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Muscle & Nerve Jun 2009Etanercept is an antagonist of tumor necrosis factor alpha that was developed to treat rheumatoid arthritis. In this report we present a patient who developed myasthenia...
Etanercept is an antagonist of tumor necrosis factor alpha that was developed to treat rheumatoid arthritis. In this report we present a patient who developed myasthenia gravis while taking etanercept and had resolution of symptoms after stopping it. This is the first report of this potential side effect and is of additional interest, because etanercept has been proposed as a treatment for myasthenia gravis.
Topics: Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Autoantibodies; Deglutition Disorders; Etanercept; Humans; Immunoglobulin G; Male; Muscle, Skeletal; Myasthenia Gravis; Neuromuscular Junction; Pharynx; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha
PubMed: 19373885
DOI: 10.1002/mus.21280 -
Dysphagia Jun 2020The purpose of this study was to identify factors associated with the severity of dysphagia after lateral medullary infarction (LMI). Patients with dysphagia after... (Comparative Study)
Comparative Study
The purpose of this study was to identify factors associated with the severity of dysphagia after lateral medullary infarction (LMI). Patients with dysphagia after lateral medullary infarction who were admitted to a rehabilitation unit were included and divided into two groups (non-severe vs. severe). Severe dysphagia was defined as the condition showing decreased bilateral pharyngeal constriction without esophageal passage in a videofluoroscopic swallowing study that initially required enteral tube feeding. Their clinical data (age, sex, lesion side, duration of the illness, penetration-aspiration scale, functional oral intake scale, Modified Barthel index, National Institutes of Health Stroke Scale, and anatomical lesion on diffusion-weighted MRI) were compared to find differences between the two groups. Twelve patients had absence of esophageal passage among a total of 30 patients with dysphagia after LMI. Only anatomical lesion location and extent were significantly different between the two groups. The severe group showed posterolateral involvement in the upper and lower parts of the medulla. Otherwise, there were no significant differences between the two groups. The location and extent of involvement in the medulla were the most important factors associated with the severity of dysphagia after LMI.
Topics: Aged; Brain Stem Infarctions; Deglutition; Deglutition Disorders; Diffusion Magnetic Resonance Imaging; Female; Humans; Male; Medulla Oblongata; Middle Aged; Oropharynx; Severity of Illness Index
PubMed: 31375916
DOI: 10.1007/s00455-019-10043-8 -
Archives of Physical Medicine and... Aug 1979In protracted forms of dysphagia associated with neuromuscular dysfunction, myotomy of the upper esophageal sphincter has been suggested. The literature, however, is...
In protracted forms of dysphagia associated with neuromuscular dysfunction, myotomy of the upper esophageal sphincter has been suggested. The literature, however, is unclear about the indications and outcome of this procedure. In this article, 3 cases are presented of dysphagia associated with the failure of relaxation of the cricopharyngeus during swallowing. Two patients had brain stem infarctions and the 3rd had an inflammatory disease of the brain stem. In all patients, barium swallow revealed aspiration of contrast material into the trachea with failure of relaxation of the cricopharyngeal sphincter. Indirect laryngoscopy demonstrated partial paralysis of one or both vocal cords. In one, an emg of the laryngeal muscles showed normal results. A complete evaluation by the speech pathologist failed to reveal abnormality of the oral musculature in all patients. All patients required gastrostomies for their nutritional needs. Therapeutic modification and control of rate, quantity and consistency of food along with counseling for prevention of aspiration. Oral feeding, without aspiration, was achieved in the 3 patients within the treatment period, allowing removal of the gastrostomy. Cricopharyngeal myotomy, therefore, was not necessary in these patients, despite the long duration of the swallowing problem.
Topics: Brain Stem; Cerebral Infarction; Cricoid Cartilage; Deglutition; Deglutition Disorders; Eating; Female; Humans; Male; Middle Aged; Pharynx; Reflex; Speech Therapy
PubMed: 464785
DOI: No ID Found -
International Immunology Mar 1994The recently identified CD27 ligand (L) is a type II transmembrane molecule with significant structural homology to tumor necrosis factor (TNF)-alpha, TNF-beta,...
