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Biomedical subjects

K Peter

Publications and source records attributed to K Peter.

At least 37 records · Page 2Linked to original sources

Effects of confinement (110 and 240 days) on neuroendocrine stress response and changes of immune cells in men.

The aim of the study was to evaluate the effects of long-term confinement on stress-permissive neuroendocrine and immune responses in humans. Two groups of four male subjects were confined 240 days (group 240) or 110 days (group 110) in two space modules of 100 or 200 m3, respectively. During confinement, none of the volunteers developed psychic stress as could be examined and verified by a current stress test. However, in group 240 but not in group 110, the diurnal rhythm of cortisol secretion was slightly depressed and the urine excretion of norepinephrine significantly increased. The innate part of the immune system became activated as seen by a rise in the number of circulating granulocytes and the enhanced expression of beta2-integrins. In contrast, the ratio of T-helper to T-suppressor cells decreased. All these effects, observed during confinement, were even more pronounced in both groups when values of endocrinological and immunological parameters were compared between before and 1 wk after the end of the confinement period. Hence, return to normal life exerts pronounced effects to a much higher degree, irrespective of how long or under which conditions individuals were confined. Because the delayed-type hypersensitivity skin reaction against recall antigens remained unaffected, it is to be presumed that confinement appears to induce distinct sympathoadrenergic activation and immunological changes but no clinically relevant immunosuppression.

Adult↗

Ropivacaine 7.5 mg/ml versus bupivacaine 5 mg/ml for interscalene brachial plexus block--a comparative study.

We investigated ropivacaine 75 mg/ml in comparison with bupivacaine 5 mg/ml in patients receiving interscalene brachial plexus block (ISB) and general anaesthesia. In this randomized, double-blind, prospective clinical trial, each patient received an ISB block according to the technique originally described by Winnie and a catheter technique as per Meier. The rapidity of onset and the quality of sensory and motor block were determined. After general anaesthesia had been induced further parameters evaluated were consumption of local anaesthetic, opioid and neuromuscular blocking drug. After arrival in the recovery room, the patients were assessed for intensity of pain using a visual analog scale (VAS). One hundred and twenty patients were included in the study. The onset and development of sensory block was similar in both groups. Development and quality of motor block was also nearly identical for both local anaesthetics. Consumption of neuromuscular blocking drug and opioid did not differ between ropivacaine and bupivacaine. In the recovery room the mean pain score was less than 25 in both groups. There were no significant differences in terms of onset and quality of sensory or motor block during the intraoperative and early postoperative period. In addition we did not identify any side-effects related to the administration of the local anaesthetics. Ropivacaine 7.5 mg/ml and bupivacaine 5mg/ml proved to be nearly indistinguishable when administered for interscalene brachial plexus block.

Adult↗

Intrinsic activating properties of GP IIb/IIIa blockers.

Potential intrinsic activating properties are probably the most controversially discussed issues with respect to GP IIb/IIIa blockers, especially since clinical trials with oral GP IIb/IIIa blockers revealed disappointing results. Based on the finding that currently clinically used GP IIb/IIIa blockers are ligand mimetics, experimental data are discussed, demonstrating an intrinsic activating effect of ligand mimetic GP IIb/IIIa blockers that potentially results in fibrinogen binding to alpha(IIb)beta(3) and in platelet aggregation. Furthermore, the inhibitory effect of aspirin on GP IIb/IIIa blocker-induced platelet aggregation is discussed as a clinically relevant finding. Finally, the potential association of GP IIb/IIIa blocker-induced thrombocytopenia with platelet activation is described.

Antibodies, Monoclonal↗

Induction of a cytotoxic T-cell response to HIV-1 proteins with short synthetic peptides and human compatible adjuvants.

The goal of this study was the induction of a strong CTL response against multiple CTL epitopes present in HIV proteins using short synthetic peptides. Four HLA-A2.1 restricted peptides (RT 476-484, p17 77-85, gp41 814-823, RT 956-964) that showed stable binding to the HLA-A2.1 molecule in an in vitro binding assay were able to elicit a strong specific immune response in HLA-A2.1 transgenic mice when injected with IFA or Montanide. The use of biodegradable microspheres (MS) as adjuvant was also successfully tested for all peptides. When the peptides were injected as a mixture the response was weaker as compared to individual injections of the peptides indicating the occurrence of immunodominance (ID). We are currently investigating whether ID can be overcome by a combined injection of peptide loaded MS with different release patterns. Taken together, it seems feasible to induce a specific CTL response in HLA-A2.1 transgenic mice against several HIV proteins using short synthetic peptides and human compatible adjuvants.

