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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Trauma und Berufskrankheit 2 (2000), S. 28-38 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Beckenverletzung ; Begleitverletzung ; Diagnostik ; Therapie ; Algorithmus ; Keywords ; Pelvic trauma ; Concomitant lesions ; Diagnosis ; Therapy ; Algorithm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: The injuries that typically accompany pelvic fractures are lesions of the urogenital tract, the lumbosacral plexus, and the retroperitoneal and intra-abdominal organs. The prognosis depends heavily on early recognition of the abdominal- and retroperitoneal injuries, which are frequently a primary threat to vital functions. Missing these injuries would be very serious, as the mortality with early diagnosis and adequate treatment is normally low; according to the results reported in the literature, delayed therapy leads to increasing mortality rates of up to 80%. Experience in trauma centres has shown that for complete ascertainment of accompanying injuries it is necessary to perform a systematic diagnosis according to a fixed algorithm. The treatment of the concomitant injuries accompanying a complex pelvic trauma is fundamentally different from the treatment of patients with isolated injuries. A high survival rate with a low postoperative complication rate cannot be achieved except with specialist surgical management tailored to the primary life-threatening lesions. After determination and recording of the injury pattern a therapy concept must be made at once. A trauma algorithm can be helpful when treatment is selected. Step-by-step treatment with several operative phases alternating with recovery and stabilization periods under intensive care conditions has proved worthwhile.
    Notes: Typische Begleitverletzungen von Beckenfrakturen sind Verletzungen des Urogenitaltrakts, des Plexus lumbosacralis und intraabdominaler Organe. Entscheidend für die Prognose ist das rechtzeitige Erkennen v. a. der häufig primär vital gefährdenden Abdominal- und Retroperitonealverletzungen. Das Übersehen dieser Verletzungen ist besonders tragisch, da bei rechtzeitiger Diagnostik und adäquater Versorgung die Letalitätsrate in der Regel gering ist; bei verzögerter Therapie resultieren nach den Angaben in der Literatur Letalitätsraten bis zu 80%. Die Erfahrung in Traumazentren hat gezeigt, dass zur vollständigen Erfassung der Begleitverletzungen die systematische Diagnostik nach einem festgelegten Algorithmus erfolgen sollte. Die Behandlung der Begleitverletzungen im Rahmen eines komplexen Beckentraumas unterscheidet sich prinzipiell von der bei Monoverletzten. Voraussetzung für eine hohe Überlebensrate mit geringer postoperativer Komplikationsrate ist ein prioritätenorientiertes chirurgisches Vorgehen. Nach Erfassung des Verletzungsmusters muss bereits initial ein Therapiekonzept erstellt werden. Zur Entscheidungsfindung kann ein Traumaalgorithmus herangezogen werden. Es hat sich eine abgestufte Versorgung mit mehreren operativen Phasen und zwischengeschalteten Erholungs- und Stabilisierungsphasen unter Intensivbedingungen bewährt.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Trauma und Berufskrankheit 2 (2000), S. 240-248 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Komplexe Schultergürtelverletzung ; Diagnostik ; Therapie ; Interdisziplinäres ¶Management ; Keywords ; Complex shoulder girdle trauma ; Diagnosis ; Therapy ; Interdisciplinary management
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: The particular injury pattern of complex joint trauma means that a standardized operative procedure would be difficult to devise and an individual therapy plant is therefore essential for each patient. One of the main problems consists in the recognition and adequate treatment of associated vascular and neural lesions. The treatment of a complex joint trauma makes extremely high demands on the trauma-team in terms of both diagnostis and therapy and is an interdisciplinary challenge. On the basis of a detailed literature search and evaluation of the procedures we have adopted in sample cases, we suggest an algorithm for interdisciplinary management of severe combination injuries of the shoulder region.
    Notes: Die Problematik des komplexen Gelenktraumas besteht darin, dass aufgrund des besonderen Verletzungsmusters ein standardisiertes operatives Vorgehen erschwert und deshalb ein individuelles Therapiekonzept essenziell ist. Ein Hauptproblem besteht in ¶der Erkennung und der adäquaten Behandlung assoziierter Gefäß- und Nervenläsionen. Die Behandlung eines komplexen Gelenktraumas stellt höchste diagnostische und therapeutische Ansprüche an das Traumateam und bedeutet eine interdisziplinäre Herausforderung. Aufgrund einer eingehenden Literaturrecherche und der Auswertung des eigenen Vorgehens anhand exemplarisch ausgewählter Fälle wird versucht, einen Algorithmus der interdisziplinären Komplexversorgung schwerer Kombinationsverletzungen der Schulterregion zu erstellen.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Trauma und Berufskrankheit 2 (2000), S. S51 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Ellbogenverletzungen ; Wachstumsalter ; Diagnostik ; Therapie ; Key words ; Ellbow joint injuries ; Adolescence ; Diagnosis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Fractures and dislocations of the elbow are some of the most common injuries in childhood and adolescence. The majority occur in the course of sport and play, for example as the result of falling from apparatus used in gymnastics or a bike, or falling while engaging in such popular sports as in-line-skating or skateboarding. Elbow injuries can be divided into dislocations of the joint alone and fractures, of the distal humerus or the proximal radius and ulna, or combinations of both dislocation and fracture. In addition, a differentiation is made between extra- and intraarticular fracture types, the latter being seen as either partial or complete joint lesions.
    Notes: Zusammenfassung Luxationen und/oder Frakturen am Ellbogen gehören zu den häufigsten Verletzungen im Wachstumsalter überhaupt. Sie entstehen überwiegend bei Sport und Spiel, z. B. durch Sturz von einem Turngerät, von Zweirädern oder während der Ausübung moderner Sportarten wie In-line-Skating, Rollschuhlauf und Skateboardfahren. Bei den Verletzungen werden reine Luxationen von Frakturen entweder am körperfernen Oberarmende oder an den gelenkbildenden Anteilen von Radius und Ulna unterschieden. Ein weiteres Unterscheidungsmerkmal ist die Abgrenzung extraartikulärer von intraartikulären Frakturformen, wobei letztere entweder als partielle oder komplette Bruchform imponieren.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Trauma und Berufskrankheit 2 (2000), S. S186 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter Schultergürtel ; Stumpfe Verletzungen ; Rotatorenmanschettenruptur ; Schulterluxation ; Therapie ; Keywords Shoulder girdle ; Blunt injuries ; Rupture of rotator cuff ; Shoulder dislocation ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract It is difficult to assess blunt injuries in the region of the shoulder girdle because of the overlying acute and chronic processes. In assessments of rotator cuff ruptures in particular, in over 50% of cases the rupture could be explained by a degenerative process. This makes the assessment difficult, and also the decision as to whether or not the injury is due to an occupational accident. The diagnostic procedures applied should exclude a degenerative aetiology immediately after an accident in all cases. Rupture of the rotator cuff is often associated with an impingement syndrome and leads to corresponding symptoms in the subacromial space. Treatment of a rotator cuff rupture always involves a diagnostic arthroscopy as the first step, after which a reconstruction can be undertaken, either by way of the anterolateral approach after Neer or, in many cases, arthroscopically. Reconstruction of the rotator cuff must include outward mobilization of the muscles and a secure, mostly transosseous suture. Transference of a pedunculated tendon is indicated for large defects in the rotator cuff. In the case of dislocation of the shoulder with subsequent shoulder instability degenerative change and any possible multidirectional instability should be defined. Unidirectional instability with a demonstrable Bankart lesion has a good prognosis when surgery is performed without delay. In view of the high recurrence rate early treatment is indicated especially in young persons and in patients with a high activity level. Following detection of the Bankart lesion an arthroscopic procedure with refixation of the capsule–labrum complex is the method of choice.
    Notes: Zusammenfassung Stumpfe Verletzungen im Bereich des Schultergürtels sind aufgrund einer Überlagerung akuter und chronischer Prozesse schwer beurteilbar. Insbesondere bei der Beurteilung der Rotatorenmanschettenruptur ist diese nachweislich in über 50% der Fälle auf dem Boden eines degenerativen Prozesses begründet. Dies macht die Begutachtung und die Abgrenzung eines Arbeitsunfalls schwierig. Die Diagnostik sollte auf jeden Fall unmittelbar nach einem Unfall eine degenerative Genese abgrenzen. Zusätzlich muss die Schmerzsymptomatik gezielt untersucht und von vertebragenen Beschwerden abgegrenzt werden. Die Rotatorenmanschettenruptur geht häufig mit einem Impingementsyndrom einher und führt zu entsprechenden Beschwerden im Subakromialraum. Die Behandlung der Rotatorenmanschettenruptur beinhaltet immer im ersten Schritt ¶eine diagnostische Arthroskopie, anschließend kann entweder über den anterolateralen Zugang nach Neer oder in vielen Fällen auch arthroskopisch eine Rekonstruktion vorgenommen werden. Die Rekonstruktion der Rotatorenmanschette muss eine ausgiebige Mobilisation der Muskulatur und eine ¶sichere, meist transossäre Naht beinhalten. Der gestielte Sehnentransfer ist bei großen Defekten der Rotatorenmanschette angezeigt. Bei der Schulterluxation mit anschließender Schulterinstabilität sind ebenfalls ¶eine degenerative Veränderung und eine mögliche multidirektionale Instabilität abzugrenzen. Bei unidirektionaler Instabilität mit nachweisbarer Bankart-Läsion ist die Prognose bei unmittelbarer operativer Versorgung gut. Gerade beim jungen Menschen und bei Patienten mit hohem Aktivitätsniveau ist aufgrund der hohen Reluxationsrate ein frühes Vorgehen angezeigt. Nach Nachweis der Bankart-Läsion ist ein arthroskopisches Vorgehen mit Refixation des Kapsel-Labrum-Komplexes die Methode der Wahl.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Trauma und Berufskrankheit 2 (2000), S. S456 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter Trauma ; Akute Belastungsstörung ; Posttraumatische Belastungsstörung ; Therapie ; Medizinische Begutachtung ; Keywords Trauma ; Acute stress disorder ; Posttraumatic stress disorder ; Therapy ; Medico-legal expertise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract ‘Psychopathology after trauma’ mostly refers to cognitive or affective impairment after direct or indirect damage to brain tissue. Patients who have suffered a whiplash injury of the cervical spine, even without direct trauma to brain tissue, also often complain of cognitive or affective dysfunction for prolonged periods after the injury. Even more difficult to evaluate is psychopathology arising in the aftermath of severely distressing events, such as major disastrous accidents, natural catastrophes or assault. The medical expert must be aware of a variety of posttraumatic psychiatric disorders with different courses and symptoms and must be able to distinguish these from endogenous or merely coincident psychiatric disorders. In this paper, we outline the relevant diagnoses and diagnostic criteria, with special refrence to posttraumatic stress disorder (PTSD). It should be emphasized that while acute stress disorder is common after stressful experiences, PTSD is most likely to develop in the presence of personality traits or a concurrent psychiatric illness predisposing to the disorder. The nature of the trauma sustained is significant: for example, trauma inflicted by human aggression causes PTSD significantly more often than similar injuries suffered as the result of a motor vehicle accident. Finally, therapeutic strategies for posttraumatic disorders are briefly reviewed.
    Notes: Zusammenfassung Mit posttraumatischen psychischen Störungen sind in der Regel kognitive oder affektive Beeinträchtigungen in der Folge direkter oder indirekter Hirngewebeschäden gemeint. Aber auch Patienten mit Halswirbelsäulenschleudertrauma beklagen häufig und über lange Zeit kognitive oder affektive Störungen ohne Nachweis einer Hirnschädigung. Noch problematischer sind psychische Störungen in der Folge erheblich belastender Ereignisse, wie Unfälle katastrophalen Ausmaßes, Naturkatastrophen oder Überfällen, zu beurteilen. Dem ärztlichen Gutachter obliegt die Aufgabe, eine Reihe posttraumatischer Störungen, die sich hinsichtlich des Verlaufs und der Symptome unterscheiden, zu kennen und von anlagebedingten oder koinzidierenden psychischen Störungen zu differenzieren. In der vorliegenden Arbeit werden die relevanten Diagnosen ¶und diagnostischen Kriterien mit besonderer Behandlung der posttraumatischen Belastungsstörung (PTSD) besprochen. Hervorzuheben ist, dass es nach erheblich belastenden Erlebnissen recht häufig zu akuten Belastungsreaktionen kommt, während die PTSD in der Regel dann auftritt, wenn eine besondere persönliche Disposition oder psychiatrische Komorbidität vorliegen. Ferner kommt der Art des belastenden Erlebnisses Bedeutung zu. So wird eine PTSD häufiger nach Ausbrüchen menschlicher Aggression als nach z. B. Verkehrsunfällen gefunden. Abschließend wird ein kurzer Überblick über therapeutische Möglichkeiten bei posttraumatischen Störungen gegeben.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Trauma und Berufskrankheit 2 (2000), S. S400 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter Schulterinstabilität ; Arthroskopische Stabilisierung ; Therapiestrategie ; Akut ; Chronisch ; Keywords Instability of the shoulder ; Arthroscopic repair ; Therapy ; Acute ; Chronic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Traumatic instability of the shoulder has to be distinguished from instability due to capsular hyperlaxity if a stable shoulder and good functional results are to be achieved after surgery. Physical examination, radiological studies and arthroscopy are the most important diagnostic tools for this distinction. On the basis of our own experience and the results reported in the literature, we propose a strategy of patient selection for an arthroscopic stabilizing procedure. This procedure is indicated for first-time, traumatic dislocation and for chronic instability with a history of fewer than five recurrences without hyperlaxity.
    Notes: Zusammenfassung Die traumatische Schulterinstabilität muss von der Instabilität aufgrund hyperlaxer Kapsel-Band-Strukturen unterschieden werden, um dem therapeutischen Ziel einer stabilen und in ihrer Funktion nicht gestörten Schulter nahe zu kommen. Hierzu sind die klinische, radiologische und arthroskopische Diagnostik entscheidend. Auch der Enstehungsmechanismus und die Häufigkeit der Luxationen müssen berücksichtigt werden. Aufgrund der bisher gemachten Erfahrung und den in der Literatur verfügbaren Ergebnissen entstand eine Therapiestrategie der traumatischen Schulterinstabilität, die in Abhängigkeit von der präoperativen Reluxationsrate, den anatomischen Gegebenheiten und dem Anspruch des Patienten eine Selektion für oder wider eine arthroskopische Stabilisierungsoperation vorschlägt. Die Indikation zu diesem Eingriff sehen wir bei der traumatischen Erstluxation und der rezidivierenden traumatischen Schulterinstabilität ohne Hyperlaxität, wenn weniger als 5 Rezidive in der Anamnese zu erheben sind.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Gefässchirurgie 5 (2000), S. 188-191 
    ISSN: 1434-3932
    Keywords: Schlüsselwörter Venöses Poplitealaneurysma ; Differentialdiagnose ; Knieschmerz ; Therapie ; Keywords Popliteal venous aneurysm ; Differential diagnosis ; Knee pain ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract  A rare cause of painful swelling of the knee cavity can be an aneurysm of the popliteal vein. Only 28 cases are reported in the literature. We treated a 20-year-old male patient who underwent three arthroscopies, one operation and one MRI; finally, phlebography detected a popliteal vein aneurysm and a malformation of the deep venous system of the popliteal and proximal calf veins. To avoid the threat of pulmonary embolism a resection of the aneurysm with interposition of a venous autograft was performed. Twelve months after the operation the patient is free of symptoms with a patent autograft.
    Notes: Zusammenfassung  Eine seltene Ursache schmerzhafter Schwellungen in der Kniekehle kann ein Aneurysma der V. poplitea sein. Bisher wurden 28 Fälle dieser Fehlbildung in der Weltliteratur beschrieben. Wir sahen einen 20-jährigen männlichen Patienten, bei dem nach 3 Arthroskopien, einer Arthrotomie und einer MRT durch eine Phlebographie ein venöses Aneurysma der V. poplitea mit venös-aneurysmatischer Malformation der proximalen Unterschenkelvenen festgestellt wurde. Um eine potentiell tödliche Lungenembolie zu vermeiden, erfolgte die Resektion mit Interposition der kontralateralen gedoppelten V. saphena magna. 12 Monate nach der Operation hat der Patient bei duplexsonographisch gutem Flow im Interponat keine Beschwerden.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S110 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Unterkiefer ; Gelenkfortsatzfrakturen ; Diagnostik ; Therapie ; Key words ; Mandible ; Condylar neck fracture ; Diagnostic ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Among mandibular fractures, those of the condylar neck hold a special position due to the exceptional anatomical situation. Computer assisted tomography and magnetic resonance tomography have improved diagnostic evaluation. Indication for surgical treatment is given in cases of severely displaced or dislocated fractures. In surgical management, the preauricular, submandibular, retromandibular, and oral approach have been established. For sufficient fixation of fragments, procedures rendering a functional stability, like osteosynthesis with lag screw or by miniplating, are required.
    Notes: Zusammenfassung Die Gelenkfortsatzfrakturen nehmen aufgrund der besonderen anatomischen Situation eine Sonderstellung innerhalb der Unterkieferfrakturen ein. Die Computertomographie und das MRT haben die Diagnostik wesentlich verbessert. Die Indikation zur operativen Behandlung besteht bei stark dislozierten oder luxierten Frakturen. Als operativer Zugang sind der präaurikuläre-, sub- bzw. perimandibuläre, retromandibuläre und orale Zugang etabliert. Zur Fixation der Fragmente sollten ausschließlich funktionsstabile Verfahren, wie die Miniplatte oder Zugschraube verwendet werden.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S177 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Malignes Melanom ; Inzidenz ; Diagnostik ; Therapie ; Key words ; Malignant melanoma ; Incidence ; Diagnostic procedure ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Malignant melanoma is one of the most frequent malignancies of the skin. This is particularly true of malignant melanoma in juveniles. Its incidence has more than doubled from the 1970s to the mid-1990s. Presently, 15 new cases are recorded per 100,000 inhabitants a year in Germany. At Fachklinik Hornheide, a tumor center specializing in skin neoplasm with patients being referred from all over Germany, the number of melanoma patients treated per year has been approximately 500–¶550 for the past 10 years. In the present study, the state-of-the-art therapy for primary melanoma and treatment of the regional lymph node system is discussed. The radical treatment formerly advocated with wide tumor resection plus radical neck dissection is no longer justified for this immunogenic malignant tumor caused by endogenic as well as exogenic factors. “Sentinel lymph node” imaging by means of radioactive substances for diagnosing possible melanoma metastases in adjacent lymph nodes has changed the therapeutical concept. Tumor staging by means of ultrasound, CT, MRT, or PET allows the differentiation of tumors without distant metastases and a favorable prognosis, from melanomas which have to be considered as generalized disease. In addition to surgical resection of the tumor and neck dissection for removal of lymph nodes, adjuvant immunotherapy with interferon-α is capable of prolonging survival without a recurrence. Palliative chemotherapy or immunotherapy are valuable options for cases with generalized melanoma. Vaccination with a melanoma-associated antigen or dendritic cells is at an experimental stage and may become part of future treatment strategies.
    Notes: Zusammenfassung Das maligne Melanom gehört, insbesondere in jugendlichen Altersgruppen, zu den häufigsten malignen Tumoren der Haut. Seine Inzidenz hat sich von den 70er Jahren bis zur Mitte der 90er mit etwa 15 Fällen/¶100.000 Einwohnern und Jahr mehr als verdoppelt. In der Fachklinik Hornheide, einer Tumorklinik der Haut mit bundesweiten Zuweisungen, hat sich dagegen im letzten Jahrzehnt die Zahl der behandelten Patienten auf etwa 500–550 Fälle pro Jahr stabilisiert. Die vorliegende Arbeit soll den aktuellen Standard der Therapie der Primärtumoren und der regionären Lymphabflussregion darstellen. Dabei soll vermittelt werden, dass das frühere radikale Behandlungskonzept mit großflächigen lokalen Tumorresektionen und einer radikalen Ausräumung aller Lymphknotenstationen des Halses diesem immunogenen bösartigen Tumor, dessen Entwicklung teils endogenen und teils exogenen Faktoren unterliegt, nicht mehr gerechtfertigt ist. Schon im Bereich der Diagnostik der fraglichen lymphogenen Metastasierung des Melanoms hat die Darstellung des „sentinel-lymph-node“ mit radioaktivem Material eine Änderung des Therapiekonzepts erzwungen. Das Tumorstaging mit Hilfe der Sonographie, der CT-, der MRT- und PET-Untersuchungen vermag prognostisch günstige Tumoren ohne Nachweis von Fernmetastasen von solchen Melanomen zu unterscheiden, die als generalisierte Erkrankung zu bewerten sind. Neben der operativen Entfernung des Tumors und der Ausräumung der Lymphknotenstationen des Halses ist in bestimmten Stadien die adjuvante Immuntherapie mit Interferon α geeignet, das rezidivfreie Überleben zu verlängern. Bei einer Generalisierung besteht die Option einer palliativen Chemo- oder Immunochemotherapie. Experimentelle Behandlungsansätze überprüfen den Einsatz von Vakzinierungsstrategien mit melanomassoziierten Antigenen und dendritischen Zellen.
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  • 10
    ISSN: 1432-2307
    Keywords: Keywords Monoclonal antibody ; Lymphoma ; Myeloma ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A new monoclonal antibody, Wue-1, which specifically recognizes normal and malignant plasma cells, is characterized. Biochemical studies showed that monoclonal antibodies (mAbs) recognize a protein of 94 kDa. Using triple-staining flow cytometry and double-labeling immunohistochemical techniques, two populations of plasma cells, i.e. lymphoplasmocytoid plasma cells located in the germinal center of lymphoid organs and reticular plasma cells at the paracortex or medullary cords of secondary lymphoid tissues, were distinguished. Wue-1 is expressed when B-cell markers become lost and secretory activity with plasma cell morphology appears. Cell surface markers were identified on normal plasma cells and compared with their malignant counterpart in vivo. Terminal plasma–cellular differentiation of malignant low- and high-grade B-cell lymphoma and anaplastic plasmacytoma, otherwise difficult to identify with conventional B-cell markers on tissue sections or fluorescence-activated cell sorter analyses, were detectable by Wue-1. In cell culture, Wue-1 enhanced the proliferation of myeloma cell lines but not normal plasma cells in a dose-dependent manner. Since Wue-1-induced proliferation was increased by interleukin (IL)-6, Wue-1 recognizes a so far unidentified antigen with functional properties. Therefore, Wue-1 represents a useful new tool for therapy and for the in vivo and in vitro studying of B-cell lymphomas and the mechanisms of B-cell differentiation.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Der Orthopäde 29 (2000), S. 802-807 
    ISSN: 1433-0431
    Keywords: Schlüsselwörter Unterschenkel ; Torsion ; Tibiatorsion ; Untersuchung ; Therapie ; Kind ; Adoleszente ; Bein ; Entwicklung ; Osteotomie ; Keywords Tibia ; Torsion ; Adolescence ; Child ; Osteotomy ; Diagnosis ; Therapy ; Developmental ; Leg
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Tibial torsion defects are usually not clinically evident and, hence, are often overlooked. Clinical examination and CT scan have proved to be the best ways of measuring static tibial torsion, whereas dynamic measurements are usually performed in the clinic and the “gait laboratory.” Only few studies have determined there to be a connection between a torsion defect in the lower leg and expected pathological conditions of the knee and ankle joints. However, patellofemoral instability, Osgood-Schlatter disease, osteochondrosis dissecans are increasingly being found in cases of increased external tibial torsion and arthrosis in reduced torsion. Although spontaneous correction may occur in certain cases, in others the only way to correct the condition is by employing physiologic torsion. Conservative treatment methods such as bandages or ortheses have been shown to not have any effect on torsion; thus, surgical treatment is the only successful way to correct a pathologic angle of rotation of the tibia. For this, supramalleolar osteotomy with fixation using Kirscher wires and plaster or an external fixator are the most common treatments.
