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Biomedical subjects

W Vanscheidt

Publications and source records attributed to W Vanscheidt.

At least 55 records · Page 3Linked to original sources

The low molecular weight Dextran 40 inhibits the adhesion of T lymphocytes to endothelial cells.

Dextrans are complex colloidal macromolecules widely used as haemorrheologic substances and anti-thrombotic agents. Here we describe a novel function of Dextran 40 by demonstrating an inhibition of T lymphocyte adhesion to endothelial cells (EC). We applied an established microassay in which constitutive and tumour necrosis factor-alpha (TNF-alpha)-induced binding of mouse T lymphoma cells (TK-1) to mouse endothelioma (eEND.2) cells is mediated by the interaction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on EC with their counter-receptors the LFA-1 heterodimer (CD11a/CD18) and VLA-4 on T cells. Dextran 40 in therapeutically achievable levels (2-32 mg/ml) reduced both constitutive and TNF-alpha-stimulated TK-1 adhesion to eEND.2. Selective preincubation of eEND.2 or TK-1 revealed that Dextran 40 acted exclusively on the T cells. To explore further the mechanisms by which Dextran 40 interfered with TK-1 adhesion, their LFA-1 and VLA-4 expression was analysed by FACS. The surface expression levels of neither receptor were affected by Dextran 40. However, confocal microscopy revealed that Dextran 40 interfered with the activation-dependent capping and clustering of LFA-1 and VLA-4 on the surface of TK-1. We conclude that Dextran 40 inhibits the capacity of TK-1 T cells to adhere to eEND.2 endothelial cells and thus may be useful for therapeutic intervention in diseases associated with enhanced T lymphocyte binding to microvascular endothelium.

Animals↗

Lipodermatosclerosis is characterized by elevated expression and activation of matrix metalloproteinases: implications for venous ulcer formation.

Lipodermatosclerosis refers to skin induration of the lower extremities and is associated with patients preceding venous ulcerations. To better understand the pathogenesis of ulcer formation we investigated the expression of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in lipodermatosclerosis. By preparing biopsies from healthy skin and liposclerotic lesions, MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were analyzed by using reverse transcriptase-polymerase chain reaction, western blot, zymography, hydrolysis of [3H]labeled collagens, and immunohistochemistry. Our investigations provide evidence that mRNA and protein expression of MMP-1, MMP-2, and TIMP-1 were significantly increased in lipodermatosclerosis, whereas the total amount of MMP-9 and TIMP-2 mRNA and protein was not altered. Western blot of liposclerotic lesions revealed an inactive proMMP-1-TIMP-1 complex, whereas MMP-2 was prominent as an active 66 kDa band. Increased proteolytic activity of MMP-2 could be proven in lesional in comparison with healthy skin by zymography and [3H] collagen degradation. Increased diffuse staining was found for MMP-1 in the epidermis and dermis in comparison with controls. In lipodermatosclerosis, MMP-2 was predominantly localized in the basal and suprabasal layers of the epidermis, in perivascular regions, and in the reticular part of the dermis. Furthermore, MMP-2 was imbalanced by locally reduced expression of TIMP-2 in the basement membrane zone of lesional skin. Our findings indicate lipodermatosclerosis to be characterized by elevated matrix turnover.

Collagen↗

Psychosocial stress of patients with port wine stains and expectations of dye laser treatment.

BACKGROUND: Port wine stains can be treated successfully with the dye laser in most cases. The indication for treatment is made on the basis of the emotional stress arising from the port wine stain. Studies of the extent of psychosocial stress to date have led to contradictory results. OBJECTIVE: To address the question how many patients with port wine stain suffer psychosocial stress and how this group can further be characterized. Moreover, the specific expectations of treatment were to be elucidated. METHODS: During dye laser treatment, 76 patients with port wine stains were evaluated by questionnaires regarding (a) emotional well-being, (b) quality of life, (c) body perception and (d) disease-specific stress and expectations of therapy. RESULTS: Patients with port wine stains showed significantly higher emotional stress than healthy controls. They were particularly impaired in quality of life with respect to their social life and felt less attractive than a healthy control group. Patients with high emotional stress placed high hopes on the laser therapy with regard to chances of employment and social contacts. CONCLUSION: The data point to the need for thorough patient consultation prior to laser therapy in order to avoid excessive expectations. Psychological consultation is recommended for emotionally labile PWS patients.

