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The evolution of microcirculatory methods and the definition of the concept of venous microangiopathy allow the study in a quantitative way of microcirculatory changes produced by pharmacologic treatments at the areas most frequently and severely affected by chronic venous insufficiency (CVI), venous hypertensive microangiopathy, and venous ulcerations. This pilot study compares subjects with CVI, in the area most affected by venous hypertension in a 2-week registry. Elastic compression, compression plus Viatromb® (lyposomal spray gel heparin), Lioton® (gel including heparin), and Viatromb® alone were compared. Subjects were evaluated for laser Doppler flux, transcutaneous partial pressure of oxygen (TcPO2), and partial pressure of carbon dioxide (PCO2) and CVI analogic symptom scale. In the Viatromb® groups (B and D), significant decreases in laser Doppler flux, PCO2, and CVI score were observed. The decrease was proportionally more important in the elastic compression plus Viatromb ® group. Partial pressure of oxygen (PO2) was significantly increased. No significant changes were observed in the Lioton® group. There was a good effect for compression only. These differences are significant, as they can be observed even in small groups (10-15 patients). No treatment side effects were observed, and compliance and tolerability were very good.

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.

The aim of this study was to assess the preventive action of Pycnogenol® (Horphag Research Ltd, UK) on cramps and muscular pain in different groups of subjects and patients. The study included a 5-week observation period (4 weeks treatment and one follow-up week after the suspension of treatment) to evaluate the efficacy of Pycnogenol after its withdrawal. Four 50 mg capsules (total dose 200 mg/day) were prescribed with suggestion to drink at least 1.5 liters of water every day. In the first part of the study 66 healthy subjects completed a 5-week follow-up period. The difference between number of cramps attacks recorded within the 2 weeks before inclusion and the number of episodes during the fourth (p

The aim of this study was to evaluate the prevention of edema during long-haul flights with an oral, anti-edema and antithrombotic agent (Pycnogenol®, Horphag, Research Management SA, Geneva, Switzerland) in asymptomatic subjects. The assessment of edema was performed by evaluating an analogue scale, the rate of ankle swelling by strain-gauge derived rate of ankle swelling (RAS), and by assessing the ankle circumference variation. The study included 211 subjects; 169 completed the study (88 in the control group and 81 in the Pycnogenol® group). There were no important differences between the two groups (comparable for age, gender, weight, body mass index, and pattern distribution). The edema score, the RAS, and the circumference at inclusion were also comparable. After the flight in those treated with Pycnogenol®, the edema score was increased only by 17.9% (vs. an increase of 58.3% in the control group) (p® group (age 44.5; SD 8) and in 23 in the control group (age 45; SD 9) was increased on average by 91% in the control group and 36% in the Pycnogenol® group (p® group (11% in the control group; p® on edema during long flights when considering subjective and objective data. No unwanted effects were observed.

Shock waves (SW) are used to control pain in different clinical conditions (eg, painful knee, elbow, and shoulder, etc). The effects of SWs may be due to cellular “stunning” (particularly nervous components). It may also be the consequence of unknown metabolic actions on tissues, which may include changes in cellular permeability, the liberation of proteins and mediators locally acting on pain and nerve endings. The aim of this study was to evaluate the reduction in pain and the improvement in microcirculation induced by SW treatment in a 2-week study in patients with chronic limb ischemia (CLI). Of the 32 patients with CLI, 30 (20 with rest pain only, 10 with necrosis) completed the study. The treatment was well tolerated. Foot radiographs performed before and after treatment indicate no bone damage after treatment. Foot (tibial arteries) blood pressure was unchanged after 2 weeks. The increase in laser Doppler flux was significant (p2) increased (p2) decreased (p

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.

The aim of this study was to evaluate the development of edema, and superficial and deep vein thrombosis (DVT) prophylaxis with an oral profibrinolytic agent (Flite Tabs, 150 mg pinokinase, Aidan, Tempe, AZ, USA) in long-haul flights (7-8 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several problems including concomitant treat ments ; 204 were randomized into 2 groups (active treatment or placebo) to evaluate the effects of prophylaxis with Flite Tabs. An exercise program was used in both groups. The femoral, popliteal, tibial, and superficial veins were scanned with ultrasound before and within 90 minutes after flights. Of the included subjects, 92 of 103 controls and 94 of 101 treated subjects completed the study. Dropouts were due to connection problems. Age, gender, and risk distribution were comparable in the groups. In the treatment group, no DVT was observed. In the control group, 5 subjects (5.4%) had a DVT and there were 2 superficial thromboses (7 events in 92 subjects; 7.6%). At inclusion, edema was comparable in the 2 groups. After flights there was an increase in score in controls (+12%) in comparison with a decrease (-15%) in the Flite Tabs group (the difference in variation was statistically significant). Intention-to-treat analysis for thrombotic events shows 18 failures in controls (11 lost to follow-up + 7 throm botic events) of 92 subjects (19.6%) in comparison with 7 failures (of 94 subjects, equivalent to 7.4%) in the treatment group (p

