Abstract Incidence trends of laryngeal cancer in Finland were analyzed, especially in relation to survival, in a patient series of 5766 patients diagnosed in 1956–1995 and identified from the Finnish Cancer Registry. The age-adjusted incidence rate decreased from 6.5 to 3.5 per 100 000 person-years in males and remained unchanged among females. Only minor improvement occurred in survival. In a hospital-based material from Northern Finland (353 patients with laryngeal squamocellular carcinoma, LSCC, diagnosed in 1976–1995), the incidence among males decreased only for supraglottic cancer, diminishing the supraglottic to glottic incidence ratio from 1.4:1 to 0.5:1. Evaluation of diagnostic delays and their impact on survival and risk of recurrence was undertaken in a sample of 66 LSCC patients. In only 38% of the patients was malignancy suspected at the initial visit to a physician; infection was the most common misdiagnosis (41%). Half of the first consultations resulted in referral, whereas 17% of the patients were neither referred nor controlled. The median patient delay was 2 months and median professional delay 3 months. The latter exceeded 12 months in 17% of the patients. The delays were not significantly related to any other clinical parameter, nor were they interrelated. Professional delay of 12 months or more resulted in increased relative hazard of death (HR = 4.74, p = 0.05), equalling the effect of advanced stage (stage IV). One-third of the patients developed a recurrence. In univariate analysis, professional delay of 12 months or more increased the risk of local (p = 0.019) and neck (p = 0.019) recurrence. In a multivariate model, professional delay of 12 months or more indicated an adjusted relative hazard ratio (HR) of 4.6 for local recurrence (p = 0.02) and 9.5 for neck recurrence (p = 0.015). Immunohistochemical factors p53, apoptosis, angiogenesis and proliferation were included in a multivariate model evaluating prognostic factors of LSCC in addition to clinical and sociodemographic factors. Advanced stage (stages III–IV) (relative hazard ratio of death (HR) 8.9, p = 0.01), supraglottic site (HR 5.6, p = 0.02) and high apoptotic index (≥ 0.3) (HR 11.1, p = 0.05) were the best indicators of impaired prognosis. Professional delay and enhanced apoptotic rate could be helpful in selecting LSCC patients for more aggressive primary treatment.

No description available.

Background: Laryngospasm is a common and often serious adverse respiratory event encountered during anesthetic care of children. We examined, in a case control design, the risk factors for laryngospasm in children. Material and Methods: The records of 130 children identified as having experienced laryngospasm under general anesthesia were examined. Cases were identified from those prospectively entered into the Mayo Clinic performance improvement database between January 1, 1996 and December 31, 2005. Potential demographic, patient, surgical and anesthetic related risk factors were determined in a 1 : 2 case-control study. Results: No individual demographic factors were found to be significantly associated with risk for laryngospasm. However, multivariate analysis demonstrated significant associations between laryngospasm and intercurrent upper respiratory infection (OR 2.03 P = 0.022) and the presence of an airway anomaly (OR = 3.35, P = 0.030). Among those experiencing laryngospasm during maintenance or emergence, the use of a laryngeal mask airway was strongly associated even when adjusted for the presence of upper respiratory infection and airway anomaly (P = 0.019). Ten patients experienced postoperatively one or more complications whereas only three complications were observed among controls (P = 0.008). No child required cardiopulmonary resuscitation and there were no deaths in either study cohort. Conclusions: In our pediatric population, the risk of laryngospasm was increased in children with upper respiratory tract infection or an airway anomaly. The use of laryngeal mask airway was found to be associated with laryngospasm even when adjusted for the presence of upper respiratory tract infection and airway anomaly.

