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[Larynx resistance produced by upper respiratory airways stimulation (author's transl)].

Larynx resistance changes during the respiratory cycle at rest and after mechanical stimulation of the epithelium on different zones of the upper airways (extrathoracic trachea, glottis, nasopharynx) were studied in the dog by isolated glottis in situ technique. In reposed breathing, the increase in larynx resistance always started when inspiratory airflow reached its maximum value. Resistance remained high during expiration and had its lowest value when expiratory airflow decreased towards zero. The electromyogram reading for the abdominal muscle evinced low or no activity during the smaller larynx resistance period. The extrathoracic trachea mechanical stimulation with cough response was determined by a significant decrease of larynx resistance. There was also a significant increase in expiratory airflow and abdominal pressure. Inspiratory and expiratory total lung resistance values were both significantly increased with regard to reposed breathing. Mechanical larynx stimulation determined reflexive closing of the glottis, expiratory apnea, minimal abdominal pressure. No potentials were formed in the expiratory abdominal electromyogram. The response was similar to a spontaneous swallowing. Larynx resistance reached its minimal value before the expiratory airflow reached zero. Mechanical nasopharyngeal stimulation significantly increased larynx resistance.

Airway Resistance↗

[Expression of glutathione-S-transferase isoenzymes in larynx cancer].

Carcinoma planoepitheliale of larynx is the most common cancer present in the upper part of the respiratory system. The molecular mechanism of this cancer generation is unknown and there is no a specific marker for its early diagnosis. The properties, physiological function, as well as the results of studies on genetic polymorphism indicate that glutathione-S-transferase (GST) may play an important role in etiology of this cancer. In the present work the studies on expession of GST isoenzymes pi, alfa, mu4, and mu5 in larynx cancer (carcinoma planoepitheliale laryngis) were performed. Specimens of larynx cancer and their corresponding normal adjacent tissues were obtained from patients by surgery. Expression was studied on the level of mRNA using RT-PCR method. The results indicated raised expression of GST pi (the major isoform in larynx) and lowered expression of GSTs mu4 and alfa in cancer as compared with the control tissue. No expression of GST mu5 was observed in tumor and normal larynx tissues. Obtained results indicate various mechanism in regulation of GSTs expression in cancerous and normal larynx tissues. They also indicate a special role of GST pi in larynx carcinogenesis.

Aged↗

Metabolic activation and carcinogen-DNA adduct detection in human larynx.

Putative carcinogen-DNA adducts in human larynx tissues (n = 25) from smoker and non/ex-smoker patients were examined by 32P-postlabeling and compared with the metabolic activation capacity of larynx microsomes and cytosols from the same tissues. Hydrophobic DNA adducts were evident only in smokers, and chromatographic profiles of the adducts were similar using either the butanol extraction or nuclease P1 enhancement method, which suggested that the adducts may be derived from polycyclic aromatic hydrocarbons but not aromatic amines. Immunoblots of larynx microsomes using anti-cytochrome P450 1A1/1A2, 2C, 3A4, 2E1, and 2A6 antibodies showed intensities ranging from 1-10% of that typically observed with human liver microsomes. Enzymatic assays of larynx microsomes showed appreciable activity for benzo(a)pyrene hydroxylation (P450 1A1 and 2C) but not for 4-aminobiphenyl N-oxidation (P450 1A2), which indicated that the observed immunoreactivity was for P450 1A1; this represents the highest level of this P450 yet detected in human extrahepatic tissues. Accordingly, total DNA adduct levels in the larynx correlated strongly with levels of P450 2C, 1A1, and 3A4 but not with P450 2E1 or 2A6. Larynx cytosols also showed appreciable aromatic amine N-acetyl-transferase activity for p-aminobenzoic acid (NAT-1) but not for sulfamethazine (NAT-2); however, NAT-1 activity was not correlated with total DNA adducts, which is again consistent with the lack of aromatic amine-DNA adducts detected by 32P-postlabeling. Thus, these results suggest that the DNA adducts detected in human larynx are largely derived from metabolic activation of polycyclic aromatic hydrocarbons in cigarette smoke by P450 2C, 3A4, and/or 1A1.

