bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and geographic distribution of haemophilia in Costa Rica
Authors: Arroyo J. , Salazar-Sánchez L. , Jiménez-Cruz G. , Chaverri P. , Arrieta-Bolaños E. , Morera B. 
Published: March 2018

SummaryHaemophilia is the most frequent hereditary haemorrhagic illness and it is due to the deficiency of coagulation factors VIII (haemophilia A, HA) or IX (haemophilia B, HB).The prevalence of this disease varies according to the country, those having better survival rates having also higher prevalences. Specifically in Costa Rica, there are around 130 HA and 30 HB families. This study reports the prevalence and a spatial distribution analysis of both types of the disease in this country. The prevalence of haemophilia in this country is 7 cases per 100 000 men, for HA it is 6 cases per 100 000 and for HB it is 1 case per 100 000 male inhabitants. The prevalence of this disease is low when compared with other populations. This low prevalence could be due to the many patients that have died because of infection with human immunodeficiency virus during the 1980s. The prevalence of haemophilia in Costa Rica is almost one half of that present in developed countries. Nevertheless, the ratio between HA and HB follows world tendency: 5 : 1. In this study, nationwide geographical distribution maps were drawn in order to visualize the origin of severe cases and how this influences the pattern of distribution for both types of haemophilia. By means of these maps, it was possible to state that there is no association between the sites of maximum prevalence of mutated alleles and ethnicity. With this study, haemophilia prevalence distribution maps can be used to improve efforts for the establishment of hemophilia clinics or specialized health centers in those areas which hold the highest prevalences in this country. Also, this knowledge can be applied to improve treatment skills and offer the possibility of developing focused genetic counseling for these populations.
Isometrische Maximalkraftmessungen der Quadrizepsmuskulatur
Authors: Tutzschke R. , Czepa D. , Gabriel H.H.W. , Hilberg T. , Herbsleb M. 
Published: March 2018

SummaryThe quadriceps femoris muscle (QF) plays an important role in locomotion. However, assessing the total number of attempts to evaluate the maximal isometric strength (Fmaxiso) regarding reliability and feasibility remain less characterised. Patients, methods: 28 patients with haemophilia (H) (26 severe, 2 moderate) and 27 healthy controls (C) matched for age (H: 44 ± 11, C: 42 ± 12) and anthropometric data were measured separately for the left and right leg for Fmaxiso of QF using m3 diagnos (SCHNELL®). We repeated the Fmaxiso measures after 48 h in 14 H and 13 C. Results: The system m3 diagnos showed strong reliability (ICC = 1.0; SEM = 0.0; CA = 1.0). H and C demonstrated significant differences in Fmaxiso (H r = 153 Nm, l = 164 Nm; K r= 289 Nm, l = 280 Nm; p ≤ 0.001). Additionally, H and C revealed significant differences between the 1st and 3rd to 6th attempts. No differences were observed between the 3rd, 4th, 5th and 6th attempts. Conclusion: Both groups showed high test-retest-reliability of Fmaxiso (ICC/SEM: H l = 0.98/7.1 r = 0.99/4.9; K l = 0.69/11.3 r = 0.95/5.8). Starting from the 3rd attempt, reliable measurements of the Fmaxiso in patients suffering from severe haemophilia are feasible.
Postoperative bleeding in paediatric ENT surgery
Authors: Olivieri M. , Stelter K. , Eberl W. , von Kries R. , Kurnik K. , Bidlingmaier C. 
Published: March 2018