The purpose of this study was to analyze and quantify the effects of a nebulized saline treatment on speech production in eight females with Primary Sjögren's Syndrome (SS). The duration, formant frequency onset and offset, and slope were measured to determine the quality of participants' production of diphthongal American English vowels. Acoustic data were examined before treatment began, immediately following treatment, and during a one-week follow-up to determine the effects of a laryngeal hydration program that used nebulized saline to increase hydration of structures in the vocal tract. The vowels produced during the initial baseline condition were acoustically relatively similar to the productions of typical speakers not diagnosed with SS. Although some differences in mean vowel duration and formant frequency values were found in the recorded vowel productions, results indicated that the participants' vowel productions remained relatively stable across the different phases of treatment. The absence of large treatment effects, in terms of vowel acoustics, may be due to the possibility that although the dryness associated with SS is an irratant for speakers, it may not affect their ability to produce diphthongal vowels in a significant manner.

The exploration of underlying pathophysiology of speech disorders is hampered by the limitations in quantitative assessment of speech production. Current assessments are driven by measures that couple underlying processes of speech production with mechanisms that compensate for speech deficits. We propose a multifactorial approach to decouple these effects and examine underlying processes of speech motor control. In study 1 we conducted a sensorimotor characterization of speech motor control via altered sensory feedback techniques. We applied these measures to investigate effects of dopaminergic medication on laryngeal and articulatory motor control mechanisms in persons with Parkinson’s disease (PwPD). The study outcomes provide preliminary indication that dopaminergic medication may have a differential effect on laryngeal sensorimotor function in PwPD, with a normalization (reduction of atypically large responses) of auditory reflexive responses and an exacerbation (further reduction of atypically small responses) of auditory adaptive responses. The study outcomes also provide insight into the differential effects of dopaminergic medication on laryngeal and articulatory speech subsystems in PwPD. We hope the outcomes will eventually serve as a basis for designing better therapeutics focused on ameliorating voice and speech dysfunctions in PwPD. In study 2 we investigated laryngeal motor control in a population of individuals with and without hyperfunctional voice disorders (HVDs) using three different laryngeal kinematic measures extracted via high-speed video endoscopy techniques. We applied these measures to investigate differential effects of laryngeal tension, movement variability, and movement asymmetry present in individuals with HVDs. Results indicate that individuals with HVDs exhibit statistically significantly higher kinematic stiffness, spatiotemporal indices, and asymmetry indices across rate and effort conditions compared to controls, indicating higher laryngeal tension, production variability, and movement asymmetry. Laryngeal kinematics suggest differing underlying motor control strategies in individuals with HVD relative to controls, which may inform better understanding of the etiology of HVDs. The study outcomes also provide insight into the ability of laryngeal kinematics to differentiate underlying motor control strategies in individuals with various voice disorders with neurological and physiological pathophysiology that could provide crucial insight to guide future clinical intervention. In study 3, a novel neurocomputational model was developed, combining an established neurological framework of speech motor control, with a physics based vocal fold model. This numerical model decouples the neurological and physiological aspects of laryngeal motor control to provide important directions in expanding the understanding of the underlying pathophysiology of laryngeal motor control in PD and HVDs. The model has demonstrated capability to simulate different modes of laryngeal motor control, ranging from short-term (i.e., reflexive) and long-term (i.e., adaptive) auditory feedback paradigms, to generating prosodic contours in speech. LaDIVA can be used to expand the understanding of the physiology of human phonation to enable, for the first time, the investigation of causal effects of neural motor control in the fine structure of the vocal signal. / 2025-02-20T00:00:00Z

No description available.