    Notes: Zusammenfassung Tibiale Torsionsfehler sind meistens klinisch nicht sehr evident und werden deshalb häufig übersehen. Zur Messung der statischen Tibiatorsion hat sich am besten die klinische Untersuchung und das CT bewährt, während für die dynamische Messung die Klinik und das Ganglabor zum Einsatz kommen. Es gibt nur wenige Studien, die einen Zusammenhang zwischen einem Torsionsfehler des Unterschenkels (US) und zu erwartenden Pathologien des Knie- und Sprunggelenks nachweisen. Immerhin wurden vermehrt patellofemorale Instabilitäten, Morbus Osgood-Schlatter, Osteochondrosis dissecans bei erhöhter Tibiaaußentorsion und Arthrose bei veminderter Torsion nachgewiesen. Während die Korrektur nach Frakturen in gewissen Fällen spontan erfolgen kann, ist bei andern Ursachen keine Korrektur außer der physiologischen Torsion zu erwarten. Konservative Maßnahmen wie Bandagen oder Orthesen haben nachgewiesenerrmaßen keinen Effekt auf die Torsion, sodass bei pathologischem Drehwinkel der Tibia nur die operative Korrektur zum Erfolg führt. Diese wird meistens in Form einer supramlleolären Osteotomie mit Fixation durch Kirscher-Drähte und Gips oder durch einen Fixateur externe durchgeführt.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Manuelle Medizin 38 (2000), S. 335-341 
    ISSN: 1433-0466
    Keywords: Schlüsselwörter Kiefergelenk ; Kraniomandibuläre Dysfunktion (CMD) ; Kraniozervikale Dysfunktion (CCE) ; Kraniosakrale Dysfunktion (CSD) ; Diagnostik ; Therapie ; Keywords Temporomandibular joint ; Craniomandibular disorder ; Craniocervical disorder ; Craniosacral disorder ; Diagnosis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Evaluating the current understanding of craniomandibular disorders means attempting to discern structures among the dysfunctions of this functional disturbance rather than recording the multitude of different forms. Most dentists understand the functioning and dysfunctions of the craniomandibular system (CMS) while most orthopedists have knowledge in the functioning and dysfunctions of the craniocervical systems (CCS), and some are well trained in the disturbances of the craniosacral system (CSS). In clinical practice, however, the specific data and the structural and functional connections are not provided by associative connections. Therefore the figure at the end of the article will help those lacking substantial experience to keep in view the variety of disorders, recognize the inner structure of the dysfunction, consult with colleagues, and begin effective therapeutic procedures.
    Notes: Zusammenfassung Eine bewertende Standortbestimmung zum Thema kraniomandibuläre Dysfunktion vorzunehmen bedeutet nicht, dass versucht wird, die facettenreichen vielgestaltigen Formen von Funktionsstörungen vollständig nachzuzeichnen, sondern vielmehr, das Krankheitsbild – anhand vereinfachter Denkmodelle – durchgängig zu strukturieren. Die meisten Zahnärzte haben Kenntisse über die Funktionen und Dysfunktionen des kraniomandibulären Systems (CMS). Dagegen kennen sich die meisten Orthopäden und Physiotherapeuten gut mit den Funktionen und Dysfunktionen des kraniozervikalen Systems (CCS) aus, etliche auch mit dem kraniosakralen System (CSS). Es sind aber eher die Einzeldaten, die strukturellen und funktionellen Zusammenhänge, die oft nicht durch Assoziationsketten strukturiert sind. Eine tabellarische Übersicht soll deshalb dem noch nicht so Erfahrenen helfen, den Überblick zu behalten und die innere Struktur der Funktionsstörungen zu erkennen, Kollegen gezielt hinzuziehen und die Therapie sinnvoll einzuleiten.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Monatsschrift Kinderheilkunde 148 (2000), S. 475-478 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Tufted Angioma ; Büschelartiges Hämangiom ; Kutane Tumoren ; Therapie ; Key words Tufted angioma ; Hemangioma ; Cutaneous tumor ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Case report: A 16-month-old girl was admitted with a 6-month history of multiple redishblue plaques on the right abdomen. These proved to have increased in size and number daturing a 1.5-year follow-up. Histologically (including histochemistry and electron microscopy), these skin changes were classified as tufted angioma. Tufted angioma is a rare, often multiple benign tumor. Half of the tumors reported develop in children 5 years and younger. The exclusion of malignant tumors (leukemia, lymphoma, neuroblastoma) is important. A punch biopsy is not very traumatic. A subsequent histological examination is highly sensitive and specific. Therapy: There are a few active therapeutic options with rather severel side effects.
    Notes: Zusammenfassung Fallbericht: Bei einem Mädchen im Alter von 16 Monaten traten seit einem halben Jahr am rechten Abdomen multiple, disseminierte rötliche bis bläulich-bräunliche infiltrierte Plaques auf, die innerhalb des 1,5-jährigen Beobachtungszeitraums weiter an Größe und Anzahl zunahmen. Mittels konventioneller Histologie, Immunhistologie und Elektronenmikroskopie sicherten wird die Diagnose eines Tufted Angioma. Das Tufted Angioma ist ein sehr seltener, häufig multipel vorkommender Tumor gutartigen Charakters. Die Hälfte der berichteten Tumoren entwickelte sich innerhalb der ersten 5 Lebensjahre. Deshalb ist der differenzialdiagnostische Ausschluss eines malignen Geschehens (Leukämie, Lymphome, Neuroblastom) von außerordentlicher Bedeutung. Hierzu ist eine Stanzbiopsie ideal geeignet, da sie einfach durchführbar und nur gering traumatisch ist. Die nachfolgende Histologie hat eine hohe Sensitivität und Spezifität. Therapie: Die aktiven therapeutischen Möglichkeiten müssen eher als eingeschränkt und nebenwirkungsreich gewertet werden. Eine spontane Rückbildung ist möglich.
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  • 14
    ISSN: 1433-0423
    Keywords: Schlüsselwörter Okuläres vernarbendes Pemphigoid ; Therapie ; Komplikationen ; Glaukom ; Key words Ocular cicatricial pemphigoid ; Therapy ; Complications ; Glaucoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Cicatricial pemphigoid (CP) is a rare autoimmune disease characterized by subepidermal blistering and progressive cicatrization affecting the skin and mucosa. Ocular involvement occurs in approximately 70% of the patients. Methods: The course of the disease, complications and putative risk factors in patients with ocular cicatricial pemphigoid (OCP) treated at the Departments of Ophthalmology and Dermatology were analyzed retrospectively from 1986 to 1998. Results: Eighteen of 28 patients (64%) with CP demonstrated ocular involvement. The mean age of patients with OCP was 73 years; 61% were female. At the time of referral to our hospital, all patients had reached advanced stage III (83%) or IV (17%) of OCP. In 38% of patients vision was already reduced to 〈20/200 at first presentation. Twenty-eight percent of patients additionally suffered from glaucoma. Two patients exhibited life-threatening extraocular manifestations of CP (larynx stricture, esophagus stricture). Conjunctival or mucosal biopsies were performed in 15 patients with OCP and showed typical immunodeposits at the basement membrane zone in 12/15 patients. Therapy with dapsone (12 patients), oral steroids (11 patients), azathioprine (5 patients), cyclophosphamide (4 patients), colchicine (2 patients) and methotrexate (1 patient) was used concomitantly or consecutively. Complications of OCP including entropion, recurrent epithelial erosions, corneal ulcers, keratitis, and corneal perforations required multiple surgical interventions such as entropion surgery (8 patients), tarsorrhaphy (3 patients), mucous membrane grafting (1 patient), amniotic membrane transplantation (1 patient), tectonic keratoplasty (1 patient), keratoprosthesis (1 patient) and enucleation (1 patient). Despite control of the inflammatory process, further visual loss occurred in 53% of eyes. Reading visual acuity could only be maintained in 35% of eyes. Discussion: Early diagnosis and therapy can prevent ocular complications of OCP. This study indicates that advanced stages of the disease often result in irreversible visual loss despite institution of immunosuppressive therapy. Whether or not the high association of OCP with glaucoma and/or anti-glaucomatous treatment in our patients represents part of the underlying disease process or plays a role in the pathogenesis of OCP must still be clarified.
    Notes: Zusammenfassung Das vernarbende Pemphigoid (cicatricial pemphigoid, CP) ist eine seltene, mit subepidermaler Blasenbildung und Vernarbung einhergehende Autoimmunerkrankung, die sich an Haut und Schleimhaut manifestiert. Eine Augenbeteiligung liegt bei etwa 70% der Patienten vor. Methode: Retrospektiv wurden Krankheitsverlauf, klinische Komplikationen und mögliche Risikofaktoren von Patienten der Augen- und Hautklinik mit vernarbendem Pemphigoid von 1986–1998 untersucht. Ergebnisse: 18/28 Patienten (64%) mit CP hatten eine okuläre Beteiligung. Das Durchschnittsalter der Patienten mit okulärem vernarbendem Pemphigoid betrug 73 Jahre, 61% der Patienten waren weiblich. Bereits bei Erstvorstellung in unserer Klinik bestand bei allen Patienten ein Krankheitsstadium III (83%) oder IV (17%), mit einem Visus 〈0.1 in 38% der Augen. Bei 28% der Patienten wurde zusätzlich ein Glaukom diagnostiziert. Zwei Patienten zeigten eine lebensgefährliche extraokuläre Schleimhautbeteiligung (Larynx- bzw. Ösophagusstriktur). Bei 15 Patienten mit okulärem vernarbendem Pemphigoid wurde eine Bindehaut- bzw. Schleimhautbiopsie aus dem Mund oder Nasen-Rachen-Raum durchgeführt, welche die Verdachtsdiagnose bei 12/15 Patienten immunhistologisch sicherte. Eine Therapie mit Dapson (12 Patienten), oraler Kortikosteroidgabe (11 Patienten), Azathioprin (5 Patienten), Cyclophosphamid (4 Patienten), Colchizin (2 Patienten) und Methotrexat (1 Patient) wurde in Folge oder Kombination eingesetzt. Komplikationen wie Lidfehlstellungen, rezidivierende Epitheldefekte, Hornhautulzera, Keratitiden und Hornhaut-Perforationen erforderten multiple operative Eingriffe wie Entropium-Operation (8 Patienten), Tarsorrhaphie (3 Patienten), Kryoepilation (2 Patienten), Mundschleimhaut-Transplantat (1 Patient), Amniontransplantat (1 Patient), tektonische Keratoplastik (1 Patient), Keratoprothese (1 Patient) und Enukleation (1 Patient). Trotz befriedigender Kontrolle des okulären vernarbenden Pemphigoids kam es bei 53% der Augen zum weiteren Visusabfall. Ein Lesevisus konnte nur in 35% der Augen erhalten werden. Schlußfolgerung: Wahrscheinlich kann die Früherkennung und rechtzeitige Behandlung des okulären vernarbenden Pemphigoids okuläre Komplikationen verhindern. Diese Studie zeigt, daß trotz immunsuppressiver Therapie in Spätstadien häufig ein irreversibler Visusverlust resultiert. Es bleibt zu untersuchen, ob die auffällig hohe Assoziation von okulärem vernarbendem Pemphigoid zu Glaukom bzw. antiglaukomatöser Therapie in unserem Patientenkollektiv als Folge der Grunderkrankung oder als pathogenetischer Faktor zu werten ist.
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  • 15
    ISSN: 1433-044X
    Keywords: Schlüsselwörter Kniegelenkverletzung ; Mediales Kollateralband ; Ruptur ; Gefäßversorgung ; Therapie ; Key words Knee injury ; Medial collateral ligament ; Rupture ; Vascularization ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Because the vascularization of ligaments is an important factor in ligament healing we wanted to examine the vascularization status of the medial collateral ligament of the knee. The type of vascularization was examined by mikroangiographie of 21 postmortem preparations. We could observe a vascularization from the proximal end of the ligament by one or two major vessels in all cases. These vessels were mostly localized in the ventral third of the ligament. From the proximal to the distal part of the ligament we found a decreasing density of blood vessels. We could not observe vessel free ligament areas. Due to this vascularization status we would advise the differentiation of two ligament areas respecting the following therapy. Because of the good vascularization in the proximal part of the ligament we can accept good conditions concerning complete healing after a non-operative treatment and an operative therapy by suture or refixation. In the case of interligamentous and distal ruptures operative reconstruction by sutures often is difficult and a conservative therapy leads to a high rate of poor results. Therefore we advise fibrin bonding in these ligament areas if a surgical procedure is indicated because of the high risk of vessel strangulation after suture.
    Notes: Zusammenfassung Da die Durchblutungsverhältnisse bei Bandrupturen einen wesentlichen Parameter insbesondere bezüglich der Erfolgsaussichten einer chirurgischen Versorgung darstellen, sollte in der vorliegenden Arbeit die Vaskularisation des Knieinnenbandes dargestellt werden. Die spezielle Durchblutungssituation wurde mittels Mikroangiographie an 21 Leichenpräparaten untersucht. Es zeigte sich dabei eine Versorgung von proximal durch 1 oder 2 Hauptgefäßstämme, die bevorzugt in den ventralen Bandanteilen verliefen. Die Gefäßdichte nahm von proximal nach distal sowie von ventral nach dorsal ab. Gefäßfreie Bandabschnitte waren nicht nachweisbar. Aufgrund des proximalen Versorgungstyps kann im proximalen Bandanteil im Vergleich zum distalen Abschnitt mit günstigeren Heilungsvoraussetzungen sowohl nach operativer als auch nach konservativer Therapie gerechnet werden. Dies entspricht den klinischen Erfahrungen. Prognostisch ungünstiger einzustufen sind interligamentäre und distale Bandverletzungen, die insbesondere nach konservativer Behandlung h6auml;ufig unbefriedigende Resultate zeigen. Angesichts der geringeren Vaskularisation der distalen Bandanteile würden wir hier die Bandrekonstruktion mittels Fibrinklebung empfehlen, die eine atraumatische Wiederherstellung ohne die Gefahr der nahtbedingten Gefäßstrangulation erlaubt.
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  • 16
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Pseudotumor orbitae ; Histopathologie ; Therapie ; Rhinochirurgische Zugänge ; Keywords Pseudotumor orbitae ; Histopathology ; Therapy ; Rhinosurgical approaches
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Orbital pseudotumor is a nonspecific inflammatory process of unknown etiology that can be divided histopathologically into three basic types: granulomatous, lymphoid, and sclerosing. Between 1995 and 1998, 12 patients with pseudotumor orbitae were treated in the ENT Department of the University of Saarland. Histopathological examination showed granulomatous type of pseudotumor in six, lymphoid in three, and sclerosing in three patients. In seven cases the pseudotumor orbitae were medially located and in four cases laterally. In one patient nearly all orbital structures were infiltrated. Diagnostic biopsy was taken endonasally in six cases, via medial orbitotomy in two cases, and via lateral orbitotomy in four cases. Due to their good delimitation lymphoid and sclerosing tumors were extracted completely during diagnostic biopsy and patients were free of complaints after a few weeks. The six patients with granulomatous pseudotumor were treated primarily with steroids after the diagnosis had been definitely confirmed by histology. In three of those six cases a second course of steroid therapy had to be given, with positive results in two cases. Follow-up was between 6 and 28 months (mean 16 months). There were no postoperative complications. The clinical and radiographic presentation of the pseudotumors can vary greatly. Therefore, the differential diagnosis of specific infections or neoplasms can only be established through diagnostic biopsy. Different rhinosurgical approaches provide clear biopsy results and in some cases the pseudotumor is even completely removed.
    Notes: Zusammenfassung Der Pseudotumor der Orbita ist ein unspezifischer entzündlicher Prozess dessen Genese unbekannt ist und der histologisch in 3 Gruppen unterteilt wird: der granulomatöse, lymphoide und sklerosierende Typ. Zwischen 1995 und 1998 haben wir 12 Patienten mit einem Pseudotumor der Orbita behandelt. Es handelte sich dabei um Fälle vom granulomatösen (n=6), lymphoiden (n=3) und sklerosierenden (n=3) Typ. Bei 7 Patienten war der Pseudotumor im medialen Bereich der Orbita und in 4 Fällen im lateralen Bereich lokalisiert. Bei einer Patientin lag eine diffuse Infiltration annähernd aller orbitalen Strukturen vor. Die Probebiopsie wurde in 6 Fällen endonasal, in 2 Fällen über eine mediale Orbitotomie und bei 4 Patienten über eine laterale Orbitotomie durchgeführt. Die gut abgrenzbaren lymphoiden (n=3) und sklerosierenden (n=3) Pseudotumoren konnten im Rahmen der Probebiopsie komplett entfernt werden, so dass die Patienten nach wenigen Wochen beschwerdefrei waren. Bei den 6 Patienten mit einem granulomatösen Pseudotumor wurde nach der definitiven Histologie eine primäre Kortikosteroidtherapie durchgeführt. In 3 der 6 Fälle kam es dadurch zu einem Rückgang der Beschwerden mit kompletter Ausheilung. Bei den restlichen 3 Patienten war eine erneute Kortisontherapie erforderlich wobei diese nur in 2 Fällen erfolgreich war. Der Nachbeobachtungszeitraum betrug 6–28 (Mittel 16) Monate. Postoperative Komplikationen traten nicht auf. Die klinische Symptomatik und die radiologische Darstellung der Pseudotumoren kann sehr variabel sein, so dass nur durch eine Probebiopsie eine genaue Differenzierung von spezifischen Infektionen und malignen Raumforderungen möglich ist. Die rhinochirurgischen Zugänge erlauben eine sichere Biopsie und in einigen Fällen auch eine komplette Entfernung des Pseudotumors.
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  • 17
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    Monatsschrift Kinderheilkunde 148 (2000), S. 895-899 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Hydroa vacciniformis ; Klinik ; Differenzialdiagnosen ; Verlauf ; Therapie ; Keywords Hydroa vacciniformis ; Clinical features ; Differential diagnoses ; Course ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Case report. This case of a 6 year old boy presents hydroa vacciniformis, a rare skin disease in children which may also affect the eyes and is caused by UVA exposure. It presents as hemorrhagic small blisters in sun exposed areas that heal with a tendency to scarring, usually with recurrent onset at the beginning of the sunny season until adult age. Differential diagnosis. As possible differential diagnoses polymorphic light eruption, erythropoetic protoporphyria and photodermatitis due to external or systemic photosensitizers must be excluded. In rare cases congenital erythropoetic porphyria, hepatic erythropoetic porphyria, Epstein-Barr virus infection, lymphomatoid papulosis and angiocentric cutaneous T-cell lymphoma may cause the clinical symptoms of hydroa vacciniformis. Therapy. Appropriate therapy consists in protection of skin and eyes against direct and indirect UV radiation, especially UVA-radiation.
    Notes: Zusammenfassung Fallbericht. Anhand der Kasuistik eines 6-jährigen Jungen wird die Hydroa vacciniformis, eine seltene, durch UVA-Exposition ausgelöste Dermatose mit möglicher Augenbeteiligung bei Kindern, vorgestellt. In lichtexponierten Bereichen treten zu Beginn der lichtreichen Jahreszeit rezidivierend bis zum Erwachsenenalter akut zahlreiche hämorrhagische Bläschen auf, die narbig abheilen. Differenzialdiagnose. Differenzialdiagnostisch müssen eine polymorphe Lichtdermatose, eine erythropoetische Protophorphyrie und eine Photodermatose durch exogene bzw. systemische Photosensibilisatoren ausgeschlossen werden. In seltenen Fällen können eine Porphyria erythropoetica congenita, eine hepatoerythropoetische Porphyrie, eine Infektion durch Epstein-Barr-Virus, eine lymphomatoide Papulose und ein angiozentrisches kutanes T-Zell-Lymphom klinisch ähnliche Symptome verursachen. Therapie. Die effektive Therapie besteht im Schutz vor direkter und indirekter UV-Exposition für Haut und Augen, insbesondere im UVA-Bereich.
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  • 18
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Hämangiom ; Büschelartiges Hämangiom ; Diagnostik ; Therapie ; Keywords Haemangioma ; Tufted angioma ; Vascular lesion ; Diagnostic ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background: Tufted angioma represents a benign vascular lesion of the skin. The knowledge of this distinctive entity is important in distinction of clinically more aggressive and malignant neoplasms respectively. Case report. We report a 8-months-old girl who developed a deep seated tufted haemangioma on her right forearm. Sonography and MRI showed a good vascularized tumor with interseptal spreading. Histological examination of the incisional biopsy revealed a cellular capillary haemangioma with morphological features of rare tufted haemangioma. Discussion. Characteristic morphological features of tufted haemangioma allow accurate diagnosis and differential diagnosis to clinically more aggressive and malignant neoplasms of skin and soft tissues, wheras radiological methods are rather unspecific and do not distinguish reliably between these vascular lesions. It is of special clinical importance that tufted haemangioma represents an enlarging but biologically benign vascular neoplasm.
    Notes: Zusammenfassung Hintergrund: Das büschelartige Hämangiom (“tufted angioma”) ist ein benigner vaskulärer Tumor der Haut, dessen Kenntnis in der Differenzialdiagnose zu aggressiveren und malignen Tumoren wichtig ist. Fallbericht. Es wird über ein 8 Monate altes Mädchen mit diesem Tumor im Unterarmbereich berichtet. Sonographie und Magnetresonanztomographie zeigten einen gut vaskularisierten Weichgewebetumor, bei dem aufgrund interseptaler Ausbreitung ein maligner Prozess nicht ausgeschlossen werden konnte. Die Histologie der Inzisionsbiopsie ergab ein zellreiches kapillares Hämangiom, dessen morphologische Veränderungen eine Einordnung als ein seltenes büschelartiges Hämangiom erlaubten. Diskussion. Eine Abgrenzung des büschelartigen Hämangioms gegenüber aggressiveren und malignen vaskulären Läsionen der Haut ist aufgrund des typischen histologischen Bilds möglich, während eine Differenzierung mit Hilfe bildgebender Verfahren nicht gelingt.
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  • 19
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Paraneoplastische zerebelläre Degeneration ; Opsoklonus-Myoklonus-Syndrom ; Limbische Enzephalitis ; Therapie ; Prognose ; Key words Paraneoplastic cerebellar degeneration ; Opsoclonus-myoclonus syndrome ; Limbic encephalitis ; Therapy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Paraneoplastic neurological syndromes are rare diseases that occur in relation to cancer. Supporting the hypothesis of an autoimmune mechanism, specific antineuronal antibodies have sometimes been detected. The current possibilities for treatment are limited. A female patient, aged 57, suffering from a breast cancer, developed a severe paraneoplastic cerebellar syndrome and limbic encephalitis within a few weeks. It is possible that the impressive partial remission that occurred during the ensuing 6 months was not due to therapy. Although the patient was still bound to a wheelchair, discharge from hospital was possible because she was still able to perform daily tasks by herself. A recurrence of the cerebellar symptoms with mild alterations of mental status occurred 2 months later but again showed a good remission.