AIDS Vaccines↗

[GPIIb/IIIa blockers for optimizing thrombolysis in acute myocardial infarct].

BACKGROUND: Thrombolytic therapy is an established strategy for the treatment of acute myocardial infarction. GPIIB/IIIA BLOCKERS + MODERN THROMBOLYTIC AGENTS: At present, the most attractive development for optimizing thrombolytic therapy includes the use of GPIIb/IIIa blockers in combination with modern thrombolytic agents such as alteplase and reteplase. The review summarizes the available results of clinical studies using standard doses of thrombolytic agents (TAMI 8, IMPACT-AMI, and PARADIGM) or reduced dosages of thrombolytic agents (TIMI 14 and SPEED) for combination therapy. The review also focuses on the implications of the combination therapy for coronary angioplasty immediately following coronary thrombolysis.

Abciximab↗

[Low alkali-hydroxide content in soda limes does not lead to reduction of compound A formation from sevoflurane during low-flow anesthesia].

The alkali hydroxide content in soda lime induces Compound A formation from Sevoflurane (Sevo). This study was designed to answer the question if the use of potassium hydroxide-free Soda Lime (SL) would lead to lower Compound A levels as compared to Sodasorb (SO). A total of 30 patients scheduled for elective laparoscopic cholecystectomy received Sevo anaesthesia under low-flow conditions (0.8 l/min fresh gas flow). Each absorbent was used in 15 patients, but 3 patients of the SO group were excluded due to technical problems with Compound A analysis. Hemodynamic parameters, parameters of ventilation and gas concentrations were documented. Compound A concentrations were measured by gas chromatography from gas samples before Sevo application and 20, 40, 60, 90 and 120 min after low-flow start. Mean endtidal Sevo concentrations were 1.94 +/- 0.17 (SO) and 1.97 +/- 0.15 (SL) vol %, the total anaesthetic exposition was 1.52 +/- 0.36 (SO) and 1.64 +/- 0.47 (SL) MAC-h (n.s). The maximum Compound A concentration was significantly higher in SL group (19.6 +/- 2.8 vs. 11.7 +/- 4.1 ppm, p < 0.001). Therefore, elimination of potassium hydroxide from carbon dioxide absorbents alone did not lead to a reduction of Compound A formation during low-flow anaesthesia.

Anesthesia, Inhalation↗

Intensive care after minimally invasive and conventional coronary surgery: a prospective comparison.

OBJECTIVE: The purpose of this study was to compare the intensive care course of patients after minimally invasive coronary surgery to conventional coronary artery bypass grafting. DESIGN: Prospective observational study. SETTING: Intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: One hundred and five patients with two-vessel disease consecutively scheduled for elective coronary bypass surgery were enrolled. INTERVENTIONS: Two techniques of revascularization were performed: the Octopus procedure via median sternotomy without cardiopulmonary bypass (n = 52) and conventional coronary artery bypass grafting CABG (n = 53). MEASUREMENTS AND RESULTS: Three major categories describing the patients' postoperative course were defined: (1) clinical and laboratory findings, i.e., transfusion rate, catecholamine support, duration of ventilation, Simplified Acute Physiology Score II (SAPS II), serum levels of cardiac enzymes and lactic acid; (2) postoperative complications, i.e., incidence of myocardial infarction (MI), atrial fibrillation (AF), and neurological deficits; (3) this category was defined as "the extent of care" as represented by the Therapeutic Intervention Scoring System (TISS), and the length of stay in the ICU and in the hospital. In the Octopus group significantly lower figures were noted for duration of ventilation [6.1(5.5/9.5) vs 10.2(8.2/11.8) h], cardiac enzymes (CK-MB-Mass [5.1(2.0/8.3) vs 31.3(21.4/39.3) ng/ml], and lactic acid [2.0(1.5/3.3) vs 3.2(2.2/6.5) mmol/l]), incidence of AF (2/52 vs 9/53), and neurological deficits (0/52 vs 4/53), TISS score [72(44/83) vs 84(73/93)], LOS in the ICU [2(1/2) vs 2(2/2) days], and in the hospital [6(5/9) vs 9(8/12) days]. Catecholamine support, SAPS II scores, and incidence of MI of each group did not differ significantly. CONCLUSIONS: Off-pump coronary surgery via the Octopus technique was superior to conventional CABG regarding the course of patients in the early postoperative period. This implies benefits for the patients and the entire healthcare system.

