[Prolactinoma of the sphenoid sinus. Case report and literature review]. / Prolaktinom der Keilbeinhöhle. Kasuistik und Literaturübersicht.

In this case study, we report on a patient complaining of headache who, after CT and MRI, was found to have a neoplasia of the left sphenoid sinus. After a transnasal biopsy and histological examination, a prolactinoma was diagnosed. Based on this case, we discuss important aspects of tumor biology, diagnostic procedures, histology as well as differential diagnosis. Prolactinoma has to be considered as a differential diagnose in all sphenoid sinus neoplasias with close contact to the pituitary gland.

[Ultrastructural localization of nitric oxide synthase (NOS I and III) in human nasal mucosa]. / Immunelektronenmikroskopische Lokalisation von NOS I und NOS III in der menschlichen Nasenschleimhaut.

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.

[Immunoelectron microscopic findings in patients with allergic rhinitis]. / Immunelektronenmikroskopische Untersuchungen bei Rhinitis allergica.

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 nerve 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 nerve 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.

[Morphological changes of nasal and duodenal mucosa in patients with cystic fibrosis]. / Elektronenmikroskopische Befunde der Nasen- und Dünndarmschleimhaut bei der Zystischen Fibrose.

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.

[Electron microscopic studies of the rabbit nasal mucosa after short-term application of naphzoline nitrate]. / Elektronenmikroskopische Untersuchungen der Nasenschleimhaut des Kaninchens nach kurzzeitiger Applikation von Naphazolinnitrat.

BACKGROUND: Vasoconstricting nasal drops are applied frequently. Especially early ultrastructural alterations of the vessels were not examined up to now in animal models. Our goal was the systematic investigation of the submucosal vessels and the epithelium after topic application of naphazoline nitrate (Privin) in an animal model. METHODS: Three times daily over 6 days 3 ml of 0.1% naphazoline nitrate solution (Privin) were instilled into the right nasal cavity of 5 rabbits. At the 7th and 14th day an incisional biopsy of the lower nasal turbinate was carried out in ketamine/rompun anesthesia. RESULTS: In the naphazoline group the capillaries showed an edematous endothelium with narrowed lumina. Thrombosis of the arterioles were frequently observed. The more cubic epithelial cells had deciliated areas with microvilli. Venules, submucosal glands and the surrounding connective tissue was normally configurated. Analogous findings were also observed after 2 weeks. CONCLUSIONS: The disturbance of the microcirculation shows impressive endothelial alterations. These structural changes can result in nonreversible mucosal damages. A regeneration time of more than 1 week is assumable. Our results should be considered critically in order to prevent damages of the nasal mucosa.

[Ames test as biomarker]. / Der Ames-Test als Biomarker.

BACKGROUND AND OBJECTIVE: The incidence of squamous cell carcinomas in the upper aerodigestive tract has increased worldwide. The main risk factors are chronic tobacco and alcohol consumption. The detection of high-risk persons is important because early diagnosis of these tumors provides a good chance for permanent healing. Biomonitoring programs may help to give precise information about the individual cancer risk among smoking and drinking persons. The aim of this study was to evaluate the Ames test as a biomarker to detect the genotoxicity of saliva. PATIENTS AND METHODS: Saliva specimens of 131 probands were investigated for their genotoxic effects using the Ames test. RESULTS: Our results showed an increased trend of genotoxic activity in the saliva of smokers. A highly significant additional increase of genotoxicity was measured in smoking and drinking individuals. CONCLUSIONS: Our study shows that the Ames test could be used to show genotoxic effects in saliva specimens. In combination with other biomarkers, this test may help to develop a valid concept for detecting cancer-endangered people.

[Basic classical, peptidergic and nitrergic innervation pattern of human nasal glands--a histochemical and immunohistochemical study]. / Die klassisch-vegetative, peptiderge und nitrerge Innervation der Drüsen der menschlichen Nasenschleimhaut1.

BACKGROUND: Seromucous glands are important components of the human nasal mucosa. The innervation patterns are relevant for understanding the control of the different physiological and pathophysiological glandular functions. Beside classic neurotransmitters some neuropeptides seem to influence the glandular secretion. METHODS: Tissue samples of 35 human inferior turbinates were taken during nasal surgery and preserved. Serial cryosections or paraffin sections were cut and incubated with antibodies either to Tyrosinhydroxilase or to Vasoactive Intestinal Peptide (VIP), Calcitonin Gene-Related Peptide (CGRP) and endothelial or brain Nitric Oxide Synthase (eNOS or bNOS). AChE- and NADPH-diaphorase-histochemistry were performed. RESULTS: Immunoreactive nerve fibers were found in the periglandular tissue around the acini, ducts and in the periglandular connective tissue. The density of positive immunoreactive structures depended on the different antibodies. VIP was found in contact to acinus cells, CGRP in the connective tissue around glandular cells. Particular immunoreactions to VIP and CGRP-antibodies could be detected near the glandular duct system. The eNOS-reactions were found in small capillaries near the acinus cells. CONCLUSIONS: Immunohistochemical and histochemical methods allow a detailed marking of nerval structures in nasal mucosa. The localization of neurons with different neurotransmitters and neuropeptides in the periglandular tissue confirms the direct nerval control of the diverse glandular functions. The detection of bNOS- and NADPH-d-positive structures around glandular cells and eNOS in the endothelium of periglandular capillaries suggests that NO takes an additional part in the regulation of nasal glands.

