[Tissue oxygenation and microcirculation in dermatoliposclerosis with different degrees of erythema at the margins of venous ulcers. A contribution to hypodermitis symptoms]
Klinik für Dermatologie und Venerologie, Medizinische Universität zu Lübeck.
BACKGROUND: In patients with chronic venous insufficiency erythematous areas in indurated skin (hypodermitis) and non erythematous areas of lipodermatosclerosis were examined. METHODS: In 13 patients with venous ulcers a total of 32 localizations in more or less erythematous and indurated ulcer edges were measured. The amount of erythema was taken as an indicator for the extent of hypodermitis. The parameters examined were erythema (a-value), skin temperature (t), laser Doppler flow (LDF), transcutaneous (tcpO2) and intracutaneous oxygen tension (icpO2). According to the amount of erythema the different localizations were separated into two groups: areas with a-values lower than 14,2 were classified as lipodermatosclerosis without or with little erythema, are-as with a-values higher than 14,2 were classified as areas of lipodermatosclerosis with extensive erythema. Identical measurements were also performed in healthy looking skin below the knee. RESULTS: Skin temperature and LDF were higher in areas with much erythema compared to those with little or no erythema. TcpO2, measured with an electrode temperature of 44 degrees C, was lower in areas with inflammation; tcpO2-values at 37 degrees C and icpO2-values showed no differences in ulcer edges with different amounts of inflammation. CONCLUSION: The results show differences of microcirculation between areas of lipodermatosclerosis with and without hypodermitis. These differences did not influence the actual tissue oxygenation in deeper parts in the dermis.
Dermatol Ther. ;23 (4):375-88 20666825
Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
The most commonly recognized form of lipodermatosclerosis (LDS), chronic LDS presents with induration and hyperpigmentation of the skin involving the one or both of the lower legs in a characteristic "inverted champagne bottle" appearance. Associated with venous insufficiency, LDS is most common in middle aged women. In addition to chronic LDS, an acute form may also occur and is often misdiagnosed as cellulitis, inflammatory morphea, or erythema nodosum. The "acute" refers to the symptoms present that are exquisite pain. Treatment of LDS is based on the clinical presentation with compression therapy as the mainstay of treatment if tolerated. For acute LDS, patients often cannot tolerate compression therapy due to pain. We advise the use of fibrinolytic therapy, if available, until the patient can tolerate compression stockings.
Department of Dermatology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
BACKGROUND Lipodermatosclerosis describes bound-down, sclerotic skin involving the lower extremities. OBJECTIVE Our purpose was to describe the demographic and clinical features of patients with lipodermatosclerosis. METHODS This was a retrospective study of patients presenting to Mayo Clinic between 1976 and 1998 with a diagnosis of lipodermatosclerosis. RESULTS Of 97 patients, 84 (87%) were women. Mean age was 62 years (range, 25-88 years). Mean body mass index was 34.3 (range, 17.8-71.5). Clinical signs were bilateral involvement in 44 patients (45%), induration localized to a discrete plaque in 49 (51%), erythema in 69 (71%), hyperpigmentation in 57 (59%), ulceration in 13 (13%), concomitant edema in 69 (71%), and varicosities in 55 (57%). Vascular studies performed on 72 patients showed abnormalities in 49: deep venous incompetence in 33 (67%), calf muscle pump abnormality in 19 (39%), abnormal pulsatility in 10 (20%), and obstruction in 1 (2%). CONCLUSION Lipodermatosclerosis was associated with female sex, middle age, high body mass index, and venous abnormalities.
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[Shave therapy for surgical treatment of persistent venous ulcer with large superficial dermatoliposclerosis]
Klinik für Dermatologie und Venerologie, Medizinische Universität zu Lübeck.
Ulcers in chronic venous insufficiency, especially in postthrombotic syndrome, are often resistant to compression therapy. They can be treated effectively by the dermatologic surgeon with a fairly simple operative procedure. The removal of the ulcer together with the extensive lipodermatosclerosis by Humby knife (shave-therapy) and immediate grafting with a meshed split skin graft-possibly in combination with ligation of insufficient perforator veins-yields very good success rates. The results in 13 patients (18 legs) with an average follow up period of 11 months (up to 20 months) are reported.
