Diabetic microangiopathy treated with elastic compression--a microcirculatory evaluation using laser-Doppler flowmetry, transcutaneous PO2/PCO2 and capillary permeability measurements

One hundred and forty patients with diabetic microangiopathy were studied by laser-Doppler flowmetry--measuring skin blood flow at rest (RF) and the venoarteriolar response (VAR)--by transcutaneous PO2 and PCO2 measurements and by evaluation of capillary permeability (rate of ankle swelling = RAS). Seventy were treated for 12 months with below-knee, elastic stockings. Seventy patients were left without compression acting as a control group. After 5 and 12 months there were no significant changes in the control group. However there was a significant improvement of microcirculatory parameters in patients treated with elastic compression. RF (increased at the beginning of the study) decreased. The VAR (impaired at the beginning of the study) improved significantly. PO2 (increased after treatment) and PCO2 (decreased) were also positively changed by elastic stockings. The abnormally increased capillary permeability was also improved. Elastic compression seems to be useful in diabetic microangiopathy improving microcirculatory parameters and decreasing capillary permeability and edema. However further studies, treating with elastic compression more patients for longer periods, are needed to confirm the positive effects of elastic stockings in improving diabetic microangiopathy and in slowing down its rate of progression.     

Skin flow the venoarteriolar response and capillary filtration in diabetics. A 3-year follow-up.

Resting skin blood flow (RF) and the venoarteriolar response (VAR = the vasoconstrictor response on standing) have been studied in 100 patients with diabetic neuropathy, in 100 diabetics without neuropathy, and in 100 normal subjects by laser Doppler flowmetry. Capillary filtration was also studied with strain gauge plethysmography. The authors followed up these patients by evaluating their microcirculation again after three years. At the beginning of the study in patients with neuropathy, RF and capillary filtration were increased. The VAR and the microangiopathy index (MI = VAR/RF) were reduced in all diabetics, to a greater extent to those with neuropathy. After three years the authors observed an increase in capillary filtration associated with a further impairment in VAR and MI, suggesting progression of microangiopathy in both groups of diabetics. These results suggest that the postural control of blood flow in the skin of the foot is impaired in diabetic microangiopathy, particularly in neuropathics. Increased skin blood flow and capillary filtration and the impaired venoarteriolar response cause edema and may contribute to the thickening of capillary basement membranes and the progressive evolution of diabetic microangiopathy.     

The venoarteriolar response in diabetics

Resting skin blood flow and the venoarteriolar response (VAR) were studied in 40 patients with diabetic microangiopathy and neuropathy, in 40 diabetics with microangiopathy, and in 30 normal subjects by means of laser-Doppler flowmetry. In patients with microangiopathy and neuropathy, resting flow (RF) was increased and the VAR was impaired to a greater extent than in patients without neuropathy. There was also a significant delay in the VAR in diabetics, particularly in patients with neuropathy. The microangiopathy index (VAR/RF) was on the average 71.3 in normal subjects, significantly lower (p less than 0.05) in diabetics without neuropathy (34.8), and even lower in those with neuropathy (13.6). The VAR was evaluated with different postural changes; The authors observed that in the passage from supine to standing the VAR is more evident. In conclusion these results confirm that the postural control of blood flow in the skin of the foot is impaired in diabetic microangiopathy, particularly in patients with neuropathy. The increased skin blood flow and the impaired VAR are causes of edema and may contribute to the thickening of capillary basement membranes observed in diabetes.     

Vascular reactivity related to postural changes in diabetics]

Resting skin flow (RF) and the venoarteriolar response (VAR) were studied in 40 patients with diabetic microangiopathy and neuropathy, in 40 diabetes with microangiopathy and in 30 normal subjects using laser-Doppler flowmetry. In patients with microangiopathy and neuropathy RF was increased and the VAR was impaired to a greater extent than in patients without neuropathy. We evaluated the microangiopathy index (VAR/RF) that was lower in diabetics without neuropathy and even lower in those with neuropathy than in normals We also evaluated the VAR with different postural changes.     

Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: a clinical prospective randomized trial with a microcirculatory model

Fifty patients with diabetic microangiopathy were studied by laser Doppler flowmetry (measuring skin blood flow at rest) (RF) and the venoarteriolar response (VAR), by transcutaneous PO2 and PCO2 measurements, and by capillary permeability evaluation (rate of ankle swelling [RAS]). Thirty of these patients were treated for 6 months with total triterpenic fraction of Centella asiatica (TTFCA) (60 mg twice daily), a drug active on microcirculation and capillary permeability. A control group of ten patients was treated with placebo and another group of ten patients was left without treatment thus acting as a second control group. After six months there were no significant changes in the two control groups. There was a significant improvement of microcirculatory parameter in patients treated with TTFCA. RF (abnormally increased at the beginning of the treatment) decreased, and the VAR (impaired at the beginning of the study) improved. PO2 increased and PCO2 decreased the abnormally increased capillary permeability was also improved (decreased). According to these data, TTFCA is useful in diabetic microangiopathy by improving microcirculation and decreasing capillary permeability. Also TTFCA protects against the deterioration of microcirculation due to diabetic microangiopathy.     

Treatment of diabetic microangiopathy and edema with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled randomized study

The aim of this study was to demonstrate in a prospective, placebo-controlled, randomized study, whether total triterpenic fraction of Centella asiatica (TTFCA) is effective in improving the microcirculation in diabetic microangiopathy and neuropathy, Patients with severe diabetic microangiopathy, neuropathy, and edema; patients with microangiopathy without neuropathy; and healthy subjects were included. Microangiopathy was defined by laser Doppler and capillary filtration (rate on ankle swelling). Inclusion criteria were increase in resting flux and rate of ankle swelling; decrease in venoarteriolar response (VAR) and alteration in flux increase with temperature. Patients were randomized: the treatment group received TTFCA (tablets, 60 mg twice daily for 12 months); those in the placebo group received similar tablets. Healthy controls were followed up as a reference. Groups were comparable; there were no dropouts. There were no differences in the treatment and placebo groups at inclusion. Treatment was well tolerated; no side effects were reported. No variations were observed in normals at 12 months. In the neuropathy A-group, decreases (p<0.05) in RF and RAS were observed in the two treatment groups. The decrease in RAS was associated with a decrease in edema (p<0.05) in both treatment groups. The differences in flux (38%) and in VAR (38%) were associated with a decrease (28%) in the rate of ankle swelling (p<0.05). In patients without neuropathy (B-group) the decrease in flux was 22%, the VAR increased 22.7%, and the RAS decreased 9.5% at 12 months. The variations in normals and the progressive deterioration observed in untreated patients in both groups indicates the difference between treatment and placebo. In conclusion, the decrease in capillary filtration and edema is associated with symptomatic improvement. The action on edema is beneficial for the evolution of neuropathy. The effects of TTFCA on flux, RAS, and edema are important in early stages of microangiopathy to avoid progression to clinical stages.     

5-Year control and treatment of edema and increased capillary filtration in venous hypertension and diabetic microangiopathy using O-(beta-hydroxyethyl)-rutosides: a prospective comparative clinical registry

