OBJECTIVE:Because of recurrent scarring of the ostiomeatal complex after paranasal sinus surgery the therapy of chronic rhinosinusitis without nasal polyps (CRSsNP) seems to be difficult. The aim of this study was to evaluate ultrastructural changes of nasal mucosa in patients with CRSsNP.MATERIAL AND METHODS:In case of revision sinus surgery we took specimens of altered mucosa from 21 patients. All subjects suffered from recurrent CRSsNP. Twelve patients without signs of chronic rhinosinusitis dealed as control group. To prepare for electron microscopy the samples were immersed in 3% phosphate-buffered glutaraldehyde and refixed in 1% osmium acid. After dehydration and heat polymerization ultrathin cuts were prepared. After double-contrasting ultrastructures were evaluated by transmission electron microscopy.RESULTS:Typical changes evaluated by electron microscopy were loss of cilia, an increase of microvilli, collagen fibres, fibrocytes, fibroblasts and myofibroblasts as well as perivascular alterations and endothelial changes.CONCLUSION:The study revealed the presence of evident ultrastructural changes in the mucosa of patients with chronic rhinosinusitis without nasal polyps. Mucosal remodeling seems to be not reversible by conservative treatment.

Nasal hyperreactivity is one of the most important underlying mechanisms in both allergic (AR) and idiopathic rhinitis (IR). In order to study the pathomorphological changes in this entity, tissue samples from patients with AR, IR, and from patients without chronic inflammation were taken during nasal surgery. Primary antibodies against Substance P (SP), calcitonin gene-related peptide (CGRP), and endothelial nitric oxide synthases (NOS III) were applied and the immunocomplexes were visualized by immunocytochemistry. The nasal mucosa of patients with AR and IR showed similarities on the ultrastructural level. Neurogenic inflammation was indicated by a strong innervation pattern with sensory nerve fibers containing SP and CGRP. We could show that extensive edema and cellular infiltration might be characteristic for AR. On other hand there was no evidence of eosinophilic or NO involvement in IR. Finally, on the ultrastructural level, AR and IR showed many similarities. Based on these findings anti-inflammatory therapy modalities could be recommended for both types of rhinitis.

Background. Nasal hyperreactivity is one of the most important underlying mechanisms in allergic rhinitis (AR) as well as idiopathic rhinitis (IR). The aim of the present study was to examine pathomorphological changes in nasal mucosa in these subgroups of rhinitis. Patients and methods. Tissue samples of human inferior turbinates from 20 patients with AR and 16 patients with IR were taken during nasal surgery and preserved in glutaraldehyde or paraformaldehyde. Ultrathin sections of specimens from 15 patients without chronic inflammation of nasal mucosa were used as controls. Primary antibodies against substance P (SP), calcitonin-gene-related peptide (CGRP), and endothelial nitric oxide synthase (NOS III) were applied, and the immunocomplexes were visualized by an immunocytochemical staining technique using gold-labeled antibodies. Immunostained structures were photodocumented using light and transmission electron microscopy. Results. The nasal mucosa of patients with AR and IR showed similarities on the ultrastructural level. A strong innervation pattern with sensory nerve fibers containing SP and CGRP demonstrated neurogenic inflammation. Extensive edema and cellular infiltrations were found in AR. A decreased presence of eosinophils and nitric oxide was observed in IR. Conclusions. On the ultrastructural level, AR and IR showed many similarities but also some differences. Based on these findings, anti-inflammatory therapy could be recommended for both types of rhinitis.

Die Pathophysiologie der allergischen (AR) und idiopathischen Rhinitis (IR) ist bis heute nicht vollständig geklärt. Die AR und die IR sind gekennzeichnet durch eine zugrunde liegende nasale Hyperreaktivität. Ziel der Untersuchung war die Suche nach pathomorphologischen Veränderungen der Nasenschleimhaut bei diesen verschiedenen Rhinitisformen.

