Biomedical subjects
T Ruzicka
Publications and source records attributed to T Ruzicka.
[Distal edema and hyperhidrosis of the arm. Symptoms of reflex sympathetic dystrophy (Sudeck's disease)].
Reflex sympathetic dystrophy is characterized clinically by the triad of autonomic sympathetic dysfunction, and motor and sensory disturbances of the affected extremity. Typical symptoms are distal generalized edema with cyanotic skin, pathologic function of eccrine sweat glands and diffuse dull pain. If reflex sympathetic dystrophy is not recognized an irreversible stage may be reached, with atrophic pale, cool, and anhidrotic skin, contractures and diffuse osteoporosis. The syndrome can be idiopathic but can also be precipitated by a variety of factors, including banal trauma, bone fracture, and traumatic nerve lesions. Pathophysiologically, a functional disturbance of sympathetic nerve fibres may result in a vicious circle of blood flow dysfunction, excitation of afferent nociceptors and maintenance of sympathetic dysfunction at the level of the spinal or central nervous system. In the patient presented in this paper, sympathetic dysregulation of reflex sympathetic dystrophy was cured by means of blockades of the stellate ganglion.
[Amelanotic polypoid malignant melanoma of the balloon cell type].
We describe a 59-year-old woman with amelanotic polypoid balloon cell melanoma. Physical examination showed exophytic erythematous tumour simulating a basal cell carcinoma or an adnexal tumour. Histopathology revealed a polypoid tumour that was composed mainly of balloon cells in sheets and nests. Examination 37 months after excision of the tumour with 3 cm safety margins disclosed no evidence of enlarged lymph nodes or cutaneous metastases. Metastases to internal organs could not be assessed because the patient repeatedly refused further examination for staging. To our knowledge our patient is the first case of amelanotic polypoid balloon cell melanoma to be reported in the German literature.
Chronic cutaneous damage after accidental exposure to ionizing radiation: the Chernobyl experience.
BACKGROUND: The hazards of acute radiation exposure are well known. Bone marrow failure from total body gamma or neutron irradiation is the most clinically relevant aspect of acute radiation disease. With nonhomogeneous exposure, as is characteristic in accidents, other organ systems, such as the skin, may be more important in determining clinical prognosis. This became obvious in the two worst radiation accidents since 1945, the Chernobyl accident in April 1986 and the Goiania accident in September 1987. OBJECTIVE: Our purpose was to describe the characteristic chronic sequelae of accidental cutaneous radiation in a group of patients who survived the Chernobyl nuclear power plant accident. METHODS: Fifteen patients with the delayed type of the cutaneous radiation syndrome were examined between September 1991 and January 1992. All patients had a history of acute radiation disease. The exposure pattern was characterized by partial body exposure with high doses of beta and gamma irradiation from radioactive water, steam, or dust. RESULTS: Radiation-induced lesions were confined primarily to the legs and distal arms, but sometimes involved up to 50% of the total body surface. In addition to telangiectases, radiation keratoses, and radiation ulcers, hemangiomas, hematolymphangiomas, splinter hemorrhages in the distal nail bed, lentiginous hyperpigmentation, and severe subcutaneous fibrosis were noted. No malignant transformation could be detected. Associated diseases included cataracts, chronic hepatitis, and recalcitrant bacterial and herpesvirus infections. CONCLUSION: After accidental partial body exposure to high doses of beta and gamma irradiation, the predominant involvement of the skin, described as the cutaneous radiation syndrome, can become the characteristic feature. This causes longlasting, serious diagnostic and therapeutic problems.
Acquired relapsing self-healing Blaschko dermatitis.
We describe a 44-year-old woman who had a unilateral relapsing linear dermatosis for 12 years. The lesions consisted of erythematous, discrete and grouped papules and papulovesicles that were localized to the left side of the upper and lower limbs, chest, abdomen, and back. They were distributed along Blaschko's lines. There was also a diffuse erythematous scaly hyperkeratosis of both palms. The lesions healed spontaneously. Examination of biopsy specimens from the back and the left palm revealed acute and subacute spongiotic dermatitis, respectively. This dermatosis was first described by Grosshans and Marot in 1990 and termed "Blaschkite de l'adulte." Because the disease is acquired, relapsing, heals spontaneously, follows Blaschko's lines, and is characterized histopathologically by a spongiotic dermatitis, we propose the term "acquired relapsing self-healing Blaschko dermatitis."
Cellular schwannoma.
We report on the clinical, histopathological, and immunohistochemical features of a case of cellular schwannoma. This rare benign nerve sheath tumor merits recognition because it frequently shows moderate nuclear atypia and mitotic activity leading in some instances to the false diagnosis of sarcoma.
Specific binding and lack of growth-promoting activity of substance P in cultured human keratinocytes.
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Psoriatic arthritis.
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Cytokine system as potential target for antipsoriatic therapy.
