[Neurofeedback-based EEG alpha and EEG beta training. Effectiveness in patients with chronically decompensated tinnitus]. / Neurofeedbackgestütztes EEG-alpha- und EEG-beta-Training. Wirksamkeit in der Therapie des chronisch-dekompensierten Tinnitus.

BACKGROUND: Persisting tinnitus is an often devastating disease condition with restricted and rarely successful therapeutic options. PATIENTS AND METHODS: The present study investigates the therapeutic effect of short term neurofeedback-based EEG-Alpha- and EEG-Beta-training in 40 patients suffering from "chronic decompensated tinnitus". Patients were assigned to the Alpha or Beta group according to results of an initial EEG monitored stress-test. Four patients were excluded because they showed abnormal reactions in both EEG patterns. RESULTS: During 12 sessions, 23 patients succeeded to increase EEG Alpha activity by 16% (p< or =0.042) while 13 patients achieved no decrease of EEG Beta activity. However, both groups showed a significant reduction of subjective tinnitus annoyance by the end of the therapy (p< or =0.001) CONCLUSIONS: The results indicate that neurofeedback may represent a new promising technique in the therapy of chronic decompensated tinnitus. However, it remains to be established whether the reduction of tinnitus annoyance results from the altered brain activity patterns supported by the neurofeedback learning process.

[Inner ear damage due to leisure and broadband noise. An experimental study on initial and permanent functional and morphological damage]. / Innenohrschäden durch Freizeitlärm und Breitbandrauschen. Eine experimentelle Studie zu initialen und permanenten funktionellen und morphologischen Schäden.

The initial and permanent effects of leisure noise (toy pistols, rock music) compared to broadband noise were examined in 68 guinea pigs. Auditory threshold shifts at 1.5, 2, 3, 4, 6, 8, 12 und 16 kHz were registered before and immediately after exposure as well as on days 1, 2, 3, 5,7 and 21 post-exposure using the auditory brain stem response (ABR) technique. In order to examine cilia and hair cell damage in eight cochlear frequency regions (<0,4 kHz, 0,4-0,8 kHz, 0,8-1.5 kHz, 1.5-3 kHz, 3-5 kHz, 5-11.5 kHz, 11.5-26 kHz und >26 kHz), cytocochleograms were performed immediately after exposure and on days 1, 7 and 21.Frequency dependent functional or morphological damage was found which depended on the type of trauma tested. All results were highly significant ( P<0.001). The results show that partial recovery of hearing occurred within 3 days of acute acoustic trauma induced by toy pistols and within 1 day after exposure to rock music or broadband noise. There was no further recovery of hearing within the following 18 and 20 days, respectively. Furthermore, permanent threshold shifts after exposure to rock music or broadband noise were not associated with cilia and/or hair cell damage.

Pharmacological influence on inner ear endothelial cells in relation to the pathogenesis of sensorineural hearing loss.

Despite an increasing incidence of acute sensorineural hearing loss, the pathogenesis of this disease remains uncertain. While viral infection of the stria vascularis, organ of Corti or spiral ganglion cells is discussed in the American literature, a vascular genesis with resulting impaired perfusion of the inner ear is favoured by European investigators. Although both hypotheses are supported by different therapeutic strategies to regain normal hearing, the influence of spontaneous remission remains unclear. This study aims at combining these seemingly opposing concepts with the assumption of an immunologically mediated vasculitis with consequent cochlear hypoperfusion. We already know from other organs that during viral vasculitis circulating immunoglobulins are deposited perivascularly, which leads to a local decrease in perfusion and tissue hypoxia. Also in autoimmune diseases, perivasculitis is common with the endothelium playing a major role at the initial stages of the disease. These endothelial cells promote vasculitis by secreting pro-inflammatory cytokines like IL-1, IL-6 or TNF-alpha in addition to the expression of adhesion molecules. Due to the persistence of these immunopathological mechanisms stenosis or atresia with ischaemic necrosis results. To examine whether this pathomechanism is also important in inner ear dysfunction, the immunological response after stimulation of the cochlear endothelium of guinea pigs was determined. In addition, the influence of corticosteroids on this immune cascade was examined.

