Search PubMed⌕ Search

Biomedical subjects

Thomas Schwarz

Publications and source records attributed to Thomas Schwarz.

At least 55 records · Page 3Linked to original sources
PubMed2004

[G-DRG Version 2004: changes in view of dermatology].

In the year 2004 the obligatory introduction of the new hospital funding system based on a Diagnosis Related Groups (DRG) system will become reality for all German hospitals. After all fundamental items of the new G-DRG version were made generally known, the possible consequences had to be considered. The first mandatory German case-based lump sum catalogue differs importantly from the previous payment models and requires intensive study. Economic considerations will increasingly play a role in the daily routine of hospitals and influence treatment patterns. Therefore, comprehensive knowledge of basic principles of G-DRG is essential. In the following aspects of the reimbursement system with special relevance to dermatology are reviewed in detail. Additionally, the revised classification system versions OPS-301 SGB V and ICD-10-GM 2004 and the German coding standards version 2004 must be appropriately applied for dermatologic purposes.

Dermatology↗
PubMed2004

Resistance of human melanoma cells against the death ligand TRAIL is reversed by ultraviolet-B radiation via downregulation of FLIP.

Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a potential anticancer drug since it induces apoptosis preferentially in malignant but not in normal cells. Not all cancer cells, however, are TRAIL susceptible. Chemotherapeutic drugs and ionizing radiation have been found to be able to sensitize resistant tumor cells for TRAIL-induced apoptosis. Since ultraviolet B radiation (UVB) is a potent inducer of apoptosis but exhibits much less adverse effects, we studied whether UVB sensitizes TRAIL-resistant melanoma cells. Therefore, we analyzed the TRAIL-sensitive human cell line A-375 in comparison to the resistant cell line IGR-37. Both cell lines showed expression of the long form of the antiapoptotic FLICE inhibitory protein FLIP(L) which, however, was partially cleaved into the 43 kDa form in A-375 cells. In addition, only IGR-37 cells expressed the short splicing variant FLIP(S), which exerts high antiapoptotic activity. Accordingly, transient overexpression of FLIP(S) rendered A-375 cells resistant to TRAIL. Upon exposure to low UVB doses, TRAIL-treated IGR-37 cells underwent pronounced apoptosis and TRAIL sensitivity of A-375 cells was dramatically increased. In both cases, UVB caused an inhibition of flip expression. This study indicates that (i) the expression level and the processing status of FLIP may play a crucial role in determining the sensitivity of melanoma cells towards TRAIL and (ii) expression of FLIP is regulated by UVB.

Apoptosis↗
PubMed2003

Collagen metabolism is a novel target of the neuropeptide alpha-melanocyte-stimulating hormone.

Suppression of collagen synthesis is a major therapeutic goal in the treatment of fibrotic disorders. We show here that alpha-melanocyte-stimulating hormone (alpha-MSH), a neuropeptide well known for its pigment-inducing capacity, modulates collagen synthesis and deposition. Alpha-MSH in vitro suppresses the synthesis of collagen types I, III, and V and down-regulates the secretion of procollagen type I C-terminal peptide (PICP) in human dermal fibroblasts treated with the fibrogenic cytokine transforming growth factor-beta1 (TGF-beta1). Alpha-MSH did not interfere with TGF-beta1 signaling, because TGF-beta1-induced expression of collagen mRNA was not affected, implying a posttranscriptional mechanism. Human dermal fibroblasts in vitro express a high affinity binding site for MSH, which was identified by reverse transcription PCR and immunofluorescence analysis as the melanocortin-1 receptor (MC-1R). Immunohistochemical studies on normal adult human skin confirmed MC-1R expression in distinct dermal fibroblastic cells. The MC-1R on fibroblasts appears to be functionally relevant because alpha-MSH increased the amount of intracellular cAMP, and coincubation with a synthetic peptide corresponding to the human Agouti signaling protein abrogated the inhibition of TGF-beta1-induced PICP secretion by alpha-MSH. To assess the in vivo relevance of these findings, a mouse model was used in which dermal fibrosis was induced by repetitive intracutaneous injections with TGF-beta1. The inductive activity of TGF-beta1 on collagen deposition and the number of dermal cells immunoreactive for vimentin and alpha-smooth muscle actin was significantly suppressed by injection of alpha-MSH. Melanocortins such as alpha-MSH may therefore represent a novel class of modulators with potential usefulness for the treatment of fibrotic disorders.

Actins↗
PubMed2003

Involvement of dectin-2 in ultraviolet radiation-induced tolerance.

