Dysregulated L-selectin expression on lymphocytes in patients with chronic venous insufficiency.

In this study we analysed blood samples taken from the dorsalis pedis vein and a brachial vein of 11 healthy test persons and 8 patients with venous leg ulcer under experimental venous hypertension in order to examine changes in the expression of leukocyte adhesion molecules (LFA-1 (CD11a), Mac-1 (CD11b), p150,95 (CD11c), CD18, VLA-4 (CD49d) and L-selectin (CD62L)) which are involved in the adhesion steps of leukocytes to endothelial cells for transmigration into tissues. Under orthostatic stress, lymphocytes in controls collected at the foot level showed a significant reduction in the expression of L-selectin (p=0.002), compared to those of patients. This finding suggests that venous stasis negatively influences the expression of L-selectin on leukocytes only in healthy volunteers. Patients with chronic venous insufficiency seem to suffer from a specific defect in the regulation of L-selectin shedding under orthostatic stress.

Morphoea is neither associated with features of Borrelia burgdorferi infection, nor is this agent detectable in lesional skin by polymerase chain reaction.

BACKGROUND: The aetiology of morphoea is still unknown. Borrelia burgdorferi as a causative agent of morphoea has been discussed since 1985, but the relationship remains uncertain. OBJECTIVES: We aimed to find evidence for infection with B. burgdorferi by combined evaluation of different clinical and laboratory data in a group of 54 patients with morphoea. METHODS: In each patient, an evaluation of the case history was performed with regard to infection with B. burgdorferi, using a standardized questionnaire. Questions focused on previous tick bites and skin changes suspicious for erythema migrans (EM). The case history data of 52 patients were compared with those of 104 matched control subjects and of 25 patients with acrodermatitis chronica atrophicans (ACA). Serological examinations were performed in 53 patients with morphoea. Furthermore, lesional skin was examined for borrelial DNA in 33 patients, using nested polymerase chain reaction (PCR) for the ospA and the borrelial rRNA gene. RESULTS: Results of the questionnaire showed no differences between patients with morphoea and matched controls. In contrast, patients with ACA showed a much higher prevalence of tick bites and skin changes suspicious for EM as compared with patients with morphoea. Serological examination was positive in only one patient with morphoea alone and in two additional patients with coexistent ACA. No borrelial DNA was detected by PCR in lesional skin of 33 patients with morphoea. CONCLUSIONS: No evidence was found for B. burgdorferi infection in patients with morphoea.

Biomechanical stimulation therapy. A novel physiotherapy method for systemic sclerosis.

To improve the mobility of joints, particularly of the finger joints and the mandibular joint, and to reduce the edema of the skin, various physical therapies have to be used in patients with SSc. As the quality of patients' life depends on the use of their fingers and of their mouth, these therapeutics belong to the basic measures in the treatment of SSc. In addition to the manually performed lymph drainage a new method, the biomechanical stimulation therapy, has proven to be efficacious to improve the mobility of the joints and to reduce the edema in SSc-patients. By devices of various size, longitudinal vibrations are transduced to patients' body: finger, hand, face, mandibular joint, the oral mucosa, the legs and the trunk. In 6 patients we found: significant (p < 0.05) increase of skin score, grip strength, mobility of joints (10-30%). No side effects were observed. We conclude from these data, that skin, mucosa, joints and patients' quality of life are improved by the biomechanical stimulation therapy in a clinical relevant degree.

The effect of compression therapy on venous haemodynamics in pregnant women.

OBJECTIVE: To study the influence of compression on the haemodynamics of the deep venous system in pregnancy. DESIGN: A prospective, observational study. SETTING: The phlebological unit of the department of dermatology at a university hospital. POPULATION: Fifteen pregnant women with no previous signs of chronic venous insufficiency. METHODS: Parameters of the venous pump function were assessed by strain-gauge plethysmography. Blood flow velocity, flow volume and vessel diameter in the superficial femoral vein were measured by duplex sonography. All examinations were performed with and without applied compression stockings (25-32 mmHg) at two different stages of gestation and after delivery. In addition, subjective symptoms were graded. RESULTS: Venous pump function improved and refilling time lengthened significantly when compression was used during gestation and postnatally. Duplex sonography showed an increase in blood flow velocity and flow volume in the superficial femoral vein with applied compression; the vessel diameter increased slightly. Subjective symptoms of the leg, graded on an arbitrary scale, were reduced by regular compression therapy. CONCLUSION: Our results indicate that compression improves the clinical symptoms of venous congestion and the venous haemodynamics of the legs during pregnancy and in the postpartum period. Thus, the regular use of compression during pregnancy and the puerperium may reduce the incidence of thromboembolic events.