Sudden sensorineural hearing loss: does application of glucocorticoids make sense?

BACKGROUND: Treatment of sudden sensorineural hearing loss (SSNHL) consists of administration of blood flow-promoting drugs with or without the addition of glucocorticoids. General guidelines based on scientific data do not currently exist. OBJECTIVE: To investigate the effect of glucocorticoids on the treatment of SSNHL. SETTING: Academic medical center. PATIENTS AND METHODS: We retrospectively analyzed the audiograms of 603 patients with SSNHL: 301 patients (cared for between January 1, 1986, and December 31, 1991) received intravenous blood flow-promoting drugs without glucocorticoids and 302 patients (cared for between January 1, 1992, and December 31, 1998) received intravenous blood flow-promoting drugs with glucocorticoids (intravenous +/- oral application). The age distribution of patients with SSNHL in lower, middle, and higher frequencies was similar in both groups. RESULTS: Patients with SSNHL in lower and middle frequencies (250-2000 Hz) who received glucocorticoids (prednisolone-21-hydrogen-succinate) showed significantly better recovery of hearing levels compared with those who did not receive glucocorticoids (P<.05). There was no significant difference at higher frequencies between the 2 groups. Patients with SSNHL throughout all frequencies (pancochlear hearing loss) who received glucocorticoids also had significantly better recovery of hearing levels compared with those who received blood flow-promoting drugs alone (P<.05). Also, patients with elevated blood sedimentation rates had better improvement of their hearing levels after receiving glucocorticoids. CONCLUSIONS: Administration of glucocorticoids should be recommended for treatment of patients with SSNHL. In particular, patients with SSNHL in the lower and middle frequency range and pancochlear hearing loss have significantly better recovery of hearing levels.

The effect of blood flow promoting drugs on cochlear blood flow, perilymphatic pO(2) and auditory function in the normal and noise-damaged hypoxic and ischemic guinea pig inner ear.

The effect of blood flow promoting drugs, such as hydroxyethyl starch (HES) either of low or high molecular weight (HES 70, HES 200), pentoxifylline, ginkgo biloba, naftidrofuryl and betahistine, and various combinations of the drugs was studied in unexposed and noise-exposed (broad-band noise, bandwidth 1-12 kHz, 106 dB SPL, 30 min) guinea pigs. The results were compared without therapy and placebo (isotonic saline, NaCl). The cochlear blood flow (CoBF) and the partial pressure of oxygen in the perilymph (PL-pO(2)) were continuously and simultaneously recorded over a period of 210 min. In addition, cochlear microphonics (CMs), compound action potentials of the auditory nerve (CAPs) and auditory brain stem responses (ABRs) were registered. Noise-induced hearing loss (NIHL) paralleled a decrease of PL-pO(2). Both were found to occur before evidence of reduced CoBF. PL-pO(2) and CoBF declined progressively post-exposure, while CMs, CAPs and ABRs showed no further deterioration or signs of recovery up to 180 min after cessation of noise. Treatment started 60 min post-exposure, respectively after 90 min, without manipulation in unexposed animals, and was then studied for a further 120 min. In unexposed animals, CoBF increased significantly during infusion of HES 70, HES 200, pentoxifylline and betahistine. NaCl, ginkgo biloba and naftidrofuryl did not alter CoBF. PL-pO(2) decreased significantly during infusion of all administered drugs and combinations, except for NaCl. CMs, CAPs and ABRs remained constant, with the exception of increased ABRs after infusion of HES 70 and HES 200. In noise-exposed animals, a sustained therapeutic effect on cochlear ischemia was achieved only by HES 200 and pentoxifylline. HES 70, betahistine and ginkgo biloba compensated cochlear ischemia only during infusion; however, 30-60 min after termination of therapy, no significant difference of values for CoBF was observed compared to the untreated noise-exposed groups. NaCl and naftidrofuryl showed no effect on CoBF. None of the applied drugs had a sustained compensatory effect on cochlear hypoxia. CMs, CAPs and ABRs improved significantly after HES 70, HES 200 and betahistine, resulting in partial recovery of CMs, and partial (betahistine) or even full (HES 70 and HES 200) recovery of CAPs and ABRs. In contrast, NaCl, pentoxifylline, ginkgo biloba and naftidrofuryl had no therapeutic effect on NIHL.

