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Die transnasale fiberoptisch-endoskopische Laryngoskopie mit Schluckuntersuchung (FEES) hat die Untersuchungsmoglichkeiten und das therapeutische Management bei kindlichen Schluckstorungen grundlegend verandert. Dieser Artikel soll eine Ubersicht uber die Untersuchungsmoglichkeiten geben und die Vorgehensweise bei der Anwendung der FEES darstellen. Hierbei erfolgt eine detaillierte Beschreibung des standardisierten Vorgehens unter Berucksichtigung der Erfahrungen der Autoren. Die FEES stellt eine geeignete Methode zur funktionellen Beurteilung des Schluckaktes und zur Beurteilung der laryngopharyngealen Strukturen unter direkter Sicht dar. Aufgrund vielfaltiger Vorteile wie die Verfugbarkeit und Wiederholbarkeit der Untersuchung, die fehlende Strahlenbelastung im Vergleich zu radiologischen Verfahren und wegen der okonomischen Uberlegenheit nimmt die Bedeutung der FEES zu. Bei einer steigenden Anzahl von kindlichen Schluckstorungen sollten mehr Arzte die FEES erlernen.

The forces required for the detachment of ferrocene (Fc) from β-cyclodextrin (βCD) in a single host (βCD)–guest (Fc) complex were investigated using force spectroscopy under electrochemical conditions. The redox state of the guest Fc moiety as well as the structure of the supporting matrix was found to decisively affect the nanomechanical properties of the complex.

PHENOTYPING SPECIFIC LANGUAGE IMPAIRMENT IN KINDERGARTEN CHILDRENOBJECTIVE: For phenotyping specific language impairment (SLI) in kindergarten children in clinical practice and research issues, we need a valid diagnostic method for dichotomous classification (language impaired, normal developing). PATIENTS AND METHODS: 27 kindergarten children belonged to SLI-group, 36 to control-group. The diagnostic accuracy of a composed language test battery was examined in comparison to a clinical assessment. The test battery was composed of 8 subtests of German norm-referenced, standardized tests. RESULTS: Several discriminant analyses showed acceptable levels of accuracy with over 80% for sensitivity and specificity. Using a single subtest the subtest „Phonologisches Arbeitsgedachtnis fur Nichtworter” (phonological short-term memory of nonwords) from Sprachentwicklungstest fur drei- bis funfjahrige Kinder (SETK 3-5; Grimm, 2001) showed best classification rates between the two groups using a Cut-off point of −0,39 SD. Means of the 8 used subtests showed significant differences for the two groups. CONCLUSION: The described method for phenotyping SLI can identify children with normal language and those with impaired language with acceptable levels of diagnostic accuracy. When using a norm-referenced standardized test for the assessment of language abilities, it is important to have empirically derived information about diagnostic accuracy (sensitivity, specificity, Cut-off score).