APACHE↗

Ecarin clotting time but not aPTT correlates with PEG-hirudin plasma activity.

BACKGROUND: Novel antithrombotic agents such as hirudin have shown promise in the therapy of acute coronary syndromes. PEG-hirudin (polyethyleneglycol conjugated hirudin) has been developed to provide a longer plasma half-life and more stable antithrombotic plasma levels. Privious trials indicated a narrow therapeutic window for hirudin and a number of aPTT (activated partial thromboplastin time)-monitored trials investigating hirudin in acute coronary syndromes had to be stopped because of intracranial bleeding complications. OBJECTIVES: The present study evaluates the ecarin clotting time (ECT), a parameter based on the conversion of prothrombin by the snake venom enzyme ecarin, for the monitoring of PEG-hirudin therapy. METHODS: Plasma from either healthy volunteers (n=20) or from patients (n=10) suffering from unstable angina pectoris (UAP) was spiked with increasing PEG-hirudin concentrations. In a prospective randomized clinical trial patients with UAP were treated with intravenous PEG-hirudin or heparin over 72 hours. Patients were randomized to the following treatment groups: (1) heparin control group, n=15; (2) PEG-hirudin low dose (0.1 mg/kg bolus, 0.01 mg/kg/h infusion), n=19; (3) intermediate dose (0.15 mg/kg and 0.015 mg/kg/h), n=17; 4) high-dose (0.2 mg/kg and 0.02 mg/kg/h), n=16. Spiked plasma samples and plasma from UAP patients treated with i.v. PEG-hirudin were analyzed for aPTT, ECT, and PEG-hirudin levels. RESULTS: A linear correlation up to the highest therapeutic concentrations could be observed between PEG-hirudin plasma concentrations and the ECT. This was true for both plasma samples spiked with PEG-hirudin in vitro as well as for samples taken from patients treated with i.v. PEG-hirudin (correlation coefficient 0.9, respect.) In contrast the aPTT did not show a reliable linear correlation to PEG-hirudin concentrations. CONCLUSION: Monitoring of PEG-hirudin therapy by ECT may help to avoid inadequate anticoagulation or overdosing. Thus, the safety and efficacy profile of PEG-hirudin therapy is likely to be enhanced by ECT monitoring.

Angina, Unstable↗

Effects of intravenous fat emulsions on lung function in patients with acute respiratory distress syndrome or sepsis.

OBJECTIVE: To investigate whether rapid or slowly infused intravenous fat emulsions affect the ratio of prostaglandin I2/thromboxane A2 in arterial blood, pulmonary hemodynamics, and gas exchange. DESIGN: Prospective, controlled, randomized, crossover study. SETTING: Operative intensive care unit of a university hospital. PATIENTS: Eighteen critically ill patients. Ten patients were stratified with severe sepsis, and eight patients had acute respiratory distress syndrome (ARDS). INTERVENTIONS: Patients were assigned randomly to receive intravenous fat emulsions (0.4 x resting energy expenditure) over 6 hrs (rapid fat infusion) or 24 hrs (slow fat infusion) along with a routine parenteral nutrition regimen, by using a crossover study design. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary hemodynamics as well as gas exchange measurements were recorded via respective indwelling catheters. Arterial thromboxane B2 and 6-keto-prostaglandin-F1alpha plasma concentrations were obtained by radioimmunoassay, and 6-keto-prostaglandin-F1alpha/thromboxane B2 ratios (P/T ratios) were calculated. Data were collected immediately before and 6, 12, 18, and 24 hrs after onset of fat infusion. In the ARDS group, P/T ratio increased by rapid fat infusion. Concomitantly, pulmonary shunt fraction, alveolar-arterial oxygen tension difference [P(a-a)o2]/Pao2, and cardiac index increased as well, whereas pulmonary vascular resistance and Pao2/Fio2 declined. After slow fat infusion, a decreased P/T ratio was revealed. This was accompanied by decreased pulmonary shunt fraction, lowered P(a-a)o2/Pao2, and increased Pao2/Fio2. Correlations between plasma concentrations of 6-keto-prostaglandin-F1alpha or thromboxane B2 and measures of respiratory performance could be shown during rapid and slow fat infusion, respectively. In the sepsis group, the P/T ratio remained unchanged at either infusion rate, but pulmonary shunt fraction and P(a-a)o2/Pao2 decreased after rapid fat infusion, whereas Pao2/Fio2 increased. CONCLUSION: Pulmonary hemodynamics and gas exchange are related to changes of arterial prostanoid levels in ARDS patients, depending on the rate of fat infusion. In ARDS but not in sepsis patients clear of pulmonary organ failure, a changing balance of prostaglandin I2 and thromboxane A2 may modulate gas exchange, presumably via interference with hypoxic pulmonary vasoconstriction.