Hapten sensitization through UV-exposed skin induces hapten-specific tolerance which can be adoptively transferred by injecting T cells into naive recipients. The exact phenotype of the regulatory T cells responsible for inhibiting the immune response and their mode of action remain largely unclear. Dectin-2 is a C-type lectin receptor expressed on APCs. It was postulated that dectin-2 interacts with its putative ligands on T cells and that the interaction may deliver costimulatory signals in naive T cells. Using a soluble fusion protein of dectin-2 (sDec2) which should inhibit this interaction, we studied the effect on contact hypersensitivity (CHS) and its modulation by UV radiation. Injection of sDec2 affected neither the induction nor the elicitation phase of CHS. In contrast, UV-induced inhibition of the CHS induction was prevented upon injection of sDec2. In addition, hapten-specific tolerance did not develop. Even more importantly, injection of sDec2 into tolerized mice rendered the recipients susceptible to the specific hapten, indicating that sDec2 can break established tolerance. FACS analysis of spleen and lymph node cells revealed a significantly increased portion of sDec2-binding T cells in UV-tolerized mice. Furthermore, transfer of UV-mediated suppression was lost upon depletion of the sDec2-positive T cells. Taken together, these data indicate that dectin-2 and its yet unidentified ligand may play a crucial role in the mediation of UV-induced immunosuppression. Moreover, sDec2-reactive T cells appear to represent the regulatory T cells responsible for mediating UV-induced tolerance.

Adoptive Transfer↗
PubMed2003

Treatment of severe lichen planus with mycophenolate mofetil.

Lichen planus (LP) is an inflammatory skin disorder with a wide range of clinical appearances. The treatment of disseminated and especially erosive forms of LP is often difficult and disappointing. Activated T cells are important in the pathogenesis of LP as indicated by the dermal lymphocytic infiltrate leading to keratinocyte destruction and lesion formation. Similar histologic findings are present in graft-versus-host disease. Since T cells are key players in the development of both disorders and mycophenolate mofetil has been successfully introduced in the treatment of graft-versus-host disease, we have examined the therapeutic potential of this agent in 3 patients suffering from disseminated and erosive LP. Mycophenolate mofetil was well tolerated and induced complete remission in 2 patients, and substantial improvement in the third patient.

Adolescent↗
PubMed2003

[Clinical aspects and pathogenesis of UV-induced pigmentary disorders].

Solar and ultraviolet (UV) radiation, respectively, are the strongest stimuli for the induction of pigmentation in human skin. UV radiation induces pigmentation by exerting direct and indirect effects on melanocytes. Melanogenesis is a very complex process whose molecular mechanisms are not yet completely understood. Acute UV exposure induces the non-protective immediate pigment darkening as well as delayed tanning which exerts photoprotective effects. Chronic UV exposure causes permanent pigmentary changes by inducing solar lentigines and pigmented actinic keratoses as well hypopigmentated areas. Artificial UV irradiation (UVA, PUVA) can also induce pigmentary disorders, including lentigines. Since the therapeutic options for UV-induced pigmentary changes are limited consequent protection as a prophylactic measure is recommended.

Humans↗
PubMed2003

[DRGs in dermatology: quality of coding and the effects of case mix].

BACKGROUND: High-quality coding of patient clinical data is mandatory for an effective DRG classification to result in adequate allocation of funding for inpatient treatment. The aim of the study was to determine the effect of controlled documentation on patient clinical data and to ascertain the outcome of calculated DRG-based yields depending on higher coding quality of patient treatment. PATIENTS AND METHODS: In a prospective study, 1914 patient clinical records from the Department of Dermatology, University of Muenster, were captured using different documentation standards and the data was analysed. Grouping was performed on the basis of the Australian Refined DRG system v4.1. Dermatological patients were broken down into eleven groups based on principle diagnosis. RESULTS: As a result of a controlled documentation, case mix, case mix index and patient clinical complexity level (PCCL) value were increased within identical samples. Furthermore, it was shown that high-quality coding may result in exact and reasonable classification of patient clinical data. CONCLUSIONS: Different documentation standards may cause undesired effects on the monetary yields of in-patient treatment. It appears that high-quality coding and controlled documentation may guarantee adequate yields. FauIty. incomplete and (up)coding could be a potential economic risk for hospitals.

Dermatology↗
PubMed2003

Coagulation factor V G allele and HR2 haplotype: factor V activity, activated protein C resistance and risk of venous thrombosis.

