Improvements in edema and microcirculation in chronic venous insufficiency with Pycnogenol® or elastic compression.

BACKGROUND: Chronic venous insufficiency (CVI) is the consequence of venous valve reflux and/or venous flow obstruction and resulting venous hypertension in the lower extremities. The aim of this prospective supplement registry study was to evaluate the efficacy of compression stockings or Pycnogenol® in controlling symptoms and edema in CVI and their efficacy on microcirculatory parameters. METHODS: Two comparable groups of 30 subjects with CVI were observed for 4 months. RESULTS: Elastic compression was less tolerated than Pycnogenol® with 12 subjects being unable to follow the compression routine. No side effects due to supplementation were observed; tolerability of the supplementation was optimal. Ambulatory venous pressure (AVP) and refilling time (RT) at inclusion indicated a significant increase in venous pressure and reflux (refilling time <16 seconds). AVP and RT did not change after 4 months. Microcirculatory and clinical measurements were comparable at inclusion between the 2 groups. After 4 months, skin resting flux (RF) and skin PO2-PCO2 were significantly improved with Pycnogenol® compared to compression (P<0.05). The significant increase in skin PO2 and the decrease in PCO2 after Pycnogenol® intake were ascribed to the decrease in the abnormally high skin resting flux, a sign of better perfusion and skin nutritional supply. Pycnogenol® reduced leg volume, on average by 18.3% in the evening compared to 4.4% of reduction with compression (P<0.05) showing an important effect on edema. The venous Clinical Severity Score (VCSS) and the composite symptom score (CSS) decreased significantly in the Pycnogenol® group compared to compression, indicating a better improvement in microcirculatory perfusion and nutritional supply produced by the supplementation of Pycnogenol® in comparison with compression. Pycnogenol® significantly improved microcirculation and clinical symptoms in comparison with compression. The decrease in local oxidative stress (OS) at the distal perimalleolar region with Pycnogenol® was significant in comparison with compression (P<0.05). A lower local OS is an important metabolic indication of a better capillary perfusion with better nutritional exchanges. At the end of the registry study, four small ulcerations and skin breaks in four limbs (between 3 and 5 mm of maximum diameters) were observed in the compression group. No ulcerations or skin breaks were observed in the Pycnogenol® group. CONCLUSIONS: Pycnogenol® relieved edema, improved microcirculation in CVI patients and reduced stationary, interstitial fluid in comparison with compression. Most symptoms of CVI are associated with interstitial water retention; the presence of extra fluid in limb tissues alters perfusion and nutrient supply. Pycnogenol® supplementation reduced water and fluid accumulation in CVI limbs and improved microcirculation and local oxidative stress thus showing important anti-edema effects.

Effects of Robuvit® on the progression of non-alcoholic fatty liver disease.

BACKGROUND: The aim of this study was to evaluate the effects of Robuvit® in preventing the progression of chronic hepatitis (CH) in non-alcoholic fatty liver disease (NAFLD) which encompasses the entire spectrum of fatty liver disease, from isolated steatosis to non-alcoholic steatohepatitis (NASH). METHODS: One group of patients followed the Standard management (SM) and were assigned as controls while the supplementation group followed the SM and additionally took 2 Robuvit® capsules daily for 3 months (200 mg/day). RESULTS: 34 subjects with NAFLD were included in the study. The two groups completing 90 days were comparable at baseline with 18 being supplemented with Robuvit® and 16 in the control group. The tolerability was very good, and no side effects were observed with the supplement. Fasting glucose levels were significantly lower after 3 months with Robuvit® (P<0.05) compared to controls. The increased serum aspartate aminotransferase levels (AST), considered the key metabolic value in these patients, decreased significantly with Robuvit® (P<0.05) compared to controls. Serum alanine aminotransferase levels (ALT) also decreased significantly with the supplement compared to controls (P<0.05). Platelet count and albumin levels improved significantly with Robuvit® (P<0.05) in comparison to standard management. No other significant changes were observed. The APRI score (the AST/platelet ratio index) was also decreased with the supplementation compared to controls (P<0.05). A high APRI score provides an estimate of the possibility of the liver to develop fibrosis and eventually cirrhosis. After Robuvit® supplementation, the ultrasound characterization showed a significant decrease in the size of the liver in association with a lower echogenicity, which represents less fibrotic changes due to collagen accumulation. CONCLUSIONS: Robuvit® improved liver function in NAFLD and prevented progression to liver fibrosis by improving hepatic metabolism in a relatively short period of time. Numerous people are affected by NAFLD, many of them with subclinical symptoms. But to date, there are no specific, definite treatment options. Prolonged evaluations of Robuvit® in a larger group of subjects is suggested.