Local cold exposure test with a new arterial photoplethysmographic sensor in healthy controls and patients with secondary Raynaud's phenomenon.

Local cold exposure tests are used to diagnose cold-induced vasospastic disorders and to evaluate therapeutic success. We investigated the pulsatile signal detected with a newly developed arterial photoplethysmography (APPG) method and the signal change induced by local cold exposure using a temperature-controlled finger holder, comparing it with laser Doppler flux (red and green laser, rLDF and gLDF) and red blood cell velocity measured in nailfold capillaries (CBV). Ten healthy volunteers and 10 age- and sex-matched patients suffering from Raynaud's phenomenon due to systemic sclerosis were investigated using a moderate cooling temperature of 16 degrees C for 5 min. All signals were recorded simultaneously. The results show a significant reduction of CBV (P < 0.0001), rLDF (P < 0.0003), and gLDF (P = 0.0214) during cooling and characteristic changes in the APPG signal (for instance a decrease in pulse wave amplitude; P < 0.0001). Significant differences in the APPG amplitude could be detected under resting conditions; at cooling temperatures there were also significant differences in CBV and APPG. The temperature-controlled finger holder with its built-in APPG probe appears to be a useful tool for evaluating the effect of local cooling on finger skin perfusion and differentiating between healthy controls and patients with secondary Raynaud's phenomenon due to systemic sclerosis. The gLDF signal was rather weak, limiting its value in cold stress tests. The differences between controls and patients in CBV were somewhat smaller than in previous studies, suggesting the advantage of lower local cooling temperatures, e.g., 12 degrees C.

[Questionable effectiveness of autologous platelet growth factors (PDWHF) in treatment of venous ulcers of the leg]. / Fragliche Wirksamkeit autologer thrombozytärer Wachstumsfaktoren (PDWHF) in der Behandlung venöser Beinulzera.

Chronic venous insufficiency (CVI) can cause ulcers of the lower limb having the character of a full thickness wound involving the subcutaneous tissues and fat. Healing requires wound contraction, connective tissue formation and finally reepithelialization. To induce wound healing, on an underlying disturbed environment due to longterm effects of CVI, artificial stimuli may be needed. In a placebo controlled study we tried topical application of autologous PDWHF (platelet derived wound healing factors), to achieve ulcer healing and improve the microangiopathy surrounding of the ulcer area, as there are decreased number of skin capillaries and reduction in cutaneous vascular reserve. Alterations of cutaneous circulation during the course of the study were documented by capillaroscopy, transcutaneous oxygen pressure and laser Doppler flux (LDF) measurements. We were able to recruit 15 patients a I suffering from chronic nonhealing venous stasis ulcers. Eleven of the 15 patients agreed to participate in a placebo-controlled double blind study, whereas 4 patients agreed to participate only if they would be treated with PDWHF. The median age and duration of ulceration of the 6 patients (3 male/3 female) treated with placebo were 71 years and 1089 days. The median age and duration of ulceration of the 9 patients (1 male/8 females) treated with PDWHF were 66 years and 732 days. Duration of therapy for the PDWHF group was 91 days, as compared to 154 days for the placebo group. Despite 2 completely healed ulcers, the expensive treatment did not reveal any significant clinical advantage. In den PDWHF group an ulcer area of 26.9 cm2 was measured at the beginning, of 26.2 cm2 at the end; in the placebo group, 34.7 cm2 and 35.5 cm2. The nonsignificant increase of the capillary density at the ulcer border in the active group as well as the increase in the tcPO2, in contrast to little change in both parameters in the placebo group, suggests neoangiogenic abilities to PDWHF, secondarily leading to a better blood distribution with higher oxygen tension.

[Physical therapy of venous diseases]. / Physikalische Therapie bei Venenerkrankungen.

If physical therapy like compression stockings and supervised outpatient vascular exercise programmes are begun early, subjective complaints can be alleviated and ankle flexibility and venous drainage can be improved. Incapacitating congestive diseases such as dermatolipofasciitis and ulcus cruris can be avoided. Once chronic venous congestion has led to joint capsule atrophy, stiffening of the ankle and muscular atrophy in the lower leg, expensive therapeutic measures involving professional physiotherapeutic care become unavoidable. In our own experience physiotherapy is most effective in combination with biomechanical stimulation therapy. Once the patient's equine gait has been eliminated, conventional walking exercise can gradually restore a physiological gait. After successful physiotherapy, an outpatient vascular exercise programme combined with optimized compression therapy contribute decisively to long-term therapeutic success in patients with advanced chronic venous insufficiency. Like coronary sports, vascular exercise programmes are covered by public health insurance. Along with compression therapy, they represent an efficient, cost-effective basic therapy for chronic venous insufficiency.

