Seed morphometrics unravels the evolutionary history of grapevine in France.

The cultivation of grapevines has spanned millennia, leading to thousands of varieties through exchanges, mutations, and crosses between genotypes, as well probably as gene flow from wild populations. These varieties are typically categorized by regional origin and primary use, either for wine production or fruit consumption. France, within the Western European group, hosts many of the world's renowned wine grape varieties. However, the historical development of cultivated grapevines in France and in the world remains poorly understood. This study applies morphometry on 19,377 charred and waterlogged archaeological grape pips to investigate the evolutionary history of grapevine in France over the last 10,000 years. The study compares seed outlines and lengths, corrected for taphonomic distortions, with a reference collection of 80 wild and 466 modern domestic grapevine accessions. Findings reveal a shift from wild grapevine exploitation to the expansion of domestic varieties around 600-500 BCE, coinciding with Mediterranean cultural influences and the introduction of eastern grape types. The identification of the East-Table group, a group of varieties of eastern origin for fruit consumption, indicates that grapes were also grown for food, especially in Mediterranean regions and near urban areas, alongside wine production. Early French viticulture featured a notable presence of Western European wine-type grapevines. The abundance of pips with wild-like morphology suggests early cultivation involved plants at an initial domestication stage and gene flow between introduced and wild grapevines. As viticulture spread northward, wild and Eastern morphotypes declined, leading to the dominance of Western European wine types in inner France during the Middle Ages.

Influence of heparin and a low molecular weight heparin fraction of the leukocytes in an experimental venous thrombosis model.

A randomized study was performed to observe the effects induced by heparin and a low molecular weight heparin fraction (at different dosages) on the leukocytes of rats in the presence of experimental venous thrombosis. The experimentation was carried out on two series of animals: the first with a ligature of the inferior vena cava inducing the formation of a thrombus, the second without any ligature. The results show that the induction of thrombosis involves: in the blood, an increase of the number leukocytes, principally polymorphonuclear cells; in the thrombi, a significant rise in the total count of leukocytes, here mononuclear cells; the latter number increases with the dosages of the administered drugs.

Effects of aprotinin on heparin activities and heparin neutralization with protamine.

In order to investigate the new situation in which aprotinin is proposed as a novel approach to reducing post operative bleeding, specially in cardiopulmonary bypass (CPB) surgery during which heparin and protamine are commonly used, preliminary in vitro and in vivo studies have been performed. Aprotinin increases the anticoagulant heparin effects in vitro, and the hemorrhage time in vivo. But in addition to protamine, there are no statistically significant differences with heparin-protamine situation, indicating aprotinin does not disturb the neutralizing activities of protamine on heparin.

Heparin and a low molecular weight fraction enhances thrombolysis and by this pathway exercises a protective effect against thrombosis.

In human volunteers unfractionated heparin and a low molecular weight fraction of heparin (LMWH) caused an increase in plasma plasminogen activator (PA) which peaked at 3 hours after subcutaneous injection. Using a perfused isolated rabbit ear model the enhancement of PA activity was confirmed and was related to the anti-Xa activity of both products infused. Using a modified rabbit Wessler model for thrombus formation it was found that, when using doses of heparin and LMWH sufficient to give a 100% antithrombotic effect, antifibrinolytic drugs (eg. epsilon-ACA and aprotinin), negated this protective effect. It is concluded that the effect of heparin and LMWH on haemostasis is mediated in part through the enhancement which these drugs have on fibrinolysis, the latter being arguably a major defence against fibrin formation during thrombosis.

Changes in plasma fibrin degradation products as a marker of thrombus evolution in patients with deep vein thrombosis.

