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Development of Caenorhabditis elegans pharynx, with emphasis on its nervous system.

The Caenorhabditis elegans pharynx is a neuromuscular tube of which the function is to pump and crush bacteria, and inject them into the intestine. The 80-cell pharynx develops via the morphogenesis and differentiation of the cells that compose its semi-spherical primordium, and requires the activity of several evolutionarily conserved genes, such as pha-4 (the homolog to the Drosophila forkhead and vertebrate FoxA), ceh-22 (the homolog to the Drosophila tinman and vertebrate Nkx2.5), and pha-2 (the homolog to the vertebrate Hex). There are 20 neurons in the pharynx, each with a reproducible unique trajectory. Developmental genetic analysis of axon guidance in the pharynx indicates that some axon trajectories are in part established without growth cones, whereas other parts necessitate growth cone function and guidance. Here we provide an overview of the developmental genetics of the Caenorhabditis elegans pharynx, with an emphasis on its nervous system.

Animals↗

Modeling of airflow in the pharynx with application to sleep apnea.

A three-dimensional numerical modeling of airflow in the human pharynx using an anatomically accurate model was conducted. The pharynx walls were assumed to be passive and rigid. The results showed that the pressure drop in the pharynx lies in the range 200-500 Pa. The onset of turbulence was found to increase the pressure drop by 40 percent. A wide range of pharynx geometries covering three sleep apnea treatment therapies (CPAP, mandibular repositioning devices, and surgery) were modeled and the resulting flow characteristics were investigated and compared. The results confirmed that the airflow in the pharynx lies in the laminar-to-turbulence transitional flow regime and thus, a subtle change in the morphology caused by these treatment therapies can significantly affect the airflow characteristics.

Humans↗

Low concentrations of mupirocin in the pharynx following intranasal application may contribute to mupirocin resistance in methicillin-resistant Staphylococcus aureus.

We describe a patient with methicillin-resistant Staphylococcus aureus (MRSA) colonizing the pharynx. The MIC of mupirocin was 0.25 microg/ml before treatment and increased after treatment to 8 microg/ml. Using pulsed-field gel electrophoresis, we confirmed that the genotypes of MRSA that colonized the pharynx before and after the use of mupirocin were identical. We measured the delivery of mupirocin to the pharynx in three normal volunteers and two patients. Low concentrations of mupirocin were present in the pharynx in all cases 10 min to 3 days after intranasal application. Our data suggested that low concentrations of the drug in the pharynx after intranasal application of mupirocin ointment might explain the selection of mupirocin resistance in MRSA.

Aged↗

Comparison of static mechanical properties of the passive pharynx between normal children and children with sleep-disordered breathing.

Collapsibility of the active pharynx, where active contraction of the upper airway muscles is evident, was previously reported to be higher in children with obstructive sleep apnea (OSA) than in those with primary snoring during sleep. Contribution of neuromuscular and anatomic factors to the increased collapsibility, however, was not estimated. We therefore evaluated collapsibility of the passive pharynx, in which upper airway muscle activities were eliminated. Our aim in the present study was to test the hypothesis that children with sleep-disordered breathing (SDB) have a structurally narrowed and a more collapsible pharynx compared with normal children. The static pressure/area relationship of the passive pharynx was endoscopically quantified in 14 children with SDB and in 13 normal children under general anesthesia with complete paralysis. The majority of children with SDB primarily closed their airways at levels of enlarged adenoids and tonsils with positive closing pressure (Pclose) (3.5+/-4.3 cm H2O), whereas half of the normal children closed their airways at the soft palate edges and the other half at the tongue bases with subatmospheric Pclose (-7.4+/-4.9 cm H2O). Cross-sectional area of the narrowest segment was significantly smaller in SDB children than in normal children. Interestingly, collapsibility of the retropalatal and retroglossal segments significantly increased in SDB children, compared with the normal subjects. We conclude that anatomic factors play a significant role in the pathogenesis of pediatric OSA and that predisposing structural abnormalities of the entire pharynx are likely to contribute to manifestation of OSA in addition to enlarged adenoids and tonsils.

