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Bei Tumorpatienten sind tiefe Venenthrombosen und Lungenembolien – trotz angewandter primarpraventiver Masnahmen – haufige, die Lebensqualitat und Prognose beeintrachtigende Komplikationen. Aufgrund der oft oligo- bis asymptomatischen Entstehung ist ihre Diagnostik erschwert. Die Therapie unterscheidet sich wesentlich vom Vorgehen bei Nichttumorpatienten. Die Leitlinien empfehlen eine prolongierte, regelhaft uber 3 Monate hinausgehende Antikoagulation unter Berucksichtigung des Malignomverlaufs. Alternativ zur parenteralen Gabe niedermolekularer Heparine stehen nun auch evidenzbasiert orale Faktor-Xa-Inhibitoren fur die Initialtherapie und Sekundarprophylaxe zur Verfugung. Bei der patientenspezifischen Entscheidung uber Art, Dauer und Intensitat der Antikoagulation bedarf die therapiebedingte Zunahme eines bei Malignompatienten vorbestehend erhohten Blutungsrisikos besonderer Berucksichtigung.

Unter einer oralen Antikoagulation mit Vitamin-K-Antagonisten (VKA) mussen sich etwa 30 % der Patienten innerhalb von 2 Jahren einem chirurgischen Eingriff unterziehen. Dabei stellt sich die Frage nach der Notwendigkeit und Art einer periinterventionellen Uberbruckungstherapie mit Heparin. Wahrend fruher fast regelhaft von der Notwendigkeit dieses sogenannten Bridgings ausgegangen wurde, wird heute auf der Grundlage neuer Studienergebnisse eher diskutiert, wer uberhaupt noch ein Bridging benotigt. Die Sichtung und wissenschaftliche Einordnung der aktuell verfugbaren Empfehlungen und Studienergebnisse lassen die Schlussfolgerung zu, dass die Indikation zum Bridging mit Heparin heute eng gefasst werden muss, unter genauer Berucksichtigung und patientenindividueller Abwagung des Blutungs- und Thromboembolierisikos. Ein Bridging mit Heparin bleibt vor allem Patienten mit sehr hohem Risiko vorbehalten. Diese Ubersicht mochte daher Orientierung fur ein risikoadaptiertes periinterventionelles Vorgehen beim Management von Patienten bieten, die einer dauerhaften Antikoagulation mit VKA bedurfen.

Tumorpatienten haben ein erhohtes Risiko fur venose Thromboembolien (VTE). Niedermolekulare Heparine (NMH) werden aufgrund ihrer raschen und zuverlassigen Wirksamkeit zur Prophylaxe und Therapie von VTE bei Tumorpatienten bevorzugt eingesetzt. Wahrend die Prophylaxe perioperativ sowie bei stationaren Tumorpatienten unter Berucksichtigung bestehender Kontraindikationen etabliert ist, wird sie bei ambulanten Tumorpatienten nicht generell empfohlen. In der Initialtherapie und Sekundarpravention von akuten VTE sind NMH effektiver als unfraktionierte Heparine und Vitamin-K-Antagonisten. Die Sekundarprophylaxe mit NMH sollte zunachst fur 3–6 Monate durchgefuhrt und bei fortbestehendem Tumorleiden und niedrigem Blutungsrisiko weitergefuhrt werden. Der Einsatz der neuen direkten oralen Antikoagulanzien (DOAC) kann bei Tumorpatienten aufgrund fehlender Studiendaten gegenwartig nicht empfohlen werden.

Wir berichten uber eine 65-jahrige Patientin mit erworbener Hemmkorperhamophilie. Die erworbene Hemmkorperhamophilie ist durch die Ausbildung von Antikorpern (Inhibitoren) gegen Gerinnungsfaktoren charakterisiert. Durch eine Beeintrachtigung der plasmatischen Gerinnung kommt es bei primar Gerinnungsgesunden zu einer schweren erworbenen Blutungsneigung mit potenziell todlichem Verlauf. In der Diskussion wird auf die Pathophysiologie, Diagnostik und Therapie der Hemmkorperhamophilie eingegangen.