The study compared, by a prospective, randomized method, 6 treatment options: A: Sclero therapy ; B: High-dose sclerotherapy; C: Multiple ligations; D: Stab avulsion; E: Foam-sclero therapy ; F: Surgery (ligation) followed by sclerotherapy. Results were analyzed 10 years after inclusion and initial treatment. Endpoints of the study were variations in ambulatory venous pressure (AVP), refilling time (RT), presence of duplex-reflux, and number of recurrent or new incompetent venous sites. The number of patients, limbs, and treated venous segments were comparable in the 6 treatment groups, also comparable for age and sex distribution. The occur rence of new varicose veins at 5 years varied from 34% for group F (surgery + sclero) and ligation (C) to 44% for the foam + sclero group (E) and 48% for group A (dose 1 sclero). At 10 years the occurrence of new veins varied from 37% in F to 56% in A. At inclusion AVP was comparable in the different groups. At 10 years the decrease in AVP and the increase in RT (indicating decrease in reflux), was generally comparable in the different groups. Also at 10 years the number of new points of major incompetence was comparable in all treatment groups. These results indicate that, when correctly performed, all treatments may be similarly effective. "Standard," low-dose sclerotherapy appears to be less effective than high-dose sclero and foam-sclerotherapy which may obtain, in selected subjects, results comparable to surgery.

Objectives: To evaluate the prevalence of stroke and transient ischaemic attack in the elderly population, including the oldest residents, of a rural Italian community. Methods: A door-to-door survey was performed between April and October 2001 in 2390 subjects aged 65 years and over. A symptom questionnaire validated by medical records and neurological examination was employed. Results: Complete information was available for 2260 subjects. The overall prevalence of stroke was 8.2% in males and 5.1% in females. In the very elderly, this increased to 10.7% in males and 10% in females and decreased only in males aged 90 years or over. The overall prevalence of transient ischaemic attack was 7% in males and 4.9% in females. This, too, increased with age, reaching 10.2% in males and 7.4% in females and decreased only in subjects of both sexes aged 85 years or over. Conclusions: An actual estimate of the high prevalence of cerebrovascular disease in the elderly population, even in very old subjects, was thus achieved. Appropriate health care services consequently need to be planned.

The aim of this study was to demonstrate whether HR (Paroven, Venoruton; 0-(β-hydroxyethyl)-rutosides), was effective in improving levels of plasma free radicals (PFRs) in patients with chronic venous insufficiency (CVI) and venous microangiopathy. Patients were randomized into the treatment group, which received oral HR (Ig sachets, twice daily, for 4 weeks), and a placebo group, which received comparable placebo. Below-knee Sigvaris stockings were used during the study. PFRs were measured with the D-Rom test at the finger and at a vein of the leg in an area of CVI. The mean age of included subjects was 46 years (SD 11) in the treatment group (20 patients; 6 females) and 46.4 (SD 8) in the placebo group (20 patients; 7 females). There were no differences between placebo and treatment groups at inclusion in age and sex distribution and in parameters indicating venous hypertension. The decrease of PFRs levels in the treatment group was significant, both at the finger and in the distal blood taken in areas of CVI. There there were no significant changes in the control group. In areas of venous hypertension, PFRs values were on average higher than at the finger (systemic) level (P < 0.05). In parallel with the progressive decrease in PFRs associated with treatment, the analogue score was significantly decreased at 2 (P < 0.05) and 4 weeks (P < 0.02) in the HR group. No changes were observed in the placebo group. No adverse effects were observed. In conclusion, HR treatment is effective in decreasing both the systemic and local values of PFRs and therefore may have a positive effect on the evolution of CVI.

This study was planned to demonstrate in a prospective, placebo-controlled, randomized study, whether HR (Paroven, Venoruton; 0-(P-hydroxyethyl)-rutosides), is effective in improving the microcirculation in subjects with diabetic microangiopathy and neuropathy. Patients with severe diabetic microangiopathy, neuropathy and edema, patients with microangiopathy, without neuropathy, and 20 healthy subjects were included. Microangiopathy was defined by laser Doppler flowmetry and capillary filtration (rate of ankle swelling (RAS)). Inclusion criteria were: increase in resting flux (RF) and RAS, a decrease in venoarteriolar response (VAR), and alterations in flux increase with temperature. The 2 groups of patients and the control group were randomized in a treatment sub-group which received HR (1 g, twice daily for 6 months); those in the placebo group received similar treatment. Results: Groups were comparable; there were no drop-outs. There were no differences in the treatment and placebo groups at inclusion. Treatment was well tolerated; no adverse effects were reported. No variations were observed in healthy subjects at 6 months. In both groups of patients, significant decreases (P < 0.05) in RF and RAS were observed in the active treatment groups. The decrease in RAS was associated with a decrease in edema (P < 0.05) in both treatment groups. The decrease in RF and the increase in VAR were associated with a proportional decrease in RAS (P < 0.05). In patients without neuropathy, the variations in RF, VAR, and RAS were larger (P < 0.05) at 6 months. The variations in healthy subjects were limited and not significant. Conclusion: The decrease in capillary filtration and edema with HR is associated with symptomatic improvement. The action on edema is beneficial for the evolution of neuropathy. The effects of HR on flux, RAS, and edema are important in early stages of microangiopathy to avoid progression to clinical stages.

