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  • Articles: DFG German National Licenses  (275)
  • 2000-2004  (275)
  • 1890-1899
  • Key words  (182)
  • Apoptosis  (93)
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  • Articles: DFG German National Licenses  (275)
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  • 1
    ISSN: 1432-2277
    Keywords: Key words Normothermic liver ischemia ; Apoptosis ; Caspases ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Normothermic ischemia and reperfusion of the liver results in microcirculatory failure followed by necrosis and cell death. Recently, another type of cell death, apoptosis or programmed cell death, was found to be activated during the early phase of reperfusion after liver ischemia. Caspases are cysteine proteinases specifically involved in the initiation and execution phases of apoptosis. The aim of this study was to demonstrate that inhibition of apoptosis by a specific inhibitor of caspases might protect the liver against ischemia/reperfusion injury. Rats were divided into three groups: group 1, control, PBS administration; group 2, Z-Asp-cmk (Z-Asp-2,6-dichlorobenzoyl-oxymethylketone) treatment; group 3, sham-operated control animals. Z-Asp-cmk (0.5 mg Z-Asp-cmk dissolved in 300 μl PBS solution containing 1 % DMSO) was injected intravenously, 2 min prior to induction of 120 min ischemia. Survival rates were compared and serum activities of aspartate aminotransferases and alanine aminotransferases were assessed in the blood collected from the suprahepatic vena cava. Histology of the liver was assessed 6 h after the end of ischemia. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick end-labeling method (TUNEL method) and by electrophoresis for analysis of DNA fragmentation. Caspase activity was determined by measuring hydrolysis of the CPP32-like substrate Ac-DEVD-pNA and absorption of paranitroaniline. Z-Asp-cmk treatment significantly increased 7-day survival (95 %) compared with that in nontreated rats (30 %, P 〈 0.001). Serum activities of aminotransferases and the extent of liver congestion and necrosis were significantly (P 〈 0.001) decreased after treatment with Z-Asp-cmk. TUNEL-positive cells were detected 3–6 h after reperfusion in the control group. In Z-Asp-cmk pretreated rats, a dramatic decrease in the number of TUNEL-positive cells was observed. Analysis of DNA fragmentation of freshly isolated hepatocytes confirmed these results. Caspase activity was increased 3–6 h after reperfusion in the control group, but significantly (P 〈 0.001) decreased after treatment with Z-Asp-cmk. These findings demonstrate that liver injury following ischemia and reperfusion can be prevented by inhibition of caspases. Caspase inhibitors may have important implications for therapy in liver disease and after liver transplantation.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 436 (2000), S. 102-108 
    ISSN: 1432-2307
    Keywords: Key words Oral ; Squamous cell carcinoma ; Proliferation ; Apoptosis ; Tumour suppressor gene ; Oncogene ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tumour progression is characterised by an imbalance between cell proliferation and apoptosis. The aim of our study was to estimate the importance of proliferation and apoptosis associated parameters in primary squamous cell carcinomas (SCCs) of the oral cavity and oropharynx. For determination of apoptosis, the enzymatic labelling of DNA fragmentation with a terminal transferase reaction was used in 156 tissue samples of 107 patients, including corresponding lymph-node metastases in nine cases. P53, bcl-2, and Ki-67 were determined immunohistologically. P53 was detectable in 50.5% of the cases. Positive staining was associated significantly with decreased apoptosis (P〈0.003). Bcl-2 was upregulated in 31.8% of the cases depending on the tumour grading (P〈0.001) and correlated negatively with apoptosis (P〈0.001). Proliferation (P〈0.006) and apoptosis (P〈0.03) were enhanced in larger tumours, though a direct correlation between these two parameters was not proven. Nevertheless, in contrast to the conventional tumour staging and grading, neither the expression of p53 or bcl-2 nor the apoptosis or Ki-67 measurements were able to predict survival or recurrence-free survival of the patients suffering from a SCC in the oral cavity or oropharynx. Our observations suggest that the function of wild-type p53 to induce apoptosis is lost in at least half of the SCCs under study and that the physiological function of bcl-2 as potent inhibitor of apoptosis is widely preserved in oral SCC.
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  • 3
    ISSN: 1432-2307
    Keywords: Key words  Pseudomelanosis coli ; Large bowel ; Colonic adenoma ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Pseudomelanosis coli is characterized by pigment deposition in the lamina propria and caused by increased epithelial apoptosis. Pseudomelanosis coli is absent in colonic neoplasia. The aim of our studies was to investigate this phenomenon in more detail. Apoptotic fragments of epithelial cells and their distribution, cell proliferation (Ki-67, MIB 1 immunostaining), macrophages (CD68 immunostaining), Bcl-2 expression and apoptosis [terminal-deoxynucleotidyl-transferase mediated dUTP fluorescein nick end labeling (TUNEL) assay] were studied in adenomas arising in normal and melanotic colonic mucosa, in normal colonic mucosa and colonic mucosa with pseudomelanosis alone. In adenomas, we found 7.0 apoptotic bodies per 100 epithelial cells in the epithelial layer and only 0.2 apoptotic bodies per high power field (HPF) in the lamina propria. In contrast, in melanotic mucosa 1.7 apoptotic bodies per 100 epithelial cells in the epithelial layer and 2.5 per HPF in the lamina propria were found. Our results show that apoptotic fragments remain in the neoplastic (adenomatous) epithelium and do not reach (at least in higher amounts) the lamina propria. They can, therefore, not contribute to the development of pseudomelanosis in these lesions. However, macrophages are diminished in adenomas. Proliferation (Ki-67) and also Bcl-2 expression are highly increased in adenomas. The pathway of mucosal macrophages is also discussed.
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  • 4
    ISSN: 1432-2307
    Keywords: Key words Colon ; Nonpolypoid adenoma ; Apoptosis ; Proliferation ; Morphogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Nonpolypoid neoplasms, as well as ordinary polypoid tumours, are occasionally found in the colorectum. To clarify whether cell kinetic status affects the macroscopic morphology of colorectal neoplasms, we investigated proliferative indices (PI), apoptotic indices (AI), and the expression of apoptosis-related gene products. We examined 110 colorectal neoplasms comprised of 36 polypoid, 38 flat elevated and 36 depressed tumours. According to WHO’s criteria these tumours consisted of 61 adenomas with low grade dysplasia (LGD), 30 adenomas with high grade dysplasia (HGD) and 19 carcinomas with submucosal invasion. Apoptotic cells were detected by TUNEL staining. Proliferating cells and apoptosis-related gene products were assessed by immunohistochemistry for Ki-67, p53, Bcl-2, and Bax antigens. AI were closely associated with macroscopic morphology in adenomas but not in carcinomas. PI were relatively constant among the three macroscopic types in adenomas and carcinomas. Median AI values of polypoid, flat elevated and depressed tumours were 1.8%, 2.1% and 4.6% for adenomas with LGD, 0.8%, 2.4% and 6.2% for adenomas with HGD and 2.9%, 4.0% and 3.6% for carcinomas, respectively. Overall PI were significantly higher in carcinomas than in adenomas with LGD, whereas AI were not different. Although the incidence of expression was significantly higher in carcinomas for p53 and in adenomas for Bcl-2 than the others, the expression of apoptosis-related gene products (p53, Bcl-2 and Bax) was similar among polypoid, flat elevated and depressed tumours. Macroscopic morphology of colorectal adenomas is determined by the apoptosis not by proliferation, and high apoptosis found in depressed adenomas implies their low net growth.
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  • 5
    ISSN: 1432-2307
    Keywords: Keywords Medullary thyroid carcinoma ; MEN2 ; Proliferation ; Apoptosis ; bcl ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  C-cell hyperplasia (CCH) and medullary thyroid carcinoma (MTC) in patients affected by germline mutations of the RET oncogene represent an exceptional opportunity to study the regulation of proliferation and apoptosis during tumour initiation and progression. In 56 specimens [CCH, n=1; MTC with CCH, n=26; MTC, n=20; lymph-node metastasis (LNM), n=9] from 46 patients [multiple endocrine neoplasia type 2a (MEN2a), n=24; MEN2b, n=2; familiar MTC (FMTC), n=4; sporadic MTC, n=16] and 3 cases of non-neoplastic CCH, proliferation activity (MIB1), the rate of apoptosis [dUTP nick end labelling (TUNEL)] and expression of p53, bcl-2, bcl-x and bax were investigated and compared with clinical data. In MEN-associated CCH and small MTC, bcl-2 was strongly expressed, bcl-x was moderately expressed and bax was only weakly expressed. Advanced tumours and LNM did show a more heterogeneous bcl-2 staining accompanied by an increased bax expression and accelerated proliferation. The rate of apoptosis was extremely low in all investigated tumours. P53 was detectable in three patients with rapidly growing and extensively metastasising MTC. No somatic p53 mutations were found. Hereditary MTC with germline RET mutations at codon 918 (MEN2b) and codon 634 revealed a bias towards a higher proliferation activity at a younger age and are more frequently accompanied by LNM. CCH and MTC are characterised with a preponderance of bcl-2 as a factor blocking the programmed cell death. While MTC, in general, is a slowly growing tumour, a minority of tumours do progress rapidly with high proliferation. The factors leading to an accelerated tumour progression do not seem to take their effect via the regulation of apoptosis. Certain alterations of RET are supposed to have a direct or indirect implication on proliferation and, because of this, an effect on the clinical course.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Der Radiologe 40 (2000), S. 35-42 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Neugeborenes ; Frühgeborenes ; Ultraschall ; Gehirn ; Rückenmark ; Key words ; Premature infant ; Newborn ; Sonography ; Brain ; Spinal cord
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Examination of the central nervous system in premature and full-term infants requires a sensible selection of the available diagnostic procedures such as ultrasound, MRI and CT to allow sufficient and accurate diagnosis and management. Ultrasound: Ultrasound, including the various Doppler techniques, is a very reliable, safe, noninvasive diagnostic tool that allows evaluation of even severely ill patients in intensive care units. It is especially well suited for the study of intracranial hemorrhage, hypoxic-ischemic encephalopathy, congenital malformations of the brain and lesions produced by intrauterine and acquired infections. Sonography is also very reliable in examination of spinal dysraphism and spinal cord injuries during birth. The necessity of surgical intervention (i.e. shunt implantation) as well as subsequent postoperative follow-up can be provided. MRI: In contrast to ultrasound, MRI is most useful to demonstrate the age-dependent myelinization pattern and clearly discriminates between the white and gray matter of the central nervous system. We therefore use MRI for the detection of complex malformations of the central nervous system in particular disorders of cell migration and for a final estimation of a perinatal brain injury. Conclusion: A precise ultrasound examination performed by an experienced physician who is familiar with the expected pathology and has access to a well-adjusted ultrasound machine should help to minimize the use of confirming CT and MRI investigations and to optimize their optional use in more complex cases.
    Notes: Zusammenfassung Zur Untersuchung des Gehirns und Rückenmarks von Früh- und Neugeborenen müssen die zur Verfügung stehenden Bildmodalitäten – Ultraschall, MR, CT – gemäß ihrer Aussagekraft in Bezug auf klinische Fragestellung und therapeutische Konsequenz angewendet werden. Ultraschall: Der Ultraschall einschließlich der verschiedenen Dopplertechniken ermöglicht ohne Sedierung die rasche, risikoarme und sehr zuverlässige Untersuchung auch schwerkranker Kinder auf der Intensivstation. Es gilt, die Hirnblutungen, die hypoxisch-ischämischen Hirnschädigungen und ihre Folgen, Hirnmissbildungen, Folgen kongenitaler und postnatal erworbener Infektionen, die Dysrhaphien des Rückenmarks und die geburtstraumatischen Rückenmarkschädigungen nachzuweisen oder auszuschließen, die Indikation zu chirurgischen Interventionen (z.B. Drainage eines Hydrozephalus) zu stellen und deren Erfolg zu beurteilen. Für den frühen Nachweis hypoxisch-ischämischer Schädigungen ist der Ultraschall wenig sensitiv. MRT: Da das MR im Gegensatz zum Ultraschall die altersabhängige Myelinisierung zeigt und die Unterscheidung zwischen grauer und weißer Substanz ermöglicht, nützen wir diese anatomische Auflösung bei der Untersuchung von sowohl sehr komplexen Hirnfehlbildungen als auch solchen, die mit Migrationsstörungen einhergehen, und gelegentlich für die abschließende Beurteilung des Ausmaßes einer perinatalen Hirnschädigung. Schlussfolgerung: Nach einer sorgfältig durchgeführten Ultraschalluntersuchung durch einen mit der zu erwartenden Pathologie vertrauten Untersucher mit einem hochauflösenden Ultraschallgerät sollten CT- und MR-Untersuchungen nur zur Bestätigung des Ultraschallbefunds überflüssig sein, zu deren evtl. notwendiger Ergänzung jedoch optimiert erfolgen.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Der Radiologe 40 (2000), S. 72-77 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Kongenitale Anomalien der Nieren ; Neonatale Hydronephrosen ; Ultraschall in der Neonatalperiode ; Key words ; Congenital anomalies of the kidneys ; Neonatal hydronephrosis ; Neonatal ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Malformations of the urinary tract are one of the most common types of anomalies in the neonatal period. Approximately 15–20% of all prenatally detected malformations require acute postnatal imaging. Sonography is the primary imaging modality in the evaluation of nephro-urologic problems in infancy. Hydronephrosis represents the most common pathology, followed by multicystic-dysplastic kidney. Discussion: The result of the sonographic examination directs further imaging. An adequate diagnostic algorithm is decisive for accurate diagnosis, for the appropriate therapeutic regimen and for the prognosis of the patients.
    Notes: Zusammenfassung Fehlbildungen der Nieren und der ableitenden Harnwege zählen zu den häufigsten kongenitalen Anomalien in der Neugeborenenperiode. Etwa 15–20% aller pränatal diagnostizierten Fehlbildungen erfordern eine akute postnatale Diagnostik. Die Sonographie ist das initiale bildgebende Verfahren der Wahl in der Abklärung nephrourologischer Fragestellungen im Kindesalter. Hydronephrosen stellen die häufigsten Pathologien dar, die multizystisch-dysplastische Niere steht an 2. Stelle. Diskussion: Das Ergebnis der Sonographie ist richtungsweisend für die Wahl der weiteren bildgebenden Verfahren. Der adäquate diagnostische Algorithmus ist entscheidend für die richtige Diagnose, das geeignete therapeutische Prozedere und letztendlich für die Prognose der Patienten.
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  • 8
    Electronic Resource
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    Springer
    Der Radiologe 40 (2000), S. 123-129 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Spiral-CT ; Herz ; Retrospektives Gating ; Zeitauflösung ; Key words ; Spiral CT ; Heart imaging ; Retrospective gating ; Temporal resolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Purpose: Spiral CT of the heart using the established ways of ECG synchronization is hampered by the relatively long acquisition times of 250 to 500 ms. This only allows to acquire diastolic images in patients with moderate heart rates. In this work, algorithms for time-optimized retrospective cardiac gating are presented, and their potential to improve temporal resolution is investigated. Material and methods: These algorithms use data from multiple gantry rotations for image reconstruction, which is possible for multi-scans at fixed slice positions as well as for overlapping spiral scans. Temporal resolution was quantified using computer simulations and compared to experimental data from pigs. Results: Using a conventional sub-second CT scanner, considerably higher temporal resolutions are possible with spiral scanning. A temporal resolution of 170 ms already provides systolic images with little motion artifacts. Higher temporal resolutions of up to 70 ms are demonstrated for multi-scans, which allows to depict ventricle wall movement over the complete cardiac cycle. Discussion: The method of time-optimized retrospective cardiac gating broadens the spectrum of conventional spiral-CT for cardiac imaging. It can be directly transferred to multi-slice scanners. Here it can be used clinically because of reduced scan time. Potential applications are the determination of functional cardiac parameters like ejection fraction and the detection of disorders of ventricle wall movement.
    Notes: Zusammenfassung Zielsetzung: Die Spiral-CT des Herzens ist mit bisherigen Verfahren zur EKG-Synchronisation nur eingeschränkt möglich. Die Aufnahmezeit von ca. 250 bis 500 ms ermöglicht nur diastolische Aufnahmen bei Patienten mit moderater Herzfrequenz. In dieser Arbeit wurden Algorithmen zum zeitoptimierten retrospektiven EKG-Gating entwickelt und untersucht, wie höhere Zeitauflösungen erreicht werden können. Material und Methode: Das Prinzip der Algorithmen ist es, Daten von mehreren Gantry-Umläufen für die Bildrekonstruktion heranzuziehen. Dies ist sowohl in einzelnen Schichten als auch bei Spiralscans mit überlappenden Aufnahmeschichten möglich. Die Zeitauflösung wurde durch Computersimulationen für verschiedene Aufnahmeparameter bestimmt und mit Experimenten an Schweinen verglichen. Ergebnisse: Es zeigt sich, dass mit einem Standard-Subsekunden-CT-Scanner mit überlappenden Spiralen deutlich höhere Zeitauflösungen möglich sind, bereits 170 ms ermöglichen eine Darstellung der Systole mit nur minimalen Bewegungsartefakten. An einzelnen Schichten wurden Zeitauflösungen von bis zu 70 ms demonstriert, womit die Herzwandbewegung über den kompletten Herzzyklus dargestellt werden kann. Diskussion: Die Methode des zeitoptimierten retrospektiven EKG-Gating erweitert die Einsatzmöglichkeiten herkömmlicher Spiral-CTs für die Bildgebung des Herzens. Sie lässt sich direkt auf Multizeilen-CTs übertragen, wo sie wegen der Reduktion der Untersuchungszeit klinisch eingesetzt werden kann. Mögliche Anwendungen sind die Bestimmung von funktionellen Herzparametern wie Ejektionsfraktion und die Detektion von Wandbewegungsstörungen.
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  • 9
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Magnetresonanztomographie ; Flussmessung ; Koronararterie ; Koronare Bypassgefäße ; Key words ; MR imaging ; Flow quantification ; Coronary artery ; Coronary bypass grafts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Purpose: To evaluate accuracy of velocity encoded cine MR imaging for determination of blood flow in coronary arteries and coronary bypass grafts. Materials and methods: 12 patients with 22 coronary bypass grafts underwent intraoperative flow quantification using the transit time ultrasound method. These values were compared to postoperative MR phase shift measurements. Flow measurements were performed preoperatively in 28 coronary arteries of 20 patients. For flow measurement, we used a velocity-encoded k-space segmented gradient echo sequence with a temporal resolution of 110 or 125 ms, respectively. 6–8 pase shift images could be acquired during one cardiac cycle. Results: There was a significant correlation between intraoperative and flow measurements using velocity-encoded MR imaging (r=0.74, p〈0.0001, t-test). Flow volumes determined by MR imaging were systemati-cally larger than those determined by the transit time ultrasound method. Mean flow in coronary arteries was reduced in severly stenosed vessels (〉70%) compared to normal vessels. Intra- and interobserver vari-ability were 10.5 and 15% (coronary bypass grafts), and 12.3 and 15.8% (coronary ar- teries), respectively. Conclusions: Velocity-encoded MR imaging enables determination of flow in coronary artery bypass grafts and coronary arteries. Future developments should aim at the improvement of spatial and temporal resolution of the method.
    Notes: Zusammenfassung Ziel: Es sollte die Genauigkeit der MR-Phasenkontrastmethode zur Ermittlung des Flusses in Koronararterien und koronaren Bypassgefäßen bestimmt werden. Material und Methode: Die MRT-Flussmessungen von 12 Patienten mit 22 Bypassgefäßen wurden mit intraoperativ mittels Ultraschalldurchflussmethode bestimmten Flüssen verglichen. Präoperativ wurden zusätzlich Flussmessungen in 28 Koronararterien von 20 Patienten durchgeführt. Zur MRT-Flussmessung wurde eine segmentierte 2D-Flash-Sequenz verwendet, die eine zeitliche Auflösung von 110 bzw. 125 ms aufwies. Dies ermöglichte die Akquisition von 6–8 Bildpaaren pro Herzzyklus. Ergebnisse: Es bestand eine signifikante Korrelation zwischen den Ergebnissen der intraoperativen und denen der postoperativen MRT-Flussmessung (r=0,76, p〈0,0001, t-Test). Das mit der MRT gemessene Flussvolumen lag über dem bei der Ultraschallmessung ermittelten. Die Bestimmung des mittleren Flusses in den Koronararterien zeigte deutliche Unterschiede zwischen Gefäßen mit höhergradiger Stenose (〉70%) und Gefäßen ohne Stenose. Die Intra- und Interbeobachtervariabilitäten betrugen 10,5 und 15% (Bypass) bzw. 12,3 und 15,8% (Koronararterien). Schlussfolgerungen: Die Phasenkontrastmethode ermöglicht – in Kenntnis ihrer Limitationen – eine relativ genaue Bestimmung des Blutflusses in Koronararterien und koronaren Bypassgefäßen. Weiterentwicklungen der Methode müssen eine verbesserte räumliche und zeitliche Auflösung zum Ziel haben.
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  • 10
    Electronic Resource
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    Der Radiologe 40 (2000), S. 177-183 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Mammakarzinom ; Früherkennung ; Qualitätssicherung ; Key words ; Breast cancer ; Screening ; Quality assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In Germany there is still an urgent need for action in regard to screening for breast cancer. The announcement of research projects for mammography screening proves this. The following reports the results of the Munich field study. In 2 years, 2489 breast cancer cases were registered (status 6/98). Screening data were available for 1319 patients. The reduction in mortality, found in randomized studies, due to mammography in women over 50 years old was confirmed. A relative reduction of 44.8% in 10-year mortality could be estimated through mammography and 25.1% through palpation, in comparison with ”doing nothing”. We could also estimate the participation of screening and the used methods in the Munich region. If the mammographies carried out today were used at 2-year intervals for women aged between 50 and 70 years, then the mammography screening could be performed with no additional costs for 70% of the women. The known facts regarding the population-based mortality and regarding the acceptance of the palpation screening and frequency of mammography are additional aspects for inclusion in the discussion of what research projects in Germany are and what they should fulfill.
    Notes: Zusammenfassung Hintergrund: Bei der Früherkennung des Mammakarzinoms besteht in Deutschland nach wie vor ein dringender Handlungsbedarf. Die Ausschreibung von Modellprojekten zur Einführung des Mammographiescreenings belegt dies. Im folgenden wird – als Diskussionsgrundlage –über erste Ergebnisse der Feldstudie München berichtet. Ergebnisse: In einem Zeitraum von 2 Jahren wurden 2489 Mammakarzinome registriert (Stand Juni 1998). Zu 1319 Patientinnen sind Angaben zur Früherkennung verfügbar. Die durch randomisierte Studien gesicherte Senkung der Mortalität durch die Mammographie im Alter 〉50 Jahre konnte bestätigt werden. Aufgrund der dokumentierten Stadienverteilung beträgt die Schätzung für die relative Senkung der 10-Jahres-Mortalität durch die Mammographie 44,8% und durch die Palpation 25,1% im Vergleich zum „Nichtstun”. Auch die Inanspruchnahme der Früherkennung und die in der Region München eingesetzten Methoden konnten abgeschätzt werden. Schlussfolgerungen: Würden die heute durchgeführten Mammographien bei Frauen im Alter zwischen 50 und 70 Jahren mit einem Abstand von 2 Jahren eingesetzt, so könnte das Mammographiescreening bei etwa 82% der Frauen kostenneutral durchgeführt werden. Die bekannten Fakten zur Mortalität und zur bundesweiten Inanspruchnahme des heutigen Früherkennungsangebots sind weitere Grundlagen für die Diskussion, was Modellprojekte in Deutschland sein und was sie wann leisten sollten.
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  • 11
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    Der Radiologe 40 (2000), S. 18-27 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; MRT ; Neugeborene ; Cerebrum ; Fetus ; Key words ; MRI ; Neonatal ; Brain ; Fetal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Magnetic resonance tomography (MRT) has become the most important method in the workup of infantile cerebral complications after primary sonography. Cerebral MR examination and image interpretation during the infantile period require extensive knowledge of morphological manifestations, their pathophysiological background, and frequency. The choice of imaging parameters and image interpretation is demonstrated in infarctions and hemorrhages of the mature and immature brain. A review of the main differential diagnoses is also given. The relevance of MR spectroscopy and fetal MRI is discussed.
    Notes: Zusammenfassung Zur Abklärung zerebraler Veränderungen bei Neugeborenen hat sich die Magnetresonanztomographie (MRT) als wichtigste weiterführende Methode nach der Sonographie entwickelt. Die Durchführung und Auswertung der MR-Untersuchungen erfordern jedoch eine genaue Kenntnis der morphologischen Manifestationen, des pathophysiologischen Hintergrunds und der Häufigkeit bestimmter zerebraler Komplikationen in diesem Lebensalter. Resümee: Ausgehend von zerebrovaskulären Erkrankungen werden diese Fragen behandelt, wobei sowohl auf die Auswahl der adäquaten Untersuchungsparameter als auch auf die Bildinterpretation und die wichtigsten Differentialdiagnosen eingegangen wird. Die Bedeutung von MR-Spektroskopie und fetaler MRT wird diskutiert.
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  • 12
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Thorax ; Neugeborene ; Frühgeborene ; Kongenitale Pathologien ; Erworbene Pathologien ; Key words ; Chest ; Newborn ; Preterm infant ; Congenital pathologies ; Acquired pathologies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In diagnostic imaging of thoracic pathologies in mature and especially immature neonates, chest X-ray has a leading position. Profound knowledge of the normal chest X-ray and the potential physiological perinatal changes is the basic requirement for interpretation of the X-ray of a neonate. Childhood pathologie: Many congenital and acquired diseases that the radiologist is faced with in neonatology are unknown in the imaging of adults. Many of these changes are life-threatening or may have an impact on the patient’s future quality of life. Therefore early diagnosis in close cooperation with the paediatrician is essential. We give here an overview of the most important pathologic changes that the radiologist may be con- fronted with in daily routine.