This independent prospective controlled trial evaluates the efficacy of O-(beta-hydroxyethyl)-rutosides (HR) during 5 years of administration against signs and symptoms and further degeneration of microcirculatory disturbances. The protective effect of HR in preventing end-point complications such as venous ulceration is evaluated. This study is based on evaluation of edema and the capillary filtration rate (CFR) in association with a clinical score scale. Patients having a severe degree of chronic venous insufficiency (CVI) and venous microangiopathy and completing at least 5 years of treatment are included. The following 4 groups are considered: group A (patients with CVI but without diabetes mellitus, receiving 1500 mg/d of HR), group B (patients with CVI and diabetes mellitus, receiving 2 g/d of HR), group C (control subjects receiving no pharmacologic or compression treatment), and group D (patients using elastic compression stockings only). All patients received the "best" available treatment. No adverse effects or intolerance is noted, with good compliance (>85%). In group A, there is a statistically significant decrease in the CFR during 5 years of follow-up. In group B, the decrease in the CFR is greater than that in group A. Reductions in edema, swelling, and the CFR during 5 years are notable, and values approach normal levels. During 5 years, HR is effective in treating venous edema and hypertension and in preventing deterioration of the distal venous system. The prevention of ulcerations with HR is another important observation. The effects of HR seem to be partially dose related, and tolerability and compliance are good.     

Improvement of diabetic microangiopathy with pycnogenol: A prospective, controlled study

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd, United Kingdom) in patients with diabetic microangiopathy. Patients without a history of diabetic ulcerations were treated with Pycnogenol. Patients received oral Pycnogenol (50 mg capsules, 3 times daily for a total of 150 mg daily for 4 weeks). A group of 30 patients was included (severe microangiopathy); 30 comparable patients were observed as controls (no treatment during the observation period). All patients (age, 59 years; range, 55-68 years; male:female = 18:12) included in the treatment group completed the 4-week study. Also, all controls completed the follow-up period. There were no drop-outs. All included subjects had signs and symptoms of diabetic microangiopathy. The duration of diabetes-from the first signs/symptoms--was on average 7.5 years (SD = 3). After 4 weeks, microcirculatory and clinical evaluations showed a progressive decrease in skin flux at rest in the foot (indicating an improvement in the level of microangiopathy), a significant decrease in capillary filtration, and a significant improvement in the venoarteriolar response in all treated subjects. There were no visible effects in controls except a slight reduction in skin flux at rest in the foot. Treatment was well tolerated in both groups. In conclusion, this study confirms the clinical efficacy of Pycnogenol in patients with diabetic microangiopathy. The study indicates the clinical role of Pycnogenol in the management, treatment, and control of this common clinical problem. The treatment may be also useful to prevent diabetic ulcerations by controlling the level of microangiopathy.     

Evaluation of the local effects of vitamin E (E-Mousse) on free radicals in diabetic microangiopathy: a randomized,controlled trial

The aims of the study were to evaluate the short-term effects of a new thermosensitive, vitamin E (V-E) mousse on local free radicals (FR) and skin flux in diabetic microangiopathy. A group of 40 patients with diabetic microangiopathy was included. The variation in measurements of skin FR was evaluated by the D-Rom test. Subjects were between 45 and 65 years with type II diabetes and good metabolic control. E-mousse, a thermoactive preparation of acetate vitamin E (20%), was applied twice daily on the whole surface of the leg (below knee) and foot for 3 weeks. The contralateral leg was untreated acting as control. Subjects with age between 45 and 65 years with type II diabetes (diagnosed at least 5 years before) and good metabolic control (blood sugar < 180 mg/dL) were included after informed consent. Patients with uncontrolled diabetes, peripheral vascular disease, and severe lower limbs infections were excluded. Local free radicals (FR) and laser Doppler flux including the venoarteriolar response (VAR) were evaluated. The tolerability was evaluated by a semiquantitative score. Of the 40 included patients 34 completed the study. The 2 groups were comparable. At 3 weeks there was no decrease in FR in controls; the decrease in the treatment group was 45.3% (p < 0.05). Also in the treatment group RF decreased (p < 0.05) and the VARveno improved from an average of 21% to an average of 38% (p < 0.05). No significant variations were observed in the control group. The variation in symptomatic score was from a total value of 8 to 5 in the control group and from 8 to 1 in the treatment group (p < 0.02). Their tolerability was good. In conclusion local treatment with E-mousse for 3 weeks in diabetic microangiopathy improves skin microcirculation and the metabolic condition as shown by the decrease in FR.     

