[Professional practice evaluation in glaucoma]. / Evaluation des pratiques professionnelles (EPP) dans le glaucome.

Professional practice evaluation (PPE) and continuous medical education (CME) have been compulsory in France since July 2005. The objectives of PPE and CME are to increase the quality of care and to improve medical practice. Relatively easy to obtain, PPE is a self-evaluation of daily practice.

[Pseudophakia and aptitude of aviation personnel]. / Pseudophakie et aptitude du personnel navigant.

UNLABELLED: Because of sensorial disruptions, aphakia post-cataract surgery is a cause of unfitness for the job of aeronautics flying personnel. Its correction thanks to intraocular lenses and a correct functional check-up permit to reconsider the fitness through a derogation given by the competent authorities. EQUIPMENT AND METHODS: The authors realized a retrospective study on the 5 last years. 27 flying personnel, 24 to 76 years old, went through a cataract surgery with implantation. The check-up includes a chemical exam completed by a morphoscopic, coloured and spatial study. RESULTS AND DISCUSSION: The files are more or less well-documented according to their origin. The flying personnel have an average of 4,010 flying hours. The average post-operative hindsight is 30 months. 3 wear intraocular lenses of rear chamber among which 1 is multifocal. 7 were examinated at the CPEMPN with satisfying morphoscopic, coloured and luminous sense compatible with the fitness. 4 are declared permanent unfit (1 professional pilot with bad results, 1 private pilot with other pathologies, 1 inexperienced stewardess getting through the admission visit with insufficient post-operative hindsight, 1 professional pilot declared unfit for its military activity in the reserve). 4 are qualified with restriction. 20 are qualified without restriction. CONCLUSION: The correction of aphakia with intraocular lenses permits in most cases to obtain good functional results compatible with the flying aptitude.

Effects of aspirin on embolization in an arterial model of laser-induced thrombus formation.

This model of arterial thrombosis induced by laser was used to evaluate the effect of aspirin (Aspegic) on embolization. A partial occlusion was induced in small mesenteric arterioles (diameter 35-40 microns) with an Argon Laser. The laser induced the formation of a vessel wall lesion with damage of endothelial cells. Thrombus formed within seconds after the laser lesion and grew rapidly. Embolization began within the minute following the laser flash. Thrombus formation and embolization were repetitive phenomena. The duration of embolization was 6.50 +/- 0.84 min in the control group. Then the thrombus became stable and partially obstructed the vessel lumen. The administration of aspirin at three doses (50, 100, 200 mg/kg) by intramuscular injection, 15 min before the laser injury, induced three different phenomena: (1) an increase of the number of laser injuries required for the thrombus formation; (2) a dose-dependent decrease in the duration of embolization, and (3) a dose-dependent decrease in the number of emboli. The highest dose injected induced the strongest reduction in the duration of embolization and the number of emboli.

Could non steroidal anti-inflammatory drugs be used to potentiate L.M.W.H. activity in thrombosis? (Part II).

Thromboembolic diseases are one of the main cause of mortality. Heparin fractions obtained by chemical or enzymatical depolymerization of unfractionated heparin are now widely used in the prevention of those illness. However, curative dosages have bad side effects which could be avoid by the potentiation of the antithrombotic efficacy of non-active dosages. A previous study (4) has shown that a non-steroidal anti-inflammatory (NSAI) drug like Phenylbutazone could favour the antithrombotic efficacy of Fraxiparine at a very low dose. The aim of this study was then to determine if other NSAI elements could present the same or better proactive effects.

In vitro platelets/endothelial cells interactions in presence of acetylsalicylic acid at various dosages.

Venous endothelium is able to release in vitro substances which modifies platelet aggregation. A vascular fragment incubated in Michaelis buffer (pH 7.30), aliquoted and tested on platelet-rich-plasma partially inhibits the aggregometry parameters. Addition of acetylsalicylic acid (ASA) at ultra low dose (0.1 nM final solution in the incubation tube) presents a reversed effect on this inhibition. To explain this phenomenon, 6-keto-PGF1 alpha and von Willebrand factor were dosed in the incubation media. After determination of an active level of 6-keto-PGF1 alpha (200 pg/100 microliters), 2 series were made: series 1 included the values below 200 pg/100 microliters incubation media, series 2, the values above 200 pg/100 microliters incubation media. When the vascular fragment was incubated as described above, the results of aggregometry ratio for series 1 were: test A (without ASA): 0.84 +/- 0.18, test B1 (with 0.1 nM of ASA): 0.87 +/- 0.13. For series 2, they became: test A: 0.75 +/- 0.27, test B1: 0.93 +/- 0.16. Control was always: 1.00 +/- 0.00. For the same groups, 6-keto-PGF1 alpha values were: for series 1, test A: 81 +/- 57, test B1: 81 +/- 60 pg/100 microliters incubation medium, for series 2, test A: 596 +/- 495, test B1: 383 +/- 263 pg/100 microliters incubation medium. Analyses were also performed with 2 high doses of ASA (B2: 10(5) nM and B3: 10(6) nM final solution) in the same experimental conditions. In these groups, aggregation parameters were decreased (0.86 +/- 0.14 for 10(5) nM, 0.84 +/- 0.15 for 10(6) nM) as well as 6-keto-PGF1 alpha production (189 +/- 199 for 10(5) nM, 152 +/- 182 for 10(6) nM). For these two last ASA treatments, comparison of the results in groups set up according to the sensitive 6-keto-PGF1 alpha value (200 pg/100 microliters solution) showed no modification. So it seems that a certain reactive state, specific of ultra low dose treatment is necessary for the vascular endothelium to be sensitive at such treatment.

