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Maximization of skin capillaries during intravital video-microscopy in essential hypertension: comparison between venous congestion, reactive hyperaemia and core heat load tests.

Intravital capillary video-microscopy is a dynamic method for studying skin capillaries. The technique of direct intravital microscopy (without dyes) depends on the presence of red blood cells inside capillaries for their identification. The aim of the present study was to compare different techniques to try to establish the best method for maximizing the number of visible perfused capillaries during intravital capillary microscopy. We compared the effects of venous congestion with those of post-occlusive reactive hyperaemia (Study 1). We also investigated venous congestion followed first by post-occlusive reactive hyperaemia and then by a core heat load test (Study 2). Finally we investigated venous congestion followed by post-occlusive reactive hyperaemia combined with venous congestion (Study 3). In Study 1, capillary density increased with venous congestion from a baseline value of 74+/-2 (mean+/-S.E.M.) per field to 82+/-3 per field (P<0.0001; analysis of variance). With reactive hyperaemia, there was an apparent decrease in visible capillary density to 69+/-2 per field. In Study 2, baseline capillary density was 69+/-4 per field, and this increased significantly with venous congestion to 74+/-4 per field (P=0.01). With both reactive hyperaemia and core heat load, the apparent density was 62+/-4 per field. In Study 3 the baseline density was 70+/-2 per field, and this increased significantly with venous congestion to 80+/-3 per field (P<0.0001). With reactive hyperaemia combined with venous congestion, the density was 81+/-3 per field (P=0.328 compared with venous congestion alone). The results show that venous congestion at 60 mmHg for 2 min is the most effective method for visualization of the maximal number of perfused skin capillaries during intravital video-microscopy.

Adult↗

[The evaluation by video capillaroscopy of the efficacy of a Ginkgo biloba extract with L-arginine and magnesium in the treatment of trophic lesions in patients with stage-IV chronic obliterating arteriopathy].

BACKGROUND AND AIMS: This study aimed to evaluate the influence of Ginkgo biloba extract with arginine and magnesium used for the treatment of trophic lesions in the lower limbs caused by both diabetic and non-diabetic microangiopathy. METHODS: A comparative study was carried out in 20 patients who were divided into two groups: 10 were treated with ASA plus Ginkgo biloba extract with arginine and magnesium and 10 with ASA plus conventional hemorheology. The observation time was extended to 6 months, taking into consideration patients with trophic lesions to the lower limbs suffering from diabetic and non-diabetic peripheral arterial occlusive disease. The evaluation was performed by clinical, ultrasonographic and perilesional video capillaroscopy monitoring. Ultrasonographic and video capillaroscopy instrumental methods were used because they provide a full picture of macro and microcirculatory conditions around lesions. RESULTS: The study showed the undoubted efficacy of Ginkgo biloba extract with magnesium and arginine in relation to the following points: reduced healing times for the trophic lesion compared to the control group, improved painful symptoms, increased perilesional neoangiogenesis. No significant differences were observed from a Doppler ultrasonographic point of view or with regard to the claudication free interval. CONCLUSIONS: Ginkgo biloba extract with arginine and magnesium can improve the dynamics of cutaneous trophism in lesions caused by diabetic and non-diabetic microangiopathy.

Aged↗

New techniques for clinical assessment of the peripheral microcirculation.

Current methods for clinical investigation of the cutaneous microcirculation in patients are based mainly on laser Doppler and capillary microscopy. The use of laser Doppler gives a semi-quantitative index of superficial tissue perfusion. The most recent devices are capable of analysing both the volumetric and velocimetric components. New instruments use two different frequencies to compare tissue perfusion at different depths beneath the skin surface. The combination of a laser probe and a small automate produces a 2-dimensional image, allowing the evaluation of spatial heterogeneity in tissue perfusion, an important pathophysiological concept in vascular diseases. Capillaroscopy has recently been improved by the emergence of the flexible videomicroscope, allowing easy exploration of not only the classical site of the nail-fold but also of the body skin surface. The use of this method was therefore extended--from peripheral vascular disease and connective tissue diseases to the whole spectrum of trophic changes in the skin of the extremities. Systems for digital image analysis allow quantification of the structure of the microvascular bed (quantitative appraisal of microangiopathies) and function (capillary haemodynamics and exchange). Laser Doppler and capillaroscopy can also be combined for the measurement of red blood cell velocity in single capillaries.