Successful treatment of noise-induced cochlear ischemia, hypoxia, and hearing loss.

Cochlear blood flow (CoBF), perilymphatic partial pressure of oxygen (PL-pO2), cochlear microphonics (CMs), compound action potentials of the auditory nerve (CAPs), and auditory brainstem responses (ABRs) were studied in noise-exposed guinea pigs during and after the following treatments: intravenous infusion of isotonic saline (placebo); blood flow promoting drugs (hydroxyethyl starch = HES, pentoxifylline, betahistine, gingko biloba, naftidrofuryl); antiinflammatory agents (prednisolone, diclofenac sodium, histamine H1-receptor antagonist); isobaric oxygenation (IBO); and hyperbaric oxygenation (HBO) with and without supplements (simultaneous infusion of isotonic saline, pentoxifylline, prednisolone, or HES). It was found that PL-pO2 declined simultaneously with deterioration of CM, CAP, and ABR amplitudes after exposure to broad-band noise (bandwidth 1-12 kHz, 30 min, 106-dB SPL). CoBF decreased only 30 min after cessation of broad-band noise and progressed with cochlear hypoxia, while the hearing loss showed no further signs of deterioration and no recovery up to 3 h after exposure. Treatment (60 min) started 60 min after cessation of noise and was studied for a further 60 min. Isotonic saline did not influence the measuring parameters. Noise-induced cochlear hypoxia was compensated by IBO and more effectively by HBO with and without supplements, while other treatments had no sustained effect. A sustained therapeutic effect on noise-induced cochlear ischemia was achieved only by HES, HBO + HES, and pentoxifylline. However, the best therapeutic effect on noise-induced hearing loss was achieved with a combination of HBO and prednisolone, followed by monotherapy with prednisolone or HES with the result that not only did the CAPs and ABRs completely recover, the CMs also showed significant improvement, although full recovery did not occur. All other therapies were significantly less effective or did not improve noise-induced reduction of auditory evoked potentials.

Effect of hyperbaric oxygen therapy in comparison to conventional or placebo therapy or no treatment in idiopathic sudden hearing loss, acoustic trauma, noise-induced hearing loss and tinnitus. A literature survey.

