Bilateral sudden sensorineural hearing loss and chronic venous cerebrospinal insufficiency: a case report.

OBJECTIVES: We report a case of bilateral sudden sensorineural hearing loss (SSHL) in a patient suffering from chronic venous cerebrospinal insufficiency (CCSVI). METHODS: Audiometric testing confirmed bilateral sensorineural hearing loss with hypoexcitability to caloric stimulation on the left side and echo-colour Doppler examination showed abnormal cerebral venous deficiency. RESULTS: The patient's condition improved after 15 days following medical treatment. CONCLUSIONS: CCSVI may explain the anatomical background which provides a predisposing factor for SSHL although further studies are needed to verify whether this observation is casual or coincidental.

Prevention of post thrombotic syndrome with Pycnogenol® in a twelve month study.

AIM: Post-thrombotic syndrome is a common complication following deep vein thrombosis. The aim of this twelve month registry study was to compare the efficacy of compression stockings and per oral administration of Pycnogenol® standardized pine bark extract on the severity and incidence of post thrombotic syndrome signs and symptoms. METHODS: One hundred fifty-six patients with a single, major episode of proximal deep vein thrombosis (DVT) were assigned to one of three groups receiving treatment with either compression stockings (group 1), Pycnogenol® (group 2) or the combination of both (group 3) over an investigational period of one year. The study evaluated treatment on edema using a scoring system, the ankle circumference, and the limb volume as ratio to the healthy contralateral limb. RESULTS: Two new incidents of DVT occurred in the group of 55 patients wearing compression stockings between the third and sixth months, whereas no DVT cases occurred in the two other groups which took Pycnogenol®. The edema symptom score was gradually decreased in all three groups during the one year treatment period. Pycnogenol® was significantly more effective from six months onwards than compression stockings for relieving edema symptoms (P<0.05). Symptoms were more effectively reduced with the combination of Pycnogenol® and compression stockings than with the individual regimen alone (P<0.05). Limb volume and ankle circumference were likewise more effectively reduced with Pycnogenol® plus stockings than with compression stockings alone after six months. Ambulatory venous pressure progressively decreased in all three groups after twelve months treatment as compared to baseline. Compression stockings and Pycnogenol® were of comparable efficacy, there were no significant differences of ambulatory venous pressure between groups following twelve months treatment. Laser Doppler flowmetry at the dorsum of feet showed improved micro-circulation which was further demonstrated by increased pO2 and decreased pCO2. Importantly, none of the patients developed ulcerations during the observational period. CONCLUSION: This study suggests that Pycnogenol® may have significant long-term protective efficacy for individuals following a thrombotic event. Moreover, Pycnogenol® appears to be at least as effective for post-thrombosis management as compression stockings, while the combination of both is superior. An important aspect is the patient compliance which was found to be much better in the Pycnogenol® group with two drop-outs due to non-medical reasons, whereas in the compression stockings group eighteen patients were lost to follow-up because wearing stockings at higher temperatures is bothersome.

Potential role of curcumin phytosome (Meriva) in controlling the evolution of diabetic microangiopathy. A pilot study.

AIM: The aim of the present study was to evaluate the improvement of diabetic microangiopathy in patients suffering from this condition since at least five years, and whose disease was managed without insulin. METHODS: Curcumin, the orange pigment of turmeric, has recently received increasing attention because of its antioxidant properties, mediated by both direct oxygen radical quenching and by induction of anti-oxidant responses via Nrf2 activation. This aspect, combined with the beneficial effects on endothelial function and on tissue and plasma inflammatory status, makes curcumin potentially useful for the management of diabetic microangiopathy. To further evaluate this, Meriva, a lecithinized formulation of curcumin, was administered at the dosage of two tablets/day (1 g Meriva/day) to 25 diabetic patients for four weeks. A comparable group of subjects followed the best possible management for this type of patients. RESULTS: All subjects in the treatment and control group completed the follow-up period; there were no dropouts. In the treatment group, at four weeks, microcirculatory and clinical evaluations indicated a decrease in skin flux (P<0.05) at the surface of the foot, a finding diagnostic of an improvement in microangiopathy, the flux being generally increased in patients affected by diabetic microangiopathy. Also, a significant decrease in the edema score (P<0.05) and a corresponding improvement in the venoarteriolar response (P<0.05) were observed. The PO2 increased at four weeks (P<0.05), as expected from a better oxygen diffusion into the skin due to the decreased edema. These findings were present in all subjects using Meriva, while no clinical or microcirculatory effects were observed in the control group. CONCLUSION: Meriva was, in general, well tolerated, and these preliminary findings suggest the usefulness of this curcumin formulation for the management of diabetic microangiopathy, opening a window of opportunities to be evaluated in more prolonged and larger studies. The molecular mechanisms involved in the beneficial effects of curcumin on microcirculation and edema are also worth investigation.

