Nasal Biopsies (nasal + biopsy)

Distribution by Scientific Domains

Selected Abstracts

Treatment of an osteoblastic osteosarcoma in an aged gelding

T. Springer
Summary A 27-year-old Thoroughbred gelding was examined for a right nasal mass visible inside the right nares. Airflow through the right nostril was absent. Endoscopy and radiography revealed the mass to occupy the entire right nasal passage. Nasal biopsies were inconclusive, so en bloc resection was performed. A diagnosis of an incompletely resected osteoblastic osteosarcoma was made. Endoscopic biopsies performed 4 weeks post surgery revealed osteosarcoma cells present in the caudal right nasal cavity. Metastatic disease was not present in mandibular lymph node aspirates or on thoracic radiographs. The right nasal passage was irradiated with 12 treatments over the course of 4 weeks. Comfort and quality of life were excellent during treatment and no adverse side effects were noted. Endoscopy and follow-up biopsies at 1, 2, 4, 12 and 14 months post radiation therapy have not found any evidence of regrowth of the osteosarcoma. [source]

CC Chemokine Receptor 4 (CCR4) in human allergen-induced late nasal responses

ALLERGY, Issue 9 2010
G. Banfield
To cite this article: Banfield G, Watanabe H, Scadding G, Jacobson MR, Till SJ, Hall DA, Robinson DS, Lloyd CM, Nouri-Aria KT, Durham SR. CC Chemokine Receptor 4 (CCR4) in human allergen-induced late nasal responses. Allergy 2010; 65: 1126,1133. Abstract Background:, CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2 lymphocytes. CCR4-mediated inflammation may be important in the pathology of allergic rhinitis. Disruption of CCR4 , ligand interaction may abrogate allergen-induced inflammation. Methods:, Sixteen allergic rhinitics and six nonatopic individuals underwent both allergen and control (diluent) nasal challenges. Symptom scores and peak nasal inspiratory flow were recorded. Nasal biopsies were taken at 8 h post challenge. Sections were immunostained and examined by light or dual immunofluorescence microscopy for eosinophils, T-lymphocytes, CCR4+CD3+ and CXCR3+CD3+ cells and examined by in situ hybridization for CCR4, IL-4 and IFN-, mRNA+ cells. Peripheral blood mononuclear cells were obtained from peripheral blood of nine normal donors and the CCR4+CD4+ cells assessed for actin polymerization in response to the CCR4 ligand macrophage-derived chemokine (MDC/CCL22) and the influence of a CCR4 antagonist tested. Results:, Allergic rhinitics had increased early and late phase symptoms after allergen challenge compared to diluent; nonatopics did not respond to either challenge. Eosinophils, but not total numbers of CD3+ T cells, were increased in rhinitics following allergen challenge. In rhinitics, there was an increase in CCR4+CD3+ protein-positive cells relative to CXCR3+CD3+ cells; CCR4 mRNA+ cells were increased and IL-4 increased to a greater extent than IFN-,. CCR4+CD4+ T cells responded to MDC in vitro, and this response was inhibited by the selective CCR4 antagonist. Conclusion:, Lymphocyte CCR4 expression is closely associated with induction of human allergen-induced late nasal responses. Blocking CCR4-ligand interaction may provide a novel therapeutic approach in allergic disease. [source]

Efficacy and tolerance of intranasal insulin administered during 4 months in severely hyperglycaemic Type 2 diabetic patients with oral drug failure: a cross-over study