Klinik für Dermatologie und Venerologie, Medizinische Universität zu Lübeck.
Chronic venous insufficiency (CVI) leads to morphological and functional changes in nutritive capillaries resulting in disturbances of the nutrition of the skin. Up to now, data obtained from transcutaneous measured pO2 were taken as an indication for a decreased oxygen supply to the skin. With the aim of obtaining direct information on the tissue oxygenation of dermis and subcutis we have measured the distribution of tissue pO2 values with needle probes (300 microns tip diameter, Eppendorf-Netheler-Hinz-GmbH, Hamburg). 12 patients with CVI III and 8 healthy volunteers were included in this study. The needle probes were inserted into the skin of the proximal third of the lower leg and, in patients, in the areas with mild and with severe sclerosis (ulcer edge). The pO2 data from the needle probes were compared with pO2 data obtained from transcutaneous surface probes (tcpO2) and with data from laser doppler flux measurements LDF). In clinically healthy skin the intracutaneously measured pO2 (icpO2) was 51 +/- 7 mmHg (mean +/- S.D.) and the subcutaneously measured pO2 (scpO2) was 47 +/- 8 mmHg. In lipodermatosclerosis invasively determined pO2-values were lower than in healthy skin, however, no hypoxic or anoxic values were found. Compared with tcpO2-values there was no considerable difference between icpO2-values measured in mild sclerosis and severe sclerosis (icpO2 28 mmHg as compared to 25 mmHg; scpO2 31 mmHg as compared to 27 mmHg). The icpO2 values obtained from the edge of the ulcer showed a large variation from patient to patient (6 mmHg to 42 mmHg). There was no correlation between the pO2 data and the LDF-values.
Differences between intracutaneous and transcutaneous skin oxygen tension in chronic venous insufficiency.
Department of Dermatology, Medical University of Lübeck, Germany.
Data obtained from transcutaneously measured PO2 (tcPO2) were taken as an indication for a decreased oxygen supply to the skin in patients with chronic venous insufficiency III. Direct (invasive) measurements in LDS have not yet been performed. We therefore measured the intracutaneous PO2 (icPO2) in healthy skin and LDS (8 healthy volunteers and 18 patients with CVI III) with needle probes (250 microns tip diameter). The icPO2 values were compared with data of tcPO2 (37 degrees C and 44 degrees C electrode temperature). In healthy skin the mean icPO2 was about 50 mmHg and no steep PO2 gradients were found. In LDS (ulcer edge) mean PO2 values were lower than in healthy skin, however, no hypoxia or anoxia was observed. At the same site most tcPO2 (44 degrees C) values were between 0 and 5 mmHg. The mean icPO2 values from ulcer edges of different patients ranged from 6 mmHg to 42 mmHg (mean 22 mmHg). In LDS very different PO2 profiles were seen. There was no correlation between tcPO2 and icPO2 data. Our present results may suggest that skin damage in patients with CVI is not necessary associated with hypoxia.
Hanse-Klinik, St-Juergen-Ring 66, D-23564 Lübeck, Germany Department of Anaesthesiology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. email@example.com
BACKGROUND Lipoedema is a painful disease in women with circumscribed increased subcutaneous fatty tissue, oedema, pain and bruising. Whereas conservative methods with combined decongestive therapy (manual lymphatic drainage, compression garments) have been well established over the past 50years, surgical therapy with tumescent liposuction has only been used for about 10years and long-term results are unknown. OBJECTIVES To determine the efficacy of liposuction concerning appearance (body shape) and associated complaints after a long-term period. METHODS A total of 164 patients who had undergone conservative therapy over a period of years, were treated by liposuction under tumescent local anaesthesia with vibrating microcannulas. In a monocentric study, 112 could be re-evaluated with a standardized questionnaire after a mean of 3years and 8months (range 1year and 1month to 7years and 4months) following the initial surgery and a mean of 2years and 11months (8months to 6years and 10months) following the last surgery. RESULTS All patients showed a distinct reduction of subcutaneous fatty tissue (average 9846mL per person) with improvement of shape and normalization of body proportions. Additionally, they reported either a marked improvement or a complete disappearance of spontaneous pain, sensitivity to pressure, oedema, bruising, restriction of movement and cosmetic impairment, resulting in a tremendous increase in quality of life; all these complaints were reduced significantly (P<0·001). Patients with lipoedema stage II and III showed better improvement compared with patients with stage I. Physical decongestive therapy could be either omitted (22·4% of cases) or continued to a much lower degree. No serious complications (wound infection rate 1·4%, bleeding rate 0·3%) were observed following surgery. CONCLUSIONS Tumescent liposuction is a highly effective treatment for lipoedema with good morphological and functional long-term results.