    Notes: Zusammenfassung Paraneoplastische neurologische Syndrome sind seltene Erkrankungen in Assoziation mit einem Tumor, die bei vermutetem Autoimmunmechanismus mit antineuronalen Antikörpern einhergehen können und deren Verlauf therapeutisch nur bedingt beeinflussbar ist. Berichtet wird von einer 57-jährigen Patientin mit Mammakarzinom, die in engem zeitlichen Rahmen sowohl eine schwere paraneoplastische Zerebellopathie als auch eine limbische Enzephalitis entwickelte. In unklarem Zusammenhang zur Therapie kam es innerhalb von 6 Monaten zu einer vergleichsweisen guten Rückbildung beider Syndrome, so dass zwar noch eine partielle Rollstuhlpflichtigkeit bestand, bei weitgehender Selbständigkeit aber eine Entlassung nach Hause möglich war. Ein Rezidiv 2 Monate später mit im Vordergrund stehender zerebellärer Symptomatik verlief ebenfalls günstig.
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  • 20
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    Der Unfallchirurg 103 (2000), S. 996-998 
    ISSN: 1433-044X
    Keywords: Schlüsselwörter Zungenbeinfraktur ; Diagnostik ; Therapie ; Keywords Hyoid bone fracture ; Diagnosis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract We present a rare case of isolated hyoid bone fracture caused by direct trauma. We will describe the mechanism of injury, how to find diagnosis and our treatment.
    Notes: Zusammenfassung Wir berichten über den seltenen Fall einer isolierten Zungenbeinfraktur bei einem Jugendlichen durch ein direktes Trauma. Erörtert werden Unfallmechanismus sowie Diagnostik und Therapie.
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  • 21
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Larynxkarzinom ; Sacculus laryngis ; Therapie ; Keywords Laryngeal carcinoma ; Sacculus laryngis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The case of a 60-year-old female patient with a supraglottic larynx carcinoma (T3N2CM0) and bilateral enlargement of the laryngeal sacculus is presented. On one side, the sacculus opened atypically into the left vestibular fold. The sacculus is a physiologic part of the roof of Morgagni's ventricle, the size of which can vary greatly. These canal-like structures can be the point of origin of cysts, laryngoceles, mucoceles, and pyoceles. Laryngoceles are present in about 5% of larynx carcinomas; their cause is not precisely known. Frequently, a computer tomogram suggests the coincidence of larynx carcinoma and laryngoceles or a large laryngeal sacculus. In oral panendoscopy, these ventricular distensions are difficult to detect even using 70° rigid endoscopes. A planned supraglottic partial resection must take into account early tumor growth along the preformed canals in the preepiglottic space. In this patient, a laryngectomy was performed due to the bilateral involvement of the vocal process and the anterior commissure.
    Notes: Zusammenfassung Es wird der Fall einer 60-jährigen Patientin mit einem supraglottischen Larynxkarzinoms (T3 N2c M0) und beidseitiger Vergrößerung des Sacculus laryngis vorgestellt. Einseitig mündete der Sacculus untypisch auf der linken Taschenfalte. Der Sacculus laryngis ist eine physiologische Ausstülpung des Daches des Morgagni-Ventrikels, dessen Größe sehr variieren kann. Diese gangartigen Strukturen können Ausgangsort von Zysten, Laryngozelen, Mukozelen und von Pyozelen sein. In ca 5% von Larynxkarzinomen liegen Laryngozelen vor, wobei der disponierende Faktor nicht genau bekannt ist. Oftmals ist der Verdacht der Koinzidenz von Larynxkarzinom und Laryngozele oder großem Sacculus laryngis in der Computertomographie zu stellen. In der Panendoskopie sind diese Erweiterungen der Ventrikel auch mit starren Winkeloptiken schwer zu sehen. Bei geplanter supraglottischer Teilresektion muss man an ein frühes Tumorwachstum entlang der präformierten Gänge in den präepiglottischen Raum denken. Bei der Patientin wurde bei beidseitiger Beteiligung der Processus vocales und der vorderen Kommissur eine Laryngektomie durchgeführt.
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  • 22
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    Der Urologe 39 (2000), S. 539-541 
    ISSN: 1433-0563
    Keywords: Schlüsselwörter Interstitielle Zystitis ; Blasendehnung ; Hydrodistension ; Blasentraining ; Keywords Interstitial cystitis ; Bladder distension ; Bladder training ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Although hydrodistension of the bladder is generally considered standard therapy for interstitial cystitis, scientific data are largely lacking. With the mechanism of action unknown, prospective studies non-existent and the therapeutic effect at best very short-lived, hydrodistension cannot be regarded as a therapeutic standard concept with scientifically validated efficacy. The value of behavioral therapy and bladder training is equally unclear; success can only be anticipated in the very rare subset of patients without pain.
    Notes: Zusammenfassung Obwohl die Hydrodistension der Harnblase ein häufig angewendetes Konzept in der Behandlung der intestitiellen Zystitis (IC) darstellt, ist die wissenschaftliche Datenlage zur therapeutischen Blasendehnung spärlich. Bei ungeklärtem Wirkungsmechanismus, fehlenden prospektiven und kontrollierten Studien und bestenfalls kurzfristiger Effektivität kann die Hydrodistension nicht als therapeutisches Standardkonzept mit wissenschaftlich nachgewiesenem Behandlungserfolg angesehen werden und besitzt eher den Stellenwert eines Heilversuchs. Die Wertigkeit von Blasentraining oder ähnlichen Miktonsverhaltensmodifikationen bei der IC bleibt ebenfalls unklar, ein gewisser Effekt kann allenfalls für die vergleichsweise kleine Untergruppe von IC-Patienten ohne Schmerzkomponente erwartet werden.
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  • 23
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    Der Gynäkologe 33 (2000), S. 104-112 
    ISSN: 1433-0393
    Keywords: Schlüsselwörter Männliche Infertilität ; Therapie ; Medikamente ; Spermatogenese ; Oligozoospermie ; Asthenozoospermie ; Key words Male infertility ; Therapy ; Drugs ; Spermatogenesis ; Oligozoospermia ; Asthenozoospermia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Causal treatment regimens of proven effectiveness in controlled studies are only available for cases of male infertility resulting from hypogonadotropic hypogonadism. Drug treatment of retrograde ejaculation is also effective but has so far not been tested in double-blind, placebo-controlled randomized studies. The results of immunosuppressive therapy in cases of immunological male infertility are still controversial . In addition, antiphlogistic and antibiotic treatment of chronic male genital tract infections has not been shown to improve male fertility. Inconsistent results have been obtained with empirical therapy – e.g., with kallikein, tamoxifen, clomiphene, pentoxifylline, mast cell blockers, testolacton, vitamin E, captopril, alpha receptor blockers, glutathione, indometacin, interferon alpha, growth hormone, zinc salts, ketoprofen, mesterone or testosterone undecanoate – or the studies performed are not sufficient to allow a final judgement. Recent studies have indicated a possible impairment of sperm function by pure FSH, while GnrH and FSH have no influence on spermatogenesis in normogonadotropic men.
    Notes: Zusammenfassung Kausale medikamentöse Therapieregime mit in kontrollierten Studien zweifelsfrei nachgewiesener Wirksamkeit stehen nur bei männlicher Infertilität als Folge des hypogonadotropen Hypogonadismus zu Verfügung. Eine medikamentöse Therapie der retrograden Ejakulation ist ebenfalls effektiv, wurde aber bisher nicht durch doppelblinde, placebokontrollierte, randomisierte Studien ü,berprü,ft. Auch immunsuppressive Therapien bei Nachweis von Spermatozoenantikörpern werden bezüglich ihrer klinischen Wirksamkeit uneinheitlich bewertet. Gleiches trifft auf die Gabe von Antibiotika bei chronisch-entzündlichen Veränderungen oder asymptomatischen Infektionen des Urogenitaltraktes zu. Im Gegensatz dazu sind die Angaben bei empirischer Therapie mit z. B. Kallikrein, Tamoxifen, Clomiphen, Pentoxifyllin, Mastzellblockern, Testolakton, Vitamin E, Captopril, α-Rezeptorenblockern, Glutathion, Indometacin, Interferon-α, Wachtumshormon, Zinksalzen, Ketoprofen, Mesterolon oder Testosteronundecanoat entweder widersprüchlich oder die vorgelegten Studien reichen für eine abschließende Bewertung noch nicht aus. Neuere Studien weisen möglicherweise auf eine Beeinflussung von Spermatozoenfunktionen durch pures FSH hin. Dahingegen haben GnRH und FSH bei normogonadotropen Männern keinen Einfluss auf die Spermatogenese.
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  • 24
    ISSN: 1433-044X
    Keywords: Schlüsselwörter Riesenzelltumor ; Sprunggelenk ; Differentialdiagnose ; Therapie ; Keywords Giant cell tumor ; Ankle joint ; Differentialdiagnosis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The giant cell synovialoma is a benign neoplasia classically located in the fingers. It mostly rises from tendon sheaths, sometimes from the synovia. Other locations than the fingers are rare. Making a differential diagnosis to lipomas, gangliomas or even malignant soft tissue tumors can be very difficult especially in rare locations. We report the case of a 21 years old man suffering from a giant cell synovialoma in the area of the right ankle joint. The clinical, radiological and patho-morphological findings are documented. The tumor was excised totally, other foci were not found. The problems of making the right diagnosis are described.
    Notes: Zusammenfassung Bei dem tenosynovialen Riesenzelltumor handelt es sich um eine benigne Neoplasie, die klassischerweise im Bereich der Finger zu finden ist. Dort geht sie in der Regel von Sehnenscheiden aus, seltener aus der Synovialis hervor. Gerade bei den seltenen und atypischen Lokalisationen kann die differentialdiagnostische Abgrenzung gegenüber Lipomen, Ganglien oder malignen Weichteiltumoren schwierig sein. Es wird über einen 21jährigen Patienten mit einem Riesenzellsynovialom im Bereich des linken Innenknöchels berichtet. Die klinischen, radiologischen und pathologisch-anatomischen Befunde werden dokumentiert. Der Tumor wurde in toto reseziert, andere Herde konnten nicht gefunden werden. Die Problematik der richtigen diagnostischen Einordnung wird dargestellt.
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  • 25
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    Monatsschrift Kinderheilkunde 148 (2000), S. 1072-1077 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Posthämorrhagische Ventrikelerweiterung ; Frühgeborene ; Therapie ; Keywords Posthemorrhagic ; Hydrocephalus ; Preterm ; Infant ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background. 35% of preterm infants with intraventricular hemorrhage develop ventricular dilatation. The posthemorrhagic ventricular dilatation can persist, be transient or be progressive. Finally 1–2% of all very low birthweight (VLBW 〈1500 g) infants require shunt placement for the treatment of the posthemorrhagic hydrocephalus. Outcome. The neurodevelopmental outcome is extremely poor in children surviving progressive posthemorrhagic ventricular dilatation. Therapy. There are no uniform guidelines for the treatment of preterm infants with progressive posthemorrhagic ventricular dilatation. Randomised multicenter trials demonstrated, that inhibition of cerebrospinal fluid production with acetazolamide and furosemide or early cerebrospinal fluid tapping did not reduce the need for shunt placement and may worsen the outcome or can be associated with adverse side-effects. Preterm infants with posthemorrhagic ventricular dilatation should be treated by standard therapy with uniform guidelines for cerebrospinal fluid tapping and shunt placement.
    Notes: Zusammenfassung Hintergrund. 35% der Frühgeborenen entwickeln nach einer intraventrikulären Blutung eine Ventrikelerweiterung. Die posthämorrhagische Ventrikelerweiterung kann persistieren, transient oder progressiv sein. Letztlich entwickeln 1–2% der Frühgeborenen mit einem Geburtsgewicht 〈1500 g einen shuntpflichtigen posthämorrhagischen Hydrozephalus. Prognose. Die Prognose von Frühgeborenen mit progressiver posthämorrhagischer Ventrikelerweiterung ist hinsichtlich Mortalität und neurologischer Morbidität noch sehr ungünstig. Therapie. Bisher gibt es keine einheitlichen Therapierichtlinien für Frühgeborene mit progressiver posthämorrhagischer Ventrikelerweiterung. Multizenterstudien zeigten, dass die medikamentöse Hemmung der Liquorproduktion mit Azetazolamid und Lasix oder frühzeitige serielle Liquorpunktionen die Shuntpflichtigkeit nicht vermindern und den Verlauf und die Prognose sogar ungünstig beeinflussen. Die Erkenntnisse aus diesen Studien mahnen zur Vorsicht. Frühgeborene mit posthämorrhagischer Ventrikelerweiterung sollten außerhalb von Studien möglichst konservativ und zurückhaltend mit einheitlichen Kriterien für Liquorpunktion und Shuntimplantation behandelt werden.
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  • 26
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Wachstumshormon ; Kleinwuchs ; Therapie ; Demographie ; Pharmakoepidemiologie ; KIGS [Kabi] Pharmacia & Upjohn International Growth Study) ; Key words Growth hormone ; Short stature ; Therapy ; Demography ; Pharmaco-epidemiology ; KIGS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Recombinant growth hormone (rGH) therapy in the treatment of children with short stature was introduced 10 years ago, and experience has shown that progress in implementing this mode of therapy depends increasingly on analyses of large pharmaco-epidemiological studies. These studies prove that the diagnosis of growth hormone deficiency, whatever the cause or pathogenetic form, is the most frequent indication for GH therapy. The remaining problems are timely and precise diagnosis, and the best possible and individual therapy aiming at the projected height and taking safety and costs into account. We are closer to solving these problems today than ever before. Apart from this, the use of GH in treating short stature in Turner syndrome and renal insufficiency has led to its acceptance as a suitable therapy for these patients. Height improvement in a number of other growth disorders is, in certain cases, also possible through GH therapy. In the light of current experience, GH therapy can thus be attempted on a rational basis in individual cases. This form of treatment clearly holds wider possibilities and its implementation is likely to go beyond short stature in the future.
    Notes: Zusammenfassung 10 Jahre nach der Einführung von rekombinantem Wachstumshormon (WH) in die Therapie kleinwüchsiger Kinder werden unsere Erfahrungen zunehmend auch durch Analyse umfangreicher pharmako-epidemiologischer Beobachtungen geprägt. Wachstumshormonmangel: Diese zeigen, daß der Wachstumshormonmangel in seinen unterschiedlichen Ursachen und pathogenetischen Erscheinungsformen nach wie vor die häufigste Indikation für WH darstellt. Die Probleme bestehen weiterhin in der rechtzeitigen und rationellen Diagnostik und in der Optimierung und Individualisierung der Therapie zum Erreichen der Wachstumsziele unter ökonomischen Gesichtspunkten und bei gleichzeitiger therapeutischer Sicherheit. Diese Probleme sind für den WH-Mangel heute lösbar. Weitere Indikationen: Ferner zeigt sich, daß auch der Kleinwuchs beim Ullrich-Turner-Syndrom und bei der Niereninsuffizienz, für welche WH zugelassen ist, erfolgreich behandelt werden kann. Bei einer Vielzahl anderer Wachstumsstörungen ist die Möglichkeit zur Größenverbesserung im Einzelfall gegeben. Vor dem Hintergrund heutiger Erfahrungen kann ein individueller Heilversuch so auf eine rationale Basis gestellt werden. Zukunftsperspektiven: In Zukunft wird das breite Wirkpotential von Wachstumshormon über die Indikation des Kleinwuchses hinaus ausgeschöpft werden.
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    Trauma und Berufskrankheit 2 (2000), S. 341-343 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Tarsaltunnelsyndrom ; Ätiologie ; Trauma ; Diagnose ; Therapie ; Keywords ; Tarsal tunnel syndrome ; Aetiology ; Trauma ; Diagnosis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: In this paper we describe the tarsal tunnel syndrome with reference to our own experience in 10 cases and the literature. Compared with the numerous injuries involving the ankle and foot, the diagnosis of tarsal tunnel syndrome is rare. In the case of a painful foot of unknown aetiology, the differential diagnosis should therefore include tarsal tunnel syndrome. Our presentation discusses the aetiology and pathology of the tarsal tunnel syndrome, and particularly that caused by trauma. We also describe an effective therapeutic approach based on surgical decompression.
    Notes: Anhand der Literatur und eigenen Erfahrungen von 10 Operationen wird das Tarsaltunnelsyndrom dargestellt. Gemessen an der Vielzahl der Traumen im Sprunggelenk- und Fersenbeinbereich wird die Diagnose selten gestellt. Bei unklaren Fußschmerzen sollte daher differenzialdiagnostisch ein Tarsaltunnelsyndrom in Erwägung gezogen werden. Es wird auf die Ätiologie, die Pathologie sowie auf den Zusammenhang zu Traumen eingegangen und die effektive Therapie durch operative Dekompression beschrieben.
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  • 28
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    Trauma und Berufskrankheit 2 (2000), S. S180 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter Humeruskopffraktur ; Diagnostik ; Therapie ; Keywords Fracture of the head of the humerus ; Diagnosis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Fractures of the head of the humerus present a challenge both at the stages of diagnosis and treatment. Fortunately, 70–80% ¶of all fractures of the humeral head can be treated conservatively because they are not dislocated. When dislocation is present detailed understanding of the morphology of such fractures and purposeful application of internal fixation techniques are essential for the achievement of good shoulder function. Every step of the treatment is aimed at stability of the joint with its components as close as possible to their original anatomical positions. This can generally be managed with minimally invasive approaches and/or with the bone fragments preserved. We regard depression fractures of the humeral head (〉 45%) in active, older patients –¶who are frequently affected – as a primary indication for a shoulder replacement. Four-fragment fractures with displacement of the head fragment in an older, physically active patient can also occasionally be an indication for primary joint replacement. Both for conservatively treated and for operatively treated fractures of the humeral head a customized schedule of follow-up treatment should be applied, to avoid the precipitation of secondary frozen shoulder by too-passive behaviour. On the other hand, neither should the follow-up treatment programme lead to a secondary dislocation. For restoration of the function it is therefore absolutely essential that the trauma surgeon monitor the treatments applied.
    Notes: Zusammenfassung Humeruskopffrakturen stellen eine Herausforderung an die Diagnostik und die Therapie dar. Glücklicherweise können 70–80% davon konservativ behandelt werden, da sie nicht disloziert sind. Im Fall der Dislokation sind ein differenziertes Verständnis der Frakturmorphologie und der zielgerichtete Einsatz osteosynthetischer Techniken unabdingbare Voraussetzung einer guten Schulterfunktion. Ziel jedweder Behandlungsmaßnahme ist das Erreichen einer stabilen Situation in möglichst anatomiegerechter Position. Dies kann überwiegend mit minimalinvasiven Zugängen bzw. unter Schonung der Knochenfragmente erreicht werden. Besonders im Fall der Humeruskopfimpressionsfrakturen (〉 45%) beim häufig betroffenen älteren, aktiven Patienten sehen wir eine primäre Indikation zur Schulterendoprothese. Ebenso stellen die 4-Fragment-Frakturen mit Verschiebung des Kopffragments bei älteren, biologisch aktiven Patienten eine gelegentliche Indikation zum primären Gelenkersatz dar. Sowohl für die konservativ als auch für die operativ behandelten Humeruskopffrakturen sollte ein differenziertes Nachbehandlungsschema Anwendung finden, um nicht durch zu passives Verhalten eine sekundäre Schultersteife zu initiieren. Auf der anderen Seite sollte ein Nachbehandlungsprogramm auch nicht zur sekundären Dislokation führen. Die unfallchirurgische Kontrolle der Behandlungsmaßnahmen ist daher zwingende Voraussetzung einer bestmöglichen Wiederherstellung der Funktion.
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  • 29
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    Trauma und Berufskrankheit 2 (2000), S. S450 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter Psychisches Trauma ; Psychische Störungen ; Versicherungsschutz ; Kausalität ; Heilverfahrenssteuerung ; Therapie ; Begutachtung ; Keywords Psychological trauma ; Psychological disorders ; Insurance cover ; Legal causality ; Case management ; Therapy ; Expert reviewing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Accident insurance agencies are confronted with an increasing number of cases in which psychological damage occurs immediately at the time of the traumatic events, or in their aftermath. This article reviews the stipulations governing insurance cover and benefits and the legal principles of causality issues in the case of psychological traumas and disorders resulting from such incidents. Insurance agencies face special challenges for case mangagement, since there are no well-established procedures for physicians and hospitals to follow in such cases. Irrespective of the often difficult causality and liability issues, immediate therapy should be given absolute priority. More attention should be paid to psychological damage, with the aims of improving methods of medical rehabilitation and establishing guidelines for expert review in such cases.
    Notes: Zusammenfassung Die Unfallversicherungsträger sind mit einer zunehmenden Zahl von Fällen konfrontiert, bei denen psychische Gesundheitsschäden unmittelbar bei dem Unfallereignis auftreten oder sich nachfolgend entwickeln. Der Beitrag gibt einen Überblick über Grundsätze des Versicherungsschutzes und Kausalitätsfragen bei psychischen Traumen und psychischen Störungen als Folge eines Versicherungsfalls. Für die Unfallversicherungsträger ergeben sich besondere Anforderungen an die Steuerung des Heilverfahrens, da nicht auf das für organische Verletzungen etablierte System besonderer Heilverfahrensarten, wie z. B. das Durchgangsarztverfahren, zurückgegriffen werden kann. Unter allen Umständen hat die Therapie unbedingten Vorrang, unabhängig von der kausalrechtlichen Fragestellung nach dem zuständigen Leistungsträger. Psychischen Gesundheitsschäden ist vermehrt Aufmerksamkeit zu schenken mit dem Ziel, geeignete Maßnahmen der medizinischen Rehabilitation weiterzuentwickeln und Konventionen für die Begutachtung zu schaffen.
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  • 30
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    Trauma und Berufskrankheit 2 (2000), S. S194 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter Fraktur ; Luxation ; Radiusköpfchen ; Olekranon ; Processus coronoideus ; Behandlung ; Keywords Fracture ; Dislocation ; Radial head ; Olecranon ; Coronoid process ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Because of its central location, the elbow joint is considered the most important joint within the upper extremity from the viewpoint of function. Trauma to osseous and ligamentous structures of the proximal forearm confronts trauma surgeons and orthopedic specialists with numerous diagnostic and therapeutic challenges. Conditions following elbow trauma are often accompanied by chronic pain and diminished range of motion, leading to functional deficits of the entire arm. There is now practically no doubt that primary osteosynthesis, anatomical joint reconstruction and early onset of functional treatment are essential for a good ¶final outcome. With our expanding knowledge of the anatomical and biomechanical condtions in the proximal lower arm in the last few decades the basic principles of therapy have also changed, and current standards of treatment for proximal forearm trauma are presented in this paper with reference to the relevant literature.