PURPOSE: Radiological-morphological response evaluation plays a major role in oncological therapy and studies for approval. Specific criteria have been developed for some tumor entities and chemotherapeutics. Application, limitations and definitions of the most frequently used criteria for tumor response evaluation will be presented. MATERIALS AND METHODS: Review based on a selective literature research. RESULTS: In clinical oncological therapy studies, WHO and RECIST are the most frequently used criteria to evaluate morphological therapy response. RECIST criteria have been modified recently, especially with respect to the evaluation of lymph nodes, and were published as RECIST 1.1 in 2009. All criteria were originally developed and defined to review clinical multicenter trials for approval. Using these criteria in a clinical situation, certain limitations have to be considered. To evaluate response, a baseline scan before therapy start is mandatory. Special tumor response criteria have been defined for some certain tumor entities. Oncologists and radiologists should define in advance which criteria are used before starting therapy. CONCLUSION: The use of defined criteria is very important in oncology response evaluation. In-depth knowledge of the criteria and their limits is required for correct usage.

The decision how to handle an antithrombotic treatment when an intervention during GI endoscopy is planned is influenced both by the risk of bleeding and by the thromboembolic risk when treatment is suspended. The risk of bleeding is negligible even when on oral anticoagulants in diagnostic procedures with standard forceps biopsies. Oral anticoagulation has to be stopped, however, when planning invasive procedures such as polypectomy or EPT. In the case of patients with a high risk of thromboembolic complications such as artificial valves in mitral position or atrial fibrillation with risk factors, one has to temporarily switch to anticoagulants with shorter action ("bridging"). Treatment with inhibitors of platelet function does not preclude procedures with a low risk of bleeding including forceps biopsy. Urgent procedures with a high risk of bleeding should be performed after stopping clopidogrel one week previously but only after consultation with the treating cardiologist. In the case of colonoscopy, in particular as a screening procedure, there are two options: 1) stopping oral anticoagulation (with or without bridging) or clopidogrel, respectively, or 2) continuing antithrombotic treatment and performing a second elective endoscopy for polypectomy with tapered antithrombotic medication if polyps are found which are not amenable to resection by biopsy forceps. The choice between these two options has to be made individually.

Haufig werden Tumorerkrankungen primar oder in ihrem Verlauf durch venose Thrombosen und/oder Lungenembolien kompliziert. Dies bedeutet fur die betroffenen Patienten ein erhohtes Mortalitatsrisiko: Venose Thromboembolien wurden in Untersuchungen als zweithaufigste zum Tode der Patienten fuhrende Komplikation identifiziert. Der Beitrag gibt einen Uberblick zur Prophylaxe und Behandlung von venosen Thromboembolien bei Tumorpatienten.

A 49-year-old man had for 30 years suffered from severe recurrent thromboembolism with leg-vein thrombosis, pulmonary emboli, mesenteric infarction, cerebrovascular accident, cerebral vein thrombosis, portal vein thrombosis and femoral artery occlusion requiring leg amputation. In addition to moderately increased clotting activation with single-fold positive demonstration of fibrin monomers and a D-dimer concentration of 1 mg/l platelet aggregation was increased and could not be influenced by aspirin, 300 mg daily. Despite aspirin there were recurrent transitory attacks of cerebral ischaemia. Fibrin monomers were threefold positive and D-dimer concentration was increased to 4 mg/l (elevated clotting activation). Ticlopidine administration (250 mg daily) reduced adenosine diphosphate-induced platelet aggregation by 30% without effect on collagen-induced platelet aggregation. In parallel to these changes the patient's general condition clearly improved: fibrin monomers were no longer demonstrated and the D-dimer level fell to 0.5 mg/l.

ZusammenfassungAusgehend von dem zunehmenden Verständnis der bei Patienten mit Sepsis beobachteten Gerinnungsstörung sowie den bisher erfolglosen Versuchen durch Modulation der Zytokinantwort die Prognose von Sepsispatienten zu verbessern, wurden in den vergangenen Jahren gerinnungstherapeutische Ansätze der Sepsisbehandlung intensiver untersucht. Während die Phase-III-Studien mit den Gerinnungsinhibitoren, Antithrombin und TFPI (tissue factor pathway inhibitor) für das Gesamtkollektiv der Patienten mit schwerer Sepsis keine Prognoseverbesserung zeigten, fand sich für rekombinantes humanes aktiviertes Protein C (rhAPC) eine signifikante, 19%ige relative Reduktion der Sterblichkeit. Weitere Analysen verdeutlichten, dass die Therapie mit rhAPC insbesondere bei Patientengruppen mit hoher Sterblichkeit im Plazeboarm zu klinisch relevanten Ergebnisverbesserungen führt.Die durch natürliche Gerinnungsinhibitoren bewirkte Hemmung der Gerinnselbildung, spiegelt sich in allen drei Studien in einer, z.T. signifikanten Zunahme der Sepsis-immanenten Blutungsneigung wider, wobei im Falle von Antithrombin die gleichzeitige Heparingabe das Blutungsrisiko deutlich erhöht und möglicherweise dem erhofften Antithrombineffekt auf die Patientenprognose entgegenwirkt. Hinweise auf einen möglicherweise positiven Effekt von Heparin in den Plazeboarmen einerseits, andererseits auf nachteilige Effekte von Heparin in den Therapiearmen (v. a. mit Antithrombin bzw. TFPI) führen zur kontroversen Diskussion des Nutzen/Risiko-Verhältnisses von Heparin in prophylaktischer Dosis bei Patienten mit schwerer Sepsis. Während die Bedeutung und optimale Applikation von Heparin bei schwerer Sepsis der weiteren Klärung bedarf, haben die Studiendaten zu rhAPC zur Zulassung dieses Therapieprinzips und seiner Verankerung in den Empfehlungen zur Behandlung von Patienten mit schwerer Sepsis geführt.