Universitätsklinik für Plastische Chirurgie und Schwerbrandverletzte, Handchirurgiezentrum, Operatives Referenzzentrum für Gliedmassentumoren, BG-Kliniken Bergmannsheil, Ruhr-Universität Bochum. firstname.lastname@example.org
Vasa. 2003 Nov ;32 (4):205-8 14694769
Changes of fascia and muscles before and 12 months after successful treatment of recalcitrant venous leg ulcers by shave therapy.
Department of Dermatology and Venerology, Medical University of Lübeck, Germany. Yvonne.Gaber@medinf.mu-luebeck.de
BACKGROUND: In chronic venous insufficiency (CVI) III typical changes of skin, subcutaneous tissue, fascia and muscle can be found. It was believed, that the thickening of the fascia is irreversible and it has been postulated that the degeneration of muscles is causative for the persistence of recalcitrant leg ulcers. PATIENTS AND METHODS: By computed tomography (CT) and magnetic resonance imaging (MRI) 8 patients with therapy resistant venous ulcers were examined. Changes of fascia and muscles were determined preoperatively and 12 months after successful shave therapy. RESULTS: By CT a thinning of the preoperatively thickened fascia could be demonstrated in all patients one year after surgery. Before shave therapy MRI showed that the fascia was not only thickened and blurred, but also had fluid accumulations perifascial. 12 months after therapy the fascia was thinner and sharply demarcated. The fluid was either absent or distinctively reduced. Referring to the thickness of fascia an average decrease of 0.084 cm (0.03-0.17 cm) was observed. Before surgery the muscles showed a fatty degeneration as a sign of atrophy; with CT and MRI no changes could be demonstrated after one year in all patients. CONCLUSION: The results after one year demonstrate for the first time, that the changes of the fascia in CVI III are reversible and that there is no direct correlation between the degeneration of muscles and the persistence of venous leg ulcers.
Hanse-Klinik, Fachklinik für Liposuktion und operativ-ästhetische Dermatologie, Lübeck. email@example.com
Autologous fat grafting is a standard method for soft tissue augmentation. The method is commonly used for volume restoration of the ageing face. Furthermore, atrophic scars, lipodystrophy and scleroderma en coup de sabre can be treated. Following liposuction, the harvested fat can be reinjected immediately or stored at minus 28 degrees C for at least 2 years. In most cases, several injections at 3 to 4 months intervals are needed for good long-term effects. The procedure is used world-wide with good results and a minimum of side effects.
Resistance to activated protein C due to factor V Leiden mutation: high prevalence in patients with post-thrombotic leg ulcers.
Department of Dermatology, Medical University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
BACKGROUND Activated protein C (APC) resistance is the most frequently diagnosed heritable thrombophilic defect predisposing to thrombosis. OBJECTIVES To determine the prevalence of APC resistance due to factor V Leiden mutation in patients with leg ulcers. METHODS Within a 2-year-period 100 consecutive patients with leg ulcers were examined for factor V Leiden mutation. RESULTS APC resistance due to factor V Leiden mutation was detected in 19 of 53 patients (36%) with post-thrombotic leg ulcers and in three of 47 patients (6%) with ulcers caused by primary varicosis. In a healthy control group APC resistance due to factor V Leiden mutation was found in five of 96 (5%) volunteers. CONCLUSIONS In view of this high prevalence of APC resistance of 36%, which has never previously been reported, patients with post-thrombotic leg ulcers should be investigated for APC resistance.