Osteoporosis of the jaw. Product evaluation: mf Odontovis Calcium®.

AIM: The aim of this study was to test mf Odondovis Calcium® as a food supplement in a 3-month product evaluation study measuring how the low jaw bone density, could be improved. The upper jaw density was tested with an ultrasound method, evaluating the grey scale median of the images (GSM). METHODS: Seventy nine subjects were enrolled; 22 normal subjects (group A) and 57 with upper jaw osteoporosis (according to DEXA values). Patients were divided into 2 groups (group B and C, respectively 28 and 29 cases). These subjects were treated with what was considered the' best treatment' and in the group B only was added mf Odontovis Calcium®, consisting of calcium salts, Vitamin D and physiological modulators with antioxidant activity. This treatment continued for 3 months. RESULTS: The GSM of osteoporotic patients was significantly lower in comparison with GSM in normal subjects. No changes were observed (between the inclusion and 3 month values) in normal subjects and minimal, non-significant changes were observed in control osteoporosis patients. Before-after treatment values of GSM in treatment patients showed a significant increase (P<0.022) at 3 months. The increase in GSM in these patients was significantly higher (P<0.05) in comparison with control patient with osteoporosis. The Tolerability of the product was very good and the compliance corresponded to 98%. CONCLUSION: the jaw density in patients with osteoporosis is increased in only 3 months with supplementation with mf Odontovis Calcium®. Long-term clinical implications should be observed in more prolonged studies.

Improvement in cochlear flow in patients with tinnitus with the complex supplement Acustop: a product evaluation.

AIM: Patients with tinnitus constitute a very large group without a real, specific therapeutic solution. With noninvasive, color duplex it is possible to measure flow in the cochlear artery and to follow duplex flow changes due to treatments in most patients. The aim of this preliminary evaluation was to study flow variations in patients with "mild-to-moderate" tinnitus, possibly associated to cochlear hypo-perfusion, after administration of Acustop (used as a food supplement). The aim was to improve cochlear flow decreasing the level of tinnitus. METHODS: Patients with "mild-to-moderate", "idiopathic", monolateral tinnitus, present for at least 4 weeks were included; no vertigo or important hearing loss had been observed. The origin of tinnitus had been sudden (hours or days). The tinnitus was associated to a decrease in cochlear flow measured by color Duplex at the affected ear. A group of 42 patients was evaluated; 25 used Acustop; there were 17 controls (follow-up only). Groups were comparable for their clinical problem and other details. The average duration of treatment was 4 weeks. RESULTS: No side effects were observed and no drop-outs were recorded. Flow velocity at the level of the affected inner ear was significantly lower (both the diastolic and systolic components; P<0.05) in comparison with the other ear. This was considered an indication of the vascular origin of the tinnitus. With Acustop treatment there was a significant improvement in systolic (P<0.05) and diastolic flow velocity (P<0.05). The increase in flow velocity was not significant in controls. An analogue scale line was used to measure symptoms in the Acustop group: it was 8.2;2 at inclusion; it decreased to 3.1;1.5 at 4 weeks (P<0.05). The score was 8.4;2 in controls at inclusion; at 4 weeks the score was 7.1;2.2 (not significant). Tinnitus scale: the value at inclusion of the tinnitus scale in the Acustop group a was 8.5;1.1 versus 8.3;1.2 in controls. After 4 weeks the score was 3.1;1.1 (P<0.05) in the Acustop group vs 7.2 in controls; the difference between the two groups was significant; P<0.025). CONCLUSION: In conclusion, these results suggest that in selected patients with tinnitus and altered inner ear perfusion Acustop appears to be effective in relieving tinnitus possibly by improving cochlear flow. More studies should be planned to evaluate better the potential applications of Acustop in this very interesting field. This clinical problem affects a large number of patients, without a real therapeutic solution at the moment, decreasing their quality of life and their performing abilities.

Investigation of Pycnogenol® in combination with coenzymeQ10 in heart failure patients (NYHA II/III).

AIM: In this study we investigated benefits of a Pycnogenol - coenzyme Q10 combination (PycnoQ10) taken as an adjunct to medical treatment in stable heart failure patients. The aim of this single-blinded, 12-week observational study was to provide functional parameters such as exercise capacity, ejection fraction and distal edema. METHODS: The essential element for inclusion was a stable level of heart failure within the past three months and stable NYHA class II or III (6 months). The heart failure management was in accordance with AHA guidelines for "best treatment." The treatment and control groups were comparable at baseline. The mean age of the PycnoQ10-treated patients was 61.3+/-7.1 years and 62.1+/-3.7 in the control group. All patients were taking medication and most patients (>75%) used three or more drugs for heart failure treatment. There were two dropouts in the PycnoQ10 treatment group and 6 in the control group (5 NYHA III patients). RESULTS: Nine PycnoQ10 treated patients (out of 32) and 3 (out of 21) taking placebo improved NYHA class. Systolic and diastolic pressure as well as heart rate and respiratory rate were significantly lowered with PycnoQ10 as compared to the control group (P<0.05). No significant changes were observed in controls. Heart ejection fraction increased by 22.4% in the treatment group (P<0.05) versus 4.0% in controls. Walking distance on treadmill increased 3.3-fold in PycnoQ10 treated patients (P<0.05) but marginally improved in the control group. Distal edema decreased significantly in PycnoQ10 treated patients and only slightly in controls. CONCLUSION: The association of Pycnogenol and CoQ10 may offer an important therapeutic option with a very good tolerability that improves heart failure management without side effects.