    Notes: Zusammenfassung In der bildgebenden Diagnostik thorakaler Pathologien bei reifen und insbesondere unreifen Neugeborenen steht das Thoraxröntgenbild an erster Stelle. Profunde Kenntnisse des normalen Thoraxbilds und der möglichen physiologischen peripartalen Veränderungen sind Voraussetzung für die Interpretation der neonatologischen Thoraxaufnahme. Kindliche Pathologien: Eine Vielzahl von kongenitalen und erworbenen Veränderungen, mit denen der Radiologe in der Neonatologie konfrontiert ist, sind in der Radiodiagnostik des erwachsenen Patienten unbekannt. Viele dieser Veränderungen sind für den Patienten lebensbedrohlich oder können die Lebensqualität in seinem weiteren Leben beeinflussen. Eine frühzeitige Diagnostik in enger Zusammenarbeit mit dem Pädiater ist daher essenziell. Hier wird ein Überblick über die wichtigsten Pathologien, mit denen der Radiologe in der täglichen Routine konfrontiert sein kann, gegeben.
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  • 13
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    Der Radiologe 40 (2000), S. 63-71 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Gastrointestinaler Notfall ; Neugeborenenalter ; Bildgebende Diagnostik ; Key words ; Gastrointestinal emergency ; Nenoate ; Diagnostic imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Gastrointestinal emergencies in neonates often demand a quick and efficient diagnos-tic imaging. The procedures have to take the special diseases and conditions in these babies and preterm children into account. Conclusion: This paper summarises the most common causes for gastrointestinal neonatal emergencies and discusses the indication and performance as well as the diagnostic value of the commonly used modalities, giving some suggestions for an efficient imaging algorithm. Most of the time conventional plain abdominal films and sonography can answer the clinically important questions, however, in certain conditions fluoroscopy with contrast administration (enema, etc.) is mandatory. Only rarely is CT, MRI or Angiography indicated.
    Notes: Zusammenfassung Der gastrointestinale Notfall im Neugeborenenalter erfordert oft eine rasche, effiziente, den Bedingungen des Neu- und Frühgeborenenalters angepasste bildgebende Diagnostik. Diese Arbeit beschreibt die in diesem Zusammenhang wichtigsten angeborenen und erworbenen Erkrankungen und diskutiert die Durchführung und Indikation bzw. den Stellenwert der zur Verfügung stehenden bildgebenden Methoden. Schlussfolgerung: Zumeist kann mit dem Abdomenübersichtsröntgen und dem Sonogramm eine ausreichende diagnostische Klärung erzielt werden. Bei bestimmten Fragestellungen ist jedoch eine weitergehende Beurteilung durch ein Kontrastmittelröntgen bzw. eine Durchleuchtungsuntersuchung (wie z.B. Schluckakt- und Magenröntgen oder Irrigoskopie) unabdingbar. CT, MRT oder Angiographie werden nur seltenst benötigt.
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  • 14
    Electronic Resource
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    Der Radiologe 40 (2000), S. 78-82 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Intranet ; Internet ; PACS ; Radiologie ; Key words ; Intranet ; Internet ; PACS ; Radiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The aim of the paper is to present the conceptual basis and capabilities of intranet applications in radiology. The intranet, which is the local brother of the internet can be readily realized using existing computer components and a network. All current computer operating systems support intranet applications which allow hard and software independent communication of text, images, video and sound with the use of browser software without dedicated programs on the individual personal computers. Radiological applications for text communication e.g. department specific bulletin boards and access to examination protocols; use of image communication for viewing and limited processing and documentation of radiological images can be achieved on decentralized PCs as well as speech communication for dictation, distribution of dictation and speech recognition. Discussion: The intranet helps to optimize the organizational efficiency and cost effectiveness in the daily work of radiological departments in outpatients and hospital settings. The general interest in internet and intranet technology will guarantee its continuous development.
    Notes: Zusammenfassung Ziel dieses Beitrags ist es, konzeptionelle Grundlagen und Möglichkeiten von Intranetanwendungen in der Radiologie aufzuzeigen. Das Intranet, das der lokale Bruder des Internets ist, kann gegenwärtig relativ einfach mit den bestehenden Computerkomponenten und einem Netzwerk realisiert werden. Alle aktuellen Betriebssysteme unterstützen Intranetanwendungen, mit denen sowohl Hardware – als auch Software – unabhängig mit Hilfe von sog. Browsern die Kommunikation von Text, Bild, Video und Ton möglich ist, ohne dass auf den peripheren Rechnern entsprechend spezielle Software vorhanden sein muss. Beispielhafte Anwendungen der Textkommunikation werden vorgestellt, wie z.B. abteilungsspezifische Informationen und Untersuchungsprotokolle, außerdem Anwendungen der Bild- und Tonkommunikation. Diskussion: Das Intranet eröffnet insbesondere im täglichen Einsatz radiologischer Abteilungen im ambulanten und stationärem Bereich neue Möglichkeiten zur organisatorischen Effizienzsteigerung und Kosteneffektivität. Das globale Interesse an der Inter- und Intranettechnologie sichert die kontinuierliche Weiterentwicklung.
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  • 15
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Herz ; Herz-MR ; Volumen ; Cine MR ; Key words ; Heart ; Cardiac MRI ; Volume ; Cine MR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Purpose: To evaluate method- and user effects as well as the required time in the determination of left- and right ventricular ejection fractions in comparing manual and semiautomatic border detection of the endocardium. Methods: In 22 patients with varying cardiac diseases endocardial borders were detected either manually or semiautomatically (seeded ROI) and subsequently the right and left ventricular volume ejection fractions were computer-calculated. Two investigators defined the endocardial borders for both ventricles using both methods. For statistical analysis two-factorial analyses of variance were performed for the four variables: VEF right ventricle, VEF left ventricle, required time right ventricle, required time left ventricle (SAS, Anova). Results: There was no user or method effect detectable for both ventricles. The required time for both ventricles also did not reveal a user effect, but there was a dramatic method effect concerning a reduction of the required time for analysis for both ventricles 〉50%. Conclusions: The semiautomatic mode for detecting the endocardial borders in determining right and left ventricular ejection fractions did not demonstrate results differing from the results of the manual method, but is significantly superior concerning the time required for analysing ejection fractions of both ventricles with a reduction of over 50%. This might significantly reduce the expenditure for personnel.
    Notes: Zusammenfassung Fragestellung: Die manuelle und semiautomatische Endokarddetektion zur Bestimmung links- und rechtsventrikulärer Volumenejektionsfraktionen (VEF) werden verglichen. Ziel dieser Arbeit ist die Evaluierung des Methoden- und Anwendereffekts sowie der Bearbeitungszeit beider Verfahren. Methode: An 22 Patienten mit unterschiedlichen kardialen Erkrankungen wurden die Endokardgrenzen manuell und mit einem semiautomatischen Verfahren (Seeded-ROI) ermittelt und anschließend die rechts- und linksventrikulären Volumenejektionsfraktionen automatisch berechnet. In allen Fällen wurden von 2 Untersuchern die Endokardgrenzen des rechten und linken Ventrikels manuell und semiautomatisch bestimmt. Zur statistischen Analyse wurden 2-faktorielle Varianzanalysen (Methoden- und Anwendereffekt einschließlich Wechselwirkungen) für die 4 Variablen durchgeführt: VEF rechtsventrikulär, VEF linksventrikulär, Zeitaufwand rechtsventrikulär, Zeitaufwand linksventrikulär (SAS, Anova). Ergebnisse: Bezüglich der Bestimmungen der rechts- und linksventrikulären VEF war weder ein Methoden- (p=0,9613) noch ein Anwendereffekt (p=0,3095) nachweisbar. Bezogen auf die benötigte Bearbeitungszeit fand sich ebenfalls kein Anwendereffekt, aber ein massiver Methodeneffekt (p〈0,0001) im Sinn einer Reduzierung der Bearbeitungszeit um 〉50% sowohl für den rechten als auch für den linken Ventrikel. Schlussfolgerung: Nach unseren Erfahrungen liefert das semiautomatische Seeding-Verfahren zur Festlegung der Endokardgrenzen bei der Bestimmung der links- und rechtsventrikulären Ejektionsfraktionen keine von der manuellen Methode abweichenden Ergebnisse, ist aber bezüglich der Bearbeitungszeit deutlich überlegen. Die über 50%ige Zeitersparnis reduziert den Personalaufwand.
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  • 16
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Koronare Herzkrankheit ; Magnetresonanztomographie ; Myokardperfusion ; SPECT ; Key words ; Coronary artery disease ; Magnetic resonance imaging ; Myocardial perfusion ; SPECT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Aim: Performance of combined rest/stress MR perfusion studies and the analysis of qualitative signal intensity parameters in comparison with 99mTc-SestaMIBI SPECT in patients with known coronary artery disease (CAD). Methods: Sixteen patients with CAD underwent MR myocardial perfusion assessment at rest and after dipyridamole-induced hyperemia. Qualitative parameters (SI increase, SI upslope) of the SI time-curves were evaluated and characteristics of normal, reversible and persistent hypoperfused myocardium as assessed by 99mTc-SestaMIBI SPECT were compared. Results: Compared with the rest values, normal myocardium showed a significant increase of the SI upslope during hyperemia (P〈0.001), whereas persistent (P=0.07) and reversible (P=0.15) hypoperfusions showed only minor changes. SI increase over baseline also showed a significant increase only in normal myocardium (P〈0.001). At rest, reversible ischemic areas showed no significant differences from normal myocardium, whereas during hyperemia SI increase was significantly lower (P=0.02). Conclusions: Qualitative SI parameters of a combined rest/stress MR myocardial perfusion study allow to differentiate normal from reversibly or persistently hypoperfused myocardium.
    Notes: Zusammenfassung Fragestellung: Die kombinierte Ruhe- und Belastungsuntersuchung der myokardialen Durchblutung in der MRT sowie die Analyse qualitativer SI-Parameter der MR-Myokardperfusion bei Patienten mit koronarer Herzkrankheit wurden mit der 99mTc-SestaMIBI SPECT verglichen. Methode: Bei 16 Patienten mit koronarer Herzkrankheit (KHK) wurde in der MRT mit einer Mehrschichtgradientenechotechnik die Myokardperfusion unter Ruhe- und Belastungsbedingungen untersucht. Qualitative Signalintensitätsparameter der Kontrastmittelanflutung wurden berechnet und die Parameter in normalen, reversibel und persistierend minderperfundierten Myokardarealen miteinander verglichen. Ergebnisse: Normales Myokard zeigte im Gegensatz zu reversiblen (P=0,15) und persistierenden (P=0,07) Ischämien eine signifikante Zunahme der SI-Anstiegssteilheit unter Belastung (P〈0,001). Die SI-Zunahme zeigte ebenfalls nur in normal perfundierten Arealen eine signifikante Zunahme (P〈0,001) nach Belastung. Unter Belastung zeigte sich bei reversiblen Ischämien eine signifikant niedrigere SI-Zunahme als in normalem Myokard (P=0,02), während sich in Ruhe kein Unterschied zeigte. Schlussfolgerung: Qualitative SI-Parameter der kombinierten MR-Perfusionsuntersuchung des Myokards in Ruhe und unter Belastung erlauben die Differenzierung zwischen normalem sowie reversibel oder persistierend minderperfundiertem Myokard.
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  • 17
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    Der Radiologe 40 (2000), S. 2-7 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Neugeborenes ; Frühgeborenes ; Bildgebung ; Key words ; Newborn ; Premature infant ; Diagnostic imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Modern neonatology comprises care for a growing number of infants with congenital abnormalities and an increasing number of premature born infants. The survival rates of premature infants have increased dramati- cally during the past decade. This increase in survival rates can be attributed to improved prenatal and obstetric management and to advances in neonatal intensive care medicine. Radiological support: Neonatology has become a pediatric subspeciality of its own resulting in the demand for an equally specialised radiological support. Therefore the availability of a children´s radiologist for radiological and sonographic examinations is mandatory (24 hours a day) for optimal patient care on a neonatal intensive care unit. A good cooperation between radiologist and neonatologist in neonatal intensive care medicine is therefore warranted.
    Notes: Zusammenfassung Die moderne Neugeborenenintensivmedizin umfasst neben den typischen neonatalen Krankheitsbildern eine wachsende Zahl kleiner Frühgeborener mit einem Geburtsgewicht 〈1500 g und eine, durch verbesserte pränatale Diagnostik, zunehmend größer werdende Gruppe von Kindern mit komplexen Fehlbildungen. Anforderungen an den Radiologen: Diese Entwicklungen stellen auch an den Radiologen neue Anforderungen; neben der zunehmenden Zahl an Frühgeborenen und ihren speziellen Krankheitsbildern ist auch die Abklärung von speziellen, beim Intensivpatienten auftretenden Problemen erforderlich. Durch die meist gegebene Dringlichkeit der radiologischen Abklärung ist die Verfügbarkeit eines Kinderradiologen rund um die Uhr unabdingbar. Zudem müssen fahrbare Röntgen- und Ultraschallgeräte zur Verfügung stehen, um eine Diagnostik direkt am Krankenbett zu ermöglichen. Diskussion: An einer Neugeborenenintensivstation ist daher eine enge Zusammenarbeit mit dem Kinderradiologen unbedingt notwendig.
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  • 18
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    Der Radiologe 40 (2000), S. 28-34 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Zerebralinfarkt ; Krampfanfall ; Neugeborenes ; Dopplersonographie ; Vasospasmus ; Key words ; Cerebral artery infarction ; Seizure ; Newborn ; Doppler sonography ; Vasospasm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A cerebral artery infarction is an important differential diagnosis in the newborn with neurological abnormalities. Based on clinical data, its incidence is estimated to be 1 in 4000 newborns. Since the course is often subclininal, the true incidence is probably higher. Diagnosis: Cerebral ultrasound and Doppler sonography as readily available screening tools play a central role in the initial diagnosis of neonatal cerebral infarction. Definitive diagnosis is made by computed tomography or magnetic resonance imaging. Beside symptomatic anticonvulsive therapy, treatment aims at the prevention of secondary ischemic injury. Discussion: Three term infants with different clinical courses of neonatal stroke are presented to sensitize the clinician and the radiologist for this probably underdiagnosed entity. The role of imaging modalities in the diagnosis and follow-up of neonatal cerebral infarction is discussed.
    Notes: Zusammenfassung Ein Infarkt im Stromgebiet der Zerebralarterien stellt eine wichtige Differentialdiagnose bei neurologischen Auffälligkeiten in der Neonatalperiode dar. Die Inzidenz wird anhand von klinischer Daten auf 1:4000 Lebendgeborene geschätzt. Da der Verlauf oft subklinisch ist, liegt die wahre Inzidenz wahrscheinlich höher. Diagnose: Bei der Diagnosestellung kommen dem Schädelultraschall und der Dopplersonographie als leicht verfügbaren Screening-Methoden eine zentrale Rolle zu. Die definitive Diagnose wird, je nach Verfügbarkeit, mittels Computertomographie oder Kernspintomographie gestellt. Die Behandlung ist neben der symptomatischen (antikonvulsiven) Therapie auf die Vermeidung von ischämischen Sekundärschäden gerichtet. Diskussion: Wir wollen mit der vorliegenden Arbeit anhand von 3 Kindern mit verschiedenen klinischen Verläufen eines sog. Neonatal stroke den Stellenwert der bildgebenden Verfahren bei der Diagnostik und Verlaufskontrolle aufzeigen und die Sensibilität für dieses vermutlich unterdiagnostizierte Krankheitsbild erhöhen.
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  • 19
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    Der Radiologe 40 (2000), S. 52-57 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Zentrale Katheter ; Neonatologie ; Radiologie ; Key words ; Central catheter ; Neonatology ; Radiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Background: Central catheters in neonatological intensive care patients are used for the prolonged application of medicataion or parenteral infusions. Dislocations and septic and thromboembolic complications may occur. Control of position: Radiologically, the correct position of the catheter must be proven. Dislocations or complications associated with central catheters must be diagnosed. For catheter monitoring plain film radiographs are the first line of investigation; however, sonography may be of additional assistance. Angiographic techniques should only be performed when conventional noninvasive methods do not supply satisfactory results. Special knowledge is necessary for monitoring catheters that are set via the umbilical artery or vein. The radiological applications for catheter monitoring in the neonate intensive care unit are discussed in this article.
    Notes: Zusammenfassung Hintergrund: Die im neonatologischen Krankengut am häufigsten verwendeten Zugänge sind Katheter, die eine prolongierte Verabreichung von Antibiotika, höher osmolarer Lösungen oder evtl. Chemotherapeutika gewährleisten. Komplikationen ergeben sich durch Fehllagen oder sind septischer und thrombembolischer Genese. Lagekontrolle: Für den Radiologen gilt es, eine adäquate Lagekontrolle des Katheters durchzuführen, um Fehllagen zu vermeiden, jedoch auch Komplikationen zu diagnostizieren. Für dieses Kathetermonitoring steht zur Lagekontrolle das Nativbild im Vordergrund, des Weiteren erweist sich jedoch die Sonographie als wesentlicher Pfeiler in der Katheterdiagnostik, insbesondere im Hinblick auf die katheterassoziierten Komplikationen. Angiographische Techniken sollten erst nach Ausschöpfen sämtlicher nichtinvasiver diagnostischer Möglichkeiten durchgeführt werden. Besondere Anforderungen ergeben sich durch die in der Neonatologie verwendeten Zugänge über den Nabel, wobei sowohl Kenntnis der exakten Topographie der Katheterlage als auch der speziellen potentiellen Komplikationen von großer Bedeutung ist. Im Folgenden sollen die radiologischen Aufgaben und Möglichkeiten beim Kathetermonitoring unter besonderer Berücksichtigung spezieller Anforderungen bei neonatologischen Intensivpatienten vorgestellt werden.
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  • 20
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    Springer
    Der Radiologe 40 (2000), S. 58-62 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Nekrotisierende Enterokolitis ; Pneumatosis intestinalis ; Pneumoportogramm ; Perforation ; Leeraufnahme des Abdomens ; Sonographie ; Key words ; Necrotizing enterocolitis ; Pneumatosis intestine ; Pneumoportogram ; Perforation ; Plain radiography ; Sonography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Necrotizing enterocolitis (NEC) is a disease of the premature neonate that requires early therapy, sometimes even surgery and therefore early diagnosis. In general, plain radiography of the abdomen and sonography are valuable imaging techniques for diagnosis of NEC. Course of NEC: The disease starts with distension of small bowel loops. Furthermore the children develop pneumatosis in the bowel wall, which is a nonspecific pattern. If the NEC persists, the air passes into the portal vein system, causing a pneumoportogram. Finally, the disease can lead to perforation. In doubtful cases, the plain radiogram must be repeated within a period of 6 h. With sonography distension of the bowel, thickening of and pneumatosis in the bowel wall, the pneumoportogram and free intraperitoneal fluid can be easily depicted. The most common complications of NEC are intestinal stenosis and strictures that can lead to ileus. Differential diagnosis: Focal perforation of ileum, volvulus and Hirschsprung’s disease are some of the differential diagnoses.
    Notes: Zusammenfassung Die nekrotisierende Enterokolitis (NEC) ist eine schwere Erkrankung des Abdomens bei Frühgeborenen, die einer raschen, nötigenfalls chirurgischen Therapie zugeführt werden muss. Dazu bedarf es einer frühen Diagnose, die mit einer Leeraufnahme des Abdomens und Sonographie gestellt werden kann. Verlauf von NEC: Die NEC beginnt mit einer Dilatation des Darms, zumeist des Dünndarms, in 2. Linie des Dickdarms. Des Weiteren entwickeln sich stehende Schlingen und eine Pneumatosis intestinalis, die ein unspezifisches Zeichen ist und bei allen ischämischen Darmerkrankungen auftreten kann. Beim Fortschreiten der Erkrankung kommt es zum Pneumoportogramm und im schlimmsten Fall zur Perforation. Bei unklaren Abdomenleerbefunden ist eine engmaschige radiologische Kontrolle notwendig. Sonographisch können sowohl die Distension des Darms als auch die Pneumatosis intestinalis als auch das Pneumoportogramm als auch freie Flüssigkeit hervorragend erfasst werden. Spätkomplikationen sind Stenosen und Strikturen, die zu Subileus und Ileus führen können. Differentialdiagnosen: Die Differentialdiagnosen reichen von fokaler Ileumperforation bis hin zu Volvulus und Morbus Hirschsprung.
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  • 21
    ISSN: 1432-1262
    Keywords: Keywords Nonsteroidal anti-inflammatory drugs ; Colon cancer ; Apoptosis ; Caspase ; Poly(ADP-ribose) polymerase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Epidemiological studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of and mortality from colon cancer. In addition, NSAIDs reduce the number and the size of polyps in patients with familial adenomatous polyposis. The mechanisms responsible for the antineoplastic effect of NSAIDs are not yet completely understood, but one of the possible mechanisms is an induction of apoptosis. We explored the role of caspase-3, a major apoptosis-executing enzyme, in NSAID-induced apoptosis of colon cancer cell line HT-29. Treatment of HT-29 cells with indomethacin induced a dramatic increase in caspase-3-like protease activity measured by a cleavage of the fluorogenic substrate Ac-DEVD-AMC. Western blot analysis showed that indomethacin treatment led both to decrease in pro-caspase-3 and to cleavage of its substrate poly(ADP-ribose) polymerase (PARP). Furthermore, the caspase- 3-like protease inhibitor Ac-DEVD-CHO attenuated indomethacin- induced DNA fragmentation dose dependently. However, mRNA expression of CASP genes was not affected by the addition of indomethacin, highlighting the importance of posttranslational modification of this enzyme for the activation. These results suggest that NSAIDs, including indomethacin, induce apoptosis in colon cancer cells through a caspase-3 dependent mechanism which may contribute to the chemopreventive functions of these agents.
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  • 22
    ISSN: 1432-1335
    Keywords: Key words Genistein ; Eicosapentaenoic acid ; Apoptosis ; Bax ; Bcl-xL ; Caspase-3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Genistein, a prominent isoflavone in soy products, produced dose- and time-dependent in vitro growth inhibition at high concentrations (at least 185 μM) with an IC50 of 7.0–274.2 μM after 72 h incubation in four breast cancer cell lines (DD-762, Sm-MT, MCF-7 and MDA-MB-231) and one breast epithelial cell line (HBL-100) of human and animal origin; it stimulated estrogen-receptor-positive MCF-7 cells at low concentrations (3.7 nM–37 μM). Genistein-exposed cells underwent apoptosis, confirmed by G2/M arrest followed by the appearance of a sub-G1 fraction in cell-cycle progression, and by a characteristic cell ultrastructure. The apoptosis cascade was due to up-regulation of Bax protein, down-regulation of Bcl-XL protein, and activation of caspase-3. Genistein acted in synergism with eicosapentaenoic acid (EPA), a fish oil component, on human breast cancer MCF-7 cells (genistein 〉 93.2 μM and EPA 〉 210.9 μM) and on MDA-MB-231 cells (genistein 〉 176.1 μM and EPA 〉 609.3 μM). Dietary intake of genistein in combination with EPA may be beneficial for breast cancer control.
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  • 23
    ISSN: 1432-1335
    Keywords: Key words 5-Fluorodeoxyuridine ; Heterodinucleoside dimers ; Prodrugs ; Prostate cancer ; Cytotoxicity ; Cell cycle ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Purpose: Current therapies have limited impact on the progression of metastatic hormone-refractory prostate cancer. Therefore, we investigated the utility of new heterodinucleoside phosphate dimers of 5-fluorodeoxyuridine (5-FdUrd) in p53-mutated and androgen-independent DU-145 human prostate tumour cells. Methods: The effects of the dimers were assessed in vitro by a cell proliferation assay for cytotoxicity, flow cytometry for cell cycle distribution, confocal laser scanning microscopy for the detection of apoptotic bodies, poly(ADP-ribose) polymerase cleavage for caspase 3 activity and by a thymidylate synthetase assay. Results: The new dimers N 4-palmitoyl-2′-deoxycytidylyl-(3′→5′)-5-fluoro-2′-deoxyuridine (dCydPam-P-FdUrd) and 2′-deoxy-5-fluorouridylyl-(3′→5′)-2′-deoxy-5-fluoro-N 4-octadecylcytidine (5-FdUrd-P-FdCydOct) caused marked cytotoxicity with IC50 values of 3–4 μM. 5-FdUrd-P-FdCydOct at 200 μM was capable of eradicating 100% of tumour cells whereas 10% of the cells were resistant to 5-FdUrd. Cytotoxicity was caused by a dramatic S-phase arrest, resulting in an increase of this cell population from 34% to 85% with 5-FdUrd-P-FdCydOct and to 81% with dCydPam-P-FdUrd. S-phase arrest was followed by apoptosis, as shown by 85% of the cells staining positive for Apo 2.7 antibody, a six- to eight-fold increased caspase 3 activity and DNA fragmentation. Thymidylate synthase activity was inhibited by 50% at 0.6–0.7 μM dimer concentration. The dimers were hydrolysed in vitro by phosphodiesterase I and human serum to the corresponding nucleosides and nucleoside monophosphates. Conclusions: The new dimers dCydPam-P-FdUrd and 5-FdUrd-P-FdCydOct are effective prodrugs of 5-FdUrd and have potential value for the treatment of p53-mutated and hormone-independent human prostate carcinomas.
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  • 24
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    Journal of cancer research and clinical oncology 126 (2000), S. 145-152 
    ISSN: 1432-1335
    Keywords: Key words Angiogenesis ; Apoptosis ; Glioma ; Thymidine phosphorylase ; Vascular endothelial growth factor ; AbbreviationsTP thymidine phosphorylase ; GBM glioblastoma ; AA anaplastic astrocytoma ; LGA low-grade astrocytoma ; VEGF vascular endothelial growth factor ; RT-PCR reverse transcriptase/polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thymidine phosphorylase (TP) has been implicated as a potent angiogenic factor and a prognostic factor in various human solid tumors. We investigated the expression of TP in a series of human astrocytic tumors using immunohistochemistry, enzyme-linked immunosorbent assay, and reverse transcriptase/polymerase chain reaction (RT-PCR) analysis. A total of 63 astrocytic tumors [27 glioblastomas (GBM), 19 anaplastic astrocytomas (AA), 17 low-grade astrocytomas (LGA)] and 5 normal brain tissues were immunohistochemically stained with antibodies to TP, vascular endothelial growth factor (VEGF), p53, MIB-1, and factor-VIII-related antigen. They were also evaluated for the degree of apoptosis by a ApopTag kit. Ten tumors (5 GBM, 2 AA, 3 LGA) and 3 normal brain tissues were evaluated for their expression of VEGF and TP by RT-PCR analysis. TP was constantly localized in the cytoplasm of astrocytic tumor cells, less intensely in the cytoplasm of vascular endothelial cells, but not in the normal brain. Some of the TP-positive cells were of macrophage origin, but most positive cells were the tumor cells themselves. Vascular density, MIB-1 positivity, p53 positivity, VEGF expression, and the apoptotic index were significantly higher in the TP-positive tumors than in TP-negative tumors. There was a significant correlation between TP and VEGF mRNA expression. In a limited number of glioblastoma cases, the apoptotic index was significantly higher in TP-positive glioblastomas than in TP-negative glioblastomas. In human astrocytic tumors, TP was expressed in the tumor, macrophage, and endothelial cells. TP was a potent angiogenic factor closely associated with cell proliferation and tumor apoptosis.
