Medical management of patients with peripheral arterial disease.

Peripheral arterial disease (PAD) is one of the most frequent manifestations of atherosclerosis and is associated with atherosclerosis in the coronary and carotid arteries, leading to a highly increased incidence of cardiovascular events. Major risk factors of PAD are similar to those that lead to atherosclerosis in other vascular beds. However, there are differences in the power of individual risk factors in the different vascular territories. Cigarette smoking and diabetes mellitus represent the greatest risks of PAD. For prevention of the progression of PAD and accompanying cardiovascular events similar preventative measures are used as in coronary artery disease (CAD). However, recent data indicate that there are some differences in the efficacy of drugs used in the prevention of atherothrombotic events in PAD. Antiplatelet treatment is indicated in virtually all patients with PAD. In spite of the absence of hard evidence- based data on the long term efficacy of aspirin, it is still considered as a first line treatment and clopidogrel as an effective alternative. The new antiplatelet drugs ticagrelol and prasugrel also represent promising options for treatment of PAD. Statin therapy is indicated to achieve the target low density lipoprotein cholesterol level of ≤2.5 mmol/L (100 mg/dL) and there is emerging evidence that lower levels are more effective. Statins may also improve walking capacity. Antihypertensive treatment is indicated to achieve the goal blood pressure (<140/90 mmHg). All classes of antihypertensive drugs including beta-blockers are acceptable for treatment of hypertension in patients with PAD. Diabetic patients with PAD should reduce their glycosylated haemoglobin to ≤7%. As PAD patients represent the group with the highest risk of atherothrombotic events, these patients need the most intensive treatment and elimination of risk factors of atherosclerosis. These measures should be as comprehensive as those in patients with established coronary and cerebrovascular disease.

Femoral and tibial stress fractures associated with vitamin D insufficiency.

We describe a case highlighting the need to consider hypovitaminosis-D when investigating background causation and treatment of femoral and tibial stress fractures. The case also suggests that prescribing calcium and vitamin D supplementation may help with fracture healing in soldiers presenting with stress fractures who may have unrecognised hypovitaminosis-D which if left untreated may delay fracture healing.

Structured care of diabetes in general practice: a qualitative study of the barriers and facilitators.

This qualitative study explored general practitioner's and practice nurse's perceptions of barriers and facilitators to the proposed transfer of diabetes care to general practice. Qualitative data were collected through five focus groups. Participants included GPs (n = 55) and practice nurses (n = 11) representing urban (44%), rural (29%) and mixed (27%) practices, in the Irish Mid-West region. Barriers and facilitators were mentioned 631 times (100%). Barriers were mentioned 461 times (73%), facilitators 170 times (27%). The most frequently identified barriers were lack of financial incentive (119/631; 19%), lack of access to secondary resources (93/631; 15%), lack of staff and increased workload (59/631; 9%) and time constraints (52/631; 8%). Identified facilitators were access to secondary care (49/631;7.8%), the holistic nature of general practice and continuity of care (48/631;7.6%). Although many are enthusiastic, there remains significant reluctance among GPs and practice nurses to take responsibility for diabetes care without addressing these barriers.

Oral paricalcitol reduces the prevalence of posttransplant hyperparathyroidism: results of an open label randomized trial.

Postkidney transplant hyperparathyroidism is a significant problem. Vitamin D receptor agonists are known to suppress parathyroid hormone (PTH) secretion. We examined the effect of oral paricalcitol on posttransplant secondary hyperparathyroidism by conducting an open label randomized trial in which 100 incident kidney transplant recipients were randomized 1:1 to receive oral paricalcitol, 2 µg per day, for the first year posttransplant or no additional therapy. Serial measurements of serum PTH, calcium and bone alkaline phosphatase, 24-h urine calcium and bone density were performed. The primary endpoint was the frequency of hyperparathyroidism 1-year posttransplant. Eighty-seven patients completed the trial. One-year posttransplant, 29% of paricalcitol-treated subjects had hyperparathyroidism compared with 63% of untreated patients (p = 0.0005). Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria. Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference. Two subjects required decreasing the dose of paricalcitol to 1 µg daily. Hypercalcemia was asymptomatic and reversible. Incidence of acute rejection, BK nephropathy and renal function at 1 year were similar between groups. Moderate renal allograft fibrosis was reduced in treated patients. Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology.

