Clinical evaluation of a venotropic drug in man. Example of Daflon 500 mg.

Chronic venous insufficiency (CVI) of the lower limbs is a complex and fluctuating disease by its pathogenic mechanisms and its clinical symptoms. Although symptoms are subjective, they affect the quality of life and socio-professional activity of many patients. This is why convincing demonstration of therapeutic activity of a venotropic drug should be carried out according to strict methodology. Only randomized double-blind controlled trials versus placebo (no reference drugs being available) could demonstrate the activity on condition that they are set up in a protocol, the statistical design of which, is adapted and defined "a priori". Inclusion, non inclusion and judgement criteria must be rigorous, taking into account many exogenous and endogenous factors which could have influence on the severity or the change in CVI and on the comparability of groups at the beginning and at the end of the study. Thus, the main risk factors of CVI (heredity, obesity, obstetrical and gynecological history, estroprogestogen treatment, profession, environment, etc.) and the season when the patient is recruited should be taken into account. With respect to all these restraints on methodology, the venotrotopic activity of a flavonoid Daflon 500 mg (2 tablets daily) was demonstrated in 200 patients (174 women, 26 men) with organic CVI (n = 83) or functional CVI (n = 117) treated for two months in two double-blind randomized trials versus placebo. The venotropic activity of Daflon 500 mg, was shown by a significant reduction of CVI signs and symptoms, whether organic or functional, and a significant improvement in venous hemodynamics according to plethysmographic parameters. Good acceptability was observed after medium and long term trials.

Comparative analgesic efficacy and tolerability of ketorolac tromethamine and glafenine in patients with post-operative pain.

In a randomized, single-dose, double-blind, parallel comparative trial of analgesic efficacy, 96 adult patients received either 10 mg ketorolac tromethamine or 400 mg glafenine orally the morning after surgery if they requested pain relief medication. Each patient provided a baseline pain assessment and then received the assigned medication. Patients assessed pain intensity and pain relief and reported any adverse events in interviews held 30 minutes after drug administration and then hourly for 6 hours. The demographic characteristics, baseline pain intensity, and surgical categories of the 47 patients who received ketorolac tromethamine and the 49 who received glafenine were similar. Both drugs provided prompt, sustained pain relief throughout the 6-hour observation period, and there were no statistically significant differences between the two groups in any of the efficacy measures analyzed. The global assessment recorded by patients suggested a slight clinical advantage for ketorolac tromethamine (32.6% of 'excellent' responses) as compared to glafenine (12.5% 'excellent'). The differences in overall response were statistically significant (p = 0.017). Fourteen (30%) patients who received ketorolac tromethamine and 17 (35%) who received glafenine reported adverse experiences that began or seemed to worsen after administration of the study drugs. The most prominent were drowsiness and sleeping, both of which are common in post-surgical patients.

[Saphenectomy in patients over 65. Indications and results]. / Saphénectomie au-delà de 65 ans. Indications et résultats.

For 779 patients who underwent varicose vein surgery at Bicêtre, between 1981 and 1984, there were 61 elderly patients between 65 and 74 years and 15 "old age" patients over 75 years. Only one severe complication occurred. Almost all patients who were operated upon were satisfied or very satisfied to see that the functional discomfort had disappeared, the trophic disorders had regressed, the superficial phlebitis or hemorrhages had not recurred and the ulcer were healed. Statistics are in favor of a surgical treatment of varicose veins or phlebitis sequellae with severe degeneration of the superficial venous network, as soon as they become uncomfortable, because of the increased life expectancy, in Europe at this time. But, because of the tremendous progress of anesthesia techniques, it seems permissible to offer this surgical procedure to those who have passed the age previously considered as reasonable and are quite disabled.

[Revascularization of the 2 lower limbs from the descending thoracic aorta without laparotomy]. / Revascularisation des deux membres inférieurs à partir de l'aorte thoracique descendante sans laparotomie.