MAB3-PD-01 Session Title: Occupational Health (II) Introduction: Livestock-based industries are key economic drivers in Mongolia. Mongolian leather tanneries process 30,000 hides per day. Although regulatory standards exist for this industry, rapid growth in production has fueled concerns about its impact on worker and community health. In 2005, we conducted a pilot investigation of chromium levels among tannery workers and environmental samples from an urban area with high tannery density. Methods: Urine samples were collected from: 51 tannery workers (42 line workers, 9 managers), 32 workers from the industrial pre-treatment plant and the central sewage treatment plant (WWTP workers), and 28 control workers (garment factory, office workers). Samples were collected in acid-cleaned polyethylene bottles, microwave digested, and analyzed for total chromium by AAS (Zeeman 4100ZL, Perkin Elmer, Norwalk, CT). Environmental samples included 11 water and 3 sediment samples from a major river receiving tannery and sewage plant effluent, and 17 wastewater and 6 sludge samples from the 2 WWTPs. Samples were collected in acid-cleaned bottles, microwave digested, and analyzed for total chromium by ICP-AES (Perkin Elmer Optima 3000). Quality control samples included field and laboratory blanks. Statistical analyses were conducted in SAS 9.1 (SAS Institute, Cary, NC). Results: Mean chromium in the field blanks (n = 3) was 6 μg/L; results were blank corrected. Urinary chromium differed significantly among tannery, WWTP, and control workers (Kruskal Wallis P = 0.0004), with 95th percentile concentrations of 18.4 μg/L (tannery), 6.9 μg/L (WWTP), and 10.5 μg/L (control). Among tannery workers, urinary chromium did not differ significantly by job description (Wilcoxon Rank Sum P = 0.1816). Blank correction and method of handling below LOD values did not change test outcomes. Mean chromium was 6208 mg/kg in central WWTP sludge and 5430 mg/kg in pre-treatment plant sludge. Mean levels in wastewater sampled August 2005 from the pre-treatment plant were 1184 mg/L before and 29 mg/L after treatment (removal efficiency ∼97.5%). Removal efficiency dropped to 58% during peak tannery production (November to March). Pre-treatment plant effluent exceeded the Mongolian national standard (5 mg/L) regardless of season. Chromium was not detected in river water samples, and ranged from 15 to 64 mg/kg in sediment samples downstream from the central WWTP outfall. Conclusion: This is the first study to collect data on chromium exposures in the Mongolian leather tanning industry. Biologic sampling showed tannery workers have higher chromium exposures than other workers. High levels of urinary chromium among control workers was surprising; follow-up studies are currently underway.

P-354 Introduction: We are investigating the validity of using urinary biomarkers to estimate dietary exposures to pyrethroid and organophosphate pesticides in a pilot sample of adult volunteers (n = 11) from a large urban area of the United States. This information is needed to help determine the most accurate way of measuring exposures to non-persistent pesticides among the general adult population. Methods: We collected four consecutive days of duplicate diet samples and 10 spot urine samples from each subject. First morning void and before bedtime spot urine samples were collected on each day of diet sampling. Additional spot urines were collected the night before the first day of diet sampling and the morning after the last day of diet sampling. Detailed diet information including food description, organic status, preparation details (e.g. raw vs. cooked, peeled vs. unpeeled, etc.) and weight (in grams) was collected for each item consumed over the four-day sampling period. The four-day protocol was repeated twice for each subject, once in summer (July–October 2005) and once in winter (January–March 2006), to examine seasonal differences. Urine samples are currently being analyzed for selected pyrethroid and organophosphate metabolites while method development is underway for quantifying parent pesticide residues in the duplicate diet samples. Results: We present findings on intra- and inter-subject variability in urinary metabolite concentrations across the four-day sampling period, and across the summer and winter sampling cycles. We also present results of multivariate longitudinal regression analyses to determine which food items are most significantly associated with urinary metabolite concentrations among subjects in our pilot sample. Discussion/conclusions: This is the first study we know of to date to measure food intake and urinary pyrethroid and organophosphate metabolites in a multi-day longitudinal sample of non-occupationally exposed adults. For food intakes showing no association, alternative strategies for measuring dietary exposure to non-persistent pesticides must be considered. For those displaying significant association, urinary levels offer a valid tool for estimating dietary exposures among similar adult populations. This study will also provide important reference data on short-term temporal variability in urinary pyrethroid and organophosphate metabolite concentrations among U.S. adults.

