The expression of vascular endothelial growth factor (VEGF) and VEGF‐C in early laryngeal cancer: relationship with radioresistance

The expression of vascular endothelial growth factor (VEGF) and VEGF‐C in early laryngeal cancer: relationship with radioresistance Angiogenesis is essential for tumour growth and invasion. Vascular endothelial growth factor (VEGF) is a prime mediator of tumour angiogenesis. VEGF‐C is a closely related protein that effects lymphatic endothelial cells and may be important in the process of lymphatic metastasis. The purpose of this study was to evaluate the expression of these cytokines in patients with T1 and T2a glottic, squamous cell carcinoma, in comparison with normal epithelial control tissue, to ascertain any association with radioresistance. Twenty‐two tumours treated by radiotherapy (13 radiosensitive, nine radioresistant) and seven normal control tissues were studied. The minimum follow‐up was 2 years after radiotherapy. Expression of VEGF and VEGF‐C was evaluated by immunohistochemistry of formalin‐fixed, paraffin‐embedded biopsy specimens. Analysis was carried out using a quantitative computer image analyser. Both VEGF and VEGF‐C were detectable in tumour and normal control specimens. There was increased expression in tumour specimens of both VEGF (P = 0.03) and VEGF‐C (P < 0.001). In addition, the expression of VEGF‐C was associated with tumours of higher histological grade (P = 0.021). There was, however, no difference in VEGF and VEGF‐C expression between radioresistant and radiosensitive tumours. The expression of VEGF and VEGF‐C is increased in early laryngeal squamous cell carcinoma (SCC). However, measuring the expression of these proteins cannot predict radioresistance in this tumour group.     

Treatment of Maxillary Sinus Carcinoma: Clinical Results Using the Kitasato Modality

The conventional therapeutic regimen for maxillary sinus carcinoma consists of dissection of the maxilla, full-dose irradiation and extensive chemotherapy. However, the results obtained with this treatment are often poor. Even when patients recover, their quality of life is significantly reduced as a result of deformity of facial structures and swallowing and articulation dysfunctions. A retrospective analysis of 68 patients with maxillary sinus carcinoma treated with the Kitasato modality between 1975 and 1999 was conducted. All patients underwent pergingival maxillary sinus surgery combined with pre- and postoperative irradiation therapy with standardized total doses of 16 Gy; the postoperative irradiation was given in combination with regional intra-arterial infusion chemotherapy administered via the superficial temporal artery. All visible tumor lesions were removed where possible in order to preserve or facilitate cellular immunity after surgery. The cumulative 5-year survival rates were 85.7% for Stage II patients, 88.1% for Stage III, 76.6% for Stage IVA and 75.0% for Stage IVB.     