Improvement in cochlear flow with Pycnogenol® in patients with tinnitus: a pilot evaluation.

AIM: The aim of this preliminary evaluation was to study the efficacy of Pycnogenol in improving cochlear flow in patients with mild-to-moderate tinnitus present for at least two weeks (without vertigo or important hearing loss), possibly associated with cochlear hypo-perfusion. METHODS: Patients with mild-to-moderate, idiopatic, monolateral tinnitus present for at least 2 weeks were included; no vertigo or important hearing loss had been found in a specific examination. The origin of tinnitus had been sudden (hours or days). Fifty-eight patients used Pycnogenol: 24 used 150 mg/day (group A; mean age 43.2+/-4.3) and 34 patients 100 mg/day (group B: mean age 42.4+/-3.8). Controls included 24 patients (mean age 42.3+/-4.5). The groups were comparable for their clinical problem and age and sex. The average duration of treatment was 34.3+/-3.1 days. No side effects were observed and no drop-outs occurred. RESULTS: The variations in cochlear flow velocity (in cm/s at the cochlear artery), at inclusion and after four weeks of treatment indicated that flow velocity at the level of the affected ear was significantly lower (both the diastolic and systolic components; P<0.05) in comparison with the other ear. The treatment favored an improvement in systolic (P<0.05) and diastolic flow velocity (P<0.05) in the two treatment groups A+B. The increase in flow velocity was very limited and not significant in controls. CONCLUSION: These results suggest that in selected patients with tinnitus and altered perfusion, Pycnogenol is effective in a short period of time in relieving tinnitus symptoms by improving cochlear blood flow. The effect is more pronounced with higher Pycnogenol dosage. More studies should be planned to better evaluate the pathology and potential applications of Pycnogenol in a larger number of patients who are currently without a real therapeutic solution.

Prevention of edema in long flights with Pycnogenol.

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<0.05). The RAS, evaluated in 22 subjects in the Pycnogenol 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<0.05). The variation on circumference at the ankle was 6% in the Pycnogenol group (11% in the control group; p<0.05). These results indicate a positive effect of Pycnogenol on edema during long flights when considering subjective and objective data. No unwanted effects were observed.

Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol.

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<0.025). The ITT (intention to treat) analysis detects 13 failures in the control group (eight lost to follow up + five thrombotic events) of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events) in the treatment group (p<0.025). No unwanted effects were observed. In conclusion, this study indicates that Pycnogenol treatment was effective in decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high risk subjects, during long-haul flights.

Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial.

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 treatments; 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 thrombotic events) of 92 subjects (19.6%) in comparison with 7 failures (of 94 subjects, equivalent to 7.4%) in the treatment group (p < 0.05). Events were asymptomatic. In conclusion, Flite Tabs were effective in reducing thrombotic events and in controlling edema in high-risk subjects in long flights.

Foam-sclerotherapy, surgery, sclerotherapy, and combined treatment for varicose veins: a 10-year, prospective, randomized, controlled, trial (VEDICO trial).

The study compared, by a prospective, randomized method, 6 treatment options: A: Sclerotherapy; B: High-dose sclerotherapy; C: Multiple ligations; D: Stab avulsion; E: Foam-sclerotherapy; 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 occurrence 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.

Effects of the total triterpenic fraction of Centella asiatica in venous hypertensive microangiopathy: a prospective, placebo-controlled, randomized trial.

The aim of this study was to demonstrate whether total triterpenic fraction of Centella asiatica (TTFCA), was effective in improving the microcirculation in venous hypertension and microangiopathy. Forty patients with severe venous hypertension, ankle swelling, lipodermatosclerosis were included. After informed consent, patients were randomized into a treatment and a placebo group: those in the treatment group received TTFCA (tablets, 60 mg, twice daily for 8 weeks). The two groups of subjects were comparable for age and sex distribution. The mean age was 48 years (SD 9; M:F= 11:11) in the treatment group (22 patients) and 47.6 (SD 7; M:F= 10:8) in the placebo group (18 patients). There were no differences between placebo and treatment group at inclusion; there was no change between inclusion and measurements at 8 weeks in the placebo group. A decrease (p < 0.05) in RF (flux at rest) and RAS (rate of ankle swelling) were 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, signs and symptoms, and filtration was clinically important at 8 weeks. No side effects were observed. In conclusion venous microangiopathy was improved by TTFCA treatment.