The variation of capillary filtration rate (CFR) and ankle edema (AE) were evaluated in three groups of patients with venous hypertension with ambulatory venous pressure > 42 mmHg and in healthy subjects before and after treatment for four weeks with HR (Paroven, Venoruton; 0-(P-hydroxyethyl)-rutosides), a venoactive drug acting on the microcirculation and on capillary permeability. Group A (30 patients) was treated with HR 500 mg tid; group B (30 patients) was treated with 1 g tid; group C (30 patients) was treated with placebo; group D (10 healthy subjects) was treated with HR 1 g/day in a randomised study. CFR was assessed by venous occlusion plethysmography. Subjective symptoms of venous hypertension were assessed by an analogue scale line considering four symptoms: swelling sensation, restless lower extremity, pain and cramps, and tiredness. Results: There were no significant differences for sex and age distribution among the groups; no significant differences were found for ambulatory venous pressure and refilling time and parameters of venous hypertension among groups. There was a significant difference between normal subjects and patients. There were no drop-outs and observed intolerance. In group A, there was a significant decrease of CFR (P < 0.01) after treatment. In group B (2 g/day), the decrease was greater than that in group A (P < 0.05). In group C (placebo) there was no significant difference before or after treatment. The variations in analogue score was higher with the higher dosage. The score of group A fell from 7.8 (SD 1.3) to 4 (1). Group B's score fell from 7.9 (2) to 3.1 (1.2). In group C (placebo) there was no change. The decrease in the score in the groups of patients was correlated with the variation in edema and CFR. Conclusion: HR is effective in venous edema and hypertension. Its effects are dose-related.

Context: Serum pituitary antibodies (Pit Abs) and tumor-infiltrating lymphocytes (TILs) have been described in pituitary adenomas, but their clinical significance remains unknown. Objective: The objective of the study was to assess Pit Abs and TILs prevalence in pituitary adenomas and their influence on clinical outcome. Design: This was a prevalence case-control study. Patients and Setting: Two hundred ninety-one pituitary adenoma cases (110 non-secreting, 30 ACTH-69 GH-71 prolactin- and 13 TSH-secreting adenoma; 177 operated and 114 untreated), 409 healthy controls, and 14 autoimmune hypophysitis were enrolled in a tertiary referral center. Intervention: Pit Abs were measured using immunofluorescence in all cases and controls (n = 714). The presence of TILs was evaluated using CD45 staining in a subset of adenomas surgically treated (n = 72). Main Outcome Measure: Clinical response of pituitary adenoma after surgery was evaluated. Results: Pit Abs prevalence was higher in adenomas (5.1%) than healthy subjects (0.7%, P < 0.0001) and lower than in autoimmune hypophysitis patients (57%, P < 0.0001). Similarly, TILs prevalence was higher in adenomas than normal pituitary (P = 0.01) and lower than in autoimmune hypophysitis (P < 0.0001). No correlation between Pit Abs and TILs was found (P = 0.78). A poor clinical outcome was more common in adenoma patients with TILs (11 of 18, 61%) than in those without (17 of 54, 31%, P = 0.026). Multivariate regression analysis identified the presence of TILs as independent prognostic factor for persistence/recurrence of pituitary adenoma. Conclusions: TILs and Pit Abs are present in a significant number of pituitary adenoma patients. Cell-mediated immunity appears to be predictive of a less favorable clinical outcome.

Background and aim: The management of pituitary adenomas secreting TSH has evolved considerably over the last decades. We report the clinical features, management, and outcome of a large monocentric series. Material and methods: A monocentric retrospective cohort of 26 patients admitted to our Department of Endocrinology between 1983 and 2007, followed for a period up to 204 months. The diagnosis of TSH-secreting adenoma was based on clinical and biochemical findings of central hyperthyroidism. Evaluation of basal and dynamic pituitary function, magnetic resonance imaging or computerized tomography scan were performed in all patients. Twenty-two patients, of whom 15 pre-treated by somatostatin analogs (SSA), underwent trans-sphenoidal surgery and were regularly re-evaluated. Results: The number of cases increased over the years. Age at diagnosis, micro- to macroadenoma ratio, and mean estimated latency between first symptoms and diagnosis did not appreciably change over time. Latency was significantly shorter in macroadenomas. Following surgery, 55% of patients obtained remission (success rate of 40 and 67% in macro- and microadenomas, respectively). SSA pre-treatment led to an apparent although not statistically-significant increase in success rate in micro- but not in macroadenomas. Conclusions: In a monocentric group of 26 TSH-secreting adenomas the high ratio between micro- and macroadenomas remained stable over time with a significantly shorter diagnosis latency in macroadenomas. A more precocious recognition of the tumors and possibly the use of presurgical SSA allowed a high remission rate. A varied combination of neurosurgery, SSA, radiotherapy, and thyroid ablation led to the control of the disease in all the patients studied.

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.

