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Biomedical subjects

F R Ochsendorf

Publications and source records attributed to F R Ochsendorf.

At least 19 recordsLinked to original sources

Psoriasis: a possible risk factor for development of coronary artery calcification.

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder affecting about 2% of white-skinned individuals. Epidemiological data on the prevalence and degree of coronary artery calcification (CAC) as an indicator for cardiovascular diseases in patients with psoriasis are contradictory. OBJECTIVES: To study the prevalence and degree of CAC as an indicator for cardiovascular diseases in 32 patients with psoriasis matched for age, sex and risk factors to an equally sized control population. METHODS: Noncontrast-enhanced 16-row spiral computed tomography was performed in patients and controls. RESULTS: We found a significantly increased prevalence (59.4% vs. 28.1%, P = 0.015) and severity (CAC score according to Agatston 3.7 vs. 0.0, P = 0.019) of CAC in patients with psoriasis. Multiple linear regression calculations identified psoriasis as a likely independent risk factor for CAC. CONCLUSIONS: Our results point towards the potentially systemic nature of the inflammatory processes underlying the pathogenesis of psoriasis, which may therefore be considered a potentially severe systemic disease.

Adult↗

Efficacy of the fully human monoclonal antibody MOR102 (#5) against intercellular adhesion molecule 1 in the psoriasis-severe combined immunodeficient mouse model.

BACKGROUND: Psoriasis is considered as a chronic immune-mediated disease characterized by inflammation and proliferation of the epidermis. OBJECTIVES: Targeting intercellular adhesion molecule 1 (ICAM-1) is an attractive therapeutic option as this molecule is critically involved in leucocyte adhesion and extravasation as well as in lymphocyte activation. METHODS: We have selected the fully human monoclonal antibody MOR102 (#5) against ICAM-1 from the Human Combinatorial Antibody Library (HuCAL). This antibody, as human IgG4 [corrected] was tested for its ability to interfere with lymphocyte activation and adhesion in vitro as well as for its antipsoriatic efficacy in vivo using the psoriasis-severe combined immunodeficient (SCID) mouse model. RESULTS: The antibody demonstrated efficient inhibition of lymphocyte adhesion to ICAM-1 in vitro, with an IC(50) of approximately 0.4 microg mL(-1) (3 nmol L(-1)). In addition, MOR102 (#5) reduced lymphocyte proliferation in mixed lymphocyte cultures by approximately 50%. The in vivo efficacy of MOR102 (#5) was tested on grafts derived from lesional skin of patients with chronic plaque-stage psoriasis transplanted on to SCID mice. Intraperitoneal injection of 10 mg kg(-1) of MOR102 (#5) antibody every alternate day over a period of 4 weeks resulted in reconstitution of orthokeratotic differentiation and a significant (P < 0.05) reduction in epidermal thickness as well as marked reduction in the inflammatory infiltrate. Therapeutic activity may be related to the targeting of ICAM-1 on keratinocytes and thus preventing efficient activation of local T cells. CONCLUSIONS: Based on the efficacy of the fully human monoclonal antibody MOR102 (#5) shown in vitro as well as in vivo in the psoriasis-SCID mouse model, initiation of clinical studies is indicated.

Animals↗

[Pre-auricular tumors in an infant. Differential diagnosis of neuroectodermal syndromes].

BACKGROUND: Neuroectodermal syndromes are complex because of their rarity and overlapping clinical manifestations making differential diagnosis problematic. CASE REPORT: A 2-year old girl presented with a phenotype characterized by bilateral pre-auricular tags, a fistula of the right cheek, hemifacial microsomia, and a limbus dermoid on the right eye. This constellation is characteristic for the Goldenhar syndrome. Following excision of the tags and fistula along with a keratoplasty, the child developed normally. CONCLUSION: The exact diagnosis of a neuroectodermal syndrome facilitates identification of associated symptoms. Early surgical therapy may prevent the development of functional deficits.

Child, Preschool↗

Prospective randomised comparison of traditional, personal bedside and problem-oriented practical dermatology courses.