    Notes: Zusammenfassung Das Ellbogengelenk ist aufgrund seiner zentralen Lage aus funktionellen Gesichtspunkten als das bedeutendste Gelenk der oberen Extremität anzusehen. Knöcherne und ligamentäre Verletzungen im Bereich des proximalen Unterarms konfrontieren den behandelnden Arzt mit einer Anzahl von diagnostischen und therapeutischen Problemen. Posttraumatische Zustände am Ellbogengelenk, die mit chronischer Schmerzsymtomatik und Bewegungseinschränkungen einhergehen, mindern zwangsläufig die Gebrauchsfähigkeit des gesamten Arms. Es besteht heute kaum noch ein Zweifel daran, dass in der Mehrzahl der Fälle eine primäre definitive osteosynthetische Versorgung mit exakter Rekonstruktion der Gelenkfläche für ein befriedigendes Resultat ebenso unverzichtbar ist wie ein frühzeitiger Beginn physiotherapeutischer Übungsmaßnahmen. Mit zunehmendem Verständnis der anatomischen und biomechanischen Besonderheiten des proximalen Unterarms vollzog sich in den letzten Dekaden ein entscheidender Wandel der therapeutischen Grundsätze, deren aktueller Stand in der vorliegenden Arbeit unter Berücksichtigung der relevanten Literatur vorgestellt wird.
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    Clinical and experimental nephrology 4 (2000), S. 273-280 
    ISSN: 1437-7799
    Keywords: Key words Chemokine ; Chemokine receptor ; Kidney ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The presence of leukocytes in the diseased kidneys is a hallmark of almost any kind of renal disease. Activated leukocytes are implicated in playing a crucial role in the pathogenesis of renal diseases. Recent investigations of the pathophysiological roles of chemokines and their cognate receptors have shed light on the detailed molecular mechanisms of leukocyte trafficking and activation in the diseased kidneys. This study summarizes findings that: (1) chemokine/chemokine receptor systems may be essentially involved in the pathogenesis of phase-specific renal disorders, (2) the measurement of urinary levels of chemokines may be clinically useful for monitoring different disease phases and activities in human renal diseases, and (3) interventions in chemokine/chemokine receptor systems may have potential as particular immunotherapeutic strategies to combat specific phases of renal diseases. Further investigations of anti-chemokine therapies for renal diseases will be required before clinical application is feasible.
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  • 32
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    Pediatric surgery international 16 (2000), S. 437-439 
    ISSN: 1437-9813
    Keywords: Key words Peutz-Jeghers syndrome ; Intestinal polyposis ; Intussusception ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a 7-year-old boy, a small-bowel polyp was found intraoperatively as a lead point of an intussusception. Histologically, a hamartoma was found and the clinical work-up revealed Peutz-Jeghers syndrome (PJS). Additionally, all four asymptomatic siblings showed intestinal polyposis. All children in a family with PJS should be properly investigated. In case of an intussusception with a polyp in a critical location, a surgical procedure should follow.
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  • 33
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    Journal of infection and chemotherapy 6 (2000), S. 196-199 
    ISSN: 1437-7780
    Keywords: Key words Anti-retroviral ; Therapy ; Nigeria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Research studies in Nigeria have been done primarily in the areas of epidemiology, clinical practice, virology, and laboratory diagnosis. Therapy for infection with human immunodeficiency virus (HIV) types 1 and 2 has largely focussed on the treatment of the HIV disease (AIDS) rather than the infection. Therefore, opportunistic infections such as tuberculosis, diarrhea, Herpes zoster, and other skin conditions, and tumors (Kaposi's sarcoma) are essentially the targets for therapy. Two reasons are responsible for the dearth of data on anti-retroviral therapy in Nigeria: there was scepticism about zidovudine, the first anti-retroviral drug to be developed, because of its toxicity, and the subsequent reluctance of the Federal Government to allow it into the country. The other reason was the prohibitive cost, making it impossible for patients to afford. That notwithstanding, there have been several uncoordinated and unpublished clinical trials by hospitals in the private sector, as expected, without firm laboratory monitoring or back-up. This review discusses such attempts and the claims of traditional medicine practitioners, as well as pilot studies on private patients with the combination therapy of zidovudine and lamivudine, which agents were allowed into the country in the late 1990s. The patients showed appreciable rises in their CD4 counts, an indirect way of monitoring viral load. This finding was corroborated with results of clinical wellbeing, indicating that they benefitted from the administration of zidovudine and lamivudine.
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  • 34
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S068 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Kraniofaziale Fehlbildungen ; Deformationen des Hirn- und Gesichtsschädels ; Therapie ; Frontoorbitales Advancement ; Key words ; Craniofacial malformations ; Craniofacial skull deformations ; Therapy ; Frontoorbital advancement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Most craniofacial malformations result from a premature fusion of skull sutures. Depending on the scope of the sutures affected, the results are more or less distinct deformations of the facial and cranial skull with substantial negative effects on functional as well as esthetic aspects. The etiopathology is still unclear. Various therapies have been developed over the past 100 years. However, Tessier’s technique of fronto-orbital advancement has been an important milestone in the treatment of these malformations. Numerous adjustments have since perfected this operational technique. It is now possible to treat practically all skull malformations with the surgical techniques available today. At the same time, these techniques have also aided the advancements in tumor surgery and traumatology.
    Notes: Zusammenfassung Kraniofaziale Fehlbildungen entstehen überwiegend durch die vorzeitige Verknöcherung von Schädelnähten. Je nach Nahtbefall resultieren daraus mehr oder weniger ausgeprägte Deformationen des Hirn- und Gesichtsschädels, die sowohl zu einer funktionellen als auch zu einer ästhetischen Beeinträchtigung führen. Die Ätiopathogenese ist noch weitgehend ungeklärt. In den vergangenen 100 Jahren wurden verschiedene Therapieansätze entwickelt, wobei Tessier mit der Technik des frontoorbitalen Advancements der entscheidende Fortschritt gelang. Aufbauend auf dieser Operationstechnik wurden bis heute zahlreiche Verbesserungen eingebracht. Mit den heutigen Operationstechniken ist es möglich, praktisch alle Schädelfehlbildungen zu therapieren. Gleichzeitig konnten durch diese Techniken auch Fortschritte in der Tumorchirurgie und der Traumatologie erzielt werden.
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S076 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Gefäßmalformation ; Nervenmalformation ; Neurofibromatose ; Hämangiom ; Therapie ; Key words ; Vascular malformation ; Neural malformation ; Neurofibromatosis ; Hemangioma ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The presentation of vascular and neural malformations in an understandable terminology permits accurate diagnosis, proper treatment, individualized prognosis, and also stimulates studies of pathogenesis. The descriptive classification includes: NF 1 and NF 2; hemangiomas, low- and high-flow vascular malformations, combined malformations, and hypertrophy; and syndromes such as, Parkes Weber, Klippel-Trénaunay, Maffuci’s, and multiple dysplasia syndromes. Lymphatic malformations are abnormalities of lymphatic development. The list of treatment includes surgical and nonsurgical treatment. Not all vascular malformations can be successfully treated. Coping with NF is a challenge for both, affected individuals and health care professionals. NF is often associated with a myriad of anomalies that present a lot of problems for plastic surgery. In certain cases watchful waiting seems justified but not in cases of severe problems, giant growth, and local complications.
    Notes: Zusammenfassung Die Frage der Terminologie ist im Zusammenhang mit vaskulären und nervalen Malformationen besonders wichtig. Dies gilt nicht nur im Hinblick auf die Wahl des richtigen Therapieverfahrens, sondern auch im Hinblick auf die individuell ausgerichtete Prognose und natürlich auch zur Beantwortung der die Pathogenese betreffenden Fragen. Es ist klar, dass bei Besprechung der Neurofibromatose zunächst an die NF 1 und NF 2 gedacht wird, die Hämangiome werden entsprechend ihrer Durchblutung und auch im Hinblick auf die Kombination mit den so ¶genannten Hypertrophiesyndromen, die später im Text genannt werden, eingeteilt. Dass die Bezeichnung Lymphangiom impliziert, es handle sich um einen Tumor, mag nicht ganz richtig sein, da anscheinend die für Tumoren üblichen Mitosen vermisst werden. Interessant ist das therapeutische Spektrum und dies gilt für alle Malformationen der Gefäße und Nerven, aber ganz besonders natürlich für die Neurofibromatose und die Hämangiome. Mit der NF konfrontiert zu sein, bedeutet für den Patienten und das ärztliche Personal eine lebenslange Herausforderung, darüber hinaus ist die NF häufig mit einer Unzahl von Einzelproblemen vergesellschaftet, die für die plastische Chirurgie z. T. schwere oder nicht zu lösende Probleme darstellen. Die große Zahl an Therapievorschlägen zeigt, dass die Gefäßmalformationen zum einen sehr unterschiedliche Probleme zeigen, und zum anderen, dass es kaum ein Therapieverfahren gibt, welches keinen Wunsch offen lässt. Wichtig ist der Hinweis, dass schnell wachsende Hämangiome durchaus im Anfangsstadium entfernt werden sollten, zuwartende Haltung ist in bestimmten Fällen gerechtfertigt, aber nicht, wenn sich schwere Probleme, Riesenwachstum und lokale Komplikationen einstellen.
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S142 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Tumoren im Kopf-Hals-Bereich ; Therapie ; DÖSAK-Richtlinien ; Key words ; Tumors in the head and neck area ; Therapy ; DÖSAK guidelines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Surgery is still the primary therapeutic approach in treatment of tumors in the head and neck area, dating back to the early nineteenth century. More than 150 years ago, hemimaxillectomies and mandibular resections as well as hemiglossectomies were already performed by leading surgeons. The block principle we are now following dates back to Crile, who also established the principle of cervical lymph node dissection. Ablative oncologic surgery has always been closely linked with plastic and reconstructive surgery, rendering radical surgical interventions possible without disfiguring patients. The development of facial reconstructive surgery proceeded in stages, in the first instance as secondary reconstruction using tube pedicled flaps. The change to the concept of primary reconstruction occurred via arterialized skin flaps and myocutaneous flaps to the widely accepted and performed free tissue transfer. Free bone grafting, inaugurated earlier and still representing the majority of bone grafting, has been supplemented for certain reconstructive purposes by free vascularized bone transfer from various donor sites. Although the five-year-survival rate of carcinoma of the oral cavity has remained unchanged in the past 30 years, distinctive improvements in tumor surgery can be recorded. This is primarily based on improved diagnostics such as modern imaging techniques and the refinement of surgical techniques. The DÖSAK has worked out distinctive guidelines for effective ablative oncologic surgery. Surgical approaches offering wide exposure and carrying low morbidity play a decisive role in radical resections. For this reason, midfacial degloving offers an essential improvement for the resection of midface tumors, especially from an aesthetic point of view. Tumors situated deep behind the viscerocranium at the skull base can be clearly exposed either through a lateral approach following a temporary osteotomy of the mandibular ramus or a transmandibular, transmaxillar, or transfacial approach with minimal morbidity. Concerning the concept of neck dissection, radical techniques are more and more abandoned in favor of a more conservative procedure. Actual inquiries concerning present surgical procedures as to the surgical strategy in “No-neck” or marginal and segmental resection in mandibular adherent carcinomas demand scientific clarification.
    Notes: Zusammenfassung Im Zentrum der Behandlung von Tumoren im Kopf-Hals-Bereich steht immer noch die Chirurgie, deren Ansätze weit in das 19. Jahrhundert zurückreichen. Schon vor weit über 150 Jahren wurden durch wegweisende Chirurgen Halbseitenresektionen des Ober- und Unterkiefers sowie der Zunge durchgeführt. Das heute von uns verfolgte Blockprinzip geht auf Crile zurück, der auch die Prinzipien der Halslymphknotenausräumung festschrieb. Eng verknüpft mit der Tumorchirurgie war stets die plastische und rekonstruktive Chirurgie, die radikalchirurgische Eingriffe ohne Entstellung der Patienten erst ermöglichte. Die Entwicklung der wiederherstellenden Gesichtschirurgie verlief in Phasen, zunächst als sekundäre Rekonstruktion mittels Rundstiellappen. Der Wandel zur primären Wiederherstellung vollzog sich über arterialisierte Hautfettlappen und die Myokutanlappen bis zum heute aktuellen mikrovaskulär anastomosierten Gewebetransfer. Die schon früh inaugurierte und heute noch praktizierte freie Knochentransplantation wurde für spezielle Indikationen durch den mikrochirurgischen Knochentransfer aus verschiedenen Spenderregionen ergänzt. Obwohl die 5-Jahres-Überlebensraten für das Mundhöhlenkarzinom in den letzten ¶30 Jahren stagnieren, sind heute doch deutliche Fortschritte in der Tumorchirurgie zu verzeichnen. Diese beruhen zunächst auf einer verbesserten Diagnostik durch die modernen bildgebenden Verfahren und die Weiterentwicklung der Operationsverfahren. Für eine erfolgreiche Tumorchirurgie hat der DÖSAK klare Richtlinien erarbeitet. Für eine radikale Tumorresektion spielen übersichtliche und wenig destruierende Zugangswege eine entscheidende Rolle. So brachte für die Tumoren des Oberkiefers das Midfacial degloving eine wesentliche Verbesserung, insbesondere auch aus ästhetischer Sicht. Versteckt hinter dem Gesichtsschädel liegende Tumoren an der Schädelbasis lassen sich entweder über einen lateralen Zugang nach temporärer Osteotomie des Unterkieferasts oder transmandibulär, transmaxillär oder transfazial übersichtlich ohne Destruktionen darstellen. Bezüglich der Halslymphknotenausräumung ist eine Abkehr vom radikalen zum konservativen Vorgehen zu verzeichnen. Derzeit aktuelle chirurgische Fragen, wie das operative Vorgehen beim „N 0 -Hals“ oder Kastenresektion bzw. Kontinuitätsresektion des Unterkiefers bei der Mandibula adhärenten Karzinomen, bedürfen einer wissenschaftlichen Klärung.
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  • 37
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    Der Anaesthesist 49 (2000), S. 788-809 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Rechtsherzfunktion ; Störung ; Ätiologie ; Pathophysiologie Diagnostik ; Therapie ; Keywords Impaired right ventricular function ; RV failure ; Diagnosis ; Monitoring ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Impaired right ventricular (RV) function may be caused by pulmonary hypertension or myocardial ischemia. It is characterized by a dilation of the RV, which is followed by an increase of wall tension and O2-consumption and a decrease of RV ejection fraction (RV ‘dysfunction’). If a drop of arterial pressure occurs this my precipitate RV failure and shock (RV ‘insufficiency’). Diagnosis of RV failure and monitoring of RV function is difficult. Sometimes, even a severe impairment of RV function goes undetected or is misinterpreted. Patients in the operating room or on intensive care units seem to be especially prone to RV dysfunction and failure. Since a causative therapy often is not readily available, adequate symptomatic therapy is of utmost importance. Four basic principles have to be considered: 1) Optimizing preload: The failing RV requires adequate filling for preservation of stroke volume. On the other hand, overdistension of the RV may result in RV ischemia, thereby further deteriorating RV function Hence, volume loading is important, but requires continuous monitoring. 2) Maintenance of aortic pressure: Vasopressors are indicated if there is a critical drop of coronary perfusion pressure. Norepinephrine presently is the drug of choice for this purpose. 3) Reduction of RV afterload: Whereas intravenous vasodilators are limited in their efficacy in dilating pulmonary vessels due to systemic side effects, inhaled vasodilators result in selective pulmonary vasodilation and may improve RV function. 4) Increase of RV contractility: In RV failure and shock, norepinephrine and epinephrine are the drugs of choice. Inodilators are well suited for reducing pulmonary vascular resistance due to their positive inotropic and vasodilating effects. Since systemic vasodilation may occur, these drugs must only be used in hemodynamically stable patients.
    Notes: Zusammenfassung Eine Störung der Rechtsherzfunktion entsteht meist als Folge einer pulmonalen Hypertension, seltener bei primärer Myokardischämie. Sie ist gekennzeichnet durch eine Dilatation des rechten Ventrikels mit Anstieg von Wandspannung und Sauerstoffverbrauch bei reduzierter Ejektionsfraktion (“Dysfunktion”). Kommt es zum Abfall von arteriellem Druck und koronarem Perfusionsdruck, kann dies ein Rechtsherzversagen mit Schock auslösen (“Insuffizienz”). Diagnostik und Monitoring des rechten Ventrikels sind schwierig. Selbst eine schwere Beeinträchtigung der rechtsventrikulären Pumpfunktion bleibt daher häufig unbemerkt oder wird fehlgedeutet. Patienten in der perioperativen Phase und auf Intensivstationen scheinen besonders häufig von dem Krankheitsbild betroffen zu sein. Da eine kausale Therapie des akuten Rechtsherzversagens nur selten möglich ist, kommt der symptomatischen Therapie besondere Bedeutung zu. Sie stützt sich auf vier Prinzipien: 1) Optimierung der Vorlast: Der insuffiziente rechte Ventrikel benötigt zur Aufrechterhaltung seines Schlagvolumens ein gute Füllung. Andererseits kann eine Überdehnung des rechten Ventrikels eine Myokardischämie induzieren und seine Funktion weiter verschlechtern. Eine adäquate Volumentherapie ist daher essenziell, muss jedoch unter engmaschigem hämodynamischem Monitoring erfolgen. 2) Aufrechterhaltung des Aortendrucks: Bei kritischem Abfall des arteriellen Drucks ist die Gabe von Vasopressoren indiziert, um den rechtskoronaren Perfusionsdruck zu erhöhen. Noradrenalin gilt derzeit wegen seiner zusätzlich positiv inotropen Wirkung als Mittel der Wahl. 3) Verminderung der rechtsventrikulären Nachlast: Während sich intravenöse Vasodilatatoren wegen systemischer Nebenwirkungen nur bedingt zur Therapie der pulmonalen Hypertension eignen, dilatieren inhalierte Vasodilatatoren die pulmonale Strombahn selektiv und verbessern so die Pumpfunktion des rechten Ventrikels. 4) Steigerung der rechtsventrikulären Kontraktilität: Mittel der Wahl bei Dekompensation und Schock sind Noradrenalin und Adrenalin. Inodilatatoren weisen neben einer positiv inotropen auch eine pulmonal vasodilatierende Wirkung auf und eignen sich daher ebenfalls zur Therapie der rechtsventrikulären Dysfunktion. Sie sollten jedoch wegen der damit verbundenen systemischen Vasodilatation nur bei kreislaufstabilen Patienten eingesetzt werden.
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  • 38
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    Der Anaesthesist 49 (2000), S. 34-42 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter ; Erworbene Hemmkörperhämophilie ; spontane Faktor-VIII-Inhibitoren ; spontane Faktor-IX-Inhibitoren ; Diagnose ; Therapie ; Key words ; Acquired haemophilia ; Spontaneous factor VIII inhibitors ; Spontaneous factor IX inhibitors ; Diagnosis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Although autoantibodies against factor VIII or factor IX are a rare phenomenon, they are associated with a high risk of bleeding and high mortality. The condition, termed ac- quired haemophilia, occurs equally in both sexes and is most frequent in higher age groups. Patients typically present with severe bleedings in muscles and skin. In contrast to patients with congenital haemophilia and inhibitors, joint bleedings are very rare. In approximately half of all cases an associated disease state can be identified as the cause of autoantibody formation. An immediate and comprehensive diagnosis is essential for a rapid initiation of therapy. Equally important are a careful diagnostic differentiation between congenital and acquired factor deficiencies and the exclusion of non-specific inhibitors, which increase the occurrence of thrombolic events. The inhibitor titre, quantified using the Bethesda assay, is an important criterion for selecting the appropriate therapy. A wide range of treatment options is now available for the management of bleedings in patients with acquired haemophilia, namely porcine factor VIII, recombinant factor VIIa, prothrombin complex concentrates, and immunoadsorptions. In addition, immunosuppressive therapies are used to achieve permanent reduction or elimination of inhibitors.
    Notes: Zusammenfassung Autoantikörper gegen Faktor VIII oder Faktor IX sind ein zwar seltenes, aber mit hohem Blutungsrisiko und hoher Letalität verbundenes Phänomen. Diese als erworbene Hemmkörperhämophilie bezeichnete Erkrankung kommt bei beiden Geschlechtern gleich häufig vor und tritt gehäuft im hohen Lebensalter auf. Die Patienten fallen klinisch v. a. durch schwere Blutungen in Muskeln und Haut auf, wogegen Gelenkeinblutungen – im Gegensatz zur angeborenen Hämophilie mit Hemmkörpern – sehr selten auftreten. In etwa der Hälfte der Fälle kann eine assoziierte Grunderkrankung als Auslöser der Autoantikörperbildung identifiziert werden. Eine rasche und umfassende Diagnostik ist entscheidend für einen schnellen Therapiebeginn. Ebenso bedeutend ist eine sorgfältige differentialdiagnostische Abgrenzung gegen einen angeborenen oder erworbenen Faktorenmangel sowie der Ausschluß unspezifischer Inhibitoren, die vermehrt zu Thrombosen führen können. Wichtig für die Auswahl der geeigneten Therapieform ist der Inhibitortiter, gemessen im Bethesda-Assay. Für die Blutstillungstherapie steht heute mit porcinem Faktor VIII, rekombinantem Faktor VIIa, Prothrombinkomplexpräparaten und Immunadsorptionen ein breites Spektrum an Möglichkeiten zur Verfügung. Für eine dauerhafte Reduktion bzw. Elimination der Autoantikörper finden immunsuppressive Therapien Anwendung.
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  • 39
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    Der Anaesthesist 49 (2000), S. 332-339 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Schädelhirntrauma ; zerebrale Hypoxie ; Diagnose ; Therapie ; Key words Brain damage ; Cerebral hypoxie ; Diagnosis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The main reason for posttraumatic secondary brain damage is cerebral hypoxia. Both, severity and duration of hypoxia are crucial in determining wether irreversible cerebral infarction will occur or not. For the clinical routine, the diagnosis of hypoxia is indirectly made by low CPP, low jugularvenous oxygen saturation (SjO2) or low tissue PO2. To minimize misleading false negative SjO2, the CT-Approach for the side of monitorig and calculation of arterial-jugularvenous lactate content for detection of anaerobic metabolism is recommended. Targeted treatment of hypoxia according to the underlying cause is mandatory. Primary goal is to increase cellular oxygen delivery by correction of low arterial oxygen content and elevation of regional CBF. Within the autoregulatory range decreasing CPP causes vasodilation and increasing CPP vasoconstriction with increasing or decreasing cerebral blood volume respectively. Initially elevation of the lower autoregulatory threshold often requires CPP 70 mmHg. Targeted treatment of intracranial hypertension must avoid decreasing CPP. In the early postrautmatic phase prevention of cerebral hypoxia relies on management of CBF by means of CPP and cerebral vascular resistance. Thereafter targeted treatment of intracranial hypertension caused by cerebral edema and hypervolemia are increasingly important.
