Prevalence of pre-operative anaemia in surgical patients: a retrospective, observational, multicentre study in Germany.

Anaemia is a risk factor for several adverse postoperative outcomes. Detailed data about the prevalence of anaemia are not available over a long time-period in Germany. In this retrospective, observational, multicentre study, patients undergoing surgery in March in 2007, 2012, 2015, 2017 and 2019 were studied. The primary objective was the prevalence of anaemia at hospital admission. The secondary objectives were the association between anaemia and the number of units of red blood cells transfused, length of hospital stay and in-hospital mortality. A total of 23,836 patients were included from eight centres. The prevalence of pre-operative anaemia in patients aged ≥ 18 years decreased slightly from 37% in 2007 to 32.5% in 2019 (p = 0.01) and increased in patients aged ≤ 18 years from 18.8% in 2007 to 26.4% in 2019 (p > 0.001). The total amount of blood administered per 1000 patients decreased from 671.2 units in 2007 to 289.0 units in 2019. Transfusion rates in anaemic patients declined from 33.8% in 2007 to 19.1% in 2019 (p < 0.001) and in non-anaemic patients from 8.4% in 2007 to 3.4% in 2019 (p < 0.001). Overall, the mortality rate remained constant over the years: 2.9% in 2007, 2.1% in 2012, 2.5% in 2015, 1.9% in 2017 and 2.5% in 2019. In the presence of anaemia, mortality was significantly increased compared with patients without anaemia (OR 5.27 (95%CI 4.13-6.77); p < 0.001). Red blood cell transfusion was associated with an increased risk of mortality (OR 14.98 (95%CI 11.83-19.03); p < 0.001). Using multivariable linear regression analysis with fixed effects, we found that pre-operative anaemia (OR 2.08 (95%CI 1.42-3.05); p < 0.001) and red blood cell transfusion (OR 4.29 (95%CI 3.09-5.94); p < 0.001) were predictors of mortality but not length of stay (0.99 (95%CI 0.98-1.00) days; p = 0.12) and analysed years (2007 vs. 2019: OR 1.49 (95%CI 0.86-2.69); p = 0.07). Pre-operative anaemia affects more than 30% of surgical patients in Germany and multidisciplinary action is urgently required to reduce adverse outcomes.

International multicentre review of perioperative management and outcome for catecholamine-producing tumours.

BACKGROUND: Surgery for catecholamine-producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected. METHODS: Twenty-one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α-receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality. RESULTS: Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α-receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex-sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α-receptor blockade and 0·9 per cent (3 of 343) among patients without α-receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non-pretreated patients. CONCLUSION: There is substantial variability in the perioperative management of catecholamine-producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.

ANTECEDENTES: La cirugía de los tumores productores de catecolaminas puede complicarse por la inestabilidad hemodinámica intraoperatoria y postoperatoria. Se han propuesto distintas estrategias de manejo perioperatorio, pero ninguna ha sido evaluada en ensayos aleatorizados. Para evaluar este tema, se han recogido los datos de los resultados y del manejo perioperatorio contemporáneo de 21 centros. MÉTODOS: Veintiún centros aportaron datos de los resultados de los pacientes operados por feocromocitoma y paraganglioma entre 2000-2017. Los datos incluyeron el número de pacientes con y sin bloqueo del receptor α, las técnicas quirúrgicas y anestésicas, las complicaciones y la mortalidad perioperatoria. RESULTADOS: Los centros en su conjunto aportaron datos de 1.860 pacientes con feocromocitoma y paraganglioma, de los cuales 343 pacientes fueron intervenidos sin bloqueo del receptor α. La gran mayoría (79%) de las cirugías se realizaron utilizando técnicas mínimamente invasivas, incluido un 17% de procedimientos con preservación de la corteza suprarrenal. La tasa de complicaciones cardiovasculares fue de 5,0% en total; 5,9% (90/1517) en pacientes con bloqueo preoperatorio de los receptores α y 0,9% (3/343) en pacientes no pretratados. La mortalidad global fue del 0,5% (9/1860); 0,5% (8/1517) en pacientes pretratados y 0,3% (1/343) en pacientes no tratados previamente. CONCLUSIÓN: Existe una variabilidad sustancial en el manejo perioperatorio de los tumores productores de catecolaminas, aunque la tasa global de complicaciones es baja. Este estudio brinda la oportunidad para efectuar comparaciones sistemáticas entre estrategias de prácticas terapéuticas variables. Se necesitan más estudios para definir mejor el enfoque de manejo óptimo y parece conveniente volver a evaluar las guías internacionales perioperatorias.