Physiologische Grundlagen einer Hörprothese

Zusammenfassung Im Bemühen, eine Hörprothese zu entwickeln, die ein Sprachverständnis erlaubt, erscheint es zumindest fürs erste am zweckmäßigsten, durch künstliche elektrische Reizung des Hörnerven die natürlichen Verhältnissen so gut als möglich zu imitieren. Der normale Hörnerv enthält etwa 30000 Nervenfasern, die sich qualitativ gleich, quantitativ jedoch unterschiedlich verhalten, wobei über die Eigenschaften der von den ÄHZ kommenden Spiralfasern im Augenblick sichere Aussagen nicht möglich sind (siehe 2.3). Die quantitativen Unterschiede zwischen den einzelnen Hörnervenfasern beziehen sich auf deren Frequenzabstimmung, Frequenzselektivität, Schwellen, Intensitätsfunktionen und — wichtig insbesondere für das Vorhaben einer künstlichen elektrischen Reizung — in Zeitunterschieden in den Aktivitätsmustern, die durch Laufzeitunterschiede auf der Basilarmembran bedingt sind (2.3). Diese Zeitunterschiede in der Aktivität einzelner Fasern liegen im Bereich mehrerer ms (2.3.6; 2.3.7). Die durch Schallreize im normalen Hörnerven ausgelösten Aktionspotentiale haben überdies einen probabilistischen Charakter, d. h. ihr Auftreten ist keineswegs streng determiniert. Es versteht sich von selbst, daß man bei künstlicher, elektrischer Reizung nicht alle verbliebenen Nervenfasern selektiv reizen kann. Somit wird eine Reizelektrode immer eine Gruppe von Nervenfasern erregen müssen. Bei jeder denkbaren elektrischen Reizung wären alle Fasern im Reizbereich einer Elektrode synchron und streng deterministisch aktiviert, was einen außerordentlich ernstzunehmenden Unterschied zu natürlichen Verhältnissen darstellt (3.2).Um die Zahl der zum Sprachverständnis mindestens notwendigen Reizkanäle abzuschätzen, wird man, in Ermangelung anderer experimenteller Daten, von psychoakustischen Untersuchungen an Normalhörenden auszugehen haben. Diese haben gezeigt, daß das Gehör neben einer außerordentlichen Fähigkeit verschiedene Tonhöhen zu unterscheiden, andererseits die Fähigkeit besitzt, bestimmte Frequenzgebiete zu sogenannten Frequenzgruppen zu integrieren. Die in eine solche Frequenzgruppe fallende Schallenergie wird zu einem einheitlichen Höreindruck verarbeitet. Es scheint also sinnvoll, die für einen Prothesenbau notwendige Zusammenfassung von Gruppen von Fasern des Hörnerven in verschiedene Reizkanäle entsprechend diesen Frequenzgruppen vorzunehmen (3.1). Demnach müßte der Sprachbereich in 15 Reizkanäle aufgeteilt werden, was wiederum, wenn man in der Cochlea reizen will, 1,2 mm Abstand von Kanal zu Kanal erlauben würde. Dabei müßte der Reizerfolg sauber auf die einzelnen Kanäle beschränkt bleiben, d.h. eine optimale Kanaltrennung erreicht werden. In Anbetracht der groben Abweichungen der neuronalen Aktivität vom normalen Verhalten, die bei künstlicher, elektrischer Reizung unvermeidlich sind, ist freilich unsicher, ob die angegebene Zahl ausreichen würde. Andererseits ist es in Anbetracht der zu erwartenden Stromverteilung im Sprachbereich kaum vorstellbar, mehr als die angegebene Zahl von Kanälen realisieren zu können.Was die Kodierung der Schallparameter innerhalb eines Elektrodenkanals betrifft, wird vorgeschlagen, die Frequenzkodierung nach dem Ortsprinzip optimal auszunutzen, und im Hinblick auf die Periodizitätsanalyse und die Lautheitskodierung sich soweit als möglich den natürlichen Verhältnissen anzunähern (3.3). Dabei wären Laufzeitunterschiede zwischen den Kanälen und der probabilistische Charakter der neuronalen Entladungen soweit als möglich einzuführen, um die Dominanz eines periodicity pitch zu vermeiden.Eine für Sprachverständnis ausreichende Prothese ist auch nur denkbar, wenn eine Prothese die zur Sprachübertragung notwendige Übertragungskapazität besitzt. Ergebnisse der Kanal-Vocoder-Technik zeigen, daß Sprache noch mit 1500 bit/s befriedigend übertragen werden kann. Eine Abschätzung der möglichen Leistungsfähigkeit einer 15-kanaligen Prothese (3.4), basierend auf der Zahl der möglichen unterscheidbaren Unterschiedsstufen der Hörempfindung, ergibt, daß diese Übertragungskapazität knapp erreicht werden könnte. Allerdings ist damit noch nicht gesagt, daß das Zentralnervensystem die angebotene Information auch im Sinne einer Phonemanalyse auswertet und damit für ein Sprachverständnis maximal ausschöpft. Nur für diesen Fall wäre ein Sprachverständnis zu erwarten.Als Reizort erscheint in erster Linie die Cochlea (5.1) geeignet. Für den Fall einer Degeneration der primären afferenten Fasern des Hörnerven ist aufgrund physiologischer Überlegungen auch der Nucleus cochlearis ventralis (5.5) interessant, allerdings würde so nur der ventrale Anteil der Hörbahn stimuliert. Doch besitzen auch andere Reizorte spezifische Vorteile (5.2–5.4).Theoretische Überlegungen (6.1) und experimentelle Messungen an implantierten Elektrodensätzen (6.3) zeigen, daß die Forderung der Kanaltrennung nur schwer zu erreichen sein wird. Deswegen wird der dynamische Bereich (im Hinblick auf Veränderung des Reizstromes) eines nach den obigen Kriterien konstruierten Reizkanals auf maximal 3 dB zu beschränken sein, so daß Erregungsausbreitung auf weitere Bereiche der Cochlea durch Ansteuerung von mehreren Reizkanälen zu imitieren wäre.Die Chancen, eine Prothese zu verwirklichen, die befriedigendes Sprachverständnis auf der Basis einer quasinatürlichen Reizung des Hörnerven erlaubt, wird von uns in Anbetracht der geschilderten mannigfaltigen Schwierigkeiten als sehr niedrig angesehen. In Anbetracht des großen Nutzens, der andererseits eventuell resultieren könnte, halten wir die Erforschung des Problems jedoch für angebracht.Es wird von uns vorgeschlagen, auch zu untersuchen, ob sich für eine prothetische Versorgung vorverarbeitete Sprache besser eignet (7.). Für Prothesen, die ein Sprachverständnis nicht anstreben, halten wir eine Implantation in die Cochlea für überflüssig. Hier erscheint uns die Implantation von Reizelektroden am runden Fenster (Douek et al., 1977; Fourcin et al., 1978; s. a. 1. und 7.) wegen des geringeren Risikos der überlegenere Weg.Die zitierten eigenen Arbeiten der Autoren wurden mit Unterstützung der DFG durchgeführt (DFG-K1 219).     

