Treatment of stage II chronic arterial disease of the lower limbs with the serotonergic antagonist naftidrofuryl: results after 6 months of a controlled, multicenter study.

A study was carried out in patients with intermittent claudication (Fontaine's stage II). The atheromatous origin of the disease was confirmed and localized by angiography or Doppler. One hundred eight-three patients were selected initially (day -30) with a pain-free walking distance on a treadmill (at a speed of 3 km/h and a slope of 10%) ranging from 150 to 300 m. During the first month (washout period) all patients received two placebo tablets daily. At the end of this run-in period (day -30; day 0) and after checking walking distance stability (allowed variation: 20% between the two measurements), patients were included in the study. According to this criterion, 112 patients were selected and 94 remained during the whole study. The study was designed in double-blind, using two parallel, randomly selected groups. Fifty-two patients received naftidrofuryl (2 x 316.5 mg tablets daily with meals) for 6 months; 42 patients received placebo under the same conditions. During this period, clinical and paraclinical examinations were carried out every quarter (day 90 and day 180). After checking the initial homogeneity of the naftidrofuryl and placebo groups, the comparison between the two groups indicates a significant improvement in the naftidrofuryl group after 3 months and 6 months of treatment, for the pain-free walking distance. For the maximal walking distance, a significant improvement was found at day 180. Nonparametric analysis (chi 2 test) also indicated a significant improvement for the naftidrofuryl group. These results confirm that naftidrofuryl is beneficial in the treatment of patients with chronic arterial disease.

A long term treatment with a venotropic drug. Results on efficacy and safety of Daflon 500 mg in chronic venous insufficiency.

UNLABELLED: Drugs for long term administration have to prove their efficacy and safety. Previously published double blind controlled studies (from single dose to two months treatment) have already demonstrated the phlebotropic activity of Daflon 500 mg in chronic venous insufficiency (CVI). The aim of the study was to investigate the safety of this agent during one year of continuous administration. Two-hundred and fifteen out-patients suffering from CVI received Daflon 500 mg, 2 tablets per day. Therapeutic activity was evaluated every 2 months on: 1) venous symptoms (functional discomfort, cramps, evening oedema) assessed by a 0 to 4 scale; 2) supramalleolar and calf circumferences; 3) overall assessment of efficacy (excellent, useful, nil). Acceptability was assessed by recording the side effects and measuring laboratory parameters. RESULTS: 170 patients completed the study. Functional symptoms were statistically significantly improved as shown by the following: functional discomfort: 0.55 +/- 0.06 vs 2.63 +/- 0.06, supra-malleolar circumference in cm: 22.5 +/- 0.2 vs 23.1 +/- 0.2, and calf circumference in cm: 34.7 +/- 0.3 vs 35.2 +/- 0.3. This improvement in the symptoms quickly appeared from the first control (M2) and reached about 50% of the total decrease. Overall assessment of efficacy was evaluated as follows: excellent = 58%, useful = 33%, nil = 9% of the cases. Laboratory parameters remained constant during the 12 months. Side effects were essentially gastralgia (n = 7). According to these results, it appears the efficacy and safety of Daflon 500 mg are corroborated even after a one year administration.

[Holter erectometry. A new approach to erectile disorders]. / Le Holter d'érectométrie. Une nouvelle approche des troubles érectiles.

A Holter-type portable computerised electronic system for measurement of the apparent volume of the penis, eye movements and heart rate over 12 hours, enables investigation of erectile disorders by the patient himself, under more physiological conditions at home. Data processing and ease of use will permit scientific use on a large scale.

[Impotence in the diabetic]. / L'impuissance chez le diabétique.

Two-hundred-and-two impotent diabetic patients gave their consent to be investigated. Impotence is linked to diabetes mellitus in 58.9% of patients so all the other etiologies have to be systematically eliminated. Neuropathy or arteriopathy, when isolated, are found with the same frequency, but these 2 etiologies are often associated (47 patients). No statistical difference between IDDM and NIDDM was found. Mercury strain gauge plethysmography and venous occlusion coupled to ECG allows detection of arterial lesions in diabetic impotence. Patients agreed to submit to all of the various therapeutic possibilities. Combination of alpha-blockade and good glycemic control induced the best results.