Position Paper of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery and the German Society of Phoniatrics and Pediatric Audiology - Current State of Clinical and Endoscopic Diagnostics, Evaluation, and Therapy of Swallowing Disorders in Children and AdultsSwallowing disorders are frequent. The main concern is mortality due to aspiration induced pneumonia and malnutrition. On the other hand quality of life is severely affected. The demographic trend indicates an increase of dysphagia in the future. Neurodegenerative diseases, tumors of the digestive tract and sequelae of tumor treatment in the head and neck region are the main pathologic entities.Predominantly ENT physicians and phoniatrists, are asked for diagnostics and therapy who will coordinate the interdisciplinary treatment according to the endoscopic findings.A differentiated approach in history, diagnostics, and symptom oriented treatment is necessary for the mostly complex disorders. The integration of non-medical personnel such as logopeds (speech language pathologists), physiotherapists, and occupational therapists in planning and executing an effective therapy expands and completes the patient-oriented care. Conservative treatment by these therapists is an important pillar in the treatment. Parts of the specific diagnostics can be taken over by them in close cooperation.In particular an interdisciplinary cooperation with the staff from intensive care medicine is indispensable.The diagnostic procedures of specific endoscopy as described in this position paper are part of the primary and fundamental tasks of ENT specialists and phoniatrists.Endoscopy is a medical service that is basically not delegable. Consequently substitution of the physician is precluded.Schluckstörungen sind häufig. Sie können zu erhöhter Mortalität durch aspirationsbedingte Lungenkomplikationen und Mangelernährung einerseits sowie einer erheblichen Beeinträchtigung der Lebensqualität andererseits führen. Die demografische Entwicklung in Deutschland lässt einen kontinuierlichen Anstieg der Dysphagie in den kommenden Jahren erwarten. Schwerpunkte sind dabei neurodegenerative Erkrankungen, die Tumoren im Verlauf der Schluckstraße und die Folgen der Tumorbehandlung im oberen Aerodigestivtrakt.Vorrangig sind die Ärzte aus dem HNO-Bereich und der Phoniatrie als kompetente Fachgruppen zentrale Ansprechpartner für die Diagnostik und Therapieplanung der Dysphagie.Die meist komplexen Störungen verlangen eine differenzierte Anamnese, Diagnostik und eine symptomorientierte Behandlung.Das Einbeziehen auch von nicht-ärztlichen Fachgruppen wie Logopäden, Physiotherapeuten und Ergotherapeuten in die Planung einer effizienten Therapie erweitert und komplettiert die kompetente patientenzentrierte Betreuung. Die konservative Dysphagietherapie durch Logopäden und ähnliche Fachgruppen ist, auch längerfristig, ein wichtiges Standbein der Behandlung. Zudem können Anteile der spezifischen Diagnostik in enger Kooperation übernommen werden.Eine interdisziplinäre Zusammenarbeit insbesondere mit den intensivmedizinischen neurologischen und internistischen Fachgruppen ist erforderlich.Die in diesem Positionspapier beschriebenen Verfahren der speziellen Endoskopie gehören zu den originären ärztlichen Leistungen, vornehmlich der Fachärzte für Hals-, Nasen-, und Ohrenheilkunde bzw. für Sprach-, Stimm- und kindliche Hörstörungen (Phoniatrie und Pädaudiologie).Die Endoskopie ist eine ärztliche Leistung, die grundsätzlich nicht delegierbar ist „In keinem Fall delegierbar sind Leistungen der Endoskopie (außer Kapselendoskopien, die durch speziell ausgebildete nichtärztliche Mitarbeiter geführt werden können) und der Sonografie“ siehe 278. Entsprechend ist eine Substitution des Arztes ausgeschlossen.

Durch seine anticholinerge Wirkung nimmt Botulinumtoxin in der Hals-Nasen-Ohren-Heilkunde eine wichtige Stellung ein. Patienten mit fazialen Hyperkinesien (z. B. Blepharospasmus, Spasmus facialis), komplexen Dystonien (oromandibulare Dystonie, spasmodische Dysphonie, zervikale Dystonie) sowie mit gustatorischem Schwitzen, Hypersalivation und Krokodilstranen werden damit behandelt. In der Behandlung von Spannungskopfschmerzen und Migrane ist Botulinumtoxin eine Alternative. Eine neue Indikation konnte sich bei nasaler Hypersekretion durch die Toxinwirkung auf die nasalen Drusen ergeben. Die Botulinumtoxinwirkung setzt nach wenigen Tagen ein und halt bei den muskularen Erkrankungen kurzer an als bei den Fehlfunktionen des autonomen Nervensystems. Der positive therapeutische Effekt ist passager, sodass erneute Behandlungen notwendig sind. Nebenwirkungen sind bei richtiger Anwendung selten. Unter Beachtung einiger spezieller Aspekte ist Botulinumtoxin ein effektives und nebenwirkungsarmes Therapeutikum bei zahlreichen muskularen Dysfunktionen und Erkrankungen des autonomen Nervensystems.

In otorhinolaryngology, botulinum toxin is a suitable therapeutic option in the muscular and the autonomic nervous system concerning dysfunctions. Respecting some special aspects, it is an effective treatment for disorders of different etiology with very few side-effects. The positive therapeutic effect is temporarily limited, so that the patients need further treatment. Beside the classical indications like the facial hyperkinesias (i.e. blepharospasms, hemifacial spasm) the treatment of complex dystonias (oromandibular dystonia, laryngeal dystonia, cervical dystonia), gustatory sweating, hypersalivation and crocodile tears is successful. Botulinum toxin is an alternative treatment of tension type headache and migraine. A new indication of botulinum toxin application may lay in the treatment of nasal hypersecretion through the effect on the nasal glands.