Cervical Reflex Induced by Click Stimuli in Cats

We studied click-evoked potentials in the anterior horn of the spinal cord in 17 cats. A concentric needle electrode was inserted into the anterior horn of the spinal cord at levels C3-C6. Potentials evoked with 105 dB SPL clicks were recorded with a peak latency of 4.89-5.10 ms only at the C3 level. These responses were observed 45-60 dB SPL above the auditory brainstem response (ABR) threshold, and no potentials were evoked by stimulation of the contralateral ear. Average was performed 100 times with changes in stimulation frequency of 1-20 Hz. The amplitude of the potentials decreased with increasing stimulus frequency, but there were no changes in ABRs. The responses disappeared after destruction of the medial vestibulospinal tract at the obex level, but ABRs were still recorded. The spinal nucleus of the accessory nerves was located in the anterior horn of the spinal cord at levels C1-C6, and the sternocleidomastoid muscle motoneurons were found at levels C1-C3. The click-evoked potentials recorded in this study reflect responses of the spinal nucleus of accessory nerves through the vestibulospinal tract to click stimulation. The responses have the same characteristics as vestibular-evoked myogenic potentials that can be recorded using surface electrodes over the sternocleidomastoid muscles of humans.     

Tongue Base Reduction with Temperature-controlled Radiofrequency Volumetric Tissue Reduction for Treatment of Obstructive Sleep Apnea Syndrome

In recent years a considerable effort has been made to establish the use of different surgical techniques for the treatment of obstructive sleep apnea syndrome (OSAS). Nevertheless, treatment of hypopharyngeal obstruction due to tongue base hypertrophy remains in many ways an unsolved problem. The aim of this study was to evaluate the safety and efficacy of tongue base reduction with temperature-controlled radiofrequency volumetric tissue reduction in the treatment of OSAS. Twenty patients with OSAS and tongue base hypertrophy were treated with radiofrequency tissue ablation. An intensified treatment protocol was used, delivering 2,800 J per treatment session under local anesthesia. Two nights of polysomnography testing were performed before and after treatment. Daytime sleepiness, snoring and postoperative morbidity were assessed using questionnaires. Mean respiratory disturbance index (RDI) was reduced from 32.1 to 24.9/h after a mean of 3.4 treatment sessions. Six patients (33%) were cured after the procedure (reduction in RDI of &#83 50% and a postoperative RDI of <15/h) and ten (55%) showed an improvement of >20% in their RDI. Daytime sleepiness and snoring improved significantly. Peri- and postoperative morbidity was low; one severe complication occurred (tongue base abscess). We were able to achieve similar cure and responder rates to those reported in a recently published pilot study but with a reduced number of treatment sessions. We believe that this technique may improve patient acceptance and have beneficial cost implications.     