Xerostomia: prevention with Pycnogenol® supplementation: a pilot study.

BACKGROUND: The aim of this pilot study was the evaluation of primary, idiopathic mucosal dryness (xerostomia or dry mouth) in subjects without cancer. METHODS: A group of non-diabetic subjects and a group of diabetics were managed with standard management (SM) or with SM+Pycnogenol® (150 mg/day) for 2 weeks. RESULTS: In total, 48 subjects were included in the study; 24 diabetics and 24 non-diabetics. 12 diabetics and 12 non-diabetics took Pycnogenol® and 12 diabetics and 12 non-diabetics were followed up with standard management only and served as controls. No side effects and no tolerability problems were observed with Pycnogenol®. The registry groups were comparable for characteristics and symptoms at baseline. All otherwise healthy subjects had a BMI<26 kg/m2. In 2 weeks, salivary flow and oxidative stress improved significantly in both groups of subjects (non-diabetics and diabetics) with 150 mg/day Pycnogenol® (P<0.05), while minimal improvements in salivary flow were seen with SM. The subjective score and the number of mucosal breaks and ulcerations, all minimal (<1 mm in length or diameter), were significantly decreased with Pycnogenol® supplementation (P<0.05) with minimal variations in the SM controls. Finally, the mean lysozyme level in parotid saliva samples was significantly increased in the Pycnogenol® group (P<0.05) both in diabetics and non-diabetics. CONCLUSIONS: Based on these preliminary results, Pycnogenol® could be a new, valid option for the treatment of xerostomia.

Prevention of recurrent venous thrombosis and post-thrombotic syndrome.

BACKGROUND: This retrospective registry study evaluated different managements on the development of post-thrombotic syndrome (PTS) and recurrent deep venous thrombosis (R-DVT). The effects of aspirin (100 mg/day), added to the "standard management" (SM) (IUA consensus), were observed in patients after a proximal DVT. METHODS: The study started after the anticoagulant period. Comparable groups used the mild-antithrombotic agent Pycnogenol® (200 mg/day), ticlopidine (250 mg/day) or sulodexide (500 ULS/day). RESULTS: The groups were comparable for sex and age distribution and clinical pictures. In the SM group, 222 patients completed the follow-up (72 months). With SM, the percentage of patients with R-DVT (requiring anticoagulants) was 17.2%; 19.8% of SM patients had a PTS. In the aspirin group (202 subjects), R-DVT was observed in 14.8% of patients; 17.32% had a PTS. The reduction in R-DVT and PTS with aspirin was significant (P<0.05) vs. the SM. There was no tolerability problem in subjects using Pycnogenol® (137 patients); they had a much lower incidence of R-DVT (5.8%) and PTS (6.5%) vs. SM and aspirin (P<0.05). Ticlopidine (121 patients) reduced the incidence of R-DVT (12.4%) and PTS (19.8% of patients) (P<0.05 vs. SM). With sulodexide the incidence of R-DVT was 6.7% (P<0.05 vs. SM); the incidence of PTS was 16.6% (P<0.05 vs. SM). The combined R-DVT+PT syndrome was observed in 14.9% of subjects using SM and in 12.9% of subjects using aspirin (P<0.05 vs. SM), in 3.6% of subjects managed with Pycnogenol® (<0.05% vs. aspirin and all other managements). The incidence was 10.74% with ticlopidine and 6.7% with sulodexide (both significantly lower than SM). CONCLUSIONS: Interaction between PTS and R-DVT are complex; recurrences cause more PTSs, and a post-thrombotic limb is prone to R-DVT. Aspirin, for patients that can tolerate it, reduces the occurrence of PTS and R-DVT. In addition, ticlopidine and sulodexide are effective. Pycnogenol® is the most effective and safe for R-DVT and particularly PTS. Its full range of anti-thrombotic activity is now under evaluation.

Postpartum Varicose Veins: Supplementation with Pycnogenol or Elastic Compression-A 12-Month Follow-Up.