Rare information exists about comparative long-term observations of patients with facial movement disorders. This retrospective analysis deals with the course of different parameters of injection over the time.In this study we compared the development of long-term botulinum toxin treatments of patients with blepharospasm, hemifacial spasm and synkinesis. 80 patients (n=30 blepharospasm, n=31 hemifacial spasm, n=19 synkinesis), who had at least 10 consultations for BTA-injections, were included in the retrospective analysis. The development for each entity in total dosage, increase in the number of injection points and change in dosages for each point were evaluated.The over-all dosage in all 3 clinical disorders and for each single disease itself increased continuously over the time. The amount of injection points increased in the treatment of hemifacial spasm and synkinesis. The dosage per point increased most in blepharospasm between the 1. and 25. injection, but was distinctly lower in patients with hemifacial spasm and synkinesis. The increase in dosage in blepharospasm is therefore, in contrast to the other indications, mostly caused by an increase in dosage per point. In patients with hemifacial spasm and synkinesis the escalation of dosage is mainly caused by an increase of the number of injection points.These new aspects of the dynamic in the treatment with botulinum toxin enable the physician to understand better the dynamic of these diseases, to optimize treatment protocols.

The peptidylarginine deiminase (PAD) enzymes hydrolyze arginine residues to create the nonnative amino acid citrulline (a process called citrullination or deimination). Five PAD enzymes (1, 2, 3, 4, 6) have been identified, and they exhibit fairly restricted tissue expression patterns. The conversion of arginine to citrulline (referred to as citrullination or deimination) results in only a small change in molecular mass (less than 1 Da) and a loss in a positive charge, which can have dramatic consequences on protein structure and protein–protein interactions. Since citrullination can lead to profound changes in protein function, it is not surprising that citrullination and the activity of the PAD enzymes has been implicated in many diseases, such as rheumatoid arthritis (RA), multiple sclerosis, Alzheimer’s disease, inflammatory bowel disease, psoriasis, and cancer. This chapter provides a general overview of the PAD enzymes and their known functions. Plasma and synovial biopsy specimen from patients with rheumatoid arthritis contain high levels of citrullinated proteins, and, in fact, rheumatoid patients often develop immune reactivity to citrullinated proteins. Here, we also discuss possible physiological pathways that may contribute to the generation of citrullinated self-antigens, which could then prime the development of anti-citrulline peptide autoantibodies in rheumatoid arthritis.

Candida albicans (C. albicans) is a major nosocomial pathogen. We examined arachidonic acid (AA) and cytokine production by monocytes stimulated with C. albicans. [14C]-AA labeled monocytes released 8.9 +/- 2.3% of the incorporated AA following stimulation with live C. albicans (C. albicans: monocyte of 16:1) (P = 0.0002). Prior studies indicate that soluble alpha-mannans and beta-glucans antagonize mannose and beta-glucan receptors, respectively. Preincubation of monocytes with alpha-mannan (100 micrograms/ml) caused 45.8 +/- 5.7% inhibition of [14C]-AA release, whereas beta-glucan (100 micrograms/ml) yielded 43.7 +/- 6.0% inhibition (P0.05 for each compared to control). Additionally, monocytes stimulated with C. albicans also released interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8). However, alpha-mannan or beta-glucan failed to inhibit IL-1 beta release. These data indicate that C. albicans induces monocytes to release AA and inflammatory cytokines. Furthermore, AA, but not cytokine liberation, is partially mediated by alpha-mannan and beta-glucan components of the fungus.

Previously, we observed both tannin and β-glucan to be agonists for arachidonic acid (AA) release from rabbit alveolar macrophages. Although tannin inhibited reincorporation of exogenous AA, β-glucan had no apparent effect, suggesting separate signal transduction pathways leading to elevated AA levels. In this study alveolar macrophages were pretreated with the tyrosine phosphatase inhibitor sodium orthovanadate then stimulated with either condensed tannin or β-glucan. Vanadate exerted opposing effects on AA release. Furthermore, vanadate reversed the ability of tannin to inhibit reacylation. Additional studies using the phospholipase A probe bis-BODIPY-C11-i-PC indicated that although the known phospholipase A2 activators, calcium ionophore A23187, insoluble immune complexes, and β-glucan, generated an increase in fluorescence consistent with phospholipase A activation, tannin had no effect. These findings suggest the increase in free AA resulting from stimulation of macrophages by either tannin or β-glucan is produced via two different mechanisms. J. Leukoc. Biol. 58: 241–248; 1995.