Limited Surgery for Cancer of the Larynx and Hypopharynx: Options and Consequences

We reviewed surgical options for laryngeal preservation (limited surgery) in laryngeal and hypopharyngeal cancers and the consequences of the options. Of 44 patients with laryngeal cancer, 11 (25%) received limited surgery and 33 (75%) received total laryngectomy. The survival rates were 91% for the limited surgery group and 73% for the total (radical) surgery group. Of 31 patients with hypopharyngeal cancer, 7 (23%) received limited surgery and 24 (77%) received total laryngopharyngectomy. The survival rates were 53% for the limited surgery group and 40% for the total (radical) surgery group. The survival rates associated with limited surgery were thus better than those for total (radical) surgery for cancers of both the larynx and hypopharynx. This was attributed to the limited surgery group comprising well-selected patients with confined lesions. Organ preservation surgery should be technically simple, reliable in terms of its functional impact and, above all, should not jeopardize the patient's survival. Supracricoid subtotal laryngectomy with cricohyoidoepiglottopexy or cricohyoido-pexy has great potential for laryngeal preservation and will become the major limited surgery modality for treating cancer of the larynx. Limited surgery, however, needs to be performed with great care and is indicated only for very well-selected patients with cancer of the hypopharynx.     

Lack of significant estrogen and progesterone receptor expression in nasal telangiectasias in hereditary hemorrhagic telangiectasia: an immunohistochemical analysis

Obstructive sleep apnea syndrome (OSAS) is characterized by snoring and apnea during sleep leading to decreased oxygen saturation and disturbed sleep, excessive daytime sleepiness and neuropsychological disturbances. This study investigates cognitive neuropsychological abilities in a group of 53 OSAS patients before and after treatment with uvulopalatopharyngoplasty. General intellectual ability, verbal learning and memory as well as executive functioning were measured at baseline and 6 months postoperatively. After surgery there were significant improvements in verbal learning and memory (mean change - 39, SD 57.3, p <0.001), recall (mean change - 24.3, SD 39.3, p <0.001) and executive functioning (as assessed by percentage of errors on the Wisconsin Card Sorting Test; mean change-9.1, SD 15.7, p <0.001). These improvements were in accordance with improvements in the degree of sleep apnea, the oxygen desaturation index (mean change -9.7, SD 15.9, p <0.001) and arterial minimum oxygen saturation (mean change 4.5%, SD 10.2%, p <0.01). Surgical treatment seems to improve verbal learning, memory and recall and executive functions in parallel with better oxygenation in OSAS.     

Measurement of chemosensory function

Although hundreds of thousands of patients seek medical help annually for disorders of taste and smell, relatively few medical practitioners quantitatively test their patients' chemosensory function, taking their complaints at face value. This is clearly not the approach paid to patients complaining of visual, hearing, or balance problems. Accurate chemosensory testing is essential to establish the nature, degree, and veracity of a patient's complaint, as well as to aid in counseling and in monitoring the effectiveness of treatment strategies and decisions. In many cases, patients perseverate on chemosensory loss that objective assessment demonstrates has resolved. In other cases, patients are malingering. Olfactory testing is critical for not only establishing the validity and degree of the chemosensory dysfunction, but for helping patients place their dysfunction into perspective relative to the function of their peer group. It is well established, for example, that olfactory dysfunction is the rule, rather than the exception, in members of the older population. Moreover, it is now apparent that such dysfunction can be an early sign of neurodegenerative diseases such as Alzheimer's and Parkinson's. Importantly, older anosmics are three times more likely to die over the course of an ensuring five-year period than their normosmic peers, a situation that may be averted in some cases by appropriate nutritional and safety counseling. This review provides the clinician, as well as the academic and industrial researcher, with an overview of the available means for accurately assessing smell and taste function, including up-to-date information and normative data for advances in this field.     

Congenital nasal masses: diagnosis and management

One hundred and nine congenital nasal masses which presented to two children's hospitals over a 20 year period are reviewed. The diagnosis of the nasal mass is discussed with respect to age, mode of presentation, and site of the lesion, and a management protocol is advocated.     

Compound Action Potential and Cochlear Microphonic Extracted from Electrocochleographic Responses to Condensation or Rarefaction Clicks

In electrocochleography (ECochG) compound action potential (CAP) and summation potential (SP) are usually separated from the cochlear microphonic (CM) by the CM cancellation technique consisting in averaging the responses evoked by rarefaction and condensation clicks. With the aim of analysing the ECochG responses evoked by monophasic clicks, we developed a numerical method based on the theory of optimal filtering, which makes no assumptions about the unknown potentials. The application of the filtering technique to the ECochG recordings obtained from 6 normally hearing children and 10 children with cochlear hearing loss allowed us to perform CAP extraction in cases where CM was not cancelled by the conventional method. Differences in SP amplitude and polarity were found between rarefaction and condensation click-evoked responses in cochlear hearing losses.     