Recent advances in the development of tissue transglutaminase (TG2) inhibitors.

Tissue transglutaminase (TG2) is a Ca(2+)-dependent enzyme and probably the most ubiquitously expressed member of the mammalian transglutaminase family. TG2 plays a number of important roles in a variety of biological processes. Via its transamidating function, it is responsible for the cross-linking of proteins by forming isopeptide bonds between glutamine and lysine residues. Intracellularly, Ca(2+) activation of the enzyme is normally tightly regulated by the binding of GTP. However, upregulated levels of TG2 are associated with many disease states like celiac sprue, certain types of cancer, fibrosis, cystic fibrosis, multiple sclerosis, Alzheimer's, Huntington's and Parkinson's disease. Selective inhibitors for TG2 both cell penetrating and non-cell penetrating would therefore serve as novel therapeutic tools for the treatment of these disease states. Moreover, they would provide useful tools to fully elucidate the cellular mechanisms TG2 is involved in and help comprehend how the enzyme is regulated at the cellular level. The current paper is intended to give an update on the recently discovered classes of TG2 inhibitors along with their structure-activity relationships. The biological properties of these derivatives, in terms of both activity and selectivity, will also be reported in order to translate their potential for future therapeutic developments.

Influence of diet transition on serum calcium and phosphorus and fatty acids in zoo giraffe (Giraffa camelopardalis).

In response to new recommendations for feeding giraffe in zoos, giraffe (n = 6) were transitioned from a typical hoofstock diet to diets containing reduced starch, protein, Ca and P and added n3 fatty acids. This diet was fed as a 50:50 mix with alfalfa and grass hay. Over the next 4 years, serum Ca, P, and fatty acids were measured every 6 months (summer and winter). Serum Ca was not affected by season (P = 0.67) or by diet (P = 0.12). Serum P was not affected season (P = 0.14), but was reduced by diet (P<0.01), and serum Ca:P was also increased by diet (P<0.01). The ratio of serum Ca:P tended to be affected by season (P = 0.07), in which animals tended to have greater Ca:P during the summer vs. the winter. The diet transition resulted in reduced serum saturated fatty acids (including lauric, myristic, palmitic, arachidic, and behenic acids), and increases in n6 fatty acids (including linolenic and arachidonic acids) and n3 fatty acids (docosahexaenoic acid) (P<0.05 for each). Overall, this diet transition resulted in blood nutrient profiles that more closely match that of values found in free-ranging giraffe.

The efficacy of a new stimulation technology to increase venous flow and prevent venous stasis.

OBJECTIVES: Electrical stimulation of calf muscles has been shown to be effective in prevention of DVT. The aim was to determine: (a) dependence of venous blood velocity and ejected volume on the rates of stimulated calf contractions: (b) clinical factors affecting efficacy in healthy individuals. METHODS: The maximum intensity stimulus tolerated was applied to calves of 24 volunteers. In popliteal veins, peak systolic velocities (PSV), ejected volume per individual stimulus (stroke volume SV) and ejected total volume flow per minute (TVF) of expelled blood were determined using ultrasound. Stimulation rates from 2 to 120 beats per minute (bpm) were applied. RESULTS: Mean baseline popliteal PSV was 10 cm/s. For stimulation rates between 2 and 8 bpm, the PSV was 10 times higher and reached 96-105 cm/s. Stroke volume (SV) per individual stimulus decreased in a similar fashion. With increasing rates of stimulation the TVF increased by a factor of 12 times (from 20 ml/min to 240 ml/min). CONCLUSION: Electrical stimulation is an effective method of activating the calf muscle pump. Enhancements of popliteal blood velocity and volume flow are key factors in the prevention of venous stasis and DVT. Further studies are justified to determine the stimulation rates in those with a compromised venous system.

Participation in dementia research: rates and correlates of capacity to give informed consent.