Microcirculatory effects of total triterpenic fraction of Centella asiatica in chronic venous hypertension: measurement by laser Doppler, TcPO2-CO2, and leg volumetry.

The aim of this prospective, randomized study was to demonstrate whether an oral preparation of TTFCA was effective in improving the microcirculation and edema (leg volume) in venous microangiopathy. Forty patients with venous hypertension were included. Treatment was prescribed for 6 weeks (tablets, 60 mg twice daily). Patients were randomized into a treatment and a placebo group. There were 20 patients in each group. In the treatment group the mean age was 42 (SD 7; M:F = 10:10); in the placebo group, the mean age was 40 (SD 9; M:F = 10:10). Tolerability and compliance were very good; there were no dropouts. At inclusion there were no differences between placebo and treatment group. After treatment there was a decrease in resting flux (29%) and an improvement (increase) in venoarteriolar response (52%); PO2 was increased (7.2%) and PCO2 decreased (9.6%). There was an important decrease in leg volume (66 mL decrease; 1.3% volume variation). The difference in flux, O2-CO2 and volume parameters were significant and clinically important at 6 weeks in the treatment group. In conclusion, TTFCA improves microcirculation and leg volume in venous hypertension. The effects of TTFCA are observed even in a limited sample of patients.

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.

Modification of the echogenicity of femoral plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, randomized, placebo-controlled trial.

The aim of this study was to evaluate whether TTFCA (total triterpenic fraction of Centella asiatica), was effective, by modulating collagen production, in a period of 12 months, increasing the echogenicity of echolucent plaques at the femoral bifurcation. Hypoechoic atherosclerotic plaques have been found to be associated with an increased evidence of cerebrovascular events. In this type of plaques stromal composition is limited as the collagen component is generally very low; the plaque composition is mainly due to lipid accumulation or thrombosis. The aim of this study was the evaluation of echogenicity of hyperechoic plaques and how it could be modified by a drug acting on the modulation of collagen synthesis. Antiplatelet agents were used in all patients; cholesterol-lowering agents were used in 34% of patients in the treatment group and in 36% in the placebo group. TTFCA was used at the dose of 60 mg thrice daily (oral tablets). Of the 60 included subjects 26 completed the study in the treatment group and 24 in the placebo group. At inclusion the average GSM in the treatment group was 14 (SD 3) and 14.3 (SD 3) in controls. At 12 months GSM was increased up to 22.8 (SD 4) in the treatment group and it was 15 (SD 3) in controls. Considering texture no significant changes were observed in controls while a qualitative increase in homogenicity was observed in the TTFCA group. Plaque size measured at the beginning and at the end of the study showed a median increase in size, in controls (23%; range 0%-44%); it was unchanged in the TTFCA group (variation 7%; 4%-26%). In conclusion in the treatment group plaques increased in echogenicity and in homogenicity; size and stenosis remained unchanged. Modulating the scarring process within echolucent plaques (low echogenicity, high echolucency, with a very low collagen/stromal component), possibly by collagen modulation, makes plaques more stable. This has been achieved and documented in the present study by an increase in the gray-scale median (plaques become more echogenic, more 'white'). The variation in GSM is generally associated with a lower risk of wall thrombosis, rupture and embolization. These observations indicate a positive action of TTFCA on the stabilization of hypoechoic, low-density femoral plaques.

Slow release nifedipine in the treatment of Raynaud's phenomenon.

An ever increasing interest is shown towards calcium-antagonist drugs and in particular to nifedipine in the treatment of Raynaud's Phenomenon (R.P.) On this matter a randomized double-blind study with 40 mg/die slow release nifedipine versus placebo was carried out for 30 days on 24 patients affected by R.P.-idiopathic in 16 cases and secondary in the remaining 8 cases. The evaluation of the clinical situation (hand ischemic attacks, pain, skin trophism) and the structural one (capillaroscopy of the finger nail bed and strain-gauge digital plethysmography) could be performed on 17 patients since 7 dropped out. From the clinical point of view an improvement was observed especially in the reduction of the ischemic attacks (88.8% of patients treated with nifedipine vs. 25.0% treated with placebo). Capillaroscopic results showed an improvement in 100% of the cases treated with nifedipine vs. 12.5% with placebo (p less than 0.001), as well as an improvement of the basal digit blood pressure values and after cold test in 88.8% of patients treated with nifedipine vs. 12.5% treated with placebo (p less than 0.005) and (p less than 0.0025) respectively.