ZusammenfassungPräklinische und klinische Untersuchungen der vergangenen Jahre erweiterten das pathophysiologische Verständnis der bei Patienten mit schwerer Sepsis ablaufenden Störungen deutlich . Dabei wurde deutlich, dass die den septischen Krankheitsbildern zugrunde liegende Infektion im engeren Sinne für die Schwere und ungünstige Prognose der Sepsis weniger verantwortlich ist. Vielmehr ist es die außer Kontrolle geratene Reaktion des Organismus auf diese Infektion, die sich bei nicht (mehr) lokalisierter Infektion in Form einer im Wesentlichen Zytokin-vermittelten Entzündungsreaktion dem systemischen inflammatorischen Response-Syndrom mit seinen Folgen widerspiegelt.Die im Rahmen dieses Syndroms freigesetzten Mediatoren, z.T. in Zusammenwirkung mit Produkten aus infektiösen Mikroorganismen, führen auch zu einer systemischen Aktivierung der Hämostase. Die Aktivierung von Monozyten/Makrophagen sowie die des Endothels stehen dabei im Zentrum des pathophysiologischen Modells. Die davon ausgehende Aktivierung von plasmatischen Kaskadensystemen betreffen auch Gerinnungs-und Fibrinolysesystem, wobei die bei Sepsis beobachtete Gerinnungsaktivierung und Fibrinolysehemmung ihrerseits mit Leukozyten und Endothel interagiert und zur zunehmenden Schädigung der Mikrozirkulation beiträgt. Als deren klinisches Korrelat können Organdysfunktionszustände aufgefasst werden. Es kommt zu einem individuell unterschiedlichen Nebeneinander von überschießender Fibrinbildung, Faktoren-, Inhibitoren-und Thrombozytenverbrauch sowie Störungen des Fibrinolysesystems. Klinisch kann dies neben Organdysfunktionen zu einer disseminierten intravasalen Gerinnung, z.T. mit Blutungskomplikationen, führen.

A resurgence of sexual risk taking, STDs, and HIV incidence has been reported among men who have sex with men (MSM) in several countries. We asked 113 MSM in 12 focus groups conducted in five California cities to identify factors leading to increased risk taking and assess prevention messages to reduce risk in this population. Participants perceived that HIV risk taking has increased because (1) HIV is not the threat it once was due to more effective therapies, (2) MSM communicate less about HIV, and social support for being safe has decreased, and (3) community norms have shifted such that unsafe sex is more acceptable. The prevention messages ranked most likely to motivate risk reduction encouraged individuals to seek social support from friends. Themes ranked least likely to succeed were those that described the negative consequences of HIV or reinforced existing safer sex messages.

Background: For monitoring of arterial blood pressure (ABP) during whole body hyperthermia (WBH) different methods have been recommended. This investigation was performed to evaluate the agreement of invasive measurements at various sites, and to compare invasive and non-invasive methods of ABP monitoring under conditions of a heat-induced extreme vasodilation. Methods: In 19 patients, 48 treatments with WBH were performed. Measurements of ABP in the radial and femoral artery by oscillometry and by sphygmomanometry were taken at four temperature levels during WBH (37, 40, 41.8 and 39°C). Results: Significant differences were observed between invasive and non-invasive methods for systolic ABP, with higher values for non-invasive measurements. When compared with both invasive measurements for diastolic blood pressures, sphygmomanometry gave higher values and oscillometry gave lower values. Sphygmomanometry also showed higher values for mean ABP compared with all other techniques, while measurements in radial and femoral artery and by oscillometry only differed by approximately 5 mmHg. Conclusion: The mean arterial pressure and not the systolic and/or diastolic pressure should guide hemodynamic management during WBH. The sphygmomanometric technique is not recommended for use during hyperthermia.