[Long QT syndrome. History, genetics, clinical symptoms, causes and therapy]. / Long-QT-Syndrom. Historie, Genetik, klinische Symptome, Ursachen und Therapie.

The long QT syndrome is caused by a change in cardiac repolarization due to functional ion channel defects. A differentiation is made between a congenital (cLQTS) and an acquired (aLQTS) form of the disease. The disease results in the name-giving prolongation of the QT interval in the electrocardiogram and represents a predisposition for cardiac arrhythmia and sudden cardiac death. This article summarizes the current knowledge on the history, pathophysiology, clinical symptoms and therapy of cLQTS and aLQTS. This knowledge of pathophysiological features of the symptoms allows the underlying anesthesiological approach for individualized perioperative concepts for patients suffering from LQTS to be derived.

[Perioperative treatment of patients with long QT syndrome]. / Perioperative Betreuung von Patienten mit Long-QT-Syndrom.

Long QT syndrome (LQTS) is caused by a change in cardiac repolarization due to functional ion channel dysfunction which is associated with an elongation of the QT interval (hence the name) in the electrocardiogram and a predisposition to cardiac rhythm disorders (e.g. torsade de pointes, TdP) as well as cardiac events up to sudden cardiac death. There is a congenital (cLQTS) and an acquired (aLQTS) form of the disease. The prevalence of cLQTS is 1 in 2000 but aLQTS is much more common and includes a grey area due to many asymptomatic patients. The LQTS is, therefore, more common than malignant hyperthermia which is much discussed in anesthesiology and has a reported prevalence in the population of 1:3000. Considering the prevalence of both aLQTS as well as cLQTS the importance of the LQTS seems to be underestimated in current perioperative care. Potential perioperative risks of such patients can be significantly reduced by appropriate patient management. This includes adequate preoperative preparation, the correct choice of anesthetic medication as well as adequate perioperative monitoring and preparedness for immediate pharmaceutical and electrical intervention in case of typical cardiac rhythm disturbances, such as TdP arrhythmia.

Efficacy and safety of 10% HES 130/0.4 versus 10% HES 200/0.5 for plasma volume expansion in cardiac surgery patients.

AIM: Hydroxyethyl starch (HES) solutions are frequently used for perioperative volume replacement. Whereas older HES specimen tended to accumulate in the plasma and to cause negative effects on hemostasis, more recent products, e.g., HES 130/0.4, are characterised by improved pharmacological properties. The present study was designed to compare the efficacy and safety of 10% HES 130/0.4 and 10% HES 200/0.5. METHODS: In this post-hoc analysis of a prospective, randomised, double-blind, multi-center therapeutic equivalence trial, 76 patients undergoing elective on-pump cardiac surgery received perioperative volume replacement using either 10% HES 130/0.4 (N.=37) or 10% HES 200/0.5 (N.=39) up to a maximum dose of 20 mL kg-1. RESULTS: Equivalent volumes of investigational medication were infused until 24 hours after the first administration (1577 vs. 1540 mL; treatment difference 37 [-150; 223] mL; P<0.0001 for equivalence). Whereas standard laboratory tests of coagulation were comparable between groups, von Willebrand factor activity on the first postoperative morning tended to be higher following treatment with 10% HES 130/0.4 as compared to 10% HES 200/0.5 (P=0.025) with this difference being statistically significant only in the per-protocol analysis (P=0.02). Treatment groups were comparable concerning other safety parameters and the incidence of adverse drug reactions. In particular, renal function was well preserved in both groups. CONCLUSION: Ten percent HES 130/0.4 was equally effective and safe as compared to 10% HES 200/0.5 for volume therapy in patients undergoing cardiovascular surgery. Postoperative coagulation and renal function, as measured by standard laboratory tests, were similar among groups.

Fibrinogen-coated albumin microcapsules reduce bleeding in severely thrombocytopenic rabbits.