[Endoscopic treatment of iatrogenic esophageal perforation]. / Endoskopische Behandlung einer iatrogenen Osophagusperforation.

BACKGROUND: Esophageal perforations are the most frequent complications of endoscopy of the upper gastrointestinal tract. Life-threatening consequences such as mediastinitis, septic disease, or multiple organ failure are possible. Traditional surgical and conservative methods of treatment should be distinguished. In serious cases, thoracotomy in particular is a high-risk operation. PATIENTS AND RESULTS: This case demonstrates the successful endoscopic treatment of an esophageal perforation with mediastinal empyema by fibrin gluing. CONCLUSIONS: Esophageal perforations up to 20 cm aboral and a maximum diameter of 1.5 cm could be treated by rigid endoscopical fibrin gluing. High-risk patients could be managed effectively avoiding extensive surgery.

Gelatin sponge-supported histoculture of human nasal mucosa.

Considerable progress has recently been made in the understanding of airway inflammation by cell culture assays and in vivo provocation studies. Inasmuch as ethical considerations limit experimental work in humans, physiologically relevant in vitro models are required to better understand cellular and molecular tissue interactions in human nasal mucosa. Here we describe a human nasal mucosa culture model utilizing a simple gelatin sponge-supported histoculture system at the air-liquid interface. Viable mucosa was preserved for at least 48 h, as shown by morphology and immunohistochemical staining with Ki-67 as marker for proliferation. Pro-inflammatory mediators (kinins, histamine, thromboxane B2, prostaglandin F2 alpha, and substance P) are detectable in serum-containing as well as serum-free culture medium. Incubation with 10(-8) M substance P increases the number of degranulated mast cells after 48 h by 26% (P < 0.01). In this model, biochemical responses can be correlated with histologic alterations of the target tissue. Inflammatory parameters can be examined and compared in various patient groups and different stimulators/inhibitors. This culture method provides a valuable research tool for analyzing all compartments present in nasal mucosa under physiologically relevant conditions, and for studying complex interactions and responses of mucosal cell populations in their natural tissue environment.

[Intraepithelial mast cells in the vocal cords and nasal mucosa]. / Intraepitheliale Mastzellen in der Stimmlippenund Nasenschleimhaut.

Leukocytes and mast cells have been described in the human nasal mucosa and epithelium of the lower airways (Bonneville 1988, Goodman and Lefrancois 1989, Guy-Grand 1991, Denburg 1992). In mast cells, heterogeneity of mucosal and connective tissue mast cells has been observed. In the present electron microscopic study, the epithelium of the upper airways (larynx and nose) of patients, suffering from chronic laryngitis, was examined with special regard to intraepithelial mast cells. Numerous mast cells were found in the stratum spinosum of the true vocal cords showing extensive elongated surface folds that had little contact to epithelial cells. Desmosomes were absent. Mucosal mast cells are characterised by four types of membrane-bounded granules, whereas serosal mast cells only showed two different types of granules and resembled blood basophiles. Migration of connective tissue mast cells into the epithelium could not be observed. According to our findings, mucosal and serosal mast cells belong to different cell lines.

Electron and fluorescence microscopic investigations on composition and structure of the epithelial basement membrane of the human inferior nasal concha.

Light and electron microscopic as well as immunohistochemical investigations were performed on the basement membrane (BM) of the nasal mucosa from the inferior nasal conchae of 20 patients, aged 15-50 years. Two of the patients served as controls. Clinical disorders requiring the turbinectomies were hyperplastic nasal inferior conchae (17 patients) and immobile cilia syndrome (1 patient). In all cases light microscopy demonstrated a 10-15 microns thick homogeneous BM underneath an intact epithelium. Electron microscopic findings revealed a typical subepithelial basal lamina (BL). The remaining parts of the BM consisted of single, isolated 25-mm-thick collagenous fibrils. Only a few cells and small unmyelinated nerves occurred in this layer. Immunohistochemical investigations showed BL components (collagen type IV, laminin, nidogen and heparan sulfate proteoglycan) directly underneath the epithelium. Collagen types I, III, V, and VI could also be demonstrated immunohistochemically in the remaining parts of the BM. Collagen type VII was allocated to the anchor filaments beneath the BL. This special BM is presumed to contribute to mechanical stabilization of the epithelium. The significance of the BL and the subepithelial connective tissue for the behavior of the epithelium--e.g. direction of differentiation--are discussed.