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Purpose New energy-based sutureless vessel ligation devices, such as the Thunderbeat (Olympus Medical Systems Corp., Tokyo, Japan), could reduce operative time and limit blood loss in head and neck surgery; however, efficacy and safety in major head and neck surgery have not been investigated in a prospective, randomized study. Methods This prospective, double-arm, randomized controlled trial consisted of two parts: total laryngectomy (TL) and neck dissection (ND). Thirty patients planned for TL were randomized in two groups. For the ND part, forty-two operative sides were likewise randomized. In both parts, Thunderbeat was used in addition to the standard instrumentation in the intervention groups, while only standard instrumentation was used in the control groups. Primary outcome values were blood loss, operative time and complication rate. Results For the TL part there was no difference in mean blood loss (p = 0.062), operative time (p = 0.512) and complications (p = 0.662) between both hemostatic techniques. For the neck dissection part, there was a reduction in blood loss (mean 210 mL versus 431 mL, p = 0.046) and in operative time (median 101 (IQR 85–130) minutes versus 150 (IQR 130–199) minutes, p = 0.014) when Thunderbeat was used. There was no difference in complication rate between both hemostatic systems (p = 0.261). Conclusion The Thunderbeat hemostatic device significantly reduces operative blood loss and operative time for neck dissections, without increase in complications. In TL, blood loss using Thunderbeat was comparable with the standard technique, but the operative time tended to be shorter. Trial registration UMCG Research Register, Reg. no. 201700041, date of registration: 18/1/2017

Head and neck cancer is worldwide the sixth most common cancer. Prognosis is linked to tumour (primary tumours, nodal stage and distant metastasis) and general patients' characteristics. Currently, the TNM-staging system is the most used staging system in the world. Beside this TNM-staging system, other prognostic factors are used to select the best treatment for each individual patient. This article is protected by copyright. All rights reserved.

OBJECTIVES: To explore the incidence and treatment pattern of head and neck cancer in different age groups.DESIGN: cohort study.SETTING: Netherlands Cancer Registry.PARTICIPANTS: All new primary head and neck cancer cases diagnosed between 2010 and 2014 were included and categorized in different age groups.MAIN OUTCOME MEASURES: Tumour site, stage, treatment modality, location of diagnosis and treatment.RESULTS: The study population was composed of 11,558 tumours. Oral cancer was the most common primary site (31%), followed by laryngeal (25%) and oropharyngeal cancer (22%). Ninety-six percent of the entire study population was diagnosed and/or treated in a certified head and neck oncology centre which was lower in the 80+ population (92%). Multimodality treatment was less frequently applied with increasing age (e.g. oral cavity: 17% in 80+ vs. 34% in 60-; pCONCLUSIONS: This study confirms that less multimodal and tumour directed treatment is applied with the increasing age of head and neck cancer patients. This article is protected by copyright. All rights reserved.

Objective The aim of this study was to evaluate the clinical feasibility of the ProTrach DualCare (Atos Medical, Horby, Sweden), a device combining a hands-free speaking valve and a Heat and Moisture Exchanger (HME) for tracheotomized patients. Study design A non-randomized, prospective single center feasibility study. Methods Sixteen adult tracheotomized patients were included. Participants were asked to test the DualCare for two weeks while continuing their normal activities. After these two weeks, participants could choose whether or not to take part in the long-term evaluation. The EuroQOL-5D, Borg scale and questionnaires on speaking, pulmonary function and patient preference were used. During the long-term evaluation, a minor redesign was implemented and all participants were asked to test the new device again for one week, with a potential long-term evaluation. Eleven decided to participate. Results The device was well-tolerated. Speaking noise was reduced (p = 0.020) and speech was considered to sound more natural compared to previously used devices according to the users (p = 0.020). Overall 11 participants preferred the DualCare to their standard device. No serious adverse events were reported. Conclusion Overall, 11 of 16 participants preferred the DualCare to their standard speaking valve or HME. Users of the DualCare were able to use hands free speech with the benefits of an HME and the device was considered clinically feasible and has the potential to improve quality of life of tracheotomized patients. Level of evidence 2b.

