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Biomedical subjects

E Christophers

Publications and source records attributed to E Christophers.

At least 235 records · Page 13Linked to original sources

Skin tumors in the European PUVA Study. Eight-year follow-up of 1,643 patients treated with PUVA for psoriasis.

In the continuation of the European PUVA Study, 1,643 patients of the original cohort of 3,175 patients enrolled in this prospective study were reevaluated for skin tumors after an average observation period of 96 months. Thirty-six patients with a total of seventy-one tumors (forty squamous cell carcinomas, twenty-three basal cell carcinomas) were observed. In contrast to the U.S. sixteen-center study, we were unable to demonstrate a clinically relevant increase in the risk of tumors induced by psoralens with ultraviolet A (PUVA), and we also failed to show a clear relationship between PUVA exposure and tumor development. Almost all patients with tumors had been exposed to various carcinogens before the initiation of PUVA. No tumors were detected in patients without such prior treatment, although 10% of the patients had received more than 3,000 joules/cm2 total cumulative phototoxic PUVA dose during the observation period. The discrepancy between the results of the U.S. study and our findings may partly be explained by a variety of factors such as a different treatment approach, a different attitude toward sun exposure, and the overall lower incidence of skin cancer in the European population.

Basal Cell Carcinoma↗

Identification of C5ades arg and an anionic neutrophil-activating peptide (ANAP) in psoriatic scales.

Scales from patients with nonpustular psoriasis were investigated for the presence of peptides capable of activating functional activities in human polymorphonuclear leukocytes (PMNL). Two compounds with similar molecular weight (12,500 and 15,000) were isolated which markedly stimulated PMNL functional activities including chemotaxis, generation of superoxide radical anion (O-2), and liberation of beta-glucuronidase as a marker enzyme. As revealed by ion-exchange and subsequent radioimmunoassay followed by chromatofocusing, one peptide proved to be the desarginated form of the complement split product C5ades arg. No C5a was detectable. As a second psoriatic scale chemotaxin we isolated an anionic neutrophil-activating peptide (ANAP) which shows a single isoelectric point at pH 6.8. This peptide shares some of the characteristics of epidermal cell-derived thymocyte-activating factor and interleukin 1 and, as shown by deactivation experiments, it cross-reacts with a monocyte-derived cytokine. The 2 newly described neutrophil-activating peptides (C5ades arg and ANAP) may play an important role in the psoriatic tissue reaction.

Cell Movement↗

[Malignant melanoma in the area of the head and neck].

The incidence of malignant melanoma is rising worldwide. Recognition of the biological types of malignant melanoma (nodular melanoma, superficial spreading melanoma, lentigo maligna melanoma, and acrolentiginous melanoma) have greatly helped to improve the prognosis in recent years. Determination of the depth of invasion in histological serial sections has proved to be of great prognostic value. Melanomas with minimal invasion have an excellent prognosis. Wide excision of the primary tumour is of utmost importance. The excisional margins should be 3-5 cm, but in superficial melanomas the width of excision may be less. Prophylactic neck dissection is unnecessary for superficial melanomas, it is necessary for lesions between 1 and 3.9 mm in thickness, whereas in tumours with a depth of invasion greater than 4 mm the outcome of the disease is not improved by prophylactic neck dissection. In metastasizing malignant melanoma the tumour mass should be reduced by surgical intervention. Survival is sometimes prolonged by several months or even longer when lymph nodes and metastases are excised. A radical neck dissection is indicated therefore when lymph nodes are clinically involved.

Combined Modality Therapy↗

Mast cells and macrophages in early relapsing psoriasis.

Five patients with widespread plaque-type psoriasis were treated continuously with clobetasol under occlusion. Clinical healing was seen after 6-10 days of treatment. All plaques treated in this way clinically relapsed approximately 12 days later. During the period of remission, sequential biopsies were taken and prepared for light and electron microscopy. Histologically, the earliest indications of relapse were endothelial alterations (swelling, intercellular widening) followed by the appearance of mast cells around the postcapillary venules; these mast cells showed signs of degranulation. Hours later, activated macrophages showing pericellular edema were present, and these migrated into the epidermis soon after. Associated with the presence of macrophages, there was a complete loss of desmosome-tonofilament complexes. Later, lymphocytes and neutrophils were seen. Under these experimental conditions, the psoriatic-tissue alterations appear to have been initiated by degranulating mast cells as well as by macrophages which later invaded the epidermis.

Clobetasol↗

Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris.

In 2,147 patients suffering from psoriasis, evaluation of the age of onset revealed two peaks, one occurring at the age of 16 years (female) or 22 years (males) and a second peak at the age of 60 years (female) or 57 years (males). Human lymphocyte antigen (HLA) tissue typing in 112 randomly assigned patients showed that HLA-Cw6, known to be at disequilibrium in psoriasis, is present in 85.3% of patients with early onset. In contrast, 14.7% patients with late onset showed this marker. Parents (father or mother) were affected in approximately half of the patients with early onset and in none belonging to the group with late onset. Furthermore, psoriasis in patients with early onset follows an irregular course and shows a strong tendency to become generalized. On the basis of clearly defined criteria (e.g., age of onset, heritability, and clinical course of disease), nonpustular psoriasis shows two distinct forms, one of which is hereditary, with early onset, and the other is sporadic and occurs in older age.

Adolescent↗

Multifunctional inhibition by anthralin in nonstimulated and chemotactic factor stimulated human neutrophils.

Treatment of human polymorphonuclear leukocytes (PMN) with anthralin (0.2-50 micrograms/ml) results in dose-dependent inhibition of nondirected as well as directed migration (chemotaxis) against the synthetic tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), the complement fragment C5a and leukotriene B4. Polymorphonuclear leukocytes (PMN) pretreated with anthralin at concentrations which inhibit cell motility also show a dose-dependent inhibition of superoxide anion generation. In contrast to anthralin two derivatives (danthrone and anthralin dimer) were ineffective. Specific binding of [3H]FMLP to neutrophil membrane receptors was impaired by anthralin at concentrations 5-10 fold higher than those which were inhibitory for cell function. Release of beta-glucuronidase from azurophilic (lysosomal) granules provoked by various chemotaxins in the presence of cytochalasin B was not affected by anthralin over a wide