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Biomedical subjects

M Levi

Publications and source records attributed to M Levi.

At least 127 records · Page 7Linked to original sources
PubMed2000

The effect of the administration of recombinant activated factor VII (NovoSeven) on perioperative blood loss in patients undergoing transabdominal retropubic prostatectomy: the PROSE study.

Transabdominal retropubic prostatectomy is associated with significant perioperative blood loss, often requiring blood transfusion. However, the administration of allogeneic blood and blood products may induce serious immunological or infectious complications. Several studies show that recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) induces short-term local hemostasis. This ongoing study will evaluate the safety and efficacy of rFVIIa on blood loss in patients with normal coagulation undergoing retropubic prostatectomy. Thirty-six patients will be randomized to three different dose levels and receive either rFVIIa as a single intravenous bolus dose or saline. Perioperative blood loss will be assessed from blood-volume suction containers and drains. Blood sample analysis, physical examination and electrocardiography will be performed postoperatively. Eighteen patients have enrolled in the study. Blood loss was 630-4455 ml (mean = 1698 ml), while the number of red cell transfusions varied between 0 and 4 units (mean = 0.9 units). None of the patients developed venous thromboembolism. An independent committee performed an interim analysis after patient 12 and identified a positive trend between treatment groups (not statistically significant). Although a single bolus injection of rFVIIa appears to decrease perioperative blood loss safely and effectively, definite conclusions must await study completion.

Blood Loss, Surgical↗
PubMed2000

Novel approaches to the management of disseminated intravascular coagulation.

OBJECTIVE: Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in the circulation. We addressed the issue of whether there is evidence that this fibrin deposition contributes to multiple organ failure. We also explored the current knowledge on the pathogenesis of DIC and reviewed current and future treatment for DIC. DATA SOURCES: We searched and reviewed published articles on experimental studies of DIC models in animals and clinical studies in patients with DIC. DATA SYNTHESIS: There is ample experimental and clinical evidence that DIC contributes to morbidity and mortality. Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with DIC. Although the trigger for the activation of the coagulation system may vary depending on the underlying condition, it is usually mediated by several cytokines. Thrombin generation proceeds via the (extrinsic) tissue factor/factor VIIa route and simultaneously occurring depression of inhibitory mechanisms, such as antithrombin III and the protein C-protein S system. Also, impaired fibrin degradation, because of high circulating levels of plasminogen activator inhibitor, type 1, contributes to enhanced intravascular fibrin deposition. CONCLUSIONS: Although the cornerstone of DIC management is the specific and vigorous treatment of the underlying disorder, strategies aimed at inhibiting coagulation activation may theoretically be justified. Such strategies have been found to be beneficial in experimental and initial clinical studies. These strategies, which follow from our current understanding of the pathophysiology of DIC, involve inhibition of tissue factor-mediated activation of coagulation or restoration of physiologic anticoagulant pathways by means of the administration of antithrombin concentrate or (activated) protein C concentrate. Although no complete evidence from controlled clinical trials is available for most of the proposed therapeutic interventions, these novel strategies are being studied.

Animals↗
PubMed2000

Platelets release thrombopoietin (Tpo) upon activation: another regulatory loop in thrombocytopoiesis?

Thrombopoietin is produced at a constant rate by the liver and kidney and is removed from the circulation upon binding and subsequent uptake via the Tpo receptor, c-Mpl, expressed by platelets and mega-karyocytes. Apart from uptake, this study shows that platelets can also function as a storage pool for Tpo. Upon stimulation with various platelet agonists, full-length biologically active Tpo was released by platelets. Platelet fractionation experiments indicated that this Tpo most likely is contained in the granules. When platelets were preincubated with Tpo-peptide mimetic or truncated Tpo prior to maximal activation, a three- to fivefold increment in Tpo release was seen. whereas, the release of other granule proteins such as vWF-propeptide or serotonin remained unchanged. Therefore, the Mpl agonists might compete with Mpl-bound Tpo, thereby releasing Tpo into the platelet supernatant. Intravascular release of Tpo by platelets might occur in patients with massive platelet activation, as occurs in patients with disseminated intravascular coagulation. The Tpo concentration in these patients is elevated (p <0.01) and correlates with markers for thrombin generation, TAT complexes and F1+2(r(p)= 0.8 and 0.9; p <0.01). This suggests that the increment in Tpo concentration was attributed to Tpo release by activated platelets in vivo, which might be instrumental in subsequent stimulation of thrombocytopoiesis.

