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Biomedical subjects

R-M Szeimies

Publications and source records attributed to R-M Szeimies.

At least 19 recordsLinked to original sources

[Nocardia farcinica infection of a vascular prosthesis].

A 61-year-old woman presented with purple-red subcutaneous nodules on her right leg. She had experienced fever up to 40 degrees C for the past 10 days and felt generally weak over the last two months. Four months earlier, a vascular graft had been implanted in her right femoral artery. Based on the diagnosis of skin infection due to implantation of an infected prosthesis, she was hospitalized and treated with an antibiotic regime. During the initial antibiotic treatment, the symptoms deteriorated, and she developed joint, hepatic and CNS abscesses. Finally, a microbiologic culture with an extended incubation time revealed the diagnosis of an infection with the slowly growing bacterium Nocardia ssp. Hereupon the patient was treated purposefully with Meropenem over six months. This treatment resulted in complete recovery.

Anti-Bacterial Agents↗

[Hemorrhagic dengue fever after trip to Malaysia].

A 39-year-old patient developed a disseminated rash with scattered petechiae, fever, malaise and arthralgia after a trip to Malaysia. The patient displayed increasing dengue IgG titers and borderline dengue IgM titers. Dengue fever with a hemorrhagic course is a rare condition in adult patients. Patients who have previously had dengue fever and retained non-neutralizing heterotypic antibodies are more likely to develop this complication via the phenomenon of antibody-dependent enhancement.

Adult↗

In vitro and in vivo comparison of two different light sources for topical photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) is an effective and safe treatment option for the treatment of actinic keratosis (AK). Incoherent lamps are often used, matching the absorption maxima of ALA. OBJECTIVES: A comparative trial was performed to evaluate the efficacy of recently developed light-emitting diodes (LEDs). METHODS: Human epidermal keratinocytes were incubated for 24 h with ALA (100, 200, 300, 400 or 500 micromol L(-1)) and irradiated consecutively using either an incoherent halogen lamp (lambda(em) = 580-750 nm; 24 J cm(-2); 40 mW cm(-2)) or an LED system (lambda(em) = 633 +/- 3 nm; 3, 6, 12 or 24 J cm(-2); 40 mW cm(-2)). Topical ALA-PDT was performed on 40 patients with AK (n = 584) in a symmetrical distribution suitable for two-sided comparison. After incubation with ALA (20% in cream base) irradiation was performed with the incoherent lamp (100 J cm(-2); 160 mW cm(-2)) on one side and the LED system (40 J cm(-2); 80 mW cm(-2)) on the opposite side followed by re-evaluation up to 6 months. RESULTS: No significant differences between the LED system (3, 6, 12 or 24 J cm(-2)) and the incoherent light source (24 J cm(-2)) regarding cytotoxicity was found in vitro. The complete remission rate yielded in the in vivo investigation was also not significantly different at 6 weeks (P = 0.95), 3 months (P = 0.75) and 6 months (P = 0.61) following therapy. Six weeks following therapy complete remission rates of 84.3% (LED system) and 82.8% (incoherent lamp) were achieved. There was also no significant difference between both light sources regarding pain during light treatment (P = 0.67), patient satisfaction (P = 1.0) or cosmesis (P = 1.0) following therapy. CONCLUSIONS: These results show the efficacy of an LED system for ALA-PDT both in vitro and in vivo. ALA-PDT with the LED system showed a noninferiority regarding the clinical outcome in the treatment of AK compared with the incoherent lamp.

Adult↗

[Anaphylactic reaction following hair bleaching].

Ammonium persulphate is a potent bleach and oxidizing agent that is commonly present in hair bleaches. Because bleaching is so commonly performed, hairdressers often develop allergic contact dermatitis to ammonium persulphate. In addition to this delayed reaction, asthma and rhinitis may develop as immediate reactions in those exposed to the fumes. Severe anaphylactic reactions are rare. We report a 24-year-old woman who acquired dermatitis following contact with bleaching substances while working as a hairdresser. After changing her profession, the dermatitis disappeared. Following the private use of a hairdressing bleach containing ammonium persulphate, she suffered a severe anaphylactic reaction with unconsciousness. The patient also developed an anaphylactic reaction three hours following patch testing with the hairdresser battery. The rub test with ammonium persulphate (2.5%) in a 1:100 solution was positive.

Adult↗

[Therapeutic options for epithelial skin tumors. Actinic keratoses, Bowen disease, squamous cell carcinoma, and basal cell carcinoma].