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 (CVI) in comparison to the combination of diosmin and hesperidin (Daflon®, Servier, France). A group of 86 patients with severe chronic venous insufficiency (CVI), venous hypertension, ankle swelling) and previous history of venous ulcerations received either oral Pycnogenol (capsules) 150 mg or 300 mg daily for 8 weeks or Daflon, 1000 mg/day. All patients completed the study without dropouts. At the end of the study, microcirculatory results indicated: a progressive decrease of skin flux at rest (RF); a significant decrease in capillary filtration (RAS); an improvement in the symptomatic venous score (ASLS); a reduction in edema; a significant improvement (increase) in pO2 and a decrease in pCO2 in the Pycnogenol group. A significant level of improvement was reached after 4 weeks of treatment in most patients (p < .05) of the Pycnogenol group while clinical improvement was significant only in 6 subjects in the Daflon group. The positive effects of treatment with Pycnogenol after 8 weeks were significantly larger in comparison with the Daflon group. In conclusion, this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy and its superiority—considering the evaluated parameters—to the combination of diosmin and hesperidin.

The aim of this independent study was to investigate differences in efficacy between oxerutins (Venoruton) and 500 mg micronized diosmin + hesperidin (D+H) (Daflon) in patients with chronic venous insufficiency (CVI), evaluating venous-related quality of life (Ve-QOL). A first group of 90 patients with severe venous hypertension (CVI, ankle swelling) was randomized to treatment with oxerutins or D+H. The oxerutins group received oral oxerutins (2 g/day); the D+H group received 3 (500 mg) tablets daily every 8 hours for 8 weeks. A second group of 122 comparable patients was included in a registry following the same study format. The 2 treatments were administered with the same methods and procedures. Clinical conditions were comparable. All patients completing 8 weeks of treatment were included in a registry. Specialists or general practitioners included patients when they considered that clinical conditions were compatible with treatment indications using 1 of the 2 treatments on the basis of their evaluation and experience. When cases were compatible with the registry, the prescribing physician communicated the case to our monitoring center. Patients were evaluated without interfering with their treatment. The main target of evaluation for this study was the change in Ve-QOL (range, 0-100) induced by treatment. A specific Ve-QOL questionnaire was used for this study. Ve-QOL score is a specific expression of the changes in QOL induced by CVI in patients between 35 and 75 years old (defined in our population studies) in which no other significant clinical disease is present (as a confounding factor affecting QOL). Two hundred twelve patients completed the 2 parts of the study. The 2 treatment groups were comparable for age and gender distribution. The mean age was 42 years (SD ±5.5) in the oxerutins group and 41.5 (SD ±6) in the D+H group. There were no differences in the severity of CVI between the treatment groups at inclusion. A significant decrease (46.8%, p

Damage to endothelial cells is common in vascular disorders and in reactions associated with transplantation. An elevated number of circulating endothelial cells indicates the extent of endothelial damage in a variety of disorders. In chronic venous insufficiency (CVI), the number of endothelial cells is abnormally increased, and this can be considered an important indication of endothelial damage. A group of 23 subjects with two levels of CVI (severe and very severe with previous ulcerations) with an increased endothelial cell count (seen by microscopy) was studied and treated for 4 weeks with oral Venoruton (0-[beta-hydroxyethyl]-rutosides) (1 g/day) to evaluate the effects of treatment on the circulating endothelial cells in blood taken from a peripheral leg vein. The controls comprised two groups with comparable age and sex distribution, one of healthy individuals and one of CVI subjects. After 4 weeks, a significant decrease was noted in endothelial cells both in subjects with CVI and in those with very severe CVI with previous ulcerations. This study suggests that endothelial cells may play a significant role in venous disease, being both an indication of severe disease and a further problem in itself. The use of Venoruton appears to decrease the number of circulating endothelial cells. This suggests an important role of this compound in protecting the endothelium and offers new potentially important therapeutic options that are not limited only to venous disease.

PTH-related peptide (PTHrP), a member of the PTH family, is widely expressed in foetal and adult tissues, and it has been found in benign and malignant tumors, including GH and PRL-secreting adenomas. Conflicting data are reported in literature on serum PTHrP concentrations in patients with Cushing's disease. The aim of the present study was to further evaluate peripheral and inferior petrosal sinus (IPS) serum PTHrP concentrations before and after CRH, in a group of consecutive patients with ACTH-dependent Cushing's disease. Nine patients with active ACTH-dependent Cushing's disease (8 women and 1 man, age +/- SD 41 +/- 13 yr) were submitted to peripheral and IPS sampling under fluoroscopic control before and after iv administration of CRH. All patients were subsequently submitted to transsphenoidal surgery and an ACTH-secreting microadenoma was found in all cases. In all patients, serum IPS and peripheral ACTH measurement were in keeping with the diagnosis of ACTH-dependent Cushing's disease. Serum PTHrP concentrations before and after CRH stimulation were below the sensitivity limit of the assay in all samples, and no gradient between IPS and peripheral sampling was observed. Our data, combined with others reported in literature, indicate that PTHrP release by ACTH-secreting tumors is not a common occurrence. Therefore, we conclude that IPS and peripheral PTHrP are of little clinical usefulness.

