Single Injection Of Gentamicin Research Articles

Low-Dose Intratympanic Gentamicin for Unilateral Ménière's Disease: Accuracy of Early Vestibulo-Ocular Reflex Gain Reduction in Predicting Long-Term Clinical Outcome.

BackgroundThe number of intratympanic gentamicin (ITG) injections needed to achieve vertigo control in patients with intractable Ménière's disease (MD) may vary from a single dose to several instillations. Changes in different vestibular test results have been used to define an endpoint of treatment, including the decrease of the vestibulo-ocular reflex (VOR) gain elicited by the head-impulse test.ObjectiveTo assess the accuracy of the VOR gain reduction after horizontal canal stimulation, as measured with the video head-impulse test (vHIT) 1 month after the first intratympanic injection, in predicting the need for one or more instillations to control vertigo spells in the long term.MethodsThe VOR gain reduction was calculated in 47 patients submitted to (ITG) therapy 1 month after the first instillation.ResultsSingle intratympanic treatment with gentamicin has a 59.6% efficacy in vertigo control in the long term. Hearing change in the immediate period after treatment (1 month) is not significant to pre-treatment result and is similar for patients who needed multiple doses due to recurrence. Chronic disequilibrium and the need for vestibular rehabilitation were less frequent in patients with a good control of vertigo with just one single injection of gentamicin. A fair accuracy was obtained for the VOR gain reduction of the horizontal canal (area under the curve = 0.729 in the Receiver Operating Characteristic analysis) in predicting the need for one or more ITG.ConclusionsSingle intratympanic treatment with gentamicin is an effective treatment for patients with MD. That modality of treatment has very limited damaging effect in hearing. The degree of vestibular deficit induced by the treatment is significant as measured by the reduction in the gain of the VOR but not useful for prognostic purposes.

Treatment of Ménière's Disease With "On-Demand" Intratympanic Gentamicin Injections

To determine the clinical response to intratympanic administration of gentamicin in patients with Ménière's disease and to ascertain whether the pure-tone average, caloric test, or disease duration might predict clinical control. Prospective study. Patients were followed for at least 2 years after the first injection (mean follow up time, 39 mo), and a Kaplan-Meier analysis was used to determine the survival curve that best explains the response to treatment. Tertiary center, University hospital. Individuals diagnosed with unilateral Ménière's disease that did not respond to previous medical treatment and who had not previously undergone surgery. Of the initial 83 patients recruited, 9 were lost during the follow-up, and thus, 74 subjects were included in the study. In the consultant's surgery, a myringotomy was performed with topic administration of phenol before the intratympanic administration of 2 to 3 ml of gentamicin (26.7 mg/ml). Further injections were administered if vertigo was not controlled and recurred. Absence of vertigo and the need for subsequent injections as measured in using a Kaplan-Meier time-to-event process. To test predictive variables, the log-rank test was used. Complete control of vertigo was obtained with a single injection of gentamicin in 53% of the patients. Subsequent injections offered a 50% chance of obtaining complete control. Better results were obtained in patients in whom disease duration was less than 3 years. On-demand administration of intratympanic gentamicin provides an alternative treatment for medically refractory Ménière's disease. Moreover, the Kaplan-Meier analysis was useful to analyze recurrent manifestations, such as vertigo attacks in Ménière's disease.

Intratympanic gentamicin treatment in Meniere's disease: Patients' experiences and outcomes

The aim of this study was to assess the experiences and outcomes of patients receiving intratympanic gentamicin treatment for Ménière's disease in Norfolk, UK. This study was based on a retrospective questionnaire survey and a review of patients' medical records. Two district hospitals. All 29 patients treated between 1999 and 2001, with a minimum follow up of two years post-treatment, were included in the study. Twenty-three patients completed the questionnaires (79 per cent response rate). Glasgow benefit inventory (GBI) and vertigo symptom scale (VSS) scores, plus change in hearing thresholds. The mean GBI total score was +36, indicating substantial improvement in patients' overall quality of life following gentamicin treatment. The VSS scores demonstrated low levels of vertigo or unsteadiness in treated patients. Three patients suffered deterioration in their hearing thresholds following a single injection of gentamicin. However, 96 per cent of responders stated that they would be willing to have such treatment again, if necessary. Intratympanic gentamicin treatment ought to be offered to Ménière's patients suffering from disabling vertigo, with the proviso that they be made aware of the possibility of hearing deterioration.

