Cats with diabetes mellitus have diastolic dysfunction in the absence of structural heart disease.

Diabetes mellitus (DM) can result in cardiovascular dysfunction and heart failure characterized by diastolic dysfunction with or without the presence of systolic dysfunction in people and laboratory animals. The objective of this prospective study was to determine if cats with newly diagnosed DM had myocardial dysfunction and, if present, whether it would progress if appropriate antidiabetic therapy was commenced. Thirty-two diabetic cats were enrolled and received baseline echocardiographic examination; of these, 15 cats were re-examined after 6 months. Ten healthy age- and weight-matched cats served as controls. Diabetic cats at diagnosis showed decreased diastolic, but not systolic function, when compared to healthy controls, with lower mitral inflow E wave (E) and E/E' than controls. After 6 months, E and E/IVRT' decreased further in diabetic cats compared to the baseline evaluation. After excluding cats whose DM was in remission at 6 months, insulin-dependent diabetic cats had lower E, E/A and E' than controls. When classifying diastolic function according to E/A and E'/A', there was shift towards impaired relaxation patterns at 6 months. All insulin-dependent diabetic cats at 6 months had abnormal diastolic function. These results indicate that DM has similar effects on diastolic function in feline and human diabetics. The dysfunction seemed to progress rather than to normalize after 6 months, despite antidiabetic therapy. In cats with pre-existing heart disease, the development of DM could represent an important additional health risk.

Use of an implantable pump for controlled subcutaneous insulin delivery in healthy cats.

The aim of this study was to examine the safety and reliability of a research-grade implantable pump for controlled delivery of insulin glargine in cats. For this purpose, a small telemetrically controlled drug delivery pump with a refillable reservoir was implanted into the subcutaneous tissues of the dorsal neck in 10 clinically healthy cats. The reservoir was filled with insulin glargine, and the pump was programmed to deliver four boluses of 0.25 IU/kg, 2-3 weeks apart. As a control, insulin glargine (0.25 IU/kg) was injected SC. Blood glucose and plasma insulin glargine concentrations were measured before each bolus and SC injection and for 8 h afterward. Cats were monitored for signs of discomfort. Pumps were easily implanted and well tolerated by all cats. The experiment was completed in five of 10 cats. In four, the pump failed because of technical reasons; another cat developed severe hypoglycaemia attributable to insulin leakage. Overall, plasma insulin glargine increased after six of eight (75%) initial boluses and after one of 16 (6%) successive boluses. Glucose decreased after seven of eight (88%) initial boluses and after four of 16 (25%) successive boluses. Only the first bolus significantly increased plasma insulin glargine (P = 0.008) and decreased glucose (P = 0.008). Of 20 SC injections, 10 (50%) increased plasma insulin glargine (P <0.001) and 12 (60%) decreased glucose (P <0.001). The pump did not cause discomfort in cats, but life-threatening hypoglycaemia occurred in one. Frequent device problems suggest that the pump needs improvements. Because successive boluses did not increase plasma insulin glargine, this type of insulin may not be appropriate with the pump.

Effect of the Glucagon-like Peptide-1 Analogue Exenatide Extended Release in Cats with Newly Diagnosed Diabetes Mellitus.

BACKGROUND: Exenatide extended release (ER) is a glucagon-like peptide-1 analogue that increases insulin secretion, inhibits glucagon secretion and induces satiation in humans with type 2 diabetes mellitus. The use of exenatide ER is safe and stimulates insulin secretion in healthy cats. OBJECTIVES: The objective of this study is to assess the safety of exenatide ER and its effect on body weight, remission and metabolic control in newly diagnosed diabetic cats receiving insulin and a low-carbohydrate diet. ANIMALS: Thirty client-owned cats. METHODS: Prospective placebo-controlled clinical trial. Cats were treated with exenatide ER or 0.9% saline, administered SC, once weekly. Both groups received insulin glargine and a low-carbohydrate diet. Exenatide ER was administered for 16 weeks, or in cats that achieved remission it was given for 4 weeks after discontinuing insulin treatment. Nonparametric tests were used for statistical analysis. RESULTS: Cats in the exenatide ER and placebo groups had transient adverse signs including decreased appetite (60% vs. 20%, respectively, P = .06) and vomiting (53% vs. 40%, respectively, P = .715). Body weight increased significantly in the placebo group (P = .002), but not in cats receiving exenatide ER. Cats on exenatide ER achieved remission or good metabolic control in 40% or 89%, respectively, whereas in control cats percentages were 20% or 58% (P = .427 and P = .178, respectively). CONCLUSION AND CLINICAL IMPORTANCE: Exenatide ER is safe in diabetic cats and does not result in weight gain. Our pilot study suggests that, should there be an additional clinically relevant beneficial effect of exenatide ER in insulin-treated cats on rate of remission and good metabolic control, it would likely approximate 20% and 30%, respectively.