Severe thrombocytopenia frequently occurs in patients receiving chemotherapy and in patients with autoimmune disorders. Thrombocytopenia is associated with bleeding, which may be serious and life threatening. Current treatment strategies for thrombocytopenia may require transfusion of allogeneic platelets, which is associated with serious drawbacks. These include the occurrence of anti-platelet antibodies, which may result in refractoriness to further platelet transfusions, and the potential risk of transfer of blood-borne diseases. Therefore, we have recently developed a platelet substitute product (Synthocytes), which is composed of human albumin microcapsules with fibrinogen immobilized on their surface. Here we show that the intravenous administration of these microcapsules not only corrects the prolonged bleeding time in rabbits rendered thrombocytopenic either by anti-platelet antibodies or by chemotherapy, but also reduces bleeding from surgical wounds inflicted in the abdominal skin and musculature. No potential systemic prothrombotic effect of the microcapsules was observed in a model of rabbit venous thrombosis. As for the mechanism of action, experiments with normal and thrombocytopenic human blood in an endothelial cell matrix-coated perfusion chamber demonstrated an interaction between the fibrinogen-coated albumin microcapsules and native platelets. It was shown that the fibrinogen-coated albumin microcapsules could facilitate platelet adhesion to endothelial cell matrix and correct the impaired formation of platelet aggregates in relatively platelet-poor blood. This study indicates that fibrinogen-coated albumin microcapsules can act to improve primary hemostasis under thrombocytopenic conditions and may eventually be a promising agent for prophylaxis and treatment of bleeding in patients with severe thrombocytopenia.

High-throughput screening of multifunctional nanocoatings based on combinations of polyphenols and catecholamines.

Biomimetic surface coatings based on plant polyphenols and catecholamines have been used broadly in a variety of applications. However, the lack of a rational cost-effective platform for screening these coatings and their properties limits the true potential of these functional materials to be unleashed. Here, we investigated the oxidation behavior and coating formation ability of a library consisting of 45 phenolic compounds and catecholamines. UV-vis spectroscopy demonstrated significant acceleration of oxidation and polymerization under UV irradiation. We discovered that several binary mixtures resulted in non-additive behavior (synergistic or antagonistic effect) yielding much thicker or thinner coatings than individual compounds measured by ellipsometry. To investigate the properties of coatings derived from new combinations, we used a miniaturized high-throughput strategy to screen 2,532 spots coated with single, binary, and ternary combinations of coating precursors in one run. We evaluated the use of machine learning models to learn the relation between the chemical structure of the precursors and the thickness of the nanocoatings. Formation and stability of nanocoatings were investigated in a high-throughput manner via discontinuous dewetting. 30 stable combinations (hits) were used to tune the surface wettability and to form water droplet microarray and spot size gradients of water droplets on the coated surface. No toxicity was observed against eukaryotic HeLa cells and Pseudomonas aeruginosa (strain PA30) bacteria after 24 h incubation at 37 °C. The strategy introduced here for high-throughput screening of nanocoatings derived from combinations of coating precursors enables the discovery of new functional materials for various applications in science and technology in a cost-effective miniaturized manner.

[Perioperative monitoring of the QT interval]. / Perioperatives Monitoring des QT-Intervalls.

The feasibility of routine perioperative monitoring of the QT interval is demonstrated for the first time in two patients suffering from acquired long QT syndrome. These cases demonstrate that automatic perioperative monitoring of the QT interval is simple and easy to achieve. Besides sufficient premedication, normalized electrolytes, a calm and quiet atmosphere, avoiding QT prolonging drugs and the possibility of immediate defibrillation, monitoring of the QT interval should be considered in the perioperative treatment of these cardiac risk patients.

[Improved survival by guideline compliant cardiopulmonary resuscitation: analysis of primary survival rates in the Hamburg emergency medical service]. / Verbessertes Überleben durch leitliniengerechte kardiopulmonale Reanimation : Analyse der primären Überlebensrate im Hamburger Rettungsdienst.