Adenoids↗

Development of the pharynx in normal and malformed fetuses.

We studied the development of the pharynx in human embryos and fetuses. Embryos and fetuses from 4.5 mm crown-rump length (CRL) to 40 mm CRL were processed for microscopic examination. Normal fetuses from 32 mm CRL to 250 mm CRL and fetuses with malformations of the central nervous system (CNS) were cut sagittally through the midline and their pharyngeal regions were examined macroscopically. Our observations suggested that, at an early embryonic stage, the notochord and basicranium might play important roles in the formation of the human pharynx. At a later stage, the growth of the maxillomandibular portion also appears to be important in the formation of the pharynx. The finding of malformation of the pharynx in fetuses with maldevelopment of the CNS suggests that the brain may play an important role in the formation of the pharynx.

Anencephaly↗

[Video-endoscopic recording of the pharynx before and following nasal continuous positive airway pressure therapy in patients with obstructive sleep apnea].

The action mechanism of nCPAP in the treatment of obstructive sleep apnea is not adequately known. We took video endoscopic pictures (chip video camera manufactured by Videotronik) of the pharynx in five patients with SA in the awake state, during apnea during sleep, and under nCPAP treatment during sleep. The patients were all in the supine position. Simultaneously with video-endoscopy, polysomnography was performed. Qualitatively good pictures were obtained in 3 patients. In the awake state, a relatively narrow pharynx was observed which, however, was completely patent during the entire respiratory cycle. During apnea and hypopnoea, a concentric collapse of the oropharynx was observed, with involvement of the lateral and posterior walls of the pharynx and the tongue, together with the soft palate over a length of several centimetres to above the epiglottis. During the hyperventilation phase following apnea, the occlusion opened up again, the diameter of the pharynx then being appreciably greater than that seen in the awake state. Under increasing CPAP pressure, occlusion became progressively less complete; when the effective pressure had been attained, the diameter of the pharynx was roughly comparable to that seen in the hyperventilation phase, that is, appreciably wider than in the awake state. During inspiration, however, even under effective nCPAP pressure, a discrete decrease in pharyngeal diameter occurred. On the basis of the visual impression, we believe that the effect of CPAP is based on a passive "pneumatic splinting" of the pharyngeal musculature.

Adult↗

Racial/ethnic patterns of care for cancers of the oral cavity, pharynx, larynx, sinuses, and salivary glands.

BACKGROUND: Among Americans, both incidence and mortality from cancers of the larynx, oral cavity, and pharynx are higher for African Americans than whites and for men than women. In addition, the 5-year survival rates for these sites are significantly lower for African Americans than whites for each disease stage, particularly among African American males. We examine racial/ethnic variation in tumor characteristics, treatment practices, and their relationship to survival for cancers of the oral cavity, pharynx, larynx, nasal cavity and salivary glands. METHODS: Eligible individuals were age 20 or older and newly diagnosed with a primary invasive cancer of the oral cavity (excluding the lip), pharynx, larynx, sinuses or salivary glands in 1997 reported to one of nine National Cancer Institute's Surveillance Epidemiology and End Results Registries (SEER). Persons meeting the eligibility criteria for each registry were first stratified by race/ethnic group and stage then selected by random sampling within strata. RESULTS: We found racial/ethnic differences in diagnoses at specific anatomic sites, disease stage and treatment. African Americans less frequently received a cancer directed treatment than both whites and Hispanics and when treated were generally less likely to receive cancer-directed surgery. In multivariate analysis, the receipt of any cancer directed treatment was significantly associated with race and age group. African Americans and Hispanics had poorer, but not significantly so, overall, but not cancer-specific, survival. CONCLUSION: We found racial differences in the receipt of cancer treatment among patients diagnosed with selected head and neck cancers. We also found a less favorable distribution of stage for African Americans and Hispanics when compared with whites. The differences in stage we noted and the lower rates of oral cancer screening previously reported for these populations suggests that differential rates of early detection may contribute to racial differences in survival and mortality from cancers of the oral cavity and pharynx. Therefore, we conclude that more equitable receipt of cancer treatment along with preventive measures and earlier detection will help reduce racial/ethnic disparities in survival and mortality from cancers of the oral cavity, pharynx and larynx.