With the published clinical data to hand on the therapeutic results of patients with idiopathic sudden hearing loss, acoustic trauma or noise-induced hearing loss, it may be confirmed that 65% of those polypragmatically treated patients demonstrated a hearing improvement of 19 +/- 4 dB. In 35% of the cases, no hearing improvement was detected independent of the drugs administered. This corresponds to the results obtained from placebo-treated patients who demonstrated a hearing improvement of 20 +/- 2 dB in 61% of cases and no hearing gain in 39% of cases (fig. 1). A different set of results was obtained from patients with a hearing loss who were treated either with prednisolone or placebo. The percentage of patients who achieved normal hearing again in the placebo-treated group amounted to 31% and 38% and in the verum-treated group 50% and 78%. It may be concluded that a placebo therapy is equally effective to that of all nonsteroidal drugs. Problems arise when comparing non-treated patients since information on spontaneous remission rates differs greatly in the references, i.e. between 25-68% for spontaneous full remissions and 47-89% for spontaneous partial remissions. From a statistical view, 35% and 39% of patients experienced no success with nonsteroidal drugs or placebo, respectively. These patients can still be helped with HBO therapy. 18 patients only underwent primary HBO therapy. In all other 50 studies evaluated here with a total of 4, 109 patients suffering from idiopathic sudden hearing loss, acoustic trauma or noise-induced hearing loss and/or tinnitus, HBO therapy was administered as a secondary therapy, i.e. following unsuccessful conventional therapy. If the onset of affliction was more than 2 weeks but no longer than 6 weeks, one half of the cases showed a marked hearing gain (in at least 3 frequencies of more than 20 dB), one-third showed a moderate improvement (10-20 dB) and 13% showed no hearing improvement at all (fig. 2). 4% no longer experienced tinnitus, 81.3% observed an intensity decrease and 1.2% an intensity increase of their tinnitus condition. 13.5% remained unchanged (fig. 2). If HBO therapy was administered at a later stage, but still within 3 months following onset of affliction, 13% showed a definite improvement in hearing, 25% a moderate improvement and 62% no improvement at all. 7% no longer suffered from tinnitus, 44% reported an intensity decrease, a similar percentage noticed no change and 5% a temporary deterioration of their tinnitus condition. If the onset of affliction was longer than 3 months up to several years, no hearing improvement can be expected in the majority of patients (fig. 3); however, one third of the cases reported an intensity decrease of tinnitus, 60-62% reported no change and 4-7% noticed a temporary intensity increase (fig. 4). In conclusion, it may be deduced that HBO therapy is recommended and warranted in those patients with idiopathic sudden deafness, acoustic trauma or noise-induced hearing loss within 3 months after onset of disorder.

The effect of prednisolone and non-steroidal anti-inflammatory agents on the normal and noise-damaged guinea pig inner ear.

The effect of anti-inflammatory agents, such as the synthetic glucocorticoid prednisolone, diclofenac sodium, and histamine H1-receptor antagonist, was studied in unexposed and noise-exposed (broad-band noise, bandwidth 1-12 kHz, 106 dB SPL, 30 min) guinea pigs. The results were compared with the results obtained from no treatment and with isotonic saline (placebo) therapy. The cochlear blood flow (CoBF) and the partial oxygen pressure in the perilymph (PL-pO2) were continuously and simultaneously recorded over a period of 210 min. In addition, cochlear microphonics (CMs), compound action potentials of the auditory nerve (CAPs), and auditory brain stem responses (ABRs) were registered. Noise-induced hearing loss paralleled a decrease of PL-pO2. Both were found to occur before evidence of reduced CoBF. PL-pO2 and CoBF progressively declined post-exposure, while CMs, CAPs, and ABRs did not further deteriorate nor showed signs of recovery up to 180 min after cessation of noise. Treatment started 60 min post-exposure, or after 90 min without manipulation and was then further studied for 120 min. In the unexposed animals, diclofenac sodium and prednisolone induced a significant decline of PL-pO2, while CoBF, CMs, CAPs, and ABRs revealed no change. Isotonic saline did not influence the measured parameters. After infusion of the histamine H1-receptor antagonist, a significant decrease of CoBF together with blood pressure and CMs was observed, while PL-pO2, CAPs, and ABRs showed no change. In the noise-exposed animals, diclofenac sodium induced partial restoration of CM and CAP amplitudes and full restoration of ABRs. Following a high dose of prednisolone (25 mg), partial restoration of CMs and full restoration of CAPs and ABRs were registered. This effect was significantly less pronounced following a low dose of prednisolone (2.5 mg). Restoration of CMs, CAPs, and ABRs was immediate (i.e. 50 min after infusion) and remained stable for another 60 min until the end of the recording period. The histamine H1-receptor antagonist and isotonic saline did not influence CMs, CAPs, and ABRs. None of the applied drugs resulted in relief of progressive noise-induced cochlear hypoxia and post-traumatic ischemia. These findings indicate direct cellular effects of prednisolone and diclofenac sodium in the cochlea taking into account no blood flow and oxygenation. The possible mechanisms involved are discussed.

Complications following butane inhalation and flash fire.