PURPOSE: This paper reports a prospective, randomised study comparing a problem-oriented practical (POP) course based on paper cases to a personal bedside teaching (PBT) practical course and a standard practical course. METHODS: During 2 consecutive terms, students were randomly allocated to either 2 POP groups/term (n = 10/group), 2 PBT groups/term (n = 10/group) or the standard practical course, which consisted of a rotating system of lectures and bedside teaching with randomly appointed tutors. Each course was evaluated with the same 12-item questionnaire and multiple-choice test administered at the beginning and end of the course. RESULTS: The numbers of students evaluated were 36 for the POP groups, 37 for the PBT groups, and 155 for the standard course. The PBT and POP courses were rated significantly better (P < 0.001) than the standard course for all items. Aggregate marks (mean +/- SD) were: 1.59 +/- 0.8 for the POP course; 1.69 +/- 0.68 for the PBT course, and 2.71 +/- 0.98 for the standard course. There were no significant differences between the POP and PBT courses. Significantly better learning rates as indicated by an increase in the number of correctly answered questions were observed in students attending the POP and PBT courses. CONCLUSION: This prospective study demonstrated that there was no difference in the rating of a POP course and a bedside teaching course by students randomly assigned to 1 of 3 different pedagogical approaches. Furthermore, both alternative options achieved better ratings than the standard course, which is current teaching practice in our medical school. The PBT and POP approaches provided superior learning success and POP helped solve the problems of standardisation and patient recruitment.

Curriculum↗

Kinetics and dose-response of photosensitivity in cream psoralen plus ultraviolet A photochemotherapy: comparative in vivo studies after topical application of three standard preparations.

BACKGROUND: Topical photochemotherapy with bath psoralen plus ultraviolet (UV) A irradiation (PUVA) has been developed to reduce possible side-effects of oral PUVA therapy. Although the efficacy of bath PUVA therapy appears to be similar to oral PUVA therapy, provision of bathing facilities has obvious economic, logistic and sanitary implications. Cream PUVA therapy has recently been developed as a variation of topical PUVA. OBJECTIVES: To understand the photobiological effects and to increase the safety and effectiveness of this novel topical PUVA therapy, we assessed the kinetics and dose-response of phototoxicity of 8-methoxypsoralen (8-MOP) cream in order to develop a treatment schedule for this treatment option. METHODS: Ninety-eight patients (63 men and 35 women) undergoing cream PUVA therapy were studied. The phototoxic properties of topically applied 8-MOP in three different water-in-oil creams as vehicles were assessed. In a dose-response study, four concentrations of 8-MOP cream (0.0006-0.005%) were used for determination of the minimal phototoxic dose (MPD). The kinetics of photosensitization were tested by determination of MPDs after different application times of 8-MOP cream (10, 20, 30 and 60 min). The persistence of phototoxicity was assessed by UVA exposure at defined time intervals after application of 8-MOP cream (0, 30, 60 and 120 min). RESULTS: The concentration required to produce sufficient but not undue photosensitization of the skin was 0.001% 8-MOP. The duration of application leading to the lowest MPD was 30 min. Greatest photosensitization was achieved when UVA irradiation was performed between 0 and 30 min after 8-MOP removal. These findings showed no significant difference between the three vehicles used. CONCLUSIONS: Based on our data we recommend application of 0.001% 8-MOP in a water-in-oil cream for 30 min. Irradiation with UVA should be performed within 30 min after removal of 8-MOP cream, as there is a rapid decrease in photosensitivity thereafter.

Administration, Cutaneous↗

Cream psoralen plus ultraviolet A therapy for granuloma annulare.

BACKGROUND: Treatment modalities for granuloma annulare (GA) often remain unsatisfactory or can be accompanied by potentially hazardous side-effects. Psoralen plus ultraviolet (UV) A (PUVA) bath photochemotherapy has been reported to be highly effective in the treatment of GA. Another form of topical PUVA therapy, using 8-methoxypsoralen-containing cream or gel preparations, has been proven to be as effective as bath PUVA therapy in the treatment of palmoplantar dermatoses. OBJECTIVES: To assess the efficacy of cream PUVA photochemotherapy in patients with GA. METHODS: Five patients with GA were treated. The diagnosis was confirmed by pretreatment skin biopsies. Cream PUVA therapy was performed four times a week: the mean number of treatments was 26 (range 17-40) and mean cumulative UVA dose was 55.9 J cm-2 (range 18.2-109.2). RESULTS: Cream PUVA photochemotherapy induced significant clinical improvement (one patient) or clearance (four patients) of GA in all patients. Clearance was documented clinically and histopathologically. CONCLUSIONS: Cream PUVA phototherapy can be highly effective in patients affected by localized forms of GA.