Objectives: The aim of this study was to determine and compare the incidence of long- and short-term complications of percutaneous dilatation tracheotomies (PDT) and surgical tracheotomies (ST). Design: A single-centre retrospective study. Participants: 305 patients undergoing a tracheotomy (PDT or ST) in the University Medical Center Groningen from 2003 to 2013 were included. Data were gathered from patient files. Main outcome measures: Short-term and long-term complications including tracheal stenosis. Results: The incidence of short- and long-term complications, including tracheal stenosis, was similar in both groups. Analysis of a small high-risk subgroup showed no difference in long-term complications. Conclusions: The rate of short- and long-term complications, including tracheal stenosis, is equal in PDT and ST. PDT is a safe alternative for ST in selected patients.

Objective Salvage surgery has a higher complication rate compared to primary surgical treatment. We evaluated clinical outcome of salvage neck dissections in relation to initial treatment modality, extent of surgery, and patient related factors. Design Single institution consecutive case series. Setting Tertiary Head and Neck Cancer Center. Participants Eighty-seven patients with head and neck squamous cell carcinoma, who underwent salvage neck dissection after initial radiotherapy (n=30), radiotherapy with carboplatin/5-fluorouracil (n=43), or radiotherapy with cetuximab (n=14). Main outcome measures Incidence of complications, disease-specific survival. Results: Complications occurred in 28% of the patients. Multivariate analysis identified extent of neck dissection as the only independent predictor of surgical complications (p = .010). Surgical complication rate was 16% after radiotherapy with systemic treatment, and 47% after radiotherapy alone (p = .171). The 5-year disease-specific survival was 55%, independent of complications, initial treatment, extent of surgery, and patient related factors. Conclusion The only predictor for surgical complications was extent of surgery. Survival was not influenced by complications. This article is protected by copyright. All rights reserved.

Oral and oropharyngeal squamous cell carcinoma (OOSCC) have a low survival rate, mainly due to metastasis to the regional lymph nodes. For optimal treatment of these metastases, a neck dissection is required; however, inaccurate detection methods results in under- and over-treatment. New DNA prognostic methylation biomarkers might improve lymph node metastases detection. To identify epigenetically regulated genes associated with lymph node metastases, genome-wide methylation analysis was performed on 6 OOSCC with (pN+) and 6 OOSCC without (pN0) lymph node metastases and combined with a gene expression signature predictive for pN+ status in OOSCC. Selected genes were validated using an independent OOSCC cohort by immunohistochemistry and pyrosequencing, and on data retrieved from The Cancer Genome Atlas. A two-step statistical selection of differentially methylated sequences revealed 14 genes with increased methylation status and mRNA downregulation in pN+ OOSCC. RAB25, a known tumor suppressor gene, was the highest-ranking gene in the discovery set. In the validation sets, both RAB25 mRNA (P = 0.015) and protein levels (P = 0.012) were lower in pN+ OOSCC. RAB25 mRNA levels were negatively correlated with RAB25 methylation levels (P < 0.001) but RAB25 protein expression was not. Our data revealed that promoter methylation is a mechanism resulting in downregulation of RAB25 expression in pN+ OOSCC and decreased expression is associated with lymph node metastasis. Detection of RAB25 methylation might contribute to lymph node metastasis diagnosis and serve as a potential new therapeutic target in OOSCC.

Objectives Evaluation of the influence of a smooth surface moulding technique of silicone rubber indwelling voice prostheses on in vitro biofilm formation and analysis of the clinical in situ lifetime. Design Biofilm formation on smooth and Groningen ultra-low resistance (URL) prostheses was studied in an artificial throat model. The clinical lifetime of smooth voice prostheses were compared to the previous lifetime of URL by counting the number of replacements in a consecutive 6 months period in the same patient. Participants: Eleven laryngectomized patients in follow up who required frequent replacement of their voice prostheses. Settings Tertiary University Medical Center. Results Use of a smoother mould and less viscous silicone rubber yielded a decrease in surface roughness from 46 nm to 8 nm, and was accompanied by a 40% reduction in the prevalence of bacteria and yeast in in vitro formed biofilms. Clinically, the lifetime was significantly (p < 0.005) increased by a factor of 2.1. Conclusions This combined in vitro and clinical study suggests that the choice of material and in particular its surface finishing, may be determining factors with respect to the clinical lifetime of silicone rubber implants and devices failing due to biofilm formation. This article is protected by copyright. All rights reserved.