    Notes: Zusammenfassung Hauptursache der sekundären Hirnschädigung ist die zerebrale Hypoxie. Abhängig von Schweregrad und Dauer entsteht eine irreversible Hirngewebsschädigung. Zur Diagnose der Hypoxie dient unter klinischen Bedingungen die kontinuierliche Messung des zerebralen Perfusionsdrucks (CPP) in Verbindung mit der zerebrovenösen O2-Sättigung (SjO2) oder der O2-Partialdruckmessung im Hirngewebe. Zur Minimierung von SjO2-Fehlinterpretationen sollte nach CT-Approach punktiert und ein anaerober Hirnstoffwechsel durch Bestimmung der arterio-jugularvenösen Laktatkonzentrationsdifferenz (avDL) ausgeschlossen werden. Die Therapie der zerebralen Hypoxie sollte kausal erfolgen. Normalisierung des arteriellen O2-Gehalts und Steigerung der Hirndurchblutung (CBF) haben Prioritöt. Bei intakter Autoregulation der CBF wird ein CPP-Abfall durch Vasodilatation mit Zunahme des zerebralen Blutvolumens und ein CPP-Anstieg durch Vasokonstriktion mit Abnahme des CBV kompensiert. Die häufige posttraumatische Rechtsverschiebung der unteren Autoregulationsschwelle erfordert in der Initialphase mit dem höchsten Hypoxierisiko CPP-Werte 70 mmHg. Die Therapie des ICP 〉 20 mmHg erfolgt CPP-orientiert. Eine ICP-Senkung zu Lasten des CPP ist zu vermeiden. Initial nach SHT hat die individuelle Optimierung der CBF durch Sicherstellung eines adäquaten CPP und zerebrovaskulären Gefäßwiderstandes (CVR) Priorität. Nachfolgend gewinnen durch SjO2 und avDL- oder Gewebe-PO2-Messung kontrollierte Maßnahmen zur Modulation von CVR und CBV sowie die Hirnödemtherapie zunehmend an Bedeutung.
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  • 40
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    Annals of hematology 79 (2000), S. 175-182 
    ISSN: 1432-0584
    Keywords: Monoclonal antibody ; Radioimmunotherapy ; Lymphoma ; Therapy ; Review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 41
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Lichen sclerosus et atrophicus ; Therapie ; CO2 Laser ; Keywords Lichen sclerosus et atrophicus ; Therapy ; Carbon dioxide laser
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract A 50 year old woman with distinct lichen sclerosus et atrophicus was suffering from severe genital itching, dyspareunia and increasing urinary burning. Therapy attempts with topical glucosteroids and estrogens had been without effort. Treatment with CO2 laser in silk touch mode under insufflation anesthesia to an improvement of her skin lesions and a nearly complete remission of her symptoms.
    Notes: Zusammenfassung Wir berichten über eine 50jährige Frau mit einem ausgeprägten Lichen sclerosus et atrophicus vulvae. Die Patientin litt unter stärkstem genitalen Pruritus, einer Dyspareunie und zunehmenden, brennenden Schmerzen beim Wasserlassen. Therapieversuche mit glukokortikosteroid- und östrogenhaltigen Externa erbrachten keine Besserung. Eine Behandlung in Intubationsnarkose mit dem CO2-Laser im Silk-touch-Modus führte zu einer Besserung der Hautveränderungen und zu einer beinahe kompletten Remission der subjektiven Beschwerden.
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  • 42
    ISSN: 1432-1076
    Keywords: Key words Long-term late effects ; Childhood ; Cancer ; Therapy ; Follow-up examinations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intensive multimodality treatment has led to a remarkable improvement of prognosis in paediatric cancer patients, however, a great number of long-term survivors suffer from considerable tumour- or treatment-related late effects. Between January 1990 and December 1998, 223 consecutive survivors of childhood malignancies entered a prospective follow-up study designed to evaluate the frequency and severity of tumour- and/or therapy-related long-term sequelae. After cessation of therapy and subsequently once a year, all patients underwent a detailed examination programme including physical examination, laboratory tests, abdominal sonography, echocardiography, electrocardiography, electroencephalography, spirometry, audiometry, ophthalmological examination and endocrine stimulation tests. Median follow-up was 5 years (range 0.4 to 9.6 years). A total of 167 patients (75%) had at least one chronic medical problem of whom 80 needed permanent medical support. The organ systems most frequently affected were the nervous system in 39%, the endocrine system in 32%, the ears/eyes in 22%, the kidneys in 17%, and the liver in 12% of the patients. Some late effects (endocrine deficits, hearing loss, tubulopathy) were primarily diagnosed only several years after the end of oncological therapy. Conclusion The results of this study indicate that a considerable number of former paediatric cancer patients suffer from remarkable long-term side-effects. Since life quality is an important parameter of cancer survival, careful follow-up of long-term survivors is mandatory with the aim to reduce or even abrogate possible side-effects at the earliest time.
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  • 43
    ISSN: 1432-1076
    Keywords: Key words Erythropoietic protoporphyria ; Ferrochelatase ; Mutation ; Inheritance ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Erythropoietic protoporphyria (EPP, MIM 177000) is an inherited disorder caused by a partial deficiency of ferrochelatase (FECH) which catalyses the chelation of iron into protoporphyrin to form haem. The majority of EPP patients experience solely a painful photosensitivity whereas a small number of them develop liver complications due to the accumulation of excessive amount of protoporphyrin in the liver. EPP is considered to be an autosomal dominant disorder, however, with a low clinical penetrance. To date, a total of 65 different mutations have been identified in the FECH gene of EPP patients. Among the 89 EPP patients who carry a “null allele” mutation which results in the formation of a truncated protein, 18 of them developed EPP-related liver complications. None of the 16 missense mutations identified among 19 patients on the other hand, have been associated with liver disease (P = 0.038). The allelic constellation of an overt patient consists of a mutated FECH allele and a “low expressed” normal allele and that of an asymptomatic carrier, a combination of a mutated and a normally expressed FECH allele. The identification of the “low expressed” allele is facilitated by haplotype analysis using two single nucleotide polymorphisms, −251 A/G in the promoter region and IVS1−23C/T. At the current time when only partially effective therapies are available, the disclosures of both “null allele” and the “low expression” mechanisms will improve patient management. Conclusion While covering the important clinical aspect of erythropoietic protoporphyria, this article emphasises the latest achievements in the molecular genetics of the disorder.
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  • 44
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    Der Hautarzt 51 (2000), S. 19-24 
    ISSN: 1432-1173
    Keywords: Schlüsselwörter ; Kutane B-Zell-Lymphome ; Therapie ; Key words ; Cutaneous B-cell lymphomas ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Background and objective: Primary cutaneous B-cell lymphomas (PCBCL) represent a unique type of extranodal B-cell lymphomas. Recently, the „European Organization for Research and Treatment of Cancer (EORTC)–Cutaneous Lymphoma Study Group” classified PCBCL into two major groups: one with low-grade malignancy and excellent prognosis (follicle center cell lymphoma, immunocytoma/marginal zone B-cell lymphoma) and the other with intermediate malignancy and worse prognosis (large B-cell lymphoma of the leg). The clinical course and the prognosis of both groups clearly distinguish them from nodal lymphomas with similar morphological aspects, thus underlying the need for different treatment modalities. Patients/Methods: We investigated retrospectively the therapeutic data from 51 patients with PCBCL (40 lowgrade lymphomas, 11 large B-cell lymphomas). Several treatment modalities were used: total excision, radiotherapy, polychemotherapy, systemic corticosteroids, systemic antibiotics, as well as a variety of combination treatments. Results: Recurrence, dissemination and/or death of the patients were not significantly related to any single treatment modality. Conclusions: In our opinion, the choice of treatment for PCBCL depends on the histologic classification, the number, spread and localization of the infiltrates, and on the general condition of the patient.
    Notes: Zusammenfassung Hintergrund und Fragestellung: Primäre kutane B-Zell-Lymphome (PKBZL) stellen eine eigenständige Krankheitsgruppe lymphoproliferativer Tumoren dar. In der vor kurzem von der „European Organization for Research and Treatment of Cancer (EORTC)-Cutaneous Lymphoma Study Group” publizierten Klassifikation kutaner Lymphome wurden 2 Hauptgruppen der PKBZL beschrieben: Eine mit niedriger Malignität und exzellenter Prognose (Keimzentrumslymphome, Immunozytom/„Marginalzonelymphom”) und eine 2. mit intermediärer Malignität und schlechterer Prognose (großzelliges B-Zell-Lymphom der unteren Extremitäten). Der Verlauf und die unterschiedlichen Prognosen weisen darauf hin, dass es notwendig ist, eine dem klinischen Verhalten entsprechende Therapieform zu wählen. Patienten/Methodik: Wir untersuchten die Verlaufsdaten von 51 Patienten mit PKBZL (40 niedrig maligne PKBZL und 11 großzellige PKBZL) retrospektiv. Als Behandlungsformen kamen Totalexzision, Strahlentherapie, systemische Kortison- und Antibiotikatherapie, Polychemotherapie sowie verschiedene Kombinationstherapien zur Anwendung. Ergebnisse: Das Auftreten von Rezidiven sowie von Lymphknoten- oder Organbeteiligungen stand in keinem signifikanten Zusammenhang mit der gewählten Therapiemodalität. Schlussfolgerungen: Aus der Vielzahl der verwendeten Behandlungsformen ist die Komplexität der Erkrankung an sich und die der Wahl der Therapie ersichtlich. Unserer Meinung nach sollte die Behandlung der PKBZL in Abhängigkeit von der histologischen Klassifikation, der Anzahl, Ausdehnung und Lokalisation der Hautinfiltrate sowie vom Allgemeinzustand des Patienten gewählt werden.
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    Intensive care medicine 26 (2000), S. 981-987 
    ISSN: 1432-1238
    Keywords: Key words Superoxide ; Reactive oxygen species ; Propofol ; Herbicide ; Therapy ; Hypnotics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To investigate whether the antioxidative sedatives propofol and thiopental can improve recovery from acute paraquat toxicity in A549 cells and in mice.¶Design: Prospective, controlled, dose-response, in vitro study and prospective, controlled animal study. Setting: A university animal research laboratory.¶Subjects: Established human lung cultured cells and male SPF ICR mice. Interventions: Paraquat-treated (0.2 mM) A549 cells were incubated either with the antioxidative sedatives propofol (0–0.56 mM) or thiopental (0–2.0 mM), or the non-antioxidative sedatives diazepam (0–3.0 mM), midazolam (0–3.0 mM) and ketamine (0–9.0 mM), as well as the antioxidative drugs, trolox (0–2.0 mM), α-tocopherol (0–4.4 mM), antioxidative-processed food (AOB; 0–1.0 mg/ml), superoxide dismutase (SOD; 0 and 3,000 U/ml) and ulinastatin (0 and 50,000 U/ml), for 48 h. Paraquat-treated mice received i. v. injections of 10 mg/kg propofol, 5 mg/kg thiopental, 4.0 mg/kg trolox, 100 mg/kg α-tocopherol, 10 mg/kg AOB or 5,000 U/kg SOD, b. i. d. for 4 days (n = 10 each). Measurements and results: Post-administered propofol and thiopental, as well as the antioxidative drugs, trolox, α-tocopherol and AOB, improved A549 cell survival in vitro. The non-antioxidative sedatives SOD and ulinastatin were not protective. An i. p. injection of 50 mg/kg of paraquat resulted in a survival rate of 40 % in mice at day 6. Propofol, trolox, α-tocopherol and AOB significantly lowered the mortality rate (80 % survival), while thiopental did not.¶Conclusion: Post i. v. injection of propofol is protective against paraquat-induced damage. Propofol can be given during mechanical ventilatory support after paraquat poisoning.
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  • 46
    ISSN: 1432-198X
    Keywords: Key words Chronic relapsing thrombotic thrombocytopenic purpura ; von Willebrand factor-cleaving protease deficiency ; Autosomal recessive inheritance ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A child with chronic relapsing thrombotic thrombocytopenic purpura (TTP/HUS) had recurrent thrombocytopenia, microangiopathic hemolytic anemia with fragmented erythrocytes, microthrombi in the lung vessels, and renal dysfunction. Assay of von Willebrand factor (vWF)-cleaving protease showed a complete protease deficiency in the patient and subnormal activities in the mother and in two asymptomatic siblings. No inhibitor of vWF-cleaving protease was detected in the patient’s plasma. Periodic transfusions of fresh-frozen plasma prevented further acute episodes of TTP/HUS. Specific diagnosis of the constitutional deficiency of vWF-cleaving protease helps to provide successful prophylactic therapy.
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  • 47
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    Der Radiologe 40 (2000), S. 989-997 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Bakterielle Meningitis ; Enzephalitis ; Diagnostik ; Therapie ; Keywords Bacterial meningitis ; Encephalitis ; Diagnosis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Despite the progress, which has been made in diagnosis and therapy of encephalitis and bacterial meningitis, these acute inflammatory diseases of the brain still display a certain amount of morbidity and mortality. History, physical examination, analysis of serum and cerebrospinal fluid and radiological examination are the mainstay for the diagnosis of these diseases. With respect to the acute inflammatory diseases of the brain computed tomography and magnetic resonance imaging fulfill three purposes: 1. They can be used to clarify the diagnosis and to rule out other diseases. 2. They can identify the focus from which a bacterial meningitis can evolve. 3. Complications like edema, cerebral vasculitis, septic sinus thrombosis, hydrocephalus or abscess can be visualized. If the diagnosis is made early, the possible complications are recognized in good time and the appropriate therapy is started immediately, then morbidity and mortality can be kept at a minimum.
    Notes: Zusammenfassung Die bakterielle Meningitis und die Enzephalitis sind akut-entzündliche Hirnerkrankungen, die trotz aller Fortschritte in der Diagnostik und Therapie mit einer nicht unerheblichen Morbidität und Mortalität behaftet sind. Die Anamnese, die körperliche Untersuchung, die laborchemische Diagnostik von Blut und Liquor und die Bildgebung sind die wesentlichen Säulen in der Diagnostik akut-entzündlicher Hirnerkrankungen. Die Bildgebung, die mittels Computertomographie bzw. Kernspintomographie erfolgt, hat in diesem Zusammenhang 3 Aufgaben: 1. Sie kann dazu beitragen, die Diagnose zu sichern bzw. differentialdiagnostisch in Erwägung zu ziehende Erkrankungen auszuschließen oder nachzuweisen. 2. Sie kann bei der bakteriellen Meningitis entzündliche Foci im Bereich der Nasennebenhöhlen, des Mastoids oder des Mittelohrs erkennen, die sofort operativ saniert werden müssen. 3. Komplikationen akut-entzündlicher Hirnerkrankungen können bei entsprechendem klinischem Verdacht mittels Bildgebung nachgewiesen werden. Hirnödem, vaskulitische Infarkte, septische Sinusthrombose, Hydrozephalus oder Abszess stellen die wesentlichen Komplikationen dar, die zur Morbidität und Mortalität akut-entzündlicher Hirnerkrankungen beitragen und die umgehend mit einer spezifischen Therapie angegangen werden müssen.
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  • 48
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    Der Schmerz 14 (2000), S. 340-345 
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Akut ; Behandlungsmodell ; Chronisch ; Langzeitbetreuung ; Muskuloskelettaler Schmerz ; Rheuma ; Schmerzverstärkung ; Therapie ; Keywords Acute ; Chronic ; Long-term therapy ; Musculosceletal pain ; Pain enhancement ; Rheumatic disease ; Therapy ; Treatment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background. In paediatrics, numerous diseases present with the leading symptome of muscular, articular, or bone-related pain. The pain as such is seldom diagnostic with regard to pain etiology. Regularly, the significance of inflammatory as well as non-inflammatory pain is underestimated. Classification of musculosceletal diseases. We present 4 case reports, illustrating the classification of musculosceletal diseases into 4 main groups, being the basis for the modelling of disease, and pain treatment. Therapy. Pain therapy is either symptomatic or based on specific pathophysiology. Pain therapy consists of the moduls analgesics, antiphlogistics, physiotherapy, psychosocial support, and complementary therapies. We give advice on differential therapy. A transparent team-oriented concept comprising physicians, physiotherapists, ergotherapists, psychologists, and social workers is the basis for any successful long-term therapy. Regular outpatient visits in consent with the family doctor are mandatory as are education and treatment periods on ward. We encourage our patients to join formal self-supportive patient groups.
    Notes: Zusammenfassung Hintergrund. Eine Vielfalt an Grunderkrankungen präsentiert sich im Kindesalter mit Schmerzen des Bewegungsapparats als Leit- oder Begleitsymptom. Die Schmerzäußerung allein lässt nur selten eine sichere ätiologische Differenzierung zu. Entzündliche sowie nichtentzündliche muskuloskelettale Beschwerden werden regelmäßig in ihrer Bedeutung unterschätzt. Hauptgruppen muskuloskelettaler Erkrankungen. Anhand von Fallbeispielen unterschiedlicher Schmerzcharakteristik und Begleitsymptomatik stellen wir 4 Hauptgruppen muskuloskelettaler Erkrankungen vor. Diese Einteilung ist Grundlage der Entwicklung von Krankheits- und Behandlungsmodellen des Schmerzes. Therapie. Die Schmerztherapie ist teils symptomatisch, teils pathophysiologisch begründet, und besteht aus den Therapiemodulen Analgetika, antiinflammatorische Therapie, Krankengymnastik, psychosoziale Begleitung und komplementäre Therapien. Hinweise für die Differenzialtherapie werden angegeben. Ein für alle Beteiligten transparentes teamorientiertes Konzept mit der Einbindung von Ärzten, Krankengymnasten, Ergotherapeuten, Psychologen und Sozialarbeitern hat sich als Grundlage einer erfolgreichen Langzeitbetreuung erwiesen. Wichtig sind regelmäßige ambulante Kontakte in Absprache mit dem Hausarzt, ggf. Schulungen und stationäre Aufenthalte. Die Zusammenarbeit mit Selbsthilfegruppen hat sich innerhalb eines solchen Therapieplans erfolgreich etabliert.
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  • 49
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    Der Schmerz 14 (2000), S. 429-434 
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Interdisziplinäre Schmerzkonferenz ; Diagnose ; Therapie ; Keywords Interdisciplinary pain conference ; Diagnosis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background. In the interdisciplinary Pain Conference, pain specialists of various disciplines discussed – partly in the presence of the concerned patient – explanations as to the cause of a specific pain. The following example portrays the events of the conference. Case report. In this case, despite extensive diagnostics, no explanation due to an organ failure could be found for a 74-year-pld man with worsening neurological pain above the knee. The patient's desire the change was so strong that after ineffective outpatient care and different operations, such as hernitomy, fibroma removal and the implantation of an epidural stimulating electrode (SCS), other inpatient pain therapies followed using anasthesiological, balneophysical and psychological techniques, as well as medications. Diagnosis and therapy. The interdisciplinary discussion, including all the various diagnostical findings and the results of the therapeutical efforts, lead to the decision by conference participants to use the new electrophysical and imaging diagnostics. This lead to the discovery of a leiomyosarcoma, which had surrounded the N. obtoratius. After the removal surgery, the pain was gone and the pain medications being used could gradually be dropped.
    Notes: Zusammenfassung Hintergrund. In interdisziplinären Schmerzkonferenzen diskutieren Fachvertreter unterschiedlicher, am Schmerz beteiligter Disziplinen – teilweise in Anwesenheit des betroffenen Patienten – um zur Klärung einer schwierigen Schmerzerkrankung beizutragen. Exemplarisch wird ein entsprechender Ablauf dargestellt. Fallbericht. Bei dem vorgestellten Fall handelt es sich um einen 74-jährigen Mann mit einem über Jahre stärker werdenden neuralgischen Oberschenkelschmerz, der trotz umfangreicher Diagnostik keinem organischen Korrelat zugeordnet werden konnte. Der Leidensdruck des Patienten war so erheblich, dass nach ineffektiven ambulanten Behandlungsversuchen verschiedene Operationen wie Herniotomie, Fibromentfernungen und die Implantation einer epiduralen Stimulationselektrode (SCS) sowie wiederholte stationäre schmerztherapeutische Interventionen mit anästhesiologischen, balneophysikalischen und psychologischen Techniken und medikamentösen Konzepten erfolgten. Diagnose und Therapie. Der interdisziplinäre Austausch, die differenzialdiagnostische Sichtung sämtlicher Befunde unter Einschluss der Ergebnisse bisheriger therapeutischer Bemühungen führte zum Beschluss der Konferenzteilnehmer, eine erneute differenzierte elektrophysiologische und bildgebende Diagnostik durchzuführen. Diese führte zur Aufdeckung eines Leiomyosarkoms, welches den N. obturatorius ummauerte. Nach operativer Entfernung stellte sich Schmerzfreiheit ein, sodass die bisherige Schmerzmedikation allmählich abgesetzt werden konnte.
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  • 50
    ISSN: 1432-1076
    Keywords: Key words Renal venous thrombosis ; Neonate ; Incidence ; Therapy ; Outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Renal venous thrombosis (RVT) occurs mainly in the neonatal period and bears a dismal prognosis for individual kidney function. There is no generally accepted therapeutic regimen as controlled clinical trials are lacking. Over the last few years, thrombolytic therapy has been successfully employed by single centres. The present study set out to gather up-to-date information on the incidence, therapy and outcome of neonatal RVT as part of a prospective nation wide survey on neonatal thrombosis in Germany to serve as a basis for therapeutic trials in the future. Between 1992 and 1994 the minimum incidence of symptomatic neonatal RVT in Germany was 2.2 per 100,000 live births (95% confidence interval 1.4–3.3). Out of 35 cases, RVT occurred in 15 premature babies (incidence 13 per 100,000 live births (95% confidence interval 5.9–24.8). Ten babies had associated caval occlusion. Therapy was supportive in 8, low dose heparin was used in 14, full heparinization in 9 and thrombolytic therapy in 4 children. On follow-up after a median time of 11.5 months, renal atrophy was present in 26 out of 39 affected kidneys. Conclusion Neonatal renal venous thrombosis still leads to irreversible kidney damage in the majority of cases. Because of the low incidence a multi-national multi-centre therapeutic trial over a long period has to be considered in order to determine the optimal therapeutic approach.
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  • 51
    ISSN: 1432-1459
    Keywords: Key words Motor neuron disease ; Amyotrophic lateral sclerosis ; Cancer ; Paraneoplastic disease ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined whether patients with both amyotrophic lateral sclerosis (ALS) and cancer differ from classical ALS patients, and whether motor neuron disease responds to oncological therapy. We analyzed clinical and immunological features of 14 patients (9 men, 5 women; mean age 65.3 years) with pure/definite ALS and cancer. Patients with solid tumor cancer and definite ALS were selected according to the El Escorial criteria; cases with ALS plus were excluded. Four patients had breast cancer, three lung adenocarcinoma, and three bowel tumor; hepatocarcinoma, kidney cancer, and mesothelioma were observed in one case each, and in one patient the primary tumor was unidentified. Patients' sera were examined for antinervous system antibodies by means of immunohistochemistry and western blot analysis. Of five patients who underwent surgical therapy, two worsened during the procedure, while the other three had no benefit. The remaining two patients did not improve after chemotherapy and radiotherapy. In none of our cases did the oncological disease progress. Death was a consequence of ALS in all eight patients who died. Median survival was 18 months and did not differ from that of 28 ALS patients matched for age, sex, and onset features (bulbar or spinal). Anti-nervous system antibodies were never detected. We conclude that our group of pure ALS patients with cancer do not significantly differ from patients with classical ALS. They usually die as a consequence of the motor neuron syndrome in the absence of cancer progression. To date we have not observed any response of ALS to antitumor therapy.
