Biomedical subjects
Publications and source records attributed to M Peschen.
For the elimination of chronic ambulatory venous hypertension, sclerotherapy and surgical measures are employed in addition to compression treatment. These various measures should always be used in combination with each other. In the present article, one of a series, indications, contraindications and the practicalities of sclerotherapy are discussed in detail.
At the core of chronic venous insufficiency (CVI) is valvular incompetence affecting the large veins, which results in ambulatory venous hypertension. Recent research has revealed the pathophysiological stages involved: damage to the endothelium of the vein, leukocyte trapping and, finally, inflammatory reconstruction of the vessel wall. Lymphangiopathy involving the small and large lymph vessels is always present. One of the measures capable of influencing elevated venous pressure is compression therapy, which is discussed in detail in the present article. Drug treatment is a rational supplement to curative therapeutic approaches to chronic venous insufficiency that in mild-to-moderate cases, can result in an alleviation of symptoms similar to that achieved with compression therapy.
Paratibial fasciotomy has been employed since 1981 to treat patients with chronic venous insufficiency (CVI) and therapy-resistant leg ulcers with severe lipodermatosclerosis. The characteristic morphological changes in CVI were evaluated shown before and after paratibial fasciotomy using computerized tomography (CT) and magnet resonance tomography (MRT). 10 patients (6 female, 4 male) were examined by CT and MRT pre- and postoperatively. Preoperatively there is a clear thickening of the dermis and subcutaneous field. In addition, the area around the achilles tendon is thickened, the fasciae are enlarged and the muscles of the lower leg show an increase of fatty tissue. A decrease of the cutaneous and subcutaneous thickening is seen postoperatively. The fasciotomy split is visible in most patients.
BACKGROUND: Leukocyte binding to endothelial cells (ECs) is thought to contribute to the pathogenesis of leg ulcers caused by chronic venous insufficiency. In other systems, such binding is mediated by the interaction of adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule- (VCAM-1) and E-selectin (on ECs), and leukocyte function-associated antigen-1(LFA-1) and very late activated antigen-4 (VLA-4) (on Leukocytes). OBJECTIVE: Our purpose was to determine whether an increased expression of these adhesion molecules contributes to the pathogenesis of chronic venous insufficiency. METHODS: Twenty-seven biopsy specimens of inflamed dermatoliposclerotic skin adjacent to venous leg ulcers were stained immunohistochemically with monoclonal antibodies against ICAM-1, VCAM-1, LFA-1, VLA-4, and E-selectin. Staining intensity was compared with that of normal skin. RESULTS: Specimens of leg ulcers caused by chronic venous insufficiency showed increased expression of ICAM-1 and VCAM-1 but not of E-selectin on The expression of LFA-1 and VLA-4 on perivascular leukocytes was increased dramatically in comparison to healthy skin. CONCLUSION: Upregulation of ICAM-1 and VCAM-1 on ECs may contribute to the increased adherence and extravasation of LFA-1 and VLA-4-positive leukocytes in chronic venous insufficiency.
Present investigations regarding the pathogenesis of chronic venous insufficiency (CVI) are focusing on microvascular changes. The aim of our investigation was to examine the correlation between the thickness of pericapillary type IV collagen depositions, basal membrane alterations and transcutaneous oxygen tension (TcPO2) in CVI-patients. Histochemical and immunohistochemical investigation of the capillary basal membrane was performed on 15 biopsies from normal controls, as well as 30 patients with CVI stage I and III (classification by Widmer & Stähelin). In all subjects TcPO2 was measured just prior to biopsy procedures in exactly the same area where the specimen was subsequently excised. The microscopically measured thickness of the collagen IV layer and the basal membrane was increased significantly in patients with CVI. Specimens from normal controls showed a collagen IV layer thinner than 0.1 micron. Patients with CVI stage III revealed strong collagen IV depositions between 0.2 and 0.3 microns. Comparison between TcPO2 and histological findings in the measured ares showed oxygen pressure varying from 62 mmHg (SEM 4.94 mmHg) in normal controls, down to 13 mmHg (SEM 3.39 mmHg) in patients with thick collagen IV layers. Besides an increased collagen IV layer, microvascular thrombosis and a thickened basal membrane have to be considered for impaired capillary perfusion.
Pentoxifylline, a methylxanthine derivative, has been shown to inhibit T-cell-mediated cutaneous immune response by yet ill-understood mechanisms. Because cell adhesion to endothelial cells is a critical step in the initiation of such immune responses, we analyzed whether pentoxifylline would affect this process. To address this issue, adhesion of mouse T-lymphoma cells (TK-1) to mouse endothelioma cells (eEnd.2), either untreated or stimulated with tumor necrosis factor-alpha (TNF alpha), was studied. Pentoxifylline reduced the ability of endothelioma cells stimulated with different concentrations of TNF alpha, but not of untreated endothelioma cells, to bind T-lymphoma cells in dose-dependent (10(-5)-10(-3) M) fashion. Selective incubation of either endothelioma cells or T-lymphoma cells revealed that pentoxifylline acted exclusively on the endothelioma cells, even when added after TNF alpha stimulation. We questioned whether pentoxifylline suppressed T-lymphoma cell/endothelioma cell interactions by interfering with adhesion molecules expressed by either cell. However, as determined by flow cytometry, pentoxifylline did not alter TNF alpha-induced upregulation of intercellular adhesion molecule-1 or vascular cellular adhesion molecule-1 on endothelioma cells nor did it affect constitutive CD11a, CD18, or alpha 4-integrin expression on T-lymphoma cells, suggesting that rather than affecting quantitative expression of these adhesion molecules, pentoxifylline might modulate their avidity. We conclude that pentoxifylline in therapeutically achievable concentrations is a potent inhibitor of TNF alpha-induced T-lymphoma cell adhesion to endothelioma cells. This finding may account, at least in part, for the recently discovered anti-inflammatory action of pentoxifylline.