Measured versus simulated dietary pesticide intakes in children.

Children's dietary pesticide intakes can be measured directly through duplicate diet samples, but instead are frequently estimated using national residue data. We compared organophosphorus and pyrethroid pesticide intakes from conventional fruit, fruit juices and vegetables measured for two cohorts of children aged 3-11 years in the Children's Pesticide Exposure Study (CPES) with corresponding intakes simulated using CPES consumption and body weight data and residue data from the US Pesticide Data Program (PDP). We calculated daily measured pesticide intakes by multiplying grams eaten with measured concentrations and dividing by body weight. For the simulated intakes we combined the CPES consumption and PDP residue data, randomly sampling the PDP data 500 times in order to create distributions of daily intakes for each cohort, including 95% uncertainty intervals for each percentile. In all cases, the measured medians fell below the lower uncertainty bounds of the simulated medians, reflecting the lower detection limits of CPES versus PDP and the high number of non-detects in each. Upper percentile measured intakes were generally lower as well, except for higher measured intakes of phosalone from watermelon. This work shows that using PDP data could generate probabilistic estimates of dietary pesticide intakes that do not differ appreciably from measured intakes except in some cases.

[Mucosal remodeling in chronic rhinosinusitis without nasal polyposis - an ultrastructural evaluation]. / Ultrastrukturelle Untersuchungen bei chronischer Rhinosinusitis ohne Polypen.

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.

Allergic and idiopathic rhinitis: an ultrastructural study.

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.

[Ultrastructural changes in allergic rhinitis vs. idiopathic rhinitis]. / Pathomorphologische Veränderungen bei der allergischen und idiopathischen 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.

Functional outcome after gamma knife treatment in vestibular schwannoma.

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.

[Ultrastructural changes in human nasal mucosa in rhinitis medicamentosa]. / Ultrastrukturelle Veränderungen der Nasenschleimhaut des Menschen nach Abusus von topischen alpha-Sympathomimetika.

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.

[Neural control of the respiratory nasal mucosa]. / Nervale Regulation der respiratorischen Nasenschleimhaut.

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.

[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.

[NPY in human nasal mucosa -- an immunocytochemical and immunoelectron microscopical study]. / Neuropeptid Y in der Nasenschleimhaut des Menschen -- eine immunhistochemische und immunelektronenmikroskopische Untersuchung.

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.

[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.

[Regulation of the swelling mechanism in the inferior turbinate of human nasal mucosa]. / Uberlegungen zur Dynamik des Schwellgewebes der unteren Nasenmuschel des Menschen.

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.

[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.

[Detection of progesterone receptors in connective tissue cells of the lower nasal turbinates in women]. / Nachweis von Progesteronrezeptoren in Bindegewebszellen der unteren Nasenmuscheln von Frauen.