[Quality of life in chronic venous insufficiency (CVI). Results of a study with the newly developed Tübingen Questionnaire for measuring quality of life of patients with chronic venous insufficiency]. / Lebensqualität bei chronisch venöser Insuffizienz (CVI). Ergebnisse einer Untersuchung mit dem neu entwickelten Tübinger Fragebogen zur Messung der Lebensqualität von CVI-Patienten (TLQ-CVI).

Across the boundaries of the medical specialties we have realized how important the concepts of quality of life and disease-related coping behavior are to understand the patients' subjective perception of the medical condition and its treatment. Although standardized instruments are already available for different medical indications and even in the related fields of peripheral vascular and cardiac diseases, phlebology still lacks standardized concepts for evaluating quality of life and/or disease-related coping behavior in patients with chronic venous insufficiency (CVI). We report on a newly developed instrument specifically designed for recording quality of life in patients with CVI. It not only meets the requirements of psychometric standards, but has also proven its applicability in clinical use. The "Tübingen Questionnaire for measuring Quality of Life in patients with CVI (TLQ-CVI)" and the results of a study on quality of life in 142 patients with various stages of chronic venous insufficiency are presented. It was possible to distinguish between Stage I/II and Stage III CVI patients with respect to parameters such as "leg complaints" and "day-to-day fears and worries". These convey clinically relevant insights into the patient's subjective perception of the disease and how they cope. The information gathered provides a set of reasonable target scores for clinical studies presently being carried out at various study centers in Germany incorporating the TLQ-CVI.

Improvement of acral circulation in a patient with systemic sclerosis with stellate blocks.

We report on a 77-year-old male patient with systemic sclerosis. He suffered from secondary Raynaud's phenomenon on the basis of systemic sclerosis. Medical treatment in the past, including the administration of calcium-channel blockers, pentoxifylline and intravenous prostaglandin therapy, was unsuccessful and the clinical situation became worse. In a final effort stellate blocks were performed over a period of several weeks and, for the first time, there was lasting clinical benefit. Complaints and Raynaud's attacks abated significantly, as documented by local cold exposure tests. Therapeutic benefit from stellate blocks in a patient with systemic sclerosis is described here for the first time.

[Development of a computer-assisted thermoelectric Peltier cold test procedure with integrated photoplethysmography unit for noninvasive evaluation of acral skin circulation]. / Entwicklung eines computerunterstützten thermoelektrischen Peltier-Kältetestverfahrens mit integrierter photoplethysmographischer Messeinheit zur nichtinvasiven Evaluation der akralen Hautdurchblutung.

Local cold provocation tests are an important, non-invasive diagnostic tool for collecting information about skin perfusion during exposure to cold. In patients suffering from vasospastic circulatory disorders such as Raynaud's phenomenon, it is of particular importance to be able to collect data about acral circulation during the cooling test in the asymptomatic intervals between naturally occurring attacks. By carrying out a series of cold provocation tests, for example, patient response to a newly initiated therapy can be assessed. Here we present a recently developed, computer-aided thermoelectric Peltier device with an integrated finger holder for carrying out local cold provocation tests. The electronic control unit of the Peltier element make it possible to cool or heat to predefined temperatures. At the same time, the temperature of both the finger holder and the skin can be measured. A photoplethysmographic sensor is also integrated within the device, enabling the response of the pulse waves to the controlled temperature changes to be monitored accurately. It is also possible to measure simultaneously laser Doppler flux and capillary pressure in the nailfold and to perform nailfold capillaroscopy to determine red blood cell velocity. The new device provides us with the technical means to study the interrelationship between acral skin perfusion and the thermal regulation of the skin.

Cutaneous inflammation limited to the region of the ulcer in chronic venous insufficiency.

