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Biomedical subjects

T Lecompte

Publications and source records attributed to T Lecompte.

At least 127 records · Page 7Linked to original sources

[Trial treatment of severe Raynaud's phenomenon with prostacyclin (PGI2)].

Severe forms of Raynaud's phenomenon are very disabling. In a randomized, single-blind trial, we have evaluated the effects of PGI2, a natural compound with strong vasodilator and anti-platelet activities, in 14 patients presenting with Raynaud's phenomenon. The patients received a 24-hour infusion of either PGI2 in doses of 10 mg/kg.min, or only the solvent (glycine buffer). All patients recorded the frequency and severity of the attacks before and after treatment, and 7 of the 8 patients who received the solvent benefited from a PGI2 infusion 30 to 60 days later. Among the 14 patients (6 men, 8 women), 10 had underlying collagen disease. The number of attacks per week was initially 15.9 +/- 5.3 (mean +/- s.e.). The resulting impairment was pronounced (+ + on a + to + + + scale). Radioimmunoassays of prostaglandins showed a strong increase in 6-keto PGF1 alpha levels during the infusion, without changes in thromboxane levels. A significant (p less than 0.05) reduction was observed in the number of attacks (2.6 +/- 2.5 per week) and in impairment (+ on average after PGI2 but not after the buffer). Improvement after PGI2 lasted from 0.5 to 12 months, and all but one patient regarded the treatment as effective in long-term, despite undesirable side-effects (flush, hypotension) which occurred regularly during PGI2 infusion. In all patients with ulcerations of the finger tips, these healed more rapidly after PGI2. It is concluded that in spite of immediate discomfort, PGI2 in 24-hour infusions seems to be of value in the treatment of severe Raynaud's phenomenon.

Drug Evaluation↗

Familial and constitutional bleeding disorder due to platelet cyclo-oxygenase deficiency.

Three family members from two successive generations had a bleeding tendency. Their template bleeding time was prolonged and platelet aggregation induced by ADP and adrenaline showed no second wave; collagen at low to moderate concentrations failed to aggregate and release ATP, whereas higher amounts aggregated and released. Aggregation and release due to thrombin, ristocetin, and synthetic epoxy derivatives (U 44069 and U 46619) were normal. Arachidonate (AA) was inactive, and was not converted either in thromboxane (TX) A2 activity evaluated on the rabbit aorta strip, nor in TXB2 evaluated by radioimmunoassay and by radiochromatography. The parallel impairment of TXB2 and PGE2 formation by the patient's platelets are compatible with a platelet cyclo-oxygenase deficiency. This study suggests that transmission is autosomal dominant, and confirms that cyclo-oxygenase is not needed for aggregation and ATP release by high amounts of collagen.

Adolescent↗

[Pharmacology of anti-platelet agents].

A new class of drugs has appeared alongside classical anti-thrombotic agents such as heparin and oral anticoagulants, characterised by their ability to modify the behaviour of platelets: "anti-platelet" agents. This article reviews the platelet actions, pharmacokinetics, conditions of use and side effects of the four chief agents available: acetylsalicylic acid (ASA), sulfinpyrazone, dipyridamole and ticlopidine. The mode of action of the first of them is that best studied. ASA opposes the conversion of arachidonic acid to prostaglandins and thromboxane, by the irreversible acetylation of cyclo-oxygenase. Nevertheless, major therapeutic trials involving ASA have yielded only poor results. There are at least two possible explanations for this state of affairs: --aggregation may occur even when thromboxane is blocked, in particular in response to thrombin; --ASA has been used at doses also capable of inhibiting the formation by the vascular wall of an anti-aggregant prostaglandin, PGI2. Current efforts by pharmacologists which should result in better adapted and hence more effective anti-thrombotic methods, are essentially concerned with the following points: --to understand why sulfinpyrazone, which in principle has the same mode of action as ASA, seems sometimes more active and sometimes less active than the latter according to whether coronary or cerebrovascular accidents are involved; --to propose a rational prescription programme for ASA, in such a way that it inhibits only little, and for as short a time as possible, the production of PGI2 (e.g. 200 mg every three days): --to perfect more active combinations; --synthesis of new substances, e.g. thromboxane synthetase inhibitors, or stable analogues of PGI2. The reasons which suggest that such substances could be used more beneficially in man are expanded.

Animals↗

Assessment of deep vein thrombosis prophylaxis in surgical patients: a study conducted at Nancy University Hospital, France.