Adult↗
PubMed2000

A new FISH protocol with increased sensitivity for physical mapping with short probes in plants.

Fluorescence in situ hybridization (FISH) is a well-established technique used for the detection of specific DNA regions, that has been applied to interphase nuclei, pachytene and metaphase chromosomes as well as to extended DNA fibres. This technique allows the physical mapping of specific DNA sequences both on individual chromosomes and extended fibres. A new FISH protocol is described here that enhances the sensitivity of the method. Probes for small unique DNA sequences of less than 2 kb give high signal-to-noise ratio with this method, and can be visualized easily by means of conventional fluorescence microscopy.

Asparagus Plant↗
PubMed2000

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.

Administration, Oral↗
PubMed1999

Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints.

BACKGROUND: Excessive bleeding may complicate cardiac surgery, and is associated with increased morbidity and mortality. Pharmacological strategies to decrease perioperative bleeding have been investigated in a large number of controlled trials, most of which have shown a decrease in blood loss. However, most studies lacked sufficient power to detect a beneficial effect on clinically more relevant outcomes. We did a meta-analysis of all randomised, controlled trials of the three most frequently used pharmacological strategies to decrease perioperative blood loss (aprotinin, lysine analogues [aminocaproic acid and tranexamic acid], and desmopressin). METHODS: Studies were included if they reported at least one clinically relevant outcome (mortality, rethoracotomy, proportion of patients receiving a transfusion, or perioperative myocardial infarction) in addition to perioperative blood loss. In addition, a separate meta-analysis was done for studies concerning complicated cardiac surgery. FINDINGS: We identified 72 trials (8409 patients) that met the inclusion criteria. Treatment with aprotinin decreased mortality almost two-fold (odds ratio 0.55 [95% CI 0.34-0.90]) compared with placebo. Treatment with aprotinin and with lysine analogues decreased the frequency of surgical re-exploration (0.37 [0.25-0.55], and 0.44 [0.22-0.90], respectively). These two treatments also significantly decreased the proportion of patients receiving any allogeneic blood transfusion. By contrast, the use of desmopressin resulted in a small decrease in perioperative blood loss, but was not associated with a beneficial effect on other clinical outcomes. Aprotinin and lysine analogues did not increase the risk of perioperative myocardial infarction; however, desmopressin was associated with a 2.4-fold increase in the risk of this complication. Studies in patients undergoing complicated cardiac surgery showed similar results. INTERPRETATION: Pharmacological strategies that decrease perioperative blood loss in cardiac surgery, in particular aprotinin and lysine analogues, also decrease mortality, the need for rethoracotomy, and the proportion of patients receiving a blood transfusion.

Aminocaproates↗
PubMed1999

[Physical diagnosis--paradoxical pulse].

Pulsus paradoxus is generally defined as a decline in the systemic systolic blood pressure by more than 10 mmHg during inspiration. The main clinical situations in which a paradoxical pulse may be observed are inflow obstruction into the heart (as in exsudative pericarditis or cardiac tamponade) or extreme respiratory variations in intrathoracal pressure (as during an asthma attack). However, clinical studies indicate that in both situations the predictive value of a present or absent pulsus paradoxus is rather limited.

Airway Obstruction↗
PubMed1999

[Physical examination--the significance of Homan's sign].

Homans's sign is often used in the diagnosis of deep venous thrombosis of the leg. A positive Homans's sign (calf pain at dorsiflexion of the foot) is thought to be associated with the presence of thrombosis. However, Homans's sign has a very poor predictive value for the presence or absence of deep vein thrombosis, like any other symptom or clinical sign of this disease.

Humans↗
PubMed1999

[Pharmacotherapeutic choices for correction of disorders of primary hemostasis].

A defective primary haemostatic system is a relatively frequent disorder, due to the increasing use of aspirin and other non-steroid anti-inflammatory agents (NSAIDs) by the general population. Impaired primary haemostasis may result in enhanced perioperative bleeding. Administration of desmopressin is an effective pharmacotherapeutic intervention that will improve the process of primary haemostasis in many cases, with or without additional interventions in the clotting system.