Administration, Cutaneous↗

Antagonistic effects of the staphylococcal enterotoxin a mutant, SEA(F47A/D227A), on psoriasis in the SCID-hu xenogeneic transplantation model.

Psoriasis is a T-cell-mediated immune dermatosis probably triggered by bacterial superantigens. This pathomechanism has been experimentally reproduced in a SCID-hu xenogeneic transplantation model. We analyzed the effects of different bacterial superantigens on the induction of psoriasis in this model. Staphylococcal enterotoxin B and exfoliative toxin triggered the onset of psoriasis when administered repetitively intracutaneously over a period of 2 wk, whereas staphylococcal enterotoxin A representing a distinct subfamily of staphylococcal enterotoxins only mimicked certain aspects of psoriasis. The biologic effects of staphylococcal enterotoxin A were more pronounced when a mutated form, SEA(H187A), of this superantigen with reduced affinity to major histocompatibility complex class II was coinjected. Another mutated variant, SEA(F47A/D227A), exhibiting no measurable major histocompatibility complex class II affinity blocked the effects triggered by wild-type staphylococcal enterotoxin A when injected in a 10-fold higher dose. Inhibition was specific as induction of psoriasiform epidermal changes by staphylococcal enterotoxin B could not be blocked. As staphylococcal enterotoxin A, in contrast to the other superantigens tested, is capable of inducing epidermal thickening but not the typical appearance of psoriasis, we conclude that bacterial superantigens may differ with regard to their effects on human nonlesional psoriatic skin. Staphylococcal-enterotoxin-A-mediated effects were blocked by a genetically engineered superantigen highlighting the potential therapeutic use of mutated superantigens.

Animals↗

[Acne inversa in Crohn's disease].

We report 2 patients with the association of Crohn's disease and acne inversa (= hidradenitis suppurativa). A 50-year-old woman with a 10-year-history of Crohn's disease developed suppurative nodules and abscesses in the genitoanal region. Over several years these lesions were hidden from everybody including the family physician. In a 42-year-old female patient abscesses appeared in the axilla 4 years after the diagnosis of Crohn's disease. During the next years these draining lesions also developed in both groins and the perineum. The differential diagnosis included cutaneous manifestations of Crohn's disease in both cases. The clinical picture with draining abscesses and sinuses with communicating channels, cystic nodules, hypertrophic scars and foul-smelling discharge were typical findings of acne inversa. In the last years this entity was reported several times in patients with Crohn's disease. Acne inversa starts with a compact hyperkeratosis of the infundibulum in terminal hair follicles, followed by a segmental rupture of the follicular epithelium and a spreading inflammatory reaction. As pathogenic factors genetic disposition and smoking were discussed. The only curative therapy is excision of the affected area. The reported association should be known in order to recognize the disease and institute the right therapy.

Abscess↗

Monitoring of phagocytic activity in histiocytic cytophagic panniculitis.

Histiocytic cytophagic panniculitis presents with subcutaneous panniculitis. Histologically, it is characterized by phagocytosis of blood cells in the subcutaneous tissue and bone marrow. One patient with histiocytic cytophagic panniculitis is described in whom hemophagocytosis macrophages and histiocytes was observed histologically and was confirmed in vitro measuring phagocytosis by peripheral blood monocytes by means of chemiluminescence. In vitro measurements of phagocytosis corresponded well with the clinical course. Chemiluminescence for measuring phagocytosis in vitro may be suitable for analyzing disease activity and for testing therapeutic compounds in vitro.

Adult↗

Lucigenin chemiluminescence in human seminal plasma.