Factor V Leiden is a well-known risk factor for venous thrombosis. The dual role of factor V as a coagulatory and anticoagulatory cofactor permits the assumption that further mutations in the factor V gene are of importance in the study of the risk of thrombosis. Relevant studies to date have given rise to a controversy over this risk for the HR2 haplotype. For the G allele, defined in our work group as a G at the nucleotide positions 2391, 2663, 2684 and 2863, there have been to date no other investigations of thrombotic risk. In a case-control study on 347 patients with deep venous thrombosis (DVT) and 282 controls, we investigated the association of the HR2 haplotype and the G allele with DVT. We found no association between HR2 haplotype and DVT [odds ratio (OR) 0.87; 95% confidence interval (CI) 0.58-1.30; P = 0.537]. The frequency of the G allele was, on the contrary, higher in the control group than among the patients (OR 0.68, 95% CI: 0.53 to 0.89; P = 0.005). The factor V activity of the HR2 carriers was lower than that of the wild type and G allele carriers. The HR2 haplotype exhibited a moderate influence on activated protein C response. This study presented no evidence of thrombotic risk for the HR2 haplotype alone. The results here permit the assumption of a protective effect of the G allele. The source of a possible protective influence of the G allele on thrombotic risk is at present unclear.

Activated Protein C Resistance↗
PubMed2003

BAY 38-7271: a novel highly selective and highly potent cannabinoid receptor agonist for the treatment of traumatic brain injury.

Traumatic brain injury (TBI) is the most common cause of mortality and morbidity in adults under 40 years of age in industrialized countries. Worldwide the incidence is increasing, about 9.5 million people are hospitalized per year due to TBI, and the death rate is estimated to be more than one million people per year. Recently BAY 38-7271 has been characterized as a structurally novel, selective and highly potent cannabinoid CB1/CB2 receptor agonist in vitro and in vivo with pronounced neuroprotective efficacy in a rat traumatic brain injury model, showing a therapeutic window of at least 5 h. Furthermore, neuroprotective efficacy was also found in models of transient and permanent occlusion of the middle cerebral artery and brain edema models as well. In this article we review the in vitro and in vivo pharmacology of BAY 38-7271, the results from acute and subacute toxicity studies, pharmacokinetics and drug metabolism in animals and healthy male volunteers. In phase I studies BAY 38-7271 was safe and well tolerated when administered by i.v. infusion for either 1 or 24 h. As the doses of BAY 38-7271 in animals needed for maximal neuroprotective efficacy were significantly lower than those inducing typical cannabinoid-like side effects, it is to be expected that the compound will offer a novel therapeutic approach with a favorable therapeutic window for the treatment of TBI or cerebral ischemia.

Animals↗
PubMed2003

Complete compression ultrasonography of the leg veins as a single test for the diagnosis of deep vein thrombosis.

Noninvasive diagnosis of deep vein thrombosis (DVT) is based on ultrasound examination of the leg veins, usually restricted to only compression of the proximal veins (CUS). Patients with negative CUS findings require a second examination or a combination with other tests, which impairs clinical efficiency. In this prospective outcome study, 1646 consecutive patients with clinically suspected DVT were examined once by a standardized protocol of complete compression ultrasound comprising all proximal and distal veins (CCUS) as the only diagnostic test. The examination was equivocal in 15 patients (1% technical failure rate). Another 366 patients (22%) were tested positive for proximal DVT, distal DVT, muscle vein thrombosis, or phlebitis. Of 1265 patients in whom CCUS findings were negative, 242 met exclusion criteria for follow-up (age <18, life expectancy <3 months, other reasons for anticoagulation, postthrombotic lesions of the leg veins, or lack of informed consent). During the 3 months of follow-up, three of 1023 patients with negative CCUS findings experienced a symptomatic venous thromboembolic event (0.3% [95% CI 0.1%-0.8%]). We conclude that the CCUS protocol has a low technical failure rate and is safe with respect to excluding DVT, thereby reducing the diagnostic workup of patients with suspected DVT to a single ultrasound examination.

Adult↗
PubMed2003

[Pathomechanisms of the elicitation phase of allergic contact dermatitis].