Peptidylarginine deiminases, or PADs, convert arginine residues to the non-ribosomally encoded amino acid citrulline in a variety of protein substrates. PAD4 is expressed in granulocytes and is essential for the formation of neutrophil extracellular traps (NETs) via PAD4-mediated histone citrullination. Citrullination of histones is thought to promote NET formation by inducing chromatin decondensation and facilitating the expulsion of chromosomal DNA that is coated with antimicrobial molecules. Numerous stimuli have been reported to lead to PAD4 activation and NET formation. However, how this signaling process proceeds and how PAD4 becomes activated in cells is largely unknown. Herein, we describe the various stimuli and signaling pathways that have been implicated in PAD4 activation and NET formation, including the role of reactive oxygen species generation. To provide a foundation for the above discussion, we first describe PAD4 structure and function, and how these studies led to the development of PAD-specific inhibitors. A comprehensive survey of the receptors and signaling pathways that regulate PAD4 activation will be important for our understanding of innate immunity, and the identification of signaling intermediates in PAD4 activation may also lead to the generation of pharmaceuticals to target NET-related pathogenesis. Published version

Previous studies with macrophages that had been prelabeled with [14C]arachidonic acid (20:4) have shown that condensed tannin is a potent agonist for the release of arachidonic acid. However, it has not been demonstrated that the percentage release of [14C]20:4 accurately reflects the metabolic activity of the endogenous 20:4 pool. In order to measure the 20:4 mass release relative to the total cellular 20:4 pool, the free fatty acids of freshly isolated alveolar macrophages were derivatized with a fluorescent reagent, and then separated and quantified by high-performance liquid chromatography. The amounts of esterified fatty acids were measured by gas chromatography of the methyl esters. Free fatty acid levels were compared to those of the total esterified plus unesterified fatty acids to determine the actual percentage release of each fatty acid. Tannin-stimulated release of 20:4 mass reflected that previously reported for the release of [14C]20:4 label but at a slower rate and at a much lower percentage indicating that [14C]20:4 had been incorporated into part of a more reactive pool. The specificity of the fatty acid release induced by tannin and beta-1,3-glucan, a known agonist for 20:4 release, was also examined. Both agonists promoted an increase in the levels of free 20:4 and of other fatty acids. A comparison of the absolute increases of each of the fatty acids indicated that tannin caused a preferential increase in the mass of free 20:4, whereas beta-1,3-glucan evoked a selective increase in the mass of 16:0.

Pneumocystis carinii is an opportunistic organism that causes severe lung injury in immunocompromised hosts. Macrophage responses to P. carinii are poorly defined. Arachidonic acid (AA) and its metabolites are potent mediators of inflammation and have been implicated in host response to microorganisms. We therefore examined the production of eicosanoids from rat and rabbit alveolar macrophages stimulated with purified P. carinii. [14C]AA-labeled rabbit macrophages released 8.50 +/- 1.33% of the incorporated [14C]AA after 90 min in response to P. carinii (P = 0.0001 compared with unstimulated controls). In contrast, a similar number of rat alveolar macrophages exhibited a smaller but significant response to P. carinii, releasing 3.84 +/- 1.54% of their [14C]AA after 90 min (P = 0.001 compared with control). We further determined that P. carinii stimulated substantial production of prostaglandin E2 and concurrently a small amount of leukotriene B4 release from alveolar macrophages. To further investigate whether serum opsonization of P. carinii enhances these alterations in AA metabolism, we assessed the effect of P. carinii immune serum on P. carinii-induced AA release. P. carinii opsonized with this antiserum caused significantly greater AA release from rat alveolar macrophages than either unopsonized P. carinii or organisms opsonized with nonimmune serum. Previous studies suggest that P. carinii interacts with macrophage beta-glucan and mannose receptors. However, incubation of macrophages with P. carinii in the presence of either soluble beta-glucan or alpha-mannan failed to alter the release of AA from macrophages in response to P. carinii. Macrophage release of eicosanoids represents a potentially important host inflammatory response to P. carinii infection.