Adult↗
PubMed1999

Antigen-specific immunosuppression: nasal tolerance to P0 protein peptides for the prevention and treatment of experimental autoimmune neuritis in Lewis rats.

Experimental autoimmune neuritis (EAN) is an autoimmune inflammatory demyelinating disease of the peripheral nervous system (PNS), and represents an animal model of the human Guillain-Barré syndrome (GBS). In this study, we report that nasal administration of the neuritogenic peptide 180-199 and of the cryptic peptide 56-71 of the rat neuritogenic P0 protein of peripheral nerve myelin prevents EAN and attenuates ongoing EAN. Both peptides effectively decreased the severity and shortened clinical EAN. Both a prophylactic and a therapeutic approach proved to be beneficial. These effects were associated with T and B cells hyporesponsiveness to the peptide antigens, reflected by downregulated Th1 cell responses (interferon-gamma secretion) and macrophage function, whereas Th2 cell responses (IL-4 secretion) and transforming growth factor-beta mRNA expression were upregulated.

Administration, Intranasal↗
PubMed1999

Induction of experimental autoimmune neuritis in CD4-8-C57BL/6J mice.

The C57BL/6J mice strain is known to be reputedly resistant to induction of experimental autoimmune neuritis (EAN), an animal model of Guillain-Barré syndrome in humans. Here we describe the induction of EAN in mice of the C57BL/6J background by transfer into naive syngeneic recipients bovine peripheral nerve myelin (BPM)-primed donor lymph node cells that had been stimulated in vitro with the bovine peripheral nervous system (PNS) myelin P2 protein peptide 57-81 followed by challenge with BPM, Freund's complete adjuvant and pertussis toxin. EAN was more severe, both clinically and histologically, and accompanied by extensive infiltration of inflammatory cells and demyelination in peripheral nerves when examined on day 30 after transfer of primed T cells from CD4- 8- mice into identical naive hosts than after transfer of cells from primed wild type, CD4-/- or CD8-/- mice to corresponding recipient animals. EAN in CD4-8- mice was also associated with elevated numbers of P2 peptide-reactive interferon-y (TFN-gamma) secreting cells and alphabeta T cells were present in lymph nodes and spleens. The data suggest that PNS myelin activated T cells from an EAN-resistant mice strain are capable of homing to the PNS. The expanded CD4-8- alphabeta T cells may have helper and effector functions, related to initiation of EAN in the CD4-8- mice. Lack of CD4+ and CD8+ expressing cells does not prevent the initiation of an autoimmune disease.

Animals↗
PubMed1999

Epitope specificity of the monoclonal anticytokeratin antibody TS1.

Due to their abundance in epithelial cells and deposition in necrotic regions intratumorally, cytokeratins (CKs) have been established as valuable targets for both radioimmunolocalization and radioimmunotherapy. The target epitope for the monoclonal anti-CK8 antibody, TS1, used for both experimental radioimmunolocalization and radioimmunotherapy, was determined by means of synthesis of 96 overlapping peptides that covered the entire CK8 molecule. A highly conserved peptide sequence, spanning amino acids (aa) 343-357 and covering the discontinuous epitope in the helical 2B domain, was identified. The epitope retains its helical structure, as shown with circular dichroism spectroscopy, although the length of the peptide (ie., >20 aa) is crucial for maintenance of immunoreactivity. To determine which aa residues are crucial for binding to the monoclonal antibody, alanine scanning was performed on a 26-mer covering aa 340-365, with the sequence QRGELAIKDANAKLSELEAALQRAKQ. The 26 modified peptides were evaluated using ELISA and BIAcore technology. The uniqueness of this epitope has been established by data base sequence comparisons.

Amino Acid Sequence↗
PubMed1999

Immunoglobulin variable genes and epitope recognition of human monoclonal anti-Ro 52-kd in primary Sjögren's syndrome.