Acetyltransferases↗

Position of the larynx in odontoceti (toothed whales).

This study examines the positional relationships of the odontocete (toothed whale) larynx to further an understanding of their breathing, swallowing, and vocalizing abilities. Seventeen specimens representing nine cetacean genera (Delphinus, Stenella, Tursiops, Grampus, Delphinapterus, Globicephala, Kogia, Mesoplodon, and Phocoena) were studied post mortem. Nine specimens were sectioned in the midsagittal plane and the position of the larynx relative to vertebral levels, skull base, and palatal structures was recorded. In eight specimens that could not be bisected for reasons of large size or condition of preservation, the larynx was removed by a ventral approach for further dissection. The results show that the upper respiratory tract of the odontocetes has evolved away from a basic mammalian pattern. Laryngeal position among terrestrial mammals usually corresponds to the level of cervical vertebrae 1-3. The odontocete larynx, however, lies rostral to the level of the atlas and extends to the presphenoidal synchondrosis. Its extension above the level of the foramen magnum is due to three factors: 1) The larynx is elongated into a tubular extension that projects beyond the soft palate into the nasopharynx; 2) the neck region is shortened owing to the highly compressed cervical vertebrae; and 3) the skull base is oriented in the same direction as the cervical vertebrae because of the horizontal and fusiform alignment of the head and thorax. Whereas the larynx of most terrestrial mammals is separable from the nasopharynx, that of the odontocetes studied may be permanently intranarial, held in place by the palatopharyngeal sphincter. Laryngeal position may affect their vocal abilities, allowing odontocetes to simultaneously swallow and echolocate.

Animals↗

Effect of basicranial flexion on larynx and hyoid position in rats: an experimental study of skull and soft tissue interactions.

The mammalian upper respiratory tract is a functionally dynamic region involved in respiration, deglutition, and phonation. As the structures of this area (e.g., larynx, hyoid) are suspended from the basicranium, changes in basicranial shape may affect both their anatomy and function. Although skeletal/soft tissue relationships have been examined through descriptive, comparative anatomy, these relationships have remained largely unexplored via experimental study. In this study, mechanical relationships between basicranial shape and positions of the larynx and hyoid bone are investigated experimentally. Skull base flexion was induced by surgically ablating the spheno-occipital synchondrosis in 13-day-old rats. Lateral radiograms were taken at 40, 60, 80, 100, and 120 days, and angular measurements made of basicranial shape and positions of the larynx and hyoid bone. Statistical analysis shows significant differences between experimental and control groups for skull base, hyoid, and larynx angles, and negative (inverse) correlations for basicranial shape change vs. hyoid position, and basicranial shape change vs. larynx position. Results show induced basicranial flexion caused inferior displacement of the larynx and hyoid bone, thus indicating a direct, mechanical relationship between skeletal and soft tissues. These observations may aid in understanding the basic biological, pathological, and evolutionary interactions of hard and soft tissues of the upper respiratory region.

Analysis of Variance↗

Effect of the larynx on ventilation and respiratory pattern in anesthetized rabbits.

The effects of the larynx on ventilation and pattern of breathing have been investigated in anesthetized, spontaneously breathing rabbits. Breathing was either via a tracheostomy or via a supralaryngeal tube in control condition, after laryngeal denervation and after subsequent bilateral midcervical vagotomy. Laryngeal resistance was measured in all experimental conditions when breathing was through the larynx. In control conditions the presence of the larynx in the breathing circuit, as compared to breathing through the tracheostomy, slightly but significantly lowered inspiratory and expiratory airflows, tidal volume, and minute ventilation and increased tracheal pressure. Inspiratory and expiratory durations were not significantly changed. Expiratory laryngeal resistance was higher than inspiratory. Laryngeal deafferentation did not significantly modify values of the respiratory variables. Subsequent motor denervation of the larynx enhanced the decrease in ventilatory parameters due to adding the larynx to the circuit and lengthened the respiratory cycle. Inspiratory laryngeal resistance increased sevenfold and expiratory resistance threefold. Subsequent midcervical vagotomy induced a further increase in inspiratory and expiratory durations and augmented tidal volume independent of the route of breathing, and also reduced laryngeal resistance previously increased by motor denervation. These results reveal the ventilatory effects of the larynx and show the importance of its patency in the pattern of breathing.