Angular Vestibulo-Ocular Reflex Gains Correlate with Vertigo Control after Intratympanic Gentamicin Treatment for Meniere's Disease

The objective of our study was to determine whether angular vestibulo-ocular reflex (aVOR) gains correlated with vertigo control after intratympanic gentamicin treatment for Meniere's disease. We conducted a prospective study of 18 subjects with unilateral Meniere's disease treated with intratympanic gentamicin injection and followed all subjects for 1 year. We measured the gain of the aVOR elicited by rapid rotary head thrusts in each of the canal planes for each subject before and after treatment with intratympanic gentamicin by using magnetic search coils to record eye movements. During the follow-up period, 11 subjects ("single-treatment group"; 61%) had control of their vertigo with a single gentamicin injection. The remaining 7 subjects ("multiple-treatment group"; 39%) experienced recurrent vertigo that required a second injection of gentamicin at a mean of 6 months after the first treatment. The 11 subjects in the single-treatment group had significantly greater reduction of labyrinthine function after the first treatment, as measured by change in ipsilateral horizontal canal gain, than did the 7 subjects with vertigo recurrence. Changes in caloric asymmetry did not correlate with vertigo control. Our results suggest that successful treatment of Meniere's disease is closely related to attenuation of semicircular canal function as measured by horizontal canal aVOR gains.

Long-term follow-up of transtympanic gentamicin for Ménière's syndrome.

Recent studies have shown that transtympanic gentamicin for Ménière's syndrome is effective. Current treatment protocols vary. One concept has been to perform a chemical ablation; the other has been to perform a chemical alteration. Ablation requires multiple injections and is effective in controlling the vertigo, but it is associated with a significant incidence of hearing loss. Chemical alteration uses a minimal dose to reduce vestibular function without affecting cochlear function. Prospective. Tertiary medical center. Patients had classic unilateral Ménière's syndrome that was unresponsive to medical therapy. A single injection of gentamicin is given, and the patient is seen 1 month after injection. If indicated, the patient receives another injection and is reevaluated 1 month later. Control of vertigo and maintenance of hearing using the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines (1995). Fifty-six patients have documented follow-up for 2 years or more, and 21 have 4 years or more of follow-up. This article presents the 4-year results as outlined by the AAO-HNS guidelines. Vertigo classes A and B were seen in 82% of patients. The patients followed 2 to 4 years had 86% vertigo class A and B results. Those followed 4 years or more show 76% with a vertigo class A or B result. In this study there has been minimal cochlear loss. There was vestibular change clinically, which was documented by electronystagmography. It appears that a single transtympanic gentamicin injection is effective in controlling the vertigo of Ménière's syndrome. Cochlear impact has been minimal. It is most useful for those patients who have failed medical management and are severely affected but not totally incapacitated by the disease.

Temporal, spatial, and morphologic features of hair cell regeneration in the avian basilar papilla.

Hair cell-selective antibodies were used in combination with the nucleotide bromode-oxyuridine (BrdU) to examine the temporal, spatial, and morphologic progression of auditory hair cell regeneration in chicks after a single gentamicin injection. New hair cells are first identifiable with an antibody to class III beta (beta) tubulin (TuJ1) by 14 hours after BrdU incorporation, but progenitor cells in S phase and M phase are TuJ1-negative. TuJ1 labeling reveals that new hair cells are first detected at 3 days after gentamicin, in the base, and the emergence and maturation of regenerating hair cells spreads apically over time. Differentiation of regenerating hair cells consists of a progressive series of morphologic changes. During early differentiation (14 hours to 1 day after BrdU), regenerating hair cells are round or fusiform and remain near the lumen, where they are generated. During intermediate differentiation (2-4 days after BrdU), regenerating hair cells resemble support cells; their somata are elongated, their nuclei are in the support cell layer, and they appear to contact both the lumenal surface and the basal lamina. The 275-kDa hair cell antigen is first expressed in regenerating hair cells during this period. During late differentiation (7 days after BrdU and later), TuJ1-positive cells acquire the globose shape of mature hair cells. Labeling with antibodies to hair cell antigen, calmodulin, and ribosomal RNA confirms this morphologic progression. Examination of sister cells born at 3 days post-gentamicin reveals that there is equal likelihood that they will assume the hair cell or support cell fate (i.e., both asymmetric and symmetric differentiation occur).

Fast, slow, and steady-state effects of contralateral acoustic activation of the medial olivocochlear efferent system in awake guinea pigs: action of gentamicin.