There has been worldwide a significant rise in the incidence of epithelial skin tumors and their precursors in the past years with an increased number of younger patients affected. The risk factors are identified. The choice of the appropriate treatment for each individual is crucial. Major consideration include high cure rate, low long-term recurrence rate and few side effects. In the following article different therapeutic approaches for actinic keratoses, Bowen's disease, basal cell carcinoma and squamous cell carcinoma are presented and analysed.

Antineoplastic Agents↗

[Skin changes with chemotherapy].

Skin changes in cancer patients have many causes and are difficult to categorize. Chemotherapy-associated cutaneous side effects are usually toxic and often show a characteristic reaction pattern, offering diagnostic clues to the consulting dermatologist. Severe chemotherapy-associated reactions which require dose reduction, change or discontinuation of the cytostatic agents are rare. Most problems are reversible and self-limiting disease. The most common chemotherapy reactions are reviewed.

Antineoplastic Agents↗

[Antibacterial photodynamic therapy. A new treatment for superficial bacterial infections?].

The basis of "antibacterial photodynamic therapy" involves the killing of bacteria by reactive oxygen species in the presence of a photosensitizer and light. Possible dermatologic indications include inactivation of bacteria in skin and wound infections and reduction in density of nosocomial multi-resistant infections. The chief advantage of antibacterial photodynamic therapy is that regardless of the resistance pattern of a bacteria, inactivation can be achieved, analogous to the use of antiseptics. The aim of the present review is to describe the physicochemical and biological mechanisms of antibacterial photodynamic therapy as well as possible clinical indications in dermatology.

Anti-Bacterial Agents↗

Primary cutaneous cryptococcosis and secondary antigenemia in a patient with long-term corticosteroid therapy.

We report a case of a 71-year-old male who developed severe cellulitis of his right forearm and hand after he had an accidental injury from the sharp edge of a metal plate of a birdhouse. The patient suffers from chronic asthma and has been treated with systemic corticosteroids for years. Culture of aspirates from two sites of the wound area revealed growth of Cryptococcus neoformans in one and Acinetobacter lwoffii in the other. After combined treatment including antibiotics, antifungal therapy with fluconazole 400 mg/d and surgical debridement followed by a mesh graft, the patient achieved complete healing of the wound. Five months after the infection, the patient was still positive for cryptococcal antigen at a titer of 1:64 despite oral treatment with fluconazole 50 mg/d, and maintenance therapy with fluconazole 200 mg/d was recommended for 6 months, or longer depending on further results. The clinical and microbiological characteristics of this patient as well as therapeutical and epidemiological aspects of primary cutaneous cryptococcosis (PCC) are discussed.

Aged↗

Novel pharmacological approaches in the treatment of psoriasis.

Progress in the understanding of psoriasis as a T-cell mediated inflammatory disease has led to the development of new immunomodulatory therapies. Currently the main focus is on the so-called biologics (or biological agents), including fusion proteins, monoclonal antibodies, cytokines and selective receptors. They mainly target single steps in the complex cascade of humoral and cellular inflammatory immuno-mechanisms that finally lead to the accelerated growth of epidermal and vascular cells in the psoriatic lesions. The most promising and advanced biological agents are discussed along with their influence on the critical pathophysiological steps in psoriasis, including depletion of T cells, blockade of initial T-cell activation and T-cell receptor (TCR) stimulation, blockade of costimulatory signals and T-cell proliferative signals as well as restoration of the T helper type 1 (Th1)/Th2 balance by diminishing type 1 cytokines and administration of type 2 cytokines. In addition to the biological agents, further development of 'classical' dermatological therapies, such as retinoids, or the discovery of new indications for non-dermatological agents contribute to the novel pharmacological approaches in the treatment of psoriasis.

Dermatologic Agents↗

Photodynamic effects of novel XF porphyrin derivatives on prokaryotic and eukaryotic cells.