Airway Resistance↗

Neuromuscular blockade at the larynx, the diaphragm and the corrugator supercilii muscle: a review.

PURPOSE: To review recent findings concerning neuromuscular blockade and monitoring at the larynx, the diaphragm, and the corrugator supercilii muscle. SOURCE: This narrative review is based on recent publications. PRINCIPAL FINDINGS: Neuromuscular blockade at the larynx and the diaphragm is less intense than at the adductor pollicis muscle; the onset and offset of neuromuscular blockade is more rapid. The corrugator supercilii muscle reflects better the time course of neuromuscular blockade of the larynx than the adductor pollicis muscle, is better suited to monitor the onset of neuromuscular blockade for intubation, and should give a better reflection of the time course and degree of neuromuscular blockade of the larynx or the diaphragm. Recovery of neuromuscular function at the end of any procedure is best reflected at the adductor pollicis muscle where neuromuscular transmission is last restored. Clinical monitoring of the larynx or the diaphragm is still limited by the absence of a simple method. Acceleromyography of the corrugator supercilii muscle is prone to artifacts that do not occur during monitoring of the adductor pollicis muscle. Phonomyography, a new method of monitoring that is currently being tested, is based on the phenomenon that muscle contraction creates low-frequency sound waves, which can be detected using special microphones to quantify neuromuscular blockade. This method seems promising because it can be easily used on all muscles of interest. CONCLUSION: Research during the last 15 years has greatly enhanced our knowledge about how muscles react differently to muscle relaxants and has enabled us to achieve better surgical conditions with safer use of muscle relaxants. Interesting technologies have been developed to reliably monitor neuromuscular blockade at the larynx and the diaphragm, but are currently restricted to research settings. Our increased understanding should help us in ongoing efforts to develop the "ideal" muscle relaxant and the "ideal" method of neuromuscular monitoring.

Diaphragm↗

The shear modulus of the human vocal fold, preliminary results from 20 larynxes.

Quantification of the elastic properties of the human vocal fold provides invaluable data for researchers deriving mathematical models of phonation, developing tissue engineering therapies, and as normative data for comparison between healthy and scarred tissue. This study measured the shear modulus of excised cadaver vocal folds from 20 subjects. Twenty freshly excised human larynxes were evaluated less than four days post-mortem. They were split along the saggital plane and mounted without tension. Shear modulus was obtained by two different methods. For method 1 cyclical shear stress was applied transversely to the mid-membranous portion of the vocal fold, and shear modulus derived by applying a simple shear model. For method 2 the apparatus was configured as an indentometer, and shear modulus obtained from the stress/strain data by applying an established analytical technique. Method 1 shear model for male larynxes yielded a range from 246 to 3,356 Pa, with a mean value of 1,008 and SD of 380. The range for female larynxes was 286-3,332 Pa, with a mean value of 1,237 and SD of 768. Method 2 indentometer model for male larynxes yielded a range from 552 to 2,741 Pa, with a mean value of 1,000 and SD of 460. The range for female larynxes was 509-1,989 Pa, with a mean value of 1,332 and SD of 428. We have successfully demonstrated two methodologies that are capable of directly measuring the shear modulus of the human vocal fold, without dissecting out the vocal fold cover tissue. The sample size of nine female and 11 male larynxes is too small to validate a general conclusion. The high degree of variability in this small cohort of subjects indicates that factors such as age, health status, and post-mortem delay may be significant; and that there is range of 'normality' for vocal fold tissue.

