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Biomedical subjects

J L David

Publications and source records attributed to J L David.

At least 19 recordsLinked to original sources
PubMed1999

[Plasma concentrations of vitamin K1 and acenocoumarol related to international normalized ratios].

Reduced vitamins K are acting as cofactors of glutamic carboxylation of procoagulant factors (II, VII, IX and X). The reduction of these vitamins is inhibited by oral anticoagulants. The response to antivitamins K is individual and may change during the treatment of a patient. The determinations of plasmatic vitamin K and acenocoumarol may help to explain the mechanism of a resistance to the anticoagulant therapy. Quantifications of vitamin K1 are realized after liquid-liquid extraction with liquid chromatography and fluorescence detection after post-column reduction. For acenocoumarol, plasma concentration is measured, after liquid-liquid extraction, by liquid chromatograph, with ion trap mass spectrometer detector.

Acenocoumarol↗
PubMed1999

[Anti-platelet agents in peripheral vascular surgery].

Prescription of platelet inhibitors after arterial surgery is common use. The major concern of the vascular surgeon is to maintain patency of arterial reconstructions. Major causes of graft failure or arterial thrombosis are the non-thromboresistant nature of the grafts and of the endarterectomised or balloon-dilated surfaces, restenosis due to intimal hyperplasia and progression of atherosclerotic disease in in- or outflow vessels. Platelet adhesion and intimal injury are the primary causes in both processes of graft thrombosis and intimal hyperplasia. To understand how antiplatelet drugs can interfere with these processes, a brief review of platelet function, and of the main platelet inhibitors (aspirin, dypiridamole, ticlopidine) is given. The pathophysiology of intimal hyperplasia is discussed. From clinical trials of peripheral vascular surgery or percutaneous transluminal angioplasty with or without periprocedural antiplatelet therapy, it appears that platelet inhibitors reduce early failure rate by 50% (thrombosis rate at one year reduced from 40 to 20%). There is also evidence that antiplatelet drugs allow to slow down the progression of the atherosclerotic degenerative process in the outflow vessels and in other vascular territories. For the polyvascular patients with charged passed history, platelet inhibitors reduce the risk of myocardial or cerebral infarction by 30% (secondary prevention). Today, there is a general consensus that antiplatelet drugs, started the day before the procedure, are beneficial for early and late patency of peripheral vascular reconstructions (carotid endarterectomy, infrainguinal bypass grafts or endovascular procedures).

Angioplasty, Balloon↗
PubMed1998

Deleterious mutation accumulation and the regeneration of genetic resources.

The accumulation of mildly deleterious mutations accompanying recurrent regeneration of plant germ plasm was modeled under regeneration conditions characterized by different amounts of selection and genetic drift. Under some regeneration conditions (sample sizes >/=75 individuals and bulk harvesting of seed) mutation accumulation was negligible, but under others (sample sizes <75 individuals or equalization of seed production by individual plants) mutation numbers per genome increased significantly during 25-50 cycles of regeneration. When mutations also are assumed to occur (at elevated rates) during seed storage, significant mutation accumulation and fitness decline occurred in 10 or fewer cycles of regeneration regardless of the regeneration conditions. Calculations also were performed to determine the numbers of deleterious mutations introduced and remaining in the genome of an existing variety after hybridization with a genetic resource and subsequent backcrossing. The results suggest that mutation accumulation has the potential to reduce the viability of materials held in germ plasm collections and to offset gains expected by the introduction of particular genes of interest from genetic resources.

Alleles↗
PubMed1998

Protective effects of WEB 2086 (PAF antagonist) and ketoprofen (NSAID) on PAF-induced changes in the morphological ultrastructure of blood platelets in calves.