The aim of this study was to evaluate the occurrence of deep venous thrombosis (DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral anti-edema and antithrombotic agent (Pycnogenol®, Horphag, Research Management SA, Geneva, Switzerland) in long-haul flights, in subjects at moderate to high-risk of DVT and SVT. The study pre-included 244 pre-selected subjects; 211 were included (33 were excluded for several reasons due to logistic problems) and 198 completed the study; 13 subjects were lost for follow-up at the end of the flight, all for non-medical problems (i.e., for difficult connections). All subjects were scanned within 90 minutes before the flight and within 2 hours after disembarking. Subjects were supplemented with 100 mg Pycnogenol® per capsule. Treatment subjects received two capsules between 2 and 3 hours before flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL of water and one capsule the next day. The control group received comparable placebo at the same intervals. The flight duration was on average 8 hours and 15 minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five thrombotic events (one DVT and four superficial thromboses) while only nonthrombotic, localized phlebitis was observed in the Pycnogenol®group (5.15% vs. no events; p® treatment was effective in decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high risk subjects, during long-haul flights.

The aim of this study was to evaluate the prevention of recurrent deep vein thrombosis (RDVT) with an oral antithrombotic agent (sulodexide) in moderate to high-risk subjects. A group of 405 patients was included into the multicenter registry. Both compression and an exercise program were used as well as a risk-factors control plan. After diagnosis of DVT, patients were treated with oral anticoagulants for 6 months. At the end of this period a coagulation study was made and patients started treatment with oral sulodexide capsules for a period of 24 months. The femoral, popliteal, tibial, and superficial veins were scanned with high-resolution ultrasound at inclusion; scans were repeated at 6, 12, 18, and 24 months. Of the 405 subjects included into the registry 178 in the control group (mean age 52.2; SD 11; M:F = 90:88) and 189 in the treatment group (mean age 53.2; SD 10.3; M:F = 93:96) completed the analysis period of 24 months. At 6 and 12 months the incidence of R-DVT was lower (p

The aim of this study was to evaluate deep venous thrombosis (DVT) prophylaxis with specific elastic stockings in longhaul flights (11-13 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several problems including concomitant treatments; 224 were randomized into two groups (stockings vs. controls) to evaluate prophylaxis with below-knee stockings. An exercise program was used in both groups. Scholl (UK) Flight Socks (14-17 mmHg of pressure at the ankle) were used. DVT was diagnosed with ultrasound scanning. The femoral, popliteal, and tibial veins were scanned before and within 90 minutes after the flights. Of the 205 included subjects, 102 controls and 103 treated subjects completed the study. Drop-outs were due to flight connection problems. Age, gender, and risk distributions were comparable in the two groups. In the treatment group (103 subjects; mean age, 42; SD 9; M:F, 55:48), one limited, distal DVT was observed (0.97%). In the control group (102 subjects; mean age, 42.1; SD 10.3; M:F, 56:46), six subjects (5.8%) had a DVT. There were no superficial thromboses. The difference in DVT incidence is significant (p

The aim of this independent study was to evaluate the protective effects, on the development of flight edema, of Venoruton. The study included patients with venous disease traveling in economy in long-haul flights (9 hours). Edema is a relevant aspect of long-haul flights affecting both patients with venous disease and normal subjects. Microcirculatory variations during flights cause a microangiopathy and biochemical and coagulation alterations. This condition may be defined as flight microangiopathy. A group of 203 subjects with chronic venous disease (uncomplicated varicose veins) at low-medium risk for DVT were contacted; 43 subjects were excluded for several nonmedical, travel-related problems or inconvenient eval uation time; the remaining 160 were randomized, after informed consent, into 2 groups to evaluate 2 prophylaxes in 7-8-hour, long-haul flights: The treatment group received Venoruton (hydroxyethyl rutosides) 1 g twice daily for 3 days (2 days before the flight and the day of the flight). The control group received comparable placebo. The edema score was based on the edema tester, ankle circumference, volume measurements, subjective swelling, and discomfort score. Items 1, 4, and 5 are based on an analogue scale line (1 to 10) directly defined by the subjects before and after the flights. Of the 160 included subjects 139 completed the study. Dropouts (21) were due to poor compliance, traveling, and/or connection problems (11 in the control group, 10 in the treatment group). Age and sex distribution were comparable in the 2 groups as were risk factors distributions. The level of edema at inclusion was comparable in the 2 groups of subjects. After the flight there was an average score of 7.2 (sd 2) in the control group, while in the Venoruton group the score was on average 3.2. (sd 1.1) (p < 0.05), 2.25 times lower than in the control group (p < 0.05). In the control group 89% of the subjects had an evident increase in ankle circumference and volume, which was clearly visible at inspec tion and associated with discomfort. In the Venoruton group edema was clearly present in 12% of subjects (associated with discomfort between 5 and 7 on the analogue scale line) and it was mild-moderate, not associated with symptoms (pain, discomfort between 2 and 4 on the analogue scale line). Therefore, the control of flight edema with Venoruton was clear both considering parametric data (circumference and volume) and nonparametric (analogue scale lines) measurements. The combined evaluation of the edema score is significantly favorable for patients treated with Venoruton. No deep vein thrombosis or superficial vein thrombosis was observed in this study.