Studies on the interrelation of plasma 6-keto-prostaglandin F1 alpha, thromboxane B2 and diabetic microangiopathy

Plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2 (TXB2) were measured in 55 diabetics and 30 controls with radioimmunoassay. The correlation between diabetic microangiopathy and the ratio of TXB2 and 6-keto-PGF1 alpha was analysed. Diabetics were divided into three groups according to the change of retina and renal function. Group A, diabetics without microangiopathy; group B, diabetics with slight microangiopathy; and group C, diabetics with severe microangiopathy. The results showed that the ratio of TXB2/6-keto-PGF1 alpha was higher in B and C groups (0.997 +/- 0.31 1.10 +/- 0.25 means +/- S) than in the controls (0.72 +/- 0.17 means +/- S) (P less than 0.01). Group A patients had slightly higher level of the ratio (0.85 +/- 0.20 means +/- S) than the controls but the difference was not significant. The results suggest that the TXB2 and 6-keto-PGF1 alpha imbalance exists only in diabetics with microangiopathy and their imbalance might have more significance in the pathogenesis of diabetic microangiopathy than their individual change.     

Rapid relief of signs/symptoms in chronic venous microangiopathy with pycnogenol: a prospective, controlled study

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd, UK) in patients with severe chronic venous insufficiency. Patients with severe venous hypertension (chronic venous insufficiency, ankle swelling) and history of venous ulcerations were treated with Pycnogenol. Patients received oral Pycnogenol (50 mg capsules, 3 times daily for a total of 150 mg daily) for 8 weeks. A group of 21 patients was included in the treatment group and 18 equivalent patients were observed as controls (no treatment during the observation period). All 21 patients (age 53 years; range, 42-60 years; M:F=11:10) in the treatment group completed the 8-week study. Also the 18 controls completed the follow-up period. There were no drop-outs. The average ambulatory venous pressure was 59.3 (SD 7.2; range 50-68) with a refilling time shorter than 10 seconds (average 7.6; SD 3). There were no differences in ambulatory venous pressure or refilling time between the treatment and control patients. The duration of the disease-from the first signs/symptoms-was on average 5.7 years (SD 2.1). At 4 and 8 weeks, in all Pycnogenol-treated subjects, microcirculatory and clinical evaluations indicated a progressive decrease in skin flux, indicating an improvement in the level of microangiopathy; a significant decrease in capillary filtration; a significant improvement in the symptomatic score; and a reduction in edema. There were no visible effects in controls. In conclusion, this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy. The study indicates the significant clinical role of Pycnogenol in the management, treatment and control of this common clinical problem. The treatment may be also useful to prevent ulcerations by controlling the level of venous microangiopathy.     

Five-year treatment of chronic venous insufficiency with O-(β-hydroxyethyl)-rutosides: safety aspects

Chronic venous insufficiency (CVI), and related signs and symptoms of venous and diabetic microangiopathy, can be effectively treated with O-(β-hydroxyethyl)-rutosides (HR). The aim of the present independent registry study was to evaluate HR in a long-term (five-year) period of administration that examined the tolerability and safety of HR. Patients with severe CVI and venous microangiopathy were included in the registry. Subjects who completed five years of treatment were considered in the analysis. Blood parameters, liver and renal function tests, microalbuminuria (in diabetic patients) and cholesterol levels were evaluated to assess the effects of HR treatment. Four groups were studied - group A (98 patients) received oral HR (1500 mg per day), group B (87 diabetic patients with CVI) was treated with 2 g of HR per day, group C (90 controls, including 42 diabetic patients) had no pharmacological treatment and group D (113 patients, including 48 diabetic patients) used elastic stockings. No significant negative changes in blood parameters were recorded at two and five years. Decreases in microalbuminuria and total cholesterol, and an increase in high-density lipoprotein cholesterol were observed in HR-treated patients, particularly in diabetic patients. Minimal (nonsignificant) variations were observed in the groups that did not use HR. In conclusion, HR treatment is safe, and some positive effects from HR on cholesterol levels and microalbuminuria (in diabetic patients) that were previously observed may suggest potential new clinical applications.     