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  • 25
    ISSN: 1432-1335
    Keywords: Key words Cycloprodigiosin hydrochloride ; Breast cancer ; Apoptosis ; Intracellular acidification ; Bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of cycloprodigiosin hydrochloride (cPrG · HCl), a H+/Cl− symporter, on five human breast cancer cell lines (KPL-1, T-47D, MCF-7, MKL-F, and MDA-MB-231), a human breast epithelial cell line (HBL-100), and a human fibroblast cell line (WI-38–40) was examined. cPrG · HCl inhibited the growth of all five breast cancer cell lines (IC50: 0.46–0.62 μM) and slightly inhibited HBL-100 and WI-38–40 cell growth (IC50: 1.75 μM and 2.26 μM respectively). cPrG · HCl treatment in KPL-1 cells increased the pH of acidic organelles, decreased intracellular pH, and caused apoptosis, which was confirmed by the appearance of a sub-G1 population by flow cytometry and DNA fragmentation. In addition, cPrG · HCl-induced apoptosis was strongly suppressed by imidazole, a cell-permeable base, suggesting that intracellular acidification was essential for the apoptosis. Further, cPrG · HCl treatment up-regulated Bax and Bak expression, down-regulated Bcl-2 expression, and activated caspase-3. Therefore, the intracellular acidification by cPrG · HCl treatment suppressed the growth of human breast cancer cell lines by inducing apoptosis.
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  • 26
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    HNO 48 (2000), S. 75-90 
    ISSN: 1433-0458
    Keywords: Schlüsselwörter ; 3D-Navigation ; Rahmenlose Stereotaxie ; Computerunterstützte Chirurgie ; Intraoperative Navigation ; Key words ; 3D-navigation ; Frameless stereotaxy ; Computer aided surgery ; CAS ; Intraoperative navigation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary 3D-navigation systems have only recently been introduced into the surgical field. Since then they have gained increasing importance not only in ENT surgery but also in neurosurgery, orthopedic surgery, maxillo-facial surgery, radiology and radiotherapy. Following a brief historical introduction this article reviews existing navigation technologies, in terms of indication, practicability, accuracy, forensic and financial aspects. The selection of the navigation system is strongly influenced by the planned procedure (endoscopic, microscopic, open approach). According to our experience most of these systems provide useful support intraoperatively. The clinical application accuracy regularly lies in the range of 1–2 mm.
    Notes: Zusammenfassung Seit der Entwicklung und der kommerziellen Verfügbarkeit von intraoperativen 3D-Navigationssystemen hat diese Technologie nicht nur in der Hals-Nasen-Ohrenchirurgie sowie der Neurochirurgie, sondern auch anderen Disziplinen, wie Orthopädie, Kieferchirurgie, Strahlentherapie und Radiologie an Bedeutung gewonnen. Nach einem kurzen historischen Überblick werden unterschiedliche Navigationstechnologien in ihrer Arbeitsweise dargestellt und anhand von klinischen Anwendungen verdeutlicht. Die Auswahl des geeigneten Navigationssystems richtet sich nach der Art des geplanten Eingriffs (endoskopisch, mikroskopisch, kombiniert). Durch intensive Weiterentwicklung dieser Systeme leisten sie bereits heute eine wertvolle Unterstützung für den HNO-Chirurgen. Die derzeit erzielbare intraoperative Genauigkeit liegt für die meisten Systeme regelhaft bei 1–2 mm.
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  • 27
    ISSN: 1433-0458
    Keywords: Schlüsselwörter ; Autogene Knorpeltransplantation ; Makroverkapselung ; Tissue engineering ; Polyelektrolytkomplexmembran ; Key words ; Cartilage ; Autogenous transplantation ; Encapsulation ; Polyelectrolyte complex membrane ; Tissue engineering
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In reconstruction of cartilage defects, autogenous transplantation is known as a reliable and experienced method. Although a clinical application has not been reported until now, tissue engineering permits in vitro production of autogenous cartilage transplants. Nevertheless, in both methods the cartilage is exposed to individually varying resorptive mechanisms. Among other methods for in vivo tissue protection, the encapsulation with a semipermeable polyelectrolytecomplex membrane could guarantee sufficient protection against resorptive influences. Human septal cartilage was encapsulated (group 1) with polyelectrolytecomplex membranes and subcutaneously implanted on the back of thymusaplastic nude mice. Cartilage implants without encapsulation (group 2) were used as control. Scanning electron microscopy and histochemical investigations were performed 1, 4, 8, 12 and 16 weeks after implantation. Group 1 showed no signs of resorption and chronic inflammation at all. In contrast, group 2 presented, correlating to the time of implanta-tion, increasing signs of cell death and fibrotic transformation, representing an increased activity of resorption. In conclusion, tissue encapsulation with a polyelectrolytecomplex membrane could ensure a sufficient protection of human cartilage transplants from resorptive influences. For the plastic-reconstructive surgeon the desired result becomes more calculable.
    Notes: Zusammenfassung In der rekonstruktiven Chirurgie könnte neben der etablierten Methode der autogenen Knorpeltransplantation das Tissue engineering humaner Knorpelgewebe zunehmend an Bedeutung gewinnen. Resorptive Mechanismen können jedoch bei beiden Methoden zu funktionell und kosmetisch unbefriedigenden Ergebnissen führen. Unter den heute zur Verfügung stehenden Verfahren der Gewebeprotektion könnte die Polyelektrolytmembranverkapselung mit Natriumzellulosesulfat und Polydialylldimethylammoniumchlorid einen ausreichenden Schutz vor resorptiven Einflüssen gewährleisten. Humaner nativer Nasenseptumknorpel wurde verkapselt (Gruppe 1) und unverkapselt (Gruppe 2) subkutan in thymusaplastische Nacktmäuse implantiert. Die Transplantate wurden nach 1, 4, 8, 12 und 16 Wochen explantiert und histologisch sowie rasterelektronenmikroskopisch untersucht. Gruppe 1 zeigte über den gesamten Implantationszeitraum keinerlei Resorptionsmerkmale bei vollständig erhaltener Knorpelgrundsubstanz. Gruppe 2 hingegen zeigte, korrelierend mit der Implantationsdauer, in zunehmendem Maße Knorpelzellnekrosen und einen bindegewebigen Umbau im Sinne einer Resorption. Die Polyelektrolytmembranverkapselung könnte somit eine sichere Methode zum Schutz humaner Knorpeltransplantate vor resorptiven Einflüssen darstellen. Für den Plastisch-rekonstruktiven Chirurgen wird hierdurch das gewünschte kosmetische und funktionelle Ergebnis kalkulierbarer.
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  • 28
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    HNO 48 (2000), S. 125-128 
    ISSN: 1433-0458
    Keywords: Schlüsselwörter ; Gehörgangexostosen ; Operative Komplikationen ; Operatives Vorgehen ; Key words ; Exostoses of external auditory canal ; Surgical management ; Surgical complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary We present a retrospective study on 22 operations of exostosis of the external auditory canal in 20 patients. 8 patients were passionated by water sports. The most frequent indication for surgery (13 operations) was recurrent external otitis or ceruminal obstruction. In 7 cases the need for a wider access to the middle ear indicated surgery. Surgery was usually performed as an outpatient procedure, maximum hospitalization was 3 days. The mean healing period was 6 (3–10) weeks. Mean follow up was 43 (3–110) months. There were no severe intraoperative complications such as facial paresis, lesions of the ossicles or of the inner ear. As intraoperative complications we found 2 perforations of the tympanic membrane, 2 expositions of the capsule of the mandibular joint, one of which was followed by chronic pain. As postoperative complications we found an early soft tissue stenosis of the external auditory canal and one late soft tissue stenosis which recurred after revision surgery. No recurrence of exostosis was seen. We describe an up to now unknown complication: the appearance of bilateral petrositis caused by staphylococcus epidermidis after bilateral surgery in an otherwise healthy patient. This study confirms that severe complications are rare, minor ones however relatively common. And that also minor complications may have a troublesome follow. Therefore and because of the potential of severe complications indication for surgery must be made cautiously and risks of the operation must not be underestimated.
    Notes: Zusammenfassung Wir präsentieren eine retrospektive Studie über die Operation von Gehörgangexostosen bei 20 Patienten. 8 Patienten waren intensive Wassersportler. Die häufigste Indikation (13 Operationen) war eine rezidivierende Otitis externa oder Zeruminalpropfen; 7mal war der die Erweiterung des Zugang für eine Mittelohroperation die Indikation. Die Operation wurde in der Regel ambulant durchgeführt, die maximale Hospitalisationszeit betrug 3 Tage. Die durchschnittliche Heilungszeit betrug im Mittel 6 (3–10) Wochen. Die Nachkontrollzeit betrug im Durchschnitt 43 (3–110) Monate. Es traten keine schweren intraoperativen Komplikationen auf wie Fazialisverletzung, Kettenverletzungen oder Innenohrverletzungen. Als intraoperative Komplikationen fanden sich 2 Trommelfellperforationen, 2 Freilegungen der Kapsel des Temporomandibulargelenks wovon eine von chronischen Schmerzen gefolgt war. Als Spätkomplikationen fanden wir eine frühe Narbenstenose des Gehörgangs und eine späte Narbenstenose, welche nach Revisionsoperation rezidivierte. Wir beobachteten kein Exostosenrezidiv. Wir beschreiben eine bisher nicht beschriebene Komplikation: das Auftreten einer beidseitigen Felsenbeinostitis durch Staphylococcus epidermidis nach beidseitiger Gehörgangexostosenoperation bei einem sonst vollständig gesunden Patienten. Die Studie bestätigt, dass schwere Komplikationen selten sind, leichtere jedoch in rund 10% der Fälle auftreten und dass auch diese unangenehme Folgen für den Patienten haben können. Deshalb kann die Operation nicht als banaler, leichter Eingriff betrachtet werden.
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  • 29
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    HNO 48 (2000), S. 129-134 
    ISSN: 1433-0458
    Keywords: Schlüsselwörter ; Ohrmuscheldefekte ; Ohrmuscheldysplasien ; Ohrmuschelrekonstruktion ; Key words ; Auricular defects ; Auricular dysplasia ; Auricular reconstruction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Surgical reconstruction of partial defects of the auricle remains an operative challenge. Operative techniques using cartilage frameworks constitute a well established method. According to the localisation and the extend of the defect there are well established procedures. Especially the inferior part of the auricle may cause difficulty due to it’s anatomy. In a retrospective study, various reconstruction techniques of partial conchal defects were examined in regard to their aesthetic results. A sytematic operative procedure due to the different techniques was developed. Large defects, extending more than 30% of the concha margin needed a high grade of stability which can be obtained by the use of autologous costal cartilage. According to the localisation of the defect and the available local tissue, the ret-ro-auricular site has to be reconstructed by the use of transposition flaps or split-thickness skin. For the reconstruction of the retroauricular site in the cranial auricular region a combined fascia-fan-flap showed the best results. The inferior auricular region can be reconstructed by the use of an infraauricular transposition flap offering also good opportunities for reconstruction of the lobulus. Second Degree Dysplasias are regarded as conchal defects which can be integrated into surgery.
    Notes: Zusammenfassung Zur Rekonstruktion größerer Defekte der äußeren Ohrmuschel haben sich trotz des größeren Aufwandes Mehrschrittechniken mit autologem Rippenknorpel bewährt. Für die unterschiedlichen Lokalisationen von solchen Defekten besteht jedoch keine einheitliche Vorgehensweise. Insbesondere die kaudale Ohrmuschelhälfte stellt aufgrund der anatomischen Beschaffenheit ein besonderes Problem dar. In einer retrospektiven Studie wurden verschiedene Rekonstruktionstechniken von Teildefekten der Ohrmuschel auf ihre plastischen Ergebnisse untersucht und eine Systematik je nach Lokalisation des Defekts erarbeitet. Bei größeren Defekten des Ohrmuschelrandes über 30% Substanzverlust haben sich wegen der größeren Stabilität Gerüstrekonstruktionen mit autologem Rippenknorpel bewährt. In Abhängigkeit von Lokalisation und Größe des Defekts stehen für die Rekonstruktion der Ohrmuschelrückseite verschiedene regionäre Lappen zur Verfügung: Defekte der kranialen Abschnitte können mit einem Faszienspalthautlappen gedeckt werden, bei kaudalen Defekten mit Lobulusrekonstruktion setzen wir einen infraaurikulären Transpositionslappen ein. Dysplasien II. Grades können bei intakten Reststrukturen, die in die Rekonstruktion mit integriert werden können, wie Ohrmuscheldefekte eingestuft und therapiert werden. Zusammenfassend haben sich für die Rekonstruktion großer peripherer Ohrmuscheldefekte Techniken mit Knorpelgerüsten aus autologer Rippe in Verbindung mit Lappenplastiken bewährt, die nach Lokalisation des Defektes modifiziert werden können.
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  • 30
    ISSN: 1433-0458
    Keywords: Schlüsselwörter ; Tonsillektomie ; Argon-Plasma-Koagulation (APC) ; Hochfrequenzchirurgie ; Key words ; Tonsillectomy ; Argon-Plasma-Coagulation ; High-frequency surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Background: The Argon-Plasma-Coagulation (APC) offers an innovative possibility for the tonsillectomy combined with a high-frequency technology. Aim of our study was to inves-tigate the differences between this high-frequency-technology and the traditional tonsillectomy. No reports exist in the use of the APC in the tonsillectomy. Methods: Argon-Plasma-Coagulation tonsillectomy (TE-APC) was compared with the traditional blunt dissection tonsillectomy (TE-trad) with hemostasis by compression and bipolar coagulation. 133 patients were stratified in two age groups in a clinical prospective randomised study. Results: Average surgical time and blood loss were markedly decreased in the TE-APC group (p〈0,01). There was no significant difference between the two techniques concerning postoperative pain, otalgia, and primary or secondary haemorrhage. In the TE-APC group more extensive fibrin layer appeared after surgery. In the TE-APC patients’ group, there was a slightly higher consume of analgetics in some postoperative days. Conclusions: The one-step dissection and coagulation procedure leads to an almost bloodfree woundground and to a reduction of operation-time. The self-limited and effective coagualative properties of the APC-method leads to a controlled penetration depth. The often associated extensive post operative pain and uncontrolled tissue- damage, known from electrical and lasersurgical techniques, was not found in TE-APC-patients-group.
    Notes: Zusammenfassung Hintergrund: Die Argon-Plasma-Koagulation (APC) bietet eine innovative Möglichkeit eine Tonsillektomie durchzuführen. Wie sich diese Hochfrequenzchirurgietechnik von konventionellen Tonsillektomieverfahren unterscheidet, soll anhand einer Studie untersucht werden. Patienten und Methode: In einer klinisch-prospektiven randomisierten Blindstudie mit 133 Patienten wurde die APC-Tonsillektomie (TE-APC) mit der stumpfen Dissektion, mit Kompression und bipolarer Koagulation zur Primärblutstillung (TE-konv), verglichen. Ergebnis: Der intraoperative Blutverlust und die durchschnittliche Operationsdauer waren bei der TE-APC signifikant erniedrigt (p〈0,01). Kein signifikanter Unterschied lies sich bei dem postoperativen Schmerz, der Otalgia und der aufgetretenen Nachblutungen zwischen den beiden Verfahren feststellen. Bei der TE-APC kam es zu vermehrter Fibrinbelagausbildung und an einzelnen postoperativen Tagen zu einem geringfügig erhöhten Analgetikaverbrauch. Schlußfolgerung: Bei der TE-APC erfolgten Dissektion und Koagulation in einem Schritt, dadurch wurde die Operationsdauer signifikant verkürzt. Durch den selbstlimitierten Effekt der Gewebepenetration der APC wird eine kontrollierte Eindringtiefe in das Gewebe erreicht. Die bei elektro- und laserchirurgischen Techniken üblicherweise festzustellende ausgeprägte postoperative Schmerzsymptomatik fand sich bei der APC-TE nicht.
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  • 31
    ISSN: 1433-0458
    Keywords: Schlüsselwörter ; Herpesviren ; Immunsuppression ; Resistenzentwicklung ; Key words ; Herpes virus ; Immunosuppression ; Treatment resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Herpes simplex viruses are known to be among the most common disease-causing microorganisms. Their prevalence can exceed 90% depending on the socioeconomic status of the population. Since the number of immunocompromised patients has increased because of the increased incidence in the acquired immunodeficiency syndrome and an increase in organ transplantation, herpes virus infection may have a greater clinical significance. While treatment of otherwise healthy individuals will not usually cause any clinical problems herpes infection in an immunocompromised patient can have severe consequences. Additionally, development of viral resistance can be observed that may require alternative drugs in treatment. We present a case history of a man with a B-cell chronic lymphocytic leukemia that was associated with a very unusual herpes simplex virus infection in the nasal vestibule. Possible causes for the development of resistance in herpes infections and the use of famciclovir and forscarnet as two therapeutic alternatives to aciclovir are discussed.
    Notes: Zusammenfassung Herpes-simplex-Viren gehören weltweit zu den häufigsten Krankheitserregern des Menschen mit einer in Abhängigkeit vom sozioökonomischen Status vorhandenen Prävalenz von über 90%. Das Bild der Herpesinfektion hat mit Zunahme der aus unterschiedlichsten Gründen (Organtransplantation, AIDS etc.) immunsupprimierten Patienten deutlich an Vielfalt gewonnen. Während die Therapie des immungesunden Patienten i. allg. keine Schwierigkeiten bereitet, kann eine Herpesinfektion bei immunsupprimierten Patienten zu einem ernsten eine Behandlung erforderlich machenden Krankheitsbild führen. Außerdem werden Resistenzentwicklungen beobachtet, die eine Therapie mit alternativen Medikamenten erforderlich machen. Wir stellen einen Patienten mit einer sehr ungewöhnlichen Manifestation einer Herpes-simplex-Infektion im Vestibulum nasi im Rahmen einer chronisch-lymphatischen B-Zell-Leukämie vor. Die möglichen Ursachen einer Resistenzentwicklung bei Herpesviren werden diskutiert und mit Famciclovir und Foscarnet zwei therapeutische Alternativen zum Aciclovir vorgestellt.
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  • 32
    ISSN: 1433-0458
    Keywords: Schlüsselwörter ; Neurootologie ; Kleinhirnbrückenwinkelsyndrom ; A.-vertebralis-Malformationen ; Zerebrale Durchblutungsstörungen ; Schwindel ; Key words ; Neuro-otologic diagnosis ; Vertigo ; Cerebellopontine angle pathology ; Nerve compression syndrome ; Vertebral artery malformations ; Cerebrovascular disorders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Introduction: The seventh and eighth cranial nerves course toward the internal auditory canal within the cerebellopontine angle. Lesions in this region are usually related to malfunctions of these cranial nerves. Although an acoustic schwannoma is one of the main etiologies of cerebellopontine angle pathology, various inflammatory processes and vascular anomalies even though rare must be considered. Patients/Methods: We describe 5 cases with vascular loops of the basilar or vertebral arteries as a possible cause for hearing loss, vertigo and pulsatile tinnitus. In two cases the vascular lesion was confirmed at surgery, in which a decompression procedure was performed. The work-up for each patient included an auditory test battery and electronystagmography. Imaging studies included MRI and angiography in two cases. Results/Conclusions: Our experiences show that while the cerebellopontine angle syndrome is mostly caused by benign tumors an abnormal vascular loop has to be considered in any differential diagnosis.
    Notes: Zusammenfassung Fragestellung: Im Kleinhirnbrückenwinkel (KHBW) vereinigen sich der N. vestibulocochlearis und facialis, bevor sie gemeinsam in den inneren Gehörgang eintreten. Pathologische Prozesse in dieser Region sind in der Regel mit Funktionseinbußen des VII. und/oder VIII. Hirnnerven verbunden. Das Akustikusneurinom gilt aus häufigste Ursache eines KHBW-Syndroms, das aber auch durch entzündliche oder vaskuläre Prozesse verursacht werden kann. Vaskuläre Malformationen stellen dabei eine Ausnahme dar. Patienten/Methoden: Es werden 5 klinische Fälle beschrieben, bei denen eine Schleifenbildung der A. basilaris, A. vertebralis oder A. cerebelli inferior anterior im KHBW-Bereich als Ursache von vestibulokochleären Störungen in Form von Drehschwindel, Hörminderung oder pulssynchronen Ohrgeräuschen in Frage kam. Bei 2 Patienten konnte diese Annahme durch eine operative Intervention bestätigt werden. Im Rahmen der Differentialdiagnostik wurden die Befunde der MRT des Cerebrums, der Angiographie, der BERA, der Tonaudiometrie und des ENG erhoben. Ergebnisse/Schlußfolgerungen: Trotz der häufigen tumorösen Ursachen können abnorme Gefäßschlingen kausal für ein KHBW-Syndrom sein und müssen differentialdiagnostisch in Erwägung gezogen werden.
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  • 33
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    Manuelle Medizin 38 (2000), S. 33-35 
    ISSN: 1433-0466
    Keywords: Schlüsselwörter ; Muscle energy technique nach Mitchel • Osteopathie • Störungen in der Beweglichkeit der Lendenwirbelsäulengelenke • Mitursache des Bandscheibenvorfalls ; Key words ; Muscle energy technique as described by Mitchel • Osteopathy • Impaired movability of the joints in the lumbar vertebral column • Concomitant cause of disk prolapse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Impaired movability of the vertebral joints causes one-sided compression and rotation of the disk. Causality can be safely assumed in view of the fact that disk prolapses occur on the side of the compression in more than 80 % of the cases. Since this impairment also reduces the foramen intervertebrale, space is even further reduced by a disk prolapse. Treatment of the impairment is recommended.
    Notes: Zusammenfassung Bewegungsstörungen der Wirbelgelenke führen zu einer einseitigen Kompression und Rotation der Bandscheibe. Da der Bandscheibenvorfall in mehr als 80 % der Fälle auf der Seite der Kompression auftritt, ist ein ursächlicher Zusammenhang anzunehmen. Da diese Störung auch das Foramen intervertebrale verkleinert, wird die Raumnot beim Bandscheibenvorfall noch größer. Die Behandlung der Störung ist zu empfehlen.
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  • 34
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    Manuelle Medizin 38 (2000), S. 42-48 
    ISSN: 1433-0466
    Keywords: Schlüsselwörter ; Neurale Steuerung • Denken in Funktionen • M. iliacus • Wirbelsäulenübergänge • Temporomandibular-Gelenk ; Key words ; Neural control • Thinking in functions • M. iliacus • Spinal transitions • Temporomandibular joint
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary With regard to clinical problems in the joints, the muscular factor is gaining increasingly importance. In musculosceletal medicine, the musculature itself is of greatest interest aside from the joints and non-contractile soft parts. In this 3-part article predominantly muscle-caused dysfunctional models are presented. It will follow Part 2: The M. psoas-model – The M. rectus femoris-model – The hip adductor model – The hip abductor model. And Part 3: The abdominal muscle model – The upper crossed syndrome model – An attempt at an overview of the spine. Although the function of the joints should be viewed within the framework of the entire motor system function, we should not let ourselves be limited by the knowledge of these models. They are only an aid to quick understanding of the current complex antalgic posture and provide interesting estimates for the prevention of recidivism.
    Notes: Zusammenfassung Bei den klinischen Funktionsstörungen an Gelenken tritt der muskuläre Faktor immer mehr in den Vordergrund. In der myoskeletalen Medizin steht außer Gelenken und nicht-kontraktilen Weichteilen vor allem die Muskulatur an erster Stelle des Interesses. In einem dreiteiligen Beitrag sollen hauptsächlich muskulär bedingte Dysfunktionsmodelle vorgestellt werden. In weiteren Heften folgen: Teil 2: Das M. psoas-Modell – Das M. rectus femoris-Modell – Das Hüftadduktoren-Modell – Das Hüftabduktoren-Modell. Und Teil 3: Das Bauchmuskel-Modell – Das Modell des oberen gekreuzten Syndroms – Ein Versuch zur Übersicht an der ganzen Wirbelsäule. Im Bewußtsein, daß die Gelenkfunktion nur im Rahmen der Funktion des ganzen Bewegungssystems zu betrachten sei, sollten wir uns durch die Kenntnisse dieser Modelle nicht limitieren lassen. Sie sind bloß eine Hilfe zum raschen Verständnis der aktuellen komplexen Schonhaltung und liefern interessante Ansätze für die Rezidivprophylaxe.
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  • 35
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    Manuelle Medizin 38 (2000), S. 3-16 
    ISSN: 1433-0466
    Keywords: Schlüsselwörter ; Halswirbelsäule • Chiropraktik • Dissektion • Manipulation • Trauma • Vertebrobasiläres Stromgebiet ; Key words ; Cervical • Chiropractic • Dissection • Manipulation • Trauma • Vertebrobasilar
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Study design: Potential precipitating events and risk factors for vertebrobasilar artery dissection were reviewed in an analysis of the English language literature published before 1993. Objectives: To assess the literature pertaining to precipitating neck movements and risk factors for vertebrobasilar artery dissection in an attempt to determine whether the incidence of these complications can be minimized. Summary of background data: Vertebrobasilar artery dissection and occlusion leading to brain stem and cerebellar ischemia and infarction are rare but often devastating complications of cervical manipulation and neck trauma. Although various investigators have suggested potential risk factors and precipitating events, the basis for these suggestions remains unclear. Methods: A detailed search of the literature using three computerized bibliographic databases was performed to identify English language articles from 1966 to 1993. Literature before 1966 was identified through a hand search of Index Medicus. References of articles obtained by database search were reviewed to identify additional relevant articles. Data presented in all articles meeting the inclusion criteria were summarized. Results: The 367 case reports included in this study describe 160 cases of spontaneous onset, 115 cases of onset after spinal manipulation, 58 cases associated with trivial trauma, and 37 cases caused by major trauma (3 cases were classified in two categories). The nature of the precipitating trauma, neck movement, or type of manipulation that was performed was poorly defined in the literature, and it was not possible to identify a specific neck movement or trauma that would be considered the offending activity in the majority of cases. There were 208 (57 %) men and 158 (43 %) women (gender data not reported in one case) with an average age of 39.3 ± 12.9 years. There was an overall prevalence of 13.4 % hypertension, 6.5 % migraines, 18 % use of oral contraception (percent of female patients), and 4.9 % smoking. In only isolated cases was specific vascular disease such as fibromuscular hyperplasia noted. Conclusions: The literature does not assist in the identification of the offending mechanical trauma, neck movement, or type of manipulation precipitating vertebrobasilar artery dissection or the identification of the patient at risk. Thus, given the current status of the literature, it is impossible to advise patients or physicians about how to avoid vertebrobasilar artery dissection when considering cervical manipulation or about specific sports or exercises that result in neck movement or trauma.