Solvent inhalation is a well-documented form of drug abuse that can cause euphoria and hallucinations. Sudden death involving a volatile substance is most commonly caused by cardiac arrythmias, asphyxia, direct drug effects, and trauma. The victim in this paper suffered superficial partial thickness (12% total body surface area) burns from a flash fire that occurred when lighting a match after inhaling butane in an enclosed vehicle. The victim was admitted to the hospital for 2 days of observation but did not develop any respiratory symptoms under 2 days following her release. The victim died during her readmission, 9 days after the flash fire. Postmortem examination showed extensive epithelial injury from the upper airway and trachea to the terminal bronchioles, most likely due in part to both the initial inhalation injury and the resulting adult respiratory distress syndrome (ARDS) and staphylococcal infection. Many victims with superficial burn injuries may not seek medical attention owing to either embarrassment or fear of legal prosecution. Even those who do seek medical assistance may not reveal solvent abuse as the cause of their injuries. It is possible that delayed death may occur at home following volatile substance abuse but may remain unrecognized even with a thorough scene investigation.

Primary Hodgkin's disease of the sigmoid colon: a case report and review of the literature.

We report the case of an 81-year-old man who underwent a segmental resection of the sigmoid colon for severe diverticular disease. Histopathologic diagnosis revealed extranodal Hodgkin's disease, and the diagnosis was confirmed by immunohistochemistry. The incidence of extranodal Hodgkin's disease is rare and represents an infrequent occurrence as a gastrointestinal neoplasm and primary gastrointestinal lymphoma. A review of the literature for gastrointestinal lymphomas with emphasis on the occurrence of Hodgkin's disease, the diagnostic features, and the site of gastrointestinal tract involvement is reported.

Noise-induced cochlear hypoxia is intensity dependent, correlates with hearing loss and precedes reduction of cochlear blood flow.

Anesthetized and artificially ventilated guinea pigs were exposed to broad-band noise of 95, 101, 106 or 115 dB SPL for 30 min and studied for 180 min after cessation of noise. The partial pressure of oxygen (pO2) in the perilymph, the cochlear blood flow (CoBF) and auditory-evoked potentials were continuously recorded. Arterial blood pressure, electrocardiogram, inspiratory and expiratory gas levels, arterial blood gas levels and acid-base status were kept stable to exclude influences of these parameters on cochlear parameters. Exposure to 95 dB SPL did not affect perilymphatic pO2 or CoBF. Cochlear microphonics (CMs) were reduced, but compound action potentials of the auditory nerve (CAPs) and auditory brainstem potentials (ABRs) increased after exposure to this low-level noise. Perilymphatic pO2 decreased during exposure to 101 dB SPL and then further decreased during the subsequent 60 min after cessation of the noise. CoBF did not change significantly during and 30 min after noise but then paralleled the decline of perilymphatic pO2. However, both parameters showed a clear indication of recovery in the second and third hours after noise. At 101 dB SPL, CMs were again reduced immediately, CAPs were unaltered and ABRs again increased. Exposure to 106 and to 115 dB SPL resulted in a decrease in both perilymphatic pO2 and CoBF; this decrease began during the exposure but became progressively worse after the noise. Hearing loss was observed immediately with exposure and showed no signs of further deterioration after cessation. The observed time courses of changes are important. They reveal that hearing loss and cochlear hypoxia precede reduction in CoBF due to noise exposure. The potential mechanisms underlying these effects are discussed.

Living isolated cells from inner ear vessels: a new approach for studying the regulation of cochlear microcirculation and vascular permeability.