The condensed tannin present in cotton mill dust profoundly alters the functional capabilities of resident alveolar macrophages. Previous studies from this laboratory have shown that in vitro exposure of rabbit resident alveolar macrophages to condensed tannin significantly inhibits the ability of these cells to produce reactive oxygen intermediates or to ingest particles. In the present study, we demonstrate that condensed tannin also alters arachidonic acid (C20:4) metabolism in these cells. Exposure of rabbit resident alveolar macrophages to condensed tannin results in the time- and dose-dependent release of C20:4 from the membrane phospholipids. The release of C20:4 occurred only at tannin concentrations greater than 25 micrograms/ml and was maximal 90 min after the onset of exposure. The EC50 for release was 75 micrograms/ml. Exposure to 100 micrograms/ml tannin resulted in the release of 20 +/- 3% of the [14C]C20:4 incorporated in the cell membrane. In comparison, exposure to 160 micrograms/ml zymosan resulted in the release of 14 +/- 4% of the [14C]C20:4. For both tannin and zymosan, phosphatidylcholine and phosphatidylinositol were the principal sources of the released C20:4. Approximately 63% of the C20:4 released after zymosan stimulation was further metabolized, mainly via the cyclooxygenase pathway. The major metabolites were 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, and prostaglandin E2. In contrast, only 24% of the C20:4 released by tannin was subsequently further metabolized. The metabolites formed were essentially evenly distributed between products of the cyclooxygenase pathway and the lipoxygenase pathway. Exposure of alveolar macrophages to 50 micrograms/ml tannin for 30 min reduced the ability of the cells to subsequently incorporate C20:4 by 50 to 70%. In contrast, exposure of the cells to 160 mg/ml zymosan for 30 min had only a minimal effect on the subsequent ability of these cells to incorporate C20:4. These results indicate that tannin promotes C20:4 release, at least in part, by inhibiting its reacylation back into phospholipids, a mechanism that differs from that of zymosan.

For phenotyping specific language impairment (SLI) in kindergarten children in clinical practice and research issues, we need a valid diagnostic method for dichotomous classification (language impaired, normal developing).27 kindergarten children belonged to SLI-group, 36 to control-group. The diagnostic accuracy of a composed language test battery was examined in comparison to a clinical assessment. The test battery was composed of 8 subtests of German norm-referenced, standardized tests.Several discriminant analyses showed acceptable levels of accuracy with over 80% for sensitivity and specificity. Using a single subtest the subtest "Phonologisches Arbeitsgedächtnis für Nichtwörter" (phonological short-term memory of nonwords) from Sprachentwicklungstest für drei- bis fünfjährige Kinder (SETK 3-5; Grimm, 2001) showed best classification rates between the two groups using a Cut-off point of -0,39 SD. Means of the 8 used subtests showed significant differences for the two groups.The described method for phenotyping SLI can identify children with normal language and those with impaired language with acceptable levels of diagnostic accuracy. When using a norm-referenced standardized test for the assessment of language abilities, it is important to have empirically derived information about diagnostic accuracy (sensitivity, specificity, Cut-off score).

The relationship between host and pathogen is inherently dynamic at the genetic level. A plethora of host defensive systems have evolved to counteract and/or eliminate invading pathogens. These strategies exert selection pressure upon the pathogen, leading to the emergence of mechanisms to combat the host including immune evasion and resistance. Consequently, effective control of rapidly evolving diseases is contingent on the ability to predict pathogen evolution prior to the emergence of resistant phenotypes. Highlighted in this article is a bacteriophage-based technology capable of screening hundreds of millions of binding events simultaneously at single molecule resolution, thus providing an in vitro mimetic of protein evolution. This technology, termed phage escape, can be utilized to model the evolution of proteins in the presence of antibodies or other selective pressure, providing a predictive solution to the coevolution of antigens and the immune system. Foresight into the evolutionary path of an antigen and subsequent neutralization strategies can facilitate more efficacious vaccination formulation and have important implications in the treatment of a range of evolving diseases, including viral infections and cancer.