BACKGROUND: Many people participating in dementia research may lack capacity to give informed consent and the relationship between cognitive function and capacity remains unclear. Recent changes in the law reinforce the need for robust and reproducible methods of assessing capacity when recruiting people for research. AIMS: To identify numbers of capacitous participants in a pragmatic randomised trial of dementia treatment; to assess characteristics associated with capacity; to describe a legally acceptable consent process for research. METHODS: As part of a pragmatic randomised controlled trial of Ginkgo biloba for mild-moderate dementia, we used a consenting algorithm that met the requirements of existing case law and the exigencies of the new Mental Capacity Act. We decided who had capacity to give informed consent for participation in the trial using this algorithm and sought predictors of capacity. RESULTS: Most participants (76%) with mild-moderate dementia in this trial were unable to give informed consent according to the legal criteria. When adjusted for confounding, the Mini Mental State examination did not predict the presence of capacity. CONCLUSION: Cognitive testing alone is insufficient to assess the presence of capacity. Researchers and clinicians need to be aware of the challenging processes regarding capacity assessment. We outline a procedure which we believe meets the ethical and legal requirements.

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.

Loss of Bcl-2 expression in Barrett's dysplasia and adenocarcinoma is associated with tumor progression and worse survival but not with response to neoadjuvant chemoradiation.

Esophageal adenocarcinoma arising on a background of Barrett's esophagus is increasing in incidence. A molecular understanding of both the progression of Barrett's esophagus and the factors determining the response of adenocarcinoma to neoadjuvant therapy is required, and this study focused on the role of proteins regulated by the bcl-2 family of genes, which are important regulators of programmed cell death (apoptosis). In total, 48 patients (36 men, 12 women) with Barrett's adenocarcinoma were studied. All patients received preoperative chemoradiotherapy followed by surgery. Bcl-2, bax and bcl-x protein expression were detected by standard avidin-biotin peroxidase method. Bcl-2, bax and bcl-x expression were detected in 84%, 80%, and 76%, respectively, of normal squamous mucosa. An increasing degree of dysplasia in Barrett's mucosa both before and after chemoradiotherapy was significantly associated with a reduction of bcl-2 expression (P = 0.03 and 0.009, respectively). Bcl-2 expression was significantly associated with tumor differentiation (P = 0.03) and a trend towards earlier T stage (P = 0.08), but not with nodal status. Pre-therapeutic bcl-2, bax and bcl-x protein expression (27%, 75%, and 87.5%, respectively) were not associated with tumor response or resistance to therapy. Bcl-2-positive patients had a significantly improved survival compared with bcl-2-negative tumors. A significant reduction of bcl-2 expression is associated with the progression of Barrett's mucosa to adenocarcinoma. Bcl-2 expression was associated with improved survival. Preoperative chemoradiotherapy induces expression of bax and bcl-x protein. The pretreatment expression of bcl-2 and related proteins did not predict response or resistance to neoadjuvant chemoradiotherapy, suggesting that regulators of apoptosis alone do not determine the response of Barrett's adenocarcinoma to neoadjuvant therapy.

Therapy-related myelodysplastic syndrome after autologous stem cell transplantation for breast cancer.

Therapy-related myelodysplastic syndrome and acute myelogenous leukemia (t-MDS/AML) are serious complications of chemotherapy and radiotherapy for cancer. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) may be associated with an increased incidence of these complications. The frequency of t-MDS/AML after ASCT for breast cancer is uncertain. We reviewed our database of 379 consecutive breast cancer ASCT patients treated with alkylator-based chemotherapy, followed for a median of 1.52 years (range 0-8.97), with a median survival of 6.16 years. Three patients have developed tMDS/AML. The probability of developing this complication at 5 years is 0.032 in our series. We have used pathologic, cytogenetic and molecular methods to evaluate which portions of therapy may have predisposed to the development of this complication. Cytogenetic abnormalities were not found in the stem cell harvests of these patients by metaphase analysis or by fluorescence in situ hybridization (FISH). One patient demonstrated a clonal X chromosome inactivation pattern in her stem cell harvest, indicating pre-transplant chemotherapy may have been responsible for the development of her leukemia. As two of our patients developed this complication at greater than 4 years post-transplant, the number of cases may increase with longer follow-up. While the incidence appears to be low, further prospective and retrospective analysis will be necessary to determine which portions of therapy predispose to the development of t-MDS/AML in patients undergoing ASCT for treatment of breast cancer.