This open registry aimed to evaluate the clinical evolution of postpartum varicose veins (VVs), in healthy women after the second pregnancy, how these veins regain shape and competence, and possible treatments. The registry included two groups of women: (1) those who used elastic compression stockings, and (2) who used an oral venotonic agent (Pycnogenol, 100 mg/d). A total of 12 evaluation targets were established. Minor symptoms were scored in an analogue scale line. A visual analogue scale line evaluated the overall satisfaction relative to elastic compression or Pycnogenol. Overall 133 women completed the registry evaluation with at least 3 months of follow-up. The resulting two registry groups were comparable. At 3 and 6 months in the Pycnogenol group the number of veins and incompetent sites were lower. At 6 months there were 13.3% of patients with edema in controls versus 3.2% in the Pycnogenol group. Spider veins decreased in Pycnogenol patients. Cramps and other minor symptoms were less common in the Pycnogenol group. In both groups there was a significant improvement at 6 months with better results in the Pycnogenol group. The need for treatment was limited with a decreased need for sclerotherapy, surgery, and conservative treatments in the Pycnogenol group. The overall satisfaction was higher among Pycnogenol patients, and compliance was optimal. Re-evaluation at 12 months indicated that the variations in VVs and spider vein clusters and the associated symptoms did not change. Most remodeling appeared to happen within 6 months after the pregnancy. It was concluded that the use of Pycnogenol improves signs/symptoms of postpartum VVs, and venous function and shape seem to return faster to prepartum, physiological pattern with its use.

An ischemic diabetic eye treated with intravenous prostaglandin E1.

PURPOSE: To present the use of intravenous prostaglandin E1 (PGE1), a powerful vasodilator of the microcirculation, in the treatment of an ischemic diabetic eye. METHODS: A 27-year-old diabetic man with ischemic diabetic retinopathy and glaucoma had a decreased visual acuity of no light perception in his right eye and hand motions in his left eye. He was started on intravenous PGE1 and has been treated for over 4.5 years. RESULTS: The visual acuity in his right eye remained unchanged and in his left eye improved gradually to 1.5/30. He has been stable for 4.5 years. CONCLUSION: Intravenous PGE1 may be useful in ischemic diabetic eyes to improve the ocular blood flow and visual acuity. It is safe and tolerated well.

The efficacy of sulodexide in the prevention of postthrombotic syndrome.

AIM: The aim of this open, observational registry was to evaluate the effects of antithrombotic treatment on the development of postthrombotic syndrome (PTS): the effects of "standard management" (SM; according to International Union of Angiology guidelines) were compared to SM in association with sulodexide or aspirin. METHODS: Postthrombotic syndrome occurrence was observed in 3 nonparallel groups after deep venous thrombosis (DVT); the registry started after the end of the anticoagulation period. The target was to observe the occurrence of PTS in 5 years. Three possible options were suggested to the patients, and the patients and their caregivers defined the type of management. A group of 167 patients was involved in the SM with reevaluation every 6 months; the sulodexide group included 124 patients and the aspirin group included 48 patients. RESULTS: The 3 groups were clinically similar and comparable for age and sex distribution. Of the 167 patients in the SM group, 154 patients completed 60 months of follow-up. The percentage of patients with PTS in the SM group ranged from 14.9% (1 year after the end of anticoagulation) to 19.5% (60 months). In the nonparallel group using sulodexide (124 comparable patients at inclusion; 115 at 60 months), the percentage of PTS was variable from 8.8% (1 year after anticoagulants) to 12.17% at 60 months. These percentages are significantly lower than those observed with SM. In the nonparallel aspirin group (48 patients at inclusion and 34 at 54 months), there was a PTS incidence of 23.5% at 54 months (vs 12.17% in the sulodexide group and 18.23% in the SM group). The incidence of PTS was significantly higher in comparison with the other 2 groups. The incidence of PTS was lower in the sulodexide group in comparison with the 2 other groups. CONCLUSIONS: Sulodexide administration after DVT appears to be effective in preventing PTS in association with recommended management and a number of recurrent DVTs. Modalities of treatment, dosages, and timing of administration should be explored in more comprehensive and complete studies.

Branch retinal arterial occlusion treated with intravenous prostaglandin e1 and steroids.