OBJECTIVE: To clone and characterize human anti-Ro/SSA autoantibodies from a patient with primary Sjögren's syndrome (pSS). METHODS: Monoclonal antibodies (mAb) were raised from the peripheral blood of a patient with pSS using Epstein-Barr virus transformation and a hybridoma technique. Specificity was determined using cell extracts, recombinant Ro 52-kd, Ro 60-kd, and La proteins as well as Ro 52-kd peptides in enzyme-linked immunosorbent assay (ELISA) and Western blot. The immunofluorescence pattern was analyzed using cultured human and mouse cell lines. Complementary DNA was amplified by polymerase chain reaction, and Ig variable (V)-region genes were directly sequenced. RESULTS: Two human anti-Ro 52-kd mAb of IgM isotype, denoted SG1 and SG3, were cloned from the peripheral blood of a patient with pSS. The 2 mAb reacted with the Ro 52-kd antigen in cell extracts of human cell lines and mouse cell lines, and with purified human recombinant Ro 52-kd protein in ELISA and Western blot. SG1 reacted specifically with 1 peptide, amino acids 136-156, of the Ro 52-kd protein, and SG3 was mapped to react with a recombinant fragment representing amino acids 136-292. Immunofluorescence studies revealed cytoplasmic staining with both mAb. Both were encoded by V(H)3-family genes. SG1 was highly homologous to the DP-77 germ-line gene, with 2 replacement mutations and 1 silent. It utilized the DPL-11 germ-line gene from the Vlambda2-family gene, with 1 silent mutation. SG3 was 100% homologous to the DP-47 germ-line gene, combined with a Vkappa1-family gene that was 100% homologous to the A30 germ-line gene. CONCLUSION: Two human mAb were demonstrated to be specific for the Ro 52-kd protein and to be directed against 2 different epitopes, 1 linear and 1 conformation-dependent, within a region previously described to be immunodominant. Somatic hypermutation appeared to be of minor importance in generating these 2 specificities.

Antibodies, Monoclonal↗
PubMed1999

Nasal administration of recombinant rat IL-4 ameliorates ongoing experimental autoimmune neuritis and inhibits demyelination.

Experimental autoimmune neuritis (EAN) is a CD4(+)T cell-mediated demyelinating disease of the peripheral nervous system (PNS) and serves as an experimental model for human immune-demyelinating neuropathies. In this study, we examined the effect of recombinant rat interleukin-4 (rrIL-4) on chronic EAN in Lewis rats induced by immunization with P0 peptide 180-199 and complete Freund's adjuvant (CFA). We estimated that nasal administration of rrIL-4, in dose ranges of 0.1-1 microg/rat/day in the initial phase of EAN, decreased the severity and the duration of clinical EAN. Hyporesponsiveness of T cells, downregulation of Th1 cell responses (INF-gamma), but increased levels of specific IgG1 isotypes document that nasal administration of rrIL-4 was systemically immune effective. Low grade inflammation and complete lack of regional demyelination within the sciatic nerves were seen in rrIL-4 treated rats. Based on these observations we suggest that nasal administration of IL-4 could be further evaluated, considering its possible use in human immune-demyelinating neuropathies.

Administration, Intranasal↗
PubMed1999

Intraperitoneal hypercoagulation and hypofibrinolysis is present in childhood peritonitis.

An increased rate of obstruction of peritoneal dialysis catheters is observed during peritonitis. Hypercoagulation and hypofibrinolysis may explain this increased occurrence. We studied plasminogen activator inhibitor type 1 antigen (PAI-1), tissue-type plasminogen activator antigen (t-PA), D-dimer (DD), plasmin-alpha2-antiplasmin complexes (PAP), and thrombin-antithrombin III complexes (TAT) in 7 children with peritonitis (group A) and 12 children during stable peritoneal dialysis (group B). Albumin, beta2-microglobulin, IgG, and alpha2-macroglobulin were measured for baseline transperitoneal protein transport. After a dwell of 6 h with 1.36% Dianeal, dialysate and serum samples were collected. Dialysate to plasma ratios of all proteins were calculated. During peritonitis (group A) TAT was higher: 34.7 versus 22.0 (P=0.01). PAI-1 was increased in group A: 76.5 versus 22.9 (P=0.004). PAP was decreased during peritonitis (group A): 24.9 versus 39.3 (P=0.01). In group A, DD were decreased. 10.8 versus 26.7 (P=0.002). t-PA was similar in both groups (23.7 in group A vs. 27.7 in group B; P=0.26). In both groups TAT, PAI-1, t-PA, PAP, and DD were significantly higher than in baseline transperitoneal transport, suggesting intraperitoneal production. Hypercoagulability and hypofibrinolysis were present during peritonitis compared with the control situation.

Adolescent↗