APACHE↗

Simulated microgravity, psychic stress, and immune cells in men: observations during 120-day 6 degrees HDT.

Because 6 degrees head-down tilt (HDT) is an established method to mimic low gravity on earth, the aim of the present study was to determine the effects of 120-day HDT on psychic stress and peripheral blood immune cells in six healthy male volunteers. Psychological state was assessed by a current stress test, and cortisol was measured in saliva. During HDT, all volunteers developed psychic stress, and the diurnal rhythm of cortisol secretion was significantly altered. In addition, urine excretion of dopamine and norepinephrine increased. The innate part of the immune response was activated, as evidenced by the increase in the expression of beta(2)-integrins on polymorphonuclear leukocytes and a rise in the number of circulating natural killer (NK) cell lymphocytes. The ratio of T-helper to T-cytotoxic and T-suppressor cells decreased, whereas no changes in T and B lymphocytes were observed. Plasma levels of interleukin-6 increased significantly and returned to basal levels after the end of the HDT period. Thus 6 degrees HDT appears to be a valid model to induce psychic stress and neuroendocrine-related changes in the immune system, changes that might also be encountered by astronauts and cosmonauts during long-duration spaceflights.

Adult↗

Effects of hypertonic saline on expression of human polymorphonuclear leukocyte adhesion molecules.

Hypertonic saline prevents vascular adherence of neutrophils and ameliorates ischemic tissue injury. We hypothesized that hypertonic saline attenuates N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated expression of adhesion molecules on human polymorphonuclear leukocytes (PMNLs). fMLP-stimulated up-regulation of beta2-integrins was diminished by hypertonic saline but not by hypertonic choline chloride-, mannitol-, or sucrose-modified Hanks' buffered salt solution. Shedding of L-selectin was decreased by hypertonic saline and choline chloride but not by hypertonic mannitol or sucrose. When the effects of hypertonic sodium chloride- and choline chloride-modified media were compared, neither solution affected fMLP-receptor binding but both equally inhibited fMLP-stimulated increase in intracellular calcium, ionophore A23187, and phorbol myristate acetate (PMA)-stimulated numerical up-regulation of beta2-integrins. Analysis of mitogen-activated protein (MAP) kinases p38 and p44/42 for phosphorylation revealed that hypertonic solutions did not differ in preventing fMLP-stimulated increases in phospho-p38 and phospho-p44/42. Resting PMNLs shrunk by hypertonic saline increased their volume during incubation and further during chemotactic stimulation. Addition of amiloride further enhanced inhibition of up-regulation of beta2-integrins. No fMLP-stimulated volume changes occurred in PMNLs exposed to hypertonic choline chloride, resulting in significant cell shrinkage. Results suggest a sodium-specific inhibitory effect on up-regulation of beta2-integrins of fMLP-stimulated PMNLs, which is unlikely to be caused by alterations of fMLP receptor binding, decrease in cytosolic calcium, attenuation of calcium or protein kinase C-dependent pathways, suppression of p38- or p44/42 MAP kinase-dependent pathways, or cellular ability to increase or decrease volumes.

CD18 Antigens↗

Attenuation by fibrates of plasminogen activator inhibitor type-1 expression in human arterial smooth muscle cells.