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  • 52
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    Journal of neurology 247 (2000), S. 102-105 
    ISSN: 1432-1459
    Keywords: Key words Polymyositis ; Dermatomyositis ; Therapy ; Pulsed ¶dexamethasone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Six patients responded. Side effects were mild. At follow-up five responders were still in remission, without ¶medication. Pulsed high-dose ¶dexamethasone seems beneficial in myositis. A larger, prednisone-controlled trial is justified to analyze long-term efficacy.
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  • 53
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    Archives of gynecology and obstetrics 263 (2000), S. 87-92 
    ISSN: 1432-0711
    Keywords: Key words Ectopic ; Tubal ; Pregnancy ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Ectopic pregnancy is a implantation occurring elsewhere than in the cavity of the uterus, whereas nintynine percent of extrauterine pregnancies occur in the fallopian tube. The incidence of extrauterine pregnancy has increased from 0.5% thirty years ago, to a present day 1–2%. The most frequent cause of tubal pregnancy is previous salpingitis. Mortality rates for tubal pregnancies used to be approximately 1.7% in the 1970 s but dropped to 0.3% in 1980 s. Diagnosis: Using transvaginal ultrasound it is possible to obtain positive evidence of an ectopic pregnancy at a very early stage. In cases of hCG titers〉2000 IU/l, intrauterine pregnancy can be diagnosed with certainty. The most important differential diagnosis of ectopic pregnancy is early intrauterine pregnancy. Clinical management and therapy: Regardless of the therapeutic strategy selected by the physician, informing the patient is a major aspect of the management of ectopic pregnancy. If surgery is considered appropriate, the patient must be informed about the nature, side effects and complications of the procedure. However, it should be remembered that in some cases, the actual chances of cure first become apparent at surgery. In asymptomatic patients with a serum hCG titer 〈1000 IU/l that is falling, it is appropriate to wait and watch. In clinically stable patients with an unruptured tubal pregnancy and steady hCG levels, systemic treatment with methotrexate might also be considered. In unruptured tubal pregnancy with a hCG titer between 1000 and 2500, a further therapeutic alternative is intratubal injection of prostaglandins, hyperosmolar glucose of NaCl. Generally speaking, the currently widespread laparoscopic surgical treatment of the fallopian tube hardly influences the risk of recurrence. If the gestational mass is larger, the serum hCG titer higher than the approximate limit of 2500 mU/ml and/or the tube already ruptured, surgery is usually required. Prevention: The most effective prevention is to avoid tubal inflammation or, in cases of preexisting inflammation, to administer effective therapy.
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  • 54
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    Archives of gynecology and obstetrics 264 (2000), S. 164-165 
    ISSN: 1432-0711
    Keywords: Keywords Factor V Leiden ; Recurrent abortion ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report a case with one intrauterine fetal death (IUFD) at 32 weeks of gestation, one premature delivery at the same week, and one abortion of unknown etiology at 12 weeks of gestation. We discuss that the presence of homozygosity for Factor V Leiden may be associated with placental insufficiency in this woman. Application of anticoagulant therapy may have been beneficial in her current pregnancy.
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  • 55
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    International journal of colorectal disease 15 (2000), S. 127-135 
    ISSN: 1432-1262
    Keywords: Keywords Acute pancreatitis ; Animal models ; Therapy ; Study design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Since randomized controlled studies of severe acute human pancreatitis can be performed only with restrictions, at least some aspects of innovative therapy concepts should first be clarified in animal experiments. In vitro trials are inadequate for this purpose since they cannot simulate the complex course of severe acute pancreatitis. Animal test results can be transferred to clinical practice if the results are based on trials with established models, standardized methods, and a study design imitating the clinical situation. This contribution discusses the demands on such an animal model of acute pancreatitis and a corresponding study protocol and presents models and protocols which meet these requirements. Concrete examples are presented to show that animal experiments are of great value under these conditions, especially in acute necrotizing pancreatitis. Further standardization of models, protocols, and monitoring should further improve future animal therapy studies at least to the extent that it is possible to select particularly promising substances, which should then be tested in randomized controlled trials.
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  • 56
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    Der Hautarzt 51 (2000), S. 604-611 
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Thrombangiitis obliterans ; Morbus Winiwarter-Buerger ; Vaskulitis ; Diagnose ; Therapie ; Keywords Thromboangiitis obliterans ; Buerger's disease ; Vasculitis ; Diagnosis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Thrombangiitis obliterans (Buerger disease) is a rare vascular disease, characterized by a multilocular, segmental, non-arteriosclerotic, thrombotic inflammation of small and medium size arterial and venous vessels and nerves. The precise etiology is unknown, but there is a cause-effect relationship with tobacco smoking. Autoimmunological, immunogenetical, infectious and hemostatic processes have been discussed as pathogenetic factors. The clinical picture is typically characterized by acrally localized, non-healing ulcerations, which frequently prompt patients to see a dermatologist. We present two patients with thromboangiitis obliterans and discuss the clinical features, the resulting differential diagnostic spectrum and possible therapeutic approaches.
    Notes: Zusammenfassung Die Thrombangiitis obliterans (Morbus Winiwarter-Buerger) ist eine seltene Gefäßerkrankung, die durch eine segmentale, multilokuläre, nichtarteriosklerotische, thrombosierende Entzündung der kleinen und mittleren Arterien und/oder Venen und Nerven charakterisiert ist. Die Ätiologie ist bis heute unklar. Es besteht ein kausaler Zusammenhang mit starkem Tabakkonsum. In der Literatur werden autoimmunologische, immungenetische, infektiöse oder hämostaseologische Ursachen diskutiert. Klinisch zeigt sich oftmals das Bild einer distalen arteriellen Ischämie mit einer akral gelegenen Ulzeration ohne Heilungstendenz. Viele Patienten suchen im Laufe einer progredienten, noch nicht diagnostizierten Thrombangiitis obliterans eine fachdermatologische Einrichtung auf. Anhand zweier Kasuistiken werden das Krankheitsbild, die differentialdiagnostische Bandbreite und die möglichen Therapieansätze dargestellt.
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  • 57
    ISSN: 1432-2013
    Keywords: Key words vitamin C (L-ascorbic acid) ; apoptosis ; human articular chondrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chondrocytes present in articular cartilage survive as a resident cell population throughout the lifespan of the individual organism. However, articular chondrocytes as other cells also undergo apoptosis and there is an ever increasing list of diverse stimuli that can induce this phenomenon in vitro. Our main interest was to investigate potential cytotoxic effects of vitamin C (L-ascorbic acid) on human articular chondrocytes. The present study suggests that vitamin C can induce apoptosis in a cell culture of chondrocytes after 18 h of cultivation. Apoptosis-inducing activity of L-ascorbic acid is dose dependent and significantly affected by the presence of serum. The increased number of vitamin C induced apoptotic cells was associated with DNA fragmentation and morphological changes of the cells.
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  • 58
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; antifolates ; apoptosis ; DNA repair ; p53 ; thymidylate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thymidylate synthase (TS) is an essential enzyme for the de novo synthesis of thymidylate and subsequently DNA synthesis. TS has been usedas a target for cancer chemotherapy in the development of fluoropyrimidinessuch as 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine and of novelfolate-based TS inhibitors such as ZD1694 (Tomudex, Raltitrexed), ZD9331,LY231514 (ALIMTA, Pemetrexed), AG337 (Thymitaq, Nolatrexed) and AG331.Although TS has been considered as a target for chemotherapy, the precisemechanism by which TS inhibition leads to cell death is still not completelyresolved. TS inhibition results in depletion of dTTP, an essential precursorfor DNA, and an increase in dUTP. This results in the so-called thymine-lessdeath due to misincorporation of dUTP into DNA; its excision, catalysed byuracil-DNA glycosylase, results in DNA damage. Both this imbalance indTTP/dUTP and DNA damage can result in induction of downstream events, leadingto apoptosis. On the other hand a specific interaction exists betweenoncogenes and TS, by binding of TS protein to the p53and c-mycRNA, while wt p53can also inhibit TS promotor activity. TSinhibition by either 5-FU or antifolates can also result in a depression ofTS protein mediated inhibition of TS mRNA translation leading to induction ofmore TS protein synthesis, and p53protein may further deregulatethis process. These complex indirect and direct interactions between oncogenesand TS may have as yet unclear clinical implications, since most data arebased on in vitroor in vivo studies and some results arecontradictive. In some preliminary clinical studies evidence was postulatedfor a combined prognostic role for TS and p53.This knowledge shouldbe used to design clinical studies with the aim to deliver effective treatmentto potentially sensitive patients both in the adjuvant setting and in advancedstage disease.
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  • 59
    ISSN: 1573-4919
    Keywords: endosulfan ; cytotoxicity ; mitochondria ; apoptosis ; Jurkat cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Several organochlorinated pesticides including DDT, PCBs and dieldrin have been reported to cause immune suppression and increase susceptibility to infection in animals. Often this manifestation is accompanied by atrophy of major lymphoid organs. It has been suggested that increased apoptotic cell death leading to altered T-B cell ratios, and loss of regulatory cells in critical numbers leads to perturbations in immune function. The major objective of our study was to define the mechanism by which endosulfan, an organochlorinated pesticide, induces human T-cell death using Jurkat, a human T-cell leukemic cell line, as an in vitro model. We exposed Jurkat cells to varying concentrations of endosulfan for 0-48 h and analyzed biochemical and molecular features characteristic of T-cell apoptosis. Endosulfan lowered cell viability and inhibited cell growth in a dose- and time-dependent manner. DAPI staining was used to enumerate apoptotic cells and we observed that endosulfan at 10-200 μM induced a significant percentage of cells to undergo apoptotic cell death. At 48 h, more than 90% cells were apoptotic with 50 μM of endosulfan. We confirmed these observations using both DNA fragmentation and annexin-V binding assays. It is now widely being accepted that mitochondria undergo major changes early during the apoptotic process. We examined mitochondrial transmembrane potential (ΔΨm) in endosulfan treated cells to understand the role of the mitochondria in T-cell apoptosis. Within 30 min of chemical exposure, a significant percentage of cells exhibited a decreased incorporation of DiOC6(3), a cationic lipophilic dye into mitochondria indicating the disruption of ΔΨm. This drop in ΔΨm was both dose- and time-dependent and correlated well with other parameters of apoptosis. We also examined whether this occurred by the down regulation of bcl-2 protein expression that is likely to increase the susceptibility of Jurkat cells to endosulfan toxicity. Paradoxically, the intracellular expression of bcl-2 protein was elevated in a dose dependent manner suggesting endosulfan-induced apoptosis occurred by a non-bcl-2 pathway. Based on these data, as well as those reported elsewhere, we propose the following sequence of events to account for T-cell apoptosis induced by endosulfan: uncoupling of oxidative phosphorylation → excess ROS production → GSH depletion → oxidative stress → disruption of ΔΨm → release of cytochrome C and other apoptosis related proteins to cytosol → apoptosis. This study reports for the first time that endosulfan can induce apoptosis in a human T-cell leukemic cell line which may have direct relevance to loss of T cells and thymocytes in vivo. Furthermore, our data strongly support a role of mitochondrial dysfunction and oxidative stress in endosulfan toxicity.
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  • 60
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    Molecular and cellular biochemistry 204 (2000), S. 83-88 
    ISSN: 1573-4919
    Keywords: FHIT ; cell cycle ; ecdysone ; tumor suppressor ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The mechanism of tumor suppressor action of the fragile histidine triad (FHIT) gene is unknown. Disruption of cell cycle regulation leads to the tumor formation and many tumor suppressor genes suppress tumorigenesis through their effect on cell cycle regulation. We examined the expression of FHIT during the cell cycle, and determined whether overexpression of FHIT affects cell cycle kinetics and apoptosis. The FHIT cDNA was cloned into the ecdysone-inducible expression vector in both the sense and antisense orientations. Overexpression of the sense or antisense construct did not affect cell proliferation, cell cycle distribution or apoptosis in human 293T cells. Analysis of the FHIT expression in 293T cells collected at various cell cycle phases showed that the expression of FHIT is not under cell cycle regulation. These results indicate that the tumor suppressor activity of the FHIT gene may be independent of an effect on the cell cycle and apoptosis mechanisms.
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  • 61
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    Molecular and cellular biochemistry 212 (2000), S. 19-28 
    ISSN: 1573-4919
    Keywords: melanoma ; transcription factors ; CREB ; invasion ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The purpose of this study was to determine the role of CREB and its associated proteins in melanoma progression. We used MeWo human melanoma cells transfected with a dominant negative construct of CREB, KCREB. KCREB has a mutation in its DNA-binding domain and can not bind the CRE element. Expression of KCREB yields proper heterodimerization with CREB and its associated proteins, but the proteins associated with KCREB do not confer the same degree of transcriptional activity as they would in the case of wild-type CREB. Here, we demonstrate that expression of KCREB in MeWo melanoma cells leads to a decrease in their tumorigenicity and metastatic potential in nude mice. We identified two mechanisms that explain at least partially this effect of KCREB. The first, is one in which CREB and its associated proteins play an essential role in invasion. We showed that the invasive properties of KCREB-transfected MeWo cells were reduced due to the downregulation of the CRE-dependent expression of the type IV collagenase MMP-2 and the adhesion molecule MCAM/MUC18. In the second mechanism, CREB and its associated proteins act as survival factors for human melanoma cells. Here we demonstrated that expression of KCREB in MeWo cells rendered them susceptible to apoptosis induced by thapsigargin, which in turn increased the intracellular level of Ca2+. Thapsigargin induced CREB and ATF-1 phosphorylation and activated CRE-dependent transcription in MeWo cells. Collectively, our data demonstrate that CREB and its associated proteins play an important role in tumor growth and metastasis of human melanoma.
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  • 62
    ISSN: 1573-4919
    Keywords: T-type Ca2+ channel ; polyglutamine-expanded androgen receptor ; CAG trinucleotide repeats ; spinobulbar muscular atrophy ; apoptosis ; motorneuron ; cell lines ; neuroblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We have analyzed Ca2+ currents in two neuroblastoma-motor neuron hybrid cell lines that expressed normal or glutamine-expanded human androgen receptors (polyGln-expanded AR) either transiently or stably. The cell lines express a unique, low-threshold, transient type of Ca2+ current that is not affected by L-type Ca2+ channel blocker (PN 200-110), N-type Ca2+ channel blocker (ω-conotoxin GVIA) or P-type Ca2+ channel blocker (Agatoxin IVA) but is blocked by either Cd2+ or Ni2+. This pharmacological profile most closely resembles that of T-type Ca2+ channels [1-3]. Exposure to androgen had no effect on control cell lines or cells transfected with normal AR but significantly changed the steady-state activation in cells transfected with expanded AR. The observed negative shift in steady-state activation results in a large increase in the T-type Ca2+ channel window current. We suggest that Ca2+ overload due to abnormal voltage-dependence of transient Ca2+ channel activation may contribute to motor neuron toxicity in spinobulbar muscular atrophy (SBMA). This hypothesis is supported by the additional finding that, at concentrations that selectively block T-type Ca2+ channel currents, Ni2+ significantly reduced cell death in cell lines transfected with polyGln-expanded AR.
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  • 63
    ISSN: 1573-4919
    Keywords: retinoic acid ; RARβ ; protein kinase A ; apoptosis ; caspase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Both cAMP and retinoids play a role in cell differentiation and the control of cell growth. A site-selective cAMP analog, 8-Cl-cAMP and retinoic acid synergistically inhibit growth and induce apoptosis in certain cancer cells. In advanced or recurrent malignant diseases, retinoic acid (RA) is not effective even at doses that are toxic to the host. The objective of our present study was to examine the mechanism(s) of synergistic effects of retinoic acid (9-cis, 13-cis or all-trans RA) and 8-Cl-cAMP on apoptosis in human ovarian cancer NIH: OVCAR-3 and OVCAR-8 cells. RA induced growth inhibition and apoptosis in OVCAR-3 and OVCAR-8 cells. 8-Cl-cAMP acted synergistically with RA in inducing and activating retinoic acid receptor β (RARβ) which correlates with growth inhibition and apoptosis in both cell types. In addition, induction of apoptosis by RA plus 8-Cl-cAMP requires caspase-3 activation followed by cleavage of anti-poly(ADP-ribose) polymerase. Furthermore, mutations in CRE-related motif within the RARβ promoter resulted in loss of both transcriptional activation of RARβ and synergy between RA and 8-Cl-cAMP. RARβ expression appears to be associated with induction of apoptosis. Introduction of the RARβ gene into OVCAR-3 cells resulted in gain of RA sensitivity. Loss of RARβ expression, therefore, may contribute to the tumorigenicity of human ovarian cancer cells. Thus, combined treatment with RA and 8-Cl-cAMP may provide an effective means for inducing RARβ expression leading to apoptosis in ovarian cancer cells.
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  • 64
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    Molecular and cellular biochemistry 203 (2000), S. 59-71 
    ISSN: 1573-4919
    Keywords: PTEN tumor suppressor ; cyclin-dependent kinase inhibitors ; apoptosis ; chemosensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The recently discovered tumor suppressor gene PTEN has been found mutated in many types of advanced tumors. When introduced into tumor cells that lack the wild-type allele of the gene, PTEN was able to suppress the growth of these cells. Here, we have analyzed how PTEN might alter cell cycle-regulatory controls to achieve this growth-inhibitory effect. We found that overexpression of PTEN stimulates the synthesis of three inhibitors of cyclin-dependent kinases, p21WAF1, p27KIP1, and p57,KIP2. This effect is very specific, as the expression of other components of the cell cycle engine, various cyclins and cyclin-dependent kinases, is not affected. For p21WAF1 we show that this induction is due to the p53-independent transcriptional activation of its promoter. In addition, increased expression of PTEN rendered the cells more sensitive to apoptotic cell death. Therefore, our data suggest a two-fold mechanism of growth inhibition by PTEN: one that acts via the increased expression of CKIs such as p21WAF1, and another that augments the cellular propensity for apoptotic cell death.
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  • 65
    ISSN: 1573-4919
    Keywords: tumour necrosis factor ; receptors ; subtypes ; calcium ; apoptosis ; cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Tumour necrosis factor-α (TNF) receptors mediate a variety of effects dependent on cell type. A role for Ca2+ in TNF-induced death remains uncertain. Here we investigated restricting intracellular/extracellular Ca2+ in HeLa epithelial carcinoma cells expressing low and high levels of p75TNFR receptor subtype and KYM-1 rhabdomyosarcoma cells, models of rapid TNF-induced apoptosis. Ca2+-chelators EGTA and BAPTA-AM as well as microsomal Ca2+-ATPase inhibitor thapsigargin, did not alter TNF-induced death. TNF was also unable to alter resting [Ca2+]i levels which remained 〈 200 nM even during times when these cells were undergoing apoptotic cell death. These findings indicate no role for modulated Ca2+ concentrations in TNF-induced apoptotic cell death.
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  • 66
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    Journal of clinical immunology 20 (2000), S. 229-239 
    ISSN: 1573-2592
    Keywords: Aging ; apoptosis ; TNF receptor ; Fas ; Fas ligand ; mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cellular and molecular basis of immune senescence is unclear. A number of mechanisms have been proposed. In this issue of the Journal of Clinical Immunology, some of the mechanisms for various immunologic abnormalities in aging are presented. In this article, various molecular steps of both death receptor and mitochondrial pathways of apoptosis in general are reviewed. In particular, the role of apoptosis in T-cell immune senescence is discussed.
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  • 67
    ISSN: 1573-4919
    Keywords: etoposide ; Bcl-XL ; Bax ; apoptosis ; K562 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Etoposide is a potent anticancer agent that is used to treat various tumors. We have investigated the dose-dependent effect of etoposide on apoptosis using chronic myeloid leukemia K562 cells treated with low (5 μM) or high (100 μM) concentrations of the drug. At a low concentration, etoposide induced little apoptosis at 24 h, while about 20% of the cells showed apoptosis morphologically at a high concentration. Processing of caspase-3 was slightly detected from 12 h and became obvious at 24 h with 100 μM etoposide. Caspase-3-like protease activity was detected at 24 h with a high concentration. Moreover, these changes were accompanied by cleavage of poly ADP ribose polymerase (PARP). Changes of the mRNA levels of most apoptosis-regulating genes were not prominent at both concentrations, except for the rapid induction of c-IAP-2/HIAP-1 and the down-regulation of Bcl-XL by 100 μM etoposide. The downregulation of Bcl-XL protein occurred from 6 h, while Bax protein conversely showed a slight increase from 6 h. Taken together, the present findings show that the dose-dependent apoptotic effect of etoposide is based on a change in the balance between Bcl-XL and Bax, which precedes the activation of caspase-3.
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  • 68
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    Molecular and cellular biochemistry 207 (2000), S. 19-27 
    ISSN: 1573-4919
    Keywords: PKC ; apoptosis ; bile acid ; hepatocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of GCDC-induced apoptosis on PKC activity and PKC's role in GCDC-induced hepatocyte apoptosis is unclear. The specific aims of this study were to determine if GCDC-induced apoptosis changed intracellular PKC activity and if modulation of PKC activity affected GCDC-induced hepatocyte apoptosis. Apoptosis was induced in isolated hepatocytes using GCDC. PKC activity was measured and specific PKC and calpain inhibitors were used to study the effects of PKC and calpain modulation on GCDC-induced apoptosis. After 4 h exposure, 50 μM GCDC induced apoptosis in 42% of hepatocytes. Intracellular PKC activity decreased to 44% of controls 2 h after exposure of hepatocytes to GCDC (p 〈 0.001). Pre-incubation of hepatocytes with the calpain protease inhibitor restored PKC activity in GCDC exposed hepatocytes to 91± 5% of control cells. Pre-incubation of hepatocytes with a calpain inhibitor decreased GCDC-induced apoptosis as did pre-incubation with the PKC activating phorbol ester, PMA. The combination of calpain inhibition and PMA further reduced GCDC-induced apoptosis but caused low level hepatic apoptosis. Inhibition of PKC with chelerythrine also substantially reduced GCDC-induced hepatocyte apoptosis. GCDC-induced apoptosis is associated with decreases in total cellular PKC activity, which appear to be dependent on intracellular calpain-like protease activity. The combination of protease inhibition and phorbol ester pretreatment preserved total cellular PKC activity and decreased GCDC-induced apoptosis but induced low level apoptosis in the absence of GCDC exposure. PKC inhibition also decreased GCDC-induced hepatocyte apoptosis highlighting the complex interactions of PKC and proteases during GCDC-induced apoptosis.