PURPOSE: To present the use of 6-methylprednisolone IV and prostaglandin E1 IV, a powerful vasodilator of the microcirculation, in the treatment of a branch retinal arterial occlusion. METHODS: A 63-year-old man presented with a 3-hour history of a sudden loss of vision in the right eye. On ophthalmic examination, the diagnosis of a superior temporal branch retinal arterial occlusion was made. The patient was immediately given 40 mg of 6-methylprednisolone IV for more than 5 minutes followed by 80 µg of prostaglandin E1 with 2 milliequivalents of potassium IV for more than 3 hours. The same treatment was repeated the following morning. RESULTS: The visual acuity in the right eye improved from 2/10 at presentation to 7/10 at the end of the second day of treatment. Clinically, there was a reduction of the posterior pole edema. Eleven days after treatment, the visual acuity was 9/10 with no retinal edema. CONCLUSION: Immediate prostaglandin E1 IV and steroids should be considered in cases of recent-onset branch retinal arterial occlusion to restore retinal blood flow and improve visual acuity.

Non-arteritic Posterior Ischaemic Optic Neuropathy Treated with Intravenous Prostaglandin E1 and Oral Corticosteroids.

Intravenous prostaglandin E1 and oral corticosteroids were used to treat the ischaemic phase of a non-arteritic posterior ischaemic optic neuropathy with immediate visual improvement. Non-arteritic posterior ischaemic optic neuropathy is a disorder of reduced blood flow to the retrobulbar optic nerve, usually of acute onset. It has been suggested that high-dose steroid therapy given soon after the onset of visual loss can result in significant visual improvement. This treatment, however, is not universally successful. The addition of a potent vasodilator to the corticosteroids could help restore ocular blood flow and improve visual acuity. This paper presents the use of prostaglandin E1 (PGE1), a powerful vasodilator of the microcirculation, to treat non-arteritic posterior ischaemic optic neuropathy. In this case report a 68-year-old white male with hereditary haemochromatosis was seen 8 hours after sudden loss of visual acuity in his left eye (OS) to 4/10. The diagnosis of non-arteritic posterior ischaemic optic neuropathy was made and he was immediately given oral corticosteroids. Intravenous PGE1 was given the next morning, 24 hours after the sudden loss of vision, once ischaemia of the optic nerve was confirmed by colour Doppler imaging. The visual acuity in the OS improved from 4/10 to 11/10 within 1 day. A visual field (VF) post treatment showed a peripheral scotoma without a central scotoma. At 12 months post treatment the vision OS remained 11/10. No complications due to the use of PGE1 were seen. The authors conclude that PGE1 should be considered in addition to steroids in cases of NA-PION to immediately restore blood flow to the optic nerve and improve visual acuity.

Arteritic anterior ischemic optic neuropathy treated with intravenous prostaglandin E(1) and steroids.

Arteritic anterior ischemic optic neuropathy (AAION) is an acute ischemia of the posterior ciliary arteries and/or ophthalmic artery due to inflammation. Therapy is immediate intervention with systemic steroids, especially to protect against vision loss in the other eye. The addition of a potent vasodilator to the steroids could help restore ocular blood flow and improve visual acuity. The objective of the current report was to present the use of prostaglandin E(1) (PGE(1)) - a powerful vasodilator of the microcirculation - in the treatment of AAION. Two patients with AAION were treated with intravenous steroids and PGE(1). The visual acuity improved from 4/50 (less than 20/200) to 6/10 (20/35) in one patient and from 1/50 (20/400) to 1/10 (20/200) in the second patient. The visual fields in both patients maintained small central islands of vision. No complications due to the use of PGE(1) were seen. Intravenous PGE(1) should be considered in addition to steroids in cases of AAION to immediately restore blood flow to the optic nerve and improve visual acuity while the steroids reduce the inflammation.

Ocular ischemia in high myopia treated with intravenous prostaglandin e1.

BACKGROUND: High myopia is associated with a decreased ocular blood flow. In some cases this ocular ischemia may be the cause of severe visual loss. METHODS: Three patients with high myopia and progressive loss of visual acuity had a diagnosis of ocular ischemia by color Doppler. Intravenous prostaglandin E1, a powerful vasodilator of the microcirculation, was used to treat the ocular ischemia in all 3 patients. RESULTS: The visual acuity improved in all three cases with one patient improving from 20/100 to 20/30. The mean deficit of the visual fields in this patient improved from -19.08 to -9.52 after treatment. The treatment was repeated every 6 weeks to 8 weeks. CONCLUSION: Patients with high myopia and progressive visual acuity loss should be evaluated for ocular ischemia. Intravenous prostaglandin E1 should be considered in those cases of ocular ischemia with visual loss. Unfortunately the effect does not last for more than 6 weeks to 8 weeks and needs to be repeated at this interval for extended periods.

