Focal gastric blood perfusion in relation with the endoscopic signs and liver function in cirrhotic patients.

Focal blood perfusion was measured, by means of a laser-Doppler technique, in the gastric upper body of 70 patients with liver cirrhosis and of 33 noncirrhotic controls. Perfusion was found to be lower in patients with pink mosaic-like pattern as compared to controls (p < 0.001). On the contrary, patients with red spots showed a marked increase of the focal gastric blood flow (p < 0.001). No different blood flow values were found between patients with red mosaic-like pattern and controls. Multiple regression showed that focal gastric blood flow perfusion was independently related to the Child score (p < 0.003), suggesting that gastric hemodynamic abnormalities can be favored by functional decompensation of cirrhosis, whereas there was no independent correlation with esophageal varices size, as assessed by their lumen occupancy percentage. Such observations may contribute to the understanding of the pathophysiology of gastric wall lesions in liver cirrhosis

Plasma levels of the molecular markers of coagulation and fibrinolysis in patients with peripheral arterial disease.

In 103 patients with peripheral arterial disease (PAD) of the lower limbs, coagulation and fibrinolytic parameters were evaluated to identify hemostatic abnormalities characteristic of this patient population. PAD was defined as clinically stable Leriche stage 2 (based on clinical history, peripheral pulses, ankle-arm index, and treadmill test) for at least 3 months, walking distance > 100 m, and no other major illnesses, rest pain, or trophic lesions. Defibrotide, a polydeoxyribonucleotide derivative with vascular effects, was administered to the patients as part of a multicenter trial. The PAD patients exhibited a prothrombotic state as evidenced by high D-dimer in all but 24% of the patients (average 797 +/- 802 vs. 163 +/- 54 ng/mL normal population; p < 0.001) and high thrombin-antithrombin III complex (TAT) levels (10.2 +/- 8.9 vs. 2.5 + 1.5 ng/mL; p < 0.001) with low to normal levels of protein C (86 +/- 25 vs. 102 +/- 18%; p < 0.01) and plasminogen activator inhibitor-1 (PAI-1) antigen (5.9 +/- 4.5 vs. 1.3 + 0.7 ng/mL; p < 0.001) were elevated in 79% of the patients. These results suggest that there is ongoing thrombosis in the majority of PAD patients. Differences from normal controls were observed for t-PA, PAI-1, protein C, and protein S; however, it is not certain that the thrombosis in patients with PAD is due to these factors.

Local deterioration of the cutaneous venoarterial reflex of the hand in cirrhosis.

Cutaneous focal blood perfusion and an index of cutaneous vascular resistance were determined on the dorsum and palm of the hand of 34 patients with liver cirrhosis and of 24 healthy control subjects. Tests were performed with a laser-Doppler technique before and during stimulation of the vasoconstrictor venoarterial reflex, performed by means of venous occlusion of the forearm. The mean arterial blood pressure of the cirrhotics turned out to be lower than that of the controls. On the dorsum of their hands a normal blood perfusion and a reduced vascular resistance were verified, suggesting the intervention of a local autoregulatory phenomenon of the blood flow. The blood perfusion turned out to be higher, whereas the vascular resistance was lower than the norm on the palm of the hands of cirrhotic patients who had palmar erythema, showing the presence of an anomalous non-autoregulatory vasodilation. The extent of venoarterial reflex on the dorsum of the hand turned out to be identical in the patients and controls, whereas that on the palm turned out depressed. This anomaly was present also in patients without palmar erythema, although less marked than in those with erythema. The data obtained suggest the presence of a disturbance in the functioning of the arteriovenous anastomoses (numerous in the palm but very scarce in the dorsum), superimposed on the venoarterial reflex. It may depend on the existence, in hepatic cirrhosis, of an impairment of the specialized autonomic nervous mechanisms that control temperature loss.

A double-blind, multicenter, placebo-controlled, dose comparison study of orally administered defibrotide: preliminary results in patients with peripheral arterial disease.

Defibrotide is a polydeoxyribonucleotide drug known to modulate the endothelial cell release of t-PA, PAI, and PGI-2 and to improve blood flow and perfusion. A double-blind, multicenter, placebo-controlled, dose comparison study was carried out to test the long-term efficacy and safety of defibrotide in patients with PAD (Leriche stage 2). Informed patients suffering from PAD were enrolled, and after a 15-day washout period were randomly allocated in a double-blind fashion to one of the three following treatments: defibrotide 400 mg (1 cps) b.i.d. for 6 months, defibrotide 400 mg o.d., or placebo. Absolute walking distance (AWD, treadmill) and ankle-arm pressure ratio (Winsor Index, WI) were evaluated at the beginning and after 30, 90, and 180 days after therapy. Two hundred twenty seven patients were recruited and 193 patients were included in the final analysis (800 mg: 67; 400 mg: 60; placebo: 66). All treatments brought about an increase in AWD placebo = +17%; 400 mg = +47%, 800 mg = +52%); however, patients treated with defibrotide exhibited a significantly better AWD at the end of treatment in comparison with placebo (p less than 0.01). AWD was not significantly different in the 400-mg and 800-mg groups. There was a trend indicating a possible improvement of WI after defibrotide, with higher WI in 800-mg patients in comparison with placebo (p less than 0.05). However, this difference was partly due to a decrease in arterial blood pressure elicited by the drug. The tolerability in all groups was optimal. These results indicate that orally administered defibrotide exerts symtomatic benefit in PAD patients and daily doses of 400 or 800 mg seem to be equivalent.

Transcutaneous oxygen pressure in systemic sclerosis: evaluation at different sensor temperatures and relationship to skin perfusion.