The ultrastructure of bovine platelets was examined by transmission electron microscopy without any pretreatment (control), and after WEB 2086 (a triazolodiazepine) or ketoprofen (NSAID) pretreatment, followed by PAF infusion. The blood platelet count was also investigated. The group of calves that received WEB 2086 pretreatment before platelet-activating factor (PAF) infusion did not show a decreased number of platelets. However, in the other group, with ketoprofen pretreatment before PAF infusion, there was a rapid decrease from 1 to 3 min, while from 5 min the number of platelets recovered to the normal value. Electron microscopy revealed that pretreatment with WEB 2086 followed by PAF infusion did not alter the morphological ultrastructure of bovine platelets, except that the microtubules were briefly modified from 1 until 3 min after PAF challenge. After ketoprofen pretreatment, bovine platelets kept their regular shape, the number of dense bodies was not significantly altered, the number of mitochondria was maintained from 5 min after PAF infusion, giant platelets were not observed and the Golgi apparatus was rarely visible. Thus pretreatment with WEB 2086 and ketoprofen before PAF infusion had a protective activity on the ultrastructure of bovine platelets and, in cattle, pretreatment with WEB 2086 and ketoprofen before PAF challenge prevented the thrombocytopenia induced by PAF.

Animals↗
PubMed1997

The effect of intravenous administration of WEB 2086 on PAF-induced platelet aggregation in healthy Friesian calves.

The in vivo ability of the specific PAF-antagonist WEB 2086, a thienotriazolodiazepine, to inhibit platelet-activating factor (PAF) in cattle was investigated by in vitro determination of platelet aggregation curves. WEB 2086 was infused intravenously into a group of 5 healthy male Friesian calves in a dose of 3 mg/kg over 1 min. The resultant inhibition peaked between 30 min and 1 h after administration of WEB 2086. The inhibition was significantly reduced after 3 h and became non-significant after 6 h, but maximal pre-treatment aggregation had not been restored by 24 h after the injection of WEB 2086. These results confirm previous results obtained in vitro and suggest that WEB 2086 is a potent antagonist of PAF activity in calves. They also suggest that further clinical studies with WEB 2086 in cattle are desirable.

Animals↗
PubMed1997

Comparative study of antiphospholipid antibody detection in eleven Belgian laboratories.

Twenty-six plasma samples have been sent to 11 different Belgian laboratories in order to detect the presence of antiphospholipid antibodies, either by immunological methods and/or by coagulation tests. A good concordance between laboratories was observed for coagulation tests. Laboratories using detection tests and performing mixing procedures and neutralisation procedures displayed the highest sensitivity as compared with laboratories which did not perform one of these two latter procedures. The concordance between laboratories for the immunological methods was much worse as compared with coagulation tests. This may be attributable either to an intrinsic problem of the immunological tests or to a selection bias due the fact that the plasmas used in this study were selected in coagulation laboratories only where the chance to find a lupus anticoagulant positive/ELISA antiphospholipid negative sample is high.

Adult↗
PubMed1997

Combined effect of Web 2086 (Paf antagonist) and ketoprofen (Nsaid) on Paf-induced ex vivo platelet aggregation in bovine.

The effect of the specific PAF-antagonist WEB 2086, a thieno-triazolo-diazepine, and ketoprofen, a NSAID, was investigated on PAF-induced bovine platelet aggregation measured ex vivo in platelet-rich plasma (PRP). WEB 2086 was infused intravenously over 1 min followed immediately by ketoprofen administration over 1 s (both drugs = 3 mg/kg), in a group of six healthy male Friesian calves. Depending on the PAF concentration, a reversible (10(-8)-10(-9) mol/l) and irreversible (10(-5)-10(-7) mol/l) platelet aggregation was observed. The reversible aggregation was completely blocked by pretreatment of the animal with WEB 2086 and ketoprofen. The inhibitory effects observed during the irreversible aggregation were 47.22%, 54.00% and 88.00% at 10(-5), 10(-6) and 10(-7) mol/l PAF, respectively. Moreover, the aggregation obtained in these condition became reversible. Maximal inhibitory effect of WEB 2086 and ketoprofen on PAF-induced platelet aggregation in calves was observed within 30 min after administration of both drugs. This inhibition persisted even after 24 h and was significantly different from control with P < 0.05. The combined effect of both drugs exceeded the sum of the individual effects (synergism). It was concluded that WEB 2086 and ketoprofen very effectively blocked PAF-induced bovine platelet aggregation in platelet-rich plasma. The study also suggested a synergism between both substances.

Analysis of Variance↗
PubMed1996

Reduction in requirements for allogeneic blood products: pharmacologic methods.