Objectives: To evaluate the frequency of submucous cleft palate (SMCP) in a group of children with clefts. The reason for suspecting submucous cleft, age of diagnosis, effect of age on speech development, problems in speech, hearing and swallowing were compared with previous literature.Methods: Retrospective chart review: Out of 33 patients with SMCP, registered by the Groninger cleft team over approximately 20 years (1990 until July 2012), 28 non-syndromic patients with a proven diagnosis of SMCP were included: 17 males and 11 females. Speech and hearing were examined and the number of patients with SMCP and age at time of diagnosis were evaluated. The percentages of problems in resonance, articulation and hearing, present at time of diagnosis, were compared with the percentages of problems found after surgery.Results: Out of 800 patients with clefts, 28 patients (3,5%) were diagnosed with SMCP at a mean age of 3;9 years. All patients presented one or more symptomatic complaints at time of diagnosis: hypernasality (65%), problems in articulation (46%), conductive hearing loss (39%) and/or swallowing problems (32%). A bifid uvula was found in 92%. Following surgery, hypernasal speech and swallowing problems were no longer observed. The articulation problems remained after surgery. Age of diagnosis seems no predictor of articulation problems. An improvement in hearing was observed but normal hearing was not achieved. Pharyngoplasty appeared to be a successful and save treatment of hypernasality.Conclusions: SMCP is a rare cleft palate which is, despite the presence of a bifid uvula and symptoms of velopharyngeal insufficiency, often diagnosed late. In children with a bifid uvula and mild problems in speech, hearing and swallowing, it is important to be alert to SMCP because SMCP may account for these persistent mild complaints. Therefore, early detecting of SMCP can yield profits. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Objective: To determine the geometry of (peri) stomas of laryngectomised patients in relation to patch use. This data will enable improvement of tracheostoma interfaces, specifically addressing patients currently unable to use stoma patches. The low use of Heat-and-Moisture-Exchange (HME) filters and (hands-free) speech valves, although very important to the quality of life of laryngectomised patients, is mainly attributed to poor fit of the adhesive patches to the stoma site. Current patch shapes are not based upon an objective (peri) stoma geometry because this geometry is unknown. Design: Observational anthropometric study of the (peri) stoma of laryngectomised patients. Setting: Ten hospitals or institutes in eight countries. Participants: About 191 laryngectomised patients, at least 1 year post operative. Main outcome measures: (Peri) stomas were photographed and measured. Patients completed a questionnaire on patch-use. Concavity of commercially available patches was measured. Results: In countries with a financial reimbursement system 58% of the patients use patches, compares to only 9% in other countries. Patches stay in situ for an average of 33.3 h. Patch and non-patch users differ on five out of ten measured geometrical parameters. Most striking differences are that patch users have much shallower peristomas (13 versus 18 mm), and stomas far more parallel to the anterior neck plane. The deepest commercially available patch is only 7 mm deep. Conclusions: This study provides detailed (peri) stoma geometry data of a divers population, and for the first time in relation to patch-use. It reveals a serious mismatch between patients and patches. With these data new patches can be developed that could dramatically improve rehabilitation after laryngectomy.

Careful selection of patients eligible for extensive head and neck cancer surgery is extremely important. A reliable predictor for postoperative outcomes in the vulnerable elderly population is not yet available. The concept of frailty describes a clinical state of increased vulnerability and can be assessed using frailty tests, such as the Groningen Frailty Indicator. In the current study, the influence of Groningen Frailty Indicator-measured frailty on clinical outcome was investigated in elderly patients surgically treated for head and neck cancer.Retrospective, explorative cohort study.Tertiary referral centre.A total of 90 patients of 65 years and older receiving surgical treatment for head and neck cancer with different primary sites.The influence of frailty (Groningen Frailty Indicator) on postoperative complications (Clavien-Dindo classification), subjective postoperative experience of both patient and surgeon and survival were analysed.A total of 36 patients were considered as frail (40%). Postoperative complications could not be predicted by frailty status. However, the Groningen Frailty Indicator dimension 'health problems' was a significant predictor for postoperative complications (P = 0.020). Unlike age and comorbidity, frailty was associated with a poor subjective patients' experience of the postoperative recovery (P 0.01). Although not statistically significant, survival analysis showed a worse 5-year overall survival in the frail group (33%) versus the non-frail group (74%).Analysis of frailty could identify elderly patients who might suffer more than expected during the postoperative period after head and neck cancer surgery. In this study, frailty was not identified as a new predictor of complications after head and neck cancer surgery.