SummaryBleeding after ear-nose-and throat surgery in children is a serious complication. With the help of the German Surveillance Unit for Rare Paediatric Disorders (Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland; ESPED) a two year survey was performed to record the incidence, severity, reasons and treatment of haemorrhages. During the study period, 1069 bleeds were reported from 720 paediatric hospitals and departments of otorhinolaryngology after adenoidectomy and tonsillectomy. 713 reports could be analyzed. Two deaths occurred after adenoidectomy. Although laboratory screening was performed in more than 70% of all cases, bleeding complications were neither foreseeable nor preventable. Inherited coagulopathies were rare and in most cases not detected, neither by laboratory screening nor by taking a history. Since preoperative measures cannot help much to improve the situation, all efforts have to be taken to improve the postoperative period, especially since more than 20% of the hemorrhages occurred during weekends. Guidelines on postoperative care and behaviour should therefore be implemented and parents and patients must be informed on bleeding risks and on what to do in case of emergency. If bleeding occurs, extensive coagulation testing is mandatory.
Immuntoleranzinduktion mit hoch dosiertem FVIII und intravenösen Immunglobulin-Pulsen
Authors: Pinkwart C. , Haase R. , Merkel N. , Forsberg D. , Mauz-Körholz C. , Stiefel M. 
Published: March 2018

SummaryThe development of neutralizing allo-antibodies against factor VIII (FVIII) or FVIII inhibitors is a severe complication in the treatment of haemophilia A. About 25% of the children with severe haemophilia A develop FVIII inhibitors. Here we report on a boy with severe haemophilia A and intron 22 inversion of the FVIII gene who was diagnosed at ten months of age. After 16 exposure days to FVIII (81 days after initial exposure) he developed a FVIII inhibitor (maximum: 9.76 BU/ml). Therapy: We started immune tolerance induction (ITI) according to the Bonn protocol with high dose plasma derived FVIII concentrate (100 IU per kg body weight) twice daily. For additional inhibitor elimination treatment the patient received intravenous immunoglobulin (ivIg) at a dose of 1–2 g/kg body weight every 4 to 6 weeks. After start of treatment a rapid decline of the inhibitor level was observed, nevertheless low FVIII inhibitor levels persisted (<5 BU/ ml). Furthermore, the FVIII half-life was still accelerated. However, after every course of ivIg the inhibitor level declined and FVIII half-life was prolonged. Currently, the FVIII half-life is approaching normal values after more than seven months of ITI duration. Conclusion: Additional application of immunoglobulin is beneficial for immune tolerance induction.
Rationale for heparin treatment of colon cancer
Authors: Ornstein D. L. , Zacharski L. R. 
Published: March 2018

SummaryIt is widely known that the systemic blood coagulation mechanism is often activated in malignancy, leading to an increased incidence of vascular thromboses in patients with cancer. It is not widely appreciated, however, that products of the coagulation mechanism may also support tumor growth and dissemination. Interest in this approach to cancer therapy has surged recently because of mounting evidence that the familiar anticoagulant drug, heparin, may impede tumor progression. Heparin has the capacity to modify angiogenesis, growth factor and protease activity, immune function, cell proliferation and gene expression in ways that may block malignant dissemination. Clinical trials in which heparin has been administered to a broad spectrum of patients to prevent or treat thrombosis have unexpectedly shown improvement in survival in the subset of patients with malignancy entered to these studies. Meta-analyses of clinical trials comparing unfractionated (UF) versus low molecular weight (LMW) heparin treating venous thromboembolism suggest that there may be substantial improvement in cancer outcome in patients with malignancy randomized to receive LMW heparin. These findings provide a rationale for definitive clinical trials of LMW heparin in cancer, and the results of several such studies that are currently underway are awaited with interest.
Tumorangiogenese: Neue Ansätze in der Krebstherapie
Authors: Marmé D. 
Published: March 2018

