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Biomedical subjects

G Agnelli

Publications and source records attributed to G Agnelli.

At least 127 records · Page 7Linked to original sources
PubMed1990

Diagnostic accuracy of computerized impedance plethysmography in the diagnosis of symptomatic deep vein thrombosis: a controlled venographic study.

The aim of our study was to evaluate the sensitivity, the specificity, and the positive and negative predictive values of a recently developed computerized impedance plethysmography (CIP) in the diagnosis of deep vein thrombosis (DVT); 117 consecutive outpatients with a clinical suspicion of DVT were evaluated. After informed consent was obtained, a CIP and, within twenty-four hours, a venography of the symptomatic lower limb were performed in each patient. The results of CIP were compared with the results of contrast venography, which was considered as the gold standard. As far as the diagnosis of both proximal and distal DVT was concerned, the accuracy of CIP was 88.5%; the sensitivity and specificity were 95.1% and 83.6%, respectively; the positive and negative predictive values were 81.2% and 95.8%, respectively. When the diagnosis of only proximal deep vein thrombosis was considered, the accuracy of CIP was 88.8%; the sensitivity and specificity were 97.1% and 83.6%, respectively; the positive and negative predictive values were 79.0% and 97.8%, respectively. The authors conclude that the newly developed CIP has a diagnostic accuracy similar to that of traditional impedance plethysmography. Moreover, being completely automated and portable, CIP can play an important role in the bedside diagnosis of DVT.

Diagnosis, Computer-Assisted↗
PubMed1990

Rationale for bolus t-PA therapy to improve efficacy and safety.

Tissue-type plasminogen activator has high affinity for fibrin and is activated by fibrin. Because of these properties, t-PA was initially expected to cause minimal bleeding complications. This prediction has been only partially confirmed in major clinical trials in which t-PA was given in the doses necessary for effective coronary thrombolysis. The risk of bleeding in patients receiving t-PA is correlated with increased levels of fibrin degradation products and hypofibrinogenemia, consistent with a link between systemic plasminemia and hemorrhage. Limiting t-PA-associated bleeding may therefore require measures aimed at decreasing hyperplasminemia. These measures include a short infusion of a high t-PA dose. This article presents new experimental evidence that has confirmed our previous results showing that a short infusion of t-PA is an effective and safe thrombolytic treatment.

Animals↗
PubMed1990

[Impedance plethysmography, Doppler echography and phlebography in deep venous thromboses of the lower limbs].

Computerized impedance plethysmography (CIP) and phlebography were performed on 165 consecutive outpatients with clinical suspicion of deep venous thrombosis (DVT) and on 220 consecutive asymptomatic patients hospitalized for hip fracture. Ninety-two asymptomatic patients were examined also with real-time B-mode US. In orthopedic patients CIP sensitivity, specificity, accuracy, positive and negative predictive values were 19.4%, 90.5%, 64.4%, 53.8% and 66.3%, respectively, for proximal and distal DVT, versus 19.7%, 88%, 77.5%, 77% and 86% for proximal DVT. In symptomatic patients CIP sensitivity, specificity, accuracy, positive and negative predictive values were 83%, 87%, 85%, 87% and 82%, respectively, for proximal and distal DVT, versus 91%, 88%, 89%, 82% and 94% for proximal DVT. CIP had great diagnostic utility in symptomatic DVT, whereas its diagnostic efficacy was low in asymptomatic patients. In orthopedic patients US sensitivity, specificity positive and negative predictive values were 44%, 99.2%, 95.7% and 81.6%, respectively. US diagnostic value was relatively high, but further investigation is needed. To date, phlebography seems to be the only effective method in the diagnosis of DVT in asymptomatic high risk patients.

Diagnosis, Computer-Assisted↗
PubMed1989

DDAVP induces systemic release of urokinase-type plasminogen activator.

The desamino-d-arginine vasopressin (DDAVP) induced enhancement of endogenous fibrinolysis is generally attributed to the release of tissue-type plasminogen activator (t-PA) from the vessel wall. The observation of concurrent release of urokinase-type plasminogen activator (u-PA), which eventually might cooperate in the enhanced fibrinolytic activity, has not been reported thus far. In a preliminary study in two healthy human volunteers we found a 1.8-fold increase of urokinase-antigen (UK-antigen) and a 1.7-fold increase of plasmin-activatable pro-urokinase (pro-UK) activity to DDAVP intravenously. The plasma-peak levels coincided with the maximal t-PA level. These responses following infusion of DDAVP were subsequently confirmed in a randomized double blind cross-over study in six human volunteers. We conclude that u-PA is released by DDAVP concurrently with t-PA and that it is presumably from the same origin as t-PA i.e. endothelial cells. u-PA and t-PA may therefore cooperate in the enhanced fibrinolytic activity upon DDAVP infusion.