BACKGROUND: The role of inflammatory reactions in the pathogenesis of chronic venous insufficiency and the persistence of venous ulcerations is still not totally clear and remains a hotly debated topic. An investigation of the intensity and distribution of ICAM-1 expression and different inflammatory cells should help clarify whether inflammatory processes are limited locally to the area of the ulcer or if an upregulation can also be observed in clinically unaffected skin of CVI-III patients, as a sign of a primary inflammatory process. PATIENTS AND METHODS: We examined two skin areas in 10 patients with venous ulcerations. One area was at the border of the ulcer and another in clinically unaffected skin (distance from the ulcer: 12.6 +/- 5.1 cm). In addition skin specimens were obtained from the perimalleolar skin of 10 healthy controls. Our histological and immunohistochemical examinations were focused on inflammatory cells (B and T lymphocytes, macrophages, and mast cells) and on the adhesion molecule ICAM-1. RESULTS: A very strong expression of ICAM-1 could be seen at the border of the ulcer. This tissue also showed a dense infiltration, mainly by T lymphocytes and macrophages. In some cases the tissue was infiltrated by an increased number of mast cells. This is the typical picture of a chronic inflammatory reaction. Compared to healthy controls, the clinically unaffected skin of patients showed not an increased expression of ICAM-1 and only in some cases we could find a slight perivascular infiltrate of T lymphocytes. CONCLUSIONS: These data imply that the upregulation of endothelial adhesion molecules (ICAM-1) and dermal infiltration by T lymphocytes and macrophages in CVI-III patients is limited to the region of the ulcer, or at least to skin areas with a severe microangiopathy, and is part of a secondary elimination of necrotic issue (an 'injury and repair' process). These local chronic inflammatory reactions are certainly an important factor in the persistence and recurrence of venous ulcerations.

[Dynamic in vivo skin pressure measurement in quality control of compression stockings]. / Dynamische In-vivo-Anpressdruckmessung zur Qualitätskontrolle der Kompressionsstrümpfe.

The well-documented positive effect of compression stocking therapy on the venous macro- and microhemodynamics of the legs can only be attained if the stockings fit well. In order to determine the effective pressure exerted by compression stockings, we usually deleted in US journals. One can get this out of journal and author's address have developed a new measuring method based on piezoresistant microprobes and a microprocessor unit. With our 2-mm-thick, 5-mm diameter probe, the pressure between the compression stocking and skin can be measured at any location desired. A temporal resolution of 50 Hz makes it possible to carry out dynamic measurements while the patient is walking or performing exercises on tiptoes. Here we present 4 typical cases out of a total of over 80 which we have evaluated. We have decided empirically that the pressure exerted by a class-2 compression stocking on the skin at the height of the ankles (b-position) should not exceed 70 mm Hg while resting and a peak of 110 mm Hg while exercising on tiptoes. At the middle of the calf (c-position) these values should not exceed 60 mm Hg at rest and 80 mm Hg on tiptoes. The pressure should decrease from the distal to proximal direction in order to produce a drainage gradient. We have found empirically that a pressure gradient of 30-40% from the b to the c measurement is favorable. Too high a proximal pressure or too high a pressure on a part of the lower leg causes pain and swelling. Too low a pressure, on the other hand, does not produce the desired vascular effect and alleviation of symptoms. Although dynamic pressure measurements take about 20-30 minutes per leg, they markedly improve patient compliance with compression therapy.

[Cap image--a new kind of computer-assisted video image analysis system for dynamic capillary microscopy]. / Cap Image--ein neuartiges computerunterstütztes Videobildanalysesystem für die dynamische Kapillarmikroskopie.

We describe a newly developed multi-function video image analysis system for the computer-aided evaluation of capillaroscopic findings in microcirculation research. The Cap image analysis system comprises an IBM-compatible PC with a Matrox image processing card and real-time video tape digitalization. The video recorder is driven by a personal computer to which it is connected via an RS-232 interface. In contrast to currently available systems, the program presented here makes it possible to select any of several integrated image analysis functions, depending on the quality of the video image. Some examples of the analysis functions available are measurements of erythrocyte flow velocity using the line shift diagram method, the spatial correlation method, and the auto flying spot method. The standard features of the new program include a number of special functions and automatic movement correction. The system thus makes it possible not only to measure numerous morphological parameters such as capillary diameter, length, torquation index and capillary density, but also to perform video densitometric analysis, for example using fluorescent dyes.

[Vascular sports in ambulatory therapy of venous circulatory disorders of the legs. Diagnostic, therapeutic and prognostic aspects]. / Gefässsport zur ambulanten Therapie venöser Durchblutungsstörungen der Beine. Diagnostische, therapeutische und prognostische Aspekte.

In 33 patients with chronic venous incompetence (CVI) caused by primary varicoses or postthrombotic syndrome stage I-III (according to Widmer) the therapeutic benefit of 6 months of medically supervised physical exercise training was documented. During the training penud there was an improvement in subjective complains such as pain and tendency for edema in the legs. Mobility in the upper ankle joint was improved asuss as venous drainage function. Clinical benefit was achieved in the reduction of ulcer size; 7 of the 10 ulcers completely healed. Medically supervised physical exercise training and optimized compression therapy are basic therapeutic approaches in conservative treatment in chronic venous insufficiency. Costs are covered by the patient's health insurance company in Germany, as long as the exercise training is medically supervised.