The role of essential vitamins in the development of thrombosis and hemorrhage--an experimental study.

To evaluate the action of essential vitamins on hemorrhage, coagulation and thrombosis, a multivitaminized solution was daily administered at three different doses for two weeks to male Wistar rats. Two experimental models were carried out: a venous thrombosis and an induced-hemorrhage model. Results indicate a low thrombogenic effect, a large and dose-dependent decrease of hemorrhage and no effect on coagulation. The observed effects on thrombosis and hemorrhage were not connected with an overdose of vitamins involving many secondary effects, since no blood viscosity parameters were modified. Three main hypotheses are envisaged to explain these results: a direct effect on platelet functions, an action on the leukocytic population, and a possible modification of the vessel wall response. However, further investigations are needed to specify the mechanisms involved.

Effects of immuno-potent drugs and their association with an unfractionated heparin on an experimental venous thrombosis.

Immuno-potent drugs are largely used in human medicine. The aim of this study was to determine the role of two immuno-modulators (sodium diethyl-dithiocarbamate, RU 41 740) and two immuno-suppressors (methylprednisolone, cyclosporin A) alone or in association with an unfractionated heparin (Calciparin), on an experimental venous thrombosis made by vena cava ligation in male Wistar rats. Each immuno-potent drug was administered for six days before the thrombus induction at the same dosage (10mg/kg b.w.), and the Calciparin, used as treatment of the thrombosis, was administered two hours after the thrombus induction at the dose of 1mg/kg b.w. Immuno-treatment potentiated thrombus formation: the increase in thrombus weight was greater with immuno-modulators (43% on average in comparison with placebo) than with immuno-suppressors (20%). In association with Calciparin the antithrombotic effect was also potentiated and more marked with the immuno-modulators than with immuno-suppressors. An increase in circulating monocytes was observed in all groups whether Calciparin was present or not. Coagulation tests were not affected by immuno-therapy. However, immuno-modulators led to an inhibition of platelet aggregation. In conclusion, this trial seems to show a probable effect of immunological cells in thrombosis and in the antithrombotic effect of heparin, but the mechanism involved is not yet determined.

Could proteolytic enzyme modulate the interaction platelets/vessel wall in presence of ASA at ultra low doses?

Acetylsalicylic acid (ASA) is known to act on platelets and vessel walls. At ultra low doses it reverses the inhibitory effects produced by a vascular fragment. Use of papain on normal platelets in vitro led to the appearance of platelet aggregation without collagen induction with a range of 20.25 +/- 28.91%. In the presence of vascular fragments (without ASA), this "spontaneous" aggregation remained but was reduced (13.26 +/- 27.73%). This effect was reversed by ASA treatment (29.41 +/- 24.17%). Reversion of vascular inhibition by ASA was not modified by papain.

Could non steroidal anti-inflammatory drugs be used to potentiate L.M.W.H activity in thrombosis? (Part I).

Heparin fractions are antithrombotic drugs prescribed for preventive treatment but their efficacy must be optimized to permit curative use without side effects. The present study was performed on 144 rats receiving a low molecular weight heparin (L.M.W.H), Fraxiparine, and a non steroidal anti-inflammatory drug (Phenylbutazone), which were injected simultaneously or separately. Neither Phenylbutazone nor L.M.W.H at their lowest dose (1 mg/kg) reduced thrombus size. However, administered together, they produced a significant limitation of thrombus growth. Variation in anti Xa activity limitation was only observed with the highest dose of Fraxiparine alone or in combination with Phenylbutazone (1 mg/kg) corresponding to its antithrombotic effect.

Comparative study of three recombinant hirudins with heparin in an experimental venous thrombosis model.