Blood Flow Velocity↗

[Capillaroscopy and vascular acrosyndromes].

Periungual capillaroscopy is a simple noninvasive exploration contributing to the clinical examination. It is highly contributive to the etiological diagnosis of Raynaud's phenomenon and is the simplest means of detecting scleroderma early. Capillaroscopy has also largely contributed to better understanding of the pathogenesis of vascular disorders encountered in acrosyndromes. Experience has shown however that clinical indications should be more precise and results interpreted with more scientific rigor (J Mal Vasc 1999; 24: 357-362).

Cyanosis↗

Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis.

OBJECTIVE: To correlate microvascular abnormalities, evaluated by nailfold videocapillaroscopy (NVC), with the duration of both Raynaud's phenomenon (RP) and systemic sclerosis (SSc) from the date of diagnosis, in a large number of patients with SSc. METHODS: Ninety-seven consecutive patients were recruited and distributed into 3 groups on the basis of the morphological NVC patterns observed: "early" (E), "active" (A), and "late" (L). In each group the age of patients, age at onset, and the duration of RP as well as of overt SSc were investigated and correlated with the different NVC pattern variables. RESULTS: The early appearance of giant capillaries and hemorrhages (E pattern) is of great relevance for the early diagnosis of SSc. Therefore, these alterations are more evident in the active phase of the disease (A pattern). Conversely, the NVC observation of loss of capillaries and vascular architectural disorganization and the presence of ramified/bushy capillaries (L pattern) represents the clearest aspect of advanced SSc microvascular damage. These morphological alterations were found to correlate significantly with the duration of both RP and SSc, as well as with age of patients (p = 0.0001). No significant differences were observed when the variables were analyzed in the patients classified as having limited cutaneous SSc or diffuse cutaneous SSc. CONCLUSION: Classification of defined major nailfold patterns may be useful in assessing the appearance and progression of sclerodermic microangiopathy. As well, nailfold changes might represent a morphological reproduction of the evolution of SSc.

Female↗

[Periungual capillaroscopy in psoriatic arthritis].

PURPOSE: The aim of the study is the evaluation of the microcirculation trough periungueal capillaroscopy in patients suffering from psoriatic arthritis. MATERIALS AND METHODS: Eighteen patients (mean age 44 years, nine males and nine females) were examined according to the different clinical forms (spondylitic, mutilans, simil-rheumatoid, onyco-arthritis, oligo-articular) of the disease. RESULTS: In most of the patients, the exam showed a reduction in ansas' density and in capillary length and calibre as well as interstitial edema and expansion of the ansa venular portion with coiling and kinking, demonstrating the re-organization of the veins and the neo-angiogenesis. Avascular areas and microaneurysm have been found only in the "mutilans" form. In the "simil-rheumatoid" form, ansa reduced in length and calibre have been observed at capillaroscopy, a pattern different from that reported by others, in rheumatoid arthritis (characterized by thin but lengthened ansa). In the "spondylitic" form, the video-microscopical pattern was negative. CONCLUSIONS: This study is still ongoing in order to evaluate the results in a more representative sample.

Adult↗

[Video-thoracoscopic sympathectomy in the treatment of Raynaud's disease and palmar hyperhidrosis].

