Measurement of the cutaneous blood flow reserve in normal humans by laser-Doppler flowmetry.

AIM: To assess the normality of the cutaneous blood flow reserve (CR). METHODS: To explore the feasibility and reproducibility of laser-Doppler flowmetry for CR measurement, we prospectively measured CR in 17 healthy subjects on the dorsum of the foot and pulp of the big toe. CR was defined as the sum of the venoarteriolar reflex (VAR), i.e. postural vasoconstriction, and postischemic reactive vasodilation (H), expressed as % of the resting supine flux and assessed by using laser-Doppler flowmetry. RESULTS: For the dorsal foot, VAR%+/-SEM was 61+/-14, H%, 752.5+/-214 and CR, 813.5+/-217. On the pulp of the big toe, VAR% was 61.6+/-4.7, H%, 588.2+/-174 and CR, 649.9+/-176. CR measurement variability was assessed by calculating the inter-individual coefficient of variation of CR, which was 1.1 for both the dorsal foot and pulp of the big toe. Reproducibility was assessed by calculating the CR intraclass correlation coefficient, which was 0.49 for the dorsal foot and 0.64 for the pulp of the big toe. CONCLUSIONS: The CR is proposed as a new parameter for assessing the microvascular integrity and contractile reserve of the skin. Laser-Doppler flowmetry is suitable for this non-invasive evaluation. The method displayed large variability, and its reproducibility varied from moderate for the dorsal foot, to substantial for the toe. Further studies are necessary to demonstrate its clinical usefulness.

Cutaneous microvascular effects of mid-term hormone replacement therapy in healthy postmenopausal women: a prospective placebo controlled trial.

OBJECTIVE: To study the mid-term effects of Hormone Replacement Therapy (HRT) on cutaneous microcirculatory blood flow and reactivity in healthy postmenopausal women. DESIGN: In a double-blind placebo controlled randomized study, 16 healthy postmenopausal women received either placebo or HRT (micronized estradiol: 1 mg/day, day 1-28, promegestrone: 0.25 mg/day, day 14-28). This regimen was completed 6 times. Cutaneous microcirculatory blood flow was recorded by laser-Doppler velocimetry on the foot dorsum, in the supine and then dependent positions, and after post-ischemic hyperemia. RESULTS: At day 0, the two groups were similar and none of the following data differed significantly between treated and placebo group: (supine flux: 11.8 +/- 1.8 u vs. 13.2 +/- 3.9, venoarteriolar reflex: 5.6 +/- 1.3 vs. 6 +/- 3.3, and post-ischemic hyperemia: 35.2 +/- 3.9 vs.48.3+/-11). At the end of the study (day 26-28 of 6th cycle), the supine flux was 9.8 +/- 2.1 in the HRT group vs.12.9 +/- 6 in the placebo group (NS), the venoarteriolar reflex, 1.2 +/- 2 vs. 7+/-1.7 (p=0.04), and post ischemic hyperemia, 31.8 +/- 5.4 vs. 39.5 +/- 4.6 (NS). Intragroup values did not change significantly for any of the microcirculatory parameters measured, which remained stable throughout the 6 months of the study. Intergroup values for these parameters did not change either, except for the venoarteriolar reflex, which was lower at the end of the study in the HRT (EP period, cycle 6 day 26-28) than placebo group (p=0.04). CONCLUSIONS: HRT does not impair the resting supine cutaneous microcirculation blood flow or post-ischemic hyperemia.

[Development and repair of vessels from bone marrow stem cells in the adult: from biology to clinical practice]. / Le développement et la réparation des vaisseaux à partir de cellules de la moelle osseuse chez l'adulte. De la biologie à la clinique.

In addition to its role in hematopoiesis, bone marrow appears to be a reservoir of stem cells that can differentiate into components of vessel wall. Upon stimulation by factors such as tissue ischemia, bone marrow stem cells can enter into circulating blood, and incorporate into areas of vascular development. Animal models suggest that bone marrow is a cellular source for tissue repair and/or regeneration. Data from humans, and clinical trials using bone marrow stem cells for the treatment of chronic ischemia in limbs and myocardium, support the view that stem cells may represent a new tool for the treatment of ischemia.

[Volumetrics: an indispensable complementary test in lymphology]. / La volumétrie: un examen complémentaire indispensable en lymphologie.

In patients with lymphedema, the volume of the affected limb is rarely measured in routine practice or may only be appreciated by a method giving a result in centimetres, an incorrect unit for volume quantification. Measurement of limb volume allows early diagnosis of lymphedema, long before the clinical signs appear. Two methods exhibit excellent reproducibility: the water displacement method which is the gold standard, with an accuracy of 0.7% and reproducibility of 1.3%, and the perimetric method, which has a good intraclass coefficient of correlation of 0.99. The water displacement method is the gold standard because it is the only one that gives the exact volume of the limb, including its extremity (hand or foot), but it has the drawback of requiring water. The perimetric method has two drawbacks: it does not include the hand or foot in the volume measure, and therefore gives an approximate volume of the affected limb, and it requires a computer to calculate the cone volumes. Taking, as an example of limb volume measurement, the case of patients operated for breast cancer, a difference between the post and pre postoperative volumes of < or = 100 mL is reassuring, a difference > 100 and < or = 250 mL requires regular surveillance, and a difference exceeding 250 mL is an indication for drainage and elastic compression. When the preoperative limb volume is unknown, the volume of the ipsilateral limb can be used.