Deamino Arginine Vasopressin↗
PubMed1989

Additive effect of dDAVP and standard heparin in increasing plasma t-PA.

The aim of this study was to evaluate the existence of an additive effect between standard heparin and dDAVP in the enhancement of endogenous fibrinolysis. Eight healthy volunteers were studied in a randomized double blind placebo controlled cross-over trial. The volunteers were treated i.v. with dDAVP, 0.4 micrograms/kg, over 15 minutes followed by an i.v. bolus dose of either standard heparin, 5,000 I.U., or saline. A 48 hour wash-out period was adopted. The infusion of dDAVP followed by standard heparin resulted in a higher increase in plasma t-PA activity, t-PA antigen, circulating t-PA specific activity and FPLA when compared with dDAVP followed by saline. The difference was already statistically significant at 15 minutes after the infusion of dDAVP and lasted for up to 60 minutes after the end of the infusion of dDAVP. Plasma PAI 1 showed a slightly higher decrease after dDAVP plus standard heparin than after dDAVP plus saline but this difference was not statistically significant. No statistically significant changes of fibrinogen and alpha 2-antiplasmin levels were observed. As expected, the infusion of standard heparin resulted in an increase in plasma anti-Xa activity and in a prolongation of aPTT. Our results demonstrated an additive effect of dDAVP and standard heparin on the increase in circulating t-PA, the effect of dDAVP being potentiated and prolonged by heparin. This observation could prospect a combined use of dDAVP and standard heparin in the prophylaxis and treatment of thromboembolic diseases.

Adult↗
PubMed1988

Effects of standard heparin and a low molecular weight heparin (Kabi 2165) on fibrinolysis.

Previous and recent reports have suggested a fibrinolysis-enhancing property of standard heparin and low molecular weight heparins, but these observations have never been confirmed in a study fulfilling appropriate methodological criteria. The aim of this study was to evaluate the effect of standard heparin and a low molecular weight heparin (Kabi 2165) on fibrinolysis in a randomized cross-over double blind placebo controlled study. Six healthy volunteers received intravenously a bolus dose of the following treatments: placebo; standard heparin, 5,000 I.U.; Kabi 2165, 5,000 anti-Xa U; Kabi 2165, 10,000 anti-Xa U. Before the injection and at established times thereafter, blood samples were collected for the following assays in plasma: t-PA activity, PA inhibitor activity, fibrin plate lysis area (FPLA), plasminogen, alpha 2-antiplasmin, fibrinogen and anti-Xa activity. Placebo and Kabi 2165, 5,000 anti-Xa U, had no effect on t-PA plasma level. Standard heparin and Kabi 2165, 10,000 anti-Xa U, produced a statistically significant increase in t-PA level at 1 hour after the infusion. This increase lasted for at least 1 hour after the infusion. No effect of any treatment on PA inhibitor, plasminogen, FLPA, alpha 2-antiplasmin and fibrinogen was observed. We conclude that an intravenous bolus dose of both standard heparin, 5,000 I.U. and Kabi 2165, 10,000 anti-Xa U produces a delayed and sustained increase in plasma t-PA.

Adult↗
PubMed1988

Platelet-tumor cell interaction: effect of prostacyclin and a synthetic analog on metastasis formation.

The antimetastatic effect of the antithrombotic agents exogenous prostacyclin (PGI2) and a synthetic analog, Iloprost, on experimental metastasis formation was studied by injecting BL6 melanoma cells into C57BL/6 mice. Suitable in vivo treatment conditions were selected according to the known properties of the two drugs, including their pharmacokinetics. Iloprost showed a greater ability to inhibit platelet aggregation induced by BL6 melanoma cells. PGI2 displayed a limited antimetastatic activity, largely dependent on the tumor cell load and treatment schedule. Iloprost showed a far superior activity, its antimetastatic effect lasting longer and remaining detectable up to 6 h after tumor cell inoculation. The present data complex provides further support to the concept of a crucial role for platelet-tumor cell interaction in the process of metastasis formation.

Animals↗
PubMed1988

Effects of cefamandole on hemostasis in patients undergoing hip replacement with heparin prophylaxis.