    Notes: Studiendesign: Potentielle vorangehende Bewegungen und Risikofaktoren einer vertebrobasilären Dissektion wurden in einer Analyse der englischsprachigen Literatur vor 1993 beurteilt. Studienziel: Ziel der vorliegenden Untersuchung war die Beurteilung der Literatur über vorangehende Halsbewegungen und Riskofaktoren einer vertebrobasilären Dissektion hinsichtlich einer Reduktion der Inzidenz dieser Komplikation. Hintergrundinformationen: Dissektionen und Verschlüsse im vertebrobasilären System, die zu einer Ischämie bzw. Infarzierung des Hirnstamms und des Kleinhirns führen, sind eine seltene, aber verheerende Komplikation einer zervikalen Manipulation bzw. eines zervikalen Traumas. Obwohl verschiedene Arbeitsgruppen potentielle Riskofaktoren und vorangehende Ereignisse erarbeitet haben, sind die Grundlagen dieser Faktoren weiterhin unklar. Methoden: Eine detaillierte Literatursuche wurde unter Einsatz von drei bibliographischen Datenbanken computergestützt durchgeführt, um englischsprachige Artikel von 1966 bis 1993 zu finden. Die Literatur vor 1966 wurde mittels des Index Medicus durchsucht. Die Literaturangaben der mittels der Datenbanken gefundenen Artikel wurden untersucht, um zusätzliche relevante Artikel zu finden. Die Daten der Artikel, die die Einschlußkriterien erfüllten, wurden zusammengefaßt. Ergebnisse: Die 367 Fallberichte, die in diese Studie eingeschlossen werden konnten, beschrieben 160 spontane Dissektionen bzw. Okklusionen, 115 Fälle nach einer Wirbelsäulenmanipulation, 58 Fälle nach einem Bagatelltrauma und 37 Fälle nach einem massiven Trauma. Drei Fälle wurden jeweils zwei Kategorien zugeordnet. Die Art des vorangehenden Traumas, der Halsbewegungen oder die angewendete Manipulationsform waren in der Literatur nur schlecht beschrieben. Aus den vorliegenden Daten war es nicht möglich, eine bestimmte Halsbewegung oder ein spezifisches Trauma als auslösende Ursache für die Mehrheit der Fälle zu identifizieren. Die in der Literatur beschriebenen Fälle bestanden aus 208 Männern (57 %) und 158 Frauen (43 %) mit einem mittleren Alter von 39,3 ± 12,9 Jahren. Eine arterielle Hypertonie war bei 13,4 % der Patienten vorhanden, Migräne bei 6,5 % der Patienten. 4,9 % der Patienten rauchten und 18 % der weibliche Patienten nahmen orale Kontrazeptiva ein. Nur in Einzelfällen war eine spezifische Gefäßerkrankung (z. B. Fibromuskuläre Hyperplasie) bekannt. Schlußfolgerungen: Die Literatur über Dissektionen im vertebrobasilären Stromgebiet ermöglicht keine Identifikation von Risikopatienten und keine eindeutige Klärung bezüglich des auslösenden mechanischen Traumas, vorangehender Halsbewegungen oder der Manipulationsform. Nach dem aktuellen Stand der Literatur ist es daher unmöglich, Patienten oder Ärzten Richtlinien zur Vermeidung einer Dissektion im vertebrobasilären Stromgebiet bei zervikaler Manipulation, spezifischen Sportarten, Übungen mit Halsbewegungen oder einem Trauma zu geben.
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  • 36
    ISSN: 1433-0474
    Keywords: Schlüsselwörter ; Gastroenteritis ; Rotavirus ; Salmonellen ; Impfstoff ; Key words ; Gastroenteritis ; Rotavirus ; Salmonella ; Vaccine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Objective: A pertussis vaccine efficacy trial included a prospective follow up of all hospitalizations involved. This allowed us to calculate the rates of hospitalization due to acute gastroenteritis in a large cohort of infants and children in Germany. Methods: 10271 healthy children were enrolled at the age of 2–4 months and followed up for a mean of 2.5 years. All hospitalizations during follow-up of the study were registered and letters of discharge from hospital in children with gastroenteritis were evaluated for the present analysis. Results: A total of 179 episodes of hospitalization due to a gastroenteritis were reported in 173 children (total observation years 25284). The mean calculated incidence was 7.1/1000 observation years, with a maximum of 11.2/1000 years in 7–12 month old children. Rotavirus and Salmonella spp. were the most frequently identified agents. Rotavirus infections were most prevalent during the cold season and the maximum incidence was between 7 and 12 months of age. Characteristic symptoms of rotavirus infections were diarrhea (90%), vomiting (85%) and signs of dehydration (58%). In contrast most Salmonella infections occurred between July and September with a peak between 19 and 24 months of age. Salmonella infections were characterized by enteritis (92%), high fever (56% 〉39°C) and significantly increased values for the c-reactive protein (68%). In this study rotavirus and Salmonella infections leading to hospitalization were associated with febrile seizures in 5% and 12% of cases, respectively. Conclusion: Gastroenteritis frequently leads to hospitalization in previously healthy infants and young children. Rotavirus and Salmonella spp. are the predominant causative agents.
    Notes: Zusammenfassung Fragestellung: Eine prospektive Pertussisimpfstudie mit engmaschiger Überwachung des gesamten Kollektivs erlaubte uns, erstmals das Risiko von Säuglingen und Kleinkindern, wegen einer Gastroenteritis hospitalisiert zu werden, in einer umfangreichen Kohorte zu bestimmen. Methode: Die Kohorte aus 10.271 gesunden Kindern wurde, beginnend im Alter von 2–4 Monaten, über einen mittleren Zeitraum von 2,5 Jahren beobachtet (Gesamtbeobachtungsdauer 25.284 Jahre). Dabei wurden u.a. alle Krankenhausbehandlungen erfaßt. Ergebnisse: Bei 173 Kindern (1,7%) registrierten wir insgesamt 179 Gastroenteritisepisoden, die stationär behandelt wurden. Dies entspricht einer mittleren Inzidenz von 7,1/1000 Beobachtungsjahren mit einem Maximum von 11,2/1000 im 7. bis 12. Lebensmonat und einer Abnahme mit steigendem Lebensalter. Die beiden am häufigsten nachgewiesenen Erreger waren Rotaviren (34%) und Salmonellen (20%). Rotavirus-Infektionen traten gehäuft in der kalten Jahreszeit auf, die höchste Inzidenz lag bei Säuglingen im 7. bis 12. Lebensmonat. Die Symptomatik war geprägt von Enteritis (90%), Erbrechen (85%) und Zeichen der Dehydratation (58%). Demgegenüber trat der Großteil aller Salmonellosen in den Monaten Juli-September auf, mit einem Altersgipfel im 19. bis 24. Lebensmonat, charakterisiert durch Enteritis (92%), hohes Fieber (56%, 〉39°C) und erhöhte Werte des C-reaktiven Proteins (68%). Bei 5% bzw. 12% der wegen Rotavirus- bzw. Salmonelleninfektionen hospitalisierten Kinder war ein Fieberkrampf Anlaß für die Klinikeinweisung. Schlußfolgerung: Gastroenteritiden führen bei primär gesunden Kindern in den ersten Lebensjahren häufig zu Krankenhausbehandlungen. Rotaviren und Salmonellen sind dabei die prädominierenden Erreger.
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  • 37
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    Monatsschrift Kinderheilkunde 148 (2000), S. 246-250 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter ; Barth-Syndrom ; X-gebundene Kardiomyopathie ; G4.5 ; Key words ; Barth syndrome ; X-linked cardiomyopathy ; G4.5
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Barth syndrome is a rare X-linked disorder characterized by dilated cardiomyopathy, myopathy and neutropenia. We describe a family with two affected males. One of them died during infancy from cardiomyopathy. The other, now adult, is less severe affected. The diagnosis was confirmed by the detection of a missense mutation in the responsible gene G4.5. In the case of two further boys, who died during the neonatal period, the same diagnosis may be said to apply retrospectively, based on available results. Discussion: Although the Barth syndrome gene was cloned in 1996, the function of its protein product is not yet known. Because of the variability of the clinical course even in one and the same familiy genetic counceling and considerations about prognosis and treatment are difficult.
    Notes: Zusammenfassung Das Barth-Syndrom ist eine seltene, X-chromosomal-rezessiv vererbte Erkrankung mit den Leitsymptomen dilatative Kardiomyopathie, Myopathie, rezidivierende Neutropenie. Es wird eine Familie beschrieben, in der 2 männliche Familienmitglieder am Barth-Syndrom erkrankt sind. Einer der Patienten verstarb im Säuglingsalter infolge der Kardiomyopathie, der andere zeigt eine weniger schwere Symptomatik und ist mittlerweile erwachsen. Bei beiden wurde die Diagnose durch den Nachweis einer Mutation im krankheitsverursachenden Gen G4.5 gesichert. Bei 2 weiteren, im Neugeborenenalter verstorbenen Jungen ist die gleiche Diagnose aufgrund der vorliegenden Befunde retrospektiv anzunehmen. Diskussion: Obwohl das krankheitsverursachende Gen 1996 kloniert wurde, ist die Funktion des Genprodukts noch weitgehend unbekannt. Das Barth-Syndrom zeigt auch innerhalb einer Familie eine große klinische Variabilität, was die genetische Beratung und Aussagen bezüglich der Prognose und Behandlung erschwert.
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  • 38
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S049 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; LKG-Spalten ; Prächirurgie ; Chirurgie ; Key words ; Cleft lip and palate ; Presurgery ; Surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In this paper an attempt is made to survey the surgical treatment of cleft lip and palate regarding all classifications and all parts of the cleft. The most important developments up to 30 years ago to have been summarized in Millard’s three-volume “Cleft Craft”. Therefore, the author tries to analyze the present state-of-the-art cleft surgery. This part is certainly of a subjective nature due to the high rate of complexity in cleft malformations.
    Notes: Zusammenfassung Die Arbeit versucht, in knapper Form einen Überblick über die chirurgische Behandlung der Lippen-Kiefer-Gaumen-Spalten in allen Klassifikationsformen und allen Spaltteilbereichen zu geben. Die notgedrungen sehr dichte Aussage legt Wert auf die wichtigen Entwicklungen der letzten 30 Jahre, da bis zu diesem Zeitraum von Millard in seinen 3 Bänden “cleft-craft” alles Wesentliche dargestellt wurde. Außerdem versucht der Autor, sicher in einem subjektiven Sinn, was sich aus der hohen Komplexizität der Fehlbildung erklären lässt, ein “State-of-the-art”-Resümee zu ziehen.
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  • 39
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S061 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Lippen-Kiefer-Gaumen-Spalte ; Oberlippe ; Nase ; Gaumen ; Oberkiefer ; Zahnersatz ; Sekundäroperation ; Key words ; Cleft lip and palate ; Upper lip ; Nose ; Palate ; Prosthodontics ; Secondary operation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In spite of all interdisciplinary efforts and functionally oriented operation procedures, there are still unsatisfying results in the treatment of cleft lip and palate (CLP) patients. Secondary corrections involve upper lip, nose, and palate (fissures). In some cases, it is necessary to reposition the complete maxilla. Finally, there are indications for speech improving measures and total septorhinoplasties. Dental treatment can be brought to a positive end by means of implant-borne prosthodontic work. In this paper, some of the anatomical and physiologic conditions and surgical procedures are described, which may serve as a basis for a functionally orientated treatment of sequelae after primary CLP care.
    Notes: Zusammenfassung Trotz interdisziplinärer Bemühungen und anatomisch sowie funktionell ausgerichteter Behandlungskonzepte wird es auch heute noch im Lauf der Therapie eines Patienten mit einer Lippen-Kiefer-Gaumen-Spalte zu unbefriedigenden Ergebnissen kommen. Sekundärkorrekturen betreffen Oberlippe und Nase, den Gaumen (Restlöcher) sowie in manchen Fällen den gesamten Oberkiefer, der in seiner Lage zu korrigieren ist. Darüber hinaus ergeben sich Indikationen zu sprachverbessernden Operationen und totalen Septorhinoplastiken. Vielfach findet die dentale Rehabilitation im implantatgetragenen Zahnersatz ihren Abschluss. Im vorliegenden Beitrag werden die anatomischen, physiologischen Grundlagen sowie Wege zur Behandlung der oben angeführten Probleme angegeben.
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  • 40
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S091 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Resorbierbare Polymere ; Osteosynthese ; Polylaktid ; Polyglykolid ; Key words ; Resorbent polymers ; Osteosynthesis ; Polylactid ; Polyglycolid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The use of resorbable osteosynthesis materials spares the need for metallic implants and second operative procedures, which are often necessary, to remove the material. Appropriate substances are polymers and copolymers of glycolic and lactic acid. In a literature review, material characteristics, their degradation, and applications in animal experiments and clinical studies are presented. Particularly, the possible reasons of foreign body reactions occurring during the degradation period and material-related difficulties in practical use are discussed. It is evident that the use of low crystalline or amorphous polymers with in vivo long-lasting strength offers a secure and uncomplicated healing of fractures. Therefore, in future these substances will be an interesting alternative to common metallic osteosynthesis materials.
    Notes: Zusammenfassung Bei der Anwendung resorbierbarer Osteosynthesematerialien entfällt der bei Metallimplantaten oft notwendige operative Zweiteingriff zur Materialentfernung, als geeignete Werkstoffe gelten besonders die Polymere und Kopolymere der Glykol- und Milchsäuren. In einer Literaturübersicht werden die Materialeigenschaften der möglichen Polymervariationen, deren Degradation und schließlich bisherige Anwendungen in tierexperimentellen und klinischen Untersuchungen dargestellt. Insbesondere werden die möglichen Ursachen auftretender Fremdkörperreaktionen während des Polymerabbaus sowie materialbedingte Schwierigkeiten bei der Anwendung diskutiert. Es wird deutlich, dass die Nutzung niedrigkristalliner bzw. amorpher Polymere mit in vivo lang anhaltenden Festigkeitseigenschaften sichere und komplikationslose Frakturheilungen ermöglicht und zukünftig eine interessante Alternative zu herkömmlichen metallischen Osteosynthesematerialien darstellen wird.
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  • 41
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S103 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Unterkieferfraktur ; Funktionsstabile Kompressionsosteosynthese ; Monokortikale Miniplattenosteosynthese ; Klassifikation ; Differenzialindikation ; Key words ; Mandibular fracture ; Functionally stable osteosynthesis ; Monocortical osteosynthesis ; Classification ; Differential indication
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Functionally stable fixation via bicortical osteosynthesis on the one hand, and monocortical non-compression osteosynthesis on the other, are still two competing concepts in treating mandibular fractures. A survey of the literature shows that complicated fractures with severe dislocation of the fragments have the lowest rate of complications after functionally stable fixation, whereas non-complicated fractures without significant dislocation in the distal part of the mandible can be treated successfully via monocortical non-compressive osteosynthesis as well. It seems that pre- and intraoperative parameters can be helpful in describing the character of a mandibular fracture in order to give a differential indication between the two therapeutical concepts. The consideration of only seven parameters, as the mandibular fracture score does, provides many combinations of describing a fracture, so that former studies with their small number of patients make only a rather inaccurate differential indication possible. As long as there is no prospective multi-center study giving a guideline to classify mandibular fractures, the rigid internal fixation via functionally stable osteosynthesis should be preferred in all cases which are not “clear, easy to handle” fractures.
    Notes: Zusammenfassung In der Versorgung von Unterkieferfrakturen konkurrieren bis heute die monokortikale und die funktionsstabile Kompressionsosteosynthese miteinander. Eine Übersicht über die bestehende Litera-tur zeigt, dass komplizierte und schwer reponierbare Unterkieferfrakturen nach einer Kompressionsosteosynthese eine deutlich geringere Komplikationsrate aufweisen, während einfache und nur gering dislozierte Frakturen im distalen Anteil der Mandibula auch mittels monokortikaler Miniplattenosteosynthese erfolgreich versorgt werden können. Wegweisend für eine geeignete Differenzialindikation zwischen beiden Therapiekonzepten scheint die Erhebung prä- und intraoperativer Parameter, die den Charakter einer Unterkieferfraktur beschreiben und additiv einen Rangwert zur Klassifikation eines Traumas bilden, zu sein. Doch bei nur 7 Einzelparametern – wie im mandibular fracture score– ergeben sich bereits so zahlreiche Kombinationen zur Beschreibung eines Unterkiefertraumas, dass sämtliche bisher angelegten Studien mit ihren geringen Fallzahlen allenfalls eine grobe Differenzialindikation ermöglichen können. Solange keine prospektive Multizenterstudie vorliegt, die eine Entscheidungshilfe in der Wahl des Osteosyntheseverfahrens geben könnte, sollte im fließenden Bereich zwischen „einfacher“ und „schwieriger“ Fraktur der funktionsstabilen Kompressionsosteosynthese mit ihrer deutlich geringeren Inzidenz postoperativer Komplikationen der Vorzug gegeben werden.
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  • 42
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S384 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Knochenersatzmaterialien ; Knochenrekonstruktion ; Lyoknorpel ; Lyoknochen ; Bone morphogenetic protein (BMP) ; Key words ; Bone reconstruction ; Lyophilized bone ; Lyophilized cartilage ; Bone substitute ; Bone morphogenetic protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The application of autogenous bone transplants is still the gold standard for all reconstructive surgery. The wish of surgeons for alternatives to autogenous bone grafts is reflected in the development of a variety of bone graft substitutes of synthetic or biological origin. The following review article is meant to provide the reader with a critical overview of all the alternative materials. In addition, we want to point to the tremendous progress made on this subject, made possible by the joint effort of surgeons and basic researchers. The results of this collaboration show that in the near future a new gold standard for successful reconstructive surgery will emerge and replace the use of autogenous bone transplants.
    Notes: Zusammenfassung Der Gebrauch von autologem Knochen im Kiefer- und Gesichtsbereich ist heute immer noch der Goldstandard bei allen rekonstruktiven Maßnahmen. Der Wunsch der Chirurgen, körperfremde Materialien für diese Zwecke zu verwenden, spiegelt sich in der Entwicklung vielfältigster Surrogate wider. Die folgenden Ausführungen sollen dem Leser einen kritischen Überblick über die verschiedenen Materialien verschaffen. Darüber hinaus sind die Fortschritte auf diesem Gebiet der Beweis dafür, dass die gemeinsamen Bemühungen von Chirurgen und Grundlagenforschern auf dem besten Weg sind, erfolgreiche Knochenrekonstruktionen mittels körperfremder Materialien zu ermöglichen.
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  • 43
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S375 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Zervikofaziale Weichteilprozesse ; Sonographie ; Halslymphknotendiagnostik ; Key words ; Head and neck area soft tissue masses ; Sonography ; Neck area lymph node diagnostics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Ultrasonography has gained acceptance in maxillofacial surgery as a first-choice diagnostic tool in soft tissue masses of the head and neck. To date, A-mode sonography of the maxillary sinus is only performed in children and pregnant women. However, B-mode sonography is primarily performed in the assessment of all cervical lymph nodes because of its superior sensitivity in comparison to CT and MR, as well as in diseases of the salivary glands, solid tumors, and monitoring of distraction osteogenesis of the mandible. With color-coded ultrasonography as a combination of B-mode and blood flow information, vessels of the head and neck area or of planned flaps can be examined in a noninvasive manner. This is especially important in secondary microsurgical reconstructions. Moreover, the blood flow in any soft tissue masses can be evaluated. In spite of all texture and image analysis techniques, positive and negative lymph nodes cannot be differentiated in a safe manner. Three-dimensional sonography, e. g., panoramic pictures, and contrast enhancement are new technologies that will improve diagnostic accuracy of head and neck ultrasonography.
    Notes: Zusammenfassung Die Sonographie stellt heute in der Mund-, Kiefer- und Gesichtschirurgie bei allen zervikofazialen Weichteilprozessen das bildgebende Verfahren der ersten Wahl dar. Während die A-Scan-Sonographie der Kieferhöhle nur noch bei Kindern und Schwangeren indiziert ist, hat die hochauflösende B-Scan-Sonographie derzeit die größte Anwendungsbreite. Sie gelangt im Rahmen des Tumorstagings wegen ihrer im Vergleich zur CT und MRT höheren Sensitivität v. a. zur Halslymphknotendiagnostik zur Anwendung. Weitere Indikationen sind Speicheldrüsenerkrankungen, Weichteiltumoren und das Monitoring der Kallusdistraktion. Die Farbduplexsonographie ermöglicht durch ihre Kombination von B-Scan-Sonographie und farbkodierter Blutflussdarstellung auf nichtinvasivem Weg nicht nur eine Gefäßdiagnostik im Rahmen der plastisch-rekonstruktiven Mikrochirurgie, sondern auch eine simultane Beurteilung der Vaskularisation von Lymphknoten und anderen Weichteiltumoren. Trotz rechnergestützter Verfahren der Signalanalyse ist jedoch eine Artdiagnostik von Lymphknoten und Tumoren nicht ausreichend zuverlässig möglich. Durch die 3D-Sonographie, beispielsweise die Panoramabildfunktion, und Kontrastverstärkung sind weitere Fortschritte in der Kopf-Hals-Sonographie zu erwarten.
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  • 44
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Visualisierung patientenbezogener Informationen ; Wissensaustausch ; Datenübertragung ; Telekonsultation ; Bildfusionierungstechnologie ; Key words ; Visualization of patient-related information ; Exchange of knowledge ; Data transfer ; Teleconsulting ; Image fusion technology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The exponential increase of medical information creates a need for new methods in the visualization of medical imaging modalities for diagnosis and therapy. In this sense, visualization includes the display of medical image data and image-guided stereotaxic navigation as well as the advice of an expert. The Artma Virtual Patient® System enables a remote expert to observe the surgical procedure via the Internet and interactively modify the interoperative visualization from the remote location. The expert in the remote location receives the planning data almost in real time over TCP/IP from a stereotaxic videoserver. In addition to live video streaming, stereotaxic navigation data are sent over the network as rigid body coordinates. The expert modifies the surgical simulation on the remote computer and the modified operating plan is sent back to the operating site. By teleconsulting, the composite images and overlapping graphics –instruments, target structures, landmarks, contour – can be seen in affiliated clinics with the possibility of interactive graphical assistance. With this image fusion technology the knowledge of a remote expert is included in virtual data structures and visualized by the overlay with live video data (augmented reality) in real time during surgery.
    Notes: Zusammenfassung Die exponentielle Zunahme des Informationsflusses in der Medizin verlangt nach neuen Methoden zur Visualisierung patientenbezogener Informationen und Verbreitung von medizinischem Wissen in Diagnose und Therapie. Visualisierung in diesem Sinn beinhaltet die Darstellung medizinischer Bilddaten und bildgeführter stereotaktischer Navigation genauso wie den Rat eines Experten. Das Artma-Virtual-Patient-System ermöglicht einem sich in räumlicher Entfernung befindenden Experten Operationen via Internet mitzuverfolgen und mit Hilfe eines Remote-Computers die interoperative Visualisierung interaktiv zu modifizieren. Der Experte erhält die Planungsdaten nahezu in Echtzeit mittels TCP/IP von einem stereotaktischen Operationsvideoserver. Zusätzlich werden stereotaktische Navigationsdaten als Rigid-body-Koordinaten über das Netzwerk übertragen. Der Experte modifiziert die chirurgische Simulation am Remote-Computer, und der modifizierte Operationsplan wird in den Operationssaal zurückgeschickt. Durch die Telekonsultation können verschiedenartige Bilddaten und überlagerte Graphiken – Instrumente, Zielstrukturen, Landmarken, Konturen – in durch Internet verbundenen Kliniken dargestellt werden, wodurch interaktiv graphische Hilfe angeboten werden kann. Mit Hilfe dieser Bildfusionierungstechnologie werden das nicht vor Ort verfügbare Expertenwissen in virtuelle Datenstrukturen eingebunden und durch Überlagerung mit Livevideo Daten in Echtzeit während der Operation visualisiert.
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  • 45
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S392 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Kiefergelenkerkrankungen ; Konservative Therapie ; Operative Therapie ; Minimalinvasive Verfahren ; Key words ; Condyle of mandible disorders ; Conservative treatment ; Surgical treatment ; Minimally invasive methods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary For the most frequent TMJ derangements, highly efficient nonsurgical treatment is preferable. Within this concept, the interdependence between the TMJ and the jaw musculature is increasingly focussed. Surgical therapy is only an option under defined circumstances in cases resistant to nonsurgical treatment, or if nonsurgical treatment is meaningless from the beginning. Within surgical concepts, arthroscopy is becoming increasingly important. A close interdisciplinary cooperation between the dentist and oral and maxillofacial surgeon seems to improve the potential outcome in these cases.
    Notes: Zusammenfassung Für die häufigsten Kiefergelenkerkrankungen stehen heute konservative Behandlungsverfahren mit hoher Erfolgswahrscheinlichkeit zur Verfügung. Zunehmend zielt diese Therapie auf die Zusammenhänge zwischen der Funktion der Kiefergelenke und der Kaumuskulatur ab. Chirurgische Therapieverfahren kommen in Frage, wenn die konservative Therapie nicht zum Erfolg führt oder von vornherein nicht sinnvoll ist. Dabei wird die offene Chirurgie zunehmend von minimalinvasiven Verfahren, z. B. der Arthroskopie, verdrängt. Eine enge Zusammenarbeit zwischen dem funktionsanalytisch und therapeutisch tätigen Zahnarzt und den Mund-Kiefer-Gesichts-Chirurgen in der Diagnostik und Therapie verbessert die Prognose bei solchen Erkrankungen.