Adult↗

Possible role of coagulation factor XIII in the pathogenesis of venous leg ulcers.

BACKGROUND: Aim of this placebo-controlled clinical study was to examine the expression pattern of coagulation factor XIIIa in patients with chronic venous leg ulcers and the impact of a 10 day topical factor XIII treatment on ulcer healing, leg ulcer size and radius reduction. PATIENTS AND METHODS: 24 patients were stratified into two groups, each consisting of 12 patients, with leg ulcers > 1.000 mm2, or < 1.000 mm2. Four patients of each study group were assigned to the control group (n = 8). All leg ulcers were treated by topical application of non-adhering dressings and compression therapy. Patients of the treatment group (n = 16) were treated by additional topical treatment off factor XIII twice daily for ten days. Immunohistochemical staining of leg ulcer specimens before and after treatment (day 10) was performed in all patients. RESULTS: The immunohistochemical staining of factor XIIIa in all specimens before and after therapy showed no significant increase in the expression of factor XIIIa. Comparison of the leg ulcer size, radius and daily radius reduction in the treatment and control group showed no significant differences in values of patients with leg ulcers > 1.000 mm2. However, a decreased leg ulcer size and radius was found in patients of the treatment group with more acute leg ulcers < 1.000 mm2 in contrast to patients with larger leg ulcers (daily ulcer radius reduction from day 0-10; 0.31 mm versus 0.13 mm, p < 0.015). CONCLUSIONS: These results indicate that locally applied factor XIII promotes especially wound healing of more acute smaller venous leg ulcers. Since immunohistochemical staining of factor XIIIa showed no significant differences before and after therapy, we propose that factor XIII is inactivated rapidly after local application on venous leg ulcers.

Administration, Topical↗

Analysis of lymphatic drainage in various forms of leg edema using two compartment lymphoscintigraphy.

The anatomical and functional status of the epifascial and subfascial lymphatic compartments was analyzed using two compartment lymphoscintigraphy in five groups of patients (total 55) with various forms of edema of the lower extremities. Digital whole body scintigraphy enabled semiquantitative estimation of radiotracer transport with comparison of lymphatic drainage between those individuals without (normal) and those with leg edema by calculating the uptake of the radiopharmaceutical transported to regional lymph nodes. A visual assessment of the lymphatic drainage pathways of the legs was also performed. In patients with cyclic idiopathic edema, an accelerated rate of lymphatic transport was detected (high lymph volume overload or dynamic insufficiency). In those with venous (phlebo) edemas, high volume lymphatic overload (dynamic insufficiency) of the epifascial compartment was scintigraphically detected by increased tracer uptake in regional nodes. In patients with deep femoral venous occlusion (post-thrombotic syndrome). subfascial lymphatic transport was uniformly markedly reduced (safety valve lymphatic insufficiency). On the other hand, in the epifascial compartment, lymph transport was accelerated. In those patients with recurrent or extensive skin ulceration, lymph transport was reduced. Patients with lipedema (obesity) scintigraphically showed no alteration in lymphatic transport. This study demonstrates that lymphatic drainage is notably affected (except in obesity termed lipedema) in various edemas of the leg. Lymphatic drainage varied depending on the specific compartment and the pathophysiologic mechanism accounting for the edema. Two compartment lymphoscintigraphy is a valuable diagnostic tool for accurate assessment of leg edema of known and unknown origin.

Adult↗

[Hereditary benign telangiectasia: a rare form of primary telangiectasia with successful treatment with flash-lamp-pumped pulsed dye laser].