ZusammenfassungSolide Tumoren können ohne Versorgung über das Blutgefäßsystem nur bis zu einem Durchmesser von wenigen Millimetern wachsen. Erst wenn der Tumor beginnt, angiogene Wachstumsfaktoren zu produzieren, setzt die Neubildung von Gefäßen durch Aussprossen aus dem bestehenden Gefäßsystem ein. Der Tumor wächst, und Krebszellen gelangen durch die neuen permeablen Kapillaren in den Kreislauf. Der »vascular endothelial growth factor« (VEGF) ist der für die Tumorangiogenese bedeutsamste angiogene Wachstumsfaktor. Er wird von fast allen soliden Tumoren gebildet. Seine Rezeptoren werden nur auf Gefäßendothelien und vornehmlich auf solchen in der Nähe des Tumors exprimiert. Das VEGF/VEGF-Rezeptorsystem bietet sich als Angriffsart für eine antiangiogene Krebstherapie an. Experimentelle Therapieversuche zeigen, dass eine Hemmung der VEGF-vermittelten Endothelzellaktivierung sowohl das Wachstum des Primärtumors als auch die Metastasierung hemmt. Entsprechende therapeutische Strategien werden derzeit klinisch erprobt.
Tumorwachstum und Hämostase
Authors: Steffens Chr. , Zurborn K.-H. , Gieseler F. , Bruhn H. D. 
Published: March 2018

ZusammenfassungHämostaseologische Vorgänge wie Aktivierung von Thrombozyten und von plasmatischer Gerinnung können für das Auftreten von Thromboembolien bei Malignomen entscheidend sein. In klinischen Studien wurden signifikante Korrelationen zwischen zytostatischer Chemotherapie und Strahlentherapie einerseits und dem Auftreten von Thromboembolien andererseits dokumentiert.Nach neueren klinischen Studien kommt es bei angeborener Thrombophilie zu einer verstärkten Reaktion des Hämostasesystems auf ein Tumorleiden mit der Konsequenz einer erhöhten Thromboemboliefrequenz (bei APC-Resistenz, bei Mutation des Prothrombin-Gens, bei Protein-C-Mangel, bei Protein-S-Mangel, bei Antithrombin-Verminderung und bei erhöhtem Lipoprotein a). Durch eine angemessene Antikoagulation können thromboembolische Komplikationen, zumindest partiell, verhindert werden.Die vermehrte Freisetzung von Thrombin bei metastasierenden Malignomen hat offensichtlich jedoch noch weitere Konsequenzen: Thrombin wirkt nicht nur als Enzym des Hämostasesystems, sondern auch als Gewebshormon (Wachstumsfaktor), so dass Thrombin bei verschiedenen Tumorzelllinien eine verstärkte Proliferation induzieren kann. In neueren Untersuchungen konnten wir jetzt zusätzlich in Zellkulturen demonstrieren, daß die Vorinkubation von Leukämiezellen (HL-60) mit Thrombin bei bestimmten Konzentrationen zu einer Resistenz dieser Zellen gegenüber Idarubicin führt und damit auch, zumindest partiell, die durch Idarubicin ausgelöste Apoptose beeinträchtigt. Damit wäre eine mögliche Erklärung für die positiven Effekte einer kombinierten Chemotherapie und Antikoagulation gefunden, welche durch weiterführende Zellkulturversuche und klinische Studien erhärtet werden müsste.
Zytostatische Chemotherapie: Einflüsse auf das Hämostasesystem
Authors: Giagounidis A. , Germing U. , Haas R. 
Published: March 2018

ZusammenfassungGerinnungsstörungen bei bösartigen Erkrankungen sind durch vielfältige Wechselwirkungen zwischen Tumorzellen, deren Produkten und dem Organismus bedingt. Diese führen zu einer verschieden stark ausgeprägten Beeinträchtigung der Hämostase und können dadurch Thromboembolien oder Blutungen verursachen. Die zugrundeliegenden Mechanismen der Einflussnahme von Zytostatika auf das Gerinnungssystem werden beschrieben. Die Daten zur prophylaktischen Antikoagulation während Chemotherapie sind widersprüchlich.
Ausgeprägte Blutungsneigungen
Authors: Meili E. O. 
Published: March 2018