Skin diseases in children in rural Kenya: long-term results of a dermatology project within the primary health care system.
Doctors in Aid of Children with Skin Diseases in Africa ('Aerzte helfen hautkranken Kindern in Afrika e.V.') Bad Soden am Taunus, Germany. firstname.lastname@example.org
BACKGROUND Following an epidemiological study on skin diseases in 5780 pupils from 13 schools in rural western Kenya in 1993, a dermatology project within the primary health care system was established in 1994 by the German non-government organization (NGO)'Doctors in Aid of Children with Skin Diseases in Africa'. Within this project trained community health workers carried out regular visits to schools and nurseries and treated children with hydrocortisone acetate 1% cream for dermatitis, gentian violet 1% solution for bacterial skin infections, Whitfield's ointment for dermatophytoses and benzylbenzoate emulsion 25% for scabies. OBJECTIVES To assess the impact of this intervention. METHODS In 1999, after a 5-year period, 4961 pupils from the same 13 schools were re-examined and the prevalence rates were compared. RESULTS Non-infective dermatitis had a prevalence of 1.7% in 1993 as well as in 1999; among the communicable diseases bacterial infections declined from 12.7% to 11.3%(not significant), fungal infections rose from 10.1% to 13.9%(P < 0.05) and arthropod infections (mainly scabies) remained at similar levels of 8.3% in 1993 and 8.0% in 1999. A distinctive reduction could only be found for tropical ulcers (0.1% in 1999 compared with 1.2% in 1993). CONCLUSIONS The prevalence of dermatoses in children in rural Africa does not only depend on treatment schemes within the primary health care system, but on the socio-economic conditions available.
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Physiol Behav. 2010 Mar 15;: 20298707
Mild hypohydration induced by exercise in the heat attenuates autonomic thermoregulatory responses to the heat, but not thermal pleasantness in humans.
Laboratory of Integrative Physiology, Health and Welfare, Faculty of Human Sciences, Waseda University, Mikajima 2-579-15, Tokorozawa, Saitama 359-1192, Japan; Sport Science Center for Active Life, Waseda University, Tokorozawa, Saitama, Japan.
Hypohydration caused by exercise in the heat attenuates autonomic thermoregulation such as sweating and skin blood flow in humans. In contrast, it remains unknown if behavioral thermoregulation is modulated during hypohydration. We assume that thermal unpleasantness could drive the behavioral response, and would also be modulated during hypohydration. Nine healthy young men participated in the present study. Body and skin temperature were monitored. Ratings of thermal sensation and pleasantness were conducted. After approximately 45min rest at 27 degrees C, they performed 50-min cycling exercise, which was at the level of 40% of heart rate range at 35 degrees C (hypohydration trial) or at the level of 10% of heart rate range at 23 degrees C (control trial), respectively. Subjects returned to the rest at 27 degrees C, and the ambient temperature was then changed from 22 to 38 degrees C. Body weight decreased by 0.9+/-0.1% immediately after exercise in the hypohydration trial and 0.4+/-0.1% in the control trial. In the cold, no significant difference in thermal sensation or pleasantness was observed between trials. There was no significant difference in thermal pleasantness between trials in the heat, although thermal sensation in the heat (32.5-36 degrees C) was significantly lower in the hypohydration trial than in the control trial. In addition, laser Doppler flow of the skin and sweat rate were attenuated in the heat in the hypohydration trial. These results may indicate that mild hypohydration after exercise in the heat has no influence on behavioral responses to the heat.
Reproducibility of transcutaneous oximetry and laser Doppler flowmetry in facial skin and gingival tissue.
Department of Clinical Dentistry - Oral Surgery and Oral Medicine, University of Bergen, Bergen, Norway.