We report about multiple cutaneous telangiectases occurring over 3 generations. The pattern of inheritance, the morphology of the lesions, and the absence of hemorrhagic episodes are consistent with an unusual variant of primary telangiectasia described as hereditary benign telangiectasia. Differential diagnosis and pathogenesis of this rare type of telangiectasia is discussed. The lesions have been treated with the flashlamp-pumped pulsed dye laser. The lesions were completely removed by two treatments. Six months later, the patient had no recurrence of the telangiectases. Without producing scars or permanent pigmentary changes a very good cosmetic result has been achieved and stigmatisation and psychic burden of this patient has been relieved.

Adult↗

[Involvement of the lymphatic system in primary non-lymphogenic edema of the leg. Studies with 2-compartment lymphoscintigraphy].

Two-compartment lymphoscintigraphy was developed to examine the sub- and epifascial lymphatics of the leg. Digital images were evaluated visually and semiquantitatively by calculating the uptake of activity within the lymph nodes. The data from patient groups with four different types of leg edema were compared with those of the control group to prove the involvement of the lymphatics in the non-lymphatic edema. The cyclic idiopathic edema demonstrated an accelerated transport of the lymph consistent with a high volume insufficiency. In phlebedema the high volume insufficiency was epifascially so distinct, that it could be detected scintigraphically. In post thrombotic syndrome the transport of the lymph was reduced dramatically corresponding to a safety valve insufficiency. Epifascially however, an accelerated lymph flow was observed due to compensatory mechanisms. The lipedema did not show any scintigraphic abnormalities. These results show that two-compartment lymphoscintigraphy can detect alterations in lymphatic function secondary to non-lymphogenic leg edema. The lymphatic function is changed according to the underlying pathophysiology which may be facilitate the differential diagnosis of such a leg edema.

Adult↗

High CD44 surface expression on primary tumours of malignant melanoma correlates with increased metastatic risk and reduced survival.

The cell surface glycoprotein CD44 has been implicated in the progression and metastasis of certain human tumours including malignant melanoma (MM). In animal models, certain MM cell lines, expressing high levels of CD44, displayed an augmented capacity for haematogenous metastasis, compared to those with low CD44 levels. To determine whether, in vivo, the level of CD44 expressed by primary tumours of MM (PMM) is related to their metastatic potential, CD44 expression on PMM was studied in 92 patients, classified by their metastatic risk based on histological measurement of vertical tumour thickness (VT): in situ PMM, low-risk PMM (VT < or = 0.7 mm), intermediate risk PMM (VT = 0.71-1.4 mm) and high-risk PMM (VT > 1.4 mm). Paraffin-embedded sections were stained immunohistochemically with a panCD44 MAb. The level of CD44 expression on PMM was analysed semiquantitatively with epidermal CD44 staining set as an internal standard. High levels of CD44 were detected in 58.3% of high-risk PMM, 40.6% of intermediate-risk PMM, 36.7% of low-risk PMM and 16.7% of in situ PMM. Seventy-four per cent (17/23) of patients who developed and/or died of MM metastasis were CD44 high, and importantly, among these were 5 patients, whose metastatic risk had been estimated low, based on the measurement of VT. Finally, Kaplan-Meier analysis revealed patients whose PMM were CD44 high to have a significantly reduced 5-year survival rate compared to those that were CD44 low (P < 0.05). We conclude that in our patient population, a high level expression of CD44 on PMM is associated with increased metastatic risk and reduced survival.

Antigens, Neoplasm↗

Detection of CD44 splice variants in formalin-fixed, paraffin-embedded specimens of human skin cancer.

The standard form of CD44 (CD44s) and CD44 isoforms, containing sequences encoded by one or several of 10 different variant CD44 exons (v1-v10), are thought to play a crucial role in the growth and metastasis of certain human tumors. Recently, monoclonal antibodies (mAbs) directed against all CD44 isoforms (panCD44), or against epitopes encoded by specific variant exons (CD44v) have been developed, which unfortunately only stain cryopreserved tissues. We wished to develop a technique to unmask chemically CD44s and CD44v epitopes in paraffin-embedded specimens of human skin cancers, so that they would be accessible for these mAbs. To address this issue, CD44s and CD44v expression was compared in cryopreserved and in formalin-fixed, paraffin-embedded biopsies obtained from the same basal cell carcinomas (BCC), squamous cell carcinomas (SCC), primary malignant melanomas (PMM) and metastatic malignant melanomas (MMM). Formalin-fixed tumors were deparaffinized and treated briefly with an antigen retrieval fluid (TUFTM) at 95 degrees C or left untreated. In untreated paraffin-embedded tissues, no CD44s or CD44v staining was detected. In contrast, in antigen retrieval fluid-treated biopsies CD44s and CD44v expression was identical to that in cryopreserved specimens of the same tumor with the exception of mAbs detecting v7/8 and v10. We conclude that antigen retrieval unmasks certain epitopes in formalin-fixed, paraffin-embedded tissues, thus facilitating future research on the relevance of CD44s and CD44v expression for human skin carcinogenesis.