ZusammenfassungIn dieser Übersicht werden die pathophysiologischen und molekulargenetischen Zusammenhänge erwähnt, die zu schweren Blutungsneigungen durch Gerinnungsfaktormängel bzw. -inhibitoren führen. Diagnostische Besonderheiten, Verlauf und Behandlung einzelner Störungen werden besprochen. Die Übersicht über die Hämophilie A und B umfasst die Konduktorinnenproblematik, Substitutionsbehandlung, ergänzende blutstillende Therapien mit Antifibrinolytika und DDAVP, die spezifische Behandlung der typischen Blutungen, Probleme der Hemmkörperbildung und zukünftige Behandlungsmöglichkeiten. Die autosomal vererbten, homozygoten Blutungsneigungen von-Willebrand-Syndrom (VWS) Typ 3, Afibrinogenämie, Faktor(F)-XIII-, FVII- und FXI-Mangel haben je ihre Spezifitäten, welche für die Behandlung bestimmend sind. Bei den erworbenen Blutungsneigungen durch Inhibitoren wird auf die Mechanismen der Inhibition, die Diagnostik und die Behandlungsprinzipien eingegangen. Besprochen werden die erworbene Hemmkörperhämophilie, das erworbene VWS, der erworbene FV-Mangel und am Rande das erworbene Hypoprothrombin-Lupusantikoagulans.
Erworbene Koagulopathien
Authors: Riess H. 
Published: March 2018

ZusammenfassungErworbene Koagulopathien sind meist Folgen einer verursachenden Grundkrankheit (z. B. Leberinsuffizienz oder Sepsis). Die adäquate Behandlung dieser Grundkrankheit ist in der Regel von langfristig prognosebestimmender Bedeutung. Bei wenigen Koagulopathien, insbesondere bei den Immunkoagulopathien, findet sich aber keine erkennbare Grundkrankheit bei einem relevanten Anteil von Patienten. Die Optimierung der Hämostase mit dem Ziel fatale Blutungskomplikationen oder Thromboembolien zu verhindern, ist in beiden Fällen in der Lage, die Prognose zu verbessern. Meist gelingt dies durch individuell angepasste laborkontrollierte Therapien, die nur schwer einer Überprüfung im Rahmen von Studien zugänglich sind. In den vergangenen Jahren wurde erstmals in plazebokontollierten randomisierten Phase-III-Studien die Bedeutung der therapeutischen Hämostasemodulation zur Mortalitätsreduktion erfolgreich überprüft.
Zell- und gentherapeutische Ansätze zur Knorpelreparatur und potenziellen Arthrosetherapie
Authors: Pfander D. , Swoboda B. , Gelse K. 
Published: March 2018

ZusammenfassungMögliche Strategien zur Arthrosebehandlung basieren auf einer Hemmung des Matrixabbaus oder vielmehr der Steigerung des Knorpelanabolismus im erkrankten Gelenk. Die Applikation antikataboler oderantiinflammatorischerZyto- kine hat sich in Studien bereits als günstig erwiesen. Der breite klinische Einsatz dieser Ansätze wird jedoch durch die enormen Kosten aufgrund der kurzen Halbwertszeit der Proteine im Gelenk eingeschränkt. Mittels Gentransfer könnten auch über längere Zeit die erforderlichen therapeutischen Proteinkonzentrationen im erkrankten Gewebe erzielt werden. Größere Knorpelschäden und fortgeschrittene Arthrosestadien erfordern die Bildung von neuem hyalinen Knorpelgewebe. Mittels chirurgischer Verfahren gelingt es oft nicht, die Gelenkoberflächewiederherzustellen; meistens führen sie nurzur Faserknorpelbildung. In experimentellen Studien konnte durch Einsatz bestimmter Wachstums- und Differenzierungsfaktoren die Chondrogenese effizient stimuliert und hyalines knorpelähnliches Reparaturgewebe generiert werden. Zielgerichteter zellvermittelter Gentransfer könnte in idealer Weise die Bereitstellung von Knorpel(vorläufer-)zellen mit der Produktion therapeutischer Faktoren kombinieren.
Wirksamkeit und Verträglichkeit eines Weidenrindenpräparates bei Erkrankungen des Bewegungsapparates
Authors: Müller J. , Bach G. , Müller-Faßbender H. 
Published: March 2018

