Desmin and dystrophin abnormalities in upper airway muscles of snorers and patients with sleep apnea.

BACKGROUND: The pathophysiology of obstruction and swallowing dysfunction in snores and sleep apnea patients remains unclear. Neuropathy and to some extent myopathy have been suggested as contributing causes. Recently we reported an absence and an abnormal isoform of two cytoskeletal proteins, desmin, and dystrophin, in upper airway muscles of healthy humans. These cytoskeletal proteins are considered vital for muscle function. We aimed to investigate for muscle cytoskeletal abnormalities in upper airways and its association with swallowing dysfunction and severity of sleep apnea. METHODS: Cytoskeletal proteins desmin and dystrophin were morphologically evaluated in the uvula muscle of 22 patients undergoing soft palate surgery due to snoring and sleep apnea and in 10 healthy controls. The muscles were analysed with immunohistochemical methods, and swallowing function was assessed using videoradiography. RESULTS: Desmin displayed a disorganized pattern in 21 ± 13% of the muscle fibres in patients, while these fibers were not present in controls. Muscle fibres lacking desmin were present in both patients and controls, but the proportion was higher in patients (25 ± 12% vs. 14 ± 7%, p = 0.009). The overall desmin abnormalities were significantly more frequent in patients than in controls (46 ± 18% vs. 14 ± 7%, p < 0.001). In patients, the C-terminus of the dystrophin molecule was absent in 19 ± 18% of the desmin-abnormal muscle fibres. Patients with swallowing dysfunction had 55 ± 10% desmin-abnormal muscle fibres vs. 22 ± 6% in patients without swallowing dysfunction, p = 0.002. CONCLUSION: Cytoskeletal abnormalities in soft palate muscles most likely contribute to pharyngeal dysfunction in snorers and sleep apnea patients. Plausible causes for the presence of these abnormalities is traumatic snoring vibrations, tissue stretch or muscle overload.

Afectación cardiovascular en el síndrome de Loeys-Dietz / Cardiovascular involvement in Loeys-Dietz syndrome

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Papiloma en úvula / Uvula papiloma

Presentamos el caso de un paciente con sensación de cuerpo extraño en la garganta y finalmente diagnosticado de papiloma invertido y papiloma escamoso de úvula. Tras la cirugía la evolución fue favorable (AU)

The present is a case of a patient with a foreign body sensation in the throat and final diagnosis of inverting papilloma and squamous papilloma of uvula. After surgery, the evolution was successful (AU)

Tumor necrosis factor-alpha expression in uvular tissues differs between snorers and apneic patients.

BACKGROUND: Inflammatory changes such as subepithelial edema and excessive inflammatory cell infiltration have been observed in uvular tissues of obstructive sleep apnea (OSA) subjects. The levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin-6 are elevated in the serum of apneic patients and have been proposed as mediators of muscle weakness. TNF-alpha has been shown to affect diaphragm contractility in mice and rabbit in vivo. OBJECTIVES: To assess total and compartmental TNF-alpha expression in uvular tissues of apneic and nonapneic patients. METHODS: Uvular tissues were collected from 14 snorers without sleep disorders breathing, 14 subjects with OSA (OSA 1 group) whose body mass index (BMI) was similar to that of snorers, and 12 additional obese OSA subjects (OSA 2 group) who underwent an uvulopalatopharyngoplasty. Sections were examined using immunohistochemistry and Western blot analysis. TNF-alpha expression was evaluated in the musculus uvulae (MU), epithelial layer, and perimuscular tissues from proximal uvular sections. RESULTS: TNF-alpha was more highly expressed in whole uvular protein extracts of apneic groups than in snorers ([mean +/- SEM] snorers, 100.5 +/- 3.0%; OSA 1 group, 127.1 +/- 6.9%; OSA 2 group, 140.7 +/- 11.0%; p = 0.01). In the muscular area, TNF-alpha levels were higher in the more obese OSA subjects than in the other two groups (snorers, 100.3 +/- 3%; OSA 1 group, 107.4 +/- 0.7%; OSA 2 group, 124.1 +/- 4.2%; p = 0.007). In the muscular area, TNF-alpha was correlated with BMI, but no relationship was found with the apnea-hypopnea index. CONCLUSIONS: We conclude that MU is the major TNF-alpha source in uvular tissue and that TNF-alpha is more highly expressed in the heaviest OSA patients compared to less obese OSA patients and nonapneic snorers.

Structure of the human uvula.