Transcutaneous oxygen pressure (TcPO2) and skin blood flow (as evaluated by laser doppler) (LD) were investigated in 24 systemic sclerosis (SSc) patients in sclerotic skin (dorsal aspect of the hand) and non-sclerotic skin (interscapular region) and in 24 controls matched for sex and age for the same sites. The two parameters were evaluated at 44 degrees C (temperature of the two sensors) in 13 patients and 13 controls, and at 36-37 degrees C in the remaining 11. At 44 degrees C, TcPO2 was lower in SSc patients than in controls for both sclerotic and non-sclerotic skin. At 37 degrees C there was no significant difference. At 44 degrees C, LD values were decreased in patients with respect to controls for both sclerotic and and non-sclerotic skin. In contrast, at 37 degrees C the values were increased in patients only for the sclerotic skin. It can be hypothesized that the increased LD values at physiological temperature are at least in part balancing a decreased tissue oxygen tension, then a normal TcPO2 is ensured. On the other hand, the decreased LD values at 44 degrees C, when TcPO2 is also decreased, indicates that there is an inability of SSc vessels to significantly increase their flow under the stimulus of a maximal hyperaemia-inducing temperature.

Effects of Centella asiatica extract on mucopolysaccharide metabolism in subjects with varicose veins.

The effects were studied of the total triterpenic fraction of Centella asiatica on serum levels of the uronic acids and lysosomal enzymes involved in mucopolysaccharide metabolism (beta-glycuronidase, beta-N-acetylglucosaminidase, arylsulfatase) in patients with varicose veins. The basal levels of uronic acids (467.7 +/- 69.3 micrograms/ml) and of lysosomal enzymes (beta-glycuronidase 1.8 +/- 0.4 microM/min/l, beta-N-acetylglucosaminidase 23.1 +/- 0.4 microM/min/l, arysulfatase 0.078 +/- 0.003 microM/min/l) were elevated, indicating an increased mucopolysaccharide turnover in subjects with varicose veins. During treatment with Centella asiatica extract (60 mg/day for three months), these levels fell progressively. At the end of treatment the serum uronic acid (231.8 +/- 51.5 micrograms/ml), beta-glycuronidase (1.2 +/- 0.05 microM/min/l), beta-N-acetylglucosaminidase (17.7 +/- 0.7 microM/min/l) and arysulfatase (0.042 +/- 0.003 microM/min/l) levels were highly significantly lower than the basal levels (p less than 0.01). The results of this trial provide an indirect confirmation of regulatory effects of the extract of Centella asiatica on metabolism in the connective tissue of the vascular wall.

A new method for the quantitative assessment of arterial insufficiency of the limbs: cutaneous postischemic hyperemia test by laser Doppler.

The cutaneous postischemic hyperemia test, by means of laser Doppler flowmetry, was carried out on 71 normal, healthy lower extremities and 138 lower limbs suffering from peripheral occlusive arterial disease. The test, a new technique for evaluating the hemodynamics of limbs, permitted a clear distinction between normal, healthy subjects and patients suffering from arterial disorders. It was also seen that the degree of deterioration in the quantitative parameters was quite obviously related to the seriousness of the clinical picture. A comparison of the more severely and less severely affected limbs of each patient and the values taken bilaterally gave a correspondence of 98.6%. A therapeutic cycle consisting of the intraarterial administration of naftidrofuryl in 20 limbs achieved a statistically significant improvement in two parameters (tL and tR). Four limbs were treated with percutaneous transluminal angioplasty. After treatment the values obtained with the test were found to be absolutely normal. It is therefore suggested that this test be widely adopted in vascular diagnostic laboratories.

Evaluation of postischemic hyperemia on the skin using laser Doppler velocimetry: study on patients with claudicatio intermittens.

A method for evaluating reactive postischemic hyperemia on the skin using the laser Doppler velocimeter is described. The study was conducted on healthy subjects and on patients affected by chronic occlusive arterial disease of the lower limbs at the second clinical stage. The laser Doppler probe is applied to the pulp of the hallux and the inflatable cuff is used for the transient occlusion of arteries both around the thigh and around the ankle. The data obtained are significant for differences between patients and controls and suggest that the cutaneous postischemic hyperemia test is of diagnostic value. The test may be used both for screening and in the follow-up of the peripheral occlusive arterial disease.

Evaluation of the effects of vasoactive drugs on cutaneous microcirculation by laser Doppler velocimetry.

The effects provoked in different points of skin circulation by a vasoactive drug injected in the femoral artery of patients affected by chronic obliterative arterial disease at clinical stage 2, were evaluated using the laser Doppler velocimeter. At the same time, by means of strain gauge plethysmography, measurements were taken of the relative variations of volume and amplitude of the pulse waves in the hallux and of blood flow in the calf. After administration of the drug, a number of phenomena were observed, the most notable of which was a rapid and intense shift of blood from skin to muscle, followed by an increase in the global perfusion of the limb. Considering the physio-pathological importance of regional blood redistribution between skin and muscle and the high frequency rate of skin lesions in vascular diseases of the limbs, the possibility of evaluating, with a practical, non-invasive technique, the effects of drugs at the skin level is of great interest.

Photo-reflex-rheographical method in the evaluation of elastocompression.

The importance of a "compression-mobilization" association in order to attain a correct therapeutical procedure is stressed. The authors then report the results of a study conducted on patients affected by varices to establish the efficacy of a treatment by means of elastic stockings with graduated compressive pressure and the efficacy of reflex-rheography as a noninvasive, economical and easy-to-use method for the assessment of the variations in venous return flow produced by the association of muscular activity and elastocompression.