[Study of the HLA system and glyoxalase in 31 insulin-dependent diabetics free from micro and macro-angiopathies after more than a 20-year development]. / Etude du système HLA et de la glyoxalase chez 31 sujets diabétiques insulinodépendants indemnes de micro et macro angiopathie après plus de 20 ans d'évolution.

Insulin-dependent diabetics are not equal as concerns vascular complications. Many factors have been incriminated. The object of this study was to determine if a genetic factor protected the insulin-dependent diabetic from vascular complications. The population included 31 unrelated, white insulin-dependent diabetic subjects (18 females and 13 males), with diabetes of over 20 years' duration (21 to 43 years, m +/- SD 27.82 +/- 6.03 years; age at diagnosis: 2 to 57 years, m +/- SD 22.7 +/- 15.19 years). The absence of vascular lesions was checked for by the following investigations: visual acuity, fundoscopic examination, retinal fluorescein angiography (Canon F 60 Z), systolic pressure on the thigh and ankle, Doppler velocimetry, plethysmography of the lower limbs, serum creatinine level, urinary protein. The study of the HLA A, B, DR specificities was carried out using the Tersaki microlymphocytotoxicity assay, those of C4 by high voltage gel electrophoresis followed by hemolytic detection, those of B1 using Alper's method and those of glyoxalase by gel electrophoresis followed by a glutathione redox reaction in order to test for a marker for a possible protective genetic factor against complications. The antigen frequencies found were compared with: 1) Those in the general Caucasian reference population (9th Histocompatibility Workshop, 1984). The study group presented the HLA characteristics known to occur in insulin-dependent diabetes: increase in A30, B8, B18, D6, DR3, DR4, BfF1 and decrease in A3, B7, DR2. Furthermore an increase in the frequency of DRw53, DQw2 and DQw3 alleles was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphometric study of human hepatic cell modifications induced by fenofibrate.

We have studied liver biopsies obtained in 12 hyperlipoproteinemic (HLP) patients (type II, 6; type IV, 6) treated with diet and fenofibrate, and in 15 patients (type II, 11; type IV, 4) receiving diet only. Electron microscopy of liver biopsies and the morphometric analysis according to the method of Weibel and Rohr showed mitrochondrial changes in patients treated with fenofibrate, these changes depending on the type of hyperlipoproteinemia. In type II HLP, we found a decreased volume of normal mitochondria (fenofibrate, 125.72 +/- 17.04 X 10(-3) cm3/cm3; diet only, 185.84 +/- 8.96 10(-3), P less than .05). In type IV HLP we found a decreased number of giant mitochondria (fenofibrate, 0.08 +/- 0.03 X 10(10) cm-3; diet only, 0.32 +/- 0.08 X 10(10) cm-3, P less than .05) and a decreased volume of altered mitochondria (fenofibrate, 6.00 +/- 1.44 X 10(-3) cm3/cm3; diet only, 13.61 +/- 1.17 X 10(-3), P less than .05). In contrast with the rodent studies, the present study shows no change in the number of volume of peroxisomes.

Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs.

Ninety-four patients suffering from venous insufficiency of the lower limbs participated in a multicenter, double-blind versus placebo study. After randomization, they were allotted for a treatment period of two months to one of three groups: TECA 120 mg/day, TECA 60 mg/day, or placebo. A significant difference (p less than 0.05) in favor of TECA was shown for the symptoms of heaviness in the lower limbs and edema, as well as for the overall evaluation by the patient. The venous distensibility measured by a mercury strain gauge plethysmograph at three occlusion pressures was improved for the TECA groups but aggravated for the placebo group.

[The flow-volume curve. Expression of emptying as a function of venous distensibility]. / La courbe débit-volume. Expression de la vidange en fonction de la distensibilité veineuse.