BACKGROUND AND AIM: Raynaud's syndrome is a clinical entity characterised by episodic vascular spasm, digital ischemia in response to cold or emotional stimuli and hyperhidrosis. Many patients suffering from Raynaud's syndrome are successfully treated using medical therapy alone. Those patients who do not respond to medical treatment undergo surgery but the indications continue to be a source of controversy. A modern approach to thoracic sympathectomy requires a video-assisted technique. The aim of this study is to attempt to use mini-invasive type surgery to treat Raynaud's disease and hyperhidrosis in order to evaluate the real efficacy of thoracic sympathectomy in a large number of patients. The results of this method were compared for the two different pathologies in question. METHODS: The methodology used by this study is based on instrumental and clinical tests performed before and after surgery on treated patients using a comparative criterion and with a minimum 5-year follow-up. The pre- and postoperative diagnostic tests were performed by the vascular surgery laboratory and using a C.W. Doppler and a reflected light photoplethysmograph. Capillaroscopy and laboratory evaluations relating to secondary Raynaud's disease were carried out by internist type structures. The patients enrolled in the study responded to the following criteria: primary Raynaud's disease, palmar hyperhidrosis and associated syndromes. The population came from a mixed sociodemographic background, albeit within a strictly regional zone (Sardinia). A total of 42 patients were studied. The surgical technique used consisted of the ablation of thoracic ganglia from the 2nd to the 4th. RESULTS: The results showed a resolution of symptoms in 95% of patients treated for hyperhidrosis, whereas a 50% recidivation rate was observed in patients with Raynaud's disease alone, although symptoms were less intense. The results for Raynaud's disease were more disappointing, but it is important to remember that surgery is the ultimate choice for cases with advanced lesions which do not respond to medical treatment. Under these circumstances, the possibility of halting the evolution of the pathology represents an auspicious achievement. CONCLUSIONS: The authors affirm that mini-invasive surgical treatment of hyperhidrosis was resolutive during a mean follow-up of 3 years. It therefore represents a valid method which causes minimum esthetic damage to the patient and the greatest functional benefit. The postoperative period is short (about 3 days) and free of major complications. There is virtually no post-surgical pain.

Adult↗

[Morphologic study of the microcirculation in connective tissue diseases].

Capillaroscopy is a non-invasive diagnostic test used to study microvascular abnormalities which are present in many disorders, particularly some rheumatic pathologies, such as connective tissue diseases. In systemic sclerosis, capillaroscopy allows detection of pathognomonic microvascular alterations. In other connective tissue diseases, including systemic lupus erythematosus, dermatopolymyositis, undifferentiated connective tissue diseases, and mixed connective tissue disease, the capillaroscopic patterns, although non-specific, can provide a valid support for the diagnosis. In Raynaud's phenomenon, capillaroscopy enables detection of early microvascular abnormalities that are useful for preclinical diagnosis of secondary Raynaud's phenomenon.

Connective Tissue Diseases↗

[Multivariate analysis as a method of determination of anthropogenic load on the course of Raynaud's disease in patients with systemic scleroderma and systemic lupus erythematosus].

AIM: To determine the effect of high industrial pollution on development of Raynaud's syndrome and impairment of pulmonary hemodynamics in patients with scleroderma systematica (SS) and systemic lupus erythematosus (SLE). Two groups of patients were examined: 20 SS and 33 SLE patients living in highly polluted territories, 15 SS and 27 SLE patients living in moderately contaminated territories. The tests included capillaroscopy, thermography, rheovasography of the fingers, zonal rheopulmonography. Semiquantitative spectral analysis measured content of 3 trace elements (Ti, Ba, Li) and 16 heavy metals (Cu, Zn, Pb, Ni, Mn, Sn, Cr, Y, Ga, Ag, Mo, Bi, Co, Cd, Fe, Zr) in the patients' hair. RESULTS: Patients living in highly polluted areas had a severe course of Raynaud's syndrome. Metal accumulation is decisive in patients of group 1; in development of staging of Raynaud's syndrome the key role belongs to lead, nickel, tin and iron; realization of the factor of the disease activity is related to lowering of zinc, copper concentrations and growing concentration of nickel. CONCLUSION: Vascular disorders in SS and SLE in patients living in heavily contaminated areas aggravate due to direct damage from heavy metals.

Environmental Pollutants↗

Nailfold capillary abnormalities in patients with familial Mediterranean fever.