The worldwide rise in the rates of antibiotic resistance of bacteria underlines the need for alternative antibacterial agents. A promising approach to the killing of gram-positive antibiotic-resistant bacteria of the skin uses light in combination with a photosensitizer to induce a phototoxic reaction. Different concentrations (0 to 100 microM) of porphyrin-based photosensitizers (CTP1, XF70, and XF73) and different incubation times (5 min, 1 h, and 4 h) were used to determine phototoxicity against two methicillin-resistant Staphylococcus aureus strains, one methicillin-sensitive S. aureus strain, one methicillin-resistant Staphylococcus epidermidis strain, one Escherichia coli strain, and human keratinocytes and fibroblasts. Incubation with 0.005 microM XF70 or XF73, followed by illumination, yielded a 3-log10 (> or = 99.9%) decrease in the viable cell numbers of all staphylococcal strains, indicating that the XF drugs have high degrees of potency against gram-positive bacteria and also that the activities of these novel drugs are independent of the antibiotic resistance pattern of the staphylococci examined. CTP1 was less potent against the staphylococci under the same conditions. At 0.005 microM, XF70 and XF73 demonstrated no toxicity toward fibroblasts or keratinocytes. No inactivation of E. coli was detected at this concentration. XF73 was confirmed to act via a reactive oxygen species from the results of studies with sodium azide (a quencher of singlet oxygen), which reduced the killing of both eukaryotic and prokaryotic cells. When a quencher of superoxide anion and the hydroxyl radical was used, cell killing was not inhibited. These results demonstrate that the porphyrin-based photosensitizers had concentration-dependent differences in their efficacies of killing of methicillin-resistant staphylococcal strains via reactive oxygen species without harming eukaryotic cells at the same concentrations.

Anti-Bacterial Agents↗

Structure-activity relationships of three differently substituted 2,7,12,17-tetrakis-(beta-methoxyethyl) porphycene derivatives in vitro.

The subcellular localization, efficacy and photooxidative mechanism of three new photosensitizing porphycenes (HexoTMPn, PeloTMPn, CpoTMPn) for photodynamic therapy with different substituents at position 9 of the tetrapyrrole macrocycle were investigated in vitro using different human skin-derived cell lines (HaCaT, SCL I, SCL II) with the aim of customizing the side-chain chemistry to accelerate cellular uptake and so enhance photodynamic activity. Cells were incubated with a porphycene and costained with organelle-specific markers. Subcellular localization was determined by fluorescence microscopy. Also, cells were incubated with different sensitizer concentrations (0-1000 nmol/l) and irradiated by an incoherent light source (lambda(em) = 600-750 nm, 40 mW/cm(2), 24 J/cm(2)) with/without quenchers or enhancers (NaN(3), histidine, mannitol or D(2)O). Cell viability was assessed. All porphycenes were localized in perinuclear lysosomes and induced a decrease in mitochondrial activity following irradiation. HexoTMPn was the most efficient in all three cell lines (EC(50) in HaCaT cells: HexoTMPn 14 nmol/l, CpoTMPn 62 nmol/l, PeloTMPn 89 nmol/l). Addition of either NaN(3) or histidine reduced the phototoxicity significantly. Due to the short lifetime of singlet oxygen, the sites of sensitizer localization are the initial subcellular targets. The cytotoxicity of each sensitizer varied depending on singlet oxygen quantum yield and cell line. Despite the different chemical structures, the biological effects were not very distinct, since they seemed to be mostly determined by the tetrapyrrole ring and only slightly modified by the substituent at position 9. Also, there was only a narrow margin between biological compatibility and efficacy.

Cell Line↗

[Skin changes in diabetes mellitus].

Diabetes mellitus is the most frequent metabolic disorder. Just under 5 million people suffer from this disease in Germany. Four types of diabetes mellitus are distinguished: type 1 diabetes, type 2 diabetes, other specific diabetes forms, and gestational diabetes. Many characteristics of diabetes mellitus including skin changes are already manifest in the "prediabetic" stage when glucose tolerance is limited so that every elevation of blood sugar levels must be considered pathological. Changes in skin due to diabetes mellitus can be categorized into four disease groups: skin infections, skin diseases found overly frequently in association with diabetes mellitus, skin alterations due to diabetic complications, and reactions to antidiabetic treatment.

Diabetes Complications↗

["Smoldering systemic mastocytosis. "Successful therapy with cladribine].

Mastocytoses are a heterogenous group of diseases characterized by proliferation and accumulation of mast cells in the skin and other organs. They are subdivided into cutaneous mastocytoses; systemic forms, which may appear with or without skin lesions; mast cell sarcomas and extracutaneous, localized, benign mastocytomas. Systemic mastocytoses apart from the skin mainly involve bone marrow, gastrointestinal tract, bones, lymph nodes, spleen and liver. Whereas indolent forms of systemic mastocytosis are mainly treated with antihistamines, glucocorticosteroids and PUVA therapy, the more aggressive forms, including mast cell leukemia, often require cytostatic chemotherapy. A 53-year old patient with beginning "smoldering systemic mastocytosis" failed to respond to high-dose systemic glucocorticosteroids and interferon-alpha. Treatment with cladribine led to an impressive improvement of skin lesions, a significant decrease in tryptase serum levels and stabilization of bone marrow infiltrates.