BACKGROUND: The syndrome of the Rhinopathia gravidarum has been frequently discussed in the literature, but the etiology is yet unknown. An increase of oestrogen and progesterone concentration is said to contribute to the pathogenesis. The aim of this study was to localize estrogen (ER) and progesterone receptors (PgR) in the nasal mucosa of women and to compare the localization with the distribution of mast cells (MC). The patients' medical history was obtained with special emphasis on nasal symptoms during pregnancy, the menstrual cycle, or with the use of oral contraceptives. METHODS: Immunohistochemistry (IHC) was performed on formalin-fixed paraffin sections (nasal mucosa, inferior turbinate of 40 women) with monoclonal antibodies against ER, PgR, and mast cell tryptase. RESULTS: PgR-positive cells were found in fibroblasts (nuclear staining). The cytoplasmic staining for ER in serous glands and excretory ducts and for PgR in the interstitium of glands is considered nonspecific. The pattern of the receptor distribution was different from the pattern seen in the MC-IHC. No significant statistical results were obtained comparing the patient's medical histories and the immunohistochemical findings. CONCLUSIONS: Our findings possibly indicate a direct influence of progesterone on fibroblasts and therefore on the consistency of the extracellular matrix. Additionally, estrogen and progesterone might cause rhinopathic symptoms indirectly by changing the concentration of neurotransmitters (e.g. substance P, NO) and their receptors.

[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.

[Electron microscopy studies of innervation of nasal mucosa glands in humans]. / Elektronenmikroskopische Untersuchungen zur Innervation der Drüsen der Nasenschleimhaut des Menschen.

BACKGROUND: Seromucous glands are one of the main components of human nasal mucosa. The innervation pattern is important to understand the control of the different physiological glandular functions. In addition to light-microscopical findings electronmicroscopic investigations were performed to get more detailed information on the innervation of nasal glands. PATIENTS AND METHODS: Tissue samples of 16 human inferior turbinates were taken during nasal surgery and preserved in Unicryl or 3.5% phosphate-buffered glutaraldehyde. After fixation ultrathin sections were cut. Electron microscopical structures were photodocumented by using a transmission-electron microscope (EM 902 A Zeiss). RESULTS: Few axons were found in the periglandular tissue. No myo- or glandular-neural tight junctions could be identified. Unmyelinated nerve fibers showed typical components such as neurofilaments, neurotubules and mitochondria in their cytoplasm. An additional control of the glandular secretion by the vascular tone of the fenestrated capillary vessels will be discussed. CONCLUSIONS: Based on these ultramorphological findings further immunoelectron microscopical investigations will follow to demonstrate the various neurotransmitters and their distribution in periglandular axons.

[Pressure-dependent flow resistance in craniospinal cerebrospinal fluid dynamics: a calculation model for diagnosis of normal pressure hydrocephalus]. / Der druckabhängige Abflusswiderstand in der kraniospinalen Liquordynamik: ein Berechnungsmodell zur Diagnostik des Normaldruckhydrozephalus.

Computer-aided processing of the results obtained with the intrathecal infusion test using our newly developed mathematical model simplifies the investigation technique and thus the diagnosis of normal pressure hydrocephalus. Simultaneous determination of resistance and compliance in a single session markedly reduces the examination-related stress on the patient. In contrast to the classical methods, the new calculation does not require the ICP to reach a plateau. Unlike the static approach, our model describes the functional pressure-dependent course of the resistance. This means that account is taken of the non-linearity of the CSF dynamics during the processing of the biosignal. The intrathecal infusion test used to measure resistance and compliance is a reliable diagnostic method in patients with a normal pressure hydrocephalus.

Histochemical and immunocytochemical study of nitrergic innervation in human nasal mucosa.

Nitric oxide (NO) is a free radical gas that has been found to be produced in neuronal cells by the action of the enzyme brain nitric oxide synthase (bNOS). The aim of this study was to identify NO-containing nerve structures in the human nasal mucosa by localizing bNOS and to find out whether NO production is attached to the parasympathetic system. For this purpose, immunocytochemistry with antibodies to bNOS and neurofilament was performed. Additionally, nicotinamide-adenine dinucleotide phosphate diaphorase (NADPH-d), an enzyme that correlates with the localization of NO synthase, and acetylcholinesterase were visualized in a histochemical double staining technique on frozen sections. The NADPH-d and bNOS reactions were found in axons of nerve bundles and in subepithelial, glandular, and vascular nerve fibers. Arteries showed a distinctly developed nitric innervation, whereas no activity was found in nerve fibers supplying veins. A high coexistence of NADPH-d in parasympathetic nerves could be detected. These findings suggest that NO takes part in the nerve control functions of the human nasal mucosa.