BACKGROUND: The use of soft elastic biomaterials in medical devices enables substantial function integration. The consequent increased simplification in design can improve reliability at a lower cost in comparison to traditional (hard) biomaterials. Functional bi-stable buckling is one of the many new mechanisms made possible by soft materials. The buckling behavior of shells, however, is typically described from a structural failure point of view: the collapse of arches or rupture of steam vessels, for example. There is little or no literature about the functional elastic buckling of small-sized silicone rubber shells, and it is unknown whether or not theory can predict their behavior. Is functional buckling possible within the scale, material and pressure normally associated with physiological applications? An automatic speech valve is used as an example application.METHOD OF APPROACH: Silicone rubber spherical shells (diameter 30mm) with hinged and double-hinged boundaries were subjected to air pressure loading. Twelve different geometrical configurations were tested for buckling and reverse buckling pressures. Data were compared with the theory.RESULTS: Buckling pressure increases linearly with shell thickness and shell height. Reverse buckling shows these same relations, with pressures always below normal buckling pressure. Secondary hinges change normal/reverse buckling pressure ratios and promote symmetrical buckling. All tested configurations buckled within or closely around physiological pressures.CONCLUSIONS: Functional bi-stable buckling of silicone rubber shells is possible with adjustable properties in the physiological pressure range. Results can be predicted using the proposed relations and equations.

DT-diaphorase (DTD) is an important enzyme for the bioreductive activation of the new alkylating indoloquinone EO9. In preclinical studies, EO9 has shown selective anti-tumour activity against solid tumours and under hypoxic conditions. The levels of three reductive enzymes have been determined in three types of human solid tumours, together with corresponding normal tissues and normal liver. DTD enzyme activities were measured in tumour extracts using 2,6-dichlorophenolindophenol (DCPIP) and NADH as substrates; cytochrome P450 reductase or cytochrome b5 reductase activities were assessed with cytochrome c and NADPH or NADH respectively. DTD activity was highest in non-small-cell lung (NSCLC) tumours (mean 123 nmol DCPIP min(-1) mg(-1)), followed by colon carcinoma (mean 75 nmol min(-1) mg(-1)) and squamous cell carcinoma of the head and neck (6-fold lower than NSCLC). DTD activity was very low in normal liver and normal lung (4-6 nmol min(-1) mg(-1)), while the levels in normal colon mucosa or normal mucosa of the head and neck region were in the same range as the corresponding tumours. The levels of the two other reductive enzymes, cytochrome P450 reductase (CP450R) and cytochrome b5 reductase (Cb5R), were 5 to 25-fold lower than those of DTD in all the tissues, except for normal liver, in which DTD was 2 to 4-fold lower. The degree of variation found for DTD (range 4-250 nmol min(-1) mg(-1)), was not observed for these enzymes (CP450R, 0.8-7.8 nmol cytochrome c min(-1) mg(-1); Cb5R, 3.5-27.6 nmol min(-1) mg(-1)). It is anticipated that NSCLC patients are more likely to respond to EO9 and other bioreductive agents, owing to the high levels of the activating enzyme in this tumour type. To prove that this assay has predictive value we need to study these enzyme levels in tumour samples obtained from patients on clinical studies with bioreductive agents.