SUMMARY In developed countries there is an age dependent increasing incidence of deep vein thrombosis. Hereditary thrombophilia is usually suspected by the clinical constellation and anamnestic informations. For economical reasons usually laboratory testing should be avoided if the results will not change directly the therapeutic process. But for hereditary defects consequences for the patient in future and for relatives should be taken into account especially as more selective strategies for prophylaxis and treatment have to be expected by increasing information in that field of research. As deficiencies of anticoagulant proteins (PC, PS, AT) have an impact on anticoagulant treatment, the indication for testing should not be held too strict. Time point for diagnostic procedures should be early after a thromboembolic event as negative results exclude hereditary defects definitely which allows the planning of the aimed treatment duration. After first onset of deep vein thrombosis, even in presence of hereditary coagulation defects the duration of anticoagulation usually depends on the clinical and anamnestic signs for a thrombophilic tendency of the individual patient. First publications suggest the need for prolonged anticoagulation of carriers with combined defects, showing an elevated rate of re-thrombosis after the first thromboembolic event, when anticoagulation is stopped. Every ongoing anticoagulation should be checked repeatedly in the sense of a risk -benefit evaluation even for patients with a thrombophilic tendency and should be adapted to actual publications.

We report a 58-year-old female patient with the suspected diagnosis of ovarian cancer. Upon surgical exploration, examination of the appendix revealed the histological diagnosis of primary mucinous adenocarcinoma. This is an unusual consideration in the differential diagnosis of the ovarian cancer. We discuss the diagnosis, classification and treatment of the cancer of the appendix in relation to ovarian cancer.

ZusammenfassungVon den verschiedenen, zur Behandlung der tiefen Venenthrombose zur Verfügung stehenden Optionen, stellt die akute Antikoagulanzientherapie mit Heparinen, insbesondere niedermolekularen Heparinen, gefolgt von der frühzeitig überlappend eingeleiteten oralen Antikoagulation, das Standardvorgehen dar. Thrombolyse, Thrombektomie und Implantation von Kavaschirmfiltern kommen nur bei wenigen Patienten sinnvoll in Betracht. Während somit die medikamentöse Therapie mit Heparinen und Cumarinen die medikamentöse Standardbehandlung darstellt, sind begleitende Therapiemaßnahmen, wie die Notwendigkeit zur initialen Immobilisation der Patienten sowie zur Kompressionsbehandlung bei tiefen Venenthrombosen in ihrer Wertigkeit ungesichert und Gegenstand kontroverser Diskussionen. Darüber hinaus werden die optimale Dauer der oralen Antikoagulation, der Stellenwert einer prolongierten Therapie mit niedermolekularen Heparinen sowie der Stellenwert neuerer Antithrombotika wie Antithrombine, Faktor-Xa-Hemmstoffe und »Tissue factor pathway inhibitor« diskutiert.

ZusammenfassungBis zur Entdeckung und Beschreibung der Resistenz gegenüber aktiviertem Protein C (»APC-Resistenz«) durch Dahlbeck et al. 1993 (1) blieb die Ursache einer familiären thrombophilen Diathese bei einem Großteil der Patienten ungeklärt. Bei weniger als einem Viertel der Patienten mit Häufung thrombembolischer Ereignisse konnten bis dahin vererbare Defekte in den bekannten Inhibitoren der plasmatischen Gerinnung nachgewiesen werden. Heute ist die familiäre APCResistenz aufgrund einer Faktor-V-Mutation mit verminderter Inaktivierbarkeit von Faktor V durch APC mit einer Inzidenz von etwa 5% der Bevölkerung als der wichtigste thrombophile Risikofaktor in der nord- und mitteleuropäischen Bevölkerung anzusehen. Bei familiärer thrombophiler Diathese zeigen bis zu 40% der Patienten diese Störung. Im Gegensatz zur initial von Dahlbeck beschriebenen funktionellen Methodik lassen sich mit modernen, einfach und schnell durchführbaren Gerinnungstesten zuverlässige Aussagen über das Vorliegen der Faktor-V-Punktmutation sowie den heterozygoten oder homozygoten Merkmalträgerstatus machen. Die Erkennung zusätzlicher hereditärer oder erworbener Risikofaktoren und ihrer Gewichtung tragen dazu bei, die Strategie einer primären oder sekundären Thromboseprophylaxe festzulegen.