OBJECTIVE: This retrospective evaluation aimed to assess the adequacy of prophylaxis against thromboembolism prescribed to surgical patients at the authors' institution, and to compare it with generally accepted published guidelines. Aspects considered were indications for prophylaxis, regimens used and monitoring. METHODS: Eleven units (nine surgical and two surgical intensive care) took part in the survey on a voluntary basis. The clinical audit system used involved developing a set of criteria based on existing guidelines, comparing observed practice with those recommendations, analysing the factors underlying any deviation and developing corrective measures. RESULTS: When the medical records of 117 patients hospitalized in October 1995 were examined, prophylaxis against deep vein thrombosis was documented in 86 (low molecular weight heparin in 85, dextran in one). No associated physical preventative measures were recorded. Indications and dosage were appropriately handled in 90.7% and 75.2% of patients, respectively. Ninety-five cases were outside the reference criteria: 74 for excluded surgical indications, 13 which involved laparoscopy, and eight in which spinal or epidural anaesthesia was administered. Platelet count was performed in 73.8% of cases before prophylactic treatment, and in 23.10% during its course. Anti-Xa activity was measured in 0.4% of cases. Analysis of causes showed that guidelines were not complied with either because of lack of organization, or because of disagreement with them. DISCUSSION: In this study, indications for prophylaxis were well established and heparin dosages used were not fundamentally flawed. The weak point in practice was a failure to carry out platelet counts, particularly during the course of treatment. Appropriate corrective action consists of disseminating guidelines and relevant information, and using a preoperative checklist to assess thromboembolic risk. CONCLUSION: Physicians agree that opportunities to improve preventative practices exist, and that the quality improvement programme should be pursued.

Adult↗

Microencapsulation of low molecular weight heparin into polymeric particles designed with biodegradable and nonbiodegradable polycationic polymers.

Owing to its lack of oral absorption, heparin has to be administered parenterally. However, parental administration has negative aspects such as multiple injections, possible infection, patient inconvenience, and high cost. Now, low molecular weight heparin (LMWH) is taking part in antithrombotic treatment and is proven to confer more advantages than unfractionated heparin. The aim of our present study was to formulate, by the w/o/w emulsification process, LMWH microparticles as potential oral carriers prepared with biodegradable (poly-epsilon-caprolactone and poly-lactic-co-glycolic acid) and nonbiodegradable polycationic polymers (Eudragit RS and RL), used alone or blended. The encapsulation efficiency ranged from 16 to 47% and was highly dependent on the presence of the positively charged polymers. In the same way, a low in vitro LMWH release was observed when Eudragit polymers composed totally or partially the polymeric matrix, compared with biodegradable polymers exhibiting higher LMWH release (40 and 60%). For each formulation, LMWH released from microparticles preserved its biological activity as shown by the antifactor Xa activity. Experiments performed with fluorescein-labeled LMWH showed the drug distribution in microparticles and may give information about the mechanisms controlling LMWH encapsulation and release.

Drug Compounding↗

The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability.

By using a "slow" fluorogenic thrombin substrate and continuous comparison to a simultaneously run calibrator, thrombin generation can be monitored automatically, on line, in clotting PPP or PRP at a throughput of up to 100 samples per hour. The resulting "Thrombogram" in PPP measures hypocoagulability (haemophilias, oral anticoagulants, heparins (-likes), direct inhibitors) and hypercoagulabilities (AT deficiency, prothrombin hyperexpression, prot. C and S deficiency, factor V Leiden, oral contraceptives). In PRP it is diminished in thrombopathies, in von Willebrand disease, by antibodies blocking GPIIb-IIIa or GPIb, or by antiplatelet drugs like aspirin and clopidogrel. Lupus anticoagulant both retards and increases thrombin generation. The thrombogram thus appears to be a broad function test of the haemostatic-thrombotic mechanism of the blood.

Blood Coagulation Disorders↗

[Prevention of venous thrombosis: role of heparins].

Prevention of venous thromboembolism is of major importance because deep vein thrombosis is an economic burden. To prevent pulmonary embolism, whether fatal or not, and the postphlebitic syndrome, virtually all patients' level of risk should be assessed in order to provide adequate prophylactic measures against venous thromboembolism. Non-pharmacological, pharmacological or combined modalities can reduce the frequency of venous thrombosis. Evidence-based guidelines are available for most situations in surgical patients. However, in medical patients there are fewer data and there are wide variations of opinion. Systematic reviews should be performed and updated to obtain practice guidelines. Cost and effectiveness as well as patients' preferences should be taken into account. Randomized control trials are ongoing: low-molecular-weight heparins are being evaluated in general medical patients; other forms of prophylaxis or combined methods are also being investigated.

Anticoagulants↗

[Prophylaxis of venous thromboembolism in medical patients: from medical decision tools to the use of low molecular weight heparin].

In France, low molecular weight heparins are largely used for prophylaxis of venous thromboembolic disease in medical patients. Although clinical trials show their efficacy in some particular clinical situations, there is no consensus about their use in non-surgical patients. A consequence is a wide disparity of prophylaxis of venous thromboembolic disease regimens: such a situation was observed during a practice survey in two medical units of the general hospital of Lunéville. So, prior assessment for pharmacists and physicians was carried out to determine tools which guide decision-making. These comprise clinical practice guidelines, a record card which allows the scoring of risk for venous thromboembolic disease and a clinical algorithm leading to the appropriate prescription according to the risk and the haematological results. A second concomitant practice survey was organized in the same two units in order to measure the appropriateness of the decision-making tools in medical practice. The four-month study included 108 medical patients. The process was successful because: (1) validated practices are improved, particularly in respect of biological monitoring during treatment, and (2) the disparity of therapeutic strategies is highly reduced, the clinical practice guidelines being followed in 81 per cent of all cases. Despite the lack of consensus, heightened awareness of the attendant risk in many medical conditions allows appropriate prophylactic measures to be taken. These measures need decision-making tools that are easy to use and that improve heparin prescribing and thus healthcare quality.

Aged↗