This study evaluated the protective effects of Venoruton on the development of flight edema in normal subjects travelling in economy in long-haul flights (8-9 hours). Edema is a relevant aspect of long-haul flights affecting both venous patients and normal subjects. Edema and flight microangiopathy were studied in a group of 164 subjects randomized (after informed consent) into two groups to evaluate prophylaxis in 8 to 9-hour flights. The treatment group received Venoruton (hydroxyethyl rutosides) 1 g twice daily for 3 days (2 days before the flight and the day of the flight). The control group received comparable placebo. Edema was evaluated with a composite edema score based on the edema tester, on the measurements of ankle circumference, volume measurements, subjective swelling, and on a discomfort score. Items 1, 4, and 5 are based on an analogue scale line (I to 10) directly defined by the subjects before and after the flights. Of the included subjects, 151 completed the study. Dropouts were due to poor compliance, travelling, or connection problems. Age and gender distribution were comparable in the two groups as were risk factor distributions. The level of edema at inclusion was comparable in the two groups of subjects. After the flight there was an average score of 6.7 (SD 1.7) in the control group, while in the Venoruton group the score was on average 3 (SD 1.1) (p < 0.05). In the control group 77% of the subjects had an evident increase in ankle circumference and volume, which was clearly visible at inspection and associated with discomfort. In the Venoruton group, edema was clearly present only in 8% of subjects (associated with discomfort rated between 3 and 6 on the analogue scale line) and it was mild, not associated with symptoms. Therefore the control of flight edema with Venoruton was clear both considering parametric data (circumference and volume) and non-parametric (analogue scale lines) measurements. The combined evaluation of the edema score is significantly favorable for subjects under prophylaxis with Venoruton.

Objectives: The aim of this study was to demonstrate whether and how HR (Venoruton1000, Paroven, 0-[beta-hydroxyethyl]-rutosides) and Daflon (diosmin, 500 mg) were comparatively effective in improving the microcirculation in venous hypertension and microangiopathy. Methods: A group of 90 patients with severe venous hypertension due to chronic venous insufficiency, ankle swelling, and lipodermatosclerosis were included. After informed consent, patients were randomized into a Venoruton and a Daflon (DF) group: patients in the Venoruton group received oral HR (2 g/day for 8 weeks); those in the Daflon group received three 500-mg tablets daily every 8 hours. The two groups were comparable for age and sex distribution. The mean age was 41 years (SD ± 11) in the Venoruton group (46 patients) and 41.3 (SD ± 12) in the DF group (44 patients). Results: There were no differences in microcirculatory parameters between the Venoruton and DF treatment groups at inclusion. There was no significant change between inclusion and measurements at 8 weeks in the DF group. In comparison, a significant decrease ( P < .05) in RF (resting skin flux) and RAS (rate of ankle swelling) was observed in the Venoruton group ( P < .00 1). The decrease in capillary filtration was associated with improvement in signs and symptoms (measured by an analogue scale line) ( P < .05). Symptomatic improvement was clinically and statistically significant and important only in the Venoruton group. No side effects and no drop-outs were observed. Conclusion: Venous microangiopathy was improved by the treatment with Venoruton. The comparison with Daflon indicates that HR is comparatively more effective both on microcirculatory parameters and on signs and symptoms.

This study evaluated the effects of HR (Paroven, Venoruton; 0-(β-hydroxyethyl)-rutosides) on the prevention and control of flight microangiopathy, and particularly on edema, in subjects with varicose veins flying for more than 7 hours. Forty patients with varicose veins, edema, and initial skin alterations due to chronic venous hypertension were included. Measurements of skin laser Doppler flowmetry resting flux, Po2 and rate of ankle swelling, were made before and after the flights (within 4 hours before the flights and within 2 hours after the flights). The length of the flights was between 7 and 9 hours; all seats were in coach class. The 2 groups were comparable for distribution. The variation of Po2 was significant in both groups. However, in subjects treated with HR, the decrease in Po2 was smaller (P < 0.05). The decrease in laser Doppler flowmetry resting flux was also significant in both groups, with a higher flux at the end of the control period in the treated subjects (P < 0.05). The venoarteriolar response progressively decreased at 7 and 9 hours. The decrease was less evident in the treatment group (P < 0.05). The rate of ankle swelling was progressively increased in the control group; the increase was not significant in the HR group. In long-haul flights, HR is useful for reducing the increased capillary filtration and in controlling edema in patients with venous hypertension and is effective in controlling perfusion disorders and microangiopathy, particularly swelling and edema, due to flights.

The aim of this study was to demonstrate whether HR (Paroven-Venoruton; 0-(β-hydroxyethyl)-rutosides), was effective in improving the microcirculation in venous hypertension and microangiopathy. Sixty patients with severe venous hypertension due to chronic venous insufficiency, ankle swelling, and lipodermatosclerosis were included. After informed consent, patients were randomized into a treatment group and a placebo group. Patients in the treatment group received oral HR (2 g/day for 8 weeks); those in the placebo group received a comparable placebo. Results: The two groups were comparable for age and sex distribution. The mean age was 45 years (SD 9) in the treatment group (31 patients) and 45.5 (SD 10) in the placebo group (29 patients). There were no differences between the placebo and treatment groups at inclusion. There was no change between inclusion and measurements at 8 weeks in the placebo group. A significant decrease (P < 0.05) in flux at rest and rate of ankle swelling was observed in the treatment group. The decrease in capillary filtration was associated with improvement in signs and symptoms (P < 0.05). The difference in flux, sign and symptoms, and filtration was clinically important at 8 weeks in the treatment group when compared with the placebo group. No adverse effects were observed. Conclusion: Venous microangiopathy was improved by HR treatment.