BACKGROUND: Numerous articles describe the reduction of perioperative bleeding by the therapeutic or prophylactic administration of drugs such as prostacyclin, desmopressin, and natural or synthetic antifibrinolytics. METHODS: A review of the literature was carried out to help the reader define the indications of these drugs during cardiopulmonary bypass operations, highlight the questions that remain concerning their indications and modes of action, and suggest future studies to answer these remaining questions. RESULTS: Prostacyclin reduces platelet trauma induced by extracorporeal circulation but does not effectively reduce postoperative bleeding and transfusion requirements. Desmopressin acts as a "glue," improving platelet adhesion, and may be effective when postoperative bleeding is excessive, but its routine use in cardiac operations cannot be recommended. Natural and synthetic antifibrinolytics inhibit plasmin and plasmin-induced platelet dysfunction. These agents have been shown to decrease bleeding and the need for allogeneic transfusions after open heart operations. However, with antifibrinolytic drugs, the risk of thromboembolic phenomena cannot be neglected. With aprotinin, this risk appears to be minimal when the drug is used at concentrations high enough to inhibit plasma kallikrein also. CONCLUSIONS: Prophylactic antifibrinolytics are efficacious, but their routine use remains controversial, both for economic reasons and for fear of thromboembolic complications.

Antifibrinolytic Agents↗
PubMed1996

Neutral genetic markers and conservation genetics: simulated germplasm collections.

This study examines the use of neutral genetic markers to guide sampling from a large germplasm collection with the objective of establishing from it a smaller, but genetically representative sample. We simulated evolutionary change and germplasm sampling in a subdivided population of a diploid hermaphrodite annual plant to create an initially large collection. Several strategies of sampling from this collection were then compared. Our results show that a strategy based on information obtained from marker genes led to retention of the maximum number of neutral and nonneutral alleles in the smaller sample. This occurred when demes were composed of self-fertilizing individuals or when no migration occurred among demes, but not when demes of an outcrossing population were connected by high levels of migration.

Algorithms↗
PubMed1996

Inhibition of PAF-induced platelet aggregation by WEB 2086 'in-vitro', an antagonist to the receptor for platelet-activating factor, in bovine.

The sensitivity of bovine platelet aggregation in response to PAF stimulation and the ability of WEB 2086 (a thieno-triazolodiazepine) to inhibit response to PAF-induced platelet aggregation were investigated in the blood from five healthy male Belgian Blue calves. The recorded response to PAF showed a plateau which was dependent on the PAF concentration. Platelet aggregation induced by PAF consists of two mechanisms: reversible and irreversible aggregations which are accompanied by the release of platelet granule contents. Reversible aggregation occurred above (2 . 10(-9) mol/l) PAF, and irreversible aggregation occurred above (2 . 10(-7) mol/l) PAF. Addition of WEB 2086 to bovine platelets in vitro induced a rightward shift in the dose-response curve to PAF. WEB 2086 inhibited PAF-induced aggregation in a competitive reversible manner (pA2 = 7.61). The results of our study show that PAF induces platelet aggregation in platelet-rich plasma (PRP) and that addition of WEB 2086 to bovine platelets in vitro inhibits PAF-induced Platelet Aggregation.

Animals↗
PubMed1995

Quantitative genetics of 4x-2x hybrid populations with first-division restitution and second-division restitution 2n gametes produced by diploid parents.

A model is proposed to describe the genetic value of 4x-2x hybrids resulting from crosses between tetraploid genitors and diploid genitors that produce 2n gametes. The model takes into account the genetic consequences of the First Division Restitution (FDR) and Second Division Restitution (SDR) meiosis, particularly on the homozygosity level that 2n gametes contribute to 4x-2x hybrids. As genes can be identical by descent, numerous parameters are needed in the classical approach to describe the inbreeding effects on the mean and variance of 4x-2x hybrids. Using the concept of test value, the model allows a large decrease in the number of required parameters. The model gives the components of genetic variance and usual covariances between relatives using these synthetic parameters. The model is then used to study the efficiency of a recurrent breeding scheme to improve diploid genitors for their combining ability with tetraploid genitors. It appears that, in presence of dominance, ignoring the meiosis pattern will lead to an overestimation of additive variance and then of genetic advance. Some genetic considerations on the differences between FDR and SDR mechanisms lead us to suggest an experimental comparison of their respective advantages and disadvantages for the type of considered recurrent selection. An experimental crossing design is proposed to obtain estimates of the genetic parameters needed for this comparison.