BACKGROUND: In 2005 revised guidelines for cardiopulmonary resuscitation (CPR) were published by the European Resuscitation Council replacing the guidelines implemented in the year 2000. The aim of this study was to test the compliance with valid guidelines and to establish the quality of pre-hospital CPR provided by paramedics over a period of 38 months. PATIENTS AND METHODS: A total of 299 CPRs performed by paramedics of the emergency medical services of Hamburg, Germany between 1(st) November 2004 and 31(st) December 2007 were analyzed. Digital recordings of automated external defibrillators and emergency protocol data were analyzed in detail. CPR was judged as incorrect if the defibrillation energy level did not correspond to the valid guidelines or if the interval between defibrillations exceeded a tolerance range of more than 30% compared to the valid guidelines. RESULTS: All CPRs (299) were included in the analysis of which 197 (65.9%) were intended to follow the 2000 guidelines and 102 (34.1%) the 2005 guidelines. Return of spontaneous circulation (ROSC) was achieved in 164 cases (54.8%) and survival to hospital admission in 125 cases (41.8%). CPR was performed accurately according to guidelines in only 26 cases (8.7%). In 273 cases (91.3%) the guidelines were not followed completely. Concerning the translation of guidelines into practice most faults occurred due to wrong intervals (89.3%), wrong defibrillation energy (33.4%) and medical errors, such as defibrillating an asystolic patient (7.0%). Primary survival rates were not significantly different when CPR accurately followed the 2000 or 2005 guidelines (40.1% versus 45.1%). Comparing primary survival rates of cases in which the guidelines were followed completely, there was no significant difference between the 2000 guidelines (15 out of 21 cases 71.4%) and 2005 guidelines (4 out of 5 cases 80.0%). However, compliance with valid guidelines significantly increased primary survival rates compared to non-compliance with valid guidelines (19 out of 26 cases 73.1% versus 106 out of 273 cases 38.8%; p=0.007). This effect was independent of the duration of CPR. Comparing CPR with monophasic defibrillation (189 cases) or biphasic defibrillation (58 cases), there was a significantly higher rate of ROSC (56.1% versus 72.4%) and a significantly higher rate of primary survival (41.3% versus 56.9%) in favour of biphasic defibrillation. CONCLUSION: The results of our study show that compliance with valid guidelines is low and furthermore suggest that compliance with guidelines significantly reduces mortality. Future research may be warranted into the question of how to increase compliance with current CPR guidelines in pre-hospital emergency care.

Enhancement of rabbit jugular vein thrombolysis by neutralization of factor XI. In vivo evidence for a role of factor XI as an anti-fibrinolytic factor.

Recent in vitro studies have shown that fibrinolytic activity may be attenuated by a thrombin-activatable fibrinolysis inhibitor (TAFI), which is activated by thrombin, generated via the intrinsic pathway of coagulation in a factor XI-dependent way. Thus factor XI may play a role in the regulation of endogenous fibrinolysis. The aim of this study was to investigate the effect of in vivo inhibition of factor XI and TAFI in an experimental thrombosis model in rabbits. Incorporation of anti-factor XI antibodies in jugular vein thrombi resulted in an almost twofold increase in endogenous thrombolysis compared with a control antibody. A similar effect was observed when the anti-factor XI antibody was administered systemically. Inhibition of TAFI activity also resulted in a twofold increase in clot lysis whereas inhibition of both factor XI and TAFI activity had no additional effect. Thus, we provide the first in vivo evidence for enhanced thrombolysis through inhibition of clotting factor XI, demonstrating a novel role for the intrinsic pathway of coagulation. Furthermore we demonstrate that inhibition of TAFI had a similar effect on thrombolysis. We postulate that inhibition of factor XI activity enhances thrombolysis because of diminished indirect activation of TAFI.

Increased epithelial cell proliferation in the ileal pouch mucosa of patients with familial adenomatous polyposis.

To eliminate the risk of colorectal cancer in patients with familial adenomatous polyposis (FAP), reconstructive proctocolectomy is performed. Although most colonic mucosa is resected during the ileal pouch anal anastomosis, adenomas and carcinomas may develop in the pouch. This may be caused by altered cell kinetics due to intraluminal changes in the pouch. In 32 patients with FAP, biopsy specimens from the mucosa of the pouch and also of the afferent ileal loop were taken. Tissue sections were immunohistochemically processed with the monoclonal antibodies M30 and MIB-1 to assess apoptotic and proliferative indices, respectively. Cell proliferation was also assessed by a modified sign test. There were no significant differences in apoptotic rates between the mucosa of the pouch and the mucosa of the afferent ileal loop. However, cell proliferation was significantly higher in the mucosa of the pouch vs afferent ileal loop, both by using the quantitative (68.3% vs 61.6%, p = 0.001) and semiquantitative methods (p < 0.05). Our newly developed semiquantitative approach outperformed previously described methods. The higher cell proliferation in the pouch as compared to the afferent ileal loop may contribute to the increased risk for adenomas and carcinomas in the pouch of patients with FAP and emphasizes the need for regular endoscopic surveillance.