Antineoplastic Agents↗

Keratinocyte-derived cytokines after photodynamic therapy and their paracrine induction of matrix metalloproteinases in fibroblasts.

BACKGROUND: Recent studies have shown that collagen-degrading matrix metalloproteinase (MMP)-1 and MMP-3 are produced by fibroblasts in response to photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) and are considered to be involved in the antisclerotic effects of ALA-PDT observed in the treatment of localized scleroderma. OBJECTIVES: As the primary target of topical PDT is epidermal keratinocytes, we studied the indirect participation of keratinocytes in the production of MMPs and collagen by dermal fibroblasts. METHODS: Keratinocytes were treated with sublethal doses of ALA (100 micromol L(-1)) and red light. The conditioned media were collected 24 h after PDT and primary human fibroblasts were exposed to these media for 6-48 h. Further, a coculture model, keratinocytes seeded on to collagen type IV-coated transwells in the upper chamber and fibroblasts in the lower chamber, was used to study paracrine effects of keratinocytes after PDT. RESULTS: Keratinocyte supernatants after PDT showed a significant, up to 10-fold increase of interleukin (IL)-1alpha and a 2.5-fold increase of tumour necrosis factor-alpha as determined by enzyme-linked immunosorbent assay, while IL-6, MMP-1 and MMP-3 were not altered significantly. Fibroblasts treated with keratinocyte-conditioned media after PDT showed an induction of MMP-1 and MMP-3 protein levels up to threefold in both models used, suggesting that ALA-PDT modulates MMP-1 and MMP-3 production via indirect mechanisms. Collagen type I mRNA expression by fibroblasts was not altered significantly in either model. The addition of an IL-1 receptor antagonist to the keratinocyte-conditioned media completely inhibited the induction of MMP-1 and MMP-3 in stimulated fibroblasts, suggesting that IL-1 is mainly responsible for the observed paracrine effects. CONCLUSIONS: We present evidence that PDT can trigger MMP production in dermal fibroblasts not only directly as has been already shown, but also by an indirect paracrine loop mediated by soluble factors released by epidermal keratinocytes.

Aminolevulinic Acid↗

Effects of light fractionation and different fluence rates on photodynamic therapy with 5-aminolaevulinic acid in vivo.

To improve efficacy of photodynamic therapy (PDT) with intravenously administered 5-aminolaevulinic acid (ALA) fractionating the light dose or reducing the light intensity may be a possibility. Therefore, Syrian Golden hamsters were fitted with dorsal skinfold chambers containing an amelanotic melanoma (n=26). PDT was performed (100 mW cm(-2), 100 J cm(-2), continuously or fractionated, and 25 mW cm(-2), 100 J cm(-2); continuously or fractionated) using an incoherent light source following i.v. application of ALA. Following fractionated irradiation, the light was paused after 20 J cm(-2) for 15 min. Prior to and up to 24 h after PDT tissue, pO(2) was measured using luminescence lifetime imaging. The efficacy was evaluated by measuring the tumour volume of amelanotic melanoma cells grown subcutaneously in the back of Syrian Golden hamsters (n=36). Only high-dose PDT resulted in a significant decrease of pO(2). Irrespective of the mode of irradiation only high-dose PDT induced complete remission of all tumours (13 out of 13). It could be shown that low-dose PDT failed to induce a significant decrease of pO(2). No significant effect of fractionated irradiation was shown regarding the therapeutic efficacy 28 days after PDT. Thus performing a fractionated PDT with ALA or reducing the light intensity seems not to be successful in clinical PDT according to the present data.

Aminolevulinic Acid↗

[Actinic keratoses].

Actinic keratoses are defined as proliferation of cytologically atypical keratinocytes in the zone of epidermal-dermal junction in photodamaged skin. In the northern hemisphere the prevalence of actinic keratoses ranges depending on different epidemiological studies from 11% to 25% for people aged 40 or older. The main cause of actinic keratoses is exposure to UVB radiation in sunlight UVB radiation induces mutations in the telomerase gene and in the tumor suppressor gene P53, which can also be detected in invasive squamous cell carcinoma. The only histological parameter to distinguish between actinic keratoses and SCC is the level of invasiveness. The risk for actinic keratoses to develop into SCC is about 16% over lo years. For this reason and because of the high prevalence of actinic keratoses, it has been suggested to replace the term,, actinic keratosis K with intraepidermal squamous cell carcinoma' to better characterize the lesion. In the following review recent aspects of pathogenesis and therapy of actinic keratoses are discussed.

Adult↗