Biomechanical Phenomena↗

Sensory receptors of the larynx.

The larynx is a highly reflexogenic area, and stimulation with mechanical and chemical stimuli results in a number of protective reflexes. Investigators have used anatomical, behavioral, and neurophysiological techniques to examine the receptors responsible for initiating these reflex responses. Histologic examination has revealed the presence of free nerve endings, Merkel cells, Meissner corpuscles, and taste buds. Mechanoreceptors have been classified in several different ways and are located either in the superficial mucosa or in muscles and laryngeal joints. Recordings from afferent fibers innervating laryngeal mechanoreceptors have revealed that some of them are spontaneously active whereas others are silent until stimulated. Laryngeal mechanoreceptors respond to stimulation with either a rapidly adapting or a slowly adapting response pattern. Often the mechanoreceptors respond to respiratory movement of the larynx, giving bursts of action potentials during inspiration. A large number of taste buds that are anatomically similar to lingual taste buds populates the laryngeal surface of the epiglottis. Taste buds of the larynx respond to a number of chemical stimuli and to water. They do not respond to NaCl solutions close to physiological concentrations (0.154 M) but do respond at both a lower and higher concentration. When water is the solvent for the chemical stimuli, most chemicals initiate a response in laryngeal taste buds. However, when 0.154 M saline is used as a solvent, chemicals that taste bitter or sweet when applied to the tongue are ineffective stimuli. Taste buds of the larynx tend to be stimulated by the pH and tonicity of the stimulating solution and not by the gustatory properties. These results reveal a fundamental difference between the chemoreceptors of the oral cavity and larynx and result in the conclusion that chemoreceptors of the larynx do not play a role in gustation but are adapted to detect chemicals that are not saline-like in composition.

Aquaporins↗

Visualization of the human larynx: a three-dimensional computer modeling tool.

The larynx is a complex compact organ. A detailed understanding of the anatomical relationships of its various structures is critical to the various workers in the field. To facilitate this goal, a 3-D model of the human larynx has been developed using multiple thin section MRI and CT images taken through a cadaver larynx. A databank of individual laryngeal structures ('units') has been built up. A software package has then been utilized which allows for representation of any of the stored 'units'. In this manner, elements of the larynx can be viewed from any direction, with the larynx static or in motion. Similarities and differences from current CD-ROM packages of the larynx are discussed.

Computer Simulation↗

[Intubation damage to the larynx. Manifestations, comments on pathogenesis, treatment and prevention].

BACKGROUND: A variety of lesions can be seen in the larynx subsequent to an intubation anaesthesia or treatment with a respirator. The larynx may already be injured by introducing an endotracheal tube. The inserted tube must necessarily chafe the laryngeal mucosa. Many studies are concerned with individual manifestations [5-10,14,16,17,20]. The following article gives an overview of the intubation lesions of the larynx observed by us and offers comments on pathogenesis and prevention. PATIENTS: 161 patients with severe lesions subsequent to an intubation or treatment with a respirator were seen at the ENT Department of the University of Marburg Hospital from 1973 to 1995. TYPES OF LESIONS CAUSED BY INTUBATION: Basing on the pathomechanisms, we can classify the lesions as follows: inflammatory reactions, lesions of the larynx caused during intubation, lesions caused by chafing by the tube or by the sealing sleeve. CONCLUSIONS: Considering the large number of performed intubations, lesions of the larynx occur rarely. However, in view of the possible sequels, it would be advisable if an experienced laryngologist would perform a careful endoscopic examination of the larynx and trachea at least after every forced or prolonged intubation and especially after every treatment with a respirator.

Adolescent↗

Tobacco smoke-associated N7-alkylguanine in DNA of larynx tissue and leucocytes.