The aim of this study was to compare the effects of the prophylactic use of cefamandole versus oxacillin plus gentamicin on hemostasis in patients undergoing hip replacement with heparin prophylaxis. Twenty-four patients with a normal hemostatic profile were randomly allocated to receive either cefamandole or oxacillin plus gentamicin. All the patients received calcium heparin. Platelet count, bleeding time, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin clotting time (TCT), fibrinogen and serum FDP were assessed before treatment and every day of antibiotic administration. Surgical bleeding was assessed using a four-grade score system. Platelet count, bleeding time, fibrinogen and serum FDP did not show any change with both treatments. PT, aPTT and TCT showed a similar and mild prolongation in the two groups of patients. No difference in the surgical bleeding was observed between the two groups. We conclude that a short-term prophylaxis with cefamandole is a safe regimen in patients undergoing hip replacement with heparin prophylaxis.

Aged↗
PubMed1987

Optimal dosage regimens of tissue-type plasminogen activator.

The optimal therapeutic regimen for t-PA in humans remains to be determined. The ideal dosage regimen for t-PA should achieve effective thrombolysis as quickly as possible with minimum fibrinogenolysis to minimize bleeding. Our findings in rabbits suggest that the present regimens in humans might be improved by using frequent rapid infusions rather than the more prolonged infusions. Clearly, the results of our animal studies will have to be confirmed in man before firm recommendations can be made.

Animals↗
PubMed1987

Effects of the new glycopeptide antibiotic teicoplanin on platelet function and blood coagulation.

Teicoplanin, a new glycopeptide antibiotic, is structurally related to ristocetin, an antibiotic known to induce human platelet agglutination and, thus, thrombocytopenia and thromboembolic side effects. The aim of this study was to evaluate the effects of teicoplanin on platelet function in vitro and ex vivo and on blood coagulation ex vivo. In the in vitro studies, spontaneous platelet aggregation; platelet aggregation induced by ADP, collagen, and ristocetin; and the release of beta-thromboglobulin from platelets were assessed. Platelets from healthy subjects were incubated with teicoplanin at final concentrations of 100, 1,500, 5,000, and 10,000 micrograms/ml. The maximal achievable concentration with therapeutic doses is 100 micrograms/ml. When compared with saline, teicoplanin at concentrations of 100 and 1,500 micrograms/ml had no effect on platelet function, but at concentrations of 5,000 and 10,000 micrograms/ml, it induced greater spontaneous platelet aggregation (P less than 0.01) and inhibited platelet aggregation induced by ADP, collagen, and ristocetin (P less than 0.01). Teicoplanin at concentrations of 100, 1,500, and 5,000 micrograms/ml did not induce the release of beta-thromboglobulin, in contrast to teicoplanin at a concentration of 10,000 micrograms/ml and ristocetin at a concentration of 1.5 mg/ml (P less than 0.01). In the ex vivo studies, platelet count, bleeding time, plasma beta-thromboglobulin, platelet aggregation induced by ADP, ristocetin, and epinephrine, activated partial thromboplastin time, prothrombin time, thrombin clotting time, and serum fibrinogen degradation products were evaluated at days 0, 3, and 6 and at 72 h after the end of therapy. All subjects completed the study without evidence of side effects. When compared with the pretreatment values, none of the values from these assays showed a significant change at any time during and after treatment. We concluded that platelet function and blood coagulation are not affected by therapeutic concentrations of teicoplanin and that in vitro platelet function is affected only by concentrations of teicoplanin far in excess of those that are clinically achievable.

Adult↗
PubMed1987

Effects of the monobactam antibiotic aztreonam on platelet function and blood coagulation.

The effects of the new monobactam antibiotic aztreonam on platelet function and blood coagulation were evaluated both in vitro and ex vivo. In the in vitro studies carried out on platelets from 6 healthy volunteers, therapeutic concentrations of aztreonam had no effect on platelet function. Aztreonam inhibited platelet aggregation only at concentrations far in excess of those clinically achievable. In the ex vivo studies carried out in 11 patients with aztreonam-sensitive infections, aztreonam, 1 g t.i.d. intravenously, did not produce any effect on platelet function and blood coagulation. We conclude that therapeutic doses of aztreonam appear not to affect haemostasis.

Adenosine Diphosphate↗
PubMed1986

Cephalosporin-induced hypoprothrombinemia: is the N-methylthiotetrazole side chain the culprit?

The reported high incidence of vitamin-K-reversible hypoprothrombinemia associated with the new beta-lactamase-stable cephalosporins prompted us to evaluate the effect on hemostasis of three cephalosporins (cefamandole, ceftriaxone, and ceftazidime) in 30 patients with serious infections. Cefamandole and ceftriaxone, both containing a sulfhydryl group, induced a significant and similar prolongation of prothrombin time and decrease in factor VII activity. Ceftazidime, in contrast, had no effect on these two parameters.