Human atherosclerotic lesions exhibit increased expression of plasminogen activator inhibitor type-1 (PAI-1) that has been implicated in atherogenesis. Although vascular smooth muscle cells are a predominant source of PAI-1 expression potentially favorable modulation of PAI-1 expression by fibrates has not yet been characterized in these cells. Human aortic smooth muscle cells were exposed to selected growth factors. PAI-1 expression was stimulated most powerfully by TGF-beta (EC50 = 0.2 ng/ml, up to 12-fold increase). Gemfibrozil inhibited basal PAI-1 expression by 23% (p = ns) and TGF-beta-induced PAI-1 expression by 52% (p = 0.017) whereas t-PA and total protein synthesis was not affected. Changes in PAI-1 protein accumulation reflected PAI-1 gene expression attributable to modulation of half-life of PAI-1 mRNA by gemfibrozil. Inhibition by other fibrates was less. Gemfibrozil specifically attenuates TGF-beta-induced PAI-1 expression in human arterial smooth muscle cells. Thus, fibrates are promising agents for normalizing increased PAI-1 expression in arterial walls in patients in whom PAI-1 expression is increased.

Aorta↗

Cystic fibrosis transmembrane conductance regulator facilitates ATP release by stimulating a separate ATP release channel for autocrine control of cell volume regulation.

These studies provide evidence that cystic fibrosis transmembrane conductance regulator (CFTR) potentiates and accelerates regulatory volume decrease (RVD) following hypotonic challenge by an autocrine mechanism involving ATP release and signaling. In wild-type CFTR-expressing cells, CFTR augments constitutive ATP release and enhances ATP release stimulated by hypotonic challenge. CFTR itself does not appear to conduct ATP. Instead, ATP is released by a separate channel, whose activity is potentiated by CFTR. Blockade of ATP release by ion channel blocking drugs, gadolinium chloride (Gd(3+)) and 4,4'-diisothiocyanatostilbene-2,2'disulfonic acid (DIDS), attenuated the effects of CFTR on acceleration and potentiation of RVD. These results support a key role for extracellular ATP and autocrine and paracrine purinergic signaling in the regulation of membrane ion permeability and suggest that CFTR potentiates ATP release by stimulating a separate ATP channel to strengthen autocrine control of cell volume regulation.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Permissive hypotension.

In trauma patients restoration of intravascular volume in an attempt to achieve normal systemic pressure faces the risk of increasing blood loss and thereby potentially affecting mortality. Due to the lack of controlled clinical trials in this field, the growing evidence that hypotensive resuscitation results in improved long-term survival mainly stems from experimental studies in animals. The main differences between concepts for the reduction of blood loss in systemic hypotension are between "deliberate hypotension" (synonym "controlled hypotension", used intraoperatively), "delayed resuscitation" (where the hypotensive period is intentionally prolonged until operative intervention) and "permissive hypotension" (where restrictive fluid therapy increases systemic pressure without reaching normotension). In this review the concept of "permissive hypotension" is delineated on the basis of macro- and microcirculatory changes secondary to hypovolaemia and low driving pressure, and the potential indications and limitations are discussed.

Humans↗

Intervesicle cross-linking with integrin alpha IIb beta 3 and cyclic-RGD-lipopeptide. A model of cell-adhesion processes.

We report the synthesis of a new integrin alpha(IIb)beta(3)-specific cyclic hexapeptide that contains an Arg-Gly-Asp (RGD) sequence and is coupled to a dimyristoylthioglyceryl anchor. We demonstrate that this ligand is useful to study specific integrin binding to membrane surfaces. With the help of biotinylated analogues of the peptide, a spacer of optimal length between the peptide and lipid moieties was searched for by evaluating the binding strength with an enzyme-coupled immunosorbent assay (ELISA) and by surface plasmon resonance (SPR). It was found to be strongly dependent on the length of the spacer introduced between the biotin and peptide moieties of the ligands, which consisted either of epsilon-aminohexanoic acid (epsilonAhx) or of epsilonAhx with two additional glycine units. Best results were obtained with c[Arg-Gly-Asp-D-Phe-Lys(Biot-Ahx-Gly-Gly)-Gly-] with dissociation constants of K(D) = 0.158 microM from ELISA and K(D) = 1.1 microM from SPR measurements. The analogous lipopeptide, c[Arg-Gly-Asp-D-Phe-Lys([dimyristoyl-3-thioglyceryl-succinimido -propanoyl]Ahx-Gly-Gly)-Gly], was used as a membrane-anchored integrin ligand. It is shown by fluorescence microscopy and cryo electron microscopy that integrin reconstituted into phospholipid vesicles binds to vesicles decorated with the lipopeptide, forming regularly spaced bridges between the two kinds of vesicles. The novel integrin-specific ligand allows establishment of new model systems for systematic studies of the self-organization of integrin clusters and focal adhesion complexes.