Radiosurgery (RS) is a noninvasive, ambulatory special neurosurgical procedure for the treatment of vestibular schwannoma (VS). We treated 123 patients with unilateral schwannomas between 1994 and 2000 at the gamma knife (GK) center in Munich using a primary stereotactic procedure. These patients were followed up until June 2004 in respect to audiological, neurological, neurootological and radiological features before and after radiosurgical intervention. The actual tumor control rate of 8.2 years (mean) after GK surgery for all patients and a single treatment was calculated to be 96.7%. The impairment of hearing was on average 18% after GK, ranking from 0% gain of hearing loss up to 90%. Facial nerve function, graded according to the House-Brackmann scale, deteriorated in none of the patients; 5.8% reported a trigeminal neuralgia. Tinnitus developed in 4.1% of the patients after RS; 13.3% had vertigo for the first time after the treatment, age apparently being a predisposing factor. Radiosurgical treatment for VS is an alternative to microsurgery (MS). It is associated with a lower rate of facial and trigeminal neuropathy, postoperative complications and hospital stay. The hearing preservation rate is equivalent to MS.

BACKGROUND:Long-term abuse of decongestive nasal drops causes rhinitis medicamentosa due to cytotoxic and ciliary-toxic effects. Nasal obstruction is caused by rebound swelling when the decongestive effect has disappeared. The patient starts using nasal drops more frequently as a result of tachyphylaxis.PATIENTS AND METHODS:Tissue samples from human inferior turbinates from 22 patients who had overused decongestive nose drops were taken during nasal surgery and preserved in phosphate-buffered paraformaldehyde or glutaraldehyde. Ultrathin sections were cut. The samples were dehydrated and embedded in Araldit. The findings were photo-documented using a light- and transmission electron microscope. Biopsies from ten patients without chronic inflammation of the nasal mucosa were used as controls.RESULTS:The electron microscopic investigations revealed epithelium showing severe damage corresponding to regions with hyperplastic and metaplastic changes. Loss of ciliated cells was observed. Under a thick basal membrane, ultrastructural changes to the endothelial lining, such as openings and rupture of the basal lamina, were detected. Prominent endothelial cells were conspicuous.CONCLUSIONS:Rhinitis medicamentosa is a drug-induced injury to human nasal mucosa associated with the prolonged abuse of topical nasal decongestants. Loss and destruction of ciliated epithelial cells are the morphological correlation to the disturbance of mucociliary clearance. Endothelial cells of capillaries, in particular, revealed ultrastructural changes indicative of increased permeability with consecutive interstitial edema.

OBJECTIVE: Nasal vasculature and seromucous glands are exposed to complex mechanisms influenced by external as well as internal stimuli. In addition to classic and peptidergic neurotransmitters, nitric oxide (NO) was increasingly found to be important in the control of various physiologic functions. NO modulates nasal immunology, influences macrophage activity, and has antiviral and bacteriostatic properties. The aim of this study was to show the localization of nitric oxide synthases (NOS) I and III in the normal human nasal mucosa by using immunoelectron microscopical techniques.STUDY DESIGN: Specimens of noninflammed inferior turbinates from 35 patients who underwent nasal surgery were fixed in phosphate-buffered glutaraldehyde. After dehydration, incubation in unicryl and polymerization, ultrathin sections were cut. Primary antibodies against NOS I and III were applied and the immunocomplexes were visualized by an immunocytochemical staining-technique using gold-labeled antibodies. Immunostained structures were photodocumented using a transmission electron microscope.RESULTS: NOS-immunoreactive nerve fibers were mainly co-located in parasympathetic nerves in the adventitia of arterial vessels and in periglandular axons. Electron microscopy showed that NOS-positive axons were in close contact with acinus cells. A strong NOS III-immunoreactivity was found in endothelial cells of capillaries near the glands as well as in arterial vessels. Furthermore, immunoreaction products were deposited throughout the cytoplasm of fibroblasts.CONCLUSION: Nitric oxide in nerve fibers, seromucous glands, and endothelial cells of capillaries and arterial vessels suggest that NO takes part in the regulation of physiologic processes of the human nasal mucosa. NOS was co-localized in parasympathetic nerves and plays a role in the neurotransmission and neuromodulation of the vascular tone and glandular secretion. Arteries showed a distinctly developed nitrergic innervation and endothelial accumulation. The NO production in axons of the adventitia and in the endothelium of arteries demonstrated that these vessels are influenced by a dual NO system. NO could mainly act on these structures with vasodilatatory effects. Finally, NO would be able to influence the functions of perivascular fibroblasts.