D. Lalej-Bennis
Abstract Aims We have evaluated the local tolerance and the metabolic efficacy of a lyophilized nasal insulin preparation in 10 severely hyperglycaemic Type 2 diabetic patients. Methods The study included two 4-month randomized periods: (A) three preprandial doses of nasal insulin secondarily combined with one evening subcutaneous NPH if the desired glycaemic control was not achieved; (B) two NPH injections daily. We assessed: (i) diabetes control on monthly HbA1c levels and occurrence of hypoglycaemic events; (ii) local tolerance on clinical symptoms, rhinoscopy, nasal muco-ciliary clearance and nasal biopsies; (iii) insulin absorption at months 0 and 4. Results One patient was withdrawn because of cough and dizziness after each nasal application. HbA1c was not significantly different at month 4 (9.4 ± 0.5% vs. 8.8 ± 0.2%, A vs. B). Blood glucose control remained only fair in the majority of our patients. Nasal insulin was able to replace the daytime fraction of the subcutaneous insulin with a 18% efficacy. Side-effects included transient nasal hyperactivity (pruritis, sneezing and rhinorrhoea) and chronic persistence of nasal crusts. Plasma insulin profiles were not significantly different between months 0 and 4. Conclusions The utilization of nasal insulin (with or without NPH) was associated with similar diabetes control compared with NPH twice daily. Nasal insulin alone was able to achieve an adequate glycaemic control in three of the 10 patients. Diabet. Med. 18, 614,618 (2001) [source]

Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation

David Mitchell
Abstract Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6,4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirwayÔ) and human skin (EpiDermÔ) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage. [source]

Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis?

ALLERGY, Issue 10 2010
J. Bogefors
To cite this article: Bogefors J, Rydberg C, Uddman R, Fransson M, Månsson A, Benson M, Adner M, Cardell LO. Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis? Allergy 2010; 65: 1222,1226. Abstract Background:, Recently, a new set of pattern-recognition receptors, the nucleotide-binding oligomerization domain (Nod)-like receptors (NLRs), have emerged. Their activation, either by allergens or microbes, triggers an inflammatory response. The knowledge about NLRs in human airways is limited. Aim of the study:, To investigate presence of NLRs in the human nose of healthy individuals and patients with intermittent allergic rhinitis outside and during pollen season. Methods:, The expression of Nod1, Nod2, and Nalp3 in nasal biopsies was determined with real-time RT-PCR and immunohistochemistry. Cultured primary human nasal epithelial cells (HNECs) were analyzed using real-time RT-PCR and flow cytometry to further verify the presence of NLRs in the epithelium. Results:, Immunohistochemical analysis revealed presence of Nod1, Nod2, and Nalp3 in the nasal epithelium. This was corroborated in cultured HNECs. Patients suffering from symptomatic allergic rhinitis exhibited lower Nod1 and Nalp3 mRNA levels than both controls and patients during pollen season. Nod2 expression was found in all specimens tested, but no differences were seen between the three groups. Conclusion:, Nod1, Nod2, and Nalp3 receptors were found to be present in the human nose. The expression of Nod1 and Nalp3 were down-regulated during pollen season among patients with allergic rhinitis. This opens up for new insights and novel therapeutic strategies in inflammatory airway disease. [source]

Genes regulating molecular and cellular functions in noninfectious nonallergic rhinitis

ALLERGY, Issue 9 2009
L. O. Cardell
Background:, Chronic noninfectious, nonallergic rhinitis (NINAR) is a complex syndrome with a principally unknown pathophysiology. New technology has made it possible to examine differentially expressed genes and according to network theory, genes connected by their function that might have key roles in the disease. Methods:, Connectivity analysis was used to identify NINAR key genes. mRNA was extracted from nasal biopsies from 12 NINAR patients and 12 healthy volunteers. Microarrays were performed using Affymetrix chips with 54 613 genes. Data were analysed with the Ingenuity Pathway System for organization of genes into annotated biological functions and, thereafter, linking genes into networks due to their connectivity. The regulation of key genes was confirmed with reverse transcription-polymerase chain reaction (RT-PCR). Results:, In all, 43 genes were differentially expressed. The functional analysis showed that these genes were primarily involved in cellular movement, haematological system development and immune response. Merging these functions, 10 genes were found to be shared. Network analysis generated three networks and two of these ,shared genes' in key positions, c-fos and cell division cycle 42 (Cdc42). These genes were upregulated in both the array and the RT-PCR analysis. Conclusion:, Ten genes were found to be of pathophysiological interest for NINAR and of these, c-fos and Cdc42 seemed to be of specific interest due to their ability to interact with other genes of interest within this context. Although the role of c-fos and Cdc42 in upper airway inflammation remains unknown, they might be used as potential disease markers. [source]