Allergic contact dermatitis (ACD) is a T-cell mediated, antigen-specific inflammatory response to repeated epicutaneous exposure to haptens. Two immunologically distinct sequential steps are required to produce the clinical picture of ACD. In the sensitization phase, naïve antigen-specific T cells are primed and differentiate into memory or effector T cells. In the elicitation phase, reapplication of the same hapten leads to local recruitment of hapten-specific T cells which are cytotoxic, release cytokines and recruit other inflammatory cells. These events lead to clinically visible tissue inflammation characterized by edema, erythema, scaling, and blistering. For the clinician, the effector phase is especially important, because sensitization is generally asymptomatic, whereas elicitation produces the clinical picture of ACD. Detailed knowledge about the mechanisms of the elicitation phase of ACD is needed in order to develop novel therapeutic approaches.

Cytokines↗
PubMed2002

DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way.

Nuclear DNA damage and death receptor (CD95) activation by ultraviolet-B radiation (UVB) play a major role in UVB-induced apoptosis. Removal of DNA damage combined with inhibition of death receptor activation resulted in pronounced but not complete suppression of apoptosis, indicating that a third independent pathway is involved. Since reactive oxygen species (ROS) cause apoptosis and are induced by UVB, the radical scavenger pyrrolidene-dithiocarbamate (PDTC) was used. PDTC prevented UVB-induced apoptosis partially, H(2)O(2)-induced cell death largely, but not CD95-mediated apoptosis. The same was observed for cytochrome c release from mitochondria, another important event during apoptosis. The proapoptotic protein Bid was cleaved upon exposure to UVB or to agonistic anti-CD95-antibodies, but not to H(2)O(2), indicating that H(2)O(2) uses a different pathway. The fact that PDTC neither inhibited CD95-mediated apoptosis nor affected UV-induced DNA damage indicated that ROS generated during UVB irradiation may directly trigger mitochondrial cytochrome c release, thereby contributing to apoptosis. Accordingly, complete inhibition of apoptosis was observed when in addition to DNA damage removal via photoreactivation and blockade of CD95 signaling by caspase-8 inhibitor zIETD, PDTC was added before UVB exposure. This indicates that DNA damage, death receptor activation and ROS formation contribute to UVB-induced apoptosis in an essential and independent way.

Apoptosis↗
PubMed2002

[SAPHO syndrome: case report of an 18-year-old man and review of the literature].

We report about an 18-year-old man, suffering from acne on his face and trunk and complaining about indefinite bone pains--without any trauma. SAPHO-syndrome was diagnosed which consists of synovitis, acne, pustulosis, hyperostosis and osteitis. Five types of this syndrome can be differentiated: spondarthritis hyperostotica pustulo-psoriatica, chronic recurrent multifocal osteomyelitis, inflammatory chest wall syndrome, isolated sternocostoclavicular hyperostosis, and the combined form of acne-associated spondarthritis and chronic recurrent osteomyelitis. Although the sapho-syndrome is very rare, it should be considered a possible diagnosis in the case of indefinite bone pains in combination with acne, pustulosis and hyperostosis.

Acne Vulgaris↗
PubMed2002

Independent contribution of three different pathways to ultraviolet-B-induced apoptosis.

Ultraviolet-B radiation (UVB) causes a variety of biological effects which include the induction of apoptosis. UVB-induced apoptosis provides a well controlled scavenging mechanism protecting cells from malignant transformation. To induce programmed cell death, UVB uses a variety of cellular signaling pathways. In this context induction of nuclear DNA damage seems to be the predominant pathway, since experimental reduction of DNA damage was associated with a strong suppression of apoptosis. Additionally, UVB has been shown to target cytoplasmatically located or membrane bound components to induce signal transduction. UVB was found to directly activate cell surface death receptors, thereby triggering the apoptotic machinery. Furthermore, UVB-induced intracellular formation of reactive oxygen species (ROS) accompanied by mitochondrial dysfunction and cytochrome c release was demonstrated to be additionally involved in the apoptotic program. The following review will briefly discuss current aspects of the interplay between the different signaling pathways involved in UVB-induced apoptosis.

Animals↗
PubMed2002

Role of immunomodulation in diseases responsive to phototherapy.

Within the last two decades phototherapy has turned out to be a major therapeutic strategy in dermatology and thus has significantly influenced the treatment of many dermatoses. The goals of therapeutic photomedicine are the suppression of ongoing disease processes and, more importantly, the prevention, modulation, or abrogation of pathogenic mechanisms causing the disease. Therapeutic photomedicine has been largely empirical and most of it is still empirical today. However, parts of it are already based on the advances in photoimmunology and molecular biology. Although, we are far from a detailed understanding of the mechanisms underlying phototherapy, there is increasing evidence that phototherapy acts via modulation of the immune system. Most of the effects of both ambient and therapeutic ultraviolet radiation are immunosuppressive in nature.

Animals↗