[Treatments of progressive systemic sclerosis]. / Evolution des traitements de fond de la sclérodermie.

Progressive Systemic Sclerosis (PSS) is still an incurable disease but there are treatments for it, and the list of proposed treatments is long. The methodology of trials concerning PSS is complex, due to the low prevalence of the disease and therefore its financial interest for pharmaceutical companies, the lack of simple end points for efficacy, and the large number of clinical expressions with various prognoses. These causes explain why most open studies are fiercely positive, and why controlled studies are so rare. The progress made during the last 10 years concern 1) the diagnosis, which is now made earlier due to capillaroscopy and antibody assays, especially of anticentromere antibodies, 2) better knowledge of the prognosis, due to the classification of PSS into limited and the diffuse forms which have different prognoses, and 3) the recognition of a serious complication of the disease, ie. pulmonary hypertension, which can now be detected by non-invasive methods. All these improvements will also improve the methodology of future trials of drugs for treating PSS. In this ocean of uncertainties, some treatments have a valid background, and 3 visceral locations of PSS can be efficiently treated: renal involvement, with angiotensin-converting enzyme inhibitors, respiratory involvement, with D-penicillamine, and pulmonary hypertension, with prostacyclin derivatives. Corticosteroids are suspected to increase the risk of renal complications. Calcium blockers are considered a useful symptomatic treatment of the associated Raynaud's phenomenon and of the risk of digital necrosis, and may also constitute a treatment of PSS itself. A recent trial conducted by the French Microcirculation Society and its acrosyndrome Study Group considered the effects of an oral derivative of prostacyclin. Beneficial effects were: a reduction of the risk of digital necroses, improved overall wellbeing, less necessity for hospitalizations, fewer giant capillaries, and a dramatic fall in the level of von-Willebrand factor.

[Critical analysis of vascular explorations in diabetic complications]. / Analyse critique des explorations complémentaires vasculaires chez le diabétique.

Diabetes mellitus is the chief medical cause of amputation. The risk of amputation is 15-fold higher in diabetic subjects and 5 out of 6 amputees are diabetic. Among the three risk factors for amputation in diabetic patients-neuropathy, ischemia, and infection-ischemia is the most difficult to quantify. Thus, functional and/or distal foot arteriopathy may be present without any clinical symptoms long before trophic changes occur. Therefore additional vascular explorations, including measurement of systolic toe pressure, must be performed. Physical examination is sufficient to diagnose lower limb arterial disease when ankle pulses are missing, but severe foot ischemia may be present despite minimal clinical signs and normal ankle pulses. Mediacalcinosis alters ankle pressure. Toe pressure is the most reliable test for quantifying ischemia of the diabetic foot. Other investigations such as TcPO(2) measurement, laser-Doppler and capillaroscopy are useful for revealing early functional diabetic microangiopathy, but they can only be done and interpreted in specialized centers.

[Diabetic angiopathy: the role of microvascular exploration in routine practice. Consequences of a new algorithm for care of the diabetic foot]. / Vasculopathie diabétique: la place des explorations microcirculatoires en pratique quotidienne. Conséquences pour une nouvelle prise en charge du pied diabétique.

Diabetes mellitus is the chief medical cause of amputation. The risk of amputation is 15-fold higher in diabetic subjects and 5 out of 6 amputees are diabetic. There are three types of clinical presentation of diabetes-neurological, infectious and ischemic. In clinical practice, these three forms are often intertwined but the most frequent clinical sequence of events is neuropathy --> ulceration --> infection --> amputation. In this sequence, ischemia is not mentioned. The explanation is that the ischemic component of the diabetic foot is only recognized when ankle pulses are missing and when duplex scanning shows stenosis or occlusion of the main arterial trunks of the legs. This manner of diagnosing the ischemic component of diabetic foot is wrong as it fails to recognize the possibility of distal diabetic arteritis. Some experts in diabetology deny the existence of this arteritis which is obvious for those who measure systolic toe pressure. This distal arteritis is present in about 15% of all diabetic patients without trophic changes and in 35% of those with trophic changes. This foot arteritis is closely related to neuropathy. Toe pressure is not usually mentioned in text books or in consensus conferences concerning the diabetic foot. This is the main explanation for the calamitous number of amputations among diabetic patients. Nothing will change as long as physicians do not include toe pressure as a useful diagnostic tool in patients with diabetes. We present here a four-stage algorithm including toe pressure measurement for the management of the diabetic foot.

[Acrocyanosis: changing concepts and nosological limitations]. / Acrocyanose, évolution des concepts et limites nosologiques.