Venous thromboembolism from air travel: the LONFLIT study.

The LONFLIT study was planned to evaluate the incidence of deep venous thrombosis (DVT) occurring as a consequence of long flights. In the Lonflit study 355 subjects at low-risk for DVT and 389 at high-risk were studied. Low-risk subjects had no cardiovascular disease and used no drugs. All flights were in economy class. The average flight duration was 12.4 hours (range, 10-15 hr). The mean age of the studied subjects was 46 years (range 20-80 yr, SD 11; 56% males). DVT diagnosis was made by ultrasound scans after the flights (within 24 hours). In low-risk subjects no events were recorded while in high-risk subjects 11 had DVT (2.8%) with 13 thromboses in 11 subjects and 6 superficial thromboses (total of 19 thrombotic events in 389 patients [4.9%]). In the Lonflit2 study the authors studied 833 subjects (randomized into 422 control subjects and 411 using below-knee stockings). Mean age was 44.8 years (range, 20-80 yr, SD 12; 57% males). The average flight duration was 12.4 hours. Scans were made before and after the flights. In the control group there were 4.5% of subjects with DVT while only 0.24% of subjects had DVT in the stockings group. The difference was significant. The incidence of DVT observed when subjects were wearing stockings was 18.75 times lower than in controls. Long-haul flights are associated to DVT in some 4-5% of high-risk subjects. Below-knee stockings are beneficial in reducing the incidence of DVT.     

Left ventricular function in well-controlled insulin-dependent (type I) diabetics--an echophonocardiographic study

A high prevalence of left ventricular dysfunction in insulin-dependent (type-I) diabetics has been reported. However, the exact influence of metabolic control and/or the coexistence of early diabetic microangiopathy is unknown. Thus, we assessed left ventricular function by echophonocardiography in 50 type-I diabetics (mean age 26 +/- 7.9 years), who showed a fairly good metabolic long-term control (mean hemoglobin A1: 8.8%) after the introduction to intensified insulin therapy in comparison with 50 age- and sex-matched controls. Type-I diabetics did not differ from controls in their left ventricular internal diameters, mean wall thickness, ratio of pre-ejection period to left ventricular ejection time and systolic shortening fraction. Isovolumetric relaxation period reflecting an early diastolic event was slightly but significantly prolonged in diabetic subjects, independent of metabolic control status or existence of early microangiopathy. Isovolumetric relaxation period showed a statistically significant correlation to age in type-I diabetics, but not in controls. Possibly, the diabetic status--although well-controlled, but not normalized--may biochemically alter the myocardium and might influence its diastolic properties.     

Tissular oxygenation and venoarteriolar reflex disturbances in diabetes mellitus: vasoregulator effect of Buflomedil

The present study was designed to investigate whether the Veno-Arteriolar Reflex (VAR) mediated via a local nervous reflex mechanism may be used as a microvascular approach to predict the effect of vasoactive drugs in diabetic patients. The vasoactive drug we studied here was Buflomedil. The effect of a single infusion of 400 mg of Buflomedil was examined on VAR and on transcutaneous oxygen pressure (TcPO2). Investigations were performed in 42 diabetic patients. The VAR was assessed on dorsal foot and dorsal big toe by measuring changes in skin blood flux induced by lowering the leg. TcPO2 was measured on dorsal foot. Before Buflomedil infusion, patients were characterized by a loss of the VAR in comparison to healthy volunteers. The loss of the VAR was associated to significant decreases in TcPO2 values. Buflomedil infusion led to significant increases in VAR at the two sites of measurement and also in TcPO2 values. These findings indicate that the VAR can be used as a sensitive microvascular test, as it allows to detect the effect of Buflomedil. Furthermore, our findings demonstrate that the Buflomedil-induced improvement in VAR is identical in the two diabetic groups with or without complications. This result emphasizes the benefit of Buflomedil not only in diabetics with microangiopathy or those suffering from a peripheral vascular disease for reducing pain or healing trophic lesions, but also in those patients without any clinically detectable macro- or microangiopathy in order to prevent or to reduce as long as possible the risk of developing diabetes related complications by the normalization of functional microangiopathy.     