Retinal and orbital venous occlusions treated with enoxaparin.

BACKGROUND: Retinal and orbital vein occlusions may cause a decrease in visual acuity. There is no known therapy to resolve ocular thrombosis. The authors used enoxaparin, a low-molecular-weight heparin, to treat 8 consecutive cases of retinal vein occlusions in 7 patients and 1 case of a superior orbital vein occlusion. METHODS: Four (4) central retinal vein occlusions in 3 patients, 4 branch retinal vein occlusions in 4 patients, and 1 superior orbital vein occlusion in 1 patient were treated with subcutaneous (SC) enoxaparin 100 IU/kg twice a day. The treatment lasted from 2 to 19 weeks. Eight (8) patients with retinal vein occlusions treated with ticlopidine were used as controls. RESULTS: The 8 retinal vein occlusions opened up in all 7 patients with the absorption of the retinal edema and hemorrhage as soon as the occlusions were open. The orbital vein occlusion resolved with the absorption of the orbital edema. Visual acuity improved in 7 of the venous occlusions and was unchanged in 2. Visual acuity in the 8 controls improved in 4, was unchanged in 2, and was worse in 2. CONCLUSIONS: Enoxaparin can be given SC twice a day in patients with retinal or orbital vein occlusions. The occlusions may take from 2 to 19 weeks to open up. Once the vein occlusions are open, the retinal edema, hemorrhage, and the orbital edema can rapidly absorb with visual improvement.

Lymphatic tissue transplant in lymphedema--a minimally invasive, outpatient, surgical method: a 10-year follow-up pilot study.

Lymphedema is mainly characterized by swelling, fibrosis, and non-pitting edema. The aim of this study was evaluation of the long-term (10 years) effects of autologous lymphatic tissue implant in lymphedema. Lymphatic tissue from 9 patients (harvested form the same patient in areas not affected by lymphedema) was reimplanted into the affected limb, and these patients were followed for 10 years. Lymph nodes were harvested at the neck, axillary, or inguinal space (contralateral limb). Results showed that limb volume was decreased in the treatment group vs. controls. In ultrasound, black, low density, lymphatic spaces were visible in 100% of patients at inclusion but in only 23% of these subjects at 10 years. Thus, this early report proposes a new, minimally invasive method to improve lymphedema. Studies in progress will indicate the role of lymphatic transplant in the management of lymphedema and the best indications for this method.

Nonarteritic anterior ischemic optic neuropathy treated with intravenous prostaglandin E1 and steroids.

BACKGROUND: Acute nonarteritic anterior ischemic optic neuropathy (NAION) is considered to be acute ischemia of the posterior ciliary arteries. Prostaglandin E1 (PGE1), a powerful microcirculation vasodilator, has been shown to improve ocular blood flow. DESIGN: A nonrandomized, comparative trial. METHODS: Eight consecutive cases of NAION were treated with intravenous steroids and PGE1. Seven control cases of NAION were treated with acetylsalicylic acid and oral steroids. Fisher's exact test was used for statistical analysis. RESULTS: The visual acuity improved in seven cases of NAION treated with PGE1 and was unchanged in one. Of the seven control cases, four had no change in vision and three lost further visual acuity on follow-up visits. CONCLUSIONS: Intravenous PGE1 and steroids should be considered in cases of NAION to immediately restore blood flow to the optic nerve and improve visual acuity.

Acute branch retinal arterial embolism successfully treated with intravenous prostaglandin E1--case reports.

The purpose of this paper is to report the use of intravenous prostaglandin E1, a potent vasodilator, to rapidly restore blood flow and vision in a patient with an acute branch retinal arterial occlusion. An 82-year-old woman with an acute decrease in the visual acuity of her left eye due to an acute superior temporal branch retinal arterial embolus was treated with 140 microg of intravenous prostaglandin E1. The medicine was repeated the following day. At the onset of the branch arterial occlusion her vision in the left eye was 20/50, the embolus could be seen in the superior temporal branch, and a white retinal edema extended down into the macula. At her first eye examination 4 days after treatment, her visual acuity had returned to 20/20, the retinal embolus was still present, but the white macular edema had disappeared. Intravenous prostaglandin E1 is a safe, potent vasodilator for the peripheral vascular system. If used immediately to treat acute branch arterial retinal occlusions, it can restore good vision. The authors report the first case of the use of intravenous prostaglandin E1 to treat a spontaneous acute branch retinal arterial embolus.