Role of colonoscopic biopsy in distinguishing between Crohn's disease and intestinal tuberculosis.

BACKGROUND: The histological differential diagnosis of Crohn's disease and intestinal tuberculosis can be very challenging, as both are chronic granulomatous disorders with overlapping histological features. AIM: To evaluate selected clinical and histological parameters in colonic biopsy specimens for their ability to discriminate between Crohn's disease and intestinal tuberculosis. METHODS: 25 patients with Crohn's disease and 18 patients with intestinal tuberculosis were selected for this study on the basis of established clinical, radiological and histological criteria. Clinical data and selected histological parameters in colonoscopic biopsy specimens were assessed retrospectively. A total of 103 and 41 biopsy sites were evaluated in patients with Crohn's disease and intestinal tuberculosis, respectively. RESULTS: Clinical parameters helpful in differentiating intestinal tuberculosis from Crohn's disease included chest radiographic features of tuberculosis (56% v 0%), perianal fistulae (0% v 40%) and extraintestinal manifestations of Crohn's disease (0% v 40%). Histopathological features that seemed to reliably differentiate between intestinal tuberculosis and Crohn's disease included confluent granulomas, > or =10 granulomas per biopsy site and caseous necrosis (in biopsy samples of 50%, 33% and 22% of patients with intestinal tuberculosis, respectively, v 0% of patients with Crohn's disease). Features that were observed more often in patients with intestinal tuberculosis than in those with Crohn's disease included granulomas exceeding 0.05 mm(2) (67% v 8%), ulcers lined by conglomerate epithelioid histiocytes (61% v 8%) and disproportionate submucosal inflammation (67% v 10%). CONCLUSION: Clinical features and selected histological parameters in colonoscopic biopsy specimens can help in differentiating between Crohn's disease and intestinal tuberculosis.

[Thalidomide for the treatment of recurrent gastrointestinal blood loss due to intestinal angiodysplasias]. / Thalidomide als behandeling bij recidiverend gastro-intestinaal bloedverlies op basis van intestinale angiodysplasieën.

Two female patients, 86 and 80 years of age, had been treated with blood transfusions for several years and several months, respectively, due to iron-deficiency anaemia caused by gastrointestinal blood loss. Angiodysplasias were detected and subsequently coagulated in the course of repeated gastroscopies and colonoscopies. Due to the failure of this treatment, treatment with thalidomide was started. Thereafter, the gastrointestinal bleeding stopped and there was no longer any need for blood transfusions. Treatment with thalidomide seems an effective therapy for patients with frequently recurring gastrointestinal blood loss due to angiodysplasias who no longer tolerate conventional and invasive procedures due to their physical condition.

Ability of recombinant factor VIIa to generate thrombin during inhibition of tissue factor in human subjects.

BACKGROUND: In view of the central role of the tissue factor-factor VIIa pathway in the initiation of blood coagulation, novel therapeutic strategies aimed at inhibiting this catalytic complex are currently being evaluated. A limitation of this new class of anticoagulants may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs. The aim of this study was to investigate the in vivo potential of recombinant factor VIIa (rVIIa) to induce thrombin generation in healthy subjects pretreated with recombinant nematode anticoagulant protein c2, a specific inhibitor of the tissue factor-factor VIIa complex, in a double-blind randomized crossover study. METHODS AND RESULTS: Administration of nematode anticoagulant protein c2 (3.5 microgram/kg) caused a prolongation of the prothrombin time from 13.7+/-0.6 to 16.9+/-1.2 seconds. The subsequent injection of rVIIa (90 microgram/kg) resulted in an immediate and complete correction of the prothrombin time and a marked generation of thrombin, reflected by increased levels of prothrombin activation fragment F1+2 and thrombin-antithrombin complexes from 0.75+/-0.64 to 3.29+/-6.3 nmol/L and from 2.4+/-0.6 to 10.7+/-3.9 microgram/mL, respectively. Factor X and IX activation peptides showed a 3.5-fold and a 3.8-fold increase, respectively, after the administration of rVIIa in the presence of nematode anticoagulant protein c2. CONCLUSIONS: During treatment with an inhibitor of the tissue factor-factor VIIa complex, the infusion of rVIIa resulted in thrombin generation. Our results indicate that rVIIa may be a good candidate as an antidote for inhibitors of tissue factor.