Arterial bypass of the lower limbs from the thoracic aorta approached through a thoracic or abdominal route has already been described. The technique reported here is original in that the descending thoracic aorta is exposed through thoracotomy, and the prosthesis is passed behind the left kidney, then, for the right leg bifurcation, through Retzius' space without laparotomy. Two patients were operated upon with this technique which is described in detail, together with its potential indications, advantages and disadvantages.

[Aneurysm of the trunk of the superior mesenteric artery and polyaneurysmal disease of the right paracolic arcade of fibromuscular hyperplasia type. A case]. / Anévrysme du tronc de l'artère mésentérique supérieure et maladie polyanévrysmale de l'arcade bordante paracolique droite à type d'hyperplasie fibro-musculaire. Une observation.

The authors report a case of an aneurysm of the mid part of the superior mesenteric artery associated with polyaneurysmal disease of the right paracolic arterial arcade. Features of special interest in this case were the rarity of the location of the aneurysm and its aetiology: a hyperplastic fibromuscular angiodysplasia.

[Peroperative sclerosis]. / La sclérose per-opératoire.

Complete, rapid destruction of the insufficient surface network as a one-stage procedure constitutes the best method for prevention of trophic disorders and especially pigmentation. Marked, rapid regression is obtained when these have unfortunately become installed. Combined surgery and multiple peroperative injections of a sclerosant allows the exclusive use of a gently acting sclerosant, 66% glucose solution, which is particularly well tolerated.

[66% glucose, a safe sclerosant. Experimental study]. / Le glucose à 66%, sclérosant de sécurité. Etude expérimentale.

Although accidents due to the intra-arterial injection of detergent sclerosant are very rarely observed, they are dramatic in their effects and often result in amputations, a risk accepted with difficulty for a treatment with a functional aim. To avoid these incidents, which may occur even when treatment is applied by the most experienced surgeons, the authors have used 66% glucose solution without accident since 1948. To confirm efficacy of the method, an experimental study compared 66% glucose (66 G) with a very commonly used product, 1% sodium tetradecyl sulfate (STD), in the rabbit. Except when enormous doses of 66 G are employed, the only effect noted was eosinophilic necrosis of the vessel wall without clinical symptoms, whereas doses eight times lower of STD produced an irreversible ischemia from obliterating endarteritis of the branches of the vascular tree injected. The 66% glucose solution appears to be a very safe, gently acting sclerosant, and the product of choice for peri- and post-operative sclerosis, particularly in regions where accidental arterial puncture is anatomically possible.

[Peroperative multi-sclerosis using 66% glucose. Treatment of choice and best prevention of pigmentations of venous origin]. / Les multi-scléroses peropératoires au glucose á 66%. Traitement d'élection et meilleure prévention des pigmentations d'origine veineuse.

The complete and rapid destruction, at the one time, of the incompetent surface venous network is the best form of prevention of trophic changes, in particular pigmentation and leads to a marked and rapid regression of these lesions when they are already present. The combined method, associating surgery and peri-operative multi-sclerosis, allows the use of a gentle sclerosant, 66% glucose, which is particularly well tolerated.

[Product of choice for maintenance sclerosis: 66% glucose solution]. / Pour la sclérose d'entretien un produit d'élection: le sérum glucosé 66%.

The use of a 66% hypertonic glucose saline solution provides absolute security in sclerosant treatment. It has no side effects and does not provoke any allergic reactions and it produces a good quality sclerosis without pigmentation or thrombus. The injection can sometimes be painful, so it should be made very slowly. Its effectiveness is good, although less than that of sodium tetradecyl sulphate. Intra-arterial injection in animals dose not cause gangrene of the limb. Extravascular injection does not cause necrosis.

[Limitation of surgical indications in postoperative recurrence of varicose veins]. / Les limites de l'indication chirurgicale dans les récidives post-opératoires des varices.