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  • 46
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S003 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Europa ; Selbstständiges medizinisches Fachgebiet ; Harmonisierung ; Mund-Kiefer-Gesichts-Chirurgie ; Key words ; Europe ; Independent medical speciality ; Harmonisation ; Oromaxillofacial surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The recognition of a medical discipline on a European level as an independent specialty depends on its registration in the medical directives of the European Union. With supreme effort, the oral and maxillofacial surgeons of the EU reached this goal in 1989. The UEMS – Section of Stomatology and Oromaxillofacial Surgery – became the forum for discussion of the relevant problems with representatives of the member states and officials of the European Commission. Thanks to its activities, oral and maxillofacial surgery is now recognized as an independent specialty with about 3800 specialists in 11 European countries.
    Notes: Zusammenfassung Die Anerkennung einer medizinischen Disziplin als selbstständiges Fachgebiet auf europäischer Ebene hängt von ihrer Aufnahme in die medizinischen Richtlinien der Europäischen Union ab. Die Mund-Kiefer-Gesichtschirurgen in der EU haben mit beharrlichem Einsatz und unter großen Anstrengungen dieses Ziel 1989 erreicht. Forum für die Diskussion der sachbezogenen Probleme unter den Vertretern der Mitgliedsstaaten und mit den Dienststellen der europäischen Kommission war die UEMS-Sektion für Stomatologie und Mund-Kiefer-Gesichtschirurgie. Dank ihres Wirkens ist die MKG-Chirurgie heute, am Ende des 20. Jahrhunderts, in 11 europäischen Ländern mit etwa 3800 Fachärzten als selbstständiges Fachgebiet anerkannt.
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  • 47
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S401 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Speicheldrüsen ; Diagnostik ; Entzündung ; Tumoren ; Lobektomie ; Key words ; Salivary gland ; Diagnostic ; Inflammation ; Tumors ; Lobectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary After more than 25 years of activity in the field of salivary gland surgery, especially parotid gland surgery, the following statements can be made. ¶1. Salivary gland diseases are extremely variable and their treatment requires vast clinical experience. ¶2. The judgement of salivary gland diseases requires highly competent pathologic assistance and a specialized laboratory in this respect. In the field of salivary gland pathology – like in many other specialized subdivisions in pathology – the need of a second opinion in order to increase the reliability of the original diagnosis has to be claimed once more. 3. A certain change has taken place in the diagnostic means. Modern techniques of visualization show a shift toward noninvasive sonography, but also toward computed tomography with or without contrast agents, and there is a steadily increasing shift toward magnetic resonance tomography as well. 4. The literature about salivary gland diseases and their therapy can no longer be overlooked and is unfortunately characterized by very different aspects of judgement, which in many cases hardly allow a comparative discussion of certain clinical and therapeutic questions. ¶5. Parotid gland surgery requires a clear concept concerning the different diseases, especially of the different oncologic entities. Surgical preparation of the facial nerve has to be mastered equally from the central and the peripheral course of the nerve.
    Notes: Zusammenfassung Nach einer über 26-jährigen Tätigkeit in der Speicheldrüsen- und insbesondere in der Parotischirurgie sind folgende Aussagen zu erbringen: 1. Die Speicheldrüsenerkrankungen sind extrem variabel und verlangen in der Behandlung einen großen klinischen Erfahrungswert. 2. Die Bewertung der Speicheldrüsenerkrankungen setzt eine hochkompetente pathologische Sekundanz und ein einschlägiges Labor voraus. Die Forderungen nach einer Referenzpathologie müssen wie für viele Organe oder Organsysteme auch für die Speicheldrüsenerkrankungen erneut und uneingeschränkt erhoben werden. 3. Ein gewisser Wandel ist in den diagnostischen Maßnahmen eingetreten. Die moderne Bildgebung zeigt eine wesentliche Verschiebung zugunsten der nichtinvasiven Sonographie und auch dem Computertomogramm mit und ohne Kontrastdarstellung sowie in zunehmendem Maß auch der Kernspintomographie. 4. Die Literatur zu den Erkrankungen der Speicheldrüsen und ihrer Therapie ist kaum noch zu überblicken und bedauerlicherweise von ganz unterschiedlichen Bewertungsaspekten charakterisiert. Sie lässt in vielen Fällen vergleichende Diskussionen über bestimmte klinische und therapeutische Fragestellungen nur schwer zu. 5. Die Parotischirurgie verlangt ein klares Konzept hinsichtlich der verschiedenen Erkrankungen insbesondere der unterschiedlichen Tumorentitäten. Die Darstellung und Präparation des N. facialis von peripher und zentral müssen gleichermaßen beherrscht werden.
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  • 48
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S026 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Mund-Kiefer-Gesichts-Chirurgie-Facharzt ; Ausbildung ; Weiterbildung ; Fortbildung ; Berufsbild ; Key words ; Oromaxillofacial surgical specialty ; Training ; Postgraduate training ; Further training
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary To qualify for further specialist training as a maxillofacial surgeon, a licence to practice in general medicine as well as a licence to practice in dentistry must be obtained beforehand. In addition to the 4-year course to qualify, maxillofacial surgeons can gain the additional qualification in the field of “plastic surgery” in a further course lasting 3 years. By the end of 1998, there were 698 maxillofacial surgeons in private practices in Germany in comparison to 322 hospital-employed maxillofacial surgeons. Of the work done by maxillofacial surgeons (in private practices), 28% is in contracted hospitals; this percentage is relatively high in comparison to other disciplines in which private specialists use contracted hospitals. It is impossible these days for an individual specialist to completely cover all areas of maxillofacial surgery. In our field, joint practices with an internal specialization will increase the spectrum and quality of treatment in the future and will counteract competition from hospital-employed specialists now that day-case surgery has been introduced in these hospitals. Further training by the individual will remain an indispensable necessity as well as personal involvement by every maxillofacial surgeon in the postgraduate medical training of doctors and dentists. This can only be achieved if the economic situation of specialists is maintained in health-politics.
    Notes: Zusammenfassung Die Weiterbildung zum Facharzt für Mund-Kiefer-Gesichts-Chirurgie erfordert neben der ärztlichen auch die zahnärztliche Approbation. Ergänzend zu der 4-jährigen Weiterbildung im Gebiet können MKG-Chirurgen während einer zusätzlichen 3-jährigen Weiterbildung die Zusatzbezeichnung im Bereich „Plastische Operationen“ erwerben. Bis zum Jahresende 1998 gab es in Deutschland 698 niedergelassene gegenüber 322 klinisch tätigen Mund-Kiefer-Gesichts-Chirurgen. Der prozentuale Anteil an der belegärztlichen Tätigkeit der Niedergelassenen ist mit 28% im Vergleich zu anderen Fachgebieten relativ hoch. Nicht jeder Arbeitsbereich der Mund-Kiefer-Gesichts-Chirurgie kann heute noch vom einzelnen Niedergelassenen umfassend beherrscht werden. Gemeinschaftspraxen bieten für die Zukunft unseres Fachs eine qualitativ hochwertige Bereicherung des Behandlungsspektrums über eine interne Spezialisierung, die ein Gegengewicht zur fachlichen Konkurrenz der Krankenhäuser, nach Öffnung für die ambulante Behandlung, darstellen wird. Eine unabdingbare Notwendigkeit bleiben die eigene Fortbildung und auch das persönliche Engagement jedes niedergelassenen Mund-Kiefer-Gesichts-Chirurgen für die Weiter- und Fortbildung der Zahnärzte und Ärzte. Das hat nur Bestand, wenn die wirtschaftliche Basis der Fachärzte von der Gesundheitspolitik her erhalten bleibt.
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  • 49
    ISSN: 1432-0843
    Keywords: Key words Taxanes ; Cervical cancer ; Apoptosis ; Tubulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using a model of human cervical cancer (ME-180 cells), the anti-tumour activity of paclitaxel was compared to that of docetaxel and IDN5109, a newly developed taxane. The growth inhibition effect of taxanes was assessed after 3 days of exposure. DNA analysis, the taxane-dependent modulation of the expression of the α and β subunits of tubulin and DNA fragmentation were assessed by flow cytometry. The presence of apoptosis was confirmed by morphological analysis using a laser scan cytometer. For the evaluation of “in vivo” anti-tumour activity, taxanes were administered to nude mice intravenously once daily, according to a q3/4d × 4 schedule. Docetaxel, IDN5109 and paclitaxel obtained “in vitro” IC50 values of 0.86, 1.4 and 2.4 nM, respectively. DNA analysis demonstrated a transient block at the G2/M phase of the cell cycle only after 12 h of culture in the presence of taxanes and an increase of nuclear fragmentation suggestive for apoptosis after additional 12 and 60 h of exposure. Morphological analysis confirmed the presence of apoptosis. Taxanes induced a down-modulation of the α subunit of tubulin in the G0/1 phase of the cell cycle, and an overexpression of the β subunit in the G2/M phase. A strong anti-tumour activity was obtained “in vivo” for nude mice xenografted using ME-180 cells (T/C=0% for all drugs). These data indicate that the three taxanes are strongly active both “in vitro” and “in vivo” toward ME-180 cells. Clinical studies are now needed to ascertain if the higher anti-tumour activity observed “in vitro” using docetaxel and IDN5109 yields a better clinical response in advanced cervical carcinoma with respect to paclitaxel.
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  • 50
    ISSN: 1432-0843
    Keywords: Key words Head and neck cancer ; Cisplatin ; Glutathione ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To evaluate the correlation between cisplatin sensitivity, intracellular glutathione, and platinum/DNA adduct formation (measured by atomic absorption spectroscopy) in a series of seven head and neck cancer cell lines, and to evaluate the effect of biochemical modulation of glutathione on platinum/DNA adduct formation and repair. Methods: Cisplatin/DNA adducts were measured by atomic absorption spectroscopy. Glutathione content was measured by enzymatic assay and was modulated with buthionine sulfoximine. Apoptosis was measured by double-labeled flow cytometry. Results: Intracellular glutathione concentration was strongly correlated with cisplatin resistance (P = 0.002, R 2=0.7). There was also a statistically significant inverse correlation between cisplatin/DNA adduct formation and the IC50 for cisplatin in these cell lines. (P=0.0004, R 2=0.67). In addition, resistant cells were able to repair approximately 70% of cisplatin/DNA adducts at 24 h, while sensitive cells repaired less than 28% of adducts in the same period. However, despite the positive correlation between cellular glutathione and cisplatin resistance, there was no direct correlation between intracellular glutathione concentration and platinum/DNA adduct formation. Further, depletion of intracellular glutathione by buthionine sulfoximine did not dramatically alter formation of cisplatin/DNA adducts even though it resulted in marked increase in cisplatin cytotoxicity and was associated with increased apoptosis. Conclusions: These results suggest that glutathione has multiple effects not directly related to formation of cisplatin/DNA adducts, but may also be an important determinant of the cell's ability to repair cisplatin-induced DNA damage and resist apoptosis.
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  • 51
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    Cancer chemotherapy and pharmacology 45 (2000), S. 183-191 
    ISSN: 1432-0843
    Keywords: Key words Epoxide-containing piperazines ; Apoptosis ; Chemotherapeutics ; AbbreviationsNCO-700 Bis[ethyl(2R,3R)-3-[(S)-3-methyl-1-[4-(2,3,4-trimethoxyphenylmethyl)piperazin-1-ylcarbonyl]butylcarbamoyl]oxirane-2-carboxylate]- sulfate ; TOP-008 Bis[ethyl(2R,3R)-3-[(S)-3-methyl-1-[4(3-phenyl-2-propenyl)piperazin-1-ylcarbonyl]butyl- carbamoyl]oxirane-2-carboxylate]sulfate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: The overall purpose of this study was to determine the potential efficacy of epoxide-containing piperazines as a new class of anti-cancer agents. Two representative compounds, specifically NCO-700, a 4-trimethoxyphenyl-substituted epoxide-piperazine, and TOP-008, a 4-phenylpropenyl-substituted epoxide-piperazine were tested in cytotoxic assays with human breast and prostate cancer cell lines. A second objective was to determine if these two compounds had anti-cancer activity in vivo when tested against xenograft tumors in nude mice or human tumors grown under the kidney capsule in mice. A final objective of this study was to establish if NCO-700 and TOP-008 achieved cancer cell killing through an apoptotic mechanism. Methods: The anti-proliferative activity of NCO-700 and TOP-008 were tested in a 7 day cell-survival assay utilizing a number of well characterized breast (HS-578T, T47D, MCF-7) and prostate (DU-145, PC-3, LNCaP) cancer cell lines. In vivo studies with the two compounds were performed, in nude mice bearing DU-145 xenograft tumors, and in normal mice in which DU-145 prostate cancer cells and HS-578T breast cancer cells were grown as solid tumors in the subrenal capsules of the animals. Apoptotic cell death of cancer cells was determined by a number of established techniques that detect apoptosis, including the confocal laser microscopy of treated cells and mitochondrial leakage assays utilizing the cationic dye, JC-1. Finally, the activation of the caspase cascade, enzymes that carry out apoptosis in mammalian cells, was examined in treated cells by immunoblot assays. Results: NCO-700 and TOP-008 displayed cytotoxicity to HS-578T human breast cancer cells, with ED50 values in the 3–6 μM range. Cytotoxicity to androgen receptor-negative human prostate cancer cells (PC-3 and DU-145 cells) occurred with ED50 values in the 5–20 μM range. Cytotoxicity to hormone receptor-positive breast and prostate cancer cell lines occurred at 10 to 20-fold higher concentrations of the two compounds. When human prostate (DU-145) or breast cancer (HS-578T) cells were grown as solid tumors in the subrenal capsules of mice, significant anti-tumor activity of NCO-700 was observed at 20 mg/kg and 50 mg/kg body weight respectively, for prostate and breast tumors. In nude mice bearing DU-145 prostate tumor xenografts, 50 mg/kg doses of the two compounds either stopped (TOP-008) tumor growth or slowed (NCO-700) growth. The mechanism of cytotoxicity was shown to be through apoptosis, (a) by confocal microscopy studies revealing nuclear fragmentation, (b) by mitochondrial studies revealing disruption of the mitochondrial membrane and release of the cationic dye, JC-1, into the cytoplasm and (c) by protein immunoblot assays indicating that over a 6 h period, TOP-008 induced a significant accumulation of the pro-apoptotic protein, bak, in the mitochondrial fraction of HS-578T human breast cancer cells, accompanied by activation, at 2.5 h, of caspase-3. Conclusions: These studies indicated that the epoxide-containing piperazines, as exemplified by NCO-700 and TOP-008, were effective anti-cancer agents when tested in vitro and in vivo against human breast and prostate tumors. Our studies also indicated that TOP-008 induced the initiation of the caspase cascade leading to apoptosis. Previous toxicology studies in rodents and dogs, as well as a Phase I study in humans, showed NCO-700 to be a well-tolerated, non-toxic compound. Taken together with our current findings, these results suggest that this class of compounds has the potential to be relatively safe, new chemotherapeutic agents for refractory breast and prostate cancers.
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  • 52
    ISSN: 1432-0843
    Keywords: Key words Gemcitabine ; Non-small-cell lung cancer ; NSCLC ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the antiproliferative and the proapoptotic ability of gemcitabine in three non-small-cell lung cancer (NSCLC) cell lines. NCI-H292 (mucoepidermoid carcinoma), NCI-CorL23 (large-cell carcinoma) and NCI-Colo699 (adenocarcinoma) cells were cultured with and without 0.5, 0.05 and 0.005 μM gemcitabine for 24, 48 and 72 h, respectively. Gemcitabine exerted a stronger and earlier antiproliferative and proapoptotic effect on H292 cells than on CorL23 or Colo699 cells. Fas receptor expression was increased in all three cell lines and was higher in Colo699 than in CorL23 cells. The incubation of NSCLC with anti-Fas agonistic monoclonal antibody (CH11) induced cell apoptosis in H292 cells, demonstrating that the Fas receptor was functionally active. Finally, gemcitabine and CH-11 exerted a synergistic effect on cell apoptosis in H292 cells. This study demonstrates that gemcitabine induces apoptosis in NSCLC and that this effect might be exerted by modulating functionally active Fas expression, and these effects of gemcitabine were stronger in H292 cells than in either CorL23 or Colo699 cells.
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  • 53
    ISSN: 1432-0738
    Keywords: Key words Acetaminophen ; Hepatotoxicity ; Apoptosis ; bcl-XL expression ; DNA fragmentation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The protein BCL-XL and protein product of proto-oncogene bcl-2 act as apoptosis antagonists, and BCL-XS serve as a dominant death promoter, including apoptosis following exposure to chemotherapeutic drugs. This investigation examined whether some aspects of the highly integrated process of acetaminophen (AAP)-induced hepatotoxicity involve down-regulation or upregulation of expression of BCL-2, BCL-XL and BCL-XS in mouse liver in vivo. Male ICR mice (CD-1; 35–45 g) were treated ip with a hepatotoxic dose of AAP (500 mg/kg) and sacrificed 0, 6, and 18 h later. Blood was collected upon sacrifice for determination of serum alanine aminotransferase (ALT) activity and the liver was sectioned for histopathological diagnosis of necrosis/apoptosis. Portions of liver tissues were also used for DNA extraction (for gel electrophoresis) and Western blot analysis. This study demonstrates that administration of a hepatotoxic dose of AAP to ICR mice results in severe liver injury (ALT leakage 〉200-fold at 6 h and 〉600-fold at 18 h) leading to massive cell death by apoptosis (diagnosed by nuclear ultrastructure, histopathology, and DNA ladder), in addition to necrosis coupled with spectacular changes in the BCL-XL expression (6 and 18 h after AAP administration). Western blot analysis of the liver proteins revealed that mouse liver expresses two proteins, BCL-XL and BCL-XS, and does not express BCL-2. As the toxicity progressed, during 6 and 18 h post-AAP administration, the BCL-XL protein band shifted to a slower mobility band which might represent a phosphorylated form of BCL-XL. Appearance of this higher molecular weight BCL-XL protein band correlated with massive apoptotic death of liver cells along with ladder-like DNA fragmentation. In the same time period, death inhibitory gene bcl-2 remained unexpressed, and the level of expression of BCL-XS remained unaltered. Whether the consistent level of expression of BCL-XS reflected inability of AAP to influence its expression remains unknown. Unaltered expression of BCL-XS in the near total absence of BCL-2 expression raises questions regarding the death promoting role of BCL-XS in vivo. The precise role of modified form of BCL-XL remains elusive. However, this study may have demonstrated for the first time drug-induced changes in the expression of anti-apoptotic gene BCL-XL, and a positive link between AAP-induced apoptotic death and modification of BCL-XL protein in vivo.
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  • 54
    ISSN: 1432-0738
    Keywords: Key words Fluoroacetate ; Apoptosis ; Testis ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fluoroacetate (FA), an inhibitor of aconitase, is known to lower the intracellular level of adenosine triphosphate (ATP), which recently has been suggested to be a possible determinant of the form of cell death, apoptosis or necrosis. To investigate which form of germ cell death occurs in FA-induced testicular toxicity, adult Sprague Dawley rats were given a single oral dose of FA (0.5 or 1.0 mg/kg) and euthanized at 3, 6, 12, 24, 48, and 72 h thereafter. Germ cell degeneration was histologically first found in early round spermatids at stage I and in spermatogonia at stages II-IV of seminiferous tubules 6 and 12 h, respectively, after dosing. Degenerating spermatogonia exhibited characteristic features of apoptosis as demonstrated by both electron microscopy and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), whereas spermatids did not. At the 24 and 48 h time points, degenerating spermatids were continually present and subsequently formed multinucleated giant cells, while the number of degenerating spermatogonia and TUNEL-labeled spermatogonia was drastically and/or significantly decreased compared to those from the control group, indicating that spontaneous male germ cell apoptosis is inhibited. Coincident with these morphological changes, DNA laddering on gel electrophoresis was apparent only 12 h after dosing. The results demonstrate that FA induces either apoptosis or necrosis of male germ cells in the early stage after dosing and subsequently inhibits spontaneous apoptosis.
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  • 55
    ISSN: 1432-0843
    Keywords: Key words Caspase family protease ; Caspase-3 ; Cisplatin resistance ; Apoptosis ; A431
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Cisplatin (cis-diamminedichloroplatinum(II), CDDP) has been reported to induce apoptosis in cancer cells, the mechanism of the apoptosis in cancer cells induced by CDDP is still unclear. Recent studies have revealed that caspase family of cystine proteases play an important role in the regulation of several apoptotic processes. In this study, whether apoptosis induced by CDDP could be mediated by the activation of caspase-3, a caspase family protease, was investigated. Methods: The CDDP-resistant subline A431/CDDP2 from the previously established human epidermoid carcinoma cell line A431 was used. The parent A431 cells (A431/P) and the A431/CDDP2 were exposed to CDDP with or without a caspase family protease inhibitor (Z-Asp-CH2-DCB), and cellular sensitivity to CDDP was determined. DNA fragmentation was then analyzed, and the caspase-3 protein levels determined by Western blotting following exposure of the cells to CDDP with or without Z-Asp-CH2-DCB. Results: In the A431/P cells, the cytotoxicity of CDDP was clearly reduced by Z-Asp-CH2-DCB compared with its cytotoxicity in A431/CDDP2 cells. Furthermore, quantitative analysis of DNA fragmentation revealed that Z-Asp-CH2-DCB inhibited DNA fragmentation induced by CDDP in A431/P cells, but not in A431/CDDP2 cells. Western blotting analysis demonstrated a marked reduction in procaspase-3 protein levels in A431/P cells treated with Z-Asp-CH2-DCB. In the A431/CDDP2 cells, procaspase-3 protein levels were no different with and without Z-Asp-CH2-DCB. Conclusions: These findings suggest that caspase-3 may mediate apoptosis induced by CDDP, and its induction could represent a novel approach to the effective treatment of malignant tumors.
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  • 56
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    Acta neuropathologica 99 (2000), S. 317-320 
    ISSN: 1432-0533
    Keywords: Key words Perineuritis ; Neuropathy ; Nerve biopsy ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 71-year-old man presented a 6-month history of progressive paresthesia of all four limbs. Sural nerve biopsy specimens showed dense mononuclear infiltrates in the perineurium and subperineurium, indicating sensory perineuritis. One section revealed disruption of the perineurial barrier. Perforin and granzyme B were present in the infiltrates, and apoptosis of perineurial cells was indicated by a terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. These findings suggest T cell-mediated apoptosis of the perineurium and nerve injury caused by perineurial damage.
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  • 57
    ISSN: 1432-0533
    Keywords: Key words Cerebellar selective injury ; Acrylamide ; Granule cell degeneration ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Oral administration of N-[4-(3-ethoxy-2-hydropropoxy)phenyl] acrylamide (EHA) induced selective granule cell destruction in the granular layer of the cerebellar cortex together with neurological signs, such as delayed righting reflex, gait or truncal ataxia, and convulsion. Neuropathologically, it caused multifocal granule cell destruction with nuclear pyknosis and spongiosis of the neuropile in the granular layer. Other neurons, including Purkinje cells, were spared. Ultrastructurally, damaged granule cells showed aggregation of nuclear chromatin and cytoplasmic edema, but cytoplasmic organelles were preserved. The brain uptake index of 14C-labeled EHA was similar to that of H2O. When EHA was added to rat cerebellar tissue cultures, only the granule cells showed nuclear pyknosis, aggregation of nuclear chromatin, and karyorrhexis with cytoplasmic swelling. These granule cells were positive for DNA fragmentation by the TUNEL method. These results suggest that EHA permeates the blood vessel wall and directly affects the cerebellar granule cells, resulting in selective granule cell apoptosis.
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  • 58
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    Acta neuropathologica 99 (2000), S. 402-408 
    ISSN: 1432-0533
    Keywords: Key words Ageing ; Dog brain ; Apoptosis ; DNA ¶fragmentation ; TUNEL method
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuronal DNA fragmentation, as revealed with the method of in situ end-labeling of nuclear DNA fragmentation (TUNEL), has been reported in both the canine and human brains in normal ageing, and in some human age-related neurodegenerative diseases. These results have suggested that apoptosis plays an important role in age-related neuronal loss. It is not clear, however, whether the TUNEL method is highly specific for apoptosis, as DNA fragmentation also occurs in the late stages o necrosis. In this study we have examined 27 dogs aged from ¶8 to 18 years, to investigate the occurrence of nuclear DNA fragmentation. An autolysis index based on current histological criteria was assigned to each animal to evaluate the effects of autolysis on nuclear DNA integrity. Our results have shown that neuronal nuclear DNA fragmentation is frequent in aged dogs, although it is not accompanied by apoptotic morphology. Yet, a positive relation between TUNEL labelling and the degree of tissue autolysis was observed. In contrast, no TUNEL labelling was detected in young control dogs despite autolysis indices being similar to those in aged dogs. Taken together, these results suggest that neuronal nuclear DNA fragmentation is an age-related phenomenon, not due to apoptosis, whenever other factors render neuronal DNA more susceptible to autolytic fragmentation. We confirm the effect of autolysis in a subpopulation of neurons in the aged canine brain, inducing nuclear DNA fragmentation.
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  • 59
    ISSN: 1432-055X
    Keywords: Schlüsselwörter ; Präanalytische Fehlerquellen ; Arterielle Blutgasanalyse ; AaDO2 ; Key words ; Pre-analytical errors ; Arterial blood-gas-analysis ; AaDO2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Objectives: The paO2 and AaDO2 are routinely measured for evaluating pulmonary gas exchange. The normal value of the AaDO2 amounts 10 mmHg when breathing atmospheric air and is said to increase with rising FIO2. This increase is discussed controversially. One possible reason for incongruities in AaDO2 measurement may be the impact of so called preanalytical errors during paO2 measurement, which are often neglected. Therefore, the aim of this study was to evaluate the relevance of preanalytical errors on the AaDO2 under hyperoxic conditions. Methods: Arterial blood gas analysis was performed on twenty patients without known pulmonary disease after tracheal intubation and 30 min of ventilation with pure oxygen. All preanalytical paO2 errors (sam- pling technique, transport and storage of samples, aspirated air bubbles) were assessed and all paO2 measurements were corrected by applying respective predetermined correction factors. Calculation of the AaDO2 was performed with corrected and uncorrected paO2 values. Results: The average amount of the AaDO2 under ventilation with FIO2=1.0 was 118.9±41.1 mmHg, calculated from uncorrected paO2 values, and 13.4±7.5 mmHg calculated from paO2 values corrected for preanalytical errors, respectively. Conclusion: The present results show that the assumption of an increasing AaDO2 with rising FIO2 is questionable. It could be proved that neglecting preanalytical paO2 errors leads to a significant overestimation of the AaDO2. The consequence would be a misinterpretation of the patient’s condition in relation to a reduced pulmonary gas exchange, which should in fact be attributed solely to the preanalytical errors.