Laser Doppler flowmetry (LDF) and transcutaneous oximetry (TcPO(2)) are non-invasive techniques, widely used in the clinical setting, for assessing microvascular blood flow and tissue oxygen tension, e.g. recording vascular changes after radiotherapy and hyperbaric oxygen therapy. With standardized procedures and improved reproducibility, these methods might also be applicable in longitudinal studies. The aim of this study was to evaluate the reproducibility of facial skin and gingival LDF and facial skin TcPO(2). The subjects comprised ten healthy volunteers, 5 men, aged 31-68 years. Gingival perfusion was recorded with the LDF probe fixed to a custom made, tooth-supported acrylic splint. Skin perfusion was recorded on the cheek. TcPO(2) was recorded on the forehead and cheek and in the second intercostal space. The reproducibility of LDF measurements taken after vasodilation by heat provocation was greater than for basal flow in both facial skin and mandibular gingiva. Pronounced intraday variations were observed. Interweek reproducibility assessed by intraclass correlation coefficient ranged from 0.74 to 0.96 for LDF and from 0.44 to 0.75 for TcPO(2). The results confirm acceptable reproducibility of LDF and TcPO(2) in longitudinal studies in a vascular laboratory where subjects serve as their own controls. The use of thermoprobes is recommended. Repeat measurements should be taken at the same time of day.
Evaluation of apoptotic cells and immunohistochemical detection of FAS, FAS-L, Bcl-2, Bax, p53 and c-Myc in the skin of patients with chronic venous leg ulcers.
Susanna Heising, Jürgen Giebel, Anna-Lena Ostrowitzki, Franziska Riedel, Hermann Haase, Kirstin Sippel, Michael Jünger
Department of Dermatology, Ernst Moritz Arndt University, D-17475 Greifswald, Germany. email@example.com.
In the present study we were interested, if apoptosis plays a role in the surrounding skin of venous ulcers, where microcirculatory disorders were already observed. For this purpose laser Doppler flow and partial oxygen pressure were measured in 17 patients at the ulcer edge, the transitional area of the lower leg and the thigh. Subsequently biopsies were taken from the respective sites and subjected to terminal deoxynucleotidyl transferase labelling (TUNEL) and immunohistochemistry using antibodies to determine the protein expression of Fas, Fas-L, Bax, Bcl-2, p53 and c-Myc. Laser Doppler flow was increased and transcutaneous oxygen partial pressure was decreased, with significant differences at the ulcer edge and the lower leg compared to the thigh. The skin biopsies did not show any differences when labelling for apoptotic cells. Keratinocytes of basal and spinous layer stained with antibodies against Fas, Fas-L and Bax in all probes of the three sites. c-Myc and p53 were negative in all keratinocytes of the skin probes. However, staining with Bcl-2 was significantly decreased at the ulcer edge in comparison to the lower leg and the thigh (p=0.017). Our study revealed that a disturbed microcirculation does not increase the number of apoptotic cells at the ulcer edge in patients with venous disease. The reduced staining pattern with Bcl-2 at the ulcer edge seems not to result in higher susceptibility to apoptosis, but it remains to be proven whether it is involved in epidermal acanthosis.
Department of Physiology, College of Medical Sciences, Nova Southeastern University, Ft. Lauderdale, Florida 33328, USA. firstname.lastname@example.org
Previous reports suggest that skin blood flow is reduced in arms of women with lymphedema due to breast cancer treatment. Since tissue oxygenation depends on blood flow, we sought to determine if transcutaneous oxygen tension (TcPO2) is also reduced and if so, if therapy that reduces edema has a beneficial effect. TcPO2 was measured in fibrotic areas of affected arms and in corresponding sites on non-affected arms of 15 women with unilateral arm lymphedema before and after CDP therapy sequences. Fibrosis was assessed by indentation recovery times (IRT) after applying an indenter-like device to tissue. Volumes and edema percentages were determined from circumferences using automated software calculations. Treatment significantly (p < 0.01) reduced arm edema from 28.6 +/- 22.9% to 18.1 +/- 17.7%(mean +/- SD) and fibrotic segment edema from 42.6 +/- 30.1% to 25.0 +/- 20.4%, and softened fibrotic tissue judged by reductions in IRT (88.7 +/- 60.7 sec vs. 23.1 +/- 38.8 sec, p < 0.001). TcPO2 did not differ between arms initially and did not change with treatment, being 60.1 +/- 8.8 mmHg at the start and 61.8 +/- 9.2 mmHg at the end of treatment. Thus, despite significant amounts of initial edema, TcPO2 was not initially less in affected arms nor was it changed by therapy that improved both edema and fibrosis.
