Accessory device fixation for voice rehabilitation in laryngectomised patients

Summary In most patients with advanced or recurrent laryngeal or hypopharyngeal cancer, total laryngectomy is indicated. This means the loss of the three main laryngeal functions: phonation; respiration; and the prevention of aspiration during deglutition. Laryngectomy patients have various options to restore phonation such as an esophageal voice, an electrolaryngeal voice or a tracheo-esophageal voice with a shunt valve. In the latter case a silicone rubber shunt valve is placed in the tracheo-esophageal wall and phonation is generated when exhaled air is forced through the shunt valve to the esophagus and neopharynx. The EUREKA project “Newvoice” aims at improving the plight of laryngectomees by realizing several subprojects. The outcome of the project should be a market ready, voiceproducing shunt prosthesis, and new biofilm-resistant silicone rubber and soft tissue interfaces like tissue connectors, which enable hands-free control of an improved “new voice” and prevention of trachea irritation. The latter is the main subject of this thesis. Difficulties in the fixation of prostheses for voice rehabilitation after laryngectomy In Chapter 2 we reviewed the literature on fixation problems with shunt valves, tracheostoma valves and heat and moisture exchange (HME) filters. Despite 22 years of experience (at the time of publication) with the implantation of tracheoesophageal shunt valves and many improvements in the materials used and 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 financial cost of shunt valves is a drawback to their use worldwide. To enable hands-free speech, different types of tracheostoma valve (TSV) have been developed. These valves are fixed to the skin or to the tracheostoma by means of an intratracheal device. An HME filter is used to protect the airway and maintain physiological balance. Such devices are only suitable for a select 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. As fixation of TSVs and HME filters is difficult, only a minority of patients uses the devices and benefit from hands-free speech. Animal models for tracheal research Preliminary research concerning tracheal reconstruction and fixation possibilities to the trachea and esophagus was necessary before prototypes were tested invivo. Tracheal research contains two main areas of interest: tracheal reconstruction and tracheal fixation. Tracheal reconstructions are aimed at rearranging or replacing parts of the tracheal tissue using implantation and transplantation techniques. The indications for tracheal reconstruction are numerous: obstructing tracheal tumors, trauma, post-intubation tissue reactions, etc. Although in past years much progress has been made, none of the new developed techniques have resulted in a large-scale clinical application for (near complete) trachea replacement. Tissue engineering is believed to be the technique that will provide a solution for reconstruction of tracheal defects. However, developing functional tracheal tissue from different cultured cell types is still a challenge. Tracheal fixation research is relatively new in the field and concentrates on solving fixation-related problems for laryngectomized patients. It was found that the animal models used for tracheal research vary widely and in most publications proper scientific arguments for animal selection are never mentioned. It showed that the choice of animal models is a multifactorial process in which non-scientific arguments tend to play a key role. In this chapter (3) the results of post-mortem investigations and information for biomaterials scientists about tracheal research and the animal models used were listed. Consequently, after design and production of tissue connector prototypes, animal experiments were designed. Goats were thought to be the best animal models for these purposes. The tracheostoma tissue connector (TS-TC) and tracheo-esophageal tissue connector (TE-TC) were reported separately. In vivo experiments with tracheostoma tissue connector prototypes In a goat model a tracheostoma was created and the prototypes were implanted. After 6 weeks of subcutaneous implantation, percutaneous screws were inserted. After twelve weeks, the experiment was terminated and the implants with the surrounding tissues were processed and examined histologically by means of light microscopy. The clinical appearance during weeks 7 to 12 varied from very poor to relatively good. Histologically, the implants showed a uniform inflammatory response. Titanium or silicone rubber rings surrounding the tracheostoma subcutaneously combined with polypropylene mesh failed to immobilize the skin and subcutaneous tissue sufficiently. As a consequence, the classical mechanism of percutaneous implant failure was demonstrated. Chapter 4 describes two prototypes and the subsequent histological analysis of the device-tissue explants. Experimental results of the tracheo-esophageal tissue connector for improved fixation of shunt valves in laryngectomized patients To solve the fixation related problems of the TE shunt valve, a TE-TC was devised to serve as an interface between the patient’s tissue (trachea and esophagus) and a shunt valve. The TE-TC was defined as a permucosal connection constructed from a titanium ring (filled with a silicon rubber plug) combined with polypropylene or titanium mesh. After implantation in adult goats for 12 weeks the implants were submitted to histological