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Insulinlike growth factor I immunoreactivity in nasal polyps.

Nasal polyps from 15 patients were all found to express increased insulinlike growth factor I immunoreactivity. A hypothesis for the formation of nasal polyps is described: macrophages, seen in allergic and infectious reactions, produce and release growth factors, tentatively including insulinlike growth factor I. In enclosed paranasal sinuses this results in an accumulation of insulinlike growth factor I stimulating the growth of both epithelium and blood vessels in the sinuses. The mucosa increasingly bulges out through the ostium after having filled out the sinusity. Continuing growth stimulation is supplied by the inflammatory reaction, endothelial cells in the polyp, and activated macrophages inside or outside the polyp.

Adolescent↗

[The role of chemokines in nasal polyps].

Nasal polyposis is an inflammatory condition of the nose and the sinuses characterised by a marked infiltration of eosinophils in addition to lymphocytes, mast cells and macrophages. The selective recruitment of eosinophils to inflammatory sites is mediated by CC chemokines such as Eotaxin and Eotaxin-2. In the present study histology, immunohistochemistry and ELISA were performed. The levels of Eotaxin and Eotaxin-2 and for comparison other chemokines RANTES and IL-8 were measured in nasal polyp tissue and in control nasal tissue. On histological examination 6 polyps showed an oedematous structure, one was glandular and one had a fibromatous pattern, while all showed a marked eosinophil infiltration. Immunohistochemistry of the polyps showed that epithelial cells were strongly positive for Eotaxin and IL-8, whereas endothelial cells stained positive for Eotaxin-2. Significantly higher amounts of Eotaxin, Eotaxin-2 and IL-8 were detected in polyp tissue when compared with control middle turbinates. The increased levels of eosinophil-stimulating chemokines, such as Eotaxin and Eotaxin-2 in nasal polyps suggest that they may be important regulators of eosinophil recruitment in this inflammatory disease.

Chemokine CCL11↗

Innervation of human nasal polyps.

Nasal polyps from 12 patients were studied by means of transmission electron microscopy. Nerve fibers in the polyp could be recognized in 4 out of the 12 polyps. Both myelinated and nonmyelinated nerve fibers were observed. The endings of the nonmyelinated nerve were adrenergic and observed in the area close to the smooth muscle cells of the artery. The secretory cells in the form of acini did not accompany nerve endings although these acini contained myoepithelial cells. Some nerves had normal features but others had a degenerated form in the pedicle of the nasal polyp. No cholinergic fibers were observed in these polyps.

Adrenergic Fibers↗

Eosinophils in nasal polyps and nasal mucosa: an immunohistochemical study.

Immunohistochemical staining was performed at the time of endoscopic sinus surgery (ESS), after 6 months, and after 1 year on nasal polyps and biopsy specimens of the macroscopically unaffected mucosa of the middle and inferior turbinate bones of 46 patients with nasal polyps. During the follow-up period the patients were treated with topical corticosteroids. At time of ESS significantly more BMK13+ and EG1+ (pan eosinophil markers) and EG2+ (activation marker) eosinophils were found in the polyps than in the macroscopically unaffected mucosa of the middle and inferior turbinate bones of the patients. In the middle and inferior turbinate bones of 10 healthy subjects no EG2+ (activated) eosinophils were detected, whereas low-to-moderate numbers of BMK13+ and EG1+ eosinophils were seen in these specimens. This emphasizes that eosinophils play a role in the pathogenesis of nasal polyps. Compared with numbers at ESS, after 6 months and 1 year of follow-up, lower numbers of BMK13+, EG1+, and especially of EG2+ eosinophils were found in recurrences of polyps and in the macroscopically unaffected mucosa of the middle and inferior turbinate bones of the patients. The decrease in number of EG2+ (activated) eosinophils is an indication of a reduced local inflammatory reaction, and could be an important factor in postponement of recurrences of nasal polyps.

Adolescent↗

Localization and quantitation of eotaxin mRNA in human nasal polyps.

Nasal Polyps (NPs) are the most common mass lesions found in the nose. NPs cause airway obstruction, prevent normal sinus function, and can lead to infection of the eye, facial bones and central nervous system. The predominant cell type inhabiting NPs is the eosinophil, and the chemokine eotaxin is believed to play an important role in NP eosinophilia. The objective of this study was to localize and quantitate expression of eotaxin mRNA in human NPs. Total RNA was isolated from NPs that were collected from 5 patients who had undergone polypectomy. Portions of these polyps were also fixed in formalin, embedded in paraffin, and sectioned onto slides for use in in situ hybridization. Total RNA from one patient was used in a reverse transcriptase polymerase chain reaction using eotaxin specific primers to generate a human eotaxin cDNA. The eotaxin cDNA was cloned and used to generate probes for Northern blot analyses and for use in in situ hybridization (ISH). Eotaxin mRNA was detected by Northern analyses in all patient samples, though the relative expression level in each patient varied. ISH localized the expression of eotaxin mRNA specifically in eosinophils in 2 of the 3 patients in the study for whom the embedded polyp tissue appeared sufficiently well preserved for mRNA localization. Our findings suggest that eosinophilia in NPs is likely a self-amplification process whereby increasing numbers of eosinophils are recruited to enter the polyp as a result of production of eotaxin by eosinophils already within the polyp.