Darbo uždaviniai buvo: Nustatyti gerklų audinio MMP-2 ir MMP-9 raiškos pokyčius kai yra nepiktybiniai gerklų dariniai (balso klosčių polipai), ikivėžinė gerklų patologija (atsinaujinanti gerklų papilomatozė ir lėtinis hiperplazinis laringitas su keratoze) bei gerklų plokščių ląstelių karcinoma ir įvertinti šių pokyčių diagnozinę vertę. Įvertinti gerklų audinio MMP-2 ir MMP-9 raiškos pokyčių sąsajas su klinikiniais ir morfologiniais nepiktybinių gerklų darinių (balso klosčių polipai), ikivėžinės gerklų patologijos (atsinaujinanti gerklų papilomatozė ir lėtinis hiperplazinis laringitas su keratoze) bei gerklų plokščių ląstelių karcinomos požymiais. Palyginti matrikso metaloproteinazes koduojančių genų MMP-2 (-735 C/T), MMP-2 (-1306 C/T), MMP-9 (-1562 C/T) ir MMP-3 (-1171 5A/6A) polimorfizmo dažnį, kai yra organinės nepiktybinės gerklų ligos bei gerklų plokščių ląstelių karcinoma. Įvertinti matrikso metaloproteinazes koduojančių genų MMP-2 (-735 C/T), MMP-2 (-1306 C/T), MMP-9 (-1562 C/T) ir MMP-3 (-1171 5A/6A) polimorfizmo sąsajas su gerklų plokščių ląstelių karcinoma bei jos klinikiniais ir morfologiniais požymiais. / The goals of the study were as follows: 1. To determine the changes in the expression of the laryngeal tissues MMP-2 and MMP-9 in patients with benign laryngeal tumors (vocal fold polyps), precancerous laryngeal lesions (recurrent respiratory papillomatosis and laryngeal keratosis) and laryngeal squamous cell carcinoma, and assess the diagnostic value of the aforementioned changes. 2. To assess the correlations between the changes in the expression of the laryngeal tissues MMP-2 and MMP-9 and the clinical and morphologic indications of benign laryngeal tumors (vocal fold polyps), precancerous laryngeal lesions (recurrent respiratory papillomatosis and laryngeal keratosis) and laryngeal squamous cell carcinoma. 3. To compare the rate of MMP-2 (-735 C/T), MMP-2 (-1306 C/T), MMP-9 (-1562 C/T) and MMP-3 (-1171 5A/6A) gene polymorphism in cases of non-malignant laryngeal lesions and laryngeal squamous cell carcinoma. 4. To assess the association between MMP-2 (-735 C/T), MMP-2 (-1306 C/T), MMP-9 (-1562 C/T) and MMP-3 (-1171 5A/6A) gene polymorphism, the laryngeal squamous cell carcinoma as well as its clinical and morphologic indications.

Thesis (MSc)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: The work presented in this thesis deals with the association between cancers of the upper gastro-intestinal tract and the tumor suppressor gene, TP53, and can be divided into three parts: (i) the analysis of the mutational spectrum of TP53 with respect to laryngeal cancer, (ii) the analysis of the mutational spectrum of TP53 with respect to esophageal cancer and (iii) the analysis of TP53 transcriptional levels in esophageal cancer. Laryngeal cancer (LC) is the 6th most common cancer in the world and the 2nd most common respiratory cancer, with approximately 500 000 new cases per annum detected worldwide. Over the last few years, LC has become increasingly prevalent within the Coloured Community of the Western Cape. The mechanisms of tumorigenesis in LC remain unknown, although smoking and alcohol consumption are considered to be major risk factors. Mutations within the gene TP53 have been strongly implicated as playing a role in cancer development, as they are frequently found in several cancer types. We therefore screened exons 5 - 8 of TP53 for mutations in DNA from tumor biopsies (n=44) and blood samples (n=42) from Coloured LC patients, using polymerase chain reaction - single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. Blood samples from a healthy, matched control group (n=40) were included in the study as controls. Significant correlations were found between the occurrence of LC and age and smoking, whereas daily meat consumption was a possible protective factor. In tumor-derived samples, mutations were found in 3 of the exons under investigation, representing 25% of the samples. The mutations were unique to the tumor biopsies, indicating a somatic origin for mutations. The data confirms that the region between codons 175 and 273 of TP53 is a mutational hotspot for cancers in general. This study reports 6 novel mutations within this same region. Esophageal cancer (EC) has a very high incidence in South Africa, relative