SUMMARY The T lymphocyte-mediated induction of angiotensin-converting enzyme (ACE) in cultured autologous peripheral blood monocytes has been proposed as a model system for the investigation of the in vivo induction of ACE in the monocyte-derived granuloma epithelioid cells of some granulomatous diseases such as sarcoidosis. The studies described here were designed to evaluate the specificity of the model system by comparing the parameters for induction of ACE with those for the induction of another monocyte metallo-ecto-peptidase, leucine aminopeptidase (LAP). The concentration of LAP in freshly isolated monocytes was 009 mU/106 monocytes (s.e.m. 0.04) and increased to a maximal value of 019 mU/106 monocytes (s.e.m. 0.32) after 3 days when monocytes were cultured alone. ACE was not detectable in freshly isolated monocytes. However, after 6 days of culture, monocytes contained 0.22 m U ACE/106 monocytes (s.e.m. 0.04). Comparison of the levels of ACE and LAP induced during culture of monocytes alone indicated that the induction of these two enzymes was correlated. The induction of both enzymes was further enhanced by the presence of T lymphocytes in a dose-dependent manner. At 4 × 106 T lymphocytes per culture, ACE levels increased to 1.81 mU/106 monocytes (s.e.m. 0.24) and LAP levels to 1.03 mU/106 monocytes (s.e.m. 0.35). The enhancement of ACE activity required autologous lymphocytes, while heterologous T lymphocytes were equally effective in inducing LAP. Comparison of the levels of ACE and LAP induced during co-culture of autologous T lymphocytes and monocytes from 21 independent donors, demonstrated no correlation between the induction of ACE and LAP. These data indicate that, although T lymphocytes also enhance the induction of LAP, the underlying mechanism must differ from that of ACE induction.

Previous studies on the platelet agonist activity of cotton bract condensed tannin have used tannins with apparent molecular weights greater than 10,000 Da as measured by dialysis and/or ultrafiltration. However, because tannins in cotton dust are heterogeneous in terms of molecular weight, it was important to determine if platelet agonist activity was related to polymer length. To accomplish this, aqueous extracts of cotton dust were fractionated by a series of graded Amicon ultrafiltrations and the resulting fractions were examined for tannin content and platelet agonist activity. All tannins with apparent molecular weight greater than 1000 Da were equally potent platelet agonists while those less than 1000 Da had no measurable platelet agonist activity. This polymer length dependence for activity was supported by the observation that two procyanidin dimers had only minimal platelet agonist activity. In addition, methylation of the tannin hydroxyl groups resulted in the loss of platelet agonist activity. Thus, the platelet agonist activity of tannin requires a minimum polymer length and the presence of free hydroxyl groups.

The human T lymphocyte proliferative response to cotton bract tannin was shown to be dependent upon the presence of monocytes. Since monocytes support the T cell mitogenic response by interleukin-1 (IL-1) production, it was anticipated that tannin has IL-1-inducing ability. To examine this possibility, human monocytes were cultured alone or with peripheral blood T lymphocytes, and stimulated with tannin. Control cultures included unstimulated cells, and cells challenged with other IL-1 inducers: concanavalin A (Con A) and lipopolysaccharide from Escherichia coli or Enterobacter agglomerans. IL-1β was measured in culture super-natants 24 h after initiation of the culture by the use of an ELISA or an RIA. The results showed that tannin stimulated monocytes to secrete IL-1β in a manner similar to Con A, i.e. substantially more cytokine was measured in the supernatants of monocyte-T-lymphocyte co-cultures than in the cultures of monocyte alone. Endotoxin from E. coli was less effective than the endotoxin from E. agglomerans in IL-1 induction. Contaminating endotoxin present in the tannin preparation accounted for the majority of IL-1β released from monocytes alone stimulated with tannin, but only 20% of the IL-1β released from tannin-stimulated monocyte-T-lymphocyte co-cultures. These results show that tannin itself has IL-1-inducing ability. The dose-response studies show that the extent of IL-1β release is dependent on tannin dose and that increased levels of monocyte-produced IL-1β precede the increase in T lymphocyte proliferation. These findings suggest that tannin stimulates T cell proliferation by a mechanism similar to that in lectin-induced T lymphocyte proliferation, namely by providing the second signal by stimulating monocytes for IL-1 production.