Isotopic test of capillary permeability to albumin in diabetic patients: effects of hypertension, microangiopathy, and duration of diabetes

Capillary permeability to albumin (CPA) was studied by performing an isotopic noninvasive test with venous compression on 87 nonselected diabetics with no edema, no cardiac failure, and no peripheral vascular disease. Excessive albumin retention (AR greater than or equal to 8%) ten minutes after removal of the compression was found in 27 patients (31%). The radioactivity disappearance curve was then analyzed using the Fast Fourier Transform (FFT). An abnormal isotopic CPA test was thus found in at least 45 out of the 87 patients. The prevalence of an abnormal test was not different in type 1 and type 2 diabetics. We studied the independent effects of hypertension, presence of specific clinical signs of microangiopathy (retinopathy and/or significant proteinuria), and duration of diabetes. Among diabetics free of specific clinical signs of microangiopathy, the prevalence of an AR greater than or equal to 8% was significantly higher in those with hypertension (11/19) than in those with normal blood pressure (2/28) and in nondiabetic hypertensive patients (0/16). Among normotensive diabetics, the prevalence of an abnormal test was higher, but not significantly, in patients with specific clinical signs of microangiopathy (8/11) than in those free of them (7/18). Seven normotensive diabetics without specific clinical signs of microangiopathy had an abnormal test; five of them had had diabetes for more than five years. The prevalence of diabetes of more than five years duration was significantly higher in patients with an abnormal test (35/45) than in normotensive diabetics free of specific clinical signs of microangiopathy with a normal test (4/11).(ABSTRACT TRUNCATED AT 250 WORDS)     

HR, 0-(beta-hydroxyethyl)-rutosides; (Venoruton): rapid relief of signs/symptoms in chronic venous insufficiency and microangiopathy: a prospective, controlled study

The aim of this independent study was to demonstrate the rapidity of the clinical action of HR 0-(beta-hydroxyethyl)-rutosides, Venoruton (Novartis Consumer Health) in patients with chronic venous insufficiency (CVI). Two groups of patients with venous hypertension and microangiopathy were treated with HR (1 or 2 g/day, for 8 weeks). Twelve patients (age 56.4; range 44-66; M:F = 6:6) were included in group 1 (1 g/day) (moderate CVI and microangiopathy); 10 patients (age 57.4; range 42-67; M:F = 5:5) in group 2 (2 g/day) with more severe CVI and microangiopathy. Average ambulatory venous pressure (AVP) was 58.6 (range 50-65) with a refilling time (RT) shorter than 10 seconds. There were no significant differences in AVP and RT between the 2 groups, but the duration of the disease was longer in group 2: 3.5 years (SD 2.0) in group 1 and 6.4 years (SD 3.3) in group 2. All included subjects completed the study and no dropouts were observed. In both dose groups there was a progressive decrease in laser Doppler resting flux (RF), indicating improvement in microangiopathy and a significant decrease in capillary filtration (RAS) associated with a significant improvement in analogue scale line score (ASLS) and edema. Although the effect in the 2 g dose group was more rapid on the microcirculatory parameters with a significant effect on RF and RAS after 4 days (effect of 1 g per day after 8 days and 6 days, respectively), there was no difference in the time to onset of a significant clinical improvement (ie, the ASLS and the edema score): 4 days in both groups. Venous microangiopathy and edema were improved by the treatment with HR within a few days. The effects were visible with both dosages, in both severity groups.     