investigation. Firm implant fixation was achieved. In nearly all animals (18/19), no signs of infection of the implant was seen. In total 11/19 animals died before the end of the experiment due to complications not related to the implant. In a pilot experiment (n=2) it was found that implantation of a TETC including punction of the dorsal tracheal wall was technically feasible and postoperatively safe for the animals. The TE-TC was considered a device with potential in the solution for fixation-related problems in tracheo-esophageal shunt valve voice rehabilitation. Histological assessment of titanium and polypropylene fiber mesh with and without fibrin tissue glue Both TS-TC and the TE-TC were stabilized by tissue ingrowth in mesh. Polypropylene (PP) and titanium (Ti) mesh are well-known surgical implants that provoke a relative low foreign body reaction. Firm stabilization of the implant is important to prevent migration and subsequent failure of the operation. Fibrin tissue glues are commercially available adhesives and are widely accepted in the medical field for hemorrhage, surgical bleeding, support of wound healing, wound and tissue gluing, sealing and closure but also as anti-adhesive agent in certain applications. Objective of this study was to evaluate the additional histological effect of fibrin glue application combined with two different types of mesh. Six pieces mesh of each (Ti, Ti with glue, PP and PP with glue), were subcutaneously implanted for 3, 6 and 12 weeks. After excision, processing and staining, light microscopic analysis was performed on the coupes using subjective histological description and histomorphometry. Capsule quality, capsule thickness, interstitial quality and total score were calculated. The samples with glue and without glue were compared by means of analysis of variance (ANOVA) tests. No complications were observed. In general the glue remnants remained visible at 3 and 6 weeks of implantation, accompanied by an inflammatory reaction and macrophage activity. In general the Ti group scored higher than the PP group, which is in line with the literature. At 12 weeks all samples showed good tissue integration without evidence of glue. The samples with glue clearly demonstrated a prolonged inflammatory response and were surrounded by fibrous tissue capsules that were significantly thicker compared to the samples without glue (P<0.05). It was demonstrated that the addition of fibrin tissue glue to the mesh implants induced a prolonged inflammatory response and thicker fibrous capsules after implantation. The Saanen goat as animal model for post-laryngectomy research: practical implications In our implantation experiments several problems and complications of the selected Saane goat model were encountered. The postoperative course of this animal model was described in detail. Surgery consisted of a laryngo-tracheal separation and implantation of a tracheoesophageal and tracheostoma tissue connector with fibrin tissue glue. Postoperative care consisted of frequent stoma care. All animals survived the surgical procedure. However, postoperative care was extensive, labor-intensive and accompanied by several complications (11 (58%) animals died before the end of the experiment). Establishment of the percutaneous connection after 6 weeks was found to be a critical point from where the tracheostoma tissue connector starts to cause infection. In one animal, the TE-TC got infected due to a seroma that had formed subcutaneously, inferior of the tracheostoma. It was concluded that this goat model has certain disadvantages and can only be used for shortterm experiments with intensive care. Further refinements of the model were considered a necessity before new experiments are carried out. Conclusions Prosthetic tracheo-esophageal voice rehabilitation can be regarded as a successful approach to regain speech after surgical removal of the larynx. Fixation-related and other problems, however, require frequent visits of patients to the ENT outpatient clinic. HME filters used in TE speech can stay attached relative successfully because fixation is supported by a finger used to close the tracheostoma. The use of automatic TSVs is only possible in selected cases. Therefore the TS-TC prototype has been proposed as an improvement of this. However, it has not proven to be a successful strategy in our animal model. Alternative research efforts are required to realize an improved fixation of these devices. Fixation of TE shunt valves is in many cases not sufficient and leads to serious problems for patients. The TE-TC proved to be successful for implantation in the tracheo-esophageal wall. Isolated experiments with TE-TCs that include perforation of the esophageal wall are necessary before a patient-ready and market-ready product can be achieved. The animal model is not ideal because the tracheostomy implies an unpredictable course concerning airway and respiratory safety and, tissues of the implantation area are very mobile. For selected purposes this model is appropriate for short time experiments. The application of mesh for fixation of implants is favorable because firm integration in tissue has been demonstrated. Following the progress of the Newvoice project, concerning the development of TE and tracheostoma tissue connectors, the results show that additional research efforts are needed. Depending on the results of the next experiments, clinical application of the tissue connectors could be possible in the future