Die respiratorische Nasenschleimhaut hat im Rahmen der Atemluftkonditionierung Klimatisierungsfunktionen zu erfüllen. Der nasale Zyklus bzw. pathologische Funktionszustände des endonasalen Schwellgewebes bestimmen die Durchgängigkeit der nasalen Atemluftpassage. Die Sekretion der seromukösen Drüsen ermöglicht die Befeuchtung der Atemluft und bildet eine wesentliche Voraussetzung für den mukoziliaren Transport. Diese physiologischen Mechanismen unterliegen einer nervalen Kontrolle. Neben den klassischen Neurotransmittern des vegetativen Nervensystems sind Neuropeptide wie VIP, CGRP, SP und NPY sowie Stickstoffmonoxid an den nervalen Kontrollmechanismen beteiligt. Ein Netzwerk aus sensorischen, sympathischen und parasympathischen Nervenfasern stellt den Schutz vor externen und internen Schleimhautirritationen sicher. Blutgefäße und Drüsen unterliegen darüber hinaus dem Einfluss von endothelialen und humoralen Faktoren. Bei verschiedenen Rhinopathien bestimmen sensorische Neuropeptide sowie einige Entzündungsmediatoren den pathophysiologischen Verlauf und können zu einer neurogenen Entzündung der Nasenschleimhaut führen.

Respiratory nasal mucosa fulfils the function of pretreating the inspired air. The periodic nasal cycle and pathologic functional disturbances of the endonasal tissue influence the nasal passages. The secretion of the seromucous glands and extravasation from the blood vessels are essential for mucocilliary transport. These physiological mechanisms are partially controlled by neural regulation. Besides classic neurotransmitter neuropeptides such as VIP, CGRP, SP and NPY, nitric oxide also shares this role. A network of sensory, sympathetic and parasympathetic nerve fibres protects the respiratory mucous membranes from external and internal irritation. In addition, blood vessels and glands are influenced by endothelial and Immoral factors. For the different types of rhinitis, sensory neuropeptides and inflammatory mediators take part in the patho-mechanisms and can lead to a so called neurogenic inflammation of the nasal mucosa.

Respiratory nasal mucosa fulfils the function of pretreating the inspired air. The periodic nasal cycle and pathologic functional disturbances of the endonasal tissue influence the nasal passages. The secretion of the seromucous glands and extravasation from the blood vessels are essential for mucocilliary transport. These physiological mechanisms are partially controlled by neural regulation. Besides classic neurotransmitter neuropeptides such as VIP, CGRP, SP and NPY, nitric oxide also shares this role. A network of sensory, sympathetic and parasympathetic nerve fibres protects the respiratory mucous membranes from external and internal irritation. In addition, blood vessels and glands are influenced by endothelial and humoral factors. For the different types of rhinitis, sensory neuropeptides and inflammatory mediators take part in the pathomechanisms and can lead to a so called neurogenic inflammation of the nasal mucosa.

BACKGROUND:The functions of the nasal mucosa are regulated by numerous endogenous and exogenous influences. The innervation patterns are important for the control of the physiological nasal functions. In addition to the classic neurotransmitters different neuropeptides might play a regulating and modulating role in the nasal mucosa. Both the significance and the localization of neuropeptide Y (NPY) have not been fully elucidated.PATIENTS AND METHODS:Tissue samples of human inferior turbinates from 42 patients were taken during nasal surgery and preserved in phosphate-buffered paraformaldehyde or glutaraldehyde. Serial sections were incubated with antibodies against NPY and the ABC method was applied. In order to identify immunoelectron microscopic reactions a streptavidin-gold-marker was used. The findings were photodocumented by using a light- and transmission-electron microscope.RESULTS:NPY-positive terminals were mainly located in the adventitia of arterial vessels. There were also NPY-immunoreactive arterioles near to the glands. Periglandular a lower density of immunoreactions could be observed. NPY-positive fibers could be detected in the subepithelial connective tissue and at the glandular ducts. Immunoelectron microscopy revealed NPY within periglandular axons.CONCLUSIONS:Immunohistochemical and immunoelectron microscopical methods allow a detailed identification of the sympathetic cotransmitter NPY in arterial vessels of nasal mucosa in man. These results indicate that NPY-containing nerve fibers innervate arteries as well as nasal glands. These findings suggest that NPY play a significant role as a neuromodulator in the control of both vasculature and glandular secretion. The localisation of NPY in periglandular and periductal nerves confirms the direct influence of glandular functions. NPY-agonists may be a beneficial additional treatment of rhinopathies to reduce nasal obstruction and mucus secretion.