Alternative Splicing↗

Low-frequency ultrasound treatment of chronic venous leg ulcers in an outpatient therapy.

Low-dose ultrasound seems to be an effective method to enhance wound healing, particularly in chronic venous leg ulcers. The aim of our investigation was to examine the effect of 30 kHz low-dose ultrasound in local treatment of chronic venous leg ulcers, when added to conventional therapy of outpatients. Twenty-four patients with chronic ulcerations of the leg due to chronic venous insufficiency were randomised in placebo-controlled parallel groups in a single-blind clinical study. Patients were randomised to conventional therapy with topical application of hydrocolloid dressings and compression therapy or conventional therapy with additional ultrasound treatment for 12 weeks. The ultrasound treatment consisted of 10 min of footbathing, with application of 30 kHz continuous ultrasound 100 mW/cm2 three times a week. The ulcer area was measured by planimetry, using a millimeter grid before treatment and after 2, 4, 6, 8, 10 and 12 weeks of therapy. The ulcer radius and the daily ulcer radius reduction were calculated. Colour photographs of the ulcers were taken under standard conditions at the same time. After each treatment local findings and side effects were recorded. After 12 weeks of treatment the control group showed a mean decrease of 16.5% in the ulcerated area. In contrast the mean ulcerated area decreased by 55.4% in the ultrasound group (p<0.007). The daily ulcer reduction in the ultrasound-treated patients was 0.08 mm+/-0.04 mm and in the placebo patients 0.03 mm+/-0.03 mm. Patients recorded only minor side-effects such as a tingling feeling and occasionally pinhead-sized bleeding in the ulcer area. The application of low-frequency and low-dose ultrasound is a helpful treatment option in chronic venous leg ulcers, especially if they do not respond to conventional ulcer treatment.

Aged↗

Changes of cytokeratin expression in the epidermis with chronic venous insufficiency.

BACKGROUND: A specific, individual pattern of cytokeratins (Cks) is expressed by each epithelial cells as part of the cytoskeleton. Cks are established as markers of epidermal differentiation. Basal cells are characterized by CK5 and 14 expression, whereas CK 1, 10 and 11 are typical for the suprabasal compartment of normal epidermis. Here, we investigated changes of Pan-CK, CK 10, and CK 14 expression in the epidermis in various stages of chronic venous insufficiency (CVI). PATIENTS AND METHODS: In punch biopsies of 24 patients with chronic venous insufficiency and of 6 volunteers with normal skin Cks were detected by indirect immunofluorescence using monoclonal antibodies against CK 10, CK 14 and Pan-CK. RESULTS: CK 10 and Pan-CK staining intensity increased with the severity of CVI changes. Suprabasal cells showed an upregulation of CK 10 and Pan-CK expression first in venous eczema. CK 14 expression is under normal condition confined to the basal cell layer of the epidermis. However in venous eczema and lipodermatosclerosis, CK 14 is detected in the suprabasal epidermal compartment. CONCLUSIONS: It is therefore concluded that altered differentiation and stratification mechanisms occur in keratinocytes in the epidermis with CVI first detectable in the stage of venous eczema. These changes are accompanied by a characteristic CK expression pattern.

Adult↗

Development and validation of a disease-specific questionnaire on the quality of life of patients with chronic venous insufficiency.