Adult↗

[Cinematographic functional diagnosis of swallowing after plastic reconstruction of large tumor defects of the mouth cavity and pharynx].

BACKGROUND: Reestablishing good swallowing function after resection and reconstruction of head and neck tumors is very important for our patients' well-being. Today many different surgical concepts for reconstruction after tumor surgery are in common use. It is necessary to establish a good diagnostic procedure for postoperative assessment of the swallowing function. High-speed cineradiography at a minimum of 50 frames per second is well established for evaluating swallowing problems in head and neck patients. METHODS: Thirty-six patients divided into three groups were examined using high speed cineradiography after surgical treatment of pharyngeal and oral cavity cancer. Group 1 (n = 12) included patients with a subtotal or total tongue resection and reconstruction with infrahyoid myofascial flap and jejunal flap; Group II (n = 8), patients with total resection of the oropharynx soft palate and velum and reconstruction with a free radial forearm flap; Group III (n = 15), patients with total laryngopharyngektomy and reconstruction with jejunal flap and siphon and with or without repair of the digastric muscle. RESULTS: Group I: All patients with tongue reconstruction were able to swallow normally from the oral cavity into the pharynx. All patients had normal bolus propulsion because of a good tongue volume and tongue motility. There was only one case of aspiration after total glossectomy with the larynx left in place. All patients could swallow with the head and neck in a normal position. Group II: All patients with reconstruction of the soft palate and velum were able to initiate proper bolus propulsion without nasal regurgitation or rhinolalia aperta. Only one patients suffered from chronic aspiration after hemiresection of the oropharynx and hypopharynx. Group III: All patients with pharynx reconstruction had no problems with bolus transfer through the reconstructed pharynx. Aspiration into the reconstructed pharynx was a major problem for those patients without repair of the digastric muscle (5/8 = 63%). Better results were observed in the patients who underwent repair of the digastric muscle. There was only one case (13%) of aspiration. CONCLUSIONS: By using high-speed cineradiography it is possible to make a detailed description of the swallowing function after extensive surgical treatment of pharyngeal and oral cavity cancer. We think that high-speed cineradiography is a very sensitive diagnostic procedure capable of detecting all functional aspects of swallowing. High-speed cineradiography should be one of the standard diagnostic studies performed surgery of the oral cavity and pharynx.

Adult↗

[Clinical study of intractable recurrent ulcer of the oral cavity and pharynx].

The etiology and clinical definition of intractable recurrent ulcer of the oral cavity and pharynx were long unknown. Then, intractable recurrent ulcer of the oral cavity and pharynx was defined as irregular ulcerative lesions occurring only in the oral cavity and pharynx, showing no specific findings in clinicohematological examinations, which recurred easily and were resistant to various treatments for at least one month. Twenty-five cases of intractable recurrent ulcer of the oral cavity and pharynx were treated in our hospital. Patient age, sex, chief complaint, past history, duration of illness, the locations and clinical findings of the ulcers, clinico-hematological examinations, the pathology of the ulcers, therapy and prognosis were analysed. Disease specificity was found in age, sex, past history, locations and clinical findings of the ulcers, and prognosis. Our results suggest that intractable recurrent ulcer of the oral cavity and pharynx is a characteristic disease. The possibility that HLA-linked genetic factors play a role in the development of intractable recurrent which ulcers, which in addition to other factors, induce local immunoreaction which then prolongs the course of this disease, was suggested.

Adult↗

Prevalence of Helicobacter pylori DNA in recurrent aphthous ulcerations in mucosa-associated lymphoid tissues of the pharynx.