Mercury strain gauge venous occlusion plethysmography is a non invasive exploration of the lower limb venous hemodynamic. Classically, venous distensibility (delta V/V %) is expressed in terms of time during venous inflow (venous occlusion) and venous outflow (after cuff deflation). The authors proposed to express the total flow Q of the limb (obtained by a differentiator of the electric signal of the strain gauge) in terms of the venous distensibility (delta V/V %) whatever recording a top each second. This new representation Q = f(delta V/V) permit a more acute visualisation of the initial part of the venous emptying: more differentiation between venous drainage and systolic arterial waves, acceleration then deceleration of the venous emptying, return of the venous wall to its initial position later than venous emptying, active venous constriction. Some parameters are proposed to described this curve and the values obtained in 50 patients without and 10 patients with deep venous thrombosis are reported.

tcpO2, arterial blood flow and lactate/pyruvate modifications induced by a single dose of naftidrofuryl IV during stage III lower-limb arteriopathies.

A single dose of 600 mg of naftidrofuryl perfused IV during three hours in 12 stage III arteriopathic patients did not modify the average blood flow at the calf but did significantly increase transcutaneous oxygen pressure (33 vs 52 mmHg) and also improved lactates (1.44 vs 0.88 mmol/liter), pyruvate (59 vs 79 mumol/liter), and lactates-pyruvates ratio (33.48 vs 20.92).

Effect of exchange of ham for boiled egg on plasma glucose and insulin responses to breakfast in normal subjects.

Blood glucose (BG) and plasma insulin (IRI) were measured during two breakfasts different only by the nature of proteins--egg (E) or ham (H)--in eight normal subjects. Compared with H, E led to a flattened BG response at 30, 40, and 50 min and to a sustained BG from 150 to 240 min. Integrated BG response was not significantly different between E and H. After E, the IRI response decreased at 90 min and 120 min (P less than 0.05). Integrated IRI response with E was significantly smaller than with H (P less than 0.025). The reasons for the effect of E ingestion on BG are not obvious; pancreatic and/or intestinal mechanisms may be involved. It is suggested that greater consideration be given to the protein composition of the test meals when they are used in studies of glucose homeostasis.

[Sympathectomy of the digital arteries in acro-syndromes]. / Les sympathectomies des artères digitales dans les acro-syndromes.

Digital sympathectomy as proposed by Flatt and al. was performed on 12 Raynaud's diseases, 6 distal arteriopathy and 4 post-trauma ischemic syndrome. Operation was performed under tourniquet. The approach depends on the number of digits involved (Brünner at the proximal part of P1, transversal in the distal palmar crease, zigzag incision at the level of each intermetacarpal space). Under microscope, adventisectomy is started on a lateral side of the artery followed by the posterior side on at least 1 cm, using the adventitia avoid all direct manipulation of the vessels. Closing skin on an aspirative drainage and simple non compressive drainage is maintaining 4 days. Index pressure and arterial blood flow are measured. Results are bad for post-trauma ischemic syndrome and arteritis but encouraging in Raynaud's disease (7 patients asked for the same operation on the opposite side).

The hepatocyte and type IIA and IIB hyperlipoproteinemia. A morphometric study.

We obtained liver biopsies in 4 patients with type IIA and 7 patients with type IIB hyperlipoproteinemia, and also in 7 healthy controls. A morphometric analysis of liver tissue was carried out by light and electron microscopy. Structural alterations of the hepatocyte and its organelles in type IIA and IIB hyperlipoproteinemia seem to fall into different categories: smaller nuclei, enlarged peroxisomes and altered mitochondria are found in both types of hyperlipoproteinemia, while an increase in the volume of hepatocytes is found only in type IIA. The enlargement of liver peroxisomes in untreated hyperlipoproteinemia is noteworthy, since it has been considered as a marker of the liver toxicity of lipid-lowering drugs.

The prevalence of retinopathy is similar in diabetes mellitus secondary to chronic pancreatitis with or without pancreatectomy and in idiopathic diabetes mellitus.