Aufgrund der zentralen Bedeutung der Leber als Syntheseort wesentlicher Hamostasekomponenten und ihrer funktionellen Rolle im retikoendothelialen System fuhren Lebererkrankungen laboranalytisch zu verminderten Werten der hepatisch synthetisierten Hamostasefaktoren und Zeichen eines vermehrten Umsatzes der plasmatischen Gerinnung und Fibrinolyse. Meist resultiert ein labiles Hamostasegleichgewicht auf niedrigem Niveau. Bei kompensierten Hamostasestorungen ergibt sich in der Regel keine Notwendigkeit zur symptomatischen Therapie der Hamostasestorung. Wird dieser labile Zustand durch verschiedene Noxen weiter gestort, treten klinisch meist Blutungen mit mehr oder weniger Verbrauchskoagulpathie- oder Hyperfibrinolyse-ahnlicher Befundkonstellation und nur ausnahmsweise Thromboembolien auf.

Heparin-coated systems for extracorporeal lung-assist (ECLA) were developed to reduce hemorrhagic risk by lowering the systemic heparinization, monitored by global tests, e.g. activated coagulation time (ACT) and activated partial thromboplastin time (APTT). Since this strategy gives no insight into procoagulant states, five ARDS patients receiving ECLA with heparin-coated systems were investivated for changes in coagulation using both global and extended tests. During ECLA onset the APTT and ACT were within or near normal ranges, platelets decreased 76.5% within 48h, fibrinogen decreased 28.7%, thrombin-antithrombin-III complexes were elevated before ECLA (53 μg/L), but demonstrated an additional peak (238 μg/L), plasminogen-activator-inhibitor-1 increased 12-fold, and the C1-inhibitor dropped 14.1%. In conclusion, after the onset of ECLA from a previous prethrombotic state, the precoagulant, anticoagulant, fibrinolytic and complement systems were activated in a similar way to that reported for non-heparinized systems with high-dose heparin. This was however only monitored by an extended test panel which was unable to predict thromboembolic events during ECLA.

To assess the technical feasibility, safety and clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) for achieving local tumour control (LTC) in isolated lymph node metastases.From January 2008 to December 2011, 10 patients (six males and four females) with isolated nodal metastases were treated with CT-HDRBT. Five lymph node metastases were para-aortic, three were at the liver hilum, one at the coeliac trunk and one was a left iliac nodal metastasis. The mean lesion diameter was 36.5 mm (range 12.0-67.0 mm). Patients were followed up by either contrast-enhanced CT or MRI 6 weeks and then every 3 months after the end of treatment. The primary end point was LTC. Secondary end points included primary technical effectiveness rate, adverse events and progression-free survival.The first follow-up examination after 6 weeks revealed complete coverage of all nodal metastases treated. There was no peri-interventional mortality or major complications. The mean follow-up period was 13.2 months (range 4-20 months). 2 out of 10 patients (20%) showed local tumour progression 9 and 10 months after ablation. 5 out of 10 patients (50%) showed systemic tumour progression. The mean progression-free interval was 9.2 months (range 2-20 months).CT-HDRBT is a safe and effective technique for minimally invasive ablation of nodal metastases.CT-HDRBT of lymph node metastases is feasible and safe. CT-HDRBT might be a viable therapeutic alternative to obtain LTC in selected patients with isolated lymph node metastases.

Thrombomodulin is a surface protein of vascular endothelial cells. A smaller form of thrombomodulin in blood and urine, the soluble (s)thrombomodulin, appears to be derived from injured endothelial cells or to be proteolytically cleaved from thrombomodulin by proteases. Several in vitro and in vivo studies have suggested (s)thrombomodulin as a marker of endothelial damage. In orthotopic liver transplantation, platelet and leukocyte activation as well as prothrombin activation are suspected of being caused by damaged endothelial cells in the graft liver. We determined (s)thrombomodulin antigen as well as thrombin-antithrombin III complexes, protein C, and antithrombin III activities in the course of 23 orthotopic liver transplantations. Samples were taken at 7 different time-points intraoperatively, as well as out of the perfusate released from the graft liver vein during the flushing procedure with arterial blood prior to the opening of the hepatocaval anastomosis. Levels of (s)thrombomodulin antigen and thrombin-antithrombin III complexes showed a significant increase with reperfusion of the graft liver and levels in the perfusate were higher (both: P = 0.0001) than the corresponding systemic levels. In parallel, antithrombin III decreased significantly with reperfusion and perfusate levels of antithrombin III and protein C activities were lower in the systemic circulation (both: P = 0.0001). In conclusion, high levels of (s)thrombomodulin antigen in the early reperfusion phase and in the perfusate strongly indicate endothelial damage to the graft liver vascular bed, paralleled and followed by signs of prothrombin activation.