OBJECTIVE: To determine the presence of Helicobacter pylori and, if detected, its potential prevalence in causing recurrent aphthous ulcers confined to mucosa-associated lymphoid tissues of the pharynx. DESIGN: Prospective, controlled clinical trial. SETTING: Otolaryngology Department of Tanta University Hospitals, Tanta, Egypt. PATIENTS: A total of 146 patients with recurrent multiple aphthous ulcers of the oral cavity and pharynx and 20 normal control subjects. INTERVENTIONS: Patients were assigned to group 1 (n = 58), in which the ulcers were strictly limited to the lymphoid tissues, or group 2 (n = 88), in which the ulcers were randomly distributed in the oral cavity and pharynx. Helicobacter pylori DNA was extracted from 3-mm-diameter tissue samples, and polymerase chain reaction amplifications were performed for the 16S ribosomal RNA gene. MAIN OUTCOME MEASURE: Positivity for H pylori. RESULTS: In group 1, 39 patients (67%) were positive for H pylori DNA, while in group 2, 9 patients (10%) were positive (chi(2) test, P<.001). It was not detected in any of the 20 control samples. CONCLUSION: Our results support a possible causative role for H pylori in recurrent aphthous ulcerations with a characteristic distribution and affinity to mucosa-associated lymphoid tissues of the pharynx.

Adolescent↗

Regulation of the pharynx of Caenorhabditis elegans by 5-HT, octopamine, and FMRFamide-like neuropeptides.

More than fifty FMRFamide-like neuropeptides have been identified in nematodes. We addressed the role of a subset of these in the control of nematode feeding by electrophysiological recording of the activity of C. elegans pharynx. AF1 (KNEFIRFamide), AF2 (KHEYLRFamide), AF8 (KSAYMRFamide), and GAKFIRFamide (encoded by the C. elegans genes flp-8, flp-14, flp-6, and flp-5, respectively) increased pharyngeal action potential frequency, in a manner similar to 5-HT. In contrast, SDPNFLRFamide, SADPNFLRFamide, SAEPFGTMRFamide, KPSVRFamide, APEASPFIRFamide, and AQTVRFamide (encoded by the C. elegans genes flp-1; flp-1; flp-3; flp-9; flp-13, and flp-16, respectively) inhibited the pharynx in a manner similar to octopamine. Only three of the neuropeptides had potent effects at low nanomolar concentrations, consistent with a physiological role in pharyngeal regulation. Therefore, we assessed whether these three peptides mediated their actions either directly on the pharynx or indirectly via the neural circuit controlling its activity by comparing actions between wild-type and mutants with deficits in synaptic signaling. Our data support the conclusion that AF1 and SAEPFGTMRFamide regulate the activity of the pharynx indirectly, whereas APEASPFIRFamide exerts its action directly. These results are in agreement with the expression pattern for the genes encoding the neuropeptides (Kim and Li, 1999) as both flp-8 and flp-3 are expressed in extrapharyngeal neurons, whereas flp-13 is expressed in I5, a neuron with synaptic output to the pharyngeal muscle. These results provide the first, direct, functional information on the action of neuropeptides in C. elegans. Furthermore, we provide evidence for a putative inhibitory peptidergic synapse, which is likely to have a role in the control of feeding.

Animals↗

Respiratory lumenal change of the pharynx and trachea in normal subjects and COPD patients: assessment by cine-MRI.

The purpose of this study was to use cine-MRI during continuous respiration to measure the respiratory lumenal diameter change in the pharynx and at an upper tracheal level. Fifteen non-smokers and 23 chronic obstructive pulmonary disease (COPD) patients with smoking history (median 50 pack-years) were included. Cine-MRI with seven frames/s was performed during continuous respiration. Minimal and maximal cross-sectional lumenal diameters within the pharynx and the upper tracheal lumen area were measured. The median diameter change in the pharynx (tracheal area) was 70% (1.4 cm(2)) in volunteers and 76% (1.7 cm(2)) in smokers (P=0.98, P=0.04). Tracheal lumenal collapse was a median of 43% in volunteers and 64% in smokers (P=0.011). No clear disease-related difference of the pharynx-lumen was found. The maximal cross-sectional area of the upper trachea lumen as well as the respiratory collapse was larger in COPD patients than in normal subjects. This information is important for the modelling of ventilation and prediction of drug deposition, which are influenced by the airway diameter.

Aged↗

Retinoic acid perturbs Otx gene expression in the ascidian pharynx.