OBJECTIVE: To determine the frequency and the degree of the nailfold capillary abnormalities in patients with familial Mediterranean fever (FMF). METHODS: We studied 67 (M/F: 28/39) patients with FMF. Thirty-seven healthy subjects (16/21), 19 patients (0/19) with systemic lupus erythematosus (SLE), and 8 patients (0/8) with scleroderma (PSS) were also studied. All participants were questioned for the presence of Raynaud's phenomenon (RP). Capillary loops of eight fingers were evaluated and scored with respect to avascular areas, tortuosity, enlargement and extravasations by the conventional capillary microscopy. Both FMF patients and healthy controls were examined in a blind manner. RESULTS: FMF patients differed from healthy controls by the presence of increased tortuosity and enlargement of capillary loops, but not by microhemorrhages. Being female and the presence of RP were the factors that correlated with the capillaroscopic findings. CONCLUSION: Capillary abnormalities are seen in patients with FMF.

Adolescent↗

Elevated plasma endothelin-1 levels and vascular dysregulation in patients with rheumatoid arthritis.

BACKGROUND: Contradictory results on plasma endothelin-1 (ET-1) levels in patients with rheumatoid arthritis have been reported in previous studies. We therefore evaluated whether plasma ET-1 levels in patients with rheumatoid arthritis differ from those of normal controls. Since systemically increased levels of ET-1 are known to occur in tandem with primary or secondary vascular dysregulation, we also measured peripheral blood flow by means of nailfold capillaroscopy combined with a cold provocation test. MATERIAL/METHODS: We measured plasma levels of ET-1 in twelve patients with different stages of rheumatoid arthritis by means of a specific radioimmunoassay, and compared ET-1 values to those of healthy controls. Capillary blood flow and the frequency of cold-induced vasospasm were studied in parallel, using nailfold capillaroscopy combined with a cold provocation test. RESULTS: Plasma ET-1 levels were significantly increased in patients with rheumatoid arthritis (p = 0.01) when compared to controls (2.38+/-0.95 pg/ml vs. 1.53+/-0.38 pg/ml). Capillary blood flow was reduced when compared to our own normal values, and a cold-induced blood standstill was seen in 58% of the patients. CONCLUSIONS: Patients with rheumatoid arthritis exhibit significantly elevated levels of ET-1, which may be associated with the symptoms of vascular dysregulation observed in nailfold capillaroscopy. Even though the clinical conclusions should be drawn from this study with caution, additional therapy with calcium channel blockers or, possibly in the future, with ET-1 receptor blockers, may be beneficial in patients with rheumatoid arthritis.

Adult↗

[Effect of elastic stockings on edema related to chronic venous insufficiency. Videocapillaroscopic assessment].

AIM: To evaluate the effect of class II (23-32 mm Hg) compression stockings on the edema of the ankle in patients with chronic venous insufficiency (CVI), and to assess the relationship between the microvascular phenomenon and the volume of the leg. MATERIAL AND METHOD: 11 patients (19 limbs, 5 women and 6 men, mean age 57 years) with CVI, CEAP 2-3 were studied through physical examination, Doppler color ultrasound test, measurement of leg volume and videocapillaroscopy. Patients were evaluated before (T0), after 7 days (T1) and 14 days (T2) of daily compression therapy with elastic stockings. Statistical comparisons used the Mac Nemar test for binomial variables and Wilcoxon test for paired quantitative data. RESULTS: All patients experienced significant improvement of symptoms, the volume of the limbs on the average decreased in the first week T0-T1=284.8 cm(3) +/- 307.5 cm(3) (6.27%, p<0.001). During the second week a small increase in volume was observed T2-T1=+ 12.23 cm(3), NS, 0.29%). The width of the capillary halo of edema decreased during the first week by an average of T0-T1=5.77 microm +/- 10.99 microm. During the second week the width of the edema halo continued diminishing, although in smaller proportion (T0-T2=7.89 microm +/- 11.77 microm). CONCLUSION: Daily use of grade II compression stockings induces a reduction in leg volume in patients with CEAP grades 2-3. This improvement of edema is paralleled by a decrease in the size of the pericapillary halo.

Bandages↗

Study of the microcirculation of oral mucosa in healthy subjects.