BACKGROUND: Photodynamic virus inactivation of fresh-frozen plasma (FFP) may result in its impaired coagulation capability. STUDY DESIGN AND METHODS: Double-volume plasmapheresis samples from 11 donors were divided in pairs of 250 mL. One group underwent methylene blue (MB) phototreatment (MB-FFP). The other group was treated according to the standards of the American Association of Blood Banks for preparation and storage of FFP. Parameters of hemostasis and clinically important plasma proteins were tested in native plasma, thawed MB-FFP, thawed FFP, and twice-frozen and thawed FFP (FFP-II). RESULTS: Mean activities of factor V (73.4 vs. 94.5%; p < 0.01), factor VIII (58.1 vs. 86.7%; p < 0.001), and fibrinogen (1.8 vs. 2.8 g/L; p < 0.001) were reduced in MB-FFP as compared to those in FFP. The comparison of MB-FFP to FFP-II revealed reduced activities of factor VIII (58.1 vs. 85.2%; p < 0.001) and fibrinogen (1.8 vs. 2.8 g/L; p < 0.001) but no changes in factor V. Activated partial thromboplastin time in MB-FFP was prolonged beyond the upper normal range (+5.3 sec; p < 0.001) and prothrombin time increased in MB-FFP versus FFP (+0.96 sec; p < 0.001). CONCLUSION: MB phototreatment reduces the in vitro coagulation capacity of FFP, most likely as a result of the effects of an additional freezing and thawing procedure and photooxidation-induced protein damage.

Background Male circumcision has been shown to reduce the transmission of HIV from women to men through vaginal sex by approximately 60%. There is concern that men may engage in risk compensation after becoming circumcised, diminishing the benefits of male circumcision. Methods and Findings We conducted qualitative interviews with 30 sexually active circumcised men in Kisumu, Kenya from March to November 2008. Most respondents reported no behavior change or increasing protective sexual behaviors including increasing condom use and reducing the number of sexual partners. A minority of men reported engaging in higher risk behaviors either not using condoms or increasing the number of sex partners. Circumcised respondents described being able to perform more rounds of sex, easier condom use, and fewer cuts on the penis during sex. Conclusions Results illustrate that information about MC's protection against HIV has disseminated into the larger community and MC accompanied by counseling and HIV testing can foster positive behavior change and maintain sexual behavior.

Confusion still exists in the diagnosis of drug-induced immune haemolysis (DIH). The aim of this study was to demonstrate antibodies specific to 5-fluorouracil (5-FU) in a patient with fatal immune haemolysis (IH). The case of a patient who died due to protracted IH is described. A 57-year-old female underwent treatment with oxaliplatin, 5-FU and folinic acid due to cholangiocarcinoma. Following drug administration, she was transfused because of a mild non-haemolytic anaemia and died following haemolysis. Serological testing including antibody screening, direct antiglobulin test and detection of drug-dependent antibodies was performed using standard techniques. The patient's serum was observed to be red in colour due to the presence of free haemoglobin prior to and following blood transfusion, and contained antibodies reactive with RBCs only in the presence of urine from several patients treated with 5-FU (ex vivo antigens). Drug-induced immune haemolysis (DIH) and metabolite-dependent antibodies should always be taken into consideration when a patient being administered any type of drug develops haemolysis.

ZusammenfassungDie Szintigraphie mit radioaktiv markierten Antikörpern findet zunehmend Anwendung bei verschiedenen Tumoren. In der vorliegenden prospektiven Studie werden die Grundzüge der Radioimmunoassay (RIS) und ihre Wertigkeit in der Diagnostik und Verlaufskontrolle des Ovarialkarzinoms im Vergleich zur Computertomographie (CT) und zur Second Look-Operation anhand von 27 Patientinnen (Primärdiagnostik) und 52 Patientinnen (Verlaufskontrolle und Re-Staging nach chirurgischer und Chemotherapie) dargestellt. Die Ergebnisse werden mit der Immunhistochemie und dem CA125-Serum-Spiegel verglichen. Wir fanden in der Primärdiagnostik eine Sensitivität für die RIS von 100% bei einer Spezifität von 60%, in der Rezidivdiagnostik von 75% bzw. 68%. Es zeigte sich, daß die RIS besonders zum Nachweis der Peritonealkarzinose gegenüber der CT eine höhere Sensitivität besitzt bei geringerer Sensitivität für Organmetastasen. Dennoch können CT und RIS die »Second Look«-Operation nicht ersetzen.