In vertebrate embryos, ectopic application of all-trans retinoic acid (RA) alters the expression of Otx genes in the developing midbrain. In conjunction with RA-induced misexpression of other regulatory genes this leads to a loss of anterior CNS. In the ascidian Herdmania curvata, RA primarily inhibits the development of the juvenile pharynx. An ascidian Otx gene, Hec-Otx, is expressed largely in this tissue, associated stomodeal structures and the anterior endostyle of the juvenile. Treatment with 10-6 M RA reduces Hec-Otx mRNA levels in the juvenile to about 12% of normal and is correlated closely with the loss of pharyngeal structures. During embryogenesis the expression of Hec-Otx becomes restricted to cell lineages fated to give rise to the anterior-most nervous system and the stomodeal component of the primordial pharynx. In hatched larvae Hec-Otx transcripts are detected only in the sensory (brain) vesicle. RA reduces Hec-Otx expression in the tailbud stomodeal pharynx primordium/anterior nervous system cell line but not in the larval sensory vesicle, suggesting that RA regulation of Hec-Otx expression is restricted to pharyngeal tissues throughout embryonic and postlarval development. RA does not affect expression of Hec-Pax2/5/8, which is normally expressed within the developing nervous system immediately posterior to Hec-Otx at the tailbud stage, lending support to the proposition that RA does not impact CNS axial patterning. These data combined with those from other chordates suggest that RA regulation of Otx expression in the anterior nerve cord and pharynx is a primitive chordate feature which has been maintained predominantly in pharyngeal tissues in the ascidian.

Animals↗

Calcitonin gene-related peptide-immunoreactive nerves in the tongue, epiglottis and pharynx of the rat: occurrence, distribution and origin.

The occurrence, distribution and nature of calcitonin gene-related peptide (CGRP) in the tongue, epiglottis and pharynx of the rat was investigated by immunocytochemistry and radioimmunoassay. Numerous CGRP-containing nerves were found to innervate and terminate freely within the epithelium of the tongue, epiglottis and pharynx. Immunoreactive fibres were also found in the muscle layer and around blood vessels in the tongue, and in motor end plates in the muscle of the epiglottis and pharynx. Section of the trigeminal nerve induced a marked reduction in the number of immunoreactive nerves in the anterior portion of the tongue, whereas glossopharyngeal denervation results in a depletion of CGRP immunoreactivity in the posterior portion of the tongue. Immunoreactive nerves of the epiglottis and pharynx were depleted only after superior laryngeal nerve section. A subpopulation of labelled primary sensory neurones were observed in trigeminal and glossopharyngeal ganglia following injection of True blue retrograde tracer in the tongue. Most of the labelled cells were also immunoreactive for CGRP. Following systemic treatment with capsaicin, a loss of intra- and subepithelial CGRP-immunoreactive nerves was observed in all investigated tissues, while immunoreactive motor end plates remained unchanged.

Animals↗

Sarcopenia in the Caenorhabditis elegans pharynx correlates with muscle contraction rate over lifespan.

In muscles, sarcopenia, the loss of muscle mass, is the major cause of aging-related functional decline and frailty. Several factors are correlated with sarcopenia during aging, including contraction-related cellular injury, oxidative stress, endocrine changes and reduced regenerative potential. However the involvement of these factors has not been experimentally investigated. Here, we report that contraction-related injury may significantly promote the progression of sarcopenia in the pharynx of the nematode, Caenorhabditis elegans, a model of aging in non-regenerative tissues. Both functional and structural declines in the pharynx during aging were significantly delayed in mutants with reduced muscle contraction rates. We also examined the role of bacteria in pharynx muscle decline during aging, as previous studies reported that antimicrobial treatments could extend C. elegans lifespan. Although microbial infection may have enhanced functional decline in the pharynx during aging, it was not the sole cause of decreased pumping rates in old animals. This study identifies contraction-related injury as a factor affecting the initiation and progression of sarcopenia during aging. Further, characterization of the specific types of damage induced by muscle contraction will be helpful for understanding the underlying causes of sarcopenia.

Aging↗

[Results of the surgical treatment of severe caustic pharyngo-esophageal stenosis. The value of complete reconstruction of the pharynx by transposition of the ileum and colon].