to the rest of the world, and is particularly common amongst the Black Transkei population. The goal of this study was to determine whether there are differences in the TP53 mutational pattern observed in the Coloured Western Cape community as compared to that observed in the Black Transkei community. This required the analysis of the molecular structure of TP53, specifically exons 5 - 8, in a group of Coloured EC patients (n=44) treated at Tygerberg Hospital, Cape Town, South Africa. DNA obtained from tumor biopsies and blood (from patients) as well as from apparently healthy surrounding tissue was screened via PCR-SSCP and direct sequencing analysis. Only 4 nucleotide changes were observed from a total of 124 sequences obtained, of which two were novel to esophageal squamous cell carcinoma. These 4 nucleotide alterations were found only within the tumor biopsy sample set, representing 9% of the tumors investigated. This study revealed that the mutational spectrum of TP53 within the Coloured population of the Western Cape greatly differs from that of the Black community of the Transkei. This suggests that a different set of etiological factors are involved in the tumorigenic process for each of these distinct geographical communities, which is the subject of an epidemiological study undertaken by the MRC. The final part of this thesis deals with the quantification and comparison of TP53 transcription levels in esophageal cancer tumor tissue to the TP53 levels in healthy esophageal tissue obtained from patients from a unique geographical and ethnic background. The cohort used in this study consisted of Coloured patients (n=2) treated at Tygerberg Hospital. The LightCycler system was implemented in order to try to accurately quantify TP53 mRNA levels. Unfortunately, the desired results were unattainable due to unforeseen difficulties encountered during the study. These difficulties included the insufficient preservation of samples for RNA based studies. Several recommendations were made concerning future similar studies, including an improved planning strategy as well as the employment of an RNA stabilizing agent. Additionally, a few important contributions were made through this study, including the design and optimization of TP53 primers specifically intended for future RNA studies. These primers would enable the identification of the presence of TP53 RNA species as well as the absence of DNA contamination in a single PCR amplification step. Other contributions include the development of a well-optimized RNA extraction method for the extraction of RNA from tough tissues (such as the human esophageal tissue used in this study). This method makes the extraction of large quantities of RNA from small amounts of tough tissue types possible. In conclusion, this study has made a significant contribution to the field of cancer research, by shedding light on the TP53 mutational spectrum with regards to laryngeal as well as esophageal cancer in a population unique to the Western Cape. The first part of this thesis has been published in Cancer Genetics and Cytogenetics (Barnard, D., K. Lehmann, E.G. Haal, P.O. van Heiden, and l.C. Victor. 2003. The spectrum of mutations in TP53 in laryngeal cancer patients from a high-incidence population shows similarities to many of the known mutational hotspots. Cancer Genetics and Cytogenetics 145:126-132), of which a copy can be found in Appendix I. This work has also been presented (by D. Barnard) at an international conference entitled "Cancer of the Esophagus and Gastric Cardia: From Gene to Cure", held in Amsterdam, the Netherlands during the period 13 - 15 December 2002. / AFRIKAANSE OPSOMMING: Die werk wat in hierdie tesis voorgelê word handel oor die assosiasie tussen kankers van die boonste gastrointestinale weg en die tumor suppressor geen, TP53, en kan in 3 dele gedeel word, (i) die analise van die mutasiespektrum van TP53 in laringiale kanker (LK), (ii) die analise van die mutasiespektrum van TP53 in slukderm kanker (SK) en (iii) die analise van die transkripsievlakke van TP53 in SK. Laringeal kanker (LK) is die 6de algemeenste kanker in die wêreld en die 2de algemeenste respiratoriese kanker, met "n benaderde 500 000 nuwe gevalle jaarliks wêreldwyd. Oor die afgelope paar jare het LK "n toenemende