The recently identified CD27 ligand (L) is a type II transmembrane molecule with significant structural homology to tumor necrosis factor (TNF)-alpha, TNF-beta, lymphotoxin beta, CD40L, and CD30L. Using a CD27L specific mAb we examined the tissue distribution of the molecule, and found its expression to be restricted to B cells in occasional germinal centers, stromal cells in the thymic medulla, and scattered T cells in tonsils, skin and gut. As the limited expression of CD27L closely resembled the reported distribution of the activation antigen CD70, we tested whether CD70 represents the human CD27L. CD70 mAb were found to react with CD27L-expressing transfected mouse fibroblasts. Moreover a number of CD70 mAb could specifically interfere with the cellular binding of CD27L mAb. Thus, CD70 is identical to the human CD27L.
Topics: Antigens, CD; Binding, Competitive; CD27 Ligand; Cell Line; Flow Cytometry; Humans; Immunoenzyme Techniques; Ligands; Lymphocytes; Membrane Proteins; Palatine Tonsil; Thymus Gland; Tumor Necrosis Factor Receptor Superfamily, Member 7
PubMed: 8186199
DOI: 10.1093/intimm/6.3.477 -
Frontiers in Immunology 2021In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral...
In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral cavity, oropharynx, esophagus, stomach and bowel. In this report, we describe an autopsy case of a COVID-19 patient who showed two undiagnosed ulcers at the level of the anterior and posterior walls of the hypopharynx. Molecular testing of viruses involved in pharyngeal ulcers demonstrated the presence of severe acute respiratory syndrome - coronavirus type 2 (SARS-CoV-2) RNA, together with herpes simplex virus 1 DNA. Histopathologic analysis demonstrated full-thickness lympho-monocytic infiltration (mainly composed of CD68-positive cells), with hemorrhagic foci and necrosis of both the mucosal layer and deep skeletal muscle fibers. Fibrin and platelet microthrombi were also found. Cytological signs of HSV-1 induced damage were not found. Cells expressing SARS-CoV-2 spike subunit 1 were immunohistochemically identified in the inflammatory infiltrations. Immunohistochemistry for HSV1 showed general negativity for inflammatory infiltration, although in the presence of some positive cells. Thus, histopathological, immunohistochemical and molecular findings supported a direct role by SARS-CoV-2 in producing local ulcerative damage, although a possible contributory role by HSV-1 reactivation cannot be excluded. From a clinical perspective, this autopsy report of two undiagnosed lesions put the question if ulcers along the GI tract could be more common (but frequently neglected) in COVID-19 patients.
Topics: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Autopsy; Blood Platelets; COVID-19; Gastrointestinal Tract; Herpesvirus 1, Human; Humans; Hypopharynx; Immunohistochemistry; Inflammation; Lymphocytes; Monocytes; Mucous Membrane; Muscle, Skeletal; Necrosis; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Thrombosis; Ulcer
PubMed: 34290701
DOI: 10.3389/fimmu.2021.676828 -
Journal of Immunology (Baltimore, Md. :... Dec 2022Nasal immunity is an ancient and conserved arm of the mucosal immune system in vertebrates. In teleost fish, we previously reported the presence of a...
Nasal immunity is an ancient and conserved arm of the mucosal immune system in vertebrates. In teleost fish, we previously reported the presence of a nasopharynx-associated lymphoid tissue (NALT) characterized by scattered immune cells located in the trout olfactory lamellae. This diffuse NALT mounts innate and adaptive immune responses to nasal infection or vaccination. In mammals, lymphoid structures such as adenoids and tonsils support affinity maturation of the adaptive immune response in the nasopharyngeal cavity. These structures, known as organized NALT (O-NALT), have not been identified in teleost fish to date, but their evolutionary forerunners exist in sarcopterygian fish. In this study, we report that the rainbow trout nasal cavity is lined with a lymphoepithelium that extends from the most dorsal opening of the nares to the ventral nasal cavity. Within the nasal lymphoepithelium we found lymphocyte aggregates called O-NALT in this study that are composed of ∼ 56% CD4+, 24% IgM+, 16% CD8α+, and 4% IgT+ lymphocytes and that have high constitutive aicda mRNA expression. Intranasal (i.n.) vaccination with live attenuated infectious hematopoietic necrosis virus triggers expansions of B and T cells and aicda expression in response to primary i.n. vaccination. IgM+ B cells undergo proliferation and apoptosis within O-NALT upon prime but not boost i.n. vaccination. Our results suggest that novel mucosal microenvironments such as O-NALT may be involved in the affinity maturation of the adaptive immune response in early vertebrates.