Background: Nasal vasculature and seromucous glands are exposed to complex mechanisms influenced by external as well as internal stimuli. In addition to classic and peptidergic neuro-transmitters, Nitric oxide (NO) was increasingly found to be important in the control of various physiological functions. NO regulates nasal immunology, influences macrophages activity and has antiviral and bacteriostatic properties. The aim of this study was to detect the localization of nitric oxide synthases (NOS) I and Ill in the normal human nasal mucosa with immunoelectron microscopical techniques. Methods: Specimens of non-inflamed inferior turbinates from 35 patients who required nasal surgery were fixed in phosphate-buffered glutaraldehyde. After dehydration, incubation in unicryl and polymerization ultrathin sections were cut. Primary antibodies against NOS I and Ill were applied and the immunocomplexes were visualized by an immunocytochemical staining-technique using a gold-labeled antibody. Immunostained structures were photodocumented by using a transmission electron microscope. Results: NOS-immunoreactive nerve fibers were mainly colocated in parasympathetic nerves in the adventitia of arterial vessels and in periglandular axons. Electron microscopy showed that NOS-positive axons were in close contact with acinus cells. A strong NOS III-immunoreactivity was found in endothelial cells of capillaries near the glands as well as in arterial vessels. Furthermore, immunoreaction products were deposited throughout the cytoplasm of fibroblasts. Conclusions: Nitric oxide in nerval fibers, seromucous glands and endothelial cells of capillaries and arterial vessels suggests that NO takes part in the regulation of physiological processes of the human nasal mucosa. NO was colocalized in parasympathetic nerves and plays a role in the neurotransmission and neuromodulation of the vascular tone and glandular secretion. Arteries showed a distinctly developed nitric innervation and endothelial accumulation. The NO production in axons of the adventitia and in the endothelium of arteries demonstrated that these vessels are influenced by a dual NO system. Mainly NO could act on these structures with vasodilatatory effects. Finally NO would be able to influence the functions of perivascular fibroblasts.

BACKGROUND:Nasal vasculature and seromucous glands are exposed to complex mechanisms influenced by external as well as internal stimuli. In addition to classic and peptidergic neurotransmitters, Nitric oxide (NO) was increasingly found to be important in the control of various physiological functions. NO regulates nasal immunology, influences macrophages activity and has antiviral and bacteriostatic properties. The aim of this study was to detect the localization of nitric oxide synthases (NOS) I and III in the normal human nasal mucosa with immunoelectron microscopical techniques.METHODS:Specimens of non-inflamed inferior turbinates from 35 patients who required nasal surgery were fixed in phosphate-buffered glutaraldehyde. After dehydration, incubation in unicryl and polymerization ultrathin sections were cut. Primary antibodies against NOS I and III were applied and the immunocomplexes were visualized by an immunocytochemical staining-technique using a gold-labeled antibody. Immunostained structures were photodocumented by using a transmission electron microscope.RESULTS:NOS-immunoreactive nerve fibers were mainly colocated in parasympathetic nerves in the adventitia of arterial vessels and in periglandular axons. Electron microscopy showed that NOS-positive axons were in close contact with acinus cells. A strong NOS III-immunoreactivity was found in endothelial cells of capillaries near the glands as well as in arterial vessels. Furthermore, immunoreaction products were deposited throughout the cytoplasm of fibroblasts.CONCLUSIONS:Nitric oxide in nerval fibers, seromucous glands and endothelial cells of capillaries and arterial vessels suggests that NO takes part in the regulation of physiological processes of the human nasal mucosa. NO was colocalized in parasympathetic nerves and plays a role in the neurotransmission and neuromodulation of the vascular tone and glandular secretion. Arteries showed a distinctly developed nitric innervation and endothelial accumulation. The NO production in axons of the adventitia and in the endothelium of arteries demonstrated that these vessels are influenced by a dual NO system. Mainly NO could act on these structures with vasodilatory effects. Finally NO would be able to influence the functions of perivascular fibroblasts.