Noninvasive macro- and microcirculatory tests provide quantitative information that offers answers to most questions posed in venous diseases. Duplex scanning is used to assess the macrocirculation, and microcirculatory methods are used to assess and quantify venous microangiopathy. Laser Doppler flowmetry is used to assess perfusion. Transcutaneous Po2 and Pco2 measurements are used to study venous hypertension, and strain-gauge plethysmography is used to assess capillary filtration. In venous hypertension, fluid filtration into the extracapillary compartment is increased. The increase in filtration is associated with a decreased venoarteriolar response. To quantify capillary filtration, two methods have been developed: venous occlusion plethysmography and rate of ankle swelling. These methods quantify filtration into the extracapillary compartment and, therefore, are an indication of the formation of edema, the most frequent sign in venous hypertension. Other methods, such as the vacuum suction chamber and the edema tester, can be used to assess changes due to treatments in venous hypertension. The techniques described in this article should be used in controlled environmental conditions

Background: Cerebral microembolism has often been documented by transcranial Doppler imaging during carotid angioplasty and stenting. However, few data are available about its characteristics during the 2 different kinds of procedure. Objectives: To compare the incidence of microemboli occurring during angioplasty alone with that during stenting in the different phases of the procedures and to relate it to periprocedural cerebrovascular complications. Patients and Methods: Thirty-eight patients underwent 41 procedures (15 angioplasty alone and 26 stenting) for symptomatic carotid stenoses of 70% or more. Transcranial Doppler monitoring was performed to detect microemboli in the middle cerebral artery during 3 phases of the procedure: (1) guidewire crossing, (2) first dilatation in case of angioplasty alone or stent release with predilatation if performed, and (3) further dilatation. Results: Microemboli occurred in all cases in phase 1 of the procedure but less frequently in the arteries treated with stenting when compared with those treated with angioplasty alone in phase 2 and particularly (P.02) in phase 3. The mean number of microemboli was highest in phase 2, predominant (P.05) during angioplasty alone, and particularly reduced (P.02) in phase 3 during the stenting procedures. During 2 (5%) of the 41 procedures, cerebrovascular complications occurred in phase 1, with the number of microemboli being higher than mean values. Conclusions: Cerebral microembolism is a very common event, especially during guidewire crossing and angioplasty alone compared with stenting. Further studies concerning the prognostic significance of this are advisable.

Study Design. Five cases of epidural spinal cavernous nemangioma submitted to magnetic resonance imaging and surgery were reviewed. Objective. To correlate different magnetic resonance imaging appearances of epidura ; spinal cavernous hemangioma with histologic findings. of Background Data. Cavernous hemangioma is an uncommon vascular malformation that may occur anywhere in the central nervous system. Purely epidural lesions are very rare. Accurate correlation between magnetic resonance imaging appearances and histoiogic findings have not been reported in the literature Methods. Five cases of epidural spinal cavernous hemangioma that had undergone magnetic resonance imaging evaluation followed by microsurgical removal, were retrospectively reviewed. Conventional spin-echo T1, proton density- and T2-weighted magnetic resonance images were obtained in all cases. and gadoiinium was used in all but one. Two cases have also been evaluated with computed tomography. Results. in two cases, magnetic resonance imaging showed mixed low- and high-signal intensity components in an sequences and pathologic examination showed degenerative phenomena and hemosiderin pigments. In tne remaining three cases, magnetic resonance imaging showed low- or intermediate-signal intensity on T1-weighted and high-signal intensity on proton density- and T2-weighted images. in those cases, pathologic examination showed an absence of degenerative phenomena and no signs of hemorrhage. All patients underwent surgery by laminectomy and microsurgical resection. In all, significant improvement was obtained. Conclusions. Epidural spinal cavernous hemangioma has a different magnetic resonance imaging appearance probably because of the presence or absence of the degenerative phenomena and hemosiderm pigments. As in cerebral locations, mixed signal intensity in an sequences on magnetic resonance images might be indicative at cavernous nemangioma. Presumptive preoperative diagnosis of the lesion may render the surgical approach less invasive.

94 patients with cerebral arteriovenous malformations were evaluated with transcranial Doppler sonography. Ultrasonographic and neuroradiological characteristics of severely altered cerebral hemodynamics were associated with the presence of intravascular mean flow velocity > 120 cm/s, pulsatility index 30 cm3. Cerebrovascular reactivity was evaluated in 9 patients by means of autoregulation to hypotension (sodium nitroprusside) and in 25 patients by means of vasomotor response to hypocapnia: it was defective proportionally to the volume of the AVMs. In 43 patients serial TCD investigation were performed during the stages of embolizations: significant mean flow velocity reduction (> 60%) occurred in 72% of cases after the first embolization, in 45% of cases after the second embolization and in no case after the third embolization. A flow velocity redistribution on basal vessels (defined as an increase in flow velocity of at least 30% of the initial value) occurred only after the first endovascular treatment (62% of the cases). It is concluded that TCD sonography is a valuable method for noninvasive hemodynamic assessment of shunt flow in arteriovenous malformations and permits a physiological monitoring of hemodynamic changes after embolization.