In order to study the induction of malignancy in normal tissues due to ionizing radiation, we reviewed the files of 2500 patients with a tumour of the head and neck treated at the Netherlands Cancer Institute (Antoni van Leeuwenhoek Ziekenhuis), Amsterdam, from 1977 to 1993. We then checked whether or not these patients had been previously irradiated. Patients with a thyroid carcinoma or skin cancer were excluded from the study, since it is generally known that previous irradiation is a risk factor in these tumours. Eighteen patients were found to have a malignancy within a previously irradiated area (0.70 per cent). The mean interval between radiation and diagnosis of the head and neck tumour was 36.5 years. There were five soft tissue sarcomas, nine squamous cell carcinomas and four salivary gland tumours. Fourteen patients were operated upon whereas four received palliative treatment only. The median survival of the total group was 3.5 years. Particularly. in young patients because of the better cancer therapy and prolonged survival one must be aware of the increased risk of radiation-induced tumours.

Objective: Hypernasality is a common problem in cleft care. It should be treated before the age of six, because of the impact it can have on speech sound development in young children. An objective method of nasalance evaluation is nasometry. To decide whether a nasometer test result is normal or abnormal, normative data and cut off points are needed. Normative data for children are not available for every language and age. For Dutch children two sets of Dutch speech stimuli, the Van Zundert sentences or the Moolenaar-Bijl, sentences, are often used in the diagnostic process for hypernasality. Primary goal of this study is to determine normative data and cut off points for two sets of Dutch speech stimuli for Dutch children from four to six years of age. Secondary is to compare those two sets of oral sentences.Method: Children without clefts were recruited from schools. According to their teachers their speech was normal. They were tested with the nasometer with the two sets of speech stimuli. The set from Van Zundert has oral and oronasal sentences, the Moolenaar-Bijl set only has oral sentences.Results: 118 children were recruited. Out of these children, 55 produced recording samples which were suitable for analysis. There were no significant differences between age groups or gender. The two different sets of speech stimuli used were significantly different, but the confidence intervals overlapped.Conclusions: Normal nasalance scores of the tested sentences are between 3 and 19% for oral sentences and between 17 and 37% for oronasal sentences. The Moolenaar-Bijl speech sentences are preferred to evaluate hypernasality in young Dutch children, because of the shortness and intelligibility. Normative nasalance scores are applicable to the whole group of children from four to six years of age. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Objectives: We performed in vitro evaluation of a novel, disposable, automatic hands-free tracheostoma speech valve for laryngectomy patients based upon the principle of inhalation. The commercially available automatic speech valves close upon strong exhalation and open again when the pressure drops. This method makes long sentences or pauses difficult. The novel iValve is designed to allow almost natural speech, with mid-sentence pausing and whispering. Methods: The inhalation closing flows and exhalation opening pressures of 6 iValve prototype versions at different settings were compared with physiological values. The airflow resistance at inhalation was compared to physiological values and to commercial valve values. Results: The iValve prototypes showed flow and pressure ranges in concordance with the physiological values in the literature. The airflow resistance in the breathing mode was within the physiological airflow resistance range, yet above the values from the two commercial valves. The resistance in the speaking mode was above the physiological airflow resistance range. Conclusions: In vitro tests show that the iValve versions can be selected and adjusted to operate within the physiological range. The airflow resistance in the breathing mode is good. In speaking mode, inhalation should, and can, be decreased. The iValve should offer the patient a more intuitively useable alternative with more dynamic speech. Its low cost allows disposability and wider use.

But de la presentation Tracheotomized patients lack the function of the upper airway moisturizing, warming and filtering air. Furthermore they are unable to speak without occluding the cannula. Heat and Moisture Exchangers (HME) and hands-free speaking valves are developed to aid patients. The Protrach DualCare (Atos Medical, Horby, Sweden) is the first device combining a fully functional HME and hands-free speaking valve for tracheotomized patients. This study is performed to determine the clinical feasibility of the Dualcare. Materiel et methodes A prospective feasibility study with 16 tracheotomized patients was performed in the UMCG. During two weeks the DualCare was tested with a 15 and/or 22 mm HME. After redesign the DualCare was tested again by 11 patients during one week. Questionnaires consisted of the EQ5D, Borg scales and device/disease specific questionnaires covering among others pulmonary function and speech aspects. Resultats Patients tolerated the device well. Speaking noise is less and speech is more natural compared to their previous device. One patient was excluded from preference analysis due to recurrent disease and canula problems. After the first period 10 of 15 patients preferred the DualCare, after the second period all 11 patients. There were no Serious Adverse Events. Registered Device Deficiencies were mainly due to stickiness of the membrane. After the redesign these were solved. Conclusion The DualCare is safe in use. Overall 11 of 15 patients preferred the DualCare. This is 100 % of patients testing the redesign. Patients benefit from the HME while being able to employ hands-free speech. The ProTrach DualCare is clinically feasible.