Mothers and fathers : Parenting practices in families with two children

The overall aim of the studies presented in this dissertation is to provide insight in the differences and similarities between mothers' and fathers' parenting practices. Further, this dissertation examines the effect of biological factors (i.e., parental sex hormones) and child factors (i.e., gender, age, and birth order) on parenting behavior of mothers and fathers. In Chapter 2 differences between mothers and fathers with respect to parental sensitivity and nonintrusiveness are studied, also examining child gender and birth order. Further, in Chapter 3 the effect of child age and birth order on mothers' and fathers' sensitivity and nonintrusiveness is examined longitudinally. Chapter 4 focuses on the association between sex hormones (i.e., testosterone) and parental sensitivity and nonintrusiveness of mothers and fathers towards their two young children. In Chapter 5 differences between mothers' and fathers' discipline strategies towards their firstborn and second-born children are examined, also taking into account child gender. Finally, in Chapter 6 the main findings and implications of the studies presented in this dissertation are discussed and suggestions for future research are made.Development Psychopathology in context: famil

Construction of an American mink Bacterial Artificial Chromosome (BAC) library and sequencing candidate genes important for the fur industry

<p>Abstract</p> <p>Background</p> <p>Bacterial artificial chromosome (BAC) libraries continue to be invaluable tools for the genomic analysis of complex organisms. Complemented by the newly and fast growing deep sequencing technologies, they provide an excellent source of information in genomics projects.</p> <p>Results</p> <p>Here, we report the construction and characterization of the CHORI-231 BAC library constructed from a Danish-farmed, male American mink (<it>Neovison vison</it>). The library contains approximately 165,888 clones with an average insert size of 170 kb, representing approximately 10-fold coverage. High-density filters, each consisting of 18,432 clones spotted in duplicate, have been produced for hybridization screening and are publicly available. Overgo probes derived from expressed sequence tags (ESTs), representing 21 candidate genes for traits important for the mink industry, were used to screen the BAC library. These included candidate genes for coat coloring, hair growth and length, coarseness, and some receptors potentially involved in viral diseases in mink. The extensive screening yielded positive results for 19 of these genes. Thirty-five clones corresponding to 19 genes were sequenced using 454 Roche, and large contigs (184 kb in average) were assembled. Knowing the complete sequences of these candidate genes will enable confirmation of the association with a phenotype and the finding of causative mutations for the targeted phenotypes.</p> <p>Additionally, 1577 BAC clones were end sequenced; 2505 BAC end sequences (80% of BACs) were obtained. An excess of 2 Mb has been analyzed, thus giving a snapshot of the mink genome.</p> <p>Conclusions</p> <p>The availability of the CHORI-321 American mink BAC library will aid in identification of genes and genomic regions of interest. We have demonstrated how the library can be used to identify specific genes of interest, develop genetic markers, and for BAC end sequencing and deep sequencing of selected clones. To our knowledge, this is the first report of 454 sequencing of selected BAC clones in mammals and re-assures the suitability of this technique for obtaining the sequence information of genes of interest in small genomics projects. The BAC end sequences described in this paper have been deposited in the GenBank data library [<ext-link ext-link-id="HN339419" ext-link-type="gen">HN339419</ext-link>-<ext-link ext-link-id="HN341884" ext-link-type="gen">HN341884</ext-link>, <ext-link ext-link-id="HN604664" ext-link-type="gen">HN604664</ext-link>-<ext-link ext-link-id="HN604702" ext-link-type="gen">HN604702</ext-link>]. The 454 produced contigs derived from selected clones are deposited with reference numbers [GenBank: <ext-link ext-link-id="JF288166" ext-link-type="gen">JF288166</ext-link>-<ext-link ext-link-id="JF288183" ext-link-type="gen">JF288183</ext-link> &<ext-link ext-link-id="JF310744" ext-link-type="gen">JF310744</ext-link>].</p

Food sharing with friends and acquaintances:A study in preschool boys and girls

IntroductionThe current study examined whether preschoolers in a (semi-)natural situation shared more food with friends or acquaintances, and whether this was different between boys and girls, older and younger children, and for preferred and non- preferred food. In order to do so, we replicated and extended the classical work of Birch and Billman in a Dutch sample.MethodsParticipants included 91 children aged between 3 to 6 years (52.7% boys, 93.4% Western European) from a middle- to upper-middle-class neighborhood in the Netherlands.ResultsThe results revealed that children shared more non-preferred than preferred food with others. Girls gave more non-preferred food to acquaintances than to friends, whereas boys gave more to friends than to acquaintances. No effect of relationship was found for preferred food. Older children shared more food than younger children. Compared to acquaintances, friends made more active attempts to get food. Moreover, children who were not shared with were just as likely to share food as children who were shared with.DiscussionOverall, only a small degree of agreement with the original study was found: Some significant findings could not be replicated, and some unconfirmed hypotheses of the original study were supported. The results underscore both the need for replications and studying the effect of social-contextual factors in natural settings

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