ZusammenfassungIn einer retrospektiven Datenerhebung mit dem Weidenrindenpräparat STW 33-1 wurden bei niedergelassenen Orthopäden und in Kliniken Daten von 333 Patienten erhoben und ausgewertet. Die Ärzte beurteilten die Wirksamkeit bei mehr als 50 % der Patienten als sehr gut oder gut und bei etwa 30% der Patienten alszufriedenstellend. Die Wirksamkeit war über die wichtigsten Diagnosesubgruppen, nämlich Arthrose, Wirbelsäulensyndrom und Weichteilrheuma hinweg, annähernd gleich gut. Bei einem Großteil der Patienten schätzten die Ärzte die Wirksamkeit des Weidenrindenpräparatesals vergleichbar mit anderen antirheumatischen Substanzen wievor allem Ibuprofen und Diclofenac ein, so dass der Schluss gerechtfertigt erscheint, dass das Präparat eine echte Alternativein der Behandlung von Schmerzen des Bewegungsapparates darstellt.
Successful eradication of a FVIII inhibitor in a 60-year-old patient with mild haemophilia A using single-agent prednisolone
Authors: Marx G. , Lentz B. , Bokemeyer C. , Langer F. , Holstein K. 
Published: March 2018

Summary
Background Development of FVIII inhibitors represents a major challenge in patients with mild haemophilia A (HA), because they tend to occur at an older age and classical immune tolerance induction appears to be less effective. Case report A man (age: 60 years) with mild HA due to the missense mutation, Leu1929Arg, received a single dose of rFVIII at 35 IU/kg prior to routine colonoscopy, totalling 25 lifetime exposure days. Two months later, rFVIII was infused for a traumatic hip haematoma. However, FVIII recovery was inappropriate, and a FVIII inhibitor of 19 BU with type-2 kinetics was detected, resulting in FVIII:C of < 1%. Two weeks later, the patient experienced spontaneous iliopsoas bleeding. Parallel to bypassing therapy, we started single-agent immunosuppression with prednisolone at 1.5 mg/kg. FVIII : C “normalized” at 10.2% after four weeks. After five months, the inhibitor titre fell to < 0.4 BU with sustained remission after one year of follow-up. Conclusion In mild HA, FVIII inhibitors may share characteristic features with FVIII autoantibodies commonly observed in acquired HA. Therefore, immunosuppressive therapy alone could be successful at least in a subset of patients.
Hämophilie und Knorpel
Authors: Seuser A. 
Published: March 2018

SummaryIt is not the blood alone! Increased loading destroys cartilage and leads to arthrosis. Reduced mechanical stimulation leads to reduced cartilage nutrition and to cartilage degeneration, which leads to arthrosis. We know about the existence of functional disturbances that occur in early childhood before any structural changes are diagnosed. This is typical for haemophilia. Those disturbances and the way movement is disturbed has a strong influence on the loading of cartilage. This involves acceleration peaks, disturbed load distribution with reduction of contact area and a change of vector direction, which leads to increased cartilage loading. The disturbed function can be analysed very early with motion analysis. Easy physiotherapeutical interventions are able to optimise function again. On top of that we have a loss of muscle contraction pattern. Around the knee joint it is the weakening of the vastus medialis and the shortening of the knee flexors. The ankle joint suffers from a weakening of the tibialis anterior and a shortening of the calf muscles. During progression of the disease there will be a shortening of the weakened muscle and a weakening of the shortened muscle as well. Kinetic superficial EMG is able to quantify the status of the muscles and enables us to prescribe an individual therapy. Subclinical influences like microbleeds, in the beginning silent synovitis, later chronic synovitis, silent symptoms and overprotection are the cause of the functional overloading of the cartilage in patient with haemophilia. Silent symptoms can be discovered by clinical examination. Again this leads to the opportunity of a symptomatic therapeutic approach. All those facts could be the reason why there is an increasing incidence of haemarthrophathy of the ankle joint, even in patients with mild haemophilia in spite of adequate factor substitution.
Risikoschwangerschaften und deren Therapie
Authors: Radtke H. , Becker R. , Schmidt F. P. , Körber K. , Vehlow N. , Kiesewetter H. 
Published: March 2018