Topics: Animals; Gastric Mucosa; Germinal Center; Mammals; Biomarkers; Adenoids; Immunoglobulin M
PubMed: 36426979
DOI: 10.4049/jimmunol.2200396 -
BMC Genomics Dec 2018The epithelium is the first line of defense against pathogens. Notably the epithelial cells lining the respiratory track are crucial in sensing airborne microbes and...
BACKGROUND
The epithelium is the first line of defense against pathogens. Notably the epithelial cells lining the respiratory track are crucial in sensing airborne microbes and mounting an effective immune response via the expression of target genes such as cytokines and chemokines. Gene expression regulation following microbial recognition is partly regulated by chromatin re-organization and has been described in immune cells but data from epithelial cells is not as detailed. Here, we report genome-wide changes of the H3K27ac mark, characteristic of activated enhancers and promoters, after stimulation of nasopharyngeal epithelial cells with the bacterial endotoxin Lipopolysaccharide (LPS).
RESULTS
In this study, we have identified 626 regions where the H3K27ac mark showed reproducible increase following LPS induction in epithelial cells. This indicated that sensing of LPS led to opening of the chromatin in our system. Moreover, this phenomenon seemed to happen extensively at enhancers regions and we could observe instances of Super-enhancer formation. As expected, LPS-increased H3K27ac regions were found in the vicinity of genes relevant for LPS response and these changes correlated with up-regulation of their expression. In addition, we found the induction of H3K27ac mark to overlap with the binding of one of the NF-kB members and key regulator of the innate immune response, RELA, following LPS sensing. Indeed, inhibiting the NF-kB pathway abolished the deposition of H3K27ac at the TNF locus, a target of RELA, suggesting that these two phenomena are associated.
CONCLUSIONS
Enhancers' selection and activation following microbial or inflammatory stimuli has been described previously and shown to be mediated via the NF-kB pathway. Here, we demonstrate that this is also likely to occur in the case of LPS-sensing by nasopharyngeal epithelial cells as well. In addition to validating previous findings, we generated a valuable data set relevant to the host immune response to epithelial cell colonizing or infecting pathogens.
Topics: Cell Line, Tumor; Epithelial Cells; Gene Expression Regulation; Histones; Humans; Immunity, Innate; Lipopolysaccharides; Nasopharynx; Transcription Factor RelA; Tumor Necrosis Factor-alpha
PubMed: 30587130
DOI: 10.1186/s12864-018-5295-4 -
The Laryngoscope Jun 2014Small, powerful magnets are increasingly available in toys and other products, and are responsible for increasing numbers of foreign body injuries in children. Small,...
OBJECTIVES/HYPOTHESIS
Small, powerful magnets are increasingly available in toys and other products, and are responsible for increasing numbers of foreign body injuries in children. Small, spherical, neodymium magnets available since 2008 are of particular concern. We aimed to identify all cases of upper aerodigestive foreign bodies at our institution over 15.5 years of study.
STUDY DESIGN
Case series including all patients treated at an urban, tertiary care children's hospital who had upper aerodigestive magnetic foreign bodies, from January 1, 1998 through April 30, 2013.
METHODS
We manually reviewed 7,049 patient records abstracted from billing data to identify all patients 0 to 20 years of age who had upper aerodigestive magnetic foreign bodies.
RESULTS
We identified four cases of upper aerodigestive magnetic foreign bodies, one involving the hypopharynx, and three involving the upper esophagus. Three occurred in 2010 or later. Two cases involve the ingestion of multiple, spherical, neodymium magnets recently marketed as desktop toys. In both of these cases, there was a rapid development of mucosal injury at the site of attraction between two magnets.
CONCLUSIONS
As small, powerful magnets become more ubiquitous, pediatric magnet foreign body injuries are increasing. Although most are gastrointestinal, we identified four recent cases involving the upper aerodigestive tract. Multiple magnets lodged in the hypopharynx or esophagus can rapidly cause pressure necrosis of mucosal tissues, and merit prompt management. Education regarding magnet safety and improved magnet safety standards are needed to reduce the risk of these injuries.
LEVEL OF EVIDENCE
4.
Topics: Child, Preschool; Databases, Factual; Deglutition; Epiglottis; Esophagoscopy; Esophagus; Female; Follow-Up Studies; Foreign Bodies; Hospitals, Urban; Humans; Hypopharynx; Incidence; Infant; Laryngoscopy; Magnets; Male; Radiography; Retrospective Studies; Risk Assessment; Sampling Studies; Tertiary Care Centers; Treatment Outcome
PubMed: 24391087
DOI: 10.1002/lary.24489 -
Journal of Oral and Maxillofacial... Jun 1995This study investigated whether wound healing after the use of purely muscular flaps for intraoral defect coverage is negatively influenced by insipient muscular atrophy...