Prostaglandins have been shown to be involved in the suppression of contact hypersensitivity (CHS) by so-far ill understood mechanisms. T-cell migration across the lining of cytokine-activated endothelial cells (EC) is thought to be a central step in the initiation of CHS. The aim of our investigation was therefore to examine whether prostaglandin E1 (PGE1) influences cytokine-induced TK-1 mouse T-cell lymphoma adhesion to eEnd.2 mouse endothelioma cells. Here, we report that PGE1 (10(-12)-10(-8) M) dose-dependently reduced TNF alpha-induced T-cell binding, while TNF alpha-unstimulated adhesion was not affected. To test whether PGE1 acted primarily on T-cells or on EC, they were separately pretreated with PGE1 prior to the adhesion assay. Selective PGE1 pretreatment of eEnd.2, but not of TK-1 dose-dependently inhibited TNF alpha, stimulated T-cell adhesion. Since binding of TK-1 to TNF alpha-treated eEnd.2 is mediated by the interaction of ICAM-1 and VCAM-1 (on EC) with their receptors LFA-1 and VLA-4 (on T-cells), we further investigated whether PGE1 would modulate the expression of these molecules. FACS-analysis revealed PGE1 to inhibit TNF alpha-induced upregulation of ICAM-1, but not of VCAM-1 on EC. Furthermore, constitutive LFA-1 and VLA-4 expression on T-cells was not affected by PGE1. We conclude that PGE1 supresses T-cell adhesion to EC by selectively inhibiting TNF alpha-induced upregulation of ICAM-1 on EC. This may be one mechanism by which prostaglandins suppress immune responses requiring T-cell EC interactions such as contact hypersensitivity in skin.
Linear basal cell carcinoma is a rare morphologic variant of basal cell carcinoma. We present two cases of linear basal cell carcinoma. Both cases, treated by Mohs' micrographic surgery, demonstrated that there was lateral spread of the tumor that was not clinically present.
A duplex ultrasonographic system was used to examine the common femoral artery in left and right legs of 49 fit young men and 15 fit young women, to find out the normal blood flow in the human leg during rest. By this method the diameter of the vessel and the time average velocity could be measured and the blood flow calculated. Each person underwent three examinations of each leg after 10-min rests. The average diameter of the common femoral artery was 91 +/- 10 mm (95 mm in the men and 80 mm in the women), the average blood flow 226.2 +/- 82.1 ml/min (235.9 ml/min in the men and 189.6 ml/min the the women). Compared with other methods used for femoral blood flow studies, we found the duplex ultrasound system reliable, non-invasive, and infinitely repeatable. This method therefore also seems appropriate for clinical studies. In a few tests carried out in trauma patients we found a pronounced increase in blood flow after a few days, and also an expected increase in a patient with arterio-venous fistula and an expected decrease in one with arterial occlusive disease. These examinations were performed to establish a method for further examinations of long-lasting blood flow alterations in trauma patients, which will be reported in another paper.
A duplex ultrasound system was used to examine the blood flow of the common femoral artery in ten young patients with fractures of the lower extremities. Two patients had fractures of both legs. In eight patients the blood flow in the injured leg was comparable with that in the not injured leg. The flow alterations were measured on 3-7 different days over a period of 6-224 days after trauma. All patients showed a significant (to twice or three times that before injury) increase in blood flow in the injured leg a few days after trauma and/or operation, whereas the blood flow in the uninjured leg remained the same or even decreased a little. In the case of undisturbed fracture healing the change in blood flow disappeared within 8-12 weeks, corresponding to fracture consolidation. When fracture healing was delayed and/or further operations on the injured leg were necessary, the blood flow was increased for much longer. The hemodynamics of an injured extremity are compared with those reported elsewhere in the literature. The increased demand for oxygen or energy can explain the changes only in part. Another function of the reflective increase in blood flow could be the temperature increase in the extremity.
Malignant cylindroma may develop via malignant transformation of cylindroma in rare instances or may develop de novo in others. We present a case of malignant cylindroma located on the left parietal-occipital scalp that was treated twice by Mohs micrographic surgery in an attempt to excise the tumor completely and to minimize the excision of normal tissue. Our case is the sixteenth reported case of malignant cylindroma in the world literature.
Growth factors which act as signalling peptides through specific cell surface receptors are involved in functions such as cell proliferation, migration, and differentiation. Here, we report on alterations of the epidermal growth factor receptor (EGFR), basic fibroblast growth factor (bFGF) and transforming growth factor beta3 (TGF-beta3) expression patterns in the skin at various stages of chronic venous insufficiency (CVI). Thirty punch biopsies were taken from patients with CVI and growth factors or the growth factor receptor were detected by indirect immunofluorescence and immunoperoxidase techniques. EGFR, bFGF, and TGF-beta3 expression is strongly increased in the stroma of venous eczema and in leg ulcer skin, and to a lesser extent in the dermis of patients with lipodermatosclerosis. Venous eczema and lipodermatosclerosis epidermis show an elevated EGFR and bFGF synthesis throughout all strata. In the different CVI stages, telangiectases and reticular veins and pigmentation EGFR and bFGF staining are limited to the basal layer. We conclude that the alterations in the expression of EGFR, bFGF and TGF-beta3 precede changes in the affected skin within progressing stages of CVI. The exact mechanisms of growth factor involvement in the pathogenesis of venous ulceration remain to be resolved.