Eleven uvular biopsies were investigated for their morphology, the presence of mast cells and the distribution of hyaluronan and its major ligand CD44. Three microanatomical sites--surface epithelium, subepithelial area and area of glands--were examined. The oral side of the uvula was covered by a 15-20 cell thick layer of keratinized/parakeratinized surface epithelium, firmly anchored to the underlying connective tissue by connective tissue papillae. The width of the intercellular spaces in the epithelium increased toward the basal lamina, a location that exhibited intense hyaluronan and anti-CD44 staining. Most mast cells were located in the vicinity of blood vessels, at which sites there was high staining intensity of hyaluronan. Tissue mast cells could also be observed in the connective tissue septa enclosing the acini. Glands and muscle fibres became more sparse from the proximal part of the uvula to the distal end, while the amount of connective tissue increased. The localization and architecture of connective tissue elements and mast cells are consistent with the ability of the uvula to resist mechanical stresses and to develop oedema and fibrosis, respectively.

Oral condyloma acuminatum associated with human papillomavirus and p53 overexpression mimicking cyclosporine effect in a transplant patient.

A case of human papillomavirus-associated condyloma acuminatum in the oral cavity, presumed to be fulminant cyclosporine-induced gingival hyperplasia, is reported in a 55-year-old cardiac transplant patient. Approximately 47 months following the transplant, the patient developed severe hyperplasia of the uvula and oral mucosa, resulting in difficulty swallowing. The histopathologic features of the lesion were typical of those of condyloma acuminatum. In situ hybridization of the paraffin-embedded material revealed infection with human papillomavirus types 6/11. This case lends further support to the putative role of long-term cellular immunosuppression in the development of human papillomavirus-associated squamous lesions. In addition, positive staining for p53 protein raises the possibility of concomitant p53 involvement in the pathogenesis of this oral lesion.

Characteristics of the genioglossus and musculus uvulae in sleep apnea hypopnea syndrome and in snorers.

Genioglossus (GG) activity has been extensively studied by electromyographic recordings in the investigation of the pathophysiology of sleep apnea-hypopnea syndrome (SAHS). However, the effective force developed by this upper airway (UA) dilator muscle depends on its metabolic and histochemical characteristics. The aim of this study was to compare the metabolic and fiber type characteristics of two UA dilator muscles, musculus uvulae (MU) and GG, in 17 patients with SAHS and in 11 nonapneic snorers. MU and GG samples were obtained during uvulopalatopharyngoplasty. Anthropomorphic characteristics were similar in snorers and patients with SAHS, who differed only in the presence of sleep-related breathing abnormalities. MU glycolytic, glycogenolytic, and anaerobic enzyme activities were significantly greater in patients with SAHS than in snorers. These differences were not observed for GG. MU and GG enzyme activities differed only in snorers. The proportion of type I muscle fiber was greater in GG than in MU, but it was similar in patients with SAHS and snorers for each muscle. Type IIA and IIB muscle fibers were, respectively, in greater and smaller proportions in patients with SAHS than in snorers. We conclude that (1) the differences in metabolic characteristics between patients with SAHS and snorers are not observed in all UA muscles, and (2) similar histochemical differences are observed in GG and MU between these two groups, thus suggesting that these differences may be implicated in the pathophysiology of SAHS.

[Nicotine concentrations in the palatine tonsil, uvula mucosa and septum cartilage of smokers--a pilot study]. / Nikotinkonzentrationen in der Tonsilla palatina, Uvulaschleimhaut und Septumknorpel von Rauchern--Eine Pilotstudie.

The concentrations of nicotine were determined via radioimmunoassay in the palatine tonsils (n = 22) and in the mucosa of the uvula (n = 5) of eleven male smokers, and in the nasal septal cartilage of four other smokers. The same tissues of five nonsmokers served as controls. The mean values of the nicotine concentrations were 77 ng/g for the tonsils (level of serum: 151 ng/g), 114.5 ng/g for the mucosa of the uvula (level of serum: 215 ng/g) and 36 ng/g for the septal cartilage (level of serum: 97 ng/g). There was no nicotine in the tissues and serum of the control group. The correlations between the nicotine concentrations of the three tissues and the levels of the serum were significant. Another significant correlation was found between the nicotine level of the serum and the daily consumption of cigarettes of the eleven patients on whom tonsillectomy had been performed. These concentrations of nicotine in the three types of tissue and in serum appear to be high after an interval of twelve hours non-smoking. With gas-chromatography/mass-spectrometry also unchanged nicotine was found in the tonsils which is considered to be the damaging substance of tobacco.