BACKGROUND: Recording of Quality of Life (QoL) is taking on increasing importance in medicine. Although QoL cannot be measured directly, numerous methods studies have demonstrated that important areas of QoL can be addressed by validated questionnaires. The present study was designed to examine a new disease-specific, German-language questionnaire, the Freiburger Questionnaire of QoL in venous diseases (FLQA), with respect to reliability, validity and patient acceptance-among patients with chronic venous insufficiency (CVI). PATIENTS AND METHODS: The FLQA consists of 83 items and differentiates between limitations in QoL in 7 scales: physical complaints, everyday life, social life, emotional status, therapy, satisfaction, occupation. Data were collected from 246 patients with CVI stage I (n = 107), II (n = 75) and III (venous ulcer, n = 64) in the Widmer classification. RESULTS: In the psychometric test, the majority of scales showed little or no top or bottom effect. The internal consistency of the scales was generally high (Cronbach's Alpha in all scales more than alpha = .70 and in 4 scales above alpha = .90). The convergent validity with the Nottingham Health Profile and the ALLTAG was high in several scales. The FLQA showed good discriminant validity and significantly differentiated between the clinical CVI stages in several areas of QoL. The change sensitivity during the course of therapy was also good. In a feasibility test, the acceptance values among patients were high with respect to ease of understanding and description of the QoL areas relevant to them. The mean time to fill out the questionnaire was 21 +/- 6 minutes. CONCLUSION: Overall, the FLQA appears suitable to reliably record characteristics of QoL in patients with CVI in both course and cross-sectional studies.

Activities of Daily Living↗

[Chronic venous insufficiency--from pathophysiology to therapy. 4: Treatment of ulcus cruris--therapy guidelines].

In the field of phlebology and angiology, leg ulcer represents a complex diagnostic and therapeutic problem. The initial steps include the taking of a careful history, inspection and palpation, and thorough angiological investigation which, where the individual situation makes this necessary, must be supplemented by such further diagnostic measures as biopsy, laboratory investigations or even allergy tests. Subsequent treatment must be stage-matched and must meet the individual needs of the patient. Both conservative and surgical forms of treatment are available.

Combined Modality Therapy↗

[Chronic venous insufficiency--from pathophysiology to therapy. 3: Physical therapy of venous diseases].

In patients with chronic venous insufficiency (CVI), stage-oriented physiotherapy can be employed in addition to surgery, drug treatment and sclerotherapy, with both prophylactic and curative intent. Apart from improving the hemodynamic situation, physiotherapy aims in particular to preserve or reactivate the active and passive pump mechanisms of the lower limbs, for example, the calf muscle pump and the ankle pump. Consequently the wide spectrum of physiotherapeutic measures includes such measures as compression therapy, anticongestion positioning, massage and exercise, all of which can be supplemented or replaced, as didacted by the condition prevailing, by hydrotherapy, electrotherapy, balneotherapy or climatic therapy.

Combined Modality Therapy↗

[Chronic venous insufficiency--from pathophysiology to therapy. 2: Sclerotherapy of varicose veins].

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.

Combined Modality Therapy↗

[Chronic venous insufficiency--from pathophysiology to therapy. 1: Pathophysiology--compression treatment--systemic pharmacotherapy].

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.

Bandages↗

[Selective photothermolysis of superficial varicose veins telangiectasias of the lower extremity].

Leg venectasia is a common problem. Although there are a variety of therapeutic modalities, none of them gives satisfactory results. The effects of sclerotherapy in the treatment of telangiectasia with a small diameter are poor. Electrocoagulation and argon laser treatment often result in scarring. We studied the effectiveness of the flashlamp pumped pulsed dye laser at a wavelength of 585 nm in the treatment of leg venectasia. After repeated treatments using this laser system, only 30% of the vessels that looked blue on clinical examination could be removed; we obtained better lightening of smaller red, telangiectatic vessels with a diameter up to 0.4 mm. However, hyperpigmentation frequently developed after treatment. In post-treatment biopsies, occlusion of the vessels was found. Based on these results, we recommend a combined therapy for leg venectasia. Larger diameter vessels should be treated with sclerotherapy, while finer telangiectasia can be treated with the flashlamp pumped pulsed dye laser.

Adult↗