Nasal endothelial interleukin-10 expression is negatively correlated with nasal symptoms after allergen provocation

ALLERGY, Issue 5 2009
B. Muller
Background:, Despite major efforts, factors that predict or correspond to the level of allergic symptoms remain elusive. Given our previous observations of mucosal interleukin-10 (IL-10) expression by local tissue cells and its described role as immune modulator, we hypothesized that, in allergic rhinitis, nasal mucosal IL-10 expression could influence the severity of symptoms. Methods:, In this study, we investigated endothelial IL-10 expression in nasal mucosa of healthy- and house dust mite allergic patients, both before and after provocation, and under nasal steroid therapy. Nasal turbinate biopsies were taken from healthy individuals as well as from house dust mite allergic patients, both before and after provocation. Allergic patients received fluticasone proprionate aqueous nasal spray or control treatment. In the allergic patients, endothelial IL-10 scores based on immunohistochemical stainings were correlated with allergic symptoms, measured by visual analog scores. Results:, At baseline, variable levels of endothelial IL-10 were detected in nasal biopsies. After nasal provocation, but not at baseline, endothelial IL-10 expression corresponded very closely to the allergic symptoms after allergen provocation. Low symptom scores were correlated with high endothelial IL-10 scores. This correlation disappeared after fluticason propionate treatment. Conclusions:, There is a large variation in the level of endothelial IL-10 expression both in healthy individuals and in house dust mite allergic patients. Endothelial IL-10 expression may affect local immune reactions resulting in reduced levels of allergic symptoms. [source]

T lymphocytes expressing CCR3 are increased in allergic rhinitis compared with non-allergic controls and following allergen immunotherapy

ALLERGY, Issue 1 2007
J. N. Francis
Background:, In T cell-associated allergic inflammation, homing of T-helper 2 (Th2) effector cells to mucosal sites may be influenced by chemokine receptor expression. Previous studies have identified CCR3 and CCR4 as putative markers of Th2 cells and CCR5 and CXCR3 as markers of Th1 cells. The aim of this study was to assess differential chemokine receptor expression from symptomatic atopic grass pollen-sensitive subjects, compared with patients on high-dose allergen injection immunotherapy (IT) and healthy controls. Methods:, We examined chemokine receptor expression (CCR1,7 and CXCR1,4) by flow cytometry of peripheral blood CD4+ and CD8+ T cells. We also depleted peripheral blood mononuclear cell (PBMC) populations of CCR3+ CD4+ cells by magnetic bead separation and cells were stimulated with grass pollen allergen for 6 days. Cytokine production was measured by enzyme-linked immunosorbent assay. Results:, On freshly isolated PBMC, atopic individuals exhibited increased numbers of CCR3+ CD4+ cells compared with normal controls (P < 0.01). CCR3 expression in IT patients was reduced compared with matched atopic rhinitic controls (P < 0.05) and comparable with that observed in normal subjects. Depletion of CCR3+ CD4+ cells from allergen-stimulated PBMC cultures resulted in decreased interleukin (IL)-5 production compared with whole CD4+ populations (P < 0.05). Freshly isolated CCR3+ CD4+ cells have significantly higher intracellular IL-4 and lower IFN- , levels than CCR3, CD4+ cells. CD4+ T cells cultured from both peripheral cells and nasal biopsies demonstrated increased expression of CCR3 in the presence of IL-4 (P < 0.05). Conclusion:, CCR3+ CD4+ T cells are increased in allergic rhinitis, are reduced by allergen IT, have a Th2 phenotype and contribute to allergen-specific responses. Strategies against CCR3+ T cells may be effective in human allergic diseases. [source]