In otorhinolaryngology, botulinum toxin is a suitable therapeutic option in the muscular and the autonomic nervous system concerning dysfunctions. Respecting some special aspects, it is an effective treatment for disorders of different etiology with very few side-effects. The positive therapeutic effect is temporarily limited, so that the patients need further treatment. Beside the classical indications like the facial hyperkinesias (i.e. blepharospasms, hemifacial spasm) the treatment of complex dystonias (oromandibular dystonia, laryngeal dystonia, cervical dystonia), gustatory sweating, hypersalivation and crocodile tears is successful. Botulinum toxin is an alternative treatment of tension type headache and migraine. A new indication of botulinum toxin application may lay in the treatment of nasal hypersecretion through the effect on the nasal glands.

The present study reports on our experience with clinical aspects and therapy of oromandibular dystonia (OMD) with botulinum toxin A. OMD is a very rare form of focal dystonias. The clinical symptoms can vary considerably, depending on the musculature affected.The various clinical forms are described. The description of the diagnostic analysis and the therapy with botulinum toxin A is explained with reference to the patients. In these cases, injections are made into the musculature of the base of the mouth, the muscles involved in chewing, the extrinsic muscles of the tongue and the caudal facial musculature.Most of the patients showed an improvement of their symptoms. The average dose of Botox(R) used was 35.4+/-23.6 units. The duration of the effect was 14+/-9.2 weeks on average.The therapy for OMD using botulinum toxin A has proved to be successful, the amount of improvement in this form of dystonia is, however, lower in comparison to other forms of mobility disorders in the head and neck region.

Hypersecretion disorders of the exocrine glands of the head and neck area are a therapeutic problem in the field of otorhinolaryngology. In the present study, we demonstrate the effectiveness of local injections of botulinum toxin A to block secretions of exocrine glands of the head and neck area.Four patients suffering from hypersecretion disorders received local injections of botulinum toxin A. Two patients suffered from disorders of the salivary glands: one presented an idiopathic hypersialorrhea and another a salivary fistula after parotidectomy. A third patient suffered from epiphora and a further patient presented severe hyperhidrosis on the pilose head region. In a retrospective clinical study, the outcome of therapy was evaluated by clinical examination and chemical parameters.Clear blocking of secretion in the treated glands could be demonstrated in all four cases. Possible side effects of the treatment could not be observed.The present study was able to demonstrate a clear blocking of secretion of the exocrine glands of the head and neck region through botulinum toxin A, offering an improvement in therapy especially for the innovative indication of blocking the salivary glands of the head.

Growth hormone (GH) has been suggested as a therapeutic tool for the treatment of osteopenia. To assess the differential influence of growth hormone on cortical and trabecular bone, bone mineral densities (BMD) of the ultradistal radius were determined in 18 men and 19 women with clinically and biochemically confirmed acromegaly using peripheral computed tomography and a specialized scanner (Stratec XCT 900). The results were expressed in equivalents to hydroxyl-apatite (mg/ccm) and compared with the BMD of healthy controls (17 men, 34 women). Cortical bone mineral density was significantly higher in acromegalic women (295.2 +/- 18.4, X +/- SEM) and men (339.4 +/- 21.2) compared to healthy women (243.0 +/- 12.8) and men (272.2 +/- 15.9). In contrast, trabecular BMD did not differ between acromegalic patients (men: 161.0 +/- 16.1; women: 116.5 +/- 10.5) and controls (men: 158.0 +/- 12.2; women: 134.1 +/- 6.3). Acromegalic women showed a significant correlation between insulin-like growth factor (IGF-I) expression and cortical BMD, whereas in acromegalic men GH levels correlated significantly with cortical BMD. Greatly increased serum osteocalcin levels in both, acromegalic men (15.5 +/- 3.3 ng/ml) and women (12.9 +/- 1.8) compared to controls (men: 6.7 +/- 1.7; women: 7.7 +/- 1.0) indicates the activation of osteoblastic bone formation. This study revealed an increase in cortical BMD at the forearm; in acromegalic patients; though trabecular BMD did not differ from controls. The differential mineralization of cortical and trabecular bone in acromegaly may be indicative of the detrimental effect accompanying pituitary insufficiency can have on trabecular bone, despite substitution therapy, but could also be due to different reactivity of cortical and trabecular bone to GH and/or IGF I. The observable increase of bone mineral density in acromegaly suggests a potential use for GH in treating osteoporosis.

