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[Accelerated hyperfractionated simultaneous radiochemotherapy in advanced head-neck carcinomas in comparison: split course and concomitant boost concept].

PATIENTS: Between 1989 and 1992, 38 patients with advanced squamous cell carcinomas of the head and neck were treated by an accelerated hyperfractionated split-course radiochemotherapy (SCRC). This therapy was carried out at the ENT department and department of radiooncology of the University of Heidelberg. Within 51 days, 70.2 Gy were applied in three courses. In every course, simultaneous chemotherapy with cisplatin (60 mg/m2/week)/5 Fu (bolus: 350 mg/m2/d)/Leucovorin (bolus: 50 mg/m2 + 100 mg/m2/24 h) was carried out. Between 1992 and 1994, 50 patients suffering from advanced head and neck cancer (stage III, V) were also treated with an accelerated hyperfractionated concomitant-boost radiochemotherapy (CBRC) at the same departments. A total dose of 66 Gy, was applied within 33 days. The patients were also treated with simultaneous chemotherapy with carboplatin (70 mg/m2/24 h) in the first and fifth week. RESULTS: In about 50% of the patients treated with SCRC, the therapy was more than 10 days longer than the scheduled period. The lack of compliance due to toxicity was considered as one of the main reasons for this delay. After the first course of SCRC, eight of 38 patients showed mucositis of the upper aerodigestive tract (WHO grade > 3); after the second course, 11 of 38 patients; and after the third course, 15 of 38 patients. Fifty-two percent of the patients developed emesis, 10% leucopenia < 1 nl, 10% nephrotoxicity, 3% pancreatitis, 3% thrombosis, 3% gastritis, and 3% auditory threshold shifts of about more than 10 dB. In about 7.5% of the patients treated with CBRC, the therapy was more than 10 days longer than the scheduled period. The mucositis of the upper aerodigestive tract (50% of the patients showed WHO-grade > 3) was considered to be the main reason for this. In four patients a neutropenia < 1 nl was detected, in one patient anemia < 7 g/dl and n 33 patients thrombocytopenia < 100/nl. CONCLUSIONS: In conclusion, the concomitant boost radiochemotherapy showed a lower toxicity and higher acceptance than the split-course radiochemotherapy. This is documented in lower protocol delays and better results in the two-years survival time in case of concomitant boost radiotherapy.

Adult↗

[Drug therapy of progressive hearing disorders in children].

In 1987 and 1988 Nickisch et al. discussed the effect of infusions of prednisolone, pentoxifylline and, partially, piracetam in Ringer lactate solvent on progressive sensorineural hearing loss in childhood and adolescence. Time of observations was 4 years. Unfortunately long-term investigations could not confirm the initially good therapeutic results of 1987/88. In 35% were found permanently and in 12.5% temporarily better auditory thresholds after infusion. The loss of progressive sensorineural hearing in childhood usually takes a fateful course that can hardly be influenced. As is the case with adults, good therapeutic results can most probably be achieved by infusions starting close to the event, i.e. within 48 hours.

Adolescent↗

The rebound phenomenon of glycerol-induced changes in the endolymphatic space.

Volumetric changes of the scala media were histologically investigated in normal guinea pigs to see whether glycerol-induced volumetric change of the scala media followed a biphasic course similar to the auditory threshold in the glycerol test. Glycerol was administered orally in a 12 ml/kg dose. The volume of the scala media was assessed by examining the cross-sectional area of the scala media in the mid-modiolar sections of the cochlea. Histological study revealed that the time-course of the change in the volume of the scala media after glycerol intake showed biphasic changes. Specifically, the early phase of the glycerol effect is a decrease in endolymph volume. The volume of the scala media significantly decreased by 11.4+/-2.9% 2 h after glycerol intake. Thereafter, the volume began to increase, and reached its peak 6-12 h after intake. In addition, the volume of the scala media significantly increased by 17.6+/-1.1% after 6 h. The present study indicated that the secondary increase in the volume of the scala media following glycerol intake played an important role in the rebound phenomenon in the glycerol test, although the mechanism underlying the hearing loss with the endolymphatic hydrops remains to be elucidated.