Transcranial Doppler examination of cerebral basal arteries by a 2 MHz probe, provides a simple and noninvasive method for studying cerebral haemodynamics. By this technique tumor vascularization and cerebral vascularization in malignant tumors, mostly cerebral circulation in meningiomas, could be studied (80 supratentorial tumors were examined: 55 gliomas, 10 metastases and 15 meningiomas). Cerebral blood flow velocities are usually reduced in presence of intracranial tumors but sometimes they can be increased due to presence of artero-venous fistulas in glioblastoma or other vascularized tumors, or by direct vascular compression. The haemodynamic effect of mannitol can easily be studied and the rebound effect can be avoided by using small mannitol doses under TCD control in the pre and the post-operative period [1, 2].

This paper presents the results of a retrospective clinical study of 250 cases of monocentric carcinoma of the mucosal surface of the cheek, i.e. all the primaries treated by radiotherapy at our Institute between January 1948 and December 1965. Neoplastic lesions found at follow-up were regarded as marginal recurrences if in the proximity of the treated area and as secondary tumors in other cases. From 1948 to 1957 conventional radium therapy was the usual treatment for the primary tumor whereas from 1958 to 1965 cobalt teletherapy was given most frequently. Surgery was reserved for lymph node metastases when present on clinical examination. In our experience radiotherapy is effective in cancers of the mucosal surface of the cheek, for it checked local spread in 50.9% of cases, however treated and regardless of initial clinical appearance, whereas in the T1-T2 cases the local failure rate dropped to 35.8%. The higher the T level the greater are the difficulties confronting radiotherapy; for more extensive lesions appropriate combination therapy (radiosurgical) in line with the well-defined rules explained in the text is useful. In our experience radiotherapy yields good long term results regardless of T level and even in the more unfavorable cases. Our study confirms the low rate of lymph spread of these carcinomas: over half of the patients were N0 before treatment; only 56.7% of the patients receiving surgical treatment on the neck had histologically positive lymph nodes; there were very few neck recurrences at follow-up; the presence of suspect or frankly metastatic nodes on clinical examination, being movable and homolateral (N1), did not worsen the prognosis. However, considering the techniques used for irradiation of the primary, some patients received a substantial dose to the neck; hence radiotherapy probably played its part in the low rate of neck metastases.

In 1975, Flitter et al. proposed a Doppler technique for evaluating CSF shunt patency. Owing to the presence of many false positives, a new method of investigation is proposed in order to achieve more reliable results by using the Doppler technique after air has been injected into the shunt reservoir. Ninety patients with a CSF shunt were examined. Fifty cases were studied both immediately after surgery (7-10 days) and at a later date (more than 2 months from surgery) in order to obtain a control group. In a further 38 cases with signs of intracranial hypertension, it was possible, by means of the air test, to distinguish surgical and non-surgical cases. In 2 cases with clinical signs of hypotension, it was possible, by means of the test, to demonstrate the hyperfunctioning of the shunt. The "Flitter test" proved to be useful in the early post-operative period only.

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 measure ments 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 infec tions 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.

Microvessel density (MVD) represents a measure of angiogenesis and may be used as an indicator of neoplastic aggressiveness. Vascular endothelial growth factor (VEGF) plays a pivotal role as angiogenic promoter by stimulating endothelial cell proliferation and migration and enhancing vascular permeability. The aim of this study was to investigate MVD and VEGF expression in human pituitary adenomas and normal pituitary gland tissues by immunohistochemistry, and to correlate data with clinical characteristics. Fragments from 46 pituitary adenomas (18 non-functioning, 12 ACTH-secreting, 12 GH-secreting, 4 PRL-secreting) and 19 specimens of normal anterior pituitary gland obtained at surgery were evaluated. MVD in normal anterior pituitary was significantly higher than in tumors (69.2 +/- 28.5 vs 29.3 +/- 19.7; p0.0001). Within adenomas, no difference was found in MVD when different histotype, size, sex, age, rate of recurrence or medical pre-surgical treatment were considered. The degree of vascularity was somewhat related only to clinical invasiveness, as evaluated by pre-surgical MRI grading (grade 0 p0.05 vs grade 1 and vs grade 2). No statistically significant difference in VEGF expression was found between normal tissue and adenomas and among tumors of different histotype (p = 0.3978). Size, sex, age, rate of recurrence and medical pre-surgical treatment did not influence VEGF expression. No correlation was found between MVD and VEGF expression. In conclusion, MVD was reduced in pituitary adenomas with respect to normal gland. VEGF expression is however well preserved in adenomas and this might contribute to adequate tumoral vascular supply with complex mechanisms other than endothelial cells proliferation.

Si indaga sulla posizione di Iosif Brodskij, Nobel per la Letteratura già americano, circa la fondazione di Costantinopoli e la affermazione storica dell'impero romano-orientale, linfa e nutrimento della civiltà russa. Brodskij, cittadino sovietico dissidente fin dai primi anni '70 del Novecento, ebreo, sente la componente cristiana e romana medievale (cioè bizantina) della civiltà russa come la versione "asiatica" di quella romana classica, una piaga che porterà all'orrore sovietico. Non a caso il saggio celebre di Brodskij si intitola "Fuga da Bisanzio": una posizione, la sua, non casuale, ma che torna in altri filoni, più o meno riconoscibili, della cultura russa tra Ottocento e Novecento.