STUDY AIM: The aim of this study was to report the results of pharyngoesophageal reconstruction in extensive corrosive strictures and to describe an original conception concerning extensive chemical burns of the pharynx with involvement of the epiglottis, oro-hypopharyngeal junction and cricopharyngeal pinchcock. PATIENTS AND METHODS: A personal series of 253 esophageal reconstructions using the colon and ileum is reported. In 124 patients, the cervical anastomosis of the graft was performed at the level of the pharynx, and these cases with extensive pharyngeal lesions were the basis of this study. The anastomosis was performed with the hypopharynx in 27 patients, with the oropharynx in nine and a total reconstruction of the pharynx or "pharyngoplasty" was carried out in 69 patients. The pharyngoplasty was classified according to the approach, in anterior, posterior, lateral, superior (transmandibular) and inferior. In high strictures with epiglottic injury, epiglottectomy was necessary in order to prevent recurrence. A visceral pharyngoplasty was performed in 61 patients, using the colon in 42 and the ileum in 19, a skin reconstruction in six patients and a myocutaneous flap in two. RESULTS: The global postoperative mortality rate was 4.7%. Stenosis of the cervical anastomosis occurred in 4.9% of the whole series. With a follow-up from 6 months to 10 years, 70% of the patients resumed a normal oral diet, 21% had mild symptoms and 7% had poor results (patients with tracheostomy and gastrostomy). CONCLUSION: Extensive chemical burns of the pharynx are very severe and their treatment very difficult. For the author, total visceral pharyngeal reconstruction is considered to be the procedure of choice, using ileopharyngoplasty with realization of an ileal pouch. Good results were obtained in 70% of the patients with extensive corrosive strictures.

Anastomosis, Surgical↗

Serotonin induces four pharmacologically separable contractile responses in the pharynx of the leech Hirudo medicinalis.

Stimulation of the serotoninergic innervation of the leech pharynx or application of serotonin to the isolated pharynx induced four distinct types of contractile activity: an increase in basal tonus, large phasic contractions of 10-15 s in duration, smaller phasic contractions occurring at approximately 1 Hz, and a relaxation after washout of serotonin. Application to the isolated pharynx of the selective serotonin agonists (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin, N-(3-trifluoromethylphenyl)piperazine, 1-(m-chlorophenyl)-piperazine, (+/-)-2,5-dimethoxy-4-iodoamphetamine, 2-methyl-5-hydroxytrypamine, alpha-methyl-5-hydroxytryptamine, and 5-methoxytryptamine induced distinct types of pharyngeal contractile activity. The results of this study suggest that the leech pharynx possesses more than one type of serotonin receptor.

5-Methoxytryptamine↗

Magnetic resonance imaging supplements ultrasonographic imaging of the posterior fossa, pharynx and neck in malformed fetuses.

OBJECTIVE: The objective of this study was to compare antepartum ultrasonography and magnetic resonance imaging (MRI) in the diagnosis and exclusion of malformations of the fetal neck, pharynx, skull base and posterior fossa in late pregnancy. MATERIALS AND METHODS: The study involved 26 women and 27 fetuses with ultrasonographically or clinically suspected abnormalities of the fetal neck, pharynx or central nervous system (CNS). Findings obtained by ultrasound were compared with those obtained by MRI (1.5 T) in the last trimester. RESULTS: In cases with CNS malformation (n = 19), MRI provided additional information on the anatomy of the foramen magnum and posterior fossa in nine cases (47%). When antepartum ultrasonography indicated malformation of the soft tissues of the neck or pharynx (n = 8), MRI provided additional information on diagnosis or exclusion of the abnormality in six cases (75%). The imaging capacity of the anatomy of the naso-, oro- and hypopharynx, trachea, esophagus and cervical skin outlines was better with MRI. CONCLUSIONS: MRI proved to be a valuable supplementary method to ultrasound in obtaining accurate information from the fetal neck, pharynx and posterior fossa, particularly when acoustic shadowing by bony structures or adjacent malformation impaired the quality of the ultrasonographic examination.

Abnormalities, Multiple↗