Varicose disorders develop further after sclerotherapy when there is clear saphenous valvular incompetence, or when the surgical operation has been too limited, or faulty. Further surgery in these cases is simple and not dangerous, and clearly brings the same results as complete initial surgery. But about 1% of the patients undergoing correct and complete surgery relapse without there being any valid explanation for the venous redevelopment whose causes we have analysed. Their cure is difficult, is more dangerous, and less satisfactory results are obtained, partly because the surface area is harder to work with. In developed forms, there is no less need of the cure, combined with rigorous checks for the sclerosis of all residual veins and the treatment of associated disfiguration by the phlebologist and general practitioner. It's only in this way that we can hope for more or less satisfactory stability in these forms.

[Varicose recurrence: opinion of a team]. / La récidive variqueuse : opinion d'une équipe.

Relapse, or the continuation of the development of varicose disorder, seems to us to be common after sclerosis when there is a manifest insufficiency of the saphenous valves. Relapse following surgical operation is rare : 0.4 p. cent in our files. Most often it follows initial surgery which has been too limited, or else faulty. However, one out of every thousand of our patients has relapsed, and there has been no possible valid explanation of the venous redevelopment, whose factors are analysed.

Reinterventions for primary varices.

Out of more than 6,000 patients operated for varices since 1949, in private practice, 281 had already been operated on once before. In 230 of these cases, the first operation performed elsewhere had been incorrect or incomplete: partial stripping, a badly performed excision of the saphenofemoral-junction, neglect of gross perforants, neglect of the saphena parva which was partly or wholly responsible for 96% of the recurrences. Moreover, a partial operation, even if correct, does not check the development of a disorder which is often bilateral (89%) and which often affects the four saphenous veins (59%). 51 had been operated by myself, hoping that they would not have to come back; 29 cases in which 2/3 of the long saphenous vein was stripped and with crossectomy of the short saphenous vein until 1964, and 22 cases of complete stripping after 1965. 49 short saphenae had been causal in the first group but we noted 14 popliteal recurrences in the second. A mistaken anatomical abnormality, sixteen perforants but more particularly 30 regrown internal saphenofemoral junctions were noted in these two groups. It is difficult to give reasons for them. Finally the post-operative phlebological follow-up is often irregular or neglected. Re-operations are difficult but, with the aid of a phlebographical control, they give good results, except for deteriorations of the deep tract necessitating certain static hygiene. The best guarantees of a satisfying and lasting result are a complete and correct initial treatment of the main varices, and regular phlebological check-up.

[Arterial complications of the treatment of varices]. / Les accidents artériels du traitement des varices.

Surgical accidents (wounding, the inept mutilation of the fork of the femoral artery) are serious only when they are not recognized, and are treated late. If they are treated immediately, or soon after their occurrence, by an able team, recovery is usually straight-forward and successful. However, if a sclerosant solution is injected by accident intra-arterially, it causes irreparable damage to the area concerned, even if diagnosis is immediate and a strongly active treatment administered. Examples are cited.

[Veins and rheumatism]. / Des veines et des rhumtismes.

Stasis and venous hypertension clash with static and arthritic disorders. These conditions do not add to the risks: they multiply them (Layani). If an orthopeadic operation is considered, the venous disorder should be treated first, as completely and as soon as possible, in order to lessen the risk of thrombo-embolism and to improve the trophicity of the skin. The patient must, however, be made aware from the outset of the indispensable rules of hygiene in case of irremediable after effects or accompanying obesity. If these points are observed the rheumatological treatment will produce the best of results.

[Sports and veins]. / Du sport et des veines.

General harmonious exercise, walking and swimming in moderate measure are beneficial for all forms of venous insufficiency. Running, however and violent sport or competition may worsen the condition, especially where the deep veins are involved in the sequellae to phlebitis or congenital malformation. An exact evaluation and precise discussion of the inter-relationship between sport and vein disorders as well as a discussion of the various therapeutic possibilities represent indispensable elements of the first consultation.

Obstruction of the iliac vein by mucoid cyst: successful result of surgical excision.

The third case, if the literature's survey has been exhaustive, of mucoid cyst of the venous wall is reported. Venous obstruction with palpable tumour in the iliac fossa is not always of poor prognosis.