Syringe exchange programs (SEPs) have been shown to be highly effective in reducing HIV transmission among injection drug users (IDUs). Despite this evidence, SEPs have not been implemented in many communities experiencing HIV epidemics among IDUs. We interviewed 17 key informants in nine U.S. cities to identify factors and conditions that facilitated or deterred the adoption of SEPs. Cities were selected to represent diversity in size, geographic location, AIDS incidence rates, and SEP implementation. Key informants included HIV prevention providers, political leaders, community activists, substance use and AIDS researchers, and health department directors. SEPs were established by one or more of three types of implementation models: (a) broad community coalition support, (b) community activist initiative, and (c) top-down decision making by government authorities. In each model, coalition building and community consultation were critical steps for the acceptance and sustainability of SEPs. When others were not prepared to act, community activists spearheaded SEP development, taking risks in the face of opposition, but often lacked the resources to sustain their efforts. Leadership from politicians and public health officials provided needed authority, clout, and access to resources. Researchers and scientific findings lent force and legitimacy to the effort. Rather than adopting adversarial positions, successful SEP implementers worked with or avoided the opposition. Fear of repercussions and lack of leadership were the greatest barriers to implementing SEPs. Communities that successfully implemented SEPs were those with activists willing to push the agenda, public officials willing to exercise leadership, researchers able to present authoritative findings, and proponents who effectively mobilized resources and worked to build community coalitions, using persistent but nonadversarial advocacy.

This article examines gender differences related to why 66 injection and noninjection drug users tested for HIV. Study participants from three northern California counties underwent an open-ended qualitative interview covering: access to HIV testing, the meaning of HIV testing and test results, drug and sexual risk behaviors, and behavior changes associated with HIV testing, as well as a brief quantitative survey. The responses were analyzed using the following categories: (a) financial incentives for testing, (b) concerns related to family members and significant others, and (c) personal anxieties due to lack of knowledge of HIV status. Analyses showed that gender differences exist regarding reasons for HIV testing. The most significant finding was that women were motivated to test with regard to concerns related to family and significant others in their life more so than men, particularly during pregnancy. The impetus to test for many individuals was dependent on a social setting, such as jail, hospital, or drug rehabilitation program. Further research examining the motivational factors why drug users test for HIV can provide valuable information for outreach and marketing of HIV counseling-and-testing services.

A common mutation in the factor V gene, the Leiden mutation, is the most frequent genetic cause of resistance to activated protein C (APC). Recent studies have shown that the prevalence of APC resistance is associated with severe pregnancy-induced hypertension (PIH). Our objective was to determine whether the factor V Leiden mutation is more prevalent in patients who developed severe PIH than in normotensive pregnant women. In 70 women with a history of severe PIH, of whom 15 had pre-eclampsia, we investigated common coagulation factors as well as APC resistance (factor V related). We found that seven of these 70 women showed low values for APC. Out of these, five were heterozygous and none was homozygous for factor V Leiden mutation. In a control group of normotensive pregnant women we found a 3.0% rate of APC resistance and a 3.0% rate of carriers of the Leiden mutation. These results indicate a significantly higher prevalence of both APC resistance and factor V Leiden mutation in women with severe PIH. Placental infarctions and micro-embolisms are considered to be one of the principle pathophysiological changes in severe PIH. Our results suggest that APC resistance is a risk factor for severe PIH, in addition to its well-known role in macrothrombo-embolism.