The presence of N7-alkylguanine adducts in DNA was analysed in a group of 46 patients with larynx tumours. All patients were subjected to laryngectomy and the tissues accessible for analysis by (32)P-post-labelling assay were larynx tumour, larynx non-tumour and peripheral blood leucocytes. N7-Alkylguanine adducts were detected in all the studied DNA samples. The average level of N7-alkylguanines was 26.2/10(7) nucleotides in tumour cells, 22.7/10(7) in non-tumour cells and 13.1/10(7) in blood leucocytes. There was significantly higher level of N7-alkylguanines in the larynx tissues in males than in females. The effect of tobacco smoking on DNA adduct levels was shown by an increase in the average levels of N7-alkylguanines in the subject groups classified according to their smoking habits. A moderate age-related increase in levels of N7-alkylguanine was demonstrated in larynx tumour tissue. The levels of N7-alkylguanine adducts in larynx cells were compared with that of aromatic DNA adducts. Pearson correlation coefficients (0.28 for tumour tissue and 0.30 for non-tumour tissue) indicate independent formation and removal of N7-alkylguanine and aromatic DNA adducts resulting from tobacco smoke exposure.

Adult↗

The descended larynx is not uniquely human.

Morphological modifications of vocal anatomy are widespread among vertebrates, and the investigation of the physiological mechanisms and adaptive functions of such variants is an important focus of research into the evolution of communication. The "descended larynx" of adult humans has traditionally been considered unique to our species, representing an adaptation for articulate speech, and debate concerning the position of the larynx in extinct hominids assumes that a lowered larynx is diagnostic of speech and language. Here, we use bioacoustic analyses of vocalizing animals, together with anatomical analyses of functional morphology, to document descended larynges in red and fallow deer. The resting position of the larynx in males of these species is similar to that in humans, and, during roaring, red-deer stags lower the larynx even further, to the sternum. These findings indicate that laryngeal descent is not uniquely human and has evolved at least twice in independent lineages. We suggest that laryngeal descent serves to elongate the vocal tract, allowing callers to exaggerate their perceived body size by decreasing vocal-tract resonant frequencies. Vocal-tract elongation is common in birds and is probably present in additional mammals. Size exaggeration provides a non-linguistic alternative hypothesis for the descent of the larynx in human evolution.

Adult↗

A contribution to simulating a three-dimensional larynx model using the finite element method.

A three-dimensional model is presented to simulate the larynx during vocalization. The finite element method is used to calculate the airflow velocity and pressure along the larynx as well as tissue displacement. It is assumed that the larynx tissue is transversely isotropic and divided into three tissues: cover, ligament, and body. A contact-impact algorithm is incorporated to deal with the physics of the collision between both true vocal folds. The results show that the simulated larynx can reproduce the vertical and horizontal phase difference in the tissue movements and that the false vocal folds affect the pressure distribution over the larynx surfaces. The effects of exciting the larynx with different pressure drops are also investigated.

Humans↗

Function of the larynx in the fetus and newborn.

The muscles of the larynx function as a part of the respiratory system before birth, and like other respiratory muscles, have experienced considerable use by the moment of birth. In late fetal life the larynx appears to influence the outward flow of pulmonary liquid and thus may play a role in lung development. Immediately after birth and in cases of neonatal lung disease, elevated pressures within the airways during expiration, probably a result of laryngeal adduction, are involved in the maintenance of FRC. This mechanism is also present, to a lesser degree, in normal ovine (and probably human) neonates during quiet sleep. Whether it exists in other species remains to be established. Expiratory resistance of the larynx is under vagal control, and pulmonary stretch receptors are the likely sensors. Species differences apparently exist in the means by which expiratory airflow is retarded. These may be due in part, however, to the widespread use of anesthetic agents that selectively depress the activity of laryngeal adductor muscles. There is clearly a need for wider use of techniques involving chronic instrumentation, particularly in the neonatal period. Because the upper airway is involved in the regulation of tidal airflow, it also seems vital that the airway remains intact wherever possible. In addition to controlling airflow, the larynx is an important sensory organ, protecting the lower airways from invasion by potentially harmful substances, e.g. during suckle feeding and regurgitation. In the neonate, laryngeal stimulation may result in prolonged respiratory arrest. Although there is some evidence that longer apnea can be elicited in the neonate than in the adult, the use of anesthesia, which may more strongly depress respiration in the young, complicates the issue. As yet, there are no firm grounds for explaining these findings, at either a peripheral or central level. Defensive mechanisms, including arousal, swallowing, and circulatory changes to cope with hypoxemia, are well established at birth. The healthy neonate would seem well equipped to survive entry of liquids into the larynx. However, it is not inconceivable that, under certain circumstances and in the absence of anesthesia, substances entering the larynx could trigger prolonged apnea or cardiac arrest.