Azoles↗
PubMed1985

The thrombolytic and hemorrhagic effects of tissue type plasminogen activator: influence of dosage regimens in rabbits.

Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals and in humans. We have previously observed that the thrombolytic effect of t-PA persists beyond its time of clearance from the circulation and that wound bleeding induced by a high dose infusion of t-PA is delayed for at least one and a half hours after commencing the infusion. These observations suggest that improved thrombolysis may be obtained with t-PA by infusing a high dose over a short period of time. To test this hypothesis we compared the thrombolytic and hemorrhagic effects of t-PA infused over 240, 60, 30 and 15 minutes in the rabbit. A 4 hour infusion of 30,000 U/kg of t-PA produced 36% thrombolysis. The same dose of t-PA infused over 60, 30 and 15 minutes produced 87%, 88% and 96% thrombolysis, respectively (p less than 0.01). The 1 hour infusion of 30,000 U/kg of t-PA produced a significant increase in blood loss relative to saline infusion (p less than 0.01). The same dose infused over 30 and 15 minutes did not produce significantly more bleeding than saline. A higher dose of t-PA, 60,000 U/kg, infused over 4 hours, produced 95% thrombolysis, but was associated with a significant increase of blood loss (p less than 0.001). Our findings suggest that improved thrombolysis with t-PA with minimal bleeding side-effects is achieved in rabbits when t-PA is administered in a relatively high dose given over a short period of time.

Animals↗
PubMed1985

A comparison of the thrombolytic and hemorrhagic effects of tissue-type plasminogen activator and streptokinase in rabbits.

Tissue-type plasminogen activator (t-PA) is a promising thrombolytic agent because it can produce thrombolysis without inducing a plasma proteolytic state. It is uncertain if this potentially important feature renders t-PA less hemorrhagic than other plasminogen activators. We have compared the hemorrhagic and thrombolytic effects of t-PA and streptokinase in rabbits. Streptokinase, 4000 U/kg/hr over 4 hr, failed to produce significant thrombolysis and 8000 U/kg/hr streptokinase over 4 hr produced only 28 +/- 6% thrombolysis. Both streptokinase regimens were associated with a plasmin-mediated plasma proteolytic state and both streptokinase regimens produced a significant increase in hemorrhage that was evident within 15 min of beginning the infusion and was progressive over the 4 hr of drug administration. In contrast, t-PA in a dose of 7500 U/kg/hr produced 35 +/- 6% thrombolysis, but it did not produce a plasmin-mediated plasma proteolytic state or a significant increase in hemorrhage over the 4 hr of infusion. t-PA in a dose of 15,000 U/kg/hr produced 85 +/- 4% thrombolysis but was associated with a plasmin-mediated proteolytic state and produced significant bleeding which, in contrast to streptokinase-induced bleeding, was delayed in onset. Therefore, t-PA induced less hemorrhage than streptokinase at doses that produced more effective thrombolysis. Bleeding with both thrombolytic agents was associated with a plasmin-mediated proteolytic state.

Animals↗
PubMed1985

Sustained thrombolysis with DNA-recombinant tissue type plasminogen activator in rabbits.

Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals. The duration of the thrombolytic effect of infused t-PA is unknown. We compared the duration of the thrombolytic effect of t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled thrombi in rabbit jugular veins at different times after a bolus injection of the fibrinolytic agents. The pharmacodynamics of both thrombolytic agents were determined in rabbits using a sensitive ex vivo fibrinolytic assay. Streptokinase and t-PA were given as a bolus dose of 15,000 U/kg. There was no detectable circulating fibrinolytic activity 30 minutes after the bolus dose of t-PA and 120 minutes after the bolus dose of streptokinase. The t-PA injection produced 34% thrombolysis at 30 minutes, 90% thrombolysis at 120 minutes, and 96% thrombolysis at 240 minutes. The streptokinase injection produced 17% thrombolysis at 30 minutes, 34% at 120 minutes, and 34% at 240 minutes. These observations indicate that the thrombolytic effect of t-PA is sustained beyond its time of clearance from the circulation whereas the thrombolytic effect of streptokinase closely parallels its activity in the circulation.

Animals↗
PubMed1983

Effect of DDAVP on plasma level of factor XII.

The effect of DDAVP on blood coagulation factors was investigated after its intravenous infusion into normal subjects. A marked increase in factor XII was observed in addition to the expected rise of factor VIII coagulant activity (VIII:C), factor VIII related antigen (VIIIR:Ag) and plasminogen activator, DDAVP also produced a concomitant but less pronounced rise of factor VII, but there was no change in factors V, IX, X and XI.

Adult↗