Medical Faculty, Saratov State Medical University, Department of Vascular Surgery, Clinical Hospital No. 1, Saratov, Russia.
Altogether 112 patients over 50 years of age suffering from varicosity and chronic trophic ulcers of the distal limb segments were examined. The work was based on an analysis of the microcirculatory flow in lower limb tissues (laser Doppler flowmetry, BLF 21 system, Transonic Systems Inc., USA) and on the evaluation of tissue metabolism by measuring partial oxygen and carbon dioxide tension (percutaneous polarography; TCM-3 system, Radiometry Company, Denmark). The postischemic and orthostatic tests were used to assess the functional microcirculatory reserve. The data obtained indicate local tissue hypoxia in elderly patients with venous trophic ulcers associated with an increase of the basal flow only in the lower third of the leg. Venous trophic ulcers are marked by a significant reduction of partial oxygen tension in the tissues adjacent to the area of trophic ulcers to 4.3+/-0.5 mm Hg on the average in the presence of the low functional microcirculatory reserve. Local tissue hypoxia in the area of trophic ulcers, which develops despite an increase of blood inflow to the microcirculatory bed evidences inhibition of tissue flow and activation of the arterio-venular bypasses. The results obtained in the course of the study allow to optimize the treatment policy in elderly patients suffering from venous trophic ulcers. In addition to the measures lowering venous hypertension, the treatment should include correction of microcirculatory disorders, which is to be carried out in the pre- and postoperative periods.
Age-related changes in microvascular blood flow and transcutaneous oxygen tension under Basal and stimulated conditions.
National Ageing Research Institute, The University of Melbourne, Poplar Road Parkville, Melbourne Victoria, 3052.
BACKGROUND Adequate cutaneous microvascular blood flow and tissue oxygen tension are important prerequisites for successful tissue repair. The efficacy of tissue repair decreases with age and is linked to the age-related functional decline of unmyelinated sensory neurons that are important for inflammation and tissue repair. However, available information on the effect of these neuronal changes on microvascular blood flow and tissue oxygen tension is limited, particularly under control and injury conditions. The authors had two aims in this study:(a) to assess age-related changes in the relationship between microvascular blood flow and tissue oxygen perfusion under basal and two different stimulated conditions (sensory dependent and sensory independent), and (b) to clarify the biological meaning of transcutaneous partial pressure of oxygen (tcPO2) measurements. METHODS The effects of a sensory-independent vasodilator (acetylcholine) and a sensory-dependent vasodilator (capsaicin) on microvascular blood flow and oxygen perfusion in persons of different ages were measured. Laser Doppler flowmetry and a commercially available transcutaneous oxygen monitor (with sensors set at 39 degrees C and 44 degrees C) were used. Healthy volunteers were recruited: 11 young, 14 middle aged, and 19 older. RESULTS Under basal conditions (skin temperature, 37 degrees C to 39 degrees C), both basal blood flow and tcPO2 increased with increasing age. However, with the sensor set at 44 degrees C, tcPO2 showed a significant decrease with age. Acetylcholine increased blood flow approximately equally in the three age groups. Capsaicin increased blood flow and tcPO2 in all age groups, with the young showing a greater increase compared with the older participants. CONCLUSIONS The age-associated changes in basal and stimulated microvascular blood flow and tcPO2 could be attributed in part to altered neuronal function. Measuring tcPO2 at 39 degrees C showed a trend toward an increase with age. In contrast, a decrease with age was observed when tcPO2 was measured at 44 degrees C, a temperature sufficient to activate sensory nerve endings. The results may reflect a decline in sensory nerve function with age rather than a decrease in oxygen delivery for vascular reasons. This is supported by the complementary data showing a significant age-related decrease in stimulated blood flow in response to capsaicin, with no change in the response to the sensory-independent vasodilator acetylcholine. Thus, for clinical purposes, data obtained using the tcPO2 monitor should be interpreted with full knowledge of the conditions under which the measurements were made. Furthermore, for scientific purposes, the tcPO2 monitor could be used to assess sensory nerve function when sensors are heated to 44 degrees C.