Blotting, Northern↗

Superantigens and nasal polyps.

Nasal polyps represent an often severe T-cell-orchestrated eosinophilic upper airway disease with currently unknown pathogenesis, often associated with lower airway disease, such as asthma. Superantigens, predominantly derived from Staphylococcus aureus, are potent activators of T cells, induce the synthesis of IgE in B cells, and have direct effects on pro-inflammatory cells, such as eosinophils. IgE antibodies to S. aureus enterotoxins have been described in polyp tissue, linked to a local polyclonal IgE production and an aggravation of eosinophilic inflammation. Furthermore, such IgE antibodies have also been described in the sera of patients with asthma, and linked to severity of disease and steroid insensitivity. This review summarizes our current understanding of the possible role of S. aureus enterotoxins in chronic severe airway disease, such as nasal polyposis.

B-Lymphocytes↗

Nasal polyps.

Nasal polyps are as common as adult onset asthma and unilateral polyps require histological examination. Medical therapy with corticosteroids should be tried before surgery. The anatomy should be demonstrated with computed tomography before endoscopic surgery.

Anti-Inflammatory Agents, Non-Steroidal↗

The nasal reactivity in patients with nasal polyps.

Nasal polyposis is a common clinical problem. The polyps commonly arise from the ethmoid sinuses and the etiology is still poorly understood. There is a connection between nasal polyps and asthma, cystic fibrosis and aspirin intolerance, but it is unclear whether there is a connection between nasal polyps and nasal hyperreactivity. The aim of this study was to investigate whether there is a connection between nasal hyperreactivity and nasal polyposis. Ten patients with nasal polyposis entered the trial. The nasal reactivity was studied with rhinostereometry during provocation with histamine. It was found that the patients with polyps did not have any nasal hyperreactivity.

Adolescent↗

Arachidonic acid metabolites in antrochoanal polyp and nasal polyp associated with chronic paranasal sinusitis.

The aim of this study was to investigate the role of arachidonic acid metabolites (AAMs) in the pathogenesis of antrochoanal polyp (ACP). Using high-performance liquid chromatography (HPLC), we assayed the tissue concentrations of 6-keto-PGF1alpha, leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETE). Concentrations of AAMs in ACP were compared with the level in the control turbinate tissues and nasal polyps associated with chronic paranasal sinusitis (NPS). The concentrations of 6-keto-PGF1alpha were not significantly different in the control turbinate, ACP and NPS groups. In ACP, concentrations of LTC4, 15-HETE and 12-HETE were significantly lower than in the control turbinate. The striking differences in the profile of AAMs between ACP and NPS included a lack of production of LTD4 and LTE4 in ACP, also detectable in NPS, and markedly lower concentrations of 15-HETE and 12-HETE in ACP. The results of this study indicate that decreased lipoxygenase pathway products in arachidonic acid metabolism may be involved in the pathogenesis of ACP. However, in the pathogenesis of NPS, increased production of LTD4 and LTE4 may have an important role. Taken together, our results demonstrate a difference in pathogenesis between ACP and NPS, particularly in terms of arachidonic acid metabolism.

6-Ketoprostaglandin F1 alpha↗

Contemporary management of nasal polyps.

Nasal polyposis is a multifactorial disease process resulting in a common pathologic structure. Better understanding of the pathophysiology has resulted in improved protocols for treatment. Different causes of polyposis are discussed with attention to both medical and surgical therapy. Recent advances in aspirin desensitization are detailed.

Combined Modality Therapy↗

[Determination of differentially expressed proteins and it's significance among chronic sinusitis, nasal polyps and normal nasal mucosa].

OBJECTIVE: To investigate the differentially expressed proteins among chronic sinusitis, nasal polyps and normal nasal mucosa by means of proteomic technology, and select the candidate biomarkers of chronic sinusitis and nasal polyps. METHODS: Proteins extracted from chronic sinusitis, nasal polyps and normal nasal mucosa were separated and the differentially expressed proteins were identified by series of proteomic tools, including immobilized pH4-7 gradient two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis, modified coomassie brilliant blue staining, images scanning by the Image Scanner apparatus, PDQuest analysis software, peptide mass fingerprinting based on matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) by in-gel digestion extract, and Mascot searching in NCBInr and SWISS-PROT databases. RESULTS: The 2-DE patterns with high resolution and reproducibility were obtained. The protein spots separated and visualized in chronic sinusitis, nasal polyps and normal nasal mucosa gel were 1020 +/- 40, 1112 +/- 10 and 1008 +/- 25, respectively. And the match rates were (93 +/- 2)%, (95 +/- 1)% [see text] (90 +/- 3)% respectively. Thirteen differentially expressed spots were found from chronic sinusitis, nasal polyps and normal nasal mucosa gel. We selected and recommend Keratin 8 and APOA1 proteins as candidate biomarkers of nasal polyps, and PLUNC protein, PACAP protein, NKEF-B and SOD as candidate biomarkers of chronic sinusitis. CONCLUSIONS: The differentially expressed proteins among chronic sinusitis, nasal polyps and normal nasal mucosa can be efficiently and relatively reliably identified via the techniques of proteomics. These techniques will play a very important role in the researches for new objective indicators possibly employed in the future classifying, staging and prognosis.