The level of fibrin degradation products (fdp) as a marker of fibrin clot dissolution was studied prospectively in 51 patients with phlebographically identified deep vein thrombosis (DVT). For this purpose a highly sensitive fdp assay using an anti D neo monoclonal antibody (McAb) was used. At the onset of the hospitalization, in 47 (92%) of the 51 patients tested, the plasma fdp level performed was high, but does not reflect the size of the thrombus, demonstrating that spontaneous thrombus lysis varies from one patient to another. During 10 days of standard heparin or low molecular weight heparin treatment, two different patterns of fdp evolution could be identified in these patients, independent of the type of heparin used. The first was characterized by a gradual decrease in fdp level and a corresponding reduction in the thrombus size. The second pattern showed a persistence of high levels of fdp after 10 days of therapy although the phlebographic score reveals a poor or partial response indicating that fibrinolysis or the balance of thrombus formation/fibrinolysis did not insure total thrombus dissolution. The 4 patients whose initial plasma fdp levels were only slightly increased during the 10 days, seem to have poor thrombolysis, as was shown by the unmodified phlebographic score after 10 days of treatment. Consequently, we conclude that the investigation of plasma fdp levels with a highly sensitive assay should contribute to the evaluation of thrombus evolution in DVT.

[Treatment of acute pulmonary embolism with a low molecular weight heparin by the intravenous route. Study of the optimal dosage]. / Traitement des embolies pulmonaires aiguës par une héparine de bas poids moléculaire par voie intraveineuse. Recherche de la posologie optimale.

Experimental studies on rabbits have shown that CY 222, a low molecular weight heparin (mean: 2.500 daltons), has the anti-thrombosis properties of heparin but reduces the risk of haemorrhage in optimal doses of 1.000 AXa IC (Institut Choay) units/kg/day. The safety and effectiveness of CY 222 were tested in 47 patients presenting with a less than 5 days' old pulmonary embolism. The patients were divided into three groups according to dosage: group I (n = 16) received 500 AXa ICu/kg/day; group II (n = 17), 750 AX ICu/kg/day, and group III (n = 14), 1.000 AXa ICu/kg/day. The drug was administered by continuous intravenous infusion during 10 days. Its effectiveness was assessed from the Miller index calculated on conventional pulmonary angiograms on days 0, 5 and 10. On the 10th day of treatment, the percentage of revascularization was similar in all three groups (group I 65.9 +/- 9.9 p. 100; group II 71 +/- 6.8 p. 100; group III 68 +/- 8.5 p. 100), but the improvement was significantly more rapid in group III patients. Embolism recurred in 5 cases (2 in group I, 1 in group II, 2 in group III) and was fatal in 1 case (group I). Haemorrhagic complications were noted in 3 cases (group III patients). Except for thromboelastography, all coagulation tests were unmodified by CY 222. The anti Xa and the (very low) anti IIa activities of the drug were directly related to the doses administered.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prophylactic and therapeutic use of a low molecular weight heparin fraction, CY 216]. / Utilisation prophylactique et thérapeutique d'une fraction d'héparine de bas poids moléculaire: CY 216.

The aim of our work was to study in a population of high risk patients with hemorrhagic and or thrombotic disease, the preventive or therapeutic effect of a low molecular weight heparin fraction, CY 216 (Choay, France), particularly in surgery. CY 216 was given to 9 patients for the treatment of a thrombosis (pulmonary embolism, acute ischemia, deep venous thrombosis) and to 40 patients in prevention of thrombosis. In this second group, 28 had a high thromboembolic risk such as valvular prosthesis, cardiac arrythmia, coronary artery bypass, etc. For all the patients, CY 216 was injected sub-cutaneously twice or three times a day at the mean dose of 1.5 mg/kg/d, equivalent to 300 U anti-Xa Choay/24 h, and always injected 24 hours before surgery. The biological tests used were: blood cells count, platelet count, prothrombin time, activated partial thromboplastin time, heparinemia levels by two technics: anti-factor-Xa activity and anti-factor IIa activity. None thrombotic complication was observed in the 40 patients prophylactically treated and a constant improvement of thrombosis was noted for the 9 patients with thrombo-embolic disease. In 3 patients, bleeding complications were observed: for 2 patients, all the coagulation tests were normal and anti-Xa activities were less than 0.55 U/ml; in one patient, the bleeding time was prolonged (15 minutes Ivy Incision) and returned to normal when the CY 216 was stopped. Concerning the biology, there was no modification except for anti-Xa activity which mean was 0.30 U/ml (01-07). However, this test is unable to predict either thrombotic or hemorrhagic events.

[CY 222, a very low molecular weight heparin, in the curative treatment of deep venous thrombosis. Apropos of 95 cases. Clinical and phlebographic results]. / Le CY 222, Héparine de trés bas poids moléculaire dans le traitement curatif des thromboses veineuses profondes. A propos de 95 observations. Résultats cliniques et phlébographiques.