probleem geraak, veral in die Kleurling gemeenskap van die Wes Kaap. Die meganismes van die tumorvorming in LK is onbekend, alhoewel rook-en alkoholgebruik vername risiko faktore is. Die voorkoms van mutasies in TP53 is verskeie kere aangetoon in verskillende kanker tipes en daar word vermoed dat dit "n rol speel in tumorvorming. In hierdie studie is dus na mutasies in eksons 5 - 8 van TP53 gesoek in tumor biopsie weefsel (n=44) en bloed isolate (n=42) van Kleurling LK pasiënte d.m.v. polimerase ketting reaksie - enkelstring konformasie polimorfisme (PKR-ESKP) analisering en direkte volgorde bepaling. Bloed monsters van "n vergelykbare groep (n=40) is ook in die studie ingesluit as "n kontrole. Betekenisvolle positiewe korrelasies is gevind tussen die voorkoms van LK en ouderdom sowel as rook. Daarmee saam is daaglikse vleisinname as potensiële beskermende faktor gevind. In tumor biopsies is mutasies in 3 van die ondersoekte eksons gevind, wat 25% van die biopsie monsters verteenwoordig. Hierdie mutasies is uniek aan die tumor biopsie weefsels en dui op "n somatiese oorsprong van mutasies. Hierdie bevindinge bevestig dat die gedeelte tussen kodons 173 - 273 van TP53 "n hipermuteerbare gebied geassosieer met kankers is. Hierdie studie bevestig 6 nuwe mutasies. Daar is 'n hoë insidensie van slukderm kanker (SK) in Suid Afrika relatief tot die res van die wêreld. Hierdie soort kanker word veral gevind by die Swart populasie van die Transkei. Die doel van hierdie studie was om verskille tussen die TP53 mutasie patroon van die Kleurling gemeenskap van die Wes Kaap en die Swart gemeenskap van die Transkei te vergelyk. Hiervoor is die molekulêre struktuur van TP53, veral eksons 5 - 8, in 'n groep Kleurling SK pasiënte (n=42) wat behandel is by Tygerberg Hospitaal, Kaapstad, Suid Afrika, geanaliseer. Analisering is gedoen deur DNS van tumor, bloed en ook oënskynlike gesonde aangrensende weefsel van dieselfde pasiënte te onderwerp aan PKR-ESKP analise en direkte volgorde bepaling. Slegs 4 nukleotied veranderings is gevind in 124 volgorde bepalings, waarvan 2 nuwe veranderings is in SK. Hierdie 4 nukleotied veranderinge verteenwoordig 9% van al die tumors wat ondersoek is in die studie. Hierdie studie bewys dat die mutasiespektrum van TP53 in die Kleurling gemeenskap van die Wes Kaap grootliks verskil van die Swart gemeenskap van die Transkei. Dit impliseer dat verskillende etiologiese faktore moontlik 'n rol mag speel op die tumorvormingsproses in die 2 afsonderlike geografiese gemeenskappe. Hierdie is die onderwerp van 'n epidemiologiese studie wat deur die MNR onderneem word. Die laaste deel van hierdie tesis handel oor die kwantifisering en vergelyking van TP53 transkripsievlakke in SK tumor weefsel teenoor TP53 vlakke in gesonde slukderm weefsel van pasiënte in 'n unieke geografiese en etniese agtergrond. Die studie populasie in hierdie projek het bestaan uit Kleurling pasiënte (n=2) wat by Tygerberg hospitaal behandel is. Die "LightCycler" sisteem is gebruik vir die akkurate kwantifisering van TP53 boodskapper RNS vlakke. Ongelukkig is die verlangde resultate nie gekry nie as gevolg van onvoorsiene probleme wat ondervind is tydens die studie. Hierdie probleme sluit in die onvoldoende preserv RNS studies. Hierdie inleiers maak dit nou moontlik om die teenwoordigheid van TP53 RNS spesies sowel as die afwesigheid van DNS kontaminasie in een PKR amplifikasie stap te kan identifiseer. 'n Ander belangrike bydrae is die ontwikkeling van 'n goed geoptimaliseerde RNS ekstraksie metode vir moeilike starre weelfsel tipes (soos menslike slukderm weefsel in hierdie studie) en maak die ekstraksie van groot hoeveelhede RNS uit klein hoeveelhede van moeilik hanteerbare weefsel tipes moontlik. Om saam te vat, hierdie studie het betekenisvolle bydraes gemaak tot die veld van kankernavorsing deur die ontrafeling van die TP53 mutasiespektrum in beide laringeale sowel as slukderm kanker, in 'n populasie uniek aan die Wes Kaap. Die eerste deel van hierdie tesis is gepubliseer in Cancer Geneties and Cytogenetics (Barnard, D., K. Lehmann, E. G. Hoal, P. D. van Heiden, and T. C. Victor. 2003. The spectrum of mutations in TP53 in laryngeal cancer patients from a high-incidence population shows similarites to many of the known mutational hotspots. Cancer Genetics and Cytogenetics 145: 126-132) en 'n afskrif van die artikel is ingesluit in Appendix I. Hierdie werk is ook voorgedra (deur D. Barnard) by 'n internasionale kongres getiteld "Cancer of the Esophagus and Gastric Cardia: From Gene to Cure", wat in Amsterdam, Nederland gehou is gedurende 13 - 15 Desember 2002