Administration, Oral↗

Internet-based tele-audiometry system for the assessment of hearing: a pilot study.

The application of tele-audiology is in its infancy. Several systems have been developed to screen hearing, yet the application of real-time diagnostic audiology to a remote location is new. This paper describes a tele-audiometric system developed for the application of realtime diagnostic audiometry via the Internet. A pilot study evaluated 31 adult participants in a double-blind study of two different systems (i.e., conventional versus Internet-based) for assessing auditory thresholds. The threshold data show substantial agreement between the two systems. Mean thresholds varied by no more than 1.3 dB, well within established variability of audiometric testing. This pilot study demonstrated the feasibility of real-time Internet-based assessment of hearing. The system allows this remote assessment of hearing without an audiologist on site. Further investigation will assess of outcomes and costs.

Audiometry↗

Recent otological evaluation of aminoglycoside antibiotics.

A survey is made of comparative studies of ototoxicity of different aminoglycoside antibiotics. Animal studies show clearly lower netilmicin ototoxicity compared with that of other aminoglycoside antibiotics. Clinical controlled comparative trials are few. Most studies have few patients in each group. The significance of auditory threshold shifts in single frequencies as criteria of ototoxicity is uncertain. An analysis of clinical and animal studies together indicates, however, that netilmicin has a higher ratio of efficacy to ototoxicity than other aminoglycoside antibiotics.

Aminoglycosides↗

Are aminoglycoside antibiotics excitotoxic?

Guinea pigs received gentamicin to induce a profound hearing loss (61 dB auditory threshold shift at 18 kHz). Concomitant administration of maleic or tartaric acid dissolved in dimethyl sulfoxide (DMSO) significantly reduced the threshold shift to < 40 dB. The results have several important implications. First, they support the hypothesis of a free-radical mechanism of gentamicin toxicity since the protective compounds are metal chelators and scavengers. Second, they caution against these and similar chemicals, commonly found in drug preparations, as vehicles in tests of aminoglycoside toxicity. For example, a recent study by others describing attenuation of aminoglycoside ototoxicity by NMDA antagonists may have been influenced by the presence of maleate, tartrate and DMSO. Third, they suggest simple antioxidants as a potentially efficient and inexpensive clinical prophylaxis of aminoglycoside-induced hearing loss.

Animals↗

Safety of ofloxacin otic and other ototopical treatments in animal models and in humans.

To assess the safety of topical agents in the middle ear, animal studies were reviewed. Compared with aminoglycoside-containing preparations, which caused significant loss of hair cells in the basal turn of the cochlea, ofloxacin caused no loss of hair cells, even at concentrations higher than used clinically. Moreover auditory brainstem testing revealed no change in auditory thresholds in the ofloxacin-treated animals, whereas neomycin-treated animals showed substantial threshold shifts. In human studies, use of topical ofloxacin 0.3% was not associated with any change in hearing. Topical ofloxacin has no demonstrable adverse effects on middle ear or cochlear function.

Aminoglycosides↗

Basilar membrane displacement related to endolymphatic sac volume.

OBJECTIVE: To demonstrate that the amount of basilar membrane displacement toward the scala tympani and its attachment to the bony wall of the scala tympani (i.e., interscalar septum) in hydropic temporal bones is related to the intraosseous endolymphatic sac volume. STUDY DESIGN: A retrospective analysis of temporal bones from individuals with the histopathologic diagnosis of "endolymphatic hydrops." METHODS: Fifty-two temporal bones, from 38 patients, with the histopathologic findings of "endolymphatic hydrops" were analyzed microscopically. Data were obtained regarding the displacement of the basilar membrane, endolymphatic sac volume, hair cell loss, strial atrophy, ganglion cell loss, and last measured auditory thresholds. The relationships between these variables were examined statistically. RESULTS: Nineteen of the 52 temporal bones (36.5%) with endolymphatic hydrops showed displacement of the basilar membrane toward the scala tympani in the apical and middle segments of the cochlea. A reduced volume of the endolymphatic sac was significantly related to increased severity of basilar membrane deformation (Rho = -.646; P < or = .001). Multiple regression analysis showed that severity of basilar membrane deformation was the single best predictor of low frequency thresholds while loss of hair cells was the best predictor of pure-tone average threshold. CONCLUSIONS: The displacement of the basilar membrane in the apical and middle segments that may occur with endolymphatic hydrops, to the extent that it impinges on the interscalar septum, is related to a reduction in the intraosseous endolymphatic sac volume.