The spiral modiolar artery with its proximal branches and the microvessels in the spiral ligament and the stria vascularis were microdissected from the guinea pig cochlea. After incubation with proteolytic and collagenolytic enzymes the mixed cell suspension was fractionated by gradient centrifugation. The cells migrated according to their buoyant densities into the fractions of 1.04 g/ml (endothelial cells), 1.06 g/ml (vascular smooth muscle cells obtained from the spiral modiolar artery; strial pericytes) and 1.08 g/ml (pericytes obtained from the spiral ligament). To test for viability cells were loaded with a fluorescent vital stain (BCECF-AM); for identification, cell-specific stains were used. Identity of endothelial cells (ECs) was confirmed using acetylated low density lipoprotein fluorescently labeled with dioctadecyl-tetramethyl-indocarbocyanine perchlorate (DiI-Ac-LDL). Pericytes were identified immunofluorescently using the method according to Nayak et al. (1988). Vascular smooth muscle cells were stained for F-actin with rhodamin-phalloidin. This in vitro technique may open new approaches to study local factors involved in microcirculation and vessel permeability of various cochlear vascular beds.

[Experimental defects of the round window membrane]. / Experimentelle Rundfenstermembrandefekte.

Previous and current studies of experimentally induced fistulas in the round window membrane (RWM) are reviewed. After puncture (or "micro-perforation") of the RWM leaking perilymph was not been observed and auditory evoked potentials have remained unaltered. In contrast, most publications have reported that gross incisions ("macro-perforations") of the RWM have resulted in the deterioration of auditory evoked potentials, with leaking perilymph and/or cerebrospinal fluid and/or with entrance of air bubbles into the scala tympani depending on the site of the perforation. Spontaneous healing was then observed within 4 to 8 days and was associated with normalization of the auditory evoked potentials. In a very few experimental studies pathophysiological mechanisms were simulated that may be involved clinically in patients with RWM fistulas, i.e. implosive rupture of the RWM due to an acute increase in middle ear pressure or explosive rupture of the RWM that may occur in patients trying to use forced Valsalva maneuvers to equalize decreased middle ear pressures due to blocked Eustachian tubes.

Influence of middle ear immune response on the immunological state and function of the inner ear.

According to clinical experience, a causative correlation between otitis media and sensorineural hearing loss is likely. During an otitis media, inflammatory mediators should be released and diffuse through the round window membrane to cause an immune response of the inner ear. Using 20 guinea pigs, an immunologically caused otitis media was induced. Auditory evoked potentials were registered by means of electrocochleography and electric response audiometry from day 0 to day 7. Each time, before and after starting the immune response serum, middle ear effusion and perilymph were sampled and the concentration of interleukin-2 (IL-2) analyzed. Decalcified temporal bones were examined immunohistochemically. In this study, IL-2 was found in the middle ear effusion and perilymph, and there was evidence of an immune response of the inner ear during an otitis media. Histological results were in close correlation with this event. Electrophysiological data showed conduction deafness and signs of sensorineural hearing loss with a maximum at day 3.

[Drug therapy of sensorineural hearing loss--critical remarks]. / Die medikamentöse Therapie der Innenohrschwerhörigkeiten--kritische Anmerkungen.

Recent placebo-controlled clinical double-blind trials failed to confirm any beneficial effects of rheological and vasodilative drugs or hemodilution in treatment of inner ear diseases. Furthermore, experimental studies have recently shown that cochlear blood flow was only temporarily improved during infusion of blood flow promoting drugs and cochlear oxygenation was deterioated with most of these drugs. Therefore treatment of basic or accompanying diseases is currently the only effective therapy and prophylaxis and general practitioners as well as internal and neurological specialists should be involved in therapeutical approach of inner ear disorders.

[Effect and effectiveness of hyperbaric oxygen therapy in chronic hearing disorders. Report of 557 cases 1989]. / Zur Wirkung und Wirksamkeit der hyperbaren Sauerstofftherapie bei alten Hörstörungen. Bericht über 557 Fälle aus dem Jahre 1989.

After ten applications of hyperbaric oxygen therapy to 557 patients with hearing loss, 27.8% of the patients experienced a hearing improvement of more than 10 dB. Tinnitus improved in 62.2% of all cases. Hyperbaric oxygen therapy should be used for all cases of extreme hearing loss or severe tinnitus that is resistant to the usual therapy.