The functions of the nasal mucosa are regulated by numerous endogenous and exogenous influences. The innervation patterns are important for the control of the physiological nasal functions. In addition to the classic neurotransmitters different neuropeptides might play a regulating and modulating role in the nasal mucosa. Both the significance and the localization of neuropeptide Y (NPY) have not been fully elucidated.Tissue samples of human inferior turbinates from 42 patients were taken during nasal surgery and preserved in phosphate-buffered paraformaldehyde or glutaraldehyde. Serial sections were incubated with antibodies against NPY and the ABC method was applied. In order to identify immunoelectron microscopic reactions a streptavidin-gold-marker was used. The findings were photodocumented by using a light- and transmission-electron microscope.NPY-positive terminals were mainly located in the adventitia of arterial vessels. There were also NPY-immunoreactive arterioles near to the glands. Periglandular a lower density of immunoreactions could be observed. NPY-positive fibers could be detected in the subepithelial connective tissue and at the glandular ducts. Immunoelectron microscopy revealed NPY within periglandular axons.Immunohistochemical and immunoelectron microscopical methods allow a detailed identification of the sympathetic cotransmitter NPY in arterial vessels of nasal mucosa in man. These results indicate that NPY-containing nerve fibers innervate arteries as well as nasal glands. These findings suggest that NPY play a significant role as a neuromodulator in the control of both vasculature and glandular secretion. The localisation of NPY in periglandular and periductal nerves confirms the direct influence of glandular functions. NPY-agonists may be a beneficial additional treatment of rhinopathies to reduce nasal obstruction and mucus secretion.

Background: The swelling mechanism of human nasal mucosa is based on a complicated vascular system and regulated by a variety of classical and peptidergic transmitters as well as by endothelial transmitters. The aim of this study was to elucidate this mechanism taking into account the distribution of these substances and the morphology of the different vessels.Methods: Tissue specimens of human inferior turbinates were evaluated by light and electron microscopy. We used frozen sections to localize enzymes of the transmitter synthesis by histochemical and immunocytochemical methods. The distribution of classical neurotransmitters, neuropeptides (calcitonin-gene-related-peptide, neuropeptide Y, substance P and vasoactive intestinal polypeptide), enzymes producing neuronal NO (neuronal nitric oxide synthase, nicotine-amid-adenine-dinucleotide-phosphate-diaphorase) as well as endothelial transmitters such as endothelin and endothelial nitric oxide were examined. For ultrastructal examination the specimens were fixed in glutaraldehyde und osmium tetroxide, embedded in araldide, cut and double contrasted.Results: Most of the axons and immunoreactivity of transmitters were located in the arterial part of the human nasal vascular system. In venous vessels only a spare innervation was observed, whereas in the subendothelial muscular bolsters of the cushion veins a rich nerve supply could be detected. Near the fenestrated subendothelial and periglandular capillaries no axons were found. Nasal vasculature is supplied by a equilibrated aminergic and cholinergic innervation. Mainly arterial vessels showed reactions to antibodies directed against endothelial transmitters.Conclusion: Because of the dense innervation of arteries and subendothelial venous muscular bolsters we conclude that the swelling mechanism of human nasal mucosa is mainly regulated by these structures. A dual (endothelial and neuronal) control exists in arterioles whereas the control in the subendothelial muscular swellings of the cushion veins appears to be mainly neuronal. The swelling of the nasal mucosa is achieved by an simultaneous relaxation of all smooth muscle cells, which leads to dilatation of arteries as well as venous sinuses. The drainage of the vascular bed is reduced by the venous muscular bolsters protruding into the lumen of the venous sinuses. Vice versa, a contraction of all smooth muscle cells leads to a contraction of the arteries and, consecutively, to a reduction of blood supply. Simultaneously the muscular bolsters are torn out of the lumen of venous sinusoids allowing blood drainage to be increased: nasal concha decongests.