Aged↗

Auditory sensitivity of the monkey.

Auditory thresholds for pure tones were determined in monkeys (three Macaca irus and one Macaca nemestrina) by the psychophysical method of constant stimuli after the animals had been trained by operant conditioning procedures. Their audible frequency range was found to extend from below 60 hertz to 40 or 45 kilohertz.

Animals↗

Clinical evaluation of efficacy, pharmacokinetics, and safety of teicoplanin for serious gram-positive infections.

Nineteen patients hospitalized for serious gram-positive infections were treated with teicoplanin, a new glycopeptide antibiotic. A variety of infections were treated, including endocarditis, septic thrombophlebitis, osteomyelitis, pyogenic arthritis, and soft tissue infection. Of 13 infections that could be evaluated in 12 patients, there were 8 clinical cures, 2 improvements, 1 recurrence, and 2 failures. Of the eight patients with Staphylococcus aureus bacteremia, seven were clinically cured or improved with teicoplanin therapy. Of the nine patients in whom the bacteriological response to treatment could be fully evaluated, six were cured; there was recurrence of infection in one, and treatment failed in two patients. In vitro testing showed the 13 bacterial isolates (9 S. aureus, 3 S. epidermidis, and 1 group B streptococcus) to be uniformly susceptible to teicoplanin, with MICs ranging from 0.12 to 0.5 microgram/ml. Every isolate was more susceptible in vitro to teicoplanin than to vancomycin. Three of the staphylococcal isolates were resistant to methicillin. Pharmacokinetic studies demonstrated that after an initial drug-accumulation period, a single daily dose adequately maintained the teicoplanin concentrations in serum within therapeutic ranges. Teicoplanin also penetrated well into synovial fluid. The drug was well tolerated by either intravenous or intramuscular administration. The most significant adverse reaction was an urticarial rash which required discontinuation of therapy in one patient; a second patient experienced a modest decrease in high-frequency auditory threshold. Asymptomatic eosinophilia and mild elevation of serum transaminases were noted as well. The results of this study suggest that teicoplanin is a safe and effective new agent for treatment of serious infections caused by gram-positive organisms.

Adult↗

Environmental enrichment improves response strength, threshold, selectivity, and latency of auditory cortex neurons.

Over the last 50 yr, environmental enrichment has been shown to generate more than a dozen changes in brain anatomy. The consequences of these physical changes on information processing have not been well studied. In this study, rats were housed in enriched or standard conditions either prior to or after reaching sexual maturity. Evoked potentials from awake rats and extracellular recordings from anesthetized rats were used to document responses of auditory cortex neurons. This report details several significant, new findings about the influence of housing conditions on the responses of rat auditory cortex neurons. First, enrichment dramatically increases the strength of auditory cortex responses. Tone-evoked potentials of enriched rats, for example, were more than twice the amplitude of rats raised in standard laboratory conditions. Second, cortical responses of both young and adult animals benefit from exposure to an enriched environment and are degraded by exposure to an impoverished environment. Third, housing condition resulted in rapid remodeling of cortical responses in <2 wk. Fourth, recordings made under anesthesia indicate that enrichment increases the number of neurons activated by any sound. This finding shows that the evoked potential plasticity documented in awake rats was not due to differences in behavioral state. Finally, enrichment made primary auditory cortex (A1) neurons more sensitive to quiet sounds, more selective for tone frequency, and altered their response latencies. These experiments provide the first evidence of physiologic changes in auditory cortex processing resulting from generalized environmental enrichment.

Acoustic Stimulation↗

Iron deficiency and hearing loss. Experimental study in growing rats.