Antithrombin (AT, fruher Antithrombin III) gehort zur Gruppe der Serinproteaseinhibitoren (Serpine), deren wesentliche Funktion in der Eliminierung im Uberflus gebildeter Proteasen besteht [21]. Das Antithrombin-Gen ist auf dem langen Arm von Chromosom 1 lokalisiert und enthalt bei einer Grose von etwa 13500 Basen 7 Exone [1, 2, 11, 12, 13]. Das definitive Genprodukt stellt ein Glykoprotein mit einem Molekulargewicht von 58200 dar, wobei die 432 Aminosauren umfassende Polypeptidkette das aktive Zentrum an der Position Arginin 393 bis Serin 394 zeigt. Das Protein enthalt drei intramolekulare Disulfidbrucken und vier Glykosilie-rungspositionen. Antithrombin ist ein wichtiger zirkulierender Regulator des Hamostasesystems, wobei es, ohne das es einer vorangehenden Aktivierung bedarf, zirkulierende Serinproteasen inhibiert. In Analogie zu anderen Serpinen, erfolgt die Proteinaseinak-tivierung durch zwei Schritte: nach Komplexbildung spaltet die Protease die Argenin (393)-Serin (394)-Bindung, wodurch es zur Konfirmationsanderung von Antithrombin und irreversiblen Protease-Inhibitor-Komplexbildung kommt [21]. Heparin - durch Bindung im aminoterminalen Bereich des Inhibitors — beschleunigt die Antithrombin-Proteinase-Komplexbildung wesentlich, wobei unter optimalen Bedingungen eine mehr als bis zu 1000-fache Beschleunigung der Inaktivierung von Thrombin durch Antithrombin berichtet wird.

Bleeding complications in transplantation surgery result both from the complexity of the operation and from specific hemostatic changes caused by the underlying organ defect. Thus, in the absence of secondary organ damage, the risk of bleeding in cardiac transplantation is basically the same as in coronary bypass surgery. The hemostatic defect that occurs as a result of decompensated heart failure with consequent multiple organ failure, sometimes aggravated by extracorporeal cardiopulmonary bypass with anticoagulation, greatly compounds the risk of bleeding during the subsequent transplantation. While we are just beginning to understand the pathophysiology of these problems and their therapeutic implications, we have a much better awareness of the problems involved in liver transplantation. We shall also consider bone marrow transplantation, whose basic principles differ substantially from those of solid organ transplantations.

We present a case of a 24 year old woman who became pregnant (twins) after human menopausal gonadotrophin (HMG)-induced ovarian stimulation, in-vitro fertilization (IVF) and subsequent embryo transfer. She developed a right internal jugular vein thrombosis as a complication of severe ovarian hyperstimulation syndrome (OHSS) 28 days after embryo transfer. The thrombosis developed in spite of anticoagulation with low-dose heparin. Later a resistance to activated protein C (APC) or Dahlback disease was diagnosed. Due to a new test procedure (accelerin inactivation test), the diagnosis was possible even under anticoagulation treatment. The coincidence of hyperstimulation and internal jugular vein thrombosis with the concurrent diagnosis of resistance to APC has not been published previously. The benefit of general screening for resistance to APC before admission to the IVF programme should be weighed. Targeted selection of a group of high-risk women would therefore be made possible.

PURPOSE: To evaluate magnetic resonance (MR) imaging-guided laser-induced thermotherapy (LITT) of liver metastases. MATERIALS AND METHODS: In a phase II study, 20 patients with 33 metastases from colorectal carcinoma (75%) or other primary tumors (25%) underwent LITT. MR thermometry performed with fast low-angle shot sequences was used to monitor therapy on-line, and dynamic and static contrast material-enhanced MR images enabled estimation of the degree of resultant necrosis. Follow-up studies were performed 3 months after thermotherapy. RESULTS: The thermosequences enabled accurate on-line monitoring in 85% of lesions. In 69% of lesions 20 mm in diameter or smaller, contrast-enhanced MR images depicted substantial necrosis, with a local tumor control rate of 69% after 6 months and 44% after 12 months. Among lesions larger than 20 mm, necrosis was frequently incomplete, with a local control rate of only 41% after 6 months and 27% after 12 months. CONCLUSION: MR imaging-guided LITT of liver metastases is ...

In contrast to hereditary platelet function defects acquired abnormalities of platelet function are very common. Platelet dysfunction, as defined by ex vivo tests or the bleeding time test, is observed after the intake of many drugs and common foods, as well as in pathological conditions such as hematological, renal or hepatic diseases, extracorporeal circulation or in the presence of antiplatelet antibodies. In addition to quantitative platelet disorders, qualitative platelet defects may result in an increased risk of bleeding or thromboembolism. Furthermore platelet function may be important in the progression of cardiovascular disease. However, evaluation of platelet function is far from being standardized and the clinical importance of a given platelet dysfunction is frequently uncertain. Thus tailoring (defining) a treatment for an individual patient is difficult.

Introduction: Biliary carcinomas, especially those of the gallbladder, are the 7th most common form of cancer in women and the 10th most common form in men. Carcinomas of the extrahepatic bile ducts a