Improvement of cutaneous microcirculation and oxygen supply in patients with chronic venous insufficiency by orally administered extract of red vine leaves AS 195: a randomised, double-blind, placebo-controlled, crossover study.
Ulrich Kalus, Juergen Koscielny, Alexandre Grigorov, Eckhard Schaefer, Hubertus Peil, Holger Kiesewetter
Institute for Transfusion Medicine, University Clinic Charité, Berlin, Germany.
OBJECTIVE: To investigate the effect of the red vine leaf extract AS 195 on cutaneous microvascular blood flow, transcutaneous oxygen pressure (tcpO2), and leg oedema in patients with chronic venous insufficiency (CVI). DESIGN AND PATIENTS: The study was a randomised, double-blind, placebo-controlled, crossover trial for which 129 men and women, aged > or =18 years, with CVI stage I or II were screened. Seventy-one fulfilled the inclusion criteria and were randomised. INTERVENTIONS: A total of 71 patients were divided into two groups. The first group (n = 36) received AS 195 360mg once daily during a first 6-week treatment period, followed by a 4-week placebo washout period and then placebo during the second 6-week treatment period. The second group (n = 35) started with placebo and received AS 195 360mg after the placebo washout. The cutaneous microvascular blood flow in the malleolar region was measured using a newly developed laser Doppler device. TcpO2 was measured using a solid-state electrode. RESULTS: After 6 weeks, patients in the AS 195 group had increased microvascular blood flow values (+241.8 +/- 18.7 arbitrary units [AU] versus a decrease of -41.0 +/- 18.7AU in the placebo group; p < 0.0001). Oxygen increased to 1.35 +/- 0.97mm Hg (placebo: decrease of -7.27 +/- 0.97mm Hg; p < 0.0001). After 6 weeks of treatment the leg circumference was decreased (ankle level: by -0.39 +/- 0.09cm versus +0.29 +/- 0.09cm; p < 0.0001; calf level: by -0.54 +/- 0.05cm versus +0.14 +/- 0.05cm; p < 0.0001). CONCLUSION: The administration of AS 195 improved objective symptoms of CVI and may prevent CVI deterioration.
Improvement of microcirculation and healing of venous hypertension and ulcers with Crystacide. Evaluation of free radicals, laser Doppler flux and PO2. A prospective-randomized-controlled study.
G Belcaro, M R Cesarone, A N Nicolaides, G Geroulakos, A Di Renzo, M Milani, A Ricci, R Brandolini, M Dugall, I Ruffini, U Cornelli, M Griffin
Irvine2 Vascular Laboratory and Physiology, Department of Biomedical Sciences, Chieti University, San Valentino Vascular Screening Project, Italy.
In 20 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of a new compound, applied onto the skin (Crystacide) were assessed in a randomized, controlled study. Duplex scanning was used to assess the presence of venous obstruction and incompetence, and microcirculatory methods were used to assess and quantify venous microangiopathy and to follow up subjects after local treatment with Crystacide. Laser Doppler flowmetry (LDF) was used to assess skin perfusion in association with transcutaneous (tc) partial pressure of oxygen (PO2) measurements. Local plasma free radicals (PFR) were evaluated in the area surrounding the venous ulcer, with the D-Rom test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatment: PO2 was increased, PFR and LDF were decreased (flux increase is associated with venous hypertension), and the ulcer area was significantly smaller at 10 days in the Crystacide group in comparison with the placebo group (p<0.05). In conclusion, in venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals improving healing.