Aging↗

Computed tomography of the larynx: correlation with anatomic and pathologic studies in cases of laryngeal carcinoma.

Seven patients with known carcinoma of the larynx underwent computed tomography (CT) of the larynx prior to surgery. Whole-mount sections of the extirpated larynx cut in the horizontal plane were compared with the corresponding level of the preoperative CT sections to demonstrate the validity of CT scanning in the evaluation of tumors of the larynx. The results indicate that CT scanning accurately demonstrates the anatomic location and gross size of laryngeal tumor, although early invasion of the laryngeal cartilages may be difficult to diagnose with CT. It is concluded that preoperative CT scanning of the larynx is the radiologic procedure of choice for evaluating carcinoma of the larynx.

Adult↗

Morphological and functional aspects of the senile larynx.

OBJECTIVE: To analyze the senile larynx, considering morphological aspects during respiration and functional aspects during phonation, comparing it to the young adult larynx. PATIENTS AND METHODS: A retrospective study was conducted of 100 laryngeal images of adults without vocal complaints, 50 laryngeal images of young adults aged 20-45 years and 50 laryngeal images of elderly individuals aged 65-85 years, of both genders. Images were produced by means of a rigid endoscope and stroboscopy. The morphological aspects analyzed were: laryngeal symmetry, vocal fold bowing, prominence of the vocal process and glottic proportion. The functional aspects analyzed were glottic closure, laryngeal vestibule behavior, phase (timing of closure) and amplitude symmetry of mucosal wave and tremor of laryngeal structures. RESULTS: Significant differences between the young adult larynx and the geriatric larynx were found for the following parameters: vocal fold bowing, prominence of the vocal process, glottic proportion, phase and amplitude symmetry of mucosal wave and tremor of laryngeal structures. CONCLUSION: The data suggests that the geriatric larynx differs from the young adult larynx in many characteristic aspects.

Adult↗

[Larynx preservation: nonsurgical approaches].

The question of larynx preservation is central in the management of patients with a carcinoma of the larynx or hypopharynx, especially to preserve the main functions of the larynx. In early stages (T1-earlyT2) Larynx preservation can generally be obtained with partial surgery or radiotherapy. Some other approaches such as exclusive chemotherapy require further investigations. In locally advanced and infiltrating larynx/hypopharynx carcinomas, (advancedT2-T3), several ways have been used to preserve the larynx including exclusive radiotherapy which can be improved by modified fractionation and acceleration. The efficacy of radiotherapy can be also markedly increased by adding concomitant cisplatin based chemotherapy, as reported recently in a large randomized trial. An alternative approach consisted in using induction chemotherapy (cisplatin-5FU) and followed by a local treatment adapted to the response to chemotherapy. The combined analysis of 3 such randomized trials (GETTEC, Veteran et EORTC) showed that this approach has to be used with caution, and could be safer in good responders to induction chemotherapy. Finally, larynx preservation is generally not proposed in patients with deeply infiltrating tumors and or tumor invading the cartilage or soft tissue in the neck (T4).

Antimetabolites, Antineoplastic↗