Adolescent↗

[Bronchial reactivity in patients with nasal polyps].

Nasal polyposis is in 25-70% complicated by the development of bronchial asthma, its attribute being bronchial hyperreactivity (BH). The authors examined 101 patients (23 with polyps and asthma, 53 with polyps and 35 controls) using the standard bronchoconstriction test as described by Cockroft and Vondra). By inhalation of increasing concentrations of histamine solutions the provoking concentration, PC20, was assessed. In the group with polyps and asthma 56% patients suffered from spontaneous bronchial obstruction and 44% from high and medium BH (PC20 less than 1.0 mg/ml). In patients with nasal polyposis alone in 21% spontaneous obstruction was found or a high BH, similarly as in the group suffering from asthma (PC20 less than 0.5 mg/ml). A medium BH was recorded in 23% and a mild BH in 26% (PC20 less than 1-2 mg/ml). 30% of patients with polyps are normoreactive (PC20 greater than 2 mg/ml). In the control group all patients were normoreactive. Patients with polyps and a high or medium BH are a risk group (44% of patients) threatened by the development of asthma. They call for longitudinal follow up of the BH and frequent check-up examinations by an ENT specialist and allergologist. Many years' verification of this hypothesis and evaluation of other risk factors is necessary for a more detailed analysis of the risk group of patients with polyps.

Bronchial Provocation Tests↗

[Expression of transforming growth factor beta receptor I and II in chronic rhinosinusitis, nasal polyps and normal nasal mucosa tissues].

OBJECTIVE: To explore the expression of transforming growth factor beta receptor(TGFpR) I, II in the chronic rhinosinusitis, nasal polyps and normal nasal mucosa tissues. METHOD: The protein expression of the TGFbetaR I and TGFbetaR II were determined by means of immunohistochemistry in chronic rhinosinusitis tissues from 25 patients, nasal polyps tissues from 21 patients and inferior turbinate mucosa tissues from 17 patients with deviation of nasal septum. RESULT: (1) In chronic rhinosinusitis and nasal polyps tissues, compared with controls, the expression of TGFbetaR I and TGFbetaR II protein was increased significantly (P < 0.01). (2) The expression of TGFbetaR I and TGFbetaR II protein in nasal polyps tissues was significant increased than that in chronic rhinosinusitis tissues (P < 0.01). CONCLUSION: The different expression level and pattern of TGFbetaR I and TGFbetaR II in chronic rhinosinusitis and nasal polyps tissues indicates TGFbetaR may play a different role in the pathogenesis chronic rhinosinusitis and nasal polyps.

Adolescent↗

Eicosanoids from biopsy of normal and polypous nasal mucosa.

In order to clarify the influence of inflammatory mediators of the arachidonic acid cascade in the mechanism of nasal polyp growth, peptido-leukotriene (pLT), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) synthesis was investigated. In addition to several stimuli, functionally intact human biopsy specimens of polypous and normal tissue were incubated. Especially remarkable was the significantly increased release of pLT by polypous tissue upon arachidonic acid stimulation, in contrast to only slightly elevated PGE2 release compared to normal tissue. Basic release of pLT and PGE2 was similar for polypous and normal tissue. Examining TXB2 release, no significant difference was observed with regard to the origin of tissues. These data support an altered pattern of the lipoxygenase and cyclo-oxygenase pathways when tissue becomes irritated and suggest their involvement in the aetiopathogenesis of nasal polyps.

Biopsy↗

Upregulation of MUC8 and downregulation of MUC5AC by inflammatory mediators in human nasal polyps and cultured nasal epithelium.

Polyps are believed to be the source of mucus hypersecretion in chronic inflammation of the sinus. However, it is not clear which mucins are responsible for the hypersecretion of mucus by nasal polyps. We describe the over-expression of MUC8 mRNA in nasal polyps and the upregulation of MUC8 mRNA expression and downregulation of MUC5AC mRNA expression by inflammatory mediators. We found that the level of MUC8 mRNA, but not the level of MUC5AC mRNA, increased in nasal polyps. We also found that there was an increase in intracellular mucin in nasal polyps, compared to the normal nasal inferior turbinate. A mixture of inflammatory mediators increased MUC8 mRNA expression and decreased MUC5AC mRNA expression in cultured normal human nasal epithelial cells. Among inflammatory mediators, IL-4 is responsible for the decrease in MUC5AC mRNA and MUC5AC mucin secretion. These results indicate that MUC8 may be one of the major mucins secreted from the polyp epithelium and that it may play an important role in the pathogenesis of mucus hypersecretion in chronic sinusitis with polyps.

Cells, Cultured↗