Topotecan in combination with carboplatin: phase I trial evaluation of two treatment schedules.

BACKGROUND: Topotecan and cisplatin combinations have shown schedule-dependent toxicity, which may in part be due to cisplatin nephrotoxicity. As carboplatin is less nephrotoxic and increasingly replacing cisplatin in clinical practice, the aim of this study was to define the optimal sequence and dose for topotecan in combination with carboplatin. PATIENTS AND METHODS: Two parallel phase I trials, with pharmacokinetic studies, were conducted administering carboplatin on day 1 with topotecan on days 1-5 (schedule A) or days 8-12 (schedule B). repeated every 3 weeks. RESULTS: Twenty-one patients were treated over two dose levels, carboplatin AUC 4 [glomerular filtration rate (GFR) calculated from 51Cr-EDTA clearance] with topotecan 0.5 or 0.75 mg/m2. At the first dose level, six patients were evaluable for each schedule. With schedule A, from 34 cycles, there were two dose reductions and 10 treatment delays due to myelosuppression. With schedule B from 25 cycles, there was one reduction and 10 delays. At dose level 2, both patients in schedule A had dose-limiting neutropenia. In contrast, there was no dose-limiting toxicity with schedule B in six patients, although the majority of cycles were delayed. CONCLUSION: The combination of topotecan and carboplatin using these 3-weekly schedules lead to significant myelotoxicity with attendant dose reductions and delays; the optimal scheduling of these agents remains to be defined.

A pathological study of tumour regression in oesophageal adenocarcinoma treated with preoperative chemoradiotherapy.

AIMS: To measure residual tumour in oesophageal adenocarcinoma treated with preoperative chemoradiotherapy, to correlate specific pathological variables with survival, and to describe morphological changes in tumour and non-neoplastic tissue resulting from preoperative treatment. METHODS: Resection specimens from 47 cases of oesophageal adenocarcinoma treated with preoperative 5-fluorouracil/cisplatin and radiotherapy were reviewed. Residual tumour was assessed in terms of tumour regression grade (TRG), pTNM stage, lymphovascular space invasion, and resection margin involvement. Survival analysis was performed using the Kaplan-Meier method and log rank test. Cox's proportional hazard model was used for multivariate analysis. RESULTS: A complete pathological response (TRG1) was present in eight cases. The absence of residual tumour was confirmed by negative immunohistochemical staining for MNF116. Tumour corresponding to TRG2 was present in five cases, to TRG3 in nine, to TRG4 in 22, and to TRG5 in three. By multivariate analysis, pN0 status (n = 35) had a positive effect on survival (p = 0.04) and TRG had no significant effect on survival (p = 0.06). Patients with pN0 tumours had a median survival of 48 months versus eight months for those with pN1 tumours (log rank test, p < 0.0001). We found that giant fibroblasts were discernible from single large residual tumour cells on haematoxylin and eosin alone. CONCLUSION: Response to preoperative chemoradiotherapy in oesophageal adenocarcinoma is variable. Although there are as yet no reliable predictors of response to treatment, patients who are identified at diagnosis as having negative loco-regional lymph nodes should benefit considerably from this treatment approach.

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.

Increase in echogenicity of echolucent carotid plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled, randomized trial.