Cochlear changes were studied in 141 growing rats raised on a basic iron-deficient diet for 7-100 days; 130 rats served as normal or chronic anemia controls. Electrophysiological findings showed that the incidence of an auditory threshold elevation of more than 15 dB was 31.85% in the iron-deficient rats, but it was unchanged in all the control animals. The main cochlear histopathological changes induced by iron deficiency were strial atrophy and reduction of spiral ganglion cells. It is concluded that the observed anomalies may be attributed solely to iron deficiency of the cochlear tissue.

Animals↗

Cognitive impairment in schizophrenia.

The cognitive functioning of 62 schizophrenic subjects was compared with that of 42 normal controls using neuropsychological tasks that included assessment of soft neurological signs, an aphasia screening test, tachistoscopic stimulation, auditory threshold determinations, and items from the Mini-Mental State, Halstead-Reitan, and Luria-Nebraska batteries. Performance was rated blindly for hemispheric, regional cortical, and global impairment. No control showed more than a mild deficit, whereas three-quarters of the schizophrenic patients exhibited moderate to severe dysfunction. Schizophrenic subjects differed significantly from controls on all measures and showed bilateral impairment that was comparatively worse in the dominant frontotemporal regions. These differences were not a function of age, sex, handedness, or drug administration.

Adult↗

Summating potential and water balance in Meniere's disease.

The summating potentials (SP) to free-field 1-, 2-, 4-, and 8-kHz, 90-dB HL tone bursts were recorded by means of transtympanic electrocochleography in 45 patients divided into three groups: those with Meniere's disease, those whose diagnosis was uncertain, and control subjects. The similarities across frequencies between the human SP (promontory) and the experimental SP (DIF component from basal turn) suggest that the SP recorded in electrocochleography originates mostly from the base of the cochlea; negative values were observed at low frequencies (1 to 2 kHz), positive values at high frequencies (8 kHz). Patients with Meniere's disease showed significantly larger SP values than control subjects. The effect of orally administered glycerol on the SP and action potential amplitudes was evaluated by means of automated recordings repeated every 5 minutes. Summating potential values were remarkably constant in the control group. A decrease in SP absolute amplitude was observed in most patients with Meniere's disease and some subjects with uncertain diagnoses, specifically at low frequencies. These changes were frequently associated with action potential amplitude and auditory threshold improvements at low frequencies. It is assumed that the glycerol-induced SP changes at low frequencies are related to modifications in the low frequency mechanical response of the basilar membrane at the basal turn.

Adult↗

Prospective crossover evaluation of four methods of clinical management of tinnitus.

This article summarizes data obtained from 34 tinnitus-afflicted patients who participated in and completed a prospective crossover evaluation of four methods of clinical management of tinnitus. The methods included a 2-week trial with each of the following: a tinnitus masker, a tinnitus instrument (a combination device consisting of a tinnitus masker and a hearing aid), a hearing aid, and conventional environmental controls. The relative effectiveness of each method of treatment was assessed by interview. The data presented summarize respondents' preferences for each method of treatment. Use of a tinnitus masker, tinnitus instrument, and hearing aid is related to stability of auditory thresholds. Comments are made on our experience with clinical management of the patient afflicted with tinnitus, and observations are offered on continued investigation in this area.

Adult↗

The perception of microsound and its musical implications.

Sound particles or microsounds last only a few milliseconds, near the threshold of auditory perception. We can easily analyze the physical properties of sound particles either individually or in masses. However, correlating these properties with human perception remains complicated. One cannot speak of a single time frame, or a "time constant" for the auditory system. The hearing mechanism involves many different agents, each of which operates on its own timescale. The signals being sent by diverse hearing agents are integrated by the brain into a coherent auditory picture. The pioneer of "sound quanta," Dennis Gabor (1900-1979), suggested that at least two mechanisms are at work in microevent detection: one that isolates events, and another that ascertains their pitch. Human hearing imposes a certain minimum duration in order to establish a firm sense of pitch, amplitude, and timbre. This paper traces disparate strands of literature on the topic and summarizes their meaning. Specifically, we examine the perception of intensity and pitch of microsounds, the phenomena of tone fusion and fission, temporal auditory acuity, and preattentive perception. The final section examines the musical implications of microsonic analysis, synthesis, and transformation.

Auditory Perception↗