A series of 7 human squamous carcinoma cell lines of the head and neck (HNSCC), grown in standard medium containing high folate concentrations and in "folate-conditioned" medium containing nanomolar concentrations of folates, were all found to be sensitive (IC50: less than or equal to 50 nM) in growth-inhibition studies to methotrexate (MTX) following drug exposure for 7 days. However, when MTX exposure was limited to 24 hr, only 2 out of 7 HNSCC cell lines were sensitive to MTX (IC50: less than 500 nM), 2 were moderately sensitive (IC50: 1-2 microM), and 3 exhibited inherent resistance to MTX (IC50: greater than 250 microM). In these last 3 cell lines, the mechanism of resistance was not correlated with altered membrane transport of MTX or changes in dihydrofolate reductase activity, but rather was associated with a 3-fold lower activity of intracellular folylpolyglutamate synthase (FPGS) activity compared to MTX-sensitive HNSCC cells. The 3 cell lines exhibiting inherent resistance to a short exposure to MTX, however, did not show inherent cross-resistance after exposure for 24 hr to one or more of 3 novel antifolate compounds. These compounds, which appear to be more efficiently transported and polyglutamylated than MTX, include: 10-ethyl-10-deazaaminopterin (10-EdAM), 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI-198,583), and 5,10-dideazatetrahydrofolic acid (DDATHF). These results indicate that antifolate membrane transport and intracellular FPGS activity are important factors in determining sensitivity or resistance of HNSCC cells to short-term antifolate compound exposures.

Purpose: To examine the prognostic value of three endogenous hypoxia markers (hypoxia inducible factor I a subunit [HIF1 alpha], carbonic anhydrase IX [CA-IX], and glucose transporter type 1 [GLUT-1]) on the clinical outcome in patients with early-stage glottic carcinoma primarily treated with radiotherapy (RT) and to determine the predictive hypoxic profile to choose the optimal treatment of early-stage laryngeal carcinoma.Methods and Materials: Immunohistochemistry for HIF1 alpha, CA-IX, and GLUT-1 was performed on formalin-fixed, paraffin-embedded, pretreatment tissue samples of 91 glottic squamous cell carcinoma specimens. The patient group consisted only of those with early-stage (T1-T2) glottic carcinoma, and all patients were treated with RT only. Relative tumor staining was scored on the tissue samples. Receiver operating curve analysis was performed to determine the optimal cutoff value for each tumor marker. Cox regression analyses for the variables HIF1 alpha, CA-IX, GLUT-1, gender, age, hemoglobin level, T category, N category, tobacco use, and alcohol use were performed with local control and overall survival as endpoints.Results: HIF1 alpha overexpression in early-stage glottic carcinoma correlated significantly with worse local control (hazard ratio [HR], 3.05; p = 0.021) and overall survival (HR, 2.92; p = 0.016). CA-IX overexpression correlated significantly with worse local control (HR, 2.93; p = 0.020). GLUT-1 overexpression did not show my correlation with the clinical outcome parameters. Tumors with a nonhypoxic profile (defined as low HIF1 alpha and low CA-IX expression) had significantly better local control (HR, 6.32; p = 0.013).Conclusion: The results of our study have shown that early-stage glottic laryngeal carcinomas with low HIF1 alpha and CA-IX expression are highly curable with RT. For this group, RT is a good treatment option. For tumors with HIF1 alpha or CA-IX overexpression, hypoxic modification before RT or primary surgical treatment should be considered. (C) 2008 Elsevier Inc.