The function of the medial olivocochlear efferent system was observed in awake guinea pigs by recording, in the absence of ipsilateral external acoustic stimulation, the ensemble background activity (EBA) of the VIIIth nerve from an electrode chronically implanted on the round window of one ear. The EBA was measured by calculating the power value of the round window signal in the 0.5- to 2.5-kHz band after digital or analog (active) filtering. This EBA was compared with and without the addition of a low-level broadband noise to the opposite ear. The contralateral broadband noise (CLBN, 55 dB SPL) induced, via the efferent system, a decrease (suppression) of this EBA. With the use of noise bursts of different durations, two components in this suppression could be observed. After the onset of a 1-s CLBN, the power value of the EBA decreased rapidly by 38.0 +/- 4.2% (mean +/- SD, n = 3), with a latency of <10 ms and a decay time constant of 13.1 +/- 1.0 ms (fast effect). At the offset of the 1-s CLBN, EBA came back to prestimulation values with a similar latency and a time constant of 15.5 +/- 2.9 ms. During longer CLBN stimulation (>/=1 min), EBA presented, after the fast decrease, an additional, slower decrease of 15.6 +/- 3.1%, with a delay of 9.8 +/- 1.3 s and a decay time constant of 16.1 +/- 5.0 s (n = 12, slow effect), and then remained remarkably constant for as long as observed, i.e., >2 h (steady state). The average global suppression was thus up to 47.8 +/- 5.8% of the basal, pre-CLBN-stimulation EBA value. At the offset of the CLBN, EBA returned to pre-CLBN level with fast and slow phases, with, for the slow phase, no delay and a time constant of 32.1 +/- 8.1 s. Fast and slow changes in EBA power values were observed after a single injection of gentamicin (GM) at different doses (150, 200, and 250 mg/kg). At 150 and 200 mg/kg, GM progressively and reversibly blocked the rapid effect, but the slow component of the efferent medial suppression remained remarkably unchanged. However, at higher doses both the fast and slow suppressions were totally yet still reversibly blocked. These observations indicate that the medial olivocochlear efferent system exerts sustained influences on outer hair cells and that this effect develops in two different steps that may have different basic cellular mechanisms.

The efferent-mediated suppression of otoacoustic emissions in awake guinea pigs and its reversible blockage by gentamicin.

The physiology of the medial efferent olivocochlear system involves suppressive interactions of contralateral sounds on ipsilateral sound-evoked responses, but its role is largely unknown to date. Medial efferents act at the level of cochlear outer hair cells via cholinergic synapses and might affect their mechanical activity, thereby modulating auditory sensitivity. The aim of the present work was to obtain noninvasive measurements of distortion-product otoacoustic emissions (DPOEs), which reflect outer hair cell function, in order to establish the characteristics of medial efferent-induced suppression in awake, restrained guinea pigs. A clear suppression of DPOEs was induced by continuous contralateral white noise presented at 20-70 dB SPL, in the absence of any confounding effect of anesthesia, middle-ear muscles, or acoustic cross talk. Recently, acute injection of a high dose of the aminoglycoside antibiotic gentamicin (150 mg/kg) was reported to alter the suppressive effect of contralateral noise on eighth nerve-compound action potentials, presumably by blocking efferent synapses to outer hair cells. This hypothesis was confirmed with DPOEs for which a single injection of gentamicin at the same dose abolished suppression after about 1-2 h, whereas no change in basal levels was observed. Complete recovery was obtained after 48 h. This experiment may provide an easy, noninvasive tool for studying auditory function with and without functioning efferents.

Mitochondrial role in hair cell survival after injury

The role of mitochondrial biogenesis in hair cell survival after injury was evaluated by inhibiting mitochondrial protein synthesis with chloramphenicol and then studying the effects on hair cell survival after exposure to two different types of ototoxins, gentamicin and acoustic trauma. Seven- to 10-day-old chicks were treated with either a single injection of gentamicin (250 mg/kg) or noise (1500 Hz at 120 dB sound pressure level for 14 hours). A subset of the gentamicin- and noise-treated animals also received chloramphenicol (1200 mg/kg during a 24-hour period) through a subcutaneous osmotic pump. A control group received chloramphenicol alone (1200 mg/kg during a 24-hour period). All animals were sacrificed after 5 days, and their basilar papillae (cochleas) were prepared for scanning electron microscopy. Hair cell loss was quantified with stereologic techniques. Animals treated with chloramphenicol alone did not have any evidence of hair cell loss. Gentamicin-treated animals had characteristic hair cell loss beginning at the basal tip and tapering out along the inferior edge more distally. The addition of chloramphenicol to gentamicin treatment significantly increased hair cell loss by 30%, extending the area of hair cell loss into the superior hair cell region at the distal boundary of the lesion. Pure-tone noise exposure characteristically produced hair cell loss along the inferior edge and occasionally included hair cells along the most superior edge. Addition of chloramphenicol to noise exposure significantly increased hair cell loss by 80%, with extension of the lesion across the full width of the sensory epithelium and basally. These results demonstrate that mitochondrial biogenesis is involved in cellular responses to injury. They suggest that mitochondrial function may regulate the probability of survival after metabolic challenges to hair cell integrity. (OTOLARYNGOL HEAD NECK SURG 1995;113:530-40.)