The research has the following aims: 1: to verify the applicability of capillaroscopic investigation to oral mucosa; 2: to propose oral mucosa as an alternative to the fingernail fold for capillaroscopic investigation; 3: to describe the characteristics of the microcirculation of oral mucosa in healthy subjects. 100 healthy patients were examined. The characteristics of the micro-circulation in the areas of gum mucosa and the mucosa covering of the lower lip were examined using computerised videomicroscopic techniques. For each patient we evaluated the visibility, the course, the density, the tortuosity and any images characteristic of capillary loops, besides the possible presence of microhaemorrhages, the average calibre of capillary loops and the number of capillary loops visible per square millimetre. The investigation was simple, non invasive and repeatable for each patient. An investigation of gum mucosa has revealed a course of capillary loops both parallel and perpendicular to the surface: often the tops of the capillary loops appear as regularly distributed dots or commas. Microcirculatory architecture in the area of the mucosa covering is characterised by capillary loops with a variable diameter, course and length; next to typical capillary loops with the appearance of horse stirrups, there are other loops similar to hairpins, commas and cork screws; there are also rare microhaemorrhages with the aspect of reddish stains, that could be caused by microtraumas. Visibility was very good in the area of the mucosa covering of the lower lip: mediocre in the area of gum mucosa. Our research has highlighted, that today it is possible to carry out a capillaroscopic investigation of oral mucosa in a simple and reliable way. Future research could evaluate how "normal microcirculation", that we describe in this paper, is modified during pathology

Adult↗

The influence of Emla cream on cutaneous microcirculation.

Emla cream is frequently used in surgical dermatology and in anesthesiology, for instance, during vascular surgery procedures. Because local anesthetics can have a vasoactive effect in addition to producing analgesia, we decided to document the effect of 5% Emla cream on cutaneous circulation in a prospective, placebo-controlled study. Skin circulation was monitored continuously under standardized conditions using video capillaroscopy, laser Doppler flowmetry and skin temperature. Recordings were made at the nailfold of the fourth finger (DIV) of the left hand of 12 volunteers with healthy veins over an observation period of 60 minutes under either Emla occlusive dressing or an occlusive dressing with placebo. Mean capillary red blood cell velocity changed only minimally under the Emla occlusive dressing, while placebo occlusive dressing led to a reduction of mean capillary red blood cell velocity from 0.21 mm/s to 0.12 mm/s (p<0.01). There was no statistically significant change of arterial capillary diameter under Emla or placebo occlusive dressing. Skin temperature dropped after 60 minutes of Emla cream occlusive dressing from an initial 26.7 to 24.0 degrees C (-10.1%; p<0.02). The same duration of placebo caused skin temperature to drop from 27.6 to 23.0 degrees C (-16.7%; p<0.001). Laser Doppler flux (543 nm) rose 13% with Emla (p=0.9) and dropped 41.9% under placebo occlusive dressing (p<0.03). Emla cream upregulated nutritive perfusion. No clinically relevant vasoconstrictive effects are expected from an application period of 60 minutes.

Adult↗

Elevated vascular endothelial growth factor in systemic sclerosis.

OBJECTIVE: To determine the serum levels of vascular endothelial growth factor (VEGF) in patients with systemic sclerosis (SSc) and to search for relationships between its serum levels and the clinical manifestations. METHODS: Serum levels of VEGF in patients with SSc and healthy controls were determined by ELISA. At the time of blood sampling, individual organ involvement was assessed, and a video microscope and PC based image processing were used to visualize nailfold capillaries and to quantify capillary density. RESULTS: Serum levels of VEGF in 48 patients with SSc were significantly higher than in 30 controls (432 +/- 356 vs 91 +/- 64 pg/ml; p < 0.001). Patients with diffuse cutaneous SSc (n = 21) had higher levels of serum VEGF than those with limited cutaneous SSc (n = 27) (432 +/- 356 vs 135 +/- 127 pg/ml; p < 0.001). Serum VEGF levels correlated well with the extent of skin sclerosis, as determined by modified Rodnan skin score (r = 0.656, p < 0.001) and serum TGF-beta levels (r = 0.530, p < 0.001). In particular, serum VEGF levels were inversely correlated with the capillary density of nailfold (r = -0.649, p < 0.001). However, no significant differences were found in the serum levels of VEGF between patients with systemic organ involvement and those without. CONCLUSION: The extent of skin sclerosis may contribute to the elevation of serum VEGF and high VEGF levels may serve as a surrogate indicator of capillary damage in SSc.

Adult↗