Efficacy of pollen immunotherapy in seasonal allergic rhinitis

Abstract Background: The efficacy of subcutaneous pollen immunotherapy has been documented in published double-blind, placebo-controlled studies related to treatment of seasonal allergic rhinitis. In the present study, subjective (symptom scores) and objective (nasal peak inspiratory flow, nasal smear, nasal biopsy) parameters were used to study the efficacy of pollen immunotherapy. Methods: Forty-eight patients (32 male), mean ± SE age 13.6 ± 2.8 years allergic to grass-pollen participated in the present study. Patients were divided into three groups: group I, 24 patients who did not receive pollen immunotherapy; group II, 12 patients who received the build-up phase of pollen immunotherapy; and group III, 12 patients who had just finished pollen immunotherapy. With regard to objective and subjective parameters these three groups were compared. Results: When group I was compared to groups II and III, the patients who had not received any immunotherapy were found to have a high daytime nasal symptoms score (P < 0.01), high daytime eye symptoms score(P < 0.01) and high night-time symptoms score (P < 0.01). In objective parameters, it was found that group I had low nasal peak inspiratory flow (P < 0.05), and a high eosinophil count in nasal smears (P < 0.05) and peripheral blood (P < 0.05). It was also demonstrated that there was an increased eosinophil infiltration (P < 0.01) and mast cell infiltration (P < 0.05) in nasal biopsy in group I. There was no significant difference between group II and group III according to these results (P > 0.05). Conclusions: Immunotherapy leads to a better clinical and histopathological prognosis in children with seasonal allergic rhinitis. [source]

In vivo expression of signal transducer and activator of transcription factor 6 (STAT6) in nasal mucosa from atopic allergic rhinitis: effect of topical corticosteroids

Background The allergen-induced late nasal response is associated with a high local expression of interleukin (IL) -4, a TH2-type cytokine implicated in immunoglobulin (Ig) E production, tissue eosinophilia and other events considered to be relevant to allergic inflammation. Interaction of IL-4 with its receptor activates at least two distinct signalling pathways that culminate in the transcription of specific target genes. One pathway involves the activation of a transcription factor termed signal transducer and activator of transcription factor 6 (STAT6). Objective To investigate the expression of STAT6 in the allergen-induced late nasal response and to examine the effect of local steroid treatment on STAT6 expression. Methods Inferior turbinate biopsies were obtained from subjects with allergic rhinitis out of the allergen season. Subjects were then randomized into topical steroid- (n = 6) and placebo-treated (n = 6) groups in a double-blind fashion. After a 6-week treatment period, a second nasal biopsy was performed 24 h after local challenge with allergen. STAT6 immunoreactivity was examined in biopsy specimens by immunocytochemistry using a specific monoclonal antibody. Numbers of inflammatory cells (CD3+ T cells and MBP+ eosinophils) and IL-4 mRNA+ cells were investigated by immunocytochemistry and in situ hybridization, respectively. Results STAT6 immunoreactivity was detected in all biopsies studied and localized predominantly to inflammatory tissue of the nasal mucosa. After allergen challenge, expression of STAT6 was markedly increased in placebo-treated patients (P < 0.01). By confocal microscopy, STAT6 was localized to the cytoplasm and the nucleus of positively-staining cells. The allergen-induced increase in STAT6 immunoreactive cells was not observed in the steroid-treated patients. The change in STAT6 immunoreactivity after allergen challenge correlated significantly with the change in numbers IL-4 mRNA+ cells (r = 0.74, P = 0.006) and CD3+ T cells (r = 0.76, P = 0.004), but not MBP+ eosinophils. Conclusion This study provides the first evidence of increased STAT6 expression in vivo in human allergic inflammation. The results support a role for STAT6 and IL-4 in the pathogenesis of late nasal response and show that decreases in STAT6 expression parallel the reduction in IL-4 expression that occurs with topical steroid treatment. [source]