In a retrospective study, we compared the prevalence of retinopathy in two groups of 88 diabetic patients (84 men, 4 women) with either diabetes mellitus secondary to chronic pancreatitis (CP-DM group) or idiopathic diabetes mellitus (I-DM group). The patients of these two groups were pair-matched according to age (48.7 +/- 1.1 versus 48.8 +/- 1.0 yr in CP-DM and I-DM groups, respectively; mean +/- SEM), sex, duration of diabetes (7.96 +/- 0.56 versus 8.08 +/- 0.8 yr) and therapy (80 on insulin and 8 on oral hypoglycemic agents in each group). Retinopathy was assessed by bilateral ophthalmoscopic examination of the fundus after pupillary dilation in all 176 patients and by fluorescein angiography in 47 patients with CP-DM and 35 patients with I-DM. Forty-one percent of patients in the CP-DM group and 45.5% of patients in the I-DM group had diabetic retinopathy (P greater than 0.5). In each group, patients with retinopathy were older than patients without retinopathy (51.6 +/- 1.3 versus 46.7 +/- 1.8 yr in the CP-DM group, P less than 0.01, and 52.1 +/- 1.5 versus 46.0 +/- 1.2 yr in the ID-M group, P less than 0.01). They had diabetes of longer duration (10.9 +/- 1.0 versus 5.9 +/- 0.6 yr in the CP-DM group, P less than 0.001, and 10.5 +/- 1.0 versus 6.0 +/- 0.6 yr in the ID-M group, P less than 0.001). The prevalence of retinopathy increased parallel to the duration of diabetes in a similar way in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of ketanserin on platelet function and red cell filterability in hypertension and peripheral vascular disease.

Serotonin is a vasoactive substance that acts on blood vessels and platelets but whose primary action lies in its role as an amplifier for other agents. The aim of this work was to study the effects on blood platelets and erythrocytes of the S2-serotonergic receptor antagonist ketanserin. Twenty-seven patients with untreated hypertension and/or intermittent claudication received a bolus intravenous (i.v.) injection of 10 mg ketanserin followed by 2 mg/h during 3 h i.v. infusion. Platelet function and erythrocyte filterability were studied before and 30 min, 3 h, and 24 h after the bolus injection. The results showed decreases of plasma beta-thromboglobulin and platelet factor 4 levels (p less than 0.001) and platelet aggregation induced by epinephrine plus serotonin (p less than 0.001), whereas ADP-induced aggregation remained unchanged 30 min and 3 h after ketanserin administration. Red cell filterability was decreased (p less than 0.01). There was a tendency toward lower mean arterial blood pressure but heart rate remained unchanged. The dual effect of ketanserin on platelet function and erythrocyte filterability might be of great clinical value in hypertension and peripheral vascular disease in which microcirculatory flow is altered.

[Pulsatility, flow and metabolic diseases]. / Pulsatilité, débit et maladies métaboliques.

Metabolic diseases, and particularly diabetes mellitus have a well-established vascular determinism. Diabetic arteriopathy is associated from its onset with elevated tissue blood flow at rest and blood and plasma hyperviscosity. These anomalies are corrected by the perfect equilibration of the glycemia with the artificial pancreas. In 8 to 28% of cases, according to the author, there is an original hemodynamic picture; the enhanced flow hyperpulsatile diabetic arteriopathy observed in a caricatural manner in ulcerated mutilating acropathies. The vasomotor inertia of the diabetic artery and the metabolic neuropathy suggest that surgery to increase blood flow might be of interest in diabetic patients, as a function of results of previous function tests.

Nightly amended IRI/BG ratio in fasting test during sleeping periods in subjects with insulinoma and in normal, diabetic and obese subjects.

In order to obtain a dynamic picture of the way abnormal insulinemia, as a function of blood glucose, occurs in the morning in subjects with insulinoma, we have measured amended plasma insulin (IRI)/blood glucose (BG) ratio during the fasting period of 4 sleeping subjects with insulinoma. Healthy subjects and subjects suffering from other diseases were used as reference in order to determine variations of this ratio during the night. BG and IRI were assayed at intervals of 15 or 30 min. Subjects with insulinoma differed from the other subjects by a very elevated ratio dispersion around the mean value with highly significant peaks (greater than 100). Mean value always remained outside the range (7-82) which covers the total range of values measured in healthy and pathological subjects.