Mitochondrial role in hair cell survival after injury.

The role of mitochondrial biogenesis in hair cell survival after injury was evaluated by inhibiting mitochondrial protein synthesis with chloramphenicol and then studying the effects on hair cell survival after exposure to two different types of ototoxins, gentamicin and acoustic trauma. Seven- to 10-day-old chicks were treated with either a single injection of gentamicin (250 mg/kg) or noise (1500 Hz at 120 dB sound pressure level for 14 hours). A subset of the gentamicin- and noise-treated animals also received chloramphenicol (1200 mg/kg during a 24-hour period) through a subcutaneous osmotic pump. A control group received chloramphenicol alone (1200 mg/kg during a 24-hour period). All animals were sacrificed after 5 days, and their basilar papillae (cochleas) were prepared for scanning electron microscopy. Hair cell loss was quantified with stereologic techniques. Animals treated with chloramphenicol alone did not have any evidence of hair cell loss. Gentamicin-treated animals had characteristic hair cell loss beginning at the basal tip and tapering out along the inferior edge more distally. The addition of chloramphenicol to gentamicin treatment significantly increased hair cell loss by 30%, extending the area of hair cell loss into the superior hair cell region at the distal boundary of the lesion. Pure-tone noise exposure characteristically produced hair cell loss along the inferior edge and occasionally included hair cells along the most superior edge. Addition of chloramphenicol to noise exposure significantly increased hair cell loss by 80%, with extension of the lesion across the full width of the sensory epithelium and basally. These results demonstrate that mitochondrial biogenesis is involved in cellular responses to injury. They suggest that mitochondrial function may regulate the probability of survival after metabolic challenges to hair cell integrity.

Contralateral suppression of transient evoked otoacoustic emissions in guinea-pigs: effects of gentamicin.

A single injection of gentamicin in the awake guinea-pig induces a transient blockade of the suppression by contralateral white noise of tone-pip evoked compound action potential (Smith et al., 1994). We report here the reversible blockade, in exactly the same experimental conditions, of the suppression of click-evoked otoacoustic emissions. These observations confirm the transient action of gentamicin at the medial efferent/outer hair cell synapse, likely via the reversible blockade of calcium channels observed in vitro (Dulon et al., 1989).

Factors affecting duration of in-vivo postantibiotic effect for aminoglycosides against Gram-negative bacilli

A murine thigh-infection model was used to determine the effect of certain host- and drug-related factors on the duration of the in-vivo postantibiotic effect (PAE) observed with aminoglycosides against Gram-negative bacilli. The role of neutrophils (PMNs), pharmacokinetics and variation among species and strains were studied. PAEs were quantitated after a single injection of gentamicin or amikacin. PAEs were several hours longer in normal mice than in neutropenic mice, in mice with renal impairment than in those with normal renal function, and with strains of Klebsiella pneumoniae than with strains of Escherichia coli, Serratia marcescens and Enterobacter cloacae. Among the 15 strains of Enterobacteriaceae studied, the duration of the in-vivo PAE did not correlate with MIC, duration of in-vitro PAE, and extent of in-vivo bactericidal activity. We conclude that prolonged PAEs are consistently observed in vivo with aminoglycosides against Enterobacteriaceae, and that this duration is enhanced in the presence of PMNs and by pharmacokinetic properties simulating those observed in humans.

Gentamicin and Bacterial Culture (Nurmi Culture) Treatments Either Alone or in Combination against Experimental Salmonella hadar Infection in Turkey Poults

The effect of three treatments on Salmonella hadar infection in turkey poults was examined. The three treatments were: (A) a single injection of gentamicin, (B) peroral treatment with anaerobic culture derived from cecal contents of an adult turkey (Nurmi culture), and (C) combination of treatments A and B. Nurmi culture was significantly more effective than gentamicin treatment. Nurmi culture along with gentamicin reduced the number of shedding birds, but a higher proportion of birds became carriers compared with the groups given Nurmi culture only. Gentamicin injection alone did not prevent the spreading of infection in larger groups raised on litter, but it did so in one experimental group raised on wire floor.