A common problem following general anesthesia is postoperative sore throat (POST) and postoperative hoarseness (PH). Symptoms directly correlated with less satisfaction according to the patients. The overall aim of this thesis was to describe patients' postoperative sore throat and hoarseness after general anesthesia with endotracheal intubation or laryngeal mask airway. As well as to investigate the risk factors that are associated with the symptoms, and to test methods that may prevent sore throat and hoarseness after a general anaesthetics. A total of 889 patients are included in the four studies. Incidence of POST varied from 21% up to 52 % depending on endotracheal tube (ETT) size in women (I-IV) and in men was the incidence 32-38% (III-IV). There were no gender difference in POST in study III and IV. The overall incidence of PH varied from 42- 59% (I-IV) in all patients, with no gender differences (III-IV). Following a laryngeal mask airway (LMA) 19% of the patients had POST and 33% of the patients reported PH. Patients with POST do seem to be able to localize their pain in the throat (IV). Different risk factors are shown to contribute to both POST and PH in men and women (II-III). To intubate with a smaller ETT size, 6.0 vs. 7.0 decreased POST in women in the early postoperative period as well as their discomfort from their POST (I). Only 6% of men who needed a laryngeal mask airway had POST compared to 26% of women. The symptoms are more discomforting after an ETT vs. an LMA up to 24 hours (IV). More patients have sore throat and hoarseness in the early postoperative period, but the symptoms can remain up to almost 5 days postoperatively (I, IV). In summary, sore throat and hoarseness following general anesthesia, affects many patients postoperatively. To intubate women with endotracheal size 6.0 decreases both sore throat and hoarseness postoperatively. Women are more likely than men to have a sore throat when a laryngeal mask airway is used.

The study's purpose was to describe selected laryngeal activity of brass-wind players during the performance of selected musical exercises. Research problems included the observation and description of three internal areas of activity of ten trumpeters as they performed each exercise. Specific areas of observation were 1) movement of the epiglottis during the performance of each exercise, 2) movement of the vocal folds/arytenoid cartilage which includes changes in the size of the glottis during the performance of each prescribed exercise, and 3) movement of the thyroid cartilage during the performance of each prescribed exercise. Musical exercises performed by each of the subjects included a sound volume change, use of vibrato, single-tonguing, step-wise descending and ascending slurs, descending and ascending lip slurs, register change, and a descending chromatic scale. In addition, each subject performed an excerpt from the second movement of the Haydn Trumpet Concerto. Data were collected through direct observation of subject performances and then described using three different means. Data analyses revealed a prominent amount of highly individual, non-patterned laryngeal activity which played an integral role in the performance of each subject. Individuals including Law (1960), Cramer (1955), Jacobs (Stewart, 1987), and Noble (1964) have advocated an unrestricted airway during brass performance. Contrary to this advice, findings in the present study indicate that a great deal of varying, involuntary restriction is present in the laryngeal area during performance. Further, such activity appears necessary to brass performance. Others, including Farkas (1962), Schuller (1962), and Wick (1971) , have endorsed conscious use of the glottis during brass performance. While findings in the present study imply that there is a presence of voluntary or reflexive glottal activity during brass performance, evidence does not support any theory which suggests conscious use of the laryngeal mechanism.