Cytokines are produced by a variety of cells and have numerous of overlapping activities. There is increasing evidence that cytokines play a crucial role in the pathogenesis of psoriasis and of other dermatologic diseases. This review summarizes current knowledge as to how the altered cytokine network is involved in the accumulation of inflammatory cells in lesional skin, and how the cytokines are involved in epidermal hyperproliferation. The actions of the most important therapeutic compounds, such as corticosteroids, dithranol, cyclosporine, retinoids, vitamin D3 analogues and ultraviolet radiation, on the cytokine system are also discussed. Consideration is given as to how the effects on the production of cytokines and/or cytokine receptors contribute to their therapeutic action.
Role of interleukin-8 receptor in skin.
Interleukin-8 (IL-8) is a potent chemotactic and proinflammatory cytokine, produced in the skin by a variety of cells in response to inflammatory stimuli. Recent studies suggest that in addition to its potent actions on leukocytes, IL-8 exerts a direct influence on several functions of human epidermal cells such as chemotaxis, Candida albicans killing activity or proliferation. The effects of IL-8 are mediated by binding to two types of specific high-affinity receptors which contain seven transmembrane domains typical of guanine nucleotide binding protein (G protein)-coupled receptors. In the skin, a broad spectrum of cells such as neutrophils, T lymphocytes, mast cells, dermal macrophages, endothelial cells and keratinocytes possess binding sites for IL-8. Recently, increased expression of epidermal IL-8 receptors has been observed in psoriasis an inflammatory and hyperproliferative skin disease. Since the effects of IL-8 may be modulated at the receptor level, the pharmacological manipulation of the IL-8 receptor may prove an important target for the therapy of skin diseases with increased IL-8 levels.
Helicobacter pylori in patients with systemic sclerosis: detection with the 13C-urea breath test and eradication.
In patients with systemic sclerosis peristaltic abnormalities may delay gastric emptying, giving rise to bacterial overgrowth, including possibly Helicobacter pylori (HP). Infection with Helicobacter is an important risk factor for esophageal and gastric diseases, including esophagitis, gastritis and gastric cancer. The purpose of this prospective study was to assess gastric HP infection in patients with systemic sclerosis. In 12 patients with systemic sclerosis the newly introduced breath test with 13C-labelled urea was used for indirect detection of gastric urease activity due to HP infection. Five out of 12 patients gave Helicobacter-positive results (42%); 7 patients were negative for Helicobacter colonization (58%). Thus, the risk for gastric diseases caused by HP infection is enhanced in patients with systemic sclerosis compared with white healthy, asymptomatic persons examined in other studies. Helicobacter-positive patients were treated with 2 x 20 mg omeprazole and 4 x 500 mg amoxicillin over 14 days. Afterwards the 13C-urea breath test was repeated and showed negative results for Helicobacter in all systemic sclerosis patients treated. Dual therapy with omeprazole and amoxicillin therapy effectively eradicated HP. The 13C-urea breath test did not cause any side-effects and is therefore considered to be a non-invasive, non-toxic and safe method for the diagnosis and therapeutic control of Helicobacter-status.
Increased expression of epidermal IL-8 receptor in psoriasis. Down-regulation by FK-506 in vitro.
IL-8 is a chemotactic cytokine with proinflammatory and growth-promoting activities. Recently it has been shown to influence several functions of keratinocytes, including HLA-DR expression, chemotaxis, and proliferation by binding to a specific receptor. Because psoriasis vulgaris is characterized by epidermal hyperproliferation and infiltration of inflammatory cells, we investigated the expression of IL-8 and its receptor in normal and psoriatic epidermis using semiquantitative reverse-transcriptase-polymerase chain reaction. In addition the mRNA levels of the proto-oncogenes c-ras, c-raf, c-myc, and HER-2 were also investigated as potential growth-promoting stimuli in psoriatic epidermis. IL-8 mRNA was only detected in lesional psoriatic epidermis, and IL-8R-specific mRNA was found to be 10 times increased in lesional psoriatic epidermis. There was no significant difference in the protooncogene mRNA levels. In order to test the relevance of the massively increased IL-8R levels in psoriatic epidermis, we investigated the effect of the antipsoriatic drug FK-506 on specific IL-8 and IL-8R mRNA expression. FK-506 dose dependently inhibited IL-8R expression and function. Our data suggest that in psoriatic skin, elevated IL-8 levels and markedly increased IL-8R expression may act in concert to induce the cardinal signs of psoriasis--epidermal hyperproliferation and leukocyte infiltration. IL-8R may prove a molecular target for antipsoriatic drugs such as FK-506.
Cyclosporine therapy in Behçet's disease.
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The lipoxygenase inhibitor 2-phenylmethyl-1-naphthol (DuP 654) is a 12(S)-hydroxyeicosatetraenoic acid receptor antagonist in the human epidermal cell line SCL-II.