    Notes: Zusammenfassung Fragestellung: Sowohl der paO2 als auch die AaDO2 werden als Standardverfahren für die Beurteilung des pulmonalen Gasaustauschs herangezogen. Als „Normalwert” der AaDO2 unter Raumluftatmung werden in der Literatur übereinstimmend Werte um 10 mmHg angegeben. Kontrovers sind die Angaben jedoch für die reine O2-Beatmung, vermutlich weil die Existenz unvermeidlicher präanalytischer Fehler bei der Bestimmung des paO2 bislang nicht beachtet wurde. Ziel dieser Studie war es daher, die Auswirkungen präanalytischer Fehler bei der Bestimmung des paO2 auf die Größe der AaDO2 und damit auf deren Aussagekraft zu untersuchen. Methodik: 20 lungengesunde Patienten wurden nach endotrachealer Intubation für 30 min mit reinem O2 beatmet. Anschließend wurden arterielle Blutgasanalysen durchgeführt, und präanalytische Fehler (Art der Probenentnahme, Art der Probenlagerung, Aspiration von Luftblasen) anhand vorbestehender Korrekturfaktoren nachträglich korrigiert. Die entsprechende AaDO2 wurde dann sowohl „korrigiert” als auch „unkorrigiert” berechnet. Ergebnisse: Die AaDO2 betrug ohne Berücksichtigung der präanalytischen Fehler im Mittel 118,9±41,1 mmHg. Nach Korrektur der präanalytischen Fehler betrug sie im Mittel jedoch nur noch 13,4±7,5 mmHg. Schlußfolgerung: Nach vorliegenden Ergebnissen entspricht die Größe der AaDO2 unter reiner O2-Beatmung beim lungengesunden Patienten derjenigen unter Raumluftatmung. Die Differenz zur „unkorrigierten” AaDO2 von vorliegend 105,5 mmHg geht offensichtlich zu Lasten der präanalytischen Fehler. Wird die AaDO2 zur Beurteilung des Patientenzustands herangezogen, so müssen präanalytische Fehler beachtet und korrigiert werden. Anderenfalls würde die Interpretation einer fälschlicherweise zu hoch errechneten AaDO2 hinsichtlich der Lungenfunktion (z.B. Zunahme venöser Beimischung) lediglich auf präanalytischen Fehlern basieren.
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  • 60
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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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  • 61
    ISSN: 1432-069X
    Keywords: Keywords HSP70 ; Human melanoma cells ; Ultraviolet B ; Apoptosis ; Caspase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The heat shock response is a highly conserved reaction common to all cells and organisms. It has been reported that hyperthermic treatment can induce the expression of the heat shock protein (HSP) and can protect cells from ultraviolet (UV) B radiation. In this study, we evaluated the effects of induced HSP70 on resistance to UV radiation. G361 amelanotic human melanoma cells were irradiated with increasing doses of UVB. UVB irradiation caused apoptotic cell death in these cells. Following transfection with MFG.hsp70.puro plasmid, the expression of HSP70 was determined. Compared to control vector-transfected cells, hsp70-transfected cells showed significantly elevated levels of HSP70 and were highly resistant to UVB irradiation. In order to investigate the effects of HSP70 on the apoptotic pathway, the changes in caspase-3 and PARP were analyzed. Following UVB irradiation, activation of caspase-3 and cleavage of PARP were observed in control vector-transfected cells, and the changes in these molecules were inhibited in the hsp70-transfected cells. These results suggest that UVB-induced apoptosis of melanoma cells is accompanied by caspase-3 activation and PARP cleavage, which can be prevented by an overexpression of HSP70.
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  • 62
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    Der Anaesthesist 49 (2000), S. 65-73 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter ; Qualitätsmanagement ; Kosteneffektivität ; Zertifizierung ; ISO 9001 ; EFQM ; Key words ; Quality management ; Cost effectiveness ; Certification ; ISO 9001 ; EFQM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Quality of care and costs are getting closer together. Whereas costs and quality management did not play a substantial role 30 years ago, the consumption of resources nowadays is part of the outcome of quality of care. The definition of quality must be seen in the dimensions of structure, process and result. Resulting from newly developed clinical practice, guidelines are planned as instruments for cost containment in near future. Those guidelines may end up in a quality management system. The most wellknown european basic of such a quality management system are the DIN EN ISO 9000 f and the EFQM. The ISO 9001 and the European Quality Award became the most common base of evaluation for certification of quality management systems in Organisations europeanwide. Whereas the ISO 9001 does not give any information about the real achieved quality, the European Quality Award reflects the process. Guidelines are necessary to prove the cost effectiveness of measures of quality control and quality assurance since too much quality control and assurance may result in increased overall consumption of resources, leading to a reduction in the quality of care when ensuring that the overall budget is covered.
    Notes: Zusammenfassung Versorgungsqualität und Kosten rücken immer näher zusammen. Während noch vor 30 Jahren weder die Kostenfrage noch ein Qualitätsmanagement eine Rolle spielten, ist inzwischen der Ressourcenverbrauch sogar zu einem Bestandteil der Ergebnisqualität geworden. Der Qualitätsbegriff wird in seinen Dimensionen Struktur-, Prozeß- und Ergebnisqualität beleuchtet. Hieraus abgeleitete Empfehlungen und Leitlinien für die ärztliche Versorgung sollen in Zukunft als Instrumente zur Kostensenkung eingesetzt werden. Diese können in Qualitätsmanagementsystemen münden, deren bekannteste Grundlage derzeit die DIN EN ISO 9000 f. darstellt. Die ISO 9001 sowie die Selbstbewertung nach EFQM haben sich europaweit als Prüfungsgrundlage für die Zertifizierung von Qualitätsmanagementsystemen in Organisationen durchgesetzt. Organisationen können ganze Kliniken oder einzelne Abteilungen wie die Anästhesie sein. Dabei werden in 20 Kapiteln der ISO 9001 organisatorische Verfahren beschrieben, die innerhalb der Organisation die Aufrechterhaltung eines bestimmten Qualitätsniveaus sicherstellen sollen. Im EFQM-Modell steht die Prozeßbeherrschung im Vordergrund, die zugrundegelegten Kriterien gliedern sich in Befähiger- und Ergebniskriterien. Der Nachweis der Kosteneffektivität von Qualitätskontroll- und -sicherungsmaßnahmen ist wichtig, denn ein Zuviel an Qualitätskontrolle und -sicherung läßt den Ressourcenverbrauch zusätzlich ansteigen. Dies führt bei einem gedeckelten Gesamtbudget zu einer Senkung der Versorgungsqualität.
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  • 63
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    Der Anaesthesist 49 (2000), S. 2-8 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter ; Schlaganfall ; Thrombolyse ; Intrakranieller Druck ; Stroke unit ; Key words ; Stroke ; Thrombolysis ; Intracranial pressure ; Stroke unit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Stroke is an emergency. Treatment must begin as soon as possible because significant sustained neurological improvement has been demonstrated when thrombolytic treatment, mainly with recombined tissue plasminogen activator (rtPA) is initiated within the first hours of stroke onset. On the other hand in the acute phase of stroke it is critical that patients get adequate management for the prevention of early complications. Management of the acute phase of stroke is the target of this article. Preclinically started treatment must be continued in the neurological emergency unit. Clinical examination is followed by technical investigations: cerebral computertomography (CCT) is the most useful radiological investigation in the acute phase. It allows to distinguish between ischemia and hemorrhagic lesions and also to rule out nonstroke brain conditions. Multimodal magnetic resonance imaging (mMRI) may provide data on viable versus irreversibly damaged tissue. Sufficient stroke treatment is based on well managed in-hospital infrastructure. Thrombolysis is the only causative treatment of stroke in selected patients. Complications of acute stroke comprise changes of blood pressure with hemodynamically relevant effects on cerebral perfusion pressure, acute post- ischemic brain edema, and intracerebral bleedings.
    Notes: Zusammenfassung Der akute Schlaganfall stellt einen Notfall dar. Zum einen, weil das funktionelle Ergebnis durch eine frühe Thrombolysetherapie signifikant verbessert wird. Zum anderen, weil beim akuten Schlaganfall eine frühzeitige Behandlung von Komplikationen die Prognose positiv beeinflußt. Der Schwerpunkt dieses Artikels liegt auf der Behandlung der akuten zerebralen Ischämie. Die Primärversorgung eines Schlaganfallpatienten bei Aufnahme in die Klinik besteht zunächst in der Fortführung der bereits präklinisch begonnenen Basisversorgung. Parallel zur klinisch-neurologischen Evaluation erfolgt die Durchführung technischer Untersuchungen. Mit der zerebralen Computertomographie (cCT) kann zwischen zerebraler Ischämie und intrazerebraler Blutung unterschieden und andere Ursachen können ausgeschlossen werden. Mit der multimodalen Magnetresonanztomographie (mMRT) kann zwischen reversibel und irreversibel geschädigtem Hirngewebe unterschieden werden. Eine weitere Voraussetzung für eine suffiziente Schlaganfalltherapie ist eine optimal aufeinander abgestimmte innerklinische Infrastruktur. Als spezielles therapeutisches Verfahren steht heute die Thrombolysetherapie für selektierte Patienten zur Verfügung. Zu den Komplikationen des akuten Schlaganfalls gehören hämodynamisch wirksame Blutdruckschwankungen, die Entwicklung eines akuten postischämischen Hirnödems und intrazerebrale Blutungen.
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  • 64
    ISSN: 1432-055X
    Keywords: Schlüsselwörter ; Periduralanalgesie ; Patientenkontrollierte Analgesie ; Postoperative Schmerztherapie ; Key words ; Epidural analgesia ; Patient-controlled analgesia ; Postoperative pain treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Objectives: Continuous epidural analgesia (EA) and patient-controlled intravenous analgesia (PCA) are widely used for postoperative pain control. Studies indicate that both analgesic regimens provide good analgesia after major surgery. However, because of the following reasons it is still unclear whether one of the two modes of application is superior. First, there are conflicting data regarding the differences in pain relief and drug use between epidural and intravenous administration of opioids. Second, in many studies epidural analgesia is performed by a combination of local anaesthetics and opioids. Third, reduced morbidity was observed only in some of the studies, in which epidural analgesia provided better pain relief than systemic opioid supply. Despite these conflicting results, EA with local anaesthetics and fentanyl as well as PCA with piritramid, a highly potent μ-agonist, are routinely used in Germany. The purpose of this study was to compare these two treatments for analgesic efficacy, pulmonary function, incidence of side effects and complications in patients undergoing thoracotomy. Methods: In this prospective randomized trial 50 patients were included. For postoperative pain control 25 patients (EA group) received thoracic epidural infusion of local anaesthetics (bupivacaine 0.125% or ropivacaine 0,2%) and fentanyl 4,5µg/ml with a flow rate of 4-10 ml/h. 25 patients received intravenous PCA with piritramid (bolus 2,5 mg, lock out 15 minutes, maximum of 25 mg/4 h, no background infusion). Results: Analgesia at rest and while coughing, as evaluated by visual analogue scale, was significantly better in the EA group. EA also resulted in superior values of pulmonary function tests, general condition and a lower incidence of sedation and nausea. In contrast, patients with EA reported distinctly more pruritus than patients with PCA. Duration of hospital stay was shorter in the EA group, but this difference did not reach statistical significance. There was one atelectasis in the EA group. No major complications related to EA or PCA were observed. Conclusion: In this study EA with local anaesthetics and fentanyl provided superior postoperative pain control and a lower incidence of sedation and nausea compared to intravenous PCA with piritramid, but there was no superiority as to pulmonary complications and duration of hospital stay.
    Notes: Zusammenfassung In einer prospektiven, randomisierten Studie wurden die beiden klinisch etablierten, postoperativen Analgesieverfahren, die kontinuierliche thorakale Periduralanalgesie (PDA) mit Lokalanästhetikum und Fentanyl und die intravenöse patientenkontrollierte Analgesie (PCA) mit Piritramid, verglichen. Bei 50 Patienten (PDA-Gruppe n=25, PCA-Gruppe n=25), die sich einer Thorakotomie unterziehen mußten, wurden Analgesie, unerwünschte Wirkungen, Allgemeinbefindlichkeit, Krankenhausaufenthaltsdauer und Komplikationen unter den jeweiligen Verfahren untersucht. Die Ergebnisse zeigen, daß sowohl die PDA als auch die PCA zur Schmerztherapie nach Thorakotomien effektiv und sicher sind. Dennoch wurde unter PDA eine signifikant bessere analgetische Wirkung sowie eine deutlich geringere Inzidenz der unerwünschten Wirkungen Sedierung und Übelkeit erzielt. Über Juckreiz klagten die Patienten mit PDA hingegen öfter. Im Hinblick auf Lungenfunktionsparameter, die subjektive Allgemeinbefindlichkeit der Patienten und die Krankenhausaufenthaltsdauer schnitt die PDA-Gruppe ebenso tendenziell besser ab. Auch die Beurteilung des jeweiligen Analgesieverfahrens durch die Patienten fiel bei insgesamt guter Bewertung beider Verfahren in der PDA-Gruppe besser aus. Trotz dieser Vorteile führte die PDA gegenüber der PCA jedoch nicht zu einer Senkung der pulmonalen Komplikationsrate.
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  • 65
    ISSN: 1432-055X
    Keywords: Schlüsselwörter ; Schmerzgedächtnis ; Akuter postoperativer Schmerz ; Key words ; Pain memory ; Acute postoperative pain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Objectiles: Clinicians use patients’ recall of pain as an important source of evidence both in diagnosis and in assessing improvements following treatment. Yet very little is known about the accuracy of these retrospective accounts up to now. Methods: We examined patients’ retrospective evaluations of the pain they experienced at the first postoperative day and related these evaluations to the pain intensity which was recorded in the PCA-report. Results: We found that recall was moderately accurate. Patients mostly overestimated their pain intensity. We could demonstrate that patients who overestimated their pain differed significantly from those who did not. The patients who overestimated showed no significant pain relief over the first three postoperative days. Other influences were the pain intensity of the third day and patients’ expectations of the postoperative pain intensity. Our results could be embedded within the theoretical framework of general memory research. Conclusions: We conclude that real-time evaluations of pain intensity should be recorded additionally to retrospective accounts. Retrospective ratings are important too, because we suggest that the memory of pain more than the experience of pain itself form the basis of patients’ future decisions about treatment including their compliance and their satisfaction with pain management.
    Notes: Zusammenfassung Retrospektive Schmerzeinstufungen durch den Patienten werden sehr häufig verwendet. Dennoch ist bislang nur sehr wenig bekannt, wie diese Einschätzungen zustande kommen und wie sie mit dem unmittelbaren Schmerzerleben zusammenhängen. Wir haben die Übereinstimmung zwischen den retrospektiven Schmerzeinstufungen von 67 Patienten, die postoperativ eine PCA-Pumpe zur Schmerzlinderung erhalten hatten, mit den Aufzeichnungen des PCA-Protokolls verglichen und fanden in Übereinstimmung mit anderen Forschungsergebnissen eine geringe Übereinstimmung. Es bestand insgesamt eine Tendenz zur Schmerzüberschätzung. Dies traf jedoch nicht auf alle Patienten zu. Eine genauere Analyse der Patienten, die ihre Schmerzen deutlich überschätzt hatten (〉 dem Median der Differenzen der Gesamtstichprobe) und denen, die dies nicht getan hatten, zeigte, dass der Schmerzverlauf für beide Gruppen unterschiedlich gewesen war. Patienten, die ihre Schmerzen überschätzten, hatten in den ersten drei Tagen keine signifikante Schmerzreduktion gegenüber dem ersten postoperativen Tag erfahren. Weitere Einflussfaktoren auf die retrospektive Schmerzeinstufung waren die Schmerzstärke des dritten postoperativen Tages und die Schmerzerwartungen, die der Patient hatte. Die Ergebnisse konnten in die Befunde der allgemeinen Gedächtnisforschung integriert werden. Neben retrospektiven Beurteilungen sollte daher nach Möglichkeit auch die aktuelle Schmerzbeurteilung des Patienten erfasst werden. Da jedoch gerade die retrospektive Einschätzung, d. h. die Erinnerung an den Schmerz vermutlich die Entscheidungen von Patienten beeinflusst und eher als Indikator für die Zufriedenheit des Patienten mit der Schmerztherapie zu werten ist, behält die retrospektive Einschätzung weiterhin ihre Berechtigung im Rahmen der Evaluation schmerztherapeutischer Massnahmen.
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  • 66
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    Der Anaesthesist 49 (2000), S. 25-28 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter ; Koronarsinusdilatation ; perioperative transösophageale Echokardiographie ; persistierende linke obere Hohlvene ; Kardioanästhesie ; Herzchirurgie ; Key words ; Dilated coronary sinus ; Perioperative transesophageal echocardiography ; Persistent left superior vena cava ; Cardiac anaesthesia ; Cardiac surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract A 36-year old woman was presented to our hospital with congenital ventricular septal defect and one-vessel coronary artery disease (75% proximal left main coronary artery) for CABG and repair of the VSD. After induction, a transesophageal echocardiographic (TEE) baseline examination was performed, showing a severely dilated coronary sinus (CS) measuring approximately 3 cm (abnormal 〉1 cm). We suggested a persistent left superior vena cava (PLSVC) draining into the CS. PLSVC is a common venous congenital anomaly, with a reported incidence of 0.5% in general population and in 3–5 % of patients with congenital heart defect. Injection of echo-contrast solution in a left arm vein, visualizing microbubbles passing through the PLSVC into the CS confirmed our suspicion. The diagnosis of a PLSVC and dilated CS is a contraindication for retrograde cardioplegia because of the loss of cardioplegia into the PLSVC resulting in a inadequate myocardial protection. It may be difficult to pass a pulmonary artery catheter (PAC) through a left internal or left subclavian vein and it may be associated with arrythmias. A chest radiograph shows the anomalous course of the PAC along the left heart.
    Notes: Zusammenfassung Eine 36jährige Frau, mit einem kongenitalen Ventrikelseptumdefekt (VSD) und einer koronaren 1-Gefäßerkrankung (75% Hauptstammstenose) wurde unserem Krankenhaus zur Koronarbypassoperation und Verschluß des VSD zugewiesen. Nach der Narkoseeinleitung führten wir eine transösophageale echokardiographische Basisuntersuchung durch. Es zeigte sich ein deutlich dilatierter Koronarsinus (CS) von ca. 3 cm Durchmesser (abnormal 〉1 cm). Man vermutete eine persistierende linke obere Hohlvene (PLSVC), die sich in den CS drainiert. Die PLSVC ist eine venöse kongenitale Annomalie mit einer Inzidenz von 0,5% in der Normalbevölkerung und von 3–5% bei Patienten mit kongenitalen Herzerkrankungen. Nach Injektion von Echokontrastmittel über eine linke Armvene zeigten sich sog. Microbubbles im CS und bestätigten unsere Verdachtsdiagnose. Die Diagnose einer PLSVC und eines dilatierten CS gilt als eine Kontraindikation für die retrograde Kardioplegie, da es über die PLSVC zum Verlust von Kardioplegie, mit daraus resultierender unzureichender Kardioprotektion kommt. Die Plazierung eines Pulmonalarterienkatheters über die linke V. jugularis interna oder die linke V. subclavia kann erschwert sein und zu Herzrhythmusstörungen führen. Eine Röntgenthoraxaufnahme zeigt den ungewöhnlichen Verlauf des PAK entlang des linken Herzschattens.
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  • 67
    ISSN: 1432-0533
    Keywords: Key words HSV ; Immunohistochemistry ; Apoptosis ; p53 ; Transcription factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To understand the mechanism of neuronal apoptosis induced by herpes simplex virus (HSV) infection in vivo, the distribution of viral antigen, the appearance of apoptotic bodies, and the expressions of the tumor suppressor gene p53 and several transcription factors such as c-fos, c-jun and NF-κB were examined immunohistochemically and histopathologically after corneal infection of mice with HSV type 2 strain 186. Five days after HSV infection, viral antigen was diffusely detected in the corneal epithelium, the trigeminal ganglion and the pars caudalis of the spinal trigeminal nucleus. Neuronal apoptosis was observed in the brain stem ipsilateral to the HSV-infected side with the immunoreactivities of c-fos, c-jun, NF-κB and p53. Dual-labeling immunohistochemical studies revealed that almost all of the viral antigen-positive neurons and glia in the brain stem also showed p53 immunoreactivity. On the other hand, no neuronal apoptosis but only with the expression of c-jun was found in the trigeminal ganglion. Our results suggest that the different expression of transcription factors between the brain stem and the trigeminal ganglion may influence the neuronal apoptosis induced by HSV infection.
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  • 68
    ISSN: 1432-0533
    Keywords: Key words Alzheimer’s disease ; Apoptosis ; β-Amyloid load ; Astrocytes ; Microglia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The extent of DNA fragmentation analysed using the TUNEL technique was evaluated in post-mortem human brain tissue. Twenty-four patients with clinical and histopathological diagnosis of Alzheimer’s disease (AD) and a short post-mortem delay were analysed. We report an increase in the count of TUNEL-labelled cells as the pathology of AD intensifies. Our results point out a significant correlation between neurofibrillary tangle and senile/neuritic plaque score and TUNEL-labelled cells. Patients with two copies of apolipoprotein (Apo) E ɛ4 allele had highest number of histopathological hallmarks lesions of AD, whereas the ApoE genotype did not significantly influence the density of TUNEL-positive cells. No significant correlation was found between β-amyloid protein load and TUNEL-labelled cells. There was no relationship between the age at death, age at onset, extent of astrogliosis or microgliosis and TUNEL-labelled cells in our material.
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  • 69
    ISSN: 1432-0533
    Keywords: Key words Skeletal muscle ; Eccentric exercise ; Apoptosis ; Dystrophin ; Dystrophin-associated proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated the basis for the high severity of damage to skeletal muscle due to eccentric exercise, i.e., to muscles generating force while lengthened. Fast and slow rat leg muscles maintained in an extended position were examined after 2–24 h of continuous stimulation. The treatment caused the injury to some regions of both muscles. Within the better preserved parts of the muscles, i.e., those without signs of necrotic processes, dystrophin, spectrin, and some of the dystrophin-associated proteins (β-dystroglycan, α-sarcoglycan, and γ-sarcoglycan) disappeared from sarcolemma of many fibers. The reduction or loss of dystrophin from the sarcolemma was more evident than that of other proteins examined, with sarcoglycans apparently being the most preserved. Several muscle fibers devoid of dystrophin contained apoptotic nuclei. Simultaneously, Bax, Bcl-2 and caspase-3 proteins appeared in many fibers. Our results indicate that a normal muscle overworking in an extended position undergoes the loss of several membrane skeletal proteins because of the excessive stress to the membrane cytoskeleton, which can lead to fiber death by either apoptosis or necrosis. This experimental model may represent a good model for mimicking the pathogenetic events in several muscular dystrophies.
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  • 70
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    Journal of biomedical science 7 (2000), S. 64-70 
    ISSN: 1423-0127
    Keywords: p53 ; Chemosensitivity ; Cell cycle ; Apoptosis ; Non-small cell lung cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract This study examined the effects of p53 gene status on DNA damage-induced cell death and chemosensitivity to various chemotherapeutic agents in non-small cell lung cancer (NSCLC) cells. A mutant p53 gene was introduced into cells carrying the wild-type p53 gene and also vice versa to introduce the wild-type p53 gene into cells carrying the mutant p53 gene. Chemosensitivity and DNA damage-induced apoptosis in these cells were then examined. This study included five cell lines, NCI-H1437, NCI-H727, NCI-H441 and NCI-H1299 which carry a mutant p53 gene and NCI-H460 which carries a wild-type p53 gene. Mutant p53-carrying cells were transfected with the wild-type p53 gene, while mutant p53 genes were introduced into NCI-H460 cells. These p53 genes were individually mutated at amino acid residues 143, 175, 248 and 273. The representative cell line NCI-H1437 cells transfected with wild-type p53 gene (H1437/wtp53) showed a dramatic increase in susceptibility to three anticancer agents (7-fold to cisplatin, 21-fold to etoposide, and 20-fold to camptothecin) compared to untransfected or neotransfected H1437 cells. An increase in chemosensitivity was also observed in wild-type p53 transfectants of H727, H441, H1299 cells. The results of chemosensitivity were consistent with the observations on apoptotic cell death. H1437/wtp53 cells, but not H1437 parental cells, exhibited a characteristic feature of apoptotic cell death that generated oligonucleosomal-sized DNA fragments. In contrast, loss of chemosensitivity and lack of p53-mediated DNA degradation in response to anticancer agents were observed in H460 cells transfected with mutant p53. These observations suggest that the increase in chemosensitivity was attributable to wild-type p53 mediation of the process of apoptosis. In addition, our results also suggest that p53 gene status modulates the extent of chemosensitivity and the induction of apoptosis by different anticancer agents in NSCLC cells.
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  • 71
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    Journal of biomedical science 7 (2000), S. 2-15 
    ISSN: 1423-0127
    Keywords: Apoptosis ; Mitochondria ; Necrosis ; Oxidative stress ; Reactive oxygen species
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Mitochondria are the major ATP producer of the mammalian cell. Moreover, mitochondria are also the main intracellular source and target of reactive oxygen species (ROS) that are continually generated as by-products of aerobic metabolism in human cells. A low level of ROS generated from the respiratory chain was recently proposed to take part in the signaling from mitochondria to the nucleus. Several structural characteristics of mitochondria and the mitochondrial genome enable them to sense and respond to extracellular and intracellular signals or stresses in order to sustain the life of the cell. It has been established that mitochondrial respiratory function declines with age, and that defects in the respiratory chain increase the production of ROS and free radicals in mitochondria. Within a certain concentration range, ROS may induce stress responses of the cell by altering the expression of a number of genes in order to uphold energy metabolism to rescue the cell. However, beyond this threshold, ROS may elicit apoptosis by induction of mitochondrial membrane permeability transition and release of cytochrome c. Intensive research in the past few years has established that mitochondria play a pivotal role in the early phase of apoptosis in mammalian cells. In this article, the role of mitochondria in the determination of life and death of the cell is reviewed on the basis of recent findings gathered from this and other laboratories.