Bacterial Interference Between Pathogens in Otitis Media and Alpha-Haemolytic Streptococci Analysed in an In Vitro Model

Bacterial interference studied by means of agar methods has shown a decreased number of inhibitory alpha-haemolytic Streptococci among otitis-prone children. Additional information was gained regarding the interplay between alphahaemolytic Streptococci (AHS) and otitis media (OM) pathogens by comparing the bacterial interference in broth with the interference activity studied using agar overlay methods. We found that non-typeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis are readily inhibited by AHS in broth. Streptococcus pneumoniae was more bacteriostatically inhibited. If two OM pathogens were inoculated simultaneously, an isolate of AHS with poor inhibitory activity was not able to inhibit the growth, in contrast to an isolate of AHS with good inhibitory activity. The initial amount of AHS inoculated with M. catarrhalis seemed to play a decisive role with respect to the inhibitory activity. M. catarrhalis developed reduced susceptibility against AHS both in vivo and in vitro . In vivo studies showed that children with secretory otitis media had fewer isolates of AHS in their nasopharynx with the ability to inhibit all the test pathogens than healthy children ( p < 0.001). Although the factor(s) responsible for the inhibitory activity have thus far not been defined, we could exclude low pH and nutrition depletion as the inhibitory mechanism of AHS with good inhibitory activity.     

Cochlear Function in Ears with Immunomediated Inner Ear Disorder

The aim of the present study was to evaluate the performance of ears with inner ear disorder, responsive to immunosuppressive drugs, in advanced tests designed to assess primary cochlear functions (temporal integration, frequency selectivity, cochlear mechanics). The results of this study suggest that immunomediated inner ear disease results, in the acute clinical stage, in the development of endolymphatic hydrops, which increases the stiffness of the vibrating structures within the inner ear and causes dysfunctions of the outer hair cells. Our patients presented with upsloping or flat sensorineural hearing loss, absence of evoked otoacoustic emissions and distortion-product otoacoustic evoked emissions and abnormal temporal integration, frequency selectivity and cochlear mechanics. Following immunosuppressive treatment, hydrops recovered, hearing subsequently returned to normal, the audiometric curve became flat at low-to-middle frequencies and primary cochlear function tended to normalize. This study seems to support the usefulness of testing primary cochlear functions in order to monitor the clinical course of immunomediated inner ear disorders.     

Findings in surgery for chronic otitis media. A retrospective data-analysis of 2225 cases followed for 2 years

Data on middle ear disease and follow-up was recorded and analysed in 2225 ears operated on for chronic otitis media between 1958 and 1975. The closure rate of tympanic membrane perforations (70–80%) was not influenced by the presence of otorrhoea, but it was significantly lower in patients aged below 15 or over 40 yr and especially when tympanic membrane homograft had been used. For all types of tympanoplasty the mean improvement in air-conduction threshold was most marked at the lower frequencies, being some 10 dB in Type I, 15 dB in Type II and 8 dB in Type III and IV and it decreased by some 3 dB per octave. The combination of cholesteatoma and tympanosclerosis appeared to be rare. The post-operative incidence of otorrhoea was 10–15% after modified radical mastioidectomy and 20–25%, after radical mastoidectomy.     

Coping together with hearing loss: a qualitative meta-synthesis of the psychosocial experiences of people with hearing loss and their communication partners

Objective: To examine the psychosocial experiences of hearing loss from the perspectives of both the person with hearing loss and their communication partner. Design: A meta-synthesis of the qualitative literature. Study Sample: From 880 records, 12 qualitative papers met the inclusion criteria, (i) adults with hearing loss, communication partners, or both, and (ii) explored psychosocial issues. Results: Four themes related to the psychosocial experience of hearing loss were found, (i) the effect of the hearing loss, (ii) the response to hearing aids, (iii) stigma and identity, and (iv) coping strategies. Hearing loss affected both people with hearing loss and communication partners. Hearing aids resulted in positive effects, however, these were often outnumbered by negative effects. Non-use of hearing aids was often influenced by stigma. Coping strategies used were related to how the person with hearing loss perceived their self and how the communication partner perceived the relationship. Aligned coping strategies appeared to have a positive effect. Conclusions: Hearing loss affects both people with hearing loss and their communication partners. Aligned coping strategies can facilitate adjustment to hearing loss.