Background: In middle Europe the prevalence of allergic rhinitis is up to 15% to 25%. Allergic rhinitis is characterised by an inflammation of the nasal mucosa induced by different allergens. The patients suffer from symptoms like sneezing, rhinorrhea and nasal airway obstruction caused by morphological changes of the nasal mucosa. This symptomatology is considered to be a result of accumulation and activation of inflammatory cells. Further some neuropeptides like Calcitonin Gene Related Peptide (CGRP) and Substance P (SP) play an additional role in pathophysiology of allergic rhinitis.Patients and Methods: Tissue samples from 28 human turbinates of patients with perennial rhinitis were taken during nasal surgery and preserved in phosphate-buffered glutaraldehyde or paraformaldehyde. Ultrathin sections were cut. The samples were dehydrated and embedded in Araldit. After polymerization an immunocytochemical staining-technique using a gold-labeled antibody was carried out. Immunostained structures were photodocumented by using a transmission electron microscope.Results: In the lamina propria mucosae an extensive edema and several inflammatory cells like lymphocytes, plasma cells, eosinophiles and macrophages was found. The capillaries showed an activated endothelium. Immunoreactive nerve fibers were found in the periglandular tissue around the acini, ducts and in the glandular connective tissue. Neuroglandular synapses with dense core vesicles and positive immunoreactions to CGRP and SP could be detected. Neuropeptidergic axons were often observed near to plasma cells.Conclusions: In the edematous nasal mucosa an infiltration with different inflammatory cells was found. Using electron microscopical techniques nerval structures near the submucosal glands could be demonstrated. Immunoreactions to the neuropeptides CGRP and SP were detected in the periglandular nerves and in neuroglandular synapses. These findings demonstrate the direct nerval control of glandular functions in allergic rhinitis. CGRP is generally known to have a vasodilatatory effect and to stimulate the secretion of nasal seromucous glands. In addition, SP as a short-acting vasodilatator may induce vascular permeability and glandular secretion. These immunoelectron microscopical findings further elucidate pathomorphological mechanisms in allergic rhinitis.

BACKGROUND:Cystic fibrosis (CF) is an inherited multisystemic disorder that results in generalized dysfunction of exocrine glands. In patients with cystic fibrosis dyscrinia with affection of exocrine glands function is a main problem of the upper and lower respiratory tract. In addition to chronic obstructive pulmonary disease, chronic sinusitis, nasal polyposis and hypertrophy of inferior turbinates with nasal airway obstruction are typical signs. To understand pathophysiological mechanisms in CF and to correlate morphological findings with clinical symptoms, investigations of nasal mucosa are important.METHODS:Tissue samples of inferior turbinates were taken during nasal surgery from 7 children, ranging from 3 to 11 years of age between September 1998 and May 2000. Histological sections were cut followed by a light- and electron microscopical examination (EM 902 A Zeiss). Additionally, specimens of duodenal mucosa were investigated.RESULTS:In comparison with sections of normal nasal mucosa the lamina propria mucosae shows different morphological changes. Under a thick layer of respiratory epithelium with a high portion of goblet cells and particulary vacuoles there is an edematous subepithelial area. The capillary layer is reduced and the seromucous glands show an atypical morphological structure with widely mucous cells and cystic dilatation. On an ultrastructural level the glandular cells show atypical and inhomogeneous glandular droplets in the supranuclear cell portion. A viscous secretion was detectable at the glandular lumen. The nucleus contains dispersed chromatin as a sign of increased activity and the structures of Golgi apparatus were obviously detectable.CONCLUSIONS:In respective literature studies on the different morphological changes on light- and electron microscopical level in CF-associated rhinopathies are rare. This histological study demonstrated various morphological changes of nasal mucosa and shows a correlation between the glandular dysfunction and the typical symptoms in CF. Additionally a comparison with ultrastructural findings of CF-enteropathies is proposed. These findings could help to look at new aspects in the pathophysiology for patients with CF.