Crosses, Genetic↗
PubMed1994

High-dose aprotinin reduces blood loss in patients undergoing total hip replacement surgery.

BACKGROUND: Aprotinin, a proteinase inhibitor, has been reported to reduce blood loss significantly during cardiac surgery. The mechanisms of this effect remain unclear. We studied the effect of aprotinin on blood loss and transfusion requirement during total hip replacement. Potential mechanisms of action and side effects also were investigated. METHODS: Forty patients scheduled for primary total hip replacement were randomized to receive, in double-blind fashion, either aprotinin given as a bolus of 2 x 10(6) kallikrein inactivator units (KIU) followed by an infusion of 5 x 10(5) KIU/h until the end of surgery or an equivalent volume of normal saline. Anesthesia and surgical techniques were standardized and systematic deep venous thrombosis prophylaxis was used. Peri- and postoperative blood loss and transfusion were measured. Fibrinolysis, coagulation pathways, and platelet function were assessed. Renal and hepatic function as well as the incidence of deep venous thrombosis also were assessed. RESULTS: Aprotinin reduced total blood loss from 1,943 +/- 700 ml to 1,446 +/- 514 ml (P < 0.05). This reduction of blood loss occurred during surgery (P < 0.05) and postoperatively (P < 0.001). Total amounts of blood transfused were 3.4 +/- 1.3 units/patient in the control group and 1.8 +/- 1.2 units/patient in the aprotinin group (P < 0.001). The activated partial thromboplastin time was significantly prolonged by aprotinin immediately after surgery, at 50.6 +/- 12.4 versus 32.3 +/- 4.6 s in control patients (P < 0.001), but results of the other coagulation tests were not different between the two groups. No side effects were observed in the aprotinin group. The incidence of deep venous thrombosis in the two groups was not significantly different. CONCLUSIONS: The use of high-dose aprotinin during total hip replacement results in a reduction in both blood loss and the amount of blood transfused. Aprotinin's mode of action, however, remains to be elucidated.

Aged↗
PubMed1991

The use of perfluorodecalin in diabetic vitrectomy.

Nine patients were operated on for severe proliferative diabetic retinopathy using a perfluorocarbon liquid, purified perfluorodecalin; 7 patients were operated on for traction-rhegmatogenous retinal detachment, 2 for severe fibrovascular proliferation complicated intraoperatively by iatrogenic holes with surrounding retinal detachment. The intraoperative use of perfluorodecalin allowed flattening of the retina and endophotocoagulation to be carried out easily. Perfluorodecalin was removed at the end of the procedure, and intraocular tamponade was provided by silicone oil in 5 eyes and by a long-acting gas in 4 eyes. Anatomic success was obtained in 8/9 cases with a minimum follow-up of six months; 4 eyes had improved vision, 2 had the same vision, and 3 had decreased vision. The main advantage of intraoperative use of perfluordecalin is to allow easy flattening of the retina and effective endophotocoagulation under optimal visual conditions.

Adult↗
PubMed1990

Hemostasis profile in women taking low-dose oral contraceptives.

Thirty-six young, healthy, nonsmoking women have been selected to check the effect of low-dose oral contraceptives on hemostasis. Two identical groups were treated by Marvelon (a monophasic oral contraceptive containing ethinyl estradiol and desogestrel) or Trigynon (a triphasic oral contraceptive containing ethinyl estradiol and levonorgestrel) for a 6-month period. In the absence, previously controlled, of substantial differences between the effects of each treatment on hemostasis, all the results were pooled at the third and sixth month of the study. The effects of oral contraceptive treatment were as follows: (1) platelet number, platelet aggregating ratio, and plasma beta-thromboglobulin level were not significantly altered, and (2) antithrombin III activity was not reduced despite a slight decrease or antigen concentration. The von Willebrand factor parameters, factor VIII:C, factor VII:C, and clottable fibrinogen were significantly increased. Plasminogen (activity and antigen concentrates) and alpha 2-antiplasmin levels were also significantly increased. Activated partial thromboplastin time and euglobulin lysis time measured after venous occlusion were significantly shortened. Although statistical analysis did not show dramatic changes in all these parameters, some individual extreme values were substantially altered. Therefore we believe that these later values are worthy of cautious consideration for weighing the role that hemostasis factors might play in individual thrombotic risk.

Adult↗