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  • 69
    ISSN: 1573-4919
    Keywords: phosphatidylserine ; base exchange ; apoptosis ; thymocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The exposure of phosphatidylserine toward the external surface of the membrane is a well-established event of programmed cell death. The possibility that an apoptotic stimulus influences the metabolism of this phospholipid could be relevant not only in relation to the previously mentioned event but also in relation to the capability of membrane phosphatidylserine to influence PKC activity. The present investigation demonstrates that treatment of mouse thymocytes with the apoptotic stimulus dexamethasone, enhances the incorporation of [3H]serine into phosphatidylserine. Cell treatment with dexamethasone also enhanced the activity of serine base exchange enzyme, assayed in thymocyte lysate. Both the effects were observed at periods of treatment preceding DNA fragmentation. The addition of unlabelled ethanolamine, together with [3H]serine to the medium containing dexamethasone-treated thymocytes lowered the radioactivity into phosphatidylserine. Serine base exchange enzyme activity was influenced by the procedure used to prepare thymocyte lysate and was lowered by the addition of fluoroaluminate, that is widely used as a G-protein activator. The increase of serine base exchange enzyme activity induced by dexamethasone treatment was observed independently by the procedure used to prepare cell lysate and by the presence or absence of fluoroaluminate.
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  • 70
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    Molecular and cellular biochemistry 212 (2000), S. 35-43 
    ISSN: 1573-4919
    Keywords: cAMP ; CRE ; Cox-2 ; NO ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Previous studies revealed that expression and activation of cyclooxygenase-2 (Cox-2) conveyed a protective principle in murine macrophages, thus attenuating pro-apoptotic actions of chemotherapeutic agents or programmed cell death as a result of massive nitric oxide (NO) generation. Expression of Cox-2 was achieved by treatment of cells with lipopolysaccharide/interferon-γ or nontoxic doses of NO releasing agents. We reasoned E-type prostanoid formation, and in turn an intracellular cAMP increase as the underlying protective mechanism. To prove our hypothesis, we analyzed the effects of lipophilic cAMP-analogs on NO, cisplatin, or etoposide induced apoptosis in RAW 264.7 macrophages. Selected apoptotic parameters comprised DNA fragmentation (diphenylamine assay), annexin V staining of phosphatidylserine, caspase activity (quantitated by the cleavage of a fluorogenic caspase-3-like substrate Ac-DEVD-AMC), and mitochondrial membrane depolarisation (ΔΨ). Western blots detected accumulation of the tumor suppressor protein p53, relocation of cytochrome c to the cytosol, and expression of the anti-apoptotic protein Bcl-xL. Prestimulation with lipophilic cAMP-analogs attenuated apoptosis with the notion that cell death parameters were basically absent. To verify gene induction by cAMP in association with protection we established activation of cAMP response element binding protein (CREB) by gel-shift analysis and moreover, treated macrophages with oligonucleotides containing a cAMP-responsive element (CRE) in order to scavenge CREB. Decoy oligonucleotides, but not control oligonucleotides, attenuated cAMP-evoked protection and reestablished pro-apoptotic parameters. We conclude that gene induction by cAMP protects macrophages towards apoptosis that occurs as a result of excessive NO formation or addition of chemotherapeutica. Attenuating programmed cell death by the cAMP-signaling system may be found in association with Cox-2 expression and tumor formation.
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  • 71
    ISSN: 1573-4978
    Keywords: apoptosis ; CD95 ; human hepatoma cell ; hydrogen peroxide ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Reactive oxygen species (ROS) play an important role in cell death induced by many different stimuli. Direct exposure of human hepatoma cell line SMMC-7221 to hydrogen peroxide (H2O2) can induce apoptosis characterized by morphological evidence and fragmentation of DNA assayed by terminal deoxynucleotidyl transferase assay (TUNEL assay). Analysis of flow cytometry indicated that H2O2 can decrease the level of CD95(APO-1/Fas), and it is confirmed that H2O2 can also activate the differential expression of some specific gene such as p53 by means of RT-PCR technique. The results indicated that CD95 signal transduction system may be involved in the H2O2-induced apoptosis, and can regulate some specific genes associated with apoptosis in transcription and translation levels such as p53.
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  • 72
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    Psychotherapeut 45 (2000), S. 356-365 
    ISSN: 0935-6185
    Keywords: Schlüsselwörter Kindes- und Jugendalter ; Borderlinestörungen ; Misshandlung ; Missbrauch ; Trauma ; Primäre Reaktionen ; Therapeutische Schritte ; Keywords Childhood and adolescence ; Borderline disorder ; Trauma ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Psychology , Medicine
    Description / Table of Contents: Summary The diagnosis of ”borderline disorder” in childhood and adolescence is controversial for different reasons. Multiple deviant be- haviour patterns in young patients are not only a consequence of disturbances in their interpersonal relationships, of their distorted perceptions and/or of their self-, affect- and impulse-regulation. they are often, par- ticularly in childhood, related to traumatic stress, which became an inherent part of their sensomotorical, physical and affective defence structure. Primary modes of reaction lead to habitual behaviour with flight-fight-mechanisms, to accomodation by dissocia- tion, paralysis and avoidance. the consequences are retraumatizations and a standstill in development. The treatment of these disorders requires specific competences of the therapist, e.g. to create safe places, to recognize and handle messages that were enacted or acted out, to work on linguistic confusion and to develop spaces for thinking and playing.
    Notes: Zusammenfassung Die Diagnose einer Borderlinestörung ist im Kindes und Jugendalter aus verschiedenen Gründen umstritten. Die multiplen Verhaltensauffälligkeiten der jungen Patienten sind nicht nur Folge ihrer Beziehungsstörungen, verzerrten Wahrnehmungen und Störungen der Selbst-, Affekt- und Impulsregulation, sondern lassen sich besonders im Kindesalter mit traumatischen Belastungen in Verbindung bringen, die in die sensomotorische, körperliche und affektive Abwehr eingeschrieben sind. Primäre Reaktionsformen führen zu habitualisiertem Verhalten mit Flight-/Fight-Mechanismen, Akkomodationsverhalten mit Dissoziation, Erstarrung und Vermeidung, die Retraumatisierungen und Entwicklungsstops zur Folge haben. Die Behandlung solcher Störungen erfordert spezifische Wahrnehmungs- und Handlungskompetenzen auf Seiten des Therapeuten. Hierzu gehören die Entwicklung sicherer Orte, das Erkennen und Bearbeiten inszenierter und gehandelter Botschaften, die Arbeit an der Sprachverwirrung und die Entwicklung von Räumen des Denkens und Spielens.
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  • 73
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    Molecular biology 34 (2000), S. 875-887 
    ISSN: 1608-3245
    Keywords: antisense oligonucleotides ; oncogenesis ; therapy of cancer ; apoptosis ; bcl family
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Members of the bcl-2 family genes are thought to be central regulators of apoptosis. Overexpression of antiapoptotic proteins, such as Bcl-2 and Bcl-xL, contributes not only to the development of cancer but also to its resistance against a wide variety of anticancer agents. Thus, downregulation of Bcl-2 and Bcl-xL can potentially be used to improve therapeutic approaches to advanced cancer. The use of antisense biotechnology to downregulate antiapoptotic bcl family members in diverse cancers in vitro and in vivo is reviewed. The effects and potential limitations of antisense strategies are also discussed in the context of a critical view of recent research in the field.
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  • 74
    ISSN: 1618-2545
    Keywords: apoptosis ; caspase-3 ; E2F factor ; Lentinula edodes ; mycelial culture broth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Extracts fromshiitake (Lentinula edodes) mycelial culture broth, by an organic solvent ethyl acetate, inhibited the proliferation of cultured cells. At lower concentrations (1.25–15 μg/ml), this inhibition, measured by the MTT assay, was dose- and cell line-dependent. Inhibition of tumor cells, such as Caski, SiHa, HeLa, HP-1 and A375, byL. edodes-436 extracts was stronger than inhibition of normal cells (3T3). At 20 μg/ml, the extracts induced changes in cell shape, DNA-fragmentation and the activation of caspase-3. The extracts also inhibited the binding of E2F protein to its promoter. The results suggest that extracts ofL. edodes culture broth contain substances that have the ability to induce apoptosis in the cultured cells.
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  • 75
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    Medizinische Klinik 95 (2000), S. 293-298 
    ISSN: 1615-6722
    Keywords: Schlüsselwörter: Renovaskuläre Hypertonie ; Renin-Angiotensin-Aldosteron-System ; Diagnose ; Therapie ; Key Words: Renovascular hypertension ; Renin-angiotensin-aldosterone system ; Diagnosis ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background: Renovascular hypertension as a secondary form of hypertension can be improved or cured in many cases by interventional radiology or vascular surgery. Basis: The renin-angiotensin-aldosterone system and the development of hypertension are linked in renovascular hypertension. Clinical Appearance: Early clinical symptoms are of special interest in diagnosing renovascular hypertension. Diagnosis and Therapy: Nowadays, angioplasty or stenting have mostly replaced surgery in view of treatment of renovascular hypertension. Conclusion: Renovascular hypertension, if diagnosed early, can be improved or cured in many cases regarding hypertension and/or renal insufficiency.
    Notes: Zusammenfassung Hintergrund: Der renovaskulären Hypertonie kommt besondere Bedeutung zu, da sie als sekundäre Hypertonieform durch interventionell-radiologische oder gefäßchirurgische Maßnahmen in vielen Fällen erfolgreich therapierbar und zum Teil auch heilbar ist. Grundlagen: Die Entstehung einer renovaskulären Hypertonie ist ursä,chlich mit dem Renin-Angiotensin-Aldosteron-System verknüpft. Klinik: Klinische Hinweise bzw. Krankheitszustände sind von großer Bedeutung für die frühzeitige klinische Verdachtsdiagnose einer renovaskulären Hypertonie. Diagnostik und Therapie: Eine renovaskuläre Hypertonie kann interventionell-radiologisch (Angioplastie oder Stentversorgung), chirurgisch oder medikamentös therapiert werden. Schlußfolgerung: Eine renovaskuläre Hypertonie kann bei frühzeitiger Diagnosestellung unter den Gesichtspunkten Hypertonie und Niereninsuffizienz in vielen Fällen geheilt oder gebessert werden.
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  • 76
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    Medizinische Klinik 95 (2000), S. 527-532 
    ISSN: 1615-6722
    Keywords: Schlüsselwörter Morbus Castleman ; Angiofollikuläre Lymphknotenhyperplasie ; Pathologie ; Präsentation/Klinik ; Therapie ; Pathogenese ; Key Words Castleman's disease ; Angiofollucular lymph node hyperplasia ; Pathology ; Presentation ; Therapy ; Pathogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background: The term “Castleman's diseas” (angiofollicular lymph node hyperplasia) comprises a heterogeneous clinicopathologic entity among lymphoproliferative disorders. Case Report: We present a rare case with retroperitoneal manifestations, and discuss several aspects of diagnosis, differential diagnosis, the clinical course and therapy of the disease. Finally, we summarize the actual knowledge about the pathogenesis of Castleman's disease.
    Notes: Zusammenfassung Hintergrund: Als Morbus Castleman (angiofollikuläre Lymphknotenhyperplasie) wird ein heterogenes, histologisch definiertes Krankheitsbild aus der Gruppe der lymphoproliferativen Krankheiten bezeichnet. Fallbeschreibung: Anhand eines seltenen Falles mit retroperitonealer Präsentation werden die verschiedenen klinischen Manifestationen und Verlaufsformen dargelegt sowie Hinweise für Diagnose, Differentialdiagnose und Therapie gegeben. Die heutigen, unvollständigen Kenntnisse der Pathophysiologie werden zusammengefaßt.
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  • 77
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    Medizinische Klinik 95 (2000), S. 286-292 
    ISSN: 1615-6722
    Keywords: Schlüsselwörter: Hypertensive Krise ; Hypertensiver Notfall ; Hypertensive Dringlichkeit ; Komplikationen ; Therapie ; Ursachen ; Key Words: Hypertensive emergency and urgency ; Etiology ; Complications ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Hypertensive crisis is defined as an extreme elevation of arterial blood pressure, with diastolic pressure 〉 120 mm Hg, and represents an imminent risk to the patient. In such cases, a rapid orientating diagnosis and adequate antihypertensive treatment to avoid sequelae are needed, sometimes even before diagnostic test are completed. Hypertensive emergencies and hypertensive urgencies can be distinguished. If the critical increase in blood pressure is associated with end-organ damage such as encephalopathy, acute left heart failure and pulmonary edema, angina pectoris, myocardial infarction or dissecting aortic aneurysm, a hypertensive emergency is presnet, that is an acute threat to the patient's life. A hypertensive emergency requires effective lowering of blood pressure within minutes, but not necessarily to normal range. The choice of suitable antihypertensive agents depends on clinical symptoms, contraindications, duration of pressure elevation and underlying conditions, prior cardiovascular, cerebrovascular and renal disorders. The risk of imminent end-organ damage must be weighed against the risk of rapid blood pressure lowering. In hypertensive urgencies without end-organ complications, blood pressure can be lowered more slowly over several hours, often with oral agents to avoid detrimental fall in blood pressure. The drugs of choice are mainly urapidil IV and nitroglycerine.
    Notes: Zusammenfassung Die hypertensive Krise stellt mit ihren kardialen, zerebralen und renalen Folgeerscheinungen eine potentiell lebensbedrohliche Komplikation der arteriellen Hypertonie dar. Bei einem hypertensiven Notfall (emergency), der den Patienten vital gefährdet, geht der kritische Blutdruckanstieg mit Organschä,den wie der Enzephalopathie, einer akuten Linksherzinsuffizienz, Angina pectoris, Herzinfarkt oder einem dissezierenden Aortenaneurysma einher. Der hypertensive Notfall erfordert eine umgehende effektive Blutdrucksenkung innerhalb von Minuten. Liegt eine Dringlichkeit (urgency) vor, bei der die oben genannten Folgeerscheinungen und Symptome bei stark erhöhten Blutdruckwerten fehlen, reicht eine langsame Absenkung des arteriellen Blutdrucks über mehrerer Stunden aus. Die Auswirkung der Hypertonie auf die Zielorganfunktion muß gegen das Risiko einer exzessiven Blutdrucksenkung abgewogen werden. Das Ausmaß der notwendigen Drucksenkung sowie die Wahl des geeigneten Antihypertensivums werden durch die klinische Symptomatik, Kontraindikationen, Dauer und Ausmaß der Blutdrucksteigerung und die zugrundeliegenden Vorerkrankungen des Patienten bestimmt. Eine zu langsame, aber auch eine zu rasche Blutdrucksenkung können zu schwerwiegenden Folgeschäden führen. Bei einer hypertensiven Dringlichkeit ohne Endorgankomplikationen ist meist eine allmähliche Blutdrucksenkung mir oral verabreichten Antihypertensiva ausreichend. Mittel der Wahl sind Urapidil intravenös und Nitroglycerin.
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    Cytotechnology 34 (2000), S. 131-139 
    ISSN: 1573-0778
    Keywords: apoptosis ; bcl-xL ; cell growth ; cell viability ; hybridoma ; myeloma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract While the ectopic expression of the anti-apoptoticprotein Bcl-2 has been shown to significantly increaseboth cell viability and antibody production in batchculture, some cell lines are refractory to thesemanipulations. For example, the NS/O and theP3x63Ag8.653 murine myelomas, which express highendogenous levels of the Bcl-2 homologue Bcl-xL, areboth resistant to the anti-apoptotic effect of Bcl-2.This indicates that, in these cells, Bcl-2 and Bcl-xLmay be functionally redundant. In order to define therole which Bcl-xL plays in hybridoma cultures, we usedthe Sp2/0-Ag14 cell line. This murine hybridomaexpresses low levels of Bcl-xL and is highly sensitiveto apoptosis induction by cycloheximide (CHX) and byamino acid depletion. Bcl-xL-transfected Sp2/0-Ag14cells were more resistant than the wild type and theplasmid-containing cells to apoptosis induced by CHXand by glutamine depletion. Moreover, when compared tothe vector-transfected control, Bcl-xL-Sp2/0 cellsexhibited a substantial increase in viability instationary batch culture. Interestingly, Sp2/0-Ag14cells overexpressing Bcl-xL showed a growth behaviourthat was similar to the parent myeloma cell lineP3x63Ag8.653. Our results suggest that Bcl-xLexpression levels are sufficient to account for therelative robustness of some hybridoma cell lines instationary batch cultures.
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  • 79
    ISSN: 1573-0778
    Keywords: antisense ; apoptosis ; cell cycle ; c-jun ; protein production
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Expression of c-jun gene induces apoptosis ofcells cultured in serum-free medium. It also promotescell-cycling in serum-containing medium, leading cellsto die by overgrowth. Previously, we established anapoptosis-suppressible, cell-cycle arrestable cellline, c-jun AS, by transfecting Friend murineerythroleukemia (F-MEL) cells with adexamethasone-inducible antisense c-jun gene.Induction of the antisense c-jun transcriptionwith dexamethasone suppressed c-jun expression.As a result, c-jun AS cells survived inserum-free medium containing dexamethasone for a longtime, while F-MEL cells died quickly in the presenceor absence of dexamethasone. In serum-containingmedium, the growth of c-jun AS cells was viablyblocked by inducing antisense c-juntranscription, and the cells survived at thenon-growth state avoiding overgrowth. In the presentstudy, protein productivity of c-jun AS cellswas examined in comparison with that of wild typeF-MEL cells. C-jun AS and F-MEL cells werefurther transfected with a vector for expressingalkaline phosphatase as a protein to be produced, andnamed c-jun AS-SEAP and F-MEL-SEAP cells,respectively. In the serum-free medium withdexamethasone, c-jun AS-SEAP cells produced theprotein for up to 6 days, while F-MEL-SEAP cellsstopped production on day 3 due to cell death causedby serum deprivation. In the serum-containing mediumwith dexamethasone, c-jun AS-SEAP cells wereviably arrested in the cell cycle, and cell death dueto overgrowth was avoided. As the result, they couldproduce the protein for up to 18 days, whileF-MEL-SEAP cells stopped production within 7 days dueto cell death caused by overgrowth.
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  • 80
    ISSN: 1573-4986
    Keywords: sialidase ; sialyltransferase ; apoptosis ; Jurkat cells ; etoposide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The present study investigated the mechanism underlying alterations of cell surface sugar chains of Jurkat cells by inducing apoptosis with etoposide, an inhibitor of topoisomerase II. Within 3[emsp4 ]h of etoposide treatment, flowcytometric analysis revealed a decrease in Maackia amurensis agglutinin recognized α2,3-linked sialic acid moieties and an increase in Ricinus communis agglutinin recognized galactose. The results suggested that asialo-sugar chains on glycoconjugates were rapidly induced on the etoposide-treated cell surface. To clarify the desialylation mechanism, we studied α2,3-sialyltransferase mRNA expression and the activity of sialidase on the cell surface during etoposide-induced apoptosis. The expression of hST3Gal III and hST3Gal IV mRNAs were down-regulated and sialidase activity on the cell surface increased threefold within 2[emsp4 ]h of etoposide treatment. Moreover, the decrease in α2,3-linked sialic acid levels was significantly suppressed in the presence of 2,3-dehydro-2-deoxy-N-acetylneuraminic acid, an inhibitor of sialidase. These results suggested that activation or exposure of sialidase on the cell surface was induced by etoposide treatment and was the main cause of the decrease in sialic acids.
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  • 81
    ISSN: 1573-7276
    Keywords: apoptosis ; Bcl-2 ; cell cycle ; invasion ; metastasis ; mobility ; melanoma B16-BL6 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Quercetin has been known to have anti-tumor and anti-oxidation activities. In the present study, we have investigated its in vitro anti-metastatic activity. Quercetin inhibited the invasion and mobility of murine melanoma B16-BL6 cells in a dose-dependent manner but did not affect their adhesion to either laminin, fibronectin, or type VI collagen. Moreover, quercetin significantly inhibited the proliferation of B16-BL6 cells only in the case of time incubation longer than 48 h. Quercetin dose-dependently decreased the cell rates in S and G2–M phases of cell cycle. The effect of quercetin to cause a remarkable apoptosis of B16-BL6 cells was also demonstrated by flow cytometric assay as well as DNA fragmentation with a typical 180-bp ladder band in agarose electrophoresis and a quantitative analysis. Furthermore, quercetin markedly inhibited the expression of anti-apoptotic protein Bcl-2 but hardly influenced Bcl-XL. These results suggest that the inhibition of quercetin on invasiveness and migration of B16-BL6 cells are closely associated with the arrest of cell cycle as well as the induction of apoptosis by decreasing the Bcl-2 expression.
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  • 82
    ISSN: 1573-7276
    Keywords: apoptosis ; butyrate ; cell cycle ; cholesteryl butyrate ; drug delivery ; melanoma ; solid lipid nanospheres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Literature data show that butyric acid derivatives bear a dose-dependent differentiative anti-proliferative activity on cancer cell lines and that apoptosis induction may play a major role. Although it was recently shown that solid lipid nanospheres (SLNs) are a suitable tool for several in vivo drug administration routes, there is little available information on melanoma cell lines. This study was aimed at evaluating the anti-proliferative and apoptotic in vitro effects of cholesteryl butyrate (chol-but) SLNs on melanoma cells. Increasing concentrations of chol-but SLNs were used to test two melanoma cell lines. Both cell lines were treated with Na-butyrate (Na-but) and chol-but SLNs for viability. Those tested with chol-but SLNs were more effective than Na-butirate (3 to 72 h). The apoptotic effects of chol-but SLNs were evaluated between 3 and 72 h by annexin-V (ANX-V)/propidium iodide (PI) staining and the antiproliferative effect by PI staining. Apoptosis anti-proliferative-regulatory proteins as bcl-2, Fas/APO1 (CD95) and PCNA (PC10) were also investigated. Flow cytometric analyses evidenced a G0/1-S transition block and a `sub-G0/1' apoptotic peak from 0.5 to 1.0 mM butyric acid. In ANX-V/PI flow cytometric staining, a dose- and time-dependent increase in the apoptotic cell percentage (ANX-V+) coupled with a down-regulation of PC10 and bcl-2 and a parallel up-regulation of Fas/APO1 (CD95) were found in both lines started after 3 to 24 h of chol-but SLNs treatment. Results show that chol-but SLNs exerts a dose/time-dependent effect in melanoma cell apoptosis induction between 3 and 24 h and a dose but not time-dependent effect after 24 h of treatment.
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  • 83
    ISSN: 1573-7373
    Keywords: apoptosis ; DNA ; glioma ; estramustine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The drug effect of estramustine phosphate (EMP), an anti-microtubule agent on human glioma cells has been studied with the focus being mainly its cytotoxity or its targeting of organelles. However, the pharmacological knowledge of estramustine with respect to its cytotoxity and mechanism is limited. To acquire such knowledge, the present study investigates the ability of EMP to induce apoptosis in a human malignant glioma cell line. Transmission electron microscope (TEM) images were examined to monitor periodic changes. Agarose gel electrophoresis was also examined. Cellular DNA fragmentation ELISA was performed to investigate the DNA fragmentation rates and an MTT assay was studied to evaluate the ID50. A TEM study revealed condensing and fragmentation of the chromatin. Laddering of the bands was observed in all EMP exposure groups in agarose gel electrophoresis. DNA fragmentation in all EMP groups began at 0.5 h following an exposure with EMP and increased in a dose- and time-dependent manner as revealed by DNA ELISA fragmentation. ID50 at 24 h was 5.0 µM according to the MTT assay, a value close to 4.8 µM of ID50 was revealed by the DNA fragmentation assay. None of the above mentioned changes was observed in the control group. These results indicated that EMP caused a drug-induced apoptosis in the human malignant glioma cell line, U87MG.