Efficacy of a very low molecular weight heparin, CY 222, in the treatment of deep venous thrombosis of lower limbs was evaluated in a prospective clinical trial instituted in November 1984. CY 222 was administered as subcutaneous injections of 0.03 ml.kg-1 daily (750 anti-Xa U.kg-1.d-1) as 3 divided doses over a minimum of 10 days. Efficacy was rated as a function of clinical and phlebographic criteria. The group of 95 patients treated was a heterogenious one: 38% medical, 62% surgical, and 48% of the total group had partial interruption of vena cava previous to study. The period between first clinical manifestations of the deep thrombosis and therapy varied between one day and 3 months (mean: 1 1/2 days). Clinical symptomatology significantly and globally regressed in 88% of the patients. Comparisons between phlebographic findings at start and end of treatment are expressed using Arnesen's score (cf. table).

[Use of a low molecular weight heparin, CY 222, in the treatment of consumption coagulopathy]. / Utilisation d'une héparine de bas poids moléculaire, la CY 222, dans le traitement des coagulopathies de consommation.

UNLABELLED: Among the different treatments used for consumption coagulopathies, the most contested is classical heparin because of the risk of worsening of a hemorrhagic syndrome. A low molecular weight heparin was evaluated to determine possible improvement of this risk. METHODS: Treatment with CY 222 (Choay) was administered over 2 years to 29 patients (mean age 40 years, range 15-74) with coagulation coagulopathies. Diagnosis was based on the presence of 3 of the following 5 signs: platelets less than 150,000/mm, fibrinogen less than 2 g/l, QT less than 50%, ethanol test positive, PDF greater than 20 micrograms/ml. Etiology could be classed in 3 groups: gravido-puerperal (12 cases), medical disorders (15 cases), post-traumatic (2 cases). Dosage was 150 U/kg every 18 hours subcutaneously. The usual symptomatic treatment included: transfusion of red cells, frozen fresh plasma, platelets and antithrombin III as necessary. A hemorrhage syndrome was present in 16 cases. The course of the disease was evaluated on clinical findings and surveillance of hemostasis parameters; anti-Xa activity was determined in 15 patients. RESULTS: Hemorrhage was arrested and biological values normalized in 22 patients (76%) including 15 (52%) survivors. In the 7 cases where the coagulopathy was not improved, the hemorrhagic syndrome persisted in 4. In the 22 successful outcomes, the hemostasis was corrected within 48 to 72 hours, with the exception of the thrombopenia, which persisted up to the 6th day. Mean anti-Xa activity was 0.32 +/- 0.16 anti-Xa U/ml. CONCLUSION: Results of this preliminary, non-randomized study show CY 222 to be as effective as heparin in the treatment of consumption coagulopathies.

[Prevention of deep venous thrombosis of the leg by a very low molecular weight heparin fraction (CY 222) in patients with hemiplegia following cerebral infarction: a randomized pilot study (30 patients)]. / Prévention des thromboses veineuses profondes des membres inférieurs par une fraction d'héparine de très bas poids moléculaire (CY 222) chez des patients porteurs d'une hémiplégie secondaire à un infarctus cérébral: étude pilote randomisée (30 patients).

The effectiveness and safety of a very low molecular weight heparin fraction were evaluated in the prevention of deep-vein thrombosis in patients confined to bed due to hemiplegia consecutive to a recent cerebral infarction. CY 222 was administered within 48 hours of the stroke by one single daily subcutaneous injection of 0.6 ml (= 15,000 U AXa IC) during 14 days. This randomized pilot study involved 30 patients. The effects of CY 222 were assessed in a group of 15 patients compared with a control group of 15 untreated patients. No deep-vein thrombosis was detected by the labelled fibrinogen test in the treated group, as against 12 patients in the control group. Six patients (3 in each group) died during the study. One case of lethal pulmonary embolism was observed and confirmed at autopsy in the control group. In the remaining 5 patients, no systematic autopsy which would have asserted the absence of pulmonary embolism or drug-induced haemorrhage was performed. Numerous standard laboratory tests confirmed that CY 222 was well tolerated.