Binding Sites↗

Flow cytometric monitoring of glycoprotein IIb/IIIa blockade and platelet function in patients with acute myocardial infarction receiving reteplase, abciximab, and ticlopidine: continuous platelet inhibition by the combination of abciximab and ticlopidine.

BACKGROUND: Improvement of thrombolysis may be achieved by concomitant strong platelet inhibition. To monitor platelet function in patients with myocardial infarction (n=46) who were treated with the fibrinolytic agent reteplase, the glycoprotein (GP) IIb/IIIa blocker abciximab, and the ADP receptor antagonist ticlopidine, we developed a flow cytometric assay. METHODS AND RESULTS: Binding of abciximab to platelets was directly monitored as the percentage of platelets stained by a goat anti-mouse antibody. Blood drawn 10 minutes and 2 hours after the start of therapy with reteplase and abciximab and during the 12-hour infusion of abciximab demonstrated a maximal blockade of GP IIb/IIIa (10 minutes, 86.2+/-10.3%; 12 hours, 85.8+/-7.1%). Starting at 24 hours, abciximab binding gradually decreased (24 hours, 74.6+/-16.2%; 48 hours, 66.8+/-14.9%; 72 hours, 60.5+/-16.7%; 96 hours, 49.4+/-17.8%; 120 hours, 35.8+/-16. 4%; and 144 hours, 29.9+/-15.3%). Binding of a chicken anti-fibrinogen antibody to platelets, indicating the level of functional blockade of GP IIb/IIIa, was inversely correlated with the binding of abciximab (r=-0.72, P:<0.0001). In blood drawn at 10 minutes, platelet aggregation was maximally inhibited but recovered within 48 hours even if the majority of GP IIb/IIIa receptors were still blocked by abciximab. Reteplase did not influence abciximab binding and did not activate platelets, as measured by P-selectin expression, fibrinogen binding, and platelet aggregation. Platelet inhibition that was achieved during the first 24 hours by abciximab was directly maintained by additional treatment with ticlopidine. CONCLUSIONS: Flow cytometric monitoring of platelet function allows differentiation of the effects of reteplase, abciximab, and ticlopidine. The combination of abciximab and ticlopidine is an attractive therapeutic strategy that provides a fast and continuous platelet inhibition.

Abciximab↗

Construction and functional evaluation of a single-chain antibody fusion protein with fibrin targeting and thrombin inhibition after activation by factor Xa.

BACKGROUND: Recombinant technology was used to produce a new anticoagulant that is preferentially localized and active at the site of the clot. METHODS AND RESULTS: The variable regions of the heavy and light chains of a fibrin-specific antibody were amplified by polymerase chain reaction (PCR) with hybridoma cDNA. To obtain a functional single-chain antibody (scFv), a linker region consisting of (Gly(4)Ser)(3) was introduced by overlap PCR. After the scFv clones were ligated with DNA encoding the pIII protein of the M13 phage, high-affinity clones were selected by 10 rounds of panning on the Bbeta15-22 peptide of fibrin (beta-peptide). Hirudin was genetically fused to the C-terminus of the variable region of the light chain. To release the functionally essential N-terminus of hirudin at the site of a blood clot, a factor Xa recognition site was introduced between scFv(59D8) and hirudin. The fusion protein was characterized by its size on SDS-PAGE (36 kDa), by Western blotting, by its cleavage into a 29-kDa (single chain alone) and 7-kDa (hirudin) fragment, by its binding to beta-peptide, and by thrombin inhibition after Xa cleavage. Finally, the fusion protein inhibited appositional growth of whole blood clots in vitro more efficiently than native hirudin. CONCLUSIONS: A fusion protein was constructed that binds to a fibrin-specific epitope and inhibits thrombin after its activation by factor Xa. This recombinant anticoagulant effectively inhibits appositional clot growth in vitro. Its efficient and fast production at low cost should facilitate a large-scale evaluation to determine whether an effective localized antithrombin activity can be achieved without systemic bleeding complications.

Amino Acid Sequence↗