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  • 84
    ISSN: 1573-7373
    Keywords: selenium ; human glioma cells ; mitochondria ; apoptosis ; fibroblasts ; ultrastructure ; MTT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the effect of the trace element selenium on human glioma cell lines: T98G, U373MG, and U87MG, in addition to dermal fibroblast cells. Cultures were incubated with sodium selenite, and the following parameters were studied: cell growth, mitochondrial function, and ultrastructure. Cell growth was assayed by counting the number of viable cells after treatment with selenium. Mitochondrial function was analyzed using the MTT (tetrazolium salt reduction) assay. Apoptosis was determined by evaluating nuclear chromatin condensation by electron microscopy. The results indicated that selenium had a significant inhibitory effect on the growth of the tumor cells but had little effect upon dermal fibroblasts which had been passaged numerous times. Selenium also induced mitochondrial damage as shown by MTT assay in two brain tumor cell lines and in minimally passaged fibroblasts, but it had little effect upon the high-passage fibroblasts. Ultrastructurally, mitochondria had electron-dense inclusions resulting from selenium treatment. High rates of apoptosis were induced by selenium in the tumor cell lines and in the minimally passaged fibroblasts, whereas the fibroblasts with a high number of passages had some resistance to selenium treatment. This study correlates the adverse effects of selenium on mitochondrial function, inhibition of cell growth, and apoptosis and shows that selenium similarly affects three different brain tumor cell lines and minimally passaged fibroblasts. Further, the results with fibroblasts show that some types of cells after repeated passages can develop resistance to selenium damage.
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  • 85
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    Journal of neuro-oncology 47 (2000), S. 31-38 
    ISSN: 1573-7373
    Keywords: glioma ; apoptosis ; vitamin K ; reactive oxygen intermediates ; Fas/APO-1 ; flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Congeners of vitamin K have been found to inhibit growth in various rodent and human tumor cells, but the mechanisms of the inhibitory action are still not well understood. To investigate the modes of actions of vitamin K, we used several vitamin K analogs and examined their cytotoxic effect for human glioma cell lines RBR17T and U251. The analogs included vitamin K1 (VK1), vitamin K2 (VK2), vitamin K3 (VK3), and geranylgeraniol (GGO) which form an unsaturated side chain of VK2. Cell viability was estimated by MTT assay. DNA fragmentation was demonstrated by gel electrophoresis and flow cytometry. In order to study the mechanism of apoptosis, we measured the changes of intracellular reactive oxygen intermediates (ROI) and Fas/APO-1 expression by flow cytometry. The results showed: (1) VK2, VK3, and GGO inhibited cell growth; (2) VK3 had a more potent cytotoxic effect than VK2, and VK3 enhanced the cytotoxic effect of antitumor agents (ACNU and IFN-beta) in RBR17T cells; (3) VK2, VK3, and GGO induce apoptosis; (4) VK3 increased the expression of Fas/APO-1 although VK2 and GGO did not increase its expression in glioma cells; (5) VK3 increased the production of intracellular ROI. Catalase and reduced glutathione (GSH) inhibited production of intracellular ROI and antagonized inhibition of cell-growth induced by VK2, but failed to antagonize that of VK2 and GGO. We hypothesize that VK3 induces apoptosis by promoting the generation of intracellular ROI and Fas/APO-1 expression. On the other hand, VK2 and GGO induce apoptosis but most likely by some other unknown pathway.
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  • 86
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    Journal of neuro-oncology 47 (2000), S. 153-160 
    ISSN: 1573-7373
    Keywords: tumour ; apoptosis ; incidence ; p53 ; bax ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We sought to determine the relative incidence of meningiomas compared to other central nervous system tumours in an Asian surgical series, as well as the demographic and biological characteristics of these meningiomas. A review of 655 consecutive cases of central nervous system tumours from 583 patients representing the last five years admissions to one hospital in Singapore was undertaken. A total of 33 malignant/atypical tumours from 19 patients and 196 benign meningiomas from 187 patients were identified. Twenty malignant/atypical and 20 benign tumours were selected at random and subjected to histochemical and immunohistochemical analysis using antibodies directed against p53, bax and 3′-DNA hydroxy groups (TUNEL). Meningiomas comprised some 35.2% of all central nervous system tumours with malignant/atypical meningiomas representing 9.2% of meningiomas. Histochemically, necrosis was the predominant finding. However, peri-necrotic areas displayed p53 positivity in 10% of cases and bax positivity in 25% of cases. Apoptotic cells were detected in the peri-necrotic areas in 90% of benign and 75% of malignant/atypical meningiomas. Meningiomas represent the predominant form of central nervous system tumour in the Singaporean population, and aberration of p53 expression is not associated with tumour formation or progression. There was a slight but non-significant reduction in apoptosis in the progression from benign to malignant meningioma, suggesting that in contrast to many other tumour types disruption of cellular apoptosis is not a predominant driving force in Asian meningioma tumourigenesis.
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  • 87
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    Journal of neuro-oncology 46 (2000), S. 135-144 
    ISSN: 1573-7373
    Keywords: apoptosis ; cRGDfV ; human gliomas ; integrin αVβ3 ; mouse glioma model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults and is invariably fatal. We have investigated the effect of cyclo-(Arg-Gly-Asp-D-Phe-Val) (cRGDfV) peptide on survival of human malignant glioma cells in vitro and in vivo. Immunofluorescent analyses revealed the presence of αVβ3 integrin on U-87MG and U-373MG cells, but minimal expression on U-251MG cells. Treatment of U-87MG and U-373MG cells in vitro with cRGDfV (20 µg/ml), but not the linear peptide, resulted in the appearance of rounded and loosely attached cells with subsequent cell death. By comparison, neither this cyclic peptide nor its linear homolog had any significant effect on growth and morphology of U-251MG cells. The death of cRGDfV-treated (20 µg/ml) glioma cells was blocked by pretreatment (10 µM) of cells with DEVD-FMK and LEHD-FMK, inhibitors of caspase-3 and caspase-9, respectively. Moreover, when glioma cells grown as spheroids were treated with cRGDfV (50 µg/ml), spheroid formation was markedly reduced. Further, treatment of intracranial U-87MG tumors in scid mice with cyclic peptide significantly (p〈0.001) prolonged their survival. These results indicated (i) that cRGDfV induced apoptosis of human glioma cells by binding αVβ3 integrin expressed on their cell surfaces and (ii) that cRGDfV may be an effective and non-toxic direct anti-tumor therapy for αVβ3-expressing GBMs.
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  • 88
    ISSN: 1573-7373
    Keywords: apoptosis ; proliferation ; p53 ; Bcl-2 ; transglutaminase ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several protocols for the adjuvant treatment of glioblastoma multiforme (GBM) are currently being evaluated. In this context, little is known about the influence of radiochemotherapy on apoptosis and the expression of apoptosis-related proteins in vivo. We have analyzed the incidence of apoptosis using in situ nick translation (ISNT) and expression of Ki-67 (MIB-1), p53 (DO-1 and DO-7), Bcl-2 and transglutaminase II (TGase II) by immunohistochemistry in 41 patients with GBM and their matched relapses. Sixteen patients received radiochemotherapy, 18 irradiation and 7 no treatment. Radiochemotherapy resulted in an increase in Bcl-2+ cells (p=0.013). Irradiation caused the reduction of MIB-1+ (p=0.0015), DO-7+ (p=0.0043) and the increase of Bcl-2+ cells (p=0.016). We calculated a positive correlation between high TGase II scores in patients preceding radiochemotherapy (p=0.0186) and no treatment (p=0.0158), low ISNT scores (p=0.0018) and high DO-1 scores (p=0.0233) in patients preceding irradiation and short time to progression. These data show that distinct postsurgical radiochemotherapy protocols differentially alter cellular proliferation and expression of p53 and Bcl-2 in GBM relapses. Furthermore, we show that ISNT, DO-1 and TGase II labeling scores are therapy-specific predictors of time to progression in GBM patients.
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  • 89
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    Journal of neuro-oncology 49 (2000), S. 117-129 
    ISSN: 1573-7373
    Keywords: apoptosis ; chemotherapy resistance ; bcl-2 ; bax ; glioma ; nucleolus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the role of apoptosis suppression in glioma chemotherapy resistance, protein levels and subcellular localization of bcl-2 family members were investigated in 2 pairs of sensitive cell lines and their in vitro generated resistant derivatives. The alkylating agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), induced apoptosis in both sensitive cell strains and apoptosis was suppressed in both resistant derivatives. Both resistant cell lines contained altered regulation of a bcl-2 related protein consistent with the suppression of apoptosis. Independent of which bcl-2 family member was dysregulated, resistance was associated with altered regulation in the subcellular localization of bax protein. Following BCNU treatment, bax accumulated in nucleoli and a nuclei containing fraction of sensitive cells but not their resistant derivatives. Nuclear accumulation was an early event in apotosis induction. These data indicates altered subcellular localization of bax may play a role in resistance. In addition, the association between an early, nucleolar localization of bax and the induction of apoptosis suggests that localization of bax to nucleoli may play a role in apoptosis-induction of glioma cells.
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  • 90
    ISSN: 1573-8469
    Keywords: apoptosis ; bacteria ; chromatin condensation ; DNA degradation analysis ; plant ; programmed cell death
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Ultrastructural details of the hypersensitive reaction induced by infiltration with avirulent race 2 Xanthomonas campestris pv. vesicatoria in pepper ‘Early Calwonder-10R’ leaves (incompatible interaction) are reported. Affected cells displayed plasmalemma undulations and disruption, lysis of the chloroplast membrane, degeneration of other organelles, general cytoplasm disorganisation and, often, protoplast shrinkage. The nuclei contained large masses of electron-dense material, apparently formed by chromatin aggregation. In many cases a single chromatin-like layer was deposited on the inner side of the nuclear envelope leaving a finely granular matrix in the centre of the nucleus; the nucleolus usually disappeared. The nuclear envelope was sometimes ruptured and the internal matrix leaked into the cytoplasm. The content of many affected cells eventually coagulated and became very electron-dense. The walls often collapsed. All these alterations were especially visible in spongy mesophyll cells at sites where bacteria occurred in the intercellular spaces. Although some of the nuclear and cytoplasmic alterations recall certain aspects of apoptotic cell death, molecular determinations did not reveal any DNA degradation in hypersensitively reacting tissues. The first cell alterations in leaves infected with the virulent bacterial race 1 (compatible interaction) were observed only 27 h after inoculation, when the cytoplasm of some cells showed limited internal disorganisation and plasmolysis at sites where bacterial colonies developed.
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  • 91
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    Cancer and metastasis reviews 19 (2000), S. 97-107 
    ISSN: 1573-7233
    Keywords: angiogenesis ; angiostatin ; cancer biology ; cancer therapy ; proteolysis ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The study of angiogenesis, and the promise of angiogenesis inhibition as a means of cancer therapy, has dramatically accelerated in the last several years. The discovery and publication of angiostatin by O'Reilly and colleagues in Judah Folkman's lab in 1994 has greatly contributed to this progress. Angiostatin is a kringle-containing fragment of plasminogen, which is a potent inhibitor of angiogenesis in-vivo, and selectively inhibits endothelial cell proliferation and migration in-vitro. There have been a number of proposed proteolytic mechanisms by which plasminogen is cleaved to form angiostatin, and the resulting cleavage products contain different NH2 and COOH termini of the angiostatin. Therefore, it is possible that there are more than one angiostatin isoforms (or angiostatin-related proteins) which occur in one or more normal or pathophysiological situations. It is also possible that some of the proteolytic processes which can convert plasminogen to angiostatin-like proteins are simply laboratory artifacts. Angiostatin-related proteins exert potent endothelial cell inhibitory activity, including the induction of apoptosis, and inhibition of migration, and the intact kringle structures are believed to be necessary for the antiangiogenic activity. Efforts are now underway to translate the understanding of the biology of angiostatin to clinical practice, which includes phase 1 clinical trials with recombinant angiostatin K1–3 (kringles 1–3) as well as phase 1 trials of an Angiostatin Cocktail, which induces the direct in vivo conversion of plasminogen to angiostatin 4.5 (kringles 1–4, plus most of kringle 5). The translation of the basic science of angiostatin and angiostatin-related proteins to clinical trial promises to provide an important new tool in the treatment of cancer by inhibition of angiogenesis.
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  • 92
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    Apoptosis 5 (2000), S. 203-209 
    ISSN: 1573-675X
    Keywords: apoptosis ; lens development ; organelle loss ; denucleation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The lens represents an ideal model system for studying many of the cellular and molecular events of differentiation. It is composed of two ectodermally-derived cell types: the lens epithelial cells and the lens fibre cells, which are derived from the lens epithelial cells by differentiation. Programmed removal of nuclei and other organelles from the lens fibre cells ensures that an optically clear structure is created, while the morphology of the degenerating nuclei is similar to that observed during apoptosis and is accompanied by DNA fragmentation. These observations suggest the existence of biochemical parallels between the process of lens fibre cell organelle loss and classical apoptosis. For example, proteins encoded by the bcl-2 and caspase gene families are expressed in developing lenses and nuclear degeneration in lens fibre cells can be inhibited in vivo by overexpression of bcl-2 and in vitro by incubation of differentiating lens epithelial cell cultures with caspase inhibitors. Thus, the developing lens may represent a particularly useful model system for researchers interested in apoptosis. In this review, the recent literature pertaining to lens fibre cell organelle loss and its relationship to apoptosis is reviewed and possible future research directions are suggested.
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  • 93
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    Apoptosis 5 (2000), S. 217-220 
    ISSN: 1573-675X
    Keywords: Daxx ; apoptosis ; Fas ; PML ; ND10
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Several reports describing Daxx and its putative role have emerged without a unifying theme. While Daxx has been implicated in apoptosis, it remains unclear whether Daxx is pro- or anti-apoptotic, and whether its role in apoptosis is direct or indirect. Moreover, whether Daxx plays alternative or additional roles in regulating transcription, centromere binding or any number of other activities within the cell, is uncertain. The ability of Daxx to interact with a wide variety of molecules in yeast-interaction trap systems (Table 1) has allowed for this range of speculation. The fact that Daxx contains no significant homology to other known proteins has rendered its study all the more challenging.
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  • 94
    ISSN: 1573-675X
    Keywords: apoptosis ; cyclin B1/CDC 2 ; G2/M arrest ; MAD 2 ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Paclitaxel (Taxol™) is a microtubule-interfering agent that induced persistent and transient G2/M arrest before apoptosis in human nasopharyngeal carcinoma (NPC) cells at high and low concentrations, respectively. In this study, we intended to explore the underlying molecular events and found that cellular cyclin B1/CDC 2 kinase activity was increased and persisted for 〉6 h upon paclitaxel treatment both at high and low concentrations. Furthermore, activation of MAD 2 checkprotein could account for the loss of cyclin B1 ubiquitination and the persistence of cyclin B1/CDC 2 activation in the cases. To investigate the involvement of cyclin B1 and MAD 2 activation in paclitaxel-induced apoptosis, we introduced affinity-purified anti-cyclin B1 and MAD 2 antibodies into NPC cells by electroporation before the further paclitaxel treatment. The antibodies against cyclin B1 and MAD 2 indeed attenuated paclitaxel-induced cytotoxicity and DNA fragmentation. Our study suggests that activation of cyclin B1/CDC 2 and MAD 2 were the M-phase events required for paclitaxel-induced apoptosis in NPC cells. The dys-regulated cyclin B1/CDC 2 activation could enhance the prometaphase progression, but activation of MAD 2 rendered cells inable to exit from the metaphase. Under this circumstance, cells were probably going to “mitotic catastrophe” and ultimately, destined to apoptosis.
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  • 95
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    Apoptosis 5 (2000), S. 211-215 
    ISSN: 1573-675X
    Keywords: adenovirus ; E4orf4 ; apoptosis ; protein phosphatase 2A (PP2A) ; caspases ; cancer ; gene therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Adenovirus E4orf4 protein is a multifunctional viral regulator that induces p53-independent apoptosis in transformed cells, but not in normal cells. E4orf4-induced apoptosis can occur without activation of known caspases, although E4orf4 induces caspase activity in some cell lines. The interaction of E4orf4 with a specific subpopulation of protein phosphatase 2A (PP2A) molecules that contain B subunits, but not with those that contain B′ subunits, is required for induction of apoptosis. This review suggests the potential use of E4orf4 in cancer therapy, and discusses whether E4orf4-induced apoptosis plays a role in the viral life cycle. Future research directions are also highlighted.
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  • 96
    ISSN: 1573-675X
    Keywords: Amphibia ; apoptosis ; cancer ; cell cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Spontaneous and induced cancers are rare in non-isogeneic or inbred amphibians. Neoplastic cells become immortalized through loss of a normal capacity to die by apoptosis. Mature lymphocytes of mammals require activation and entry into the cell cycle in order to become susceptible to apoptosis. Whether Xenopus lymphocytes differ from mammalian lymphocytes in this regard is examined. In vitro exposure of PMA, or its analogue, MPMA, to adult splenocytes of Xenopus laevis was used to affect apoptosis. Flow cytometric analysis of FITC-Annexin V/propidium iodide (PI) fluorescence (apoptosis) and BrdU uptake (DNA synthesis) were assayed concurrently in the same lymphocyte population over time. Significant increases in apoptotic levels were induced throughout a 72 hour period in PMA-treated cells only. Lymphocytes were also separated by size for analysis. Several sub-populations of lymphocytes were identified, the most interesting of which was small and apoptotic within 4 hours, after PMA exposure. PMA-induced DNA synthesis did not become elevated until after 24 hours. “Direct” apoptosis, i.e. without cell cycle entry, was found only in these small, mature lymphocytes. Since small lymphocytes make up the vast majority of those being analyzed, “direct” apoptosis may be a determining mechanism in the resistance to neoplasia observed in Amphibia. Cells that die more readily are less likely to transform into neoplastic cells.
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  • 97
    ISSN: 1573-675X
    Keywords: apoptosis ; caspase-3 ; nuclease ; endo-exonuclease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Single-strand DNase and poly rAase, activities characteristic of endo-exonuclease, were co-activated in nuclear fractions of HL-60 cells by caspase-3. Activation was accompanied by cleavages of large soluble polypeptides (130–185 kDa) and a 65 kDa inactive chromatin-associated polypeptide related to the endo-exonuclease of Neurospora crassa as detected on immunoblots. The major products seen in vitro were a 77 kDa soluble polypeptide and an active chromatin-associated 34 kDa polypeptide. When HL-60 cells were induced to undergo apoptosis by treating with 50 μM etoposide (VP-16) for 4 hours, 77 kDa and 40 kDa polypeptides accumulated in nuclear fractions. Chromatin DNA fragmentation activity was also activated in cytosol and nuclear extract either by pre-treating the cells in vivo with VP-16 or by treating the cytosol in vitro with caspase-3 or dATP and cytochrome c. Endo-exonuclease activated by caspase-3 in cytosol-derived fractions augmented chromatin DNA fragmentation activity in vitro. Endo-exonuclease is proposed to act in vivo in conjunction with the caspase-activated DNase (CAD) to degrade chromatin DNA during apoptosis of HL-60 cells.
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  • 98
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    Apoptosis 5 (2000), S. 307-314 
    ISSN: 1573-675X
    Keywords: apoptosis ; cancer ; cross-priming ; cross-tolerance ; dendritic cells ; T lymphocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Induction of cell death by apoptosis, also called programmed cell death, and clearance of apoptotic bodies by scavenger cells has long thought to be an efficient means to dispose of unwanted cells without causing inflammatory responses able to mediate specific reactions. However, a number of evidences have been accumulated suggesting that apoptotic cell death is implicated in the pathogenesis of systemic and organ specific autoimmune diseases. In addition, recognition and engulfement of apoptotic cells by professional antigen presenting cells, such as dendritic cells, and their interaction with effector immune cells have been recently described to result in apoptotic cell-derived antigen specific tolerance. This review will summarise the most recent findings on the immunogenic potential of cells undergoing programmed death.
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  • 99
    ISSN: 1573-675X
    Keywords: Angiogenesis ; angiopoietins ; apoptosis ; integrins ; vascular endothelial growth factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Angiogenesis is essential for the growth and metastasis of solid tumors. The balance of endothelial cell (EC) proliferation and apoptosis is a major determinant in tumor angiogenesis. Recently, several studies demonstrated that numerous angiogenic factors not only induce angiogenesis but also function as EC survival factors. Vascular endothelial growth factor (VEGF), a potent angiogenic factor, is also an EC survival factor in embryonic vasculogenesis and tumor angiogenesis. VEGF activates specific intracellular survival pathways in ECs including Bcl-2, A1, IAP, Akt, and Erk. Integrins may function as EC survival factors by preventing anoikis by enhancing binding to the extracellular matrix. In addition, integrins may function in concert with VEGF to promote EC survival. Angiopoietin-1 (Ang-1) has recently been shown to stabilize EC networks by binding to the EC-specific tyrosine kinase receptor Tie-2. Pericytes also function as EC survival factors, by cell-cell contact, secretion of survival factors, or both. Targeting any of the above mechanisms for EC survival may provide novel antineoplastic strategies.
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  • 100
    ISSN: 1573-675X
    Keywords: apoptosis ; antimicrotubule agent ; cell cycle ; dolastatin 10 ; TZT-1027
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract TZT-1027, a newly synthesized dolastatin 10 derivative, is a potent antitumor agent which inhibits microtubule polymerization and perturbs microtubule dynamics. In this report, we investigated whether TZT-1027 inhibited the growth of various human cancer cells, and the cell death caused by TZT-1027 was due to apoptosis. In addition, we elucidated the apoptosis machinery induced by treatment with TZT-1027. The 50% growth-inhibitory concentrations (IC50 values) of TZT-1027 on cancer cells derived from various sources were not more than 5.9 ng/ml. TZT-1027 showed superior cytotoxicity than any other antitumor agents. Next, we evaluated morphological nuclear change, namely, chromatin condensation and DNA fragmentation. We used three cancer cell lines derived from different types in view of having apoptosis related protein, human leukemia HL-60 (in the presence of both Caspase-3 and Bcl-2), human breast cancer MCF-7 (in the absence of Caspase-3), and human prostate cancer DU145 (in the absence of Bcl-2). TZT-1027 induced DNA fragmentation in the presence but not absence of Caspase-3. Nevertheless, apoptic chromatin condensation was observed in all cancer cells even if there was no Caspase-3. Furthermore, we examined whether TZT-1027, microtubule-disrupting agent, influenced cell cycle progression. Flow cytometric analysis revealed the cells treated with TZT-1027, and with the other antimicrotubule agents, to be arrested at the G2/M phase and subsequently to show fragmented DNA smaller than that of G1 phase cells. Moreover, we tested TZT-1027 for its ability to induce Bcl-2 phosphorylation in human cancer cell lines. TZT-1027 and other agents which interacted with microtubules induced Bcl-2 phosphorylation, whereas DNA-damaging agents did not. The present results suggested an association of the growth-inhibitory effect of TZT-1027 with the induction of apoptosis and indicated that the apoptosis induced by TZT-1027 was followed by G2/M arrest even if there was no Caspase-3 or Bcl-2.
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