SummaryRecurrent abortions are a common problem. A therapy with low-molecular-weight heparin is usual in deep vein thrombosis with thrombophilia, in woman with recurrent abortions or other risks, like EPH-gestosis or HELLP-Syndrom. Patients, method: The efficacy of a mono-therapy with LMWH (3000–16 000 daily) in women with risk pregnancies has been examined prospectively. The dates of 676 pregnant women have been analysed and compared to the current literature about live birth rates without therapy and tot he results of other, similar studies. The live birth rate has been the target variable. Results: We obtained main a live birth rate of 98.6%.There has been no record of serious adverse effects. We obtained a live birth rate of 95.8% if NMH therapy starts early, and a live birth rate of 100% if NMH therapy starts between week 20 and 25. For the live birth rate the existence of thrombophilic gene polymorphisms is irrelevant. Conclusion: The high live birth weight is depended on early starting the therapy with NMH. For the late risk it is favourable to start the therapy with heparin between week 20 and 25 week of pregnancy.
Neuropathic pain in patients with haemophilia, that is the question
Authors: Krüger S. , Hilberg T. 
Published: March 2018

SummaryChronic pain caused by recurrent joint bleedings affects a large number of patients with haemophilia (PwH). The basis of this pain, nociceptive or neuropathic, has not been investigated so far. In other pain-related chronic disorders such as osteoarthritis or rheumatoid arthritis, initial studies showed nociceptive but also neuropathic pain features. 137 PwH and 33 controls (C) completed the painDETECT-questionnaire (pDq), which identifies neuropathic components in a person´s pain profile. Based on the pDq results, a neuropathic pain component is classified as positive, negative or unclear. A positive neuropathic pain component was found in nine PwH, but not in C. In 20 PwH an unclear pDq result was observed. In comparison to C the allocation of pDq results is statistically significant (p≤0.001). Despite various pDq results in PwH and C a similar appraisal pain quality, but on a different level, was determined. Summarising the results, there is a potential risk to misunderstand underlying pain mechanisms in PwH. In chronic pain conditions based on haemophilic arthopathy, a differential diagnosis seems to be unalterable for comprehensive and individualised pain management in PwH.
Complex strength performance in patients with haemophilia A
Authors: Kappelhoff M. , Hilberg T. , Runkel B. 
Published: March 2018

SummaryThe aim of this study was to develop a complex strength measurement method and to apply this new method for the first time in patients with haemophilia (PwH). 20 PwH with severe haemophilia A and 20 controls were included into the study. All subjects completed ten measurements of maximum isometric strength. Furthermore, the 20 control subjects completed re-test-measurements to evaluate the method.As a result, the method showed a high reliability (ICC 0.764 to 0.934). Between the two groups significant reductions in PwH between –(19–35%) were detected, regarding the relative force of the M. triceps brachii (–19%; p = 0.008), M. biceps brachii (–19%; p = 0.031), M. latissimus dorsi (–17%; p = 0.019), M. biceps femoris right (–20%; p = 0.036) and M. quadriceps femoris (right: –29%; p = 0.004; left: –35%; p = 0.002). No differences were found for M. rectus abdominis and in the hand strength. Thus, there is no general deficit in the muscle strength in PwH. The most obvious deficits exist in the upper and lower extremities and in the back muscles.PwH should carry out complex muscle strength training and integrate it early into a comprehensive treatment concept.