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  • 72
    ISSN: 1423-0127
    Keywords: Apoptosis ; Differential display ; Glioma ; Okadaic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract To identify novel genes associated with apoptosis in glioma cells, we treated T98G glioma cells with okadaic acid (OA). Differential display using 15 random primers was performed on RNA extracted from these cells. Upregulated bands were excised from polyacrylamide gels and cloned. Northern blots were used to confirm RNA expression in T98G cells. 18 RNA fragments corresponding to the untranslated region of genes were identified and sequenced. Three unknown gene fragments were used to screen a fetal brain cDNA library resulting in three complete cDNA sequences. The three sequences corresponded to a human gene homologous to the yeast translation initiation factor Sui-1, a cAMP-regulated phosphoprotein, ARPP-16/19, and a novel gene designated O48. Transcription of Sui-1 increased in response to all stress factors tested, whereas ARPP only responded to OA. 2-kb and 4-kb O48 RNA species were identified. OA and stress factors increased 2-kb expression while K252a (protein kinase inhibitor) increased 4-kb expression. Differential display is effective for identifying genes associated with apoptosis. Novel genes may be identified by further analysis of the gene fragments identified in this study. The function of O48 is unknown.
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  • 73
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    Journal of biomedical science 7 (2000), S. 195-199 
    ISSN: 1423-0127
    Keywords: Opioid ; Enkephalin ; DADLE ; Transplantation ; Hibernation ; Apoptosis ; Methamphetamine ; Dopamine ; Ischemia ; Reperfusion ; PC12 cells ; Neuroprotection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract By studying the hibernation in ground squirrels, a protein factor termed hibernation induction trigger (HIT) was found to induce hibernation in summer-active ground squirrels. Further purification of HIT yielded an 88-kD peptide that is enriched in winter hibernator. Partial sequence of the 88-kD protein indicates that it may be related to the inhibitor of metalloproteinase. Delta opioid [D-Ala2,D-Leu5]enkephalin (DADLE) also induced hibernation. HIT and DADLE were found to prolong survival of peripheral organs preserved en bloc or as a single preparation. These organs include the lung, the heart, liver and kidney. DADLE also promotes survival of neurons in the central nervous system. Methamphetamine (METH) is known to cause destruction of dopaminergic (DA) terminals in the brain. DADLE blocked and reversed the DA terminal damage induced by METH. DADLE acted against this effect of METH at least in part by attenuating the mRNA expressions of a tumor necrosis factor p53 and an immediate early gene c-fos. DADLE also blocked the neuronal damage induced by ischemia-reperfusion following a transient middle cerebral artery occlusion. In PC12 cells, DADLE blocked the cell death caused by serum deprivation in a naltrexone-sensitive manner. Thus, DADLE, and by extension the endogenous delta opioid peptides and delta opioid receptors, may play an important role in organ and neuronal survival. Here, critical developments concerning these fascinating cell protective properties of DADLE are reviewed.
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  • 74
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    Journal of biomedical science 7 (2000), S. 459-465 
    ISSN: 1423-0127
    Keywords: Apoptosis ; Thermal brain injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apoptosis has been implicated recently as a prominent response of the brain to a variety of insults, such as ischemia and trauma. In this study, we demonstrate that apoptosis is a prominent part of the brain's response to a thermal insult. To examine the brain's response to a thermal insult, a new model of thermal brain injury in the laboratory rat was developed. Water heated to 60°C was passed over an area of thinned calvarium for 1 min. This resulted in an actual brain temperature of 47–48°C. A uniform area of 2,3,5-triphenyl-tetrazolium chloride pallor was demonstrated and pyknotic neurons were seen in the area of injury by hematoxylin-eosin staining. Apoptosis was demonstrated by the characteristic DNA fragmentation seen by agarose gel electrophoresis, ApopTag in situ staining and electron microscopy. The findings of apoptosis were localized to the area of thermal injury and were time dependent, starting 6 h after the insult and peaking approximately 18 h after the insult. This represents one of the first demonstrations that apoptosis occurs in the brain in response to a thermal injury.
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  • 75
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    Journal of biomedical science 7 (2000), S. 322-333 
    ISSN: 1423-0127
    Keywords: Apoptosis ; HIV ; SIV ; Vpr ; Vpx ; Bcl-2 ; Bax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The growth inhibitory effects of Vpr and Vpx are species-and cell type-dependent. HIV-1, HIV-2 and SIV Vpr are primarily cytostatic in mammalian cells and HIV-1 Vpr has been reported to induce apoptosis in human cells. Our previous studies have shown that HIV-1, HIV-2 and SIV Vpr and Vpx have differential cytostatic and cytotoxic effects in the yeast cells [Zhang et al.: Virology, 230:103–112; 1997]. Here, we further examined the apoptosis function of HIV-1 Vpr in different species of mammalian cells and investigated if other primate lentiviral Vpr and Vpx exert similar functions. Our results show that none of the primate lentiviral Vpr or Vpx we tested induces apoptosis in nonhuman species of mammalian cells. However, HIV-1 Vpr, but not HIV-2 or SIV Vpr and/or Vpx, induced apoptosis in different types of human cell lines. Further, the apoptotic effect of HIV-1 Vpr can be distinguished from that of the human interferon-γ, a known proapoptotic protein, that HIV-1 Vpr shows little to no paracrine and/or bystander effect. When coexpressed with Bcl-2 or Bcl-XL, the apoptotic effect of HIV-1 Vpr became markedly attenuated. These results indicate that the apoptotic effect of HIV-1 Vpr is species-dependent and is intracellularly modulated by the Bcl-2 family of proteins. Our study also suggests that the proapoptotic function of HIV-1 Vpr is developmentally associated with human but not nonhuman primate species.
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  • 76
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    Cancer immunology immunotherapy 48 (2000), S. 673-683 
    ISSN: 1432-0851
    Keywords: Key words CD20 ; Apoptosis ; Mechanisms ; Lymphomas ; Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anti-CD20 monoclonal antibodies have been successfully employed in the clinical treatment of non-Hodgkin's lymphomas in both unmodified and radiolabeled forms. Previous publications have demonstrated that the antitumor effects of unmodified anti-CD20 mAb are mediated by several mechanisms including antibody-dependent cellular cytotoxicity, complement-mediated cell lysis, and induction of apoptosis by CD20 cross-linking. In this report, we demonstrate induction of apoptosis by three anti-CD20 monoclonal antibodies [1F5, anti-B1, and C2B8 (Rituximab)]. The magnitude of apoptosis induction was greater with the chimeric Rituximab antibody than with the murine 1F5 and anti-B1 antibodies. Apoptosis could be enhanced with any of the antibodies by cross-linking with secondary antibodies (or Fc-receptor-bearing accessory cells). The signaling events involved in anti-CD20-induced apoptosis were investigated, including activation of protein tyrosine kinases, increases in intracellular Ca2+ concentrations, caspase activation, and cleavage of caspase substrates. Our results indicate that anti-CD20-induced apoptosis can be attenuated by PP1, an inhibitor of protein tyrosine kinases Lck and Fyn, chelators of extracellular or intracellular Ca2+, and inhibitors of caspases, suggesting that anti-CD20-induced apoptosis may involve modulation of these signaling molecules. We also demonstrated that varying the expression of Bcl-2 did not affect the magnitude of anti-B1-induced apoptosis, possibly because of the sequestering effects of other Bcl-2 family members, such as Bad. These studies identify several of the signal-transduction events involved in the apoptosis of malignant B cells that transpire following ligation of CD20 by anti-CD20 antibodies in the presence of Fc-receptor-expressing cells or secondary goat anti-(mouse Ig) antibodies and which may contribute to the tumor regressions observed in mouse models and clinical trials.
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  • 77
    ISSN: 1432-0851
    Keywords: Key words Drug therapy ; T cells ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Noscapine, a phthalideisoquinoline alkaloid derived from opium, has been used as an oral anti-tussive agent and has shown very few toxic effects in animals or humans. Recently, we reported that noscapine binds stoichiometrically to tubulin and promotes microtubule polymerization. Noscapine causes growth arrest of tumor cells in mitosis and induces apoptosis of tumor cells in vitro. Previous experiments also showed that noscapine has potent antitumor activity in mice when administered parenterally or by gastric lavage. Here, we report that the anti-mitotic effect was specific to noscapine since closely related compounds did not inhibit the growth of a lymphoma cell line. In addition, noscapine was shown to be effective in reducing the growth of the lymphoma and increasing the survival of tumor-bearing mice when administered in the drinking water. It is noteworthy that, noscapine showed little or no toxicity to kidney, liver, heart, bone marrow, spleen or small intestine at tumor-suppressive doses. Furthermore, oral noscapine did not inhibit primary immune responses, which are critically dependent upon proliferation of lymphoid cells. Thus, our results indicate that noscapine has the potential to be an effective chemotherapeutic agent for the treatment of human cancer.
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  • 78
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    Cancer immunology immunotherapy 49 (2000), S. 335-345 
    ISSN: 1432-0851
    Keywords: Key words Immunotherapy ; CD95 ; Lymphocyte activation ; Apoptosis ; Gene expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A variety of malignancies express Fas ligand (FasL), which can induce apoptosis in effector lymphocytes and may limit the success of cellular immunotherapy. Our laboratory has been investigating a population of ex vivo activated T cells, termed cytokine-induced killer (CIK) cells. These cells share functional and phenotypic properties with natural killer cells and a subset of cytolytic cells have the phenotype CD3+CD56+. CIK cells expand in culture, have significant antitumor activity and are presently being tested in phase I/II clinical trials. In this study, we investigated the sensitivity of CIK cells to Fas-mediated apoptosis. Fas engagement leads to apoptosis in small numbers of CIK cells and does not significantly influence antitumor cytotoxicity. CIK cells will undergo apoptosis following Fas engagement when protein synthesis is inhibited, suggesting the expression of antiapoptotic genes. Evaluation of antiapoptotic gene transcripts shows an up-regulation in the expression of cFLIP, Bcl-2, Bcl-xL, DAD1 and survivin. Resistance to Fas-mediated apoptosis may come about through an in vitro selection for Fas resistance, since CIK cells synthesize FasL and supernatant from CIK cultures contains biologically active soluble FasL, which can be inhibited with Fas:Fc. These results indicate that CIK cells are a suitable form of immunotherapy against FasL-positive tumors.
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  • 79
    ISSN: 1432-0738
    Keywords: Key words Fumonisin B1 ; C6 Glioma cells ; DNA fragmentation ; Comet assay ; Apoptosis ; Prevention by Vitamin E
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fumonisin B1 (FB1), produced by the fungus Fusarium moniliforme, belongs to a class of sphingosine analogue mycotoxins that occur widely in the food chain. Epidemiological studies have associated consumption of Fusarium moniliforme-contaminated food with human oesophageal cancer in China and South Africa. FB1 also causes equine leucoencephalomalacia. Evidence for induction of apoptosis by FB1 was first obtained when C6 glioma cells were incubated with fumonisin B1 (3–27 μM) causing DNA fragmentation profiles showing DNA laddering in gel electrophoresis and apoptotic bodies revealed by chromatin staining with acridine orange and ethidium bromide. Further confirmation experiments and comet assays have been performed under similar conditions. The results of the comet test show that FB1 at 9 and 18 μM induces respectively 50 ± 2% and 40 ± 1% of cells with a comet with an increased tail length of 93 ± 9 μm and 102 ± 17 μm respectively. Under these concentrations, FB1 induced DNA fragmentation and laddering and many apoptotic bodies. Pre-incubation of the cells with vitamin E (25 μM) for 24 h before FB1 (18 μM) significantly reduced DNA fragmentation and apoptotic bodies induced by FB1.
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  • 80
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    Archives of dermatological research 292 (2000), S. 522-523 
    ISSN: 1432-069X
    Keywords: Key words Serum soluble Fas ; Systemic sclerosis ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 81
    ISSN: 1432-069X
    Keywords: Key words Docosahexaenoic acid (DHA) ; 15-hydroxyeicosatrienoic acid (15-HETrE) ; AP-1 ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to ascertain whether the antiproliferative effect of 15-hydroxyeicosatrienoic acid (15-HETrE), a monohydroxy fatty acid generated from dihomo-Á-linolenic acid, in an experimentally induced guinea pig hyperproliferative model involves alterations in nuclear transcription factor (AP-1) and apoptosis. The topical application of docosahexaenoic acid (DHA) to normal guinea pig skin elicited a severe hyperplasia which was accompanied by the suppression of AP-1 expression in a time-dependent manner. Since apoptosis is pivotal in tissue turnover, the expression of two apoptotic proteins (Bcl-2 and caspase-3) after DHA and 15-HETrE treatment was explored. DHA-induced hyperproliferation enhanced the expression of Bcl-2 (an antiapoptotic protein) but inhibited the expression of caspase-3 (an apoptotic protein). 15-HETrE, on the other hand, reversed the DHA-induced epidermal hyperplasia, and upregulated epidermal AP-1 expression. These events paralleled the suppression of Bcl-2 and the elevation of caspase-3. Taken together, these results suggest that the antiproliferative effect of 15-HETrE may, at least in part, be via the modulation of AP-1 and apoptosis.
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  • 82
    ISSN: 1432-069X
    Keywords: Key words Granuloma annulare ; Cytokine ; Apoptosis ; Lymphocytes ; Macrophages
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Granuloma annulare, a prototype noninfectious granulomatous dermatitis, is morphologically characterized by a necrobiotic core surrounded by a cellular infiltrate. Because of many morphological similarities to tuberculosis, granuloma annulare has been suggested to represent a delayed-type hypersensitivity (Th1) reaction in the course of which inflammatory cells elicit matrix degradation. In the present study we (1) investigated the expression of interferon-Á as the most important Th1-associated cytokine, (2) sought in situ evidence for the coexpression of the proinflammatory cytokine tumor necrosis factor-· and cytokine-regulated matrix metalloproteinases 2 (gelatinase A) and 9 (gelatinase B), and (3) sought to determine whether shrunken cells seen within necrobiotic areas of granuloma annulare are apoptotic cells. In situ hybridization combined with immunofluorescence showed that large numbers of infiltrating CD3+ lymphocytes express interferon-Á. Application of catalyzed signal amplification in immunodetection revealed that the vast majority of CD3+ lymphocytes and CD68+ macrophages contained tumor necrosis factor-·. Immunohistochemistry demonstrated that macrophages producing tumor necrosis factor-· coexpress matrix metalloproteinases 2 and 9. In situ end-labeling combined with immunofluorescence detected few apoptotic T cells in perivascular regions and numerous apoptotic macrophages within necrobiotic areas. These results suggest that in granuloma annulare interferon-Á+ Th-1 lymphocytes may cause a delayed-type hypersensitivity reaction whereby macrophages are differentiated to aggressive effector cells expressing tumor necrosis factor-α and matrix metalloproteinases. In parallel, activation-induced apoptosis in lymphocytes and macrophages may serve to restrict the destructive potential of the inflammatory cells.
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  • 83
    ISSN: 1432-069X
    Keywords: Key words Ceramide ; 1α,25-Dihydroxyvitamin D3 ; TNFα ; Apoptosis ; Bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract During the last few years increasing evidence has shown that sphingolipid metabolites are highly bioactive compounds that play important roles in cellular regulation. The induction of ceramide signalling in primary human keratinocytes and HaCaT keratinocytes has recently been demonstrated using 1·,25-dihydroxyvitamin D3. The data obtained indicate that approximately one-third of the proapoptotic effect of 1·,25-dihydroxyvitamin D3 is mediated by an intracellular ceramide increase induced via tumor necrosis factor · expression and autocrine stimulation of sphingomyelin hydrolysis. In the present study the role of bcl-2 in this process was investigated. HaCaT keratinocytes were transfected with bcl-2 and the effects of C2-ceramide, tumor necrosis factor · and 1·,25-dihydroxyvitamin D3 on HaCaT keratinocytes stably overexpressing bcl-2 were determined. Apoptosis was measured by detection of soluble DNA-histone complexes using the ELISA technique. In situ analysis of apoptotic cells was also carried out by detecting phosphatidylserine flip using the annexin V method and by detecting DNA fragmentation using the TUNEL assay. The results obtained showed that apoptosis induced by C2-ceramide, tumor necrosis factor · or 1·,25-dihydroxyvitamin D3 occurred in a vector-transfected clone but not in a bcl-2-transfected HaCaT clone. This indicates the important role of bcl-2 in the regulation of ceramide-mediated signalling pathways in human keratinocytes and supports the involvement of ceramide as a signalling molecule in 1α,25-dihydroxyvitamin D3-induced biological responses.
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  • 84
    ISSN: 1432-0584
    Keywords: Nitric oxide ; Bone marrow ; Proliferation ; Apoptosis ; Sepsis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: α , interferon γ and interleukin-1β for 48 h. The basal proliferation rate of the cells remained unchanged, but granulocyte–macrophage colony stimulating factor-induced proliferation was suppressed and the percentage of apoptotic cells significantly raised. Levels of nitrite in the culture supernatants were inversely correlated with the suppression of proliferation, but directly correlated with apoptosis. The NO synthesis inhibitor N-methyl-arginine inhibited the suppression of proliferation as well as the induction of apoptosis and NO synthesis. Our results indicate that NO is a negative feedback regulator of cell turnover in sepsis, which limits growth-factor-induced proliferation and induces apoptosis of bone marrow cells.
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  • 85
    ISSN: 1432-0584
    Keywords: Key words Down syndrome ; Transient abnormal myelopoiesis ; Apoptosis ; bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transient abnormal myelopoiesis (TAM) is a haematological complication found in Down syndrome. To determine the mechanisms of sustained proliferation of TAM cells, we studied the expression of apoptosis-related proteins, such as bcl-2, Fas (APO-1/CD95) and p-53, in peripheral blood cells from a new-born infant with Down syndrome and TAM. Using flow cytometry, peripheral blood mononuclear cells (PBMCs), consisting mostly of blast cells, showed marked expression of bcl-2 protein but not of Fas or p-53 products. DNA gel electrophoresis of PBMCs, cultured in the absence of serum factors, revealed no marked fragmentation. Our findings suggest that bcl-2 overexpression may be associated with prolonged cell survival of TAM cells.
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  • 86
    ISSN: 1432-0584
    Keywords: Key words Gemcitabine ; Apoptosis ; Chronic lymphocytic leukemia ; Acute myeloid leukemia ; Cell lines ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Induction of apoptosis in vitro using gemcitabine (dFdC) in combination with cladribine (2-CdA) and other cytotoxic drugs on malignant mononuclear cells (MNCs) of patients with acute myeloid leukemia (AML, n=20) and chronic lymphocytic leukemia (CLL, n=20) in myeloid (HL60, HEL) and lymphatic cell lines (HUT78, JURKAT) was investigated using different incubation conditions (simultaneous and consecutive). Furthermore, the influence of dFdC on the level of intracellular metabolites of 2-CdA was studied using high-performance liquid chromatography (HPLC). Apoptosis was evaluated using flow cytometry with 7-aminoactinomycin D. In MNCs of patients with CLL, dFdC+2-CdA showed an antagonistic effect when applied simultaneously. This antagonism was reduced by consecutive application. The combination of dFdC with doxorubicin was synergistic, independent of incubation schedule. In blasts from newly diagnosed patients with de novo AML, all drug combinations (dFdC+2-CdA, doxorubicin, or cytosine arabinoside) were antagonistic by simultaneous incubation. Reduced antagonism or even synergism was shown (P〈0.001) by consecutive incubation. The simultaneous combination of dFdC with 2-CdA in all tested cell lines resulted in a competitive inhibition on the rate of apoptosis. By changing the incubation period to a consecutive schedule, the antagonism was diminished or synergism of apoptosis was measured (P〈0.001). Using similar incubation conditions, these experiments were supported by HPLC measurement of intracellular metabolites of 2-CdA influenced by dFdC application. In conclusion, we demonstrated that the efficacy of dFdC in vitro in combination with other cytotoxic drugs depends on the incubation condition and on the origin of neoplastic cells (lymphatic vs myeloid). The data suggest that simultaneous combination therapy with purine and pyrimidine analogues may not improve the clinical efficacy of one or the other drug administered alone.
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  • 87
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    Der Radiologe 40 (2000), S. 8-17 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Pathologische Befunde ; Frühgeburt ; Therapiefolgen ; Key words ; Pathomorphology ; Preterm ; Therapeutic sequelae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Pathomorphology in the preterm infant represents an interaction of morphological organ immaturity and neonatal management with their respective sequelae. Pathomorphological examples include the modification in the morphology of hyaline membrane disease and bronchopulmonary dysplasia as a consequence of modern neonatal therapy. Hemorrhagic and ischemic/ hypoxic lesions of the central nervous system may occur in age- and agent-related distributional patterns, with subependymal hemorrhage and periventricular leukomalacia representing the most important examples. The most common intestinal finding, namely, necrotizing enterocolitis, typically shows segmental alterations, the morphology of which largely depends on the dominating causative agent. Hepatic cholestasis and fatty change are mostly consequences of parenteral nutrition or hypoxic/ischemic stress. Hepatic necrosis can be associated with the latter, but may also indicate disseminated intravascular coagulation. Vascular pathomorphology is represented by thromembolic lesions, in most instances corresponding to sequelae of neonatal mangement.
    Notes: Zusammenfassung Die Pathomorphologie des Frühgeborenen kann als Wechselspiel von Morphologie der Organunreife und Therapie sowie deren Folgen angesehen werden. Beispiele zur Pathomorphologie: Beispiele inkludieren den Wandel im morphologischen Bild des sog. Hyaline-Membranen-Syndroms und der bronchopulmonalen Dysplasie, die infolge moderner neonatologischer Therapie kaum mehr in ihrer ursprünglich definierten Form gesehen werden. Hämorrhagische und ischämisch-hypoxische Läsionen des ZNS weisen oft alters- und ursachenabhängige Verteilungsmuster auf, wobei subependymäre Blutungen und periventrikuläre Leukomalazie mit ihren Spätfolgen die wichtigsten Beispiele darstellen. Das häufigste intestinale Krankheitsbild, die nekrotisierende Enterokolitis, präsentiert sich mit segmentalen Läsionen, deren Morphologie in Abhängigkeit vom dominierenden auslösenden Faktor variieren kann. Hepatische Cholestase und Verfettung kommen als Folge von parenteraler Ernährung, aber auch von Ischämie und Hypoxie vor. Lebernekrosen sind vorrangig mit Letzterer, aber auch mit disseminierter intravasaler Koagulation assoziiert. Als Beispiele vaskulärer pathologischer Befunde werden thrombembolische Läsionen mit Extremitäten- und Organinfarkten genannt, die gleichzeitig typische Therapiefolgen darstellen.
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  • 88
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Herz ; MR ; Herzinfarkt ; Vitalitätsdiagnostik ; Gd-DTPA-Spätaufnahmen ; Key words ; Heart ; MR ; Myocardial infarction ; Myocardial viability ; Gd-DTPA-delayed enhancement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Purpose: The aim of the study was to correlate delayed contrast enhancement of dysfunctional regions of the myocardium after injection of Gd-DTPA with the improvement of regional contractility 3 months after revascularization. Material and methods: Eleven patients with coronary artery disease and wall motion abnormalities underwent MR imaging before and 3 months after revascularization therapy (PTCA or CABG). Short-axis images were acquired using a cine gradient echo sequence. After revascularization, a representative slice was analyzed 14±1 min after injection of 0.1 mmol/kg Gd-DTPA using a T1-weighted turbo fast low-angle shot sequence. Improved systolic wall thickening 3 months after revascularization served as criterion of viability and was correlated with delayed contrast enhancement patterns. Results: After revascularization, 6 patients showed complete recovery of the dysfunctional area, 1 patient partial recovery, and 4 patients remained unchanged. All 4 patients with persisting wall motion abnormalities, 1/6 patients with recovery and the patient with partial recovery revealed a delayed enhancement. Conclusions: Three months after revascularization, delayed enhancement of dysfunctional myocardium is evident in patients without regional wall motion improvement, while the lack of delayed enhancement correlates with improvement of regional contractility.
    Notes: Zusammenfassung Zielsetzung: Die Korrelation der Signalintensität motilitätsgestörter Myokardareale in Spätaufnahmen nach der Gabe von Gd-DTPA mit der Erholung der regionalen Funktion nach Revaskularisierung sollte untersucht werden. Material und Methode: 11 Patienten mit Koronararterienstenosen und Wandbewegungsstörungen wurden mit einer CINE-GRE-Sequenz in der kurzen Herzachse vor und 3 Monate nach Revaskularisierung (PTCA oder Bypassoperation) untersucht. Bei der Kontrolle wurde eine repräsentative Schicht im motilitätsgestörten Areal 14±1 min nach der Gabe von 0,1 mmol/kg Gd-DTPA mit einer T1-w-TurboFLASH-Sequenz untersucht. Eine regionale Kontraktilitätsverbesserung wurde als vermehrte systolische Wanddickenzunahme nach Revaskularisierung definiert und mit der Signalintensität in Spätaufnahmen korreliert. Ergebnisse: Bei 6 Patienten erholte sich nach Revaskularisierung das gesamte motilitätsgestörte Areal, bei 1 Patienten partiell, bei 4 Patienten blieben die Wandbewegungsstörungen unverändert. Bei 4/4 Patienten mit persistierenden Wandbewegungsstörungen, bei 1/6 Patienten mit erholtem Myokard sowie bei dem Patienten mit dem partiell erholten Areal war ein spätes Enhancement nachweisbar. Schlussfolgerungen: Ein Enhancement von Myokardarealen in Spätaufnahmen nach der Gabe von Gd-DTPA 3 Monate nach der Revaskularisierung ist bei persistierenden Wandbegungsstörungen zu beobachten, wogegen das Fehlen eines späten Enhancements mit einer Verbesserung der regionalen Wandfunktion korreliert.