The lipoxygenase inhibitor 2-phenylmethyl-1-naphthol (DuP 654) has been shown to be an active anti-inflammatory drug in a murine skin inflammation model. Since 12-HETE is assumed to have a pathophysiological role in inflammatory skin diseases, and epidermal cells possess high affinity binding sites for 12(S)-HETE, we studied the effect of DuP 654 on 12(S)-HETE binding to the human epidermal cell line SCL-II. DuP 654 antagonized 12(S)-HETE binding in a dose-dependent manner with a Ki of 3.41 +/- 0.23 nM. The antagonistic effect was reversible. After 1- and 24-hour preincubation, the drug had no more significant inhibitory effect at concentrations between 10(-10) and 10(-5) M on specific 12(S)-HETE binding (Bmax of 215,000 +/- 21,000 receptors per cell) or on receptor affinity (Kd of 3.25 +/- 0.42 nM). Our results show that DuP 654, in addition to its 5-lipoxygenase inhibitory activity, exhibits 12-HETE receptor antagonist effect, and therefore may be of benefit in skin diseases with elevated 12-HETE levels.
Therapeutic efficacy of oral low-dose cyclosporin A in severe psoriatic arthritis.
Six male patients with severe psoriatic arthritis (PA) unresponsive to various topical and systemic therapies have been treated with oral cyclosporin A (CyA; Sandimmun) solution at daily doses ranging usually from 1.5 to 5.0 mg/kg. In 1 case the dose had to be increased to 7 mg/kg/day. At initiation of CyA therapy skin involvement was between 40 and 90% of total body surface. Initiation of CyA therapy resulted in marked improvement of skin lesions within 2-7 weeks accompanied by impressive relief from arthralgias and improvement of joint function. The requirement for nonsteroidal anti-inflammatory drugs was markedly reduced in all cases. All patients in whom CyA therapy was continued remained clinically stable for several months (follow-up period 2-7 months). Although mild to moderate relapses occurred, rebound phenomena were not observed after discontinuation of treatment. Side effects which comprised serum creatinine increases in 3 out of 6 cases were reversed by adjustment of CyA dosage.
Down-regulation of epidermal growth factor receptors by dithranol.
Dithranol is highly effective in the treatment of psoriasis, but the exact mechanism of action is not known. Since persistent expression of epidermal growth factor (EGF) receptors in psoriatic epidermis is assumed to have pathogenetic significance, we have studied the effects of dithranol on EGF binding to the human epidermal cell line SCL-II. After treatment of cells with dithranol or its therapeutically inactive oxidation product, danthrone, radioligand binding assays were performed with 125I-EGF. In therapeutically active concentrations (0.25-1 micrograms/ml) dithranol induced a decrease in EGF binding in a dose dependent manner. Danthrone was inactive. The inhibition occurred after a latency period of 6 h and reached its maximum at 24 h. At the concentration of 1 microgram/ml, the drug led to approximately a 70% decrease in the number of specific high-affinity EGF receptors (Bmax), whereas receptor affinity (Kd) showed no change. The down-regulation of EGF receptors on epidermal cells by dithranol may contribute to its antipsoriatic action.
Increased expression of the epidermal growth factor receptor in human epidermal keratinocytes after exposure to ionizing radiation.
The effect of exposure of human epidermal keratinocytes to ionizing radiation, both in vivo and in vitro, on the expression of the epidermal growth factor receptor (EGF-R) was studied on the protein, mRNA, and functional levels. Quantitative fluorometry of short-term organ cultures incubated with a monoclonal antibody against human EGF-R revealed a dose-dependent increase of EGF-R expression 24 h after irradiation with 4 and 6 Gy, with an additional increase after 48 h. In biopsy specimens from patients undergoing radiation therapy a markedly increased expression could be determined by quantitative fluorometry during radiation therapy which wa still considerably above the baseline level 4 weeks after termination of treatment. Radioligand binding assays demonstrated a 50% increase in 125I-EGF binding to primary keratinocytes and A431 cells, at doses of 1 Gy, with a further increase after 72 and 96 h. Northern blots were performed with total RNA from two human epidermal cell lines (SCLII and A431). In A431 cells, increased EGF-R transcript levels could be detected 48 h after irradiation. In cells of the SCLII cell line, EGF-R expression was not affected by irradiation. These results were confirmed by semiquantitative polymerase chain reaction of primary cultured keratinocytes, demonstrating an increase of transcripts of EGF-R 24 h after irradiation with single doses of 6 Gy. Thus exposure to ionizing radiation leads to an increased expression of functionally intact EGF-R in human keratinocytes, at the protein and mRNA levels, both in vitro and in vivo; we hypothesize that this effect is part of a stress program of epidermal cells in response to ionizing radiation, ensuring rapid repopulation of irradiated areas.
[Psoriasis arthropathica].
BACKGROUND: Five to seven percent of patients with psoriasis suffer additionally from accompanying arthritis. AIM OF THE STUDY: In this article, we review the current knowledge on clinical, diagnostic and therapeutic aspects of the disease. PATIENTS AND RESULTS: Data are presented on the treatment of six patients with the immunosuppressant ciclosporin. Therapeutic results with this drug are superior to agents traditionally used for management of psoriatic arthritis. CONCLUSION: The therapeutic options have been enlarged by the introduction of new immunosuppressive drugs, particularly ciclosporin.