The aim of this study was to evaluate whether total triterpenic fraction of Centella asiatica (TTFCA), was effective in modulating collagen production over 12 months, by producing an increase in echogenicity in echolucent carotid plaques. Part I was a pilot study aimed at evaluating the effects of TTFCA on different types of plaques. Part II was a prospective, randomized, placebo-controlled trial aimed at evaluating the effects of TTFCA on hypoechoic-echolucent plaques. The sonographic examination of carotid plaques was made with high-resolution ultrasound. Capturing, digital image processing, and normalization were standardized, interobserver, intrascanner, gain-level variability were standardized using as reference blood (black) for the most echolucent parts of the plaque and the adventitia (white) as the most echogenic part. Normalization of echo texture was obtained and plaque characterization differentiated echo-texture of plaque associated with events and those that did not cause embolization, thrombosis, or cardiovascular events. After identifying plaques at higher risk, patients were treated with TTFCA (oral tablets, 60 mg, thrice daily for 12 months) to evaluate whether this compound, by modulating collagen synthesis, could increase the echogenicity and therefore the stability of echolucent plaques. Part II was aimed at evaluating the effects of TTFCA on hypoechoic-echolucent plaques. Asymptomatic patients with echolucent plaques (GSM<18) were treated with TTFCA (60 mg, oral tablets three times daily for 12 months) or with comparable placebo after informed consent. All patients were also treated with antiplatelet agents. In part 1, at inclusion the GSC in the hypoechoic group was 15 (range, 12-18) while in the hyperechoic group it was 26 (range, 24-31); at 6 months it was increased in the hypoechoic group and at 12 months the increase was significant (19.5; p<0.05). There was a minor increase in GSM in the hyperechoic group (30; ns). In part II in the treatment group there was a significant difference in GSM (increase) at 12 months (p<0.05), improvement in texture (p<0.05) and a nonsignificant decrease in stenosis. No changes were observed in the placebo group. Events were observed in 6.5% of patients in the TTFCA group and in 11% in the control group (p<0.05). In conclusion these observations suggest a positive action of TTFCA on the stabilization of hypoechoic, low-density carotid plaques.

Flight microangiopathy in medium- to long-distance flights: prevention of edema and microcirculation alterations with total triterpenic fraction of Centella asiatica.

The aim of this study was the evaluation of microcirculatory alterations associated with edema in passengers travelling for more than 3 hours and the study of the effects of TTFCA (total triterpenic fraction of Centella asiatica) on the development of microcirculation alterations and edema, in a prospective, randomized study. Laser Doppler flowmetry (LDF), transcutaneous PO2 and PCO2, rate of ankle swelling (RAS) were used. Subjects were randomized after informed consent into two groups: one control group (no drug or other treatment), and a treatment group (TTFCA 60 mg thrice daily for 2 days before the flight, the day of the flight, and for another day after the flight). Inclusion criteria were age range between 30 and 50, mild-moderate superficial venous disease with varicose veins. Subjects traveled in economy class. In controls there was a progressive increase in CO2, RAS, and edema score and a progressive decrease in flux (RF) and venoarteriolar response with flying time. The variations in all parameters were milder (p>0.05) in the TTFCA group. RAS and edema were significantly lower in the TTFCA-treated group (p<0.025). The progressive increase in RAS, PCO2, and the decrease in VAR and O2 were linearly associated with flight time (up to 10 hours). These results are very interesting and indicate an option for patients prone to edema and microcirculation disturbances during long flights.

Capillary filtration in venous hypertension: evaluation with the vacuum suction chamber device and strain-gauge plethysmography.

The aim of this study was to evaluate local capillary filtration with the vacuum suction chamber (VSC) and the rate of ankle swelling (RAS) in patients with ankle edema due to venous hypertension before and after treatment with oral TTFCA (60 mg tablets twice daily) for 4 weeks. Strain-gauge plethysmography (SGP) was used to assess RAS and local capillary filtration was studied with the VSC (applied on the perimalleolar region); the disappearance of the weal was measured (minutes). Fifty patients with chronic venous insufficiency and edema were included (M:F= 25:25) after informed consent and randomized into a treatment (mean age 43; SD 7) and a control (mean age 44; SD 8) group. Compliance was very good (100% completed the 4-week trial); no side effects were observed. The two groups were comparable for age/sex distribution. Values of RAS and VSC time were comparable in the two groups, at inclusion. After 4 weeks there were no changes in the control group. A significant reduction was observed in the treatment (RAS decreased to 34% of the initial value; the VSC time decreased 48%; p<0.02). Treatment with TTFCA in chronic venous insufficiency is useful as soon as edema is detected to control the progressive alterations leading to ulcerations. This action is produced by complex actions on the microcirculation reducing and controlling edema and modulating collagen synthesis. This results in an improvement of the microcirculation, skin and subcutaneous tissue perfusion and functions.

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.