Department of Dermatology, Ruhr-University Bochum, Bochum, Germany. M.Stuecker@derma.de
It has been known since the nineteenth century that oxygen is taken up by the human skin. With a newly developed sensor it became possible to examine the influence of the vascular supply on the oxygen flux into the skin, tcJ(O2). tcJ(O2) was measured optically by determining the oxygen partial pressure difference, DeltapO2 across a diffusion test membrane, which itself was brought into close contact to the skin surface. Under these conditions DeltapO2 is proportional to the tcJ(O2). The skin perfusion was varied by the application of a hyperemizing ointment on the abdomen of 12 volunteers and by suprasystolic occlusion at the thigh of 20 volunteers. The tcJ(O2) was measured at a temperature of 33 degrees C of the humid skin. It was compared with the skin perfusion monitored by laser Doppler flow, and the capillary oxygen supply measured by transcutaneous partial pressure of oxygen, tcpO2, at an electrode temperature of 37 degrees C. The transcutaneous O2 flux produced a distinct DeltapO2 of 81.8 +/- 8.2 Torr (abdomen) and 72.8 +/- 12.3 Torr (ankle). In hyperemic skin on the abdomen the O2 flux was reduced (DeltapO2 = 57.7 +/- 10.6 Torr). The tcpO2 increased from 8.7 +/- 10.7 to 35.1 +/- 16.9 Torr. During suprasystolic occlusion, DeltapO2 increased by 6.4 +/- 2.3 Torr, whereas laser Doppler flow and tcpO2 decreased significantly. These results indicate that the total oxygen supply of the epidermis and the upper dermis is guaranteed even if the perfusion varies.
A new measuring device for non-invasive determination of oxygen partial pressure and oxygen conductance of the skin and other tissues.
Bereich Klinische Physiologie Private Universität Witten/Herdecke, Germany.
About fifty percent of the oxygen consumption of the skin is supplied by diffusion through the surface. This portion of the skin oxygen supply becomes of high importance in case of arterial occlusion. The oxygen permeation coefficient (P) of the upper layers and the oxygen pressure field within the skin determine the diffusive oxygen uptake from the outside. To our knowledge, the permeation coefficient (P) until now was only estimated by indirect methods of little practicability (Baumberger et al., 1951; Eberhard et al., 1978). An oxygen partial pressure of the skin is conventionally measured by modified CLARK type electrodes. A disadvantage of this so-called transcutaneous electrode is its oxygen consumption and the fixed coupling of the consumption with the oxygen pressure to be determined. Therefore the measurement always induces a systematic error (the so-called stirring effect) which depends, among other factors, on the oxygen availability of the skin under the electrode. The new device combines a consumption-free oxygen partial pressure detector on the basis of luminescence quenching by oxygen with an independently working specific oxygen consumer realized by an active galvanic chain (silver-lead element). The chain permits setting any oxygen mass flow (mO2) in a certain range by varying the electrode current choosing different resistors within the electrical circuit. According to the diffusion law, the surface oxygen pressure (ePO2) being measured is a linear function of the oxygen flow (mO2) directed to the cathode: ePO2 identical to -(1/P).(mO2/A)+ icPO2; A: area under the cathode. The intracutaneous oxygen partial pressure (icPO2) is a virtual quantity defined by the equation given. Only by using an active electrode different oxygen mass flows can be set and so the oxygen conductance of the upper skin layers can be assessed. First experiments on human skin in the gluteal region of an adult delivered an estimated value of the permeation coefficient (P): 2.2.10(-5) ml O2 (STPD)/(atm.s.cm2) at 42 degrees C skin surface temperature; the intracutaneous partial pressure obtained was 5.5 kPa (41 mmHg)(STPD:"standard temperature pressure dry" conditions of the gas). At 42 degrees C skin temperature no burning occurs. The determined O2-conductance is in the same range as estimated formerly (see above). The intracutaneous oxygen partial pressure determined seems to be a realistic value of the tissue at 42 degrees C. By in vitro measurements with technical membranes the new device and procedure was validated giving precise values of the oxygen conductance. Hence the new method may be used for calibration of the oxygen flux optode (Holst et al., 1993). The O2-permeation coefficient (P) could be an important parameter for evaluating dermatological applications (which attempt to increase P) in the treatment of local dermal oxygen deficiency. The intracutaneous oxygen partial pressure found is a reasonable value for a surface temperature of 42 degrees. Because of the independence of the O2-partial pressure determined and the O2-consumption the new device exhibits no stirring effect and it provides more insight into the limitations of conventional transcutaneous oxygen measurement.