Prevention of edema and flight microangiopathy with Venoruton (HR), (0-[beta-hydroxyethyl]-rutosides) in patients with varicose veins

The aim of this open study was the evaluation of the effects of HR (Venoruton) at a dose of 1 g/day on the prevention and control of flight microangiopathy and edema in subjects with varicose veins and moderate chronic venous insufficiency flying for more than 11 hours. Patients with varicose veins, edema, but without initial skin alterations or complications, were included. Measurements of skin laser Doppler (LDF) resting flux (RF) venoarteriolar response (VAR), ankle swelling (RAS), and edema were made within 12 hours before and within 3 hours after the flights. The resulting edema after the flights was evaluated with a composite edema score (analogue scale line). A group of 20 subjects was treated with HR (1 g/day, starting 2 days before the flight and 1 g for every 12 hours on day of travel). Another group of 18 subjects formed the control group. The length of the flights was between 11 and 13 hours; all seats were in coach class. Fifty patients were enrolled and 38 patients were evaluable at the end of the trial. The 2 groups (treatment and control) were comparable for age and sex distribution. The decrease in RF was significant in both groups with a higher flux at the end of the flight in the HR group (p < 0.05). The venoarteriolar response was decreased at the end of the flights; the decrease was lower in the HR group (p < 0.05). The increase in RAS and the edema score were significantly lower in the HR group. In conclusion HR is useful for reducing the level of microangiopathy and the increased capillary filtration and in controlling edema in patients with venous disease in long flights. The higher level of flux and VAR and the reduction in edema indicate a positive effect of HR on the microcirculation. This study confirms that HR prophylaxis is effective to control flight microangiopathy associated with edema.     

Fibrinolytic enhancement in diabetic microangiopathy with defibrotide.

Skin microcirculation was evaluated in 117 patients with diabetic microangiopathy over a period of six months. They were divided into two groups. Group 1 (64 patients) was treated with oral defibrotide, a new profibrinolytic drug, in association with diet and oral antidiabetic drugs. Group 2 (53 patients) was treated only with diet and antidiabetic agents. The microcirculation was studied by means of laser-Doppler flowmetry transcutaneous partial pressure of oxygen and carbon dioxide pressure measurements, and evaluation of capillary filtration. After six months, patients in group 1 improved their microcirculatory parameters in association with an improvement in signs and symptoms. Moreover, 30 patients in group 1 and 36 in group 2 were followed up for eighteen months, and the authors observed that the deterioration of the microcirculatory parameters was significantly slowed in diabetics treated with defibrotide. A decrease in plasma fibrinogen during defibrotide treatment was observed in all treated patients in association with an increased fibrinolytic activity. In conclusion, it appears that defibrotide, enhancing fibrinolysis, improved the microcirculation in diabetics, preventing further, progressive deterioration.     

Prevention of deep vein thrombosis in potential neurosurgical patients. A randomized trial comparing graduated compression stockings alone or graduated compression stockings plus intermittent pneumatic compression with control

In a randomized trial of neurosurgical patients, groups wearing graduated compression stockings alone (group 1) or graduated compression stockings plus intermittent pneumatic compression (IPC) (group 2) were compared with an untreated control group in the prevention of deep vein thrombosis (DVT). In both active treatment groups, the graduated compression stockings were continued for 14 days or until hospital discharge, if earlier. In group 2, IPC was continued for seven days. All patients underwent DVT surveillance with iodine 125-labeled fibrinogen leg scanning and impedance plethysmography. Venography was carried out if either test became abnormal. Deep vein thrombosis occurred in seven (8.8%) of 80 patients in group 1, in seven (9.0%) of 78 patients in group 2, and in 16 (19.8%) of 81 patients in the control group. The observed differences among these rates are statistically significant. The results of this study indicate that graduated compression stockings alone or in combination with IPC are effective methods of preventing DVT in neurosurgical patients.