Three recombinant hirudins (r-hirudins) produced by genetic processes from Escherichia coli and yeast were studied. r-Hirudins could be an alternative treatment to heparin; so, the antithrombotic activity of these drugs should be compared to heparin, the reference substance, in an experimental venous thrombosis model. In this model, the effect of these r-hirudins on thrombus weight reduction were not identical. They varied depending on the original product (E. coli or yeast). The growth-inhibiting activity of r-hirudins on existing thrombi is not dose dependent, whereas that of heparin is. Moreover, in the conditions of this study, higher doses of heparin, but not of hirudins, increased the bleeding time. Although hirudin has limited applications for the time being, it seems an interesting anticoagulant drug, and the availability of r-hirudin opens new therapeutic anticoagulation perspectives.

Modifications of biological activities of heparin and fraxiparine induced by the size and the age of a thrombus. Experimental study.

Heparin and its fractions have often been tested on fresh experimental thrombosis. However in human clinic, drugs are administered not on fresh, but rather on old constituted thrombi. In order to evaluate the effects of antithrombotic agents in these conditions, both drugs (unfractionated heparin and Fraxiparine) were administered on 150 rats at different times and so, could take effect on thrombi with different ages. Heparin was more active as its fraction on fresh thrombi (2 hours old), but no more effects could be observed for all drugs when the thrombus was 52 hours old. Biological activities (A.P.T.T., anti-IIa and anti-Xa activities) decreased as the thrombi increased in weight and age.

Aspirin at very ultra low dosage in healthy volunteers: effects on bleeding time, platelet aggregation and coagulation.

Aspirin at very ultra low dosage was tested in healthy volunteers (n = 20) in a randomized, double-blind and placebo-controlled trial. The results showed a bleeding time reduction (p less than 0.05) in volunteers having previously ingested aspirin. Platelet aggregation on platelet-rich plasma was not statistically modified after aspirin ingestion. Thrombin clotting time was always higher (p less than 0.05) in the treated group.

[How to standardize low molecular weight heparins]. / Quel standard utiliser pour les héparines de bas poids moléculaire?

Heparin, used in anticoagulant and antithrombotic therapeutic for over fifty years, turns out to mean important side effects and serious haemorrhagic risk. The obtaining, from 1976, of the first low molecular weight heparins (LMWH) preparations is partly allowed to overcome those problems. The LMWH present an identical or greater antithrombotic capacity than the unfractioned heparin and mean a lower haemorrhagic risk. Thus their use in antithrombotic therapy is very interesting. However, the existence of different units for the LMWH sets a standardization problem for their clinical use and for their biological follow up. The first international LMWH standard introduction by the World Health Organisation in 1986 may be useful to give a great homogeneity of the interlaboratory results, to serve as reference to the biologists, as activity standardization for the manufacturers or as security for the clinicians. However, it seems its definition mode and its validity call into question by several authors. The anti Xa activity, advocated in the biological surveillance, does not seem to perfectly fit to the LMWH therapy. The debate about the standardization of the low molecular weight heparins keeps open.

Could thrombus age be a modulator of heparin or L.M.W.H. activities?

The main thrombotic diseases are caused by old constituted thrombi. However, experiments to demonstrate the effects of heparin or heparin fragments on tPA release have been on fresh thrombi. This study on thrombi induced 6, 24, 48 or 72 hours before sampling shows variations in the main biological activities of both heparin and heparin fragment (CY222) as the thrombus ages. This effect is particularly observed on tPA release which is statistically reduced (p less than 0.001). Thrombus age seems to be a modulator of heparin and heparin fragment biological activities.

Comparative pharmacology of low molecular weight heparins: implications of manufacturing processes on biological effects.

With the recent development of numerous low molecular weight heparins (LMWHs), a certain amount of concern has become evident as to the equivalency of each agent. In a comprehensive study, we have taken the seven available LMWHs to directly compare their in vitro and in vivo (subcutaneous) antithrombotic properties in one laboratory setting. Where possible, various batches of one LMWH were evaluated. Our findings were that variations of in vivo activity were observed between the LMWHs studied. Some activities were significantly different from placebo, whereas others were not. Depending on the assay chosen significant differences could also be observed for the in vitro activity.

Antithrombotic activity of recombinant hirudin in the rat: a comparative study with heparin.

Hirudin, a potent inhibitor of blood coagulation, differs in its antithrombotic activity according to the source of isolation. It was therefore of interest to study recombinant hirudin. Hirudin was obtained by a genetic process from E. coli. Its antithrombotic action was investigated in an experimental (rat) model of venous thrombosis and was compared to heparin whose results are known. Heparin (400 micrograms/kg) and hirudin (12.5, 25 and 50 micrograms/kg) present an antithrombotic effect and limit the extension of an existing thrombus (p less than 0.05). Higher heparin dosages increase the bleeding time mean value (p less than 0.05) whereas hirudin does not. So, recombinant hirudin presents the same antithrombotic action as heparin but with very inferior dosage. This activity seems not dose-dependent and is associated to weak hemorrhagic effects.