It is essential to determine whether the results obtained from animal models actually reflect human disease processes. Tannin is a component of cotton dust that acts as a polyclonal cell activator in vitro. Most of the effects of tannin on alveolar macrophages (AM phi) have been studied in rabbit AM phi. Therefore, we compared tannin-mediated in vitro neutrophil chemotactic factor (NCF) secretion from normal human and rabbit AM phi. For both species the NCF secretion from AM phi was dependent on tannin dose and time of exposure. The NCF released was a lipid with a molecular weight of less than 800 daltons, suggesting that it may be a metabolite of arachidonic acid. Tannin stimulation of both human and rabbit AM phi resulted in the release of 90% unmetabolized arachidonic acid derived from both phosphatidyl choline and phosphatidyl inositol membrane lipids. The NCF secreted was not leukotriene B4 or platelet-activating factor. In conclusion, tannin mediates the release of a so far undescribed NCF from resident AM phi in rabbits and human subjects that may contribute to the pathogenesis of the acute neutrophilic alveolitis associated with cotton dust inhalation. The similarity of results obtained from human and rabbit cells supports the pertinence of using rabbit cells to study tannin-mediated effects.

The role of Ca2+ was investigated in the response of alveolar macrophages to cotton tannin, an agent implicated in the lung disease byssinosis in textile mill workers. A physiological concentration of extracellular Ca2+ was found to be required for tannin-mediated release of radiolabeled arachidonic acid (AA). Flow cytometry using indo 1 indicated that tannin caused a rapid and dose-dependent Ca2+ increase in macrophages that also required extracellular Ca2+. Ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid virtually abolished the Ca2+ influx mediated by tannin but had little effect on intracellular Ca2+ release induced by thapsigargin, N-formylmethionyl-leucylphenylalanine, or thimerosal. A mechanism for extracellular Ca2+ influx was demonstrated by rapid Mn2+ quenching of indo 1 by tannin. Verapamil inhibited tannin-mediated Ca2+ influx and AA release, but the effective concentration was 100 microM. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid chelated all Ca2+ in the cells and effectively abolished the tannin response. Exposure to tannin was not associated with cytotoxicity, as judged by 51Cr release. The data suggest that tannin induces Ca2+ influx in alveolar macrophages, which represents an important prerequisite for a cell-signaling pathway resulting in the accumulation of free AA.

Candida albicans is an increasingly important fungal pathogen. Alveolar macrophages respond to fungal components such as zymosan by releasing arachidonic acid (AA) and AA metabolites. However, few studies hypothesized that macrophages respond to C. albicans by releasing AA and generating AA metabolites as a consequence of interaction of mannose and beta-glucan receptors with fungal cell wall components. [14C]AA-labeled rabbit alveolar macrophages released AA following stimulation with either live or heat-killed C. albicans. High-pressure liquid chromatography analysis revealed that 55% of the AA released was metabolized via cyclooxygenase and lipoxygenase pathways. The metabolites consisted of prostaglandin E2, prostaglandin F2 alpha, 6-ketoprostaglandin F1 alpha, thromboxane B2, and leukotrienes B4 and D4. We further examined the roles of alpha-mannan and beta-glucan components of C. albicans in mediating these alterations of eicosanoid metabolism. Prior work in our laboratory has shown that soluble alpha-mannan and beta-glucan inhibit macrophage mannose and beta-glucan receptors, respectively. Incubation of alveolar macrophages with soluble alpha-mannan derived from C. albicans (1 mg/ml) resulted in 49.8% +/- 2.6% inhibition of macrophage AA release during stimulation with intact C. albicans (P = 0.0001 versus control). Macrophage AA release in response to C. albicans was also inhibited to a significant but lesser degree by soluble beta-glucan (36.2% +/- 1.3%; P = 0.008 versus control). These results indicate that C. albicans stimulates macrophage AA metabolism and that these effects are partly mediated by alpha-mannan and beta-glucan constituents of the fungus.