Aromatase inhibition with 4-hydroxyandrostenedione in the treatment of postmenopausal patients with advanced breast cancer: a phase II study.

Estrogen deprivation by aromatase inhibition is an effective treatment in breast cancer. Between October 1986 and March 1988, 91 postmenopausal patients with advanced breast cancer entered a phase II study performed jointly in three center to investigate the new aromatase inhibitor 4-hydroxyandrostenedione. Patients received 500 mg 4-hydroxyandrostenedione intramuscularly (IM) every 2 weeks for 6 weeks, and 250 mg every 2 weeks thereafter. There were two complete (CRs) and 19 partial remissions (PRs) (response rate, 23%). Disease stabilization (no change; NC) was seen in 26 patients, and in 44 patients (48%), disease progression occurred. Duration of the CRs is 20+ months, median durations of PR and NC are 13+ and 8 months, respectively. Receptor status, relapse-free interval, and sites of metastatic lesions did not appear to influence treatment results. However, efficacy of previous tamoxifen treatment favorably predicted response to 4-hydroxyandrostenedione. Serum estradiol levels decreased significantly in patients after 2 weeks of treatment. Side effects were mostly nonspecific and of low degree, requiring discontinuation of treatment in only 3% of the patients. We conclude that aromatase inhibition with 4-hydroxyandrostenedione is efficacious in the treatment of postmenopausal breast cancer.

[Fast-track surgery in radical retropubic prostatectomy. First experiences with a comprehensive program to enhance postoperative convalescence]. / Radikale retropubische "Fast-track-Prostatektomie". Erste Erfahrungen mit einem interdisziplinären, multimodalen Behandlungskonzept zur Beschleunigung der postoperativen Rehabilitation.

Fast-track surgery is a comprehensive program for the optimization of perioperative care in elective surgery reducing potential postoperative complications and speeding up convalescence. Recent data from randomized colon resection trials emphasize that fast-track surgery is possible in most major operations. Our initial results in radical retropubic prostatectomy fast-track surgery have been encouraging. Fast-track surgery in major urological operations needs validation using randomized trials.

Inversion of Ca2+ current modulation during recovery of neuroblastoma cells from pertussis toxin pretreatment.

Human neuroblastoma cells (SH-SY5Y) differentiated by retinoic acid exhibited high threshold-activated N-type Ca2+ currents, which were largely inhibited by the two enkephalins, DAGO and DPDPE, as well as by dopamine and somatostatin. The inhibitory effects were fully abolished after pretreatment of cells with pertussis toxin. After washing out the toxin, the inhibitory effects re-established with a time constant of about 16 h. The recovery of Ca2+ current inhibition was similar for all tested agonists. Unexpectedly, we observed a neurotransmitter-induced stimulation of Ca2+ currents in approximately 10% of all investigated cells during the recovery phase. Such a stimulatory effect by otherwise inhibitory receptors was never seen in control cells. It did also not occur when exogenous purified G-proteins of the Gi family were reconstituted via the patch pipette, suggesting that additional mechanisms may play a role in the appearance of stimulatory effects during the recovery phase after pertussis toxin pretreatment.

Successful attenuation of venous thrombus growth in rabbits after the administration of a novel oral thrombin inhibitor.

Current antithrombotic compounds have several limitations in clinical practice. The present study was designed to investigate a novel orally available direct thrombin inhibitor, BSF 208791. Intravenous administration of BSF 208791 showed superior antithrombotic properties as compared with Polyethylenglycol-Hirudin (PEG-Hirudin) and low molecular weight heparin (LMWH) in a model of venous thrombosis in rabbits. The thrombus growth was 22%, 30%, 37% and 50% after BSF 208791, PEG-Hirudin. LMWH, and saline administration, respectively. Moreover, bleeding time was less affected after administration of BSF 208791 as compared with PEG-Hirudin. The oral administration of BSF 208791 resulted in adequate bioavailability and significantly reduced venous thrombus growth to 36% as compared with 60% in the saline treated rabbits. The antithrombotic effect of BSF 208791 appears to be superior to PEG-Hiridin and LMWH without affecting the bleeding time. BSF 208791 is an orally available agent that might be a promising candidate for future antithrombotic therapy.