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  • 89
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    Der Radiologe 40 (2000), S. 130-135 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Herz ; Koronargefäße ; Koronarer Bypass ; Bypassverschluss ; EKG-getriggertes CT ; Key words ; Heart ; Coronary vessels ; Coronary artery bypass graft ; CABG patency ; ECG-triggered CT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Purpose: Assessment of coronary artery bypass graft (CABG) patency with computed tomography methods has been demonstrated as an alternative to coronary angiography. The evaluation of the bypass anastomoses is still of limited success. Prospective ECG triggering of conventional CT scanners al- lows heart phase-triggered single-slice acquisition in the sub-second range. The goal of this study was to evaluate whether the use of ECG triggering can optimize the evaluation of proximal CABG anastomoses. Materials and methods: In ten patients after CABG surgery, ECG-triggered CT with thin (2 mm), contiguous slices was performed in the region of the proximal bypass anastomoses in the ascending aorta. The data evaluation was done on axial images and on reconstructed 2D and 3D data sets. Results: The applied technique demonstrat-ed good imaging quality, which allowed evaluation of the CABG anastomoses in all cases. Overall 18 CABG anastomoses could be visualized; 17 anastomoses could be assessed as normal, non-stenotic and patent. Discussion: ECG-triggered thin-slice CT permits reliable assessment of proximal CABG anastomoses and expands the usage of CT in the evaluation of CABG.
    Notes: Zusammenfassung Hintergrund: Die computertomographische Durchgängigkeitsprüfung koronararterieller Bypässe hat sich zu einer Alternative neben dem Herzkatheter entwickelt. Die Beurteilbarkeit der Anastomosen gelingt noch nicht mit zufriedenstellender Sicherheit. Der Einsatz der prospektiven EKG-Triggerung an einem konventionellen CT ermöglicht herzphasengesteuerte Einzelschichtaufnahmen im Subsekundenbereich. Ziel der Studie war es, zu prüfen, ob der Einsatz einer EKG-Triggerung zu Verbesserungen in der Beurteilung der proximalen Bypassanastomosen führt. Methode: Bei 10 Patienten wurde nach Bypassoperation eine EKG-getriggerte CT mit dünnen (2 mm), kontinuierlichen Schichten von den proximalen Bypassanastomosen im Bereich der Aorta ascendens durchgeführt. Die Datenauswertung erfolgte an axialen Einzelschichten und nachverarbeiteten 2D- und 3D-Datensätzen. Ergebnisse: Die Untersuchungstechnik ergab in allen Fällen eine gute Bildqualität und Beurteilungsmöglichkeit der Anastomosenverhältnisse. Insgesamt wurden 18 Bypassanastomosen dargestellt. Von diesen Anastomosen konnten 17 als unauffällig, durchgängig und ohne Stenosierung gewertet werden. Schlussfolgerung: Die EGK-getriggerte CT in dünnen Schichten erlaubt eine Beurteilung der proximalen Anastomosenverhältnisse aortokoronarer Bypässe und erweitert somit das Einsatzspektrum der CT.
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  • 90
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Echokardiographie ; Klappeninsuffizienz ; Bildverarbeitung ; Virtuelle RealitätEchocardiography ; Heart valve disease ; Image processing ; Virtual reality ; Key words ; Echokardiographie ; Klappeninsuffizienz ; Bildverarbeitung ; Virtuelle RealitätEchocardiography ; Heart valve disease ; Image processing ; Virtual reality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Background: Echocardiography is a standard imaging technique for the assessment of heart valve disease. The good spatial and temporal resolution is the basis for different methods which provide information about the severity of such defects. Dynamic colour visualisation and volumetric measurements of regurgitant jets are a new evaluating tool for the assessment of heart valve insufficiencies. Methods: The regurgitant jet volume of 58 patients was evaluated on an external workstation after segmentation of the left atrium and compared to regurgitant volume; the correlation was good. This result is valid for central jets as well as for eccentric jets. Conclusions: Measurement of regurgitant jet volume is a method which considers the three-dimensional shape of the examined volume. Real-time visualisation techniques which support the interactive clipping of morphological structures provide dynamic visualisation of intracardiac flow during the heart cycle. Dynamic colour visualisation of jets together with myocardial structures allows the assignment of intracardiac flow to morphological structures.
    Notes: Zusammenfassung Fragestellung: Für die Bewertung von Klappendefekten ist die Echokardiographie ein bildgebendes Standardverfahren. Die gute räumliche und zeitliche Auflösung dient als Grundlage für eine Vielzahl unterschiedlicher Auswertungsverfahren, die die Beurteilung von Klappendefekten erlauben. Die dynamische Farbvisualisierung und die Volumetrie von Regurgitationsjets stellen eine neue Methode der Beurteilung von Klappeninsuffizienzen dar. Methode: Die Volumen der Regurgitationsjets von 58 Patienten wurden auf einer externen Workstation nach Segmentierung des linken Vorhofs vermessen und mit dem Regurgitationsvolumen verglichen. Ergebnisse: Die Volumen der Regurgitationsjets zeigen eine signifikante Korrelation mit den Regurgitationsvolumen, das mit gepulstem Doppler gewonnen wurde. Dieses Ergebnis gilt sowohl für zentrale als auch für exzentrische Jets. Schlussfolgerungen: Die Volumetrie von Regurgitationsjets ist ein Verfahren, das die dreidimensionale Form der zu untersuchenden Volumen besonders berücksichtigt. Die dynamische Farbvisualisierung der Jets im Kontext der Myokardstrukturen erlaubt eine Zuordnung von intrakardialen Flüssen zu den morphologischen Strukturen. Eine Echtzeitvisualisierung, die die Möglichkeit bietet, Teile des Myokards interaktiv aus der Rekonstruktion zu entfernen, erlaubt eine dynamische Darstellung des intrakardialen Flusses während eines Herzzyklus.
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  • 91
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Mehrschicht-CT ; Spiral-CT ; Kardio-CT ; Retrospektives EKG-Gating ; Key words ; Multi-slice CT ; Spiral-CT ; Cardio CT ; Retrospective ECG-gating
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Purpose: In this paper a method for cardiac imaging with fast multi-slice CT and retrospectively ECG-gated spiral acquisition is presented. Methods: A fast multi-slice CT system with 4 simultaneously acquired slices and 0.5 s rotation time is used (Siemens Somatom VolumeZoom). Continuous spiral data of the entire heart volume is acquired together with the patient’s ECG and reconstructed with dedicated spiral algorithms providing 250 ms temporal resolution. Three-dimensional image data sets are built up from overlapping slices that are reconstructed in an arbitrary, user-defined phase of the heart cycle (e.g. diastolic phase). To evaluate the capability of the method for functional imaging complete three-dimensional image volumes are reconstructed from the same spiral data set in different phases of the heart cycle. Results: A spiral data set of the entire heart volume may be acquired within a single breath-hold. Typical scan times for standard examinations with 3 mm slice width are 10–15 s, and for high-resolution CT angiographies of the coronary arteries with 1.25 mm slice width about 30–35 s. Motion-free reconstruction of the heart and coronary arteries with high spatial resolution is possible in the diastolic phase of the heart cycle. Multi-phase reconstructions from the same spiral scan data set are possible, however, motion artifacts in heart phases with fast cardiac motion may not be completely avoided. Conclusion: Fast multi-slice spiral CT with retrospectively ECG-gated spiral reconstruction is well suited for three-dimensional and functional imaging of the heart, especially for high-resolution imaging of calcified coronary plaques and CT-angiography of the coronary arteries.
    Notes: Zusammenfassung Zielsetzung: In dieser Arbeit werden Verfahren zur Anwendung der schnellen Mehrschichtspiral-CT für die kardiale Bildgebung mittels EKG-synchronisierter Spiralakquisition dargestellt. Methode: Es wird ein schnelles Mehrschicht-CT-System mit simultaner Aufnahme von 4 Schichten und 0,5 s Rotationszeit verwendet (Siemens Somatom VolumeZoom). Kontinuierliche Spiraldatensätze des gesamten Herzvolumens werden zusammen mit dem EKG aufgenommen und mit dedizierten Spiralalgorithmen bei 250 ms zeitlicher Auflösung rekonstruiert. Dreidimensionale Bilddatensätze können in einer frei wählbaren Phase des Herzzyklus (z.B. diastolische Phase) aus überlappend rekonstruierten Einzelschichten zusammengesetzt werden. Durch die Rekonstruktion mehrerer dreidimensionaler Bilddatensätze in verschiedenen Phasen des Herzzyklus kann die Herzfunktion analysiert werden. Ergebnisse: Für ein gesamtes Herzvolumen kann ein Spiraldatensatz in einer Atemanhalteperiode aufgenommen werden. Die Scanzeiten für Standarduntersuchungen mit 3 mm Schichtdicke liegen bei 10–15 s, für hochaufgelöste CT Angiographien der Koronararterien mit 1,25 mm Schichtdicke bei 30–35 s. Ein dreidimensionales Bild des Herzens und der Koronararterien kann ohne Bewegungsartefakte und mit hoher räumlicher Auflösung in der diastolischen Phase des Herzzyklus erzeugt werden. Erste Ansätze zur funktionellen Bildgebung mit Mehrphasenrekonstruktionen aus demselben Spiraldatensatz werden vorgestellt. In Herzphasen mit starker Bewegung können Bewegungsartefakte auftreten. Schlußfolgerung: Die schnelle Mehrschichtspiral-CT mit retrospektiv EKG-synchronisierter Spiralrekonstruktion (EKG-Gating) eignet sich für die dreidimensionale und funktionelle Bildgebung des Herzens, insbesondere für die hochaufgelöste Abbildung kalzifizierter Plaques und für die CTA der Koronararterien.
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  • 92
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Herzvitien ; Klappenersatz ; MR-Imaging ; 31P-MR-Spektroskopie ; Energiestoffwechsel ; Key words ; Valve disease ; Valve replacement ; MR-imaging ; 31P-MR-spectroscopy ; Energy metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Purpose: Heart valve disease combined with left ventricular hypertrophy leads to derangements in cardiac energy metabolism, which can be detected non-invasively by 31P-MR-spectroscopy. The purpose of the present study was to examine whether the derangements in cardiac metabolism are reversible after surgical valve replacement. Patients and methods: 10 healthy volunteers and 10 patients with aortic stenosis (pressure gradients 〉60 mmHg) were included. For assessment of energy metabolism, 31P-MR spectra were obtained with a double oblique 3D-CSI technique (voxel size 25 cm3). In 5 of 10 patients, follow-up examination was performed 3 months after surgical valve replacement (SVR). Left ventricular (LV) function was analyzed by cine MRI. Results: Before SVR the myocardial phosphocreatine to adenosinetriphosphate (PCr-ATP) ratio was significantly (p=0.0002) reduced to 0.80±0.25 in patients compared to 1.65±0.21 in volunteers. 3 months after SVR, LV mass had significantly (p=0.04) decreased from 238±33 g to 206±47 g. At the same time a significant (p=0.04) increase of the PCr-ATP ratio from 0.80±0.25 to 1.28±0.22 was observed. A slight, but not significant, reduction of the phosphodiester ATP ratio was observed before SVR, with a trend towards normalization after SVR. Conclusions: After SVR, the deranged energy metabolism shows a trend towards normalization. Further follow-up is necessary to determine whether complete normalization of the energetic derangement can be observed over longer periods of time following SVR.
    Notes: Zusammenfassung Zielsetzung: Mit einer linksventrikulären Hypertrophie einhergehende Herzvitien führen zu Veränderungen des kardialen Energiestoffwechsels, die mit der 31P-MR-Spektroskopie nichtinvasiv erfasst werden können. Ziel der vorliegenden Studie war es, zu untersuchen, ob nach chirurgischem Klappenersatz eine Normalisierung des Energiestoffwechsels beobachtet werden kann. Patienten und Methode: 10 gesunde Probanden und 10 Patienten mit Aortenklappenstenose (Druckgradient 〉60 mmHg) wurden untersucht. Zur Erfassung des kardialen Energiestoffwechsels wurde eine doppelt angulierbare 3D-CSI-Technik verwendet (Voxelgröße 25 ccm). 3 Monate nach Aortenklappenersatz (AKE) erfolgte bei 5 Patienten eine Nachkontrolle. Bei den Patienten wurden zusätzlich linksventrikuläre (LV) Funktionsparameter mittels cine-MRI-Technik analysiert. Ergebnisse: Vor Klappenersatz war bei den Patienten das Phosphokreatin-Adenosintriphosphat(PCr-ATP)-Verhältnis mit 0,80±0,25 signifikant im Vergleich zu Gesunden (1,65±0,21; p=0,0002) erniedrigt. 3 Monate nach AKE konnte eine signifikante (p=0,04) Verringerung der LV-Masse von 238±33 g auf 206±47 g nachgewiesen werden. Die LV-Ejektionsfraktion änderte sich jedoch nicht wesentlich (von 61±11% auf 65±7%; p=0,22). Zur selben Zeit zeigte sich ein signifikanter (p=0,04) Anstieg des PCr-ATP-Verhältnis von 0,80±0,25 auf 1,28±0,22 an. Für das Phosphodiester-ATP-Verhältnis zeigte sich eine geringe, jedoch nicht signifikante Reduzierung vor AKE, mit einer Tendenz zum Wiederanstieg nach AKE. Schlussfolgerungen: Nach Klappenersatz ist eine Tendenz zur Normalisierung des pathologisch veränderten Energiestoffwechsels zu beobachten. Weitere Nachkontrollen sind notwendig, um zu klären, ob es zu einem späteren Zeitpunkt zu einer vollständigen Normalisierung des Energiestoffwechsels kommt.
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  • 93
    ISSN: 1534-4681
    Keywords: Gastric cancer ; Apoptosis ; Fas ; Fas ligand ; Cytotoxic T lymphocyte.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Previous studies indicate that gastric carcinomas express Fas ligand and downregulate Fas to escape from the host immune attack; however, the prognostic importance of Fas/FasL expression in this tumor is yet to be evaluated. Methods: Specimens from 87 gastric carcinoma patients of different stages treated in a defined period with curative intent were evaluated for apoptosis, Fas, FasL, and CD8 expression using an immunohistochemical method. Results: The percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells expressed as apoptotic index (AI) was higher in 43 patients when the cut-off value was set at the median value. There were no significant correlations between AI and clinicopathologic parameters. Thirty-nine patients showed a high number of CD81 cells within cancer nests. Positive FasL and Fas expression was seen in 53 and 72 patients, respectively. CD8 and FasL expressions were related only to patients’ age. Fas expression had significant correlations with tumor invasion and Lauren classification. There were significant direct correlations between AI and number of nest CD81 cells and between AI and grade of Fas expression. Apoptotic index, pT stage, CD8 expression, and Fas expression were identified as independent prognostic factors. Conclusions: Spontaneous apoptosis in gastric carcinoma may be an independent prognosticator for survival and is significantly influenced by tumor Fas expression and number of nest CD81 cells.
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  • 94
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    Gastric cancer 3 (2000), S. 39-44 
    ISSN: 1436-3305
    Keywords: Key words Chemosensitivity ; Apoptosis ; TUNEL ; Gastric cancer ; Small specimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Because chemosensitivity tests usually require a large amount of tissue, they are not used routinely in patients with unresectable gastric cancer. The aim of this study was to investigate whether apoptosis can be used as a sensitivity assay for chemosensitivity in small gastric cancer specimens. Methods. Apoptosis, detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick labeling (TUNEL), was investigated in small specimens of the MKN-1, MKN-45, and TMK-1 human gastric cancer cell lines as a marker of chemosensitivity following exposure to antineoplastic agents. Results. Doxorubicin (DXR), SN-38 (active metabolite of irinotecan), and paclitaxel (Taxol) induced DNA fragmentation in MKN-45 and TMK-1 cells, but not in MKN-1. In contrast, neither 5-fluorouracil (5-FU) nor cisplatin (CDDP) induced DNA fragmentation in any of the three cell lines. Small pieces cut from tumors implanted in nude mice were exposed to the antineoplastic agents in culture medium for 24 h, and the percentage of TUNEL-positive cancer cells (TUNEL positivity) was examined. TUNEL positivity in all three cancers increased after exposure to DXR, SN-38, and Taxol, but not after exposure to CDDP or 5-FU. MKN-45 showed the highest TUNEL positivity with SN-38 and Taxol, and TMK-1 TUNEL positivity was highest with DXR. MKN-45 and TMK-1 were the most sensitive to these three antineoplastic agents in vitro, while MKN-1, with the lowest TUNEL positivity, was the least sensitive to these three antineoplastic agents. TUNEL positivity after exposure to Taxol correlated with the antitumor effects of this compound in an animal model. Conclusion. These results suggest that, in small gastric cancer specimens where apoptosis is implicated, TUNEL positivity may be applicable to a chemosensitivity test.
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  • 95
    ISSN: 1530-0358
    Keywords: Anus ; High-grade squamous intraepithelial lesion ; Carcinoma ; Proliferation ; Apoptosis ; Microvessel density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Management of anal high-grade squamous intraepithelial lesions is controversial. Anal and cervical high-grade squamous intraepithelial lesions are similar in that they occur in transitional squamous epithelium, are associated with human papilloma virus infection, and have increased incidence in the immunocompromised population. Ablation of cervical high-grade squamous intraepithelial lesions is preferred, but similar ablation or excision of anal high-grade squamous intraepithelial lesions may compromise bowel control; thus, there is a need to define the malignant potential of anal high-grade squamous intraepithelial lesions. METHODS: We analyzed 50 paraffin sections of normal anoderm, anal low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and anal squamous-cell carcinoma. Microvessels were detected immunohistochemically with von Willebrand factor and counted manually along the epithelial-stromal junction. Proliferation and apoptosis were determined in the epithelial cells with MIB-1 antibody immunostaining and the terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling, respectively. RESULTS: Microvascular density was significantly greater in anal high-grade squamous intraepithelial lesions (mean, 0.50 vessels/cm)vs. normal anoderm (mean, 0.21 vessels/cm;P=0.0017, Mann-WhitneyU test). The proliferative percentages were greater in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and squamous-cell carcinoma (mean, 20.4, 21.8, and 23.6 percent)vs. normal anoderm (mean, 14.4 percent), although not significantly (P=0.06, Kruskal-Wallis statistic). Although the mean proliferative proportions were similar in low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, the apoptotic proportion was lower for high-grade squamous intraepithelial lesions than low-grade squamous intraepithelial lesions (10.13vs. 19.96 percent, respectively;P=NS, Mann-WhitneyU test). CONCLUSIONS: Angiogenesis, increased proliferation, and decreased apoptosis occur in anal high-grade squamous intraepithelial lesions as they do in the cervix before the development of malignancy. These biologic markers support the importance of anal high-grade squamous intraepithelial lesions as a potential premalignant lesion warranting surgical intervention.
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  • 96
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    Diseases of the colon & rectum 43 (2000), S. 775-781 
    ISSN: 1530-0358
    Keywords: Locally recurrent rectal cancer ; Survival ; Prognostic factor ; Angiogenesis ; Apoptosis ; PCNA labeling index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: It has recently been demonstrated that the tumor growth rate is a stronger determinant of survival than the extent of the growth in local recurrence of rectal cancer. We studied which factors controlled the tumor growth rate using modern immunohistochemical methods. METHODS: In 51 patients who underwent extended resection for this condition, paraffin-embedded specimens were examined for 1) tumor angiogenesis by CD31 staining and microvessel counting, 2) apoptosis by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling staining, and 3) cellular proliferative activity using anti-proliferative cell nuclear antigen antibody. The results were compared with carcinoembryonic antigen doubling time and survival. RESULTS: The five-year survival rate was 20 percent. The postoperative carcinoembryonic antigen doubling time, which was the strongest predictor of survival, correlated highly with proliferative cell nuclear antigen labeling index, but did not correlate with the apoptotic index or microvessel counts. CONCLUSION: Our study shows that cancer cell proliferation rather than apoptosis or angiogenesis is a major determinant of tumor growth rate and survival in patients with locally recurrent rectal cancer.
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  • 97
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    Diseases of the colon & rectum 43 (2000), S. S23 
    ISSN: 1530-0358
    Keywords: Apoptosis ; Flat-type carcinoma ; Colorectal neoplasms ; p53 ; p21 (WAF1/CIP1) ; Bax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to investigate the relationship among apoptotic cell death, proliferative activity, and the expression of apoptosis-regulating proteins (p53, p21 (WAF1/CIP1), and bax) in flat-type early colorectal carcinoma and to compare these factors with those in polypoid-type early colorectal carcinoma. METHODS: Formalin-fixed, paraffin-embedded tissues of 11 flat-type early colorectal carcinomas and 17 polypoid-type early carcinomas were studied. The histologic diagnosis was either well-differentiated adenocarcinoma or carcinoma in adenoma, and the depth of invasion was limited to mucosa or submucosa. Apoptotic cells were detected by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling method, and proliferative activity was determined by Ki-67 immunohistochemistry using monoclonal antibody MIB-1. Apoptosis-regulating proteins were determined by immunohistochemistry using antibody DO-7 (p53), Cip1 (p21 (WAF1/CIP1)), and Bax (bax). RESULTS: There was no significant difference in terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index between flat-type early colorectal carcinoma and polypoid-type early carcinoma, at 1.9vs. 1.1, respectively. In flat-type carcinoma terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index in the p53 protein overexpression group was significantly smaller than that in the p53 protein-negative group (P〈0.05). The Ki-67 labeling index/terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index ratio in the p53 protein overexpression group was significantly higher than that in the p53 protein-negative group (P〈0.05). In polypoid-type carcinoma, the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index and Ki67/terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index ratio showed no significant difference between the p53 protein overexpression group and p53 protein-negative group. CONCLUSION: p53-dependent apoptosis may contribute to the development of flat-type early colorectal carcinoma. Apoptosis and its regulation in flat-type early colorectal carcinoma may differ from those in polypoid-type carcinoma.
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  • 98
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    Diseases of the colon & rectum 43 (2000), S. 1227-1236 
    ISSN: 1530-0358
    Keywords: Rectal cancer ; Apoptosis ; p53 ; bcl-2 ; Prognosis ; Recurrence ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to evaluate the prognostic value of the apoptotic index for recurrence and disease-free survival after curative surgery for rectal cancer, particularly in relation to clinicopathologic variables, p53− and bcl-2 expression. METHODS: Formalin-fixed, paraffin-embedded tissue samples of rectal carcinomas resected curatively within a five-year period were used (N=160). Apoptotic cells with fragmented DNA were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatase-biotin nick-end-labeling method. The ratio of apoptotic tumor cells (in percent) was classified into low apoptotic index (less than 10 percent) and high apoptotic index (10 percent or more). Immunohistochemical analysis was performed using monoclonal antibodies (DO-1 for p53 and clone 124 for bcl-2). Statistics included univariate and multivariate analysis, and survival was calculated using the Kaplan-Meier method. RESULTS: Seventy-five percent of tumors showed a low apoptotic index, and 25 percent had a high apoptotic index. No correlation was found between apoptotic index and International Union Against Cancer stage (P〉0.05). However, significant correlations were documented with histologic differentiation (mean apoptotic index, 5.74 percent in moderatelyvs. 3.98 percent in poorly differentiated carcinomas; P=0.0173), lymph node involvement (mean apoptotic index, 6.11 percent in pN1vs. 3.72 percent in pN2; P=0.0074), p53 status (mean apoptotic index, 6.26 percent in p53−vs. 4.42 percent in p53+; P=0.0085), and bcl-2 expression (mean apoptotic index, 5.13 percent in bcl-2−vs. 6.51 percent in bcl-2+; P=0.0418). Tumors of the lower rectum had a lower apoptotic index than those of the upper rectum (P=0.0277). Neither univariate nor multivariate analysis assessed apoptotic index as predictor of prognosis: Recurrence rates did not differ between tumors related to apoptotic index (22 percent with low apoptotic indexvs. 15 percent with high apoptotic index; P〉0.05), and no significant differences were found regarding survival (P〉0.05). On multivariate analysis, International Union Against Cancer stage (P=0.0002), p53 (P=0.0002), gender (P=0.0136), and bcl-2 (P=0.0243) were independent predictors of recurrence. These variables, except for bcl-2, were also independently related to disease-free survival. CONCLUSIONS: Reflecting tumor biology, apoptotic index as single variable showed no prognostic significance, whereas p53 was an independent predictor for both recurrence and survival, and bcl-2 was independently related to recurrence, but not to survival. Clinically, International Union Against Cancer stage and gender were independent prognostic factors after curative surgery for rectal cancer.
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  • 99
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    Methods in cell science 22 (2000), S. 209-215 
    ISSN: 1573-0603
    Keywords: Apoptosis ; Campylobacter ; Cytometry ; Infection ; Macrophage ; Necrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We detail two methods for detection of cell death induced by infection of a human monocytic cell line with invasive Campylobacter bacteria. Staining with a natural ligand for exposed phosphatidylserine residues coupled with propidum iodide discriminated between apoptosis and necrosis. Additionally, cells infected with a bacterial strain expressing green fluorescent protein stained with dye sensitive to mitochondrial membrane potential demonstrated a direct association of bacteria with dying cells. Analyses of cells stained by these methods employing flow cytometry enumerated proportions of cell populations undergoing either apoptosis or necrosis after bacterial infection in vitro.
    Type of Medium: Electronic Resource
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  • 100
    Electronic Resource
    Electronic Resource
    Springer
    Methods in cell science 22 (2000), S. 225-231 
    ISSN: 1573-0603
    Keywords: Apoptosis ; Cell cycle ; DNA ; DNA hypoploidy ; Flow cytometry ; NCC ; Necrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Flow cytometric techniques have not been previously used on a routine basis to study teleost cell growth and development. In the present chapter, flow instrumentation and cell preparation protocols are given in order to provide evaluation criteria characteristic of different phases of the cell cycle. Flow cytometry is used as an analytical and diagostic tool to measure DNA ploidy as well as to measure alterations in cell cycle profiles characteristic of random DNA fragmentation (necrosis) compared to patterned DNA cleavage (apoptosis). The types of information obtained by flow analysis include the visualization of cell subpopulations with differing DNA content. For each identified nuclei subpopulation, the parameters of population size, fractions of nuclei in each phase of the cell cycle and computation of DNA ratios can be discerned. Data are presented of ex vivo prepared teleost nonspecific cytotoxic cells (NCC) at resting phase compared to NCC undergoing DNA hypoploid changes characteristic of apoptosis. These cells are compared with a teleost tissue cultured cell line maintained under optimum cell growth conditions versus cells undergoing necrotic cellular pathology. Finally, the requirements for optimum flow analysis are described. Techniques including gating strategies, voltage and gain settings, discrimination options and data collection and interpretation are provided.
    Type of Medium: Electronic Resource
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