper aerodigestive tract as a result of smoking crack or freebase cocaine. Two of seven patients underwent an emergency tracheotomy, probably because of delayed diagnosis and inadequate early medical intervention. This article reviews the history behind cocaine use, its different modes of administration, potential complications associated with smoking cocaine, diagnostic workup, and treatment options.

Guinea Pig Vestibular Blood Flow in Response to Calcitonin-Gene Related Peptide

Little is known about the physiologic regulation of the vestibular end organ blood flow. The purpose of the current study was to examine posterior semicircular canal ampulla blood flow in addition to systemic factors during intravenous infusions of calcitonin-gene related peptide (CGRP), a factor involved in the tonic regulation of blood flow. Receptors for this factor are known to be available to the vascular supply of the vestibular organs. Local blood flow using laser Doppler flowmetry and systemic parameters were monitored during infusion of CGRP. CGRP antagonists and control vehicle. The results show relatively stable vestibular blood flow (VBF), concentration-dependent decreases in systemic blood pressure, and elevations in heart rate. Pretreatment with CGRP(8-37), a specific receptor antagonist, attenuated these responses to subsequent CGRP infusions. These findings suggest a rigid regulation of VBF in the presence of a systemically active vasodilator.

Magnetic resonance imaging of the facial nerve in children with idiopathic facial paralysis

The role of gadolinium-enhanced MRI (Gd-MRI) in the diagnosis of idiopathic facial paralysis (IFP) in children is not well defined. Fourteen children with IFP were evaluated to assess the use of Gd-MRI for the presence and pattern of enhancement and its usefulness in predicting the recovery of facial function. Six of 14 children had enhancement of the facial nerve on Gd-MRI, whereas 8 had none. Enhancement was noted in the tympanic, mastoid, and most commonly in the distal intracanalicular and labyrinthine segments. The average time from onset of paresis to recovery in patients with enhancement was 19.3 weeks, whereas in those with no enhancement, mean recovery time was 9.5 weeks (P = 0.003, t test). All 14 patients eventually had recovery to House-Brackmann grade I or II. Gd-MRI is not required for all children with IFP but may yield information about the time course of recovery of facial function.

Evaluation of hydroxyapatite ossicular chain prostheses

Hydroxyapatite (HA) middle ear prostheses have gained popularity as an alternative to human autografts and homografts. This study reports on 3 HA prostheses types: total ossicular chain prostheses, used for grafting the stapes footplate to the tympanic membrane; partial ossicular chain prostheses, used for grafting the stapes superstructure to the tympanic membrane; and Kartush incus struts (Smith & Nephew Richards Inc), used for grafting the stapes superstructure to the undersurface of the malleus. This single-surgeon study of 33 consecutive cases revealed a statistically significant difference in mean postoperative air-bone gap and air-bone gap closure between incus struts (14/26 dB) or partial (22/11 dB) or total (25/10 dB) ossicular chain prostheses (t test: P < 0.05). Prognostic risk factors graded by the Middle Ear Risk Index indicate a tendency for worse postoperative hearing with increasing Middle Ear Risk Index. This study supports the use of HA ossicular prostheses and, in particular, the use of the malleus for ossicular chain construction. (Otolaryngol Head Neck Surg 2000;123:425-9.)

The effects of flunarizine and pentoxifylline on vestibular blood flow in the guinea pig

Abstract Several authors have proposed that complications arising from vestibular disorders are the result of compromised circulation. The purpose of the current study was to assess the ability of flunarizine and pentoxifylline to increase peripheral vestibular blood flow (VBF), since flunarizine is a selective calcium-channel entry blocker that inhibits calcium-related contraction of smooth muscle, while pentoxifylline is a xanthine derivative that promotes microcirculation by affecting red blood cell malleability. Both of these treatment strategies have received considerable attention in clinics and laboratory, but their effects on blood flow are unclear. Changes in VBF were evaluated from the posterior semicircular canal ampulla in guinea pigs using a laser Doppler flowmeter. One group of animals was infused with pentoxifylline at concentrations of 10–40 mg/ml, while a second group was treated with 0.3–1.5 mg/kg flunarizine. VBF, blood pressure (BP) and heart rate (HR) were monitored continuously. Findings showed that pentoxifylline induced a concentration-dependent increase in VBF. In contrast, no increase in VBF occurred in response to flunarizine infusions. These studies suggest that the effectiveness of pentoxifylline in the clinical treatment of vestibular disorders may be the result of improved blood flow.