Dopamine (DA) released from lateral olivocochlear (LOC) terminals may have a neuroprotective effect in the cochlea. To explore the role of N-methyl-D-aspartate (NMDA) receptors and nitric oxide (NO) in the modulation of a cochlear DA release, we measured the release of [(3)H]DA from isolated mouse cochlea in response to the application of NMDA. NMDA at 100 mu M significantly increased the electrical-field stimulation-evoked and resting release of DA from the cochlea. The NO donor sodium nitroprusside enhanced the basal outflow of DA but failed to influence the evoked release. The administration of the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) alone was ineffective, but it significantly inhibited the initial phase of the NMDA-induced elevation of DA outflow, which suggested the role of NO in the NMDA-induced DA release. The DA uptake inhibitor nomifensine increased the electrically evoked release of DA. Nomifensine failed to change the effect of NMDA on the resting or electrically-evoked DA release, which suggested that the uptake mechanism does not play a role in NMDA-evoked and NO-mediated DA release. In summary, we provide evidence that NO can modulate the release of DA from the cochlea following NMDA receptor activation, but does not affect the uptake of DA. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

Contains fulltext : 49044.pdf (Publisher’s version ) (Closed access) In most patients with advanced or recurrent laryngeal or hypopharyngeal cancer, total laryngectomy is indicated. This means the loss of three main functions: phonation; respiration; and the prevention of aspiration during deglutition. Laryngectomy patients have various options to restore phonation: an oesophageal voice; an electrolaryngeal voice; or a tracheo-oesophageal voice. In the last case a silicone rubber shunt valve is placed in the tracheo-oesophageal wall and phonation is generated when exhaled air is forced through the oesophagus and neopharynx. This method is widely applied in Western Europe. In this paper we review the literature on fixation problems with shunt valves, tracheostoma valves and heat and moisture exchange (HME) filters. Tracheo-oesophageal speech without a valve is not considered. Despite 22 years of experience with the implantation of tracheo-esophageal shunt valves and many improvements in the design, problems still remain, such as biofilm formation with subsequent leakage through the valve, the need for frequent and inconvenient replacements, fistula enlargement leading to leakage around the device and reduced fixation, and infections. The high cost of shunt valves is a drawback to their use worldwide. To enable hands-free speech, different types of tracheostoma valve have been developed. These valves are fixed to the skin or to the tracheostoma by means of an intra-tracheal device. An HME filter is used to protect the airway and maintain physiological balance. Such devices are only suitable for a selected group of patients as fixation to the skin or trachea can be a major problem. Speaking and coughing cause pressure increases, which often result in mucous leakage and disconnection of the valve and/or HME filter. Recommendations are made for future improvements in fixation techniques.

A number of growth factors have been implicated as stimuli of thyroid cell proliferation; overexpression of these growth factors and/or their receptors may play a role in the growth of thyroid tumors. To determine if immunohistochemical detection of growth factors and/or their receptors correlates with morphological alterations in proliferative lesions of thyroid, we examined the localization of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and their common receptor, EGF-receptor (EGF-R), insulin-like growth factor-1 (IGF-1), IGF-1-receptor (IGF-R) and IGF binding proteins (IGFBP)-1, -2, -3, and -4, nerve growth factor (NGF), and its receptor NGF-receptor (NGF-R), transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (bFGF), in normal thyroid tissue and various thyroid tumors. We applied the streptavidin-biotin technique to formalin-fixed, paraffin-embedded tissues. We studied 8-16 different cases of each of the following: normal human thyroid, multi-nodular hyperplasia, follicular adenoma, papillary carcinoma, follicular carcinoma, medullary carcinoma, and anaplastic carcinoma. EGF, TGF-alpha, and their receptor EGF-R were widely expressed in normal thyroid and in all the thyroid lesions examined. IGF-1 and IGFBP-1 were diffusely present in all different thyroid tissues as well. There was no difference in staining intensity or distribution that correlated with the pathological process. IGFBP-4 seemed to have a variable expression. IGFBP-2 and -3 were detected only in medullary carcinomas. NGF immunoreactivity was found in thyroid tissues and tumors of all types; interestingly, NGF-R staining was found in the vascular stroma and immunoreactivity correlated with the degree of vascularization, but no staining was seen in normal or lesional thyroid cells. TGF-beta expression was highly variable, whereas bFGF was not detected by this method in thyroid tissues. This study indicates that growth factors and growth factor receptors are expressed by thyroid follicular cells and C-cells. While they most likely play a role in cell regulation and proliferation in these tissues, their immunohistochemical profile does not correlate with the pathological condition.