Acrocyanosis is undoubtedly the most commonplace acrosyndrome, both in terms of pathogenesis and prognosis. Patients experience functional impairment and an esthetic prejudice that must not be neglected. Adopting the nosological classifications described for Raynaud's syndrome, primary acrocyanosis must be distinguished from exceptional secondary phenomena that have a radically different clinical course. Primary acrocyanosis is generally observed in a young woman who appears thin or has recently lost weight. No paroxysmal episode (syncope, cyanosis, suspicious event involving the fingers) is found. The physical examination is negative and no complementary explorations are needed. Current pathophysiological hypotheses remain insufficient but suggest that vasospasticity rather than hemorheology is involved. The hypothesis that a thermoregulation disorder could be associated with weight loss deserves further study. Symptomatic care relies on dietary and hygiene counseling, emphasizing the importance of warm clothing. The psychological element must also be considered even in the most common forms.

[Placebo controlled efficacy of class 1 elastic stockings in chronic venous insufficiency of the lower limbs]. / Efficacité versus placebo de la contention classe 1 dans l'insuffisance veineuse chronique des membres inférieurs.

OBJECTIVE: To compare, in a 4-week clinical trial, the efficacy of class 1 Elastic Compression Stockings (pressure at the ankle 10 to 15 mmHg) to that of Placebo Stockings (pressure at the ankle 3 to 6 mmHg) in women consulting in general practice for mild, symptomatic, chronic venous insufficiency of the lower limbs. PATIENTS AND METHODS: This was a 4-week multicentre, randomised, double-blind, placebo-controlled clinical trial conducted on two parallel groups of patients presenting with mild chronic venous insufficiency grade C(1-3S) E(p) A(S1-5) according to the CEAP classification. Treatment efficacy was assessed by the following criteria: global impairment as assessed at each visit on a visual analogue scale (primary efficacy parameter), Quality of Life measured by the CIVIQ questionnaire, symptoms index (sum of individual scores for pain, limb heaviness, paresthesias, cramps and evening limb oedema), limb volume measured by volumetry, and the evolution of global impairment during the course of the trial as assessed by repeated auto-evaluations on visual analogue scales. Compliance was assessed by the number of days patients wore the stockings for at least ten hours per day. Treatment tolerability was assessed by the record of the possible adverse events. RESULTS: Three hundred and forty one patients were included in total. Statistically significant differences were observed on global score of quality of life in favour of class 1 Elastic Compression Stockings group. In the subgroup of patients with evening limb oedema at inclusion, the decrease of limb volume noted with class 1 Elastic Compression Stockings was all the more marked that evening limb oedema was more pronounced at baseline. A good compliance was observed in 76% to 80% of patients according to the treatment group. Tolerability of class 1 Elastic Compression Stockings was comparable to that of the Placebo Stockings. CONCLUSIONS: After four weeks of treatment, compression with class 1 Elastic Compression Stockings allows a statistically significant improvement of Quality of Life and a decreasing of limb oedema in patients presenting with mild chronic venous insufficiency of the lower limbs. Moreover, the tolerability of class 1 Elastic Compression Stockings was confirmed by the high level of patient compliance.

Limb salvage and popliteal aneurysms: advantages of preventive surgery.

OBJECTIVES: to assess the prognosis of atherosclerotic popliteal aneurysms (APAs), according to whether they were occluded or patent at the time of diagnosis. DESIGN: retrospective study. PATIENTS AND METHODS: fifty-two APAs were investigated in 35 patients. Nineteen were occluded (group I) and 33 patent (group II). In group I, 11 lower limbs had critical ischaemia, and eight had severe claudication. In group II, 27 were asymptomatic, 3 were painful, and 3 presented with symptomatic distal occlusion. In group I, treatment consisted of six bypasses, five thrombectomies, four thrombolyses, but for five APAs, no revascularisation was possible due to lack of runoff. In group II, 30/33 APAs were treated by graft replacement; the other three were not operated on due to the patients>> poor general condition. RESULTS: the 4-year survival rate was 72% in group I vs. 77% in group II, and the limb salvage rate was 72% in group I vs. 100% in group II, p<0.01. CONCLUSION: prophylactic treatment of asymptomatic popliteal aneurysms may avoid amputation caused by thrombosis and embolisation of runoff.

[Teaching targets in vascular medicine]. / Objectifs pédagogiques en médecine vasculaire.

The reference list presented here is a selection of educative objectives performed by the French "Collège des Enseignants de Médecine Vasculaire" for the different levels of the medical initial education course. It was produced through a collective procedure, after selecting the most relevant topics and setting up writing rules based upon docimology, and favoring practical rather than theoretical objectives. The main topics are peripheral obstructive arterial disease, polyatherosclerosis, atherosclerosis risk factors, venous thromboembolic disease, thrombophilia, chronic venous insufficiency, lymphatic insufficiency, leg ulcers, vascular acrosyndromes, cerebrovascular diseases and connective tissue diseases, vascular occupational diseases, vascular adverse effects of drugs, diabetic vascular disease, the vascular consequences of hypertension, vascular malformations and angiodysplasia, inflammatory arterial diseases, and vascular explorations. As a whole they include about 300 objectives for the five teaching levels. We hope that this list will help stimulate production of training courses and documents strongly needed in this field.