PURPOSE
This study investigated whether wound healing after the use of purely muscular flaps for intraoral defect coverage is negatively influenced by insipient muscular atrophy and the absence of a covering layer.
MATERIALS AND METHODS
In an experimental study, microsurgical transplantation of muscle flaps from the anterior abdominal wall was carried out in 18 Lewis rats. A nerve anastomosis for motor reinnervation was not performed. Atrophy of the muscle flaps was determined by measuring the reduction of their size and weight after 3, 8, and 20 weeks. In the clinical part of the study, free muscle transplants from different donor regions (vastus lateralis, pectoralis major, internal oblique, and temporalis muscles) were used for defect coverage in various areas of the oral cavity. To study epithelization, punch biopsy specimens from the muscle surface were taken at periods of 2 to 4 weeks up to 6 months for histologic evaluation. Final evaluation of reconstruction results with special regard to speech, tongue mobility, mouth opening, chewing, and swallowing took place after 6 months.
RESULTS
In the experimental study, average weight loss of the muscle flaps was 67% after 20 weeks, and the remaining surface area was 71%. The number of myocytes was only about 30% compared with control muscles, and parts of the flap appeared as a thin fibrous membrane. Clinically, this atrophy led to restricted mobility in such areas as the floor of the mouth, the buccal plane, and the tongue. Muscle flaps covering solid structures such as bones or reconstruction plates adapted well to the transplant bed, and the atrophy of the muscle led to no constriction of the surrounding tissue. Atrophy also did not have a negative effect when muscle flaps were placed in the region of the pharyngeal wall. Epithelization started from the edges after 2 weeks and was concluded after 8 weeks in all transplants if no additional radiation was performed. The muscle tissue was sufficiently resistant so that infection, fistulization, and necrosis did not occur.
CONCLUSIONS
Muscle flaps undergo considerable atrophy with a cicatricial transformation and reduction of flexibility. Despite these disadvantages they can be used in the hard palate, the alveolar crest, and in the pharyngeal wall without causing functional restriction. Because of constriction of the surrounding tissues, mobile areas such as the buccal plane, the floor of the mouth, and the tongue are not suitable as sites for muscle transplants.
Topics: Abdominal Muscles; Animals; Atrophy; Deglutition; Epithelium; Follow-Up Studies; Humans; Male; Mastication; Microsurgery; Mouth; Muscle, Skeletal; Organ Size; Pectoralis Muscles; Pharynx; Postoperative Complications; Rats; Rats, Inbred Lew; Speech; Temporal Muscle; Tongue
PubMed: 7776051
DOI: 10.1016/0278-2391(95)90170-1 -
Environmental Toxicology and... Sep 2013To study the effect of air pollution on the microecology of the respiratory tracts and the relationship of the biotopes with respiratory diseases, Wistar rats exposed to...
To study the effect of air pollution on the microecology of the respiratory tracts and the relationship of the biotopes with respiratory diseases, Wistar rats exposed to mixed air pollutants were used as poisoning models. The bacterial floras of respiratory tract were analyzed as well as expression of pro-inflammatory mediators of the respiratory epithelium. The mRNA and protein expression levels of pro-inflammatory factor and cytokines measured showed that there were significant changes in the microbiocenosis of the respiratory tract. The microorganisms underwent quantitative and qualitative changes following exposure to mixed air pollutants including a decline of indigenous microflora and increase of the content of conditionally pathogenic microorganisms. These changes depended on the degree of air pollution severity. Measurement of pro-inflammatory factors CC16, TNF-α and IL-6 revealed a similar time-dependent relationship between the content of conditionally pathogenic microorganisms and the interference of CC16 secretion, as well as up-expression of TNF-α and IL-6.
Topics: Air Pollutants; Animals; Bronchoalveolar Lavage Fluid; Dose-Response Relationship, Drug; Female; Gene Expression Regulation; Inflammation Mediators; Inhalation Exposure; Interleukin-6; Male; Pharynx; RNA, Messenger; Rats; Rats, Wistar; Time Factors; Tumor Necrosis Factor-alpha; Uteroglobin
PubMed: 23834961
DOI: 10.1016/j.etap.2013.04.012