Seminal plasma protects spermatozoa from the detrimental effects of reactive oxygen species such as hydrogen peroxide. We investigated the lucigenin-dependent chemiluminescence in cell-free seminal plasma from andrological patients. The seminal plasma was separated from cells by centrifugation. In all seminal plasmas studied lucigenin-dependent chemiluminescence (LCL) was detected. The LCL showed a strong pH-dependence. The signal was stable if samples were stored at +4 degrees C for up to 4 days or up to 8 days at -80 degrees C. Filtration of the samples (0.45 and 0.22 microm pore size) did not lower their luminescence. The addition of superoxide dismutase (SOD) and ascorbic acid oxidase (AAO) lowered LCL nearly to baseline values while trolox and desferal showed moderate effect, whereas allopurinol had no effect. Electron paramagnetic resonance spectroscopy demonstrated ascorbyl radicals in seminal plasma. Physiological concentrations of ascorbic acid yielded SOD-inhibitable lucigenin-chemiluminescence. The nitroblue-tetrazolium assay showed that ascorbic acid in buffer solution produced formazan. Superoxide-anion radicals were not detected in seminal plasma by the spin-trap DEPMPO due to their low steady state concentration. It is concluded that in seminal plasma ascorbate reacts with molecular oxygen yielding ascorbyl radicals and superoxide anion. If lucigenin is added to seminal plasma, reducing substances present, such as ascorbate, reduce lucigenin to the corresponding radical; this radical reacts with molecular oxygen and also forms O2-. So LCL in human seminal plasma results from the autoxidation of ascorbate and the oxidation of the reduced lucigenin. While the physiological relevance of the former mechanism is unknown, the latter is an artifact.

Acridines↗

[The UV record. Document for quality control, therapy planning and risk assessment in dermatologic photo- and photochemotherapy].

Ultraviolet (UV-) radiation therapy as a mono- or combination therapy (UV-A, UV-A1, UV-B, SUP, UV-B311) or as photochemotherapy with photosensitization (systemic PUVA-, bath PUVA-, topical PUVA-therapy) are successfully used for the treatment of several dermatological disorders. Long-term side effects of natural UV (sun light) include photoaging and induction of skin tumors. At present, the relevance of in-vitro findings of potential tumor induction in animals through therapeutic levels of UV radiation is a matter of debate. To assess these risks, information on treated location, kind of UV radiation and cumulative UV doses are required. Practically this information is barely accessible. This makes decisions on possible therapies difficult. To solve this problem we propose to use an "UV pass". At the end of each UV radiation cycle, the body location, the type of radiation and the cumulative dose are documented and this pass is given to the patient. This will improve the information transfer if the doctor is changed, as well as facilitating decisions about certain therapies and calculation of long-term risks of UV radiation. Finally it will improve the quality of UV photo- and photochemotherapy.

Dose-Response Relationship, Radiation↗

[Prospective detection of important bacterial pathogens in pyoderma and their in vitro antibiotic susceptibility].

BACKGROUND AND OBJECTIVE: For rational therapeutic recommendations the spectrum and resistance of bacteria in skin diseases were investigated. PATIENTS/METHODS: Within 4 months 911 swabs of dematoses possibly caused by bacteria were taken prospectively (481 outpatients, 430 inpatients) and the material cultured on standard media. The positive cultures including resistance screening of 210 swabs of 168 outpatients and of 175 swabs of 85 inpatients could be evaluated, the remaining cultures were sterile. RESULTS: Staphylococcus aureus was the most frequent pathogen (outpatient 67%, inpatient 61% of all positive cultures), followed by streptococci (groups A and B; 25%). In patients Pseudomonas aeruginosa was the most common pathogen in leg ulcers and between the toes (45% and 70% respectively). 13% of the Staphylococcus aureus isolates were resistant to tetracyclines and erythromycin; one strain proved to be methicillin resistant. CONCLUSIONS: Cephalosporins (I. generation), penicillins with beta-lactamase-inhibitors, and to a lesser extent isoxazoyl-penicillin and clindamycin can be recommended for the treatment of skin infections. Oral quinolones are suited for infections with gram-negative bacteria (such as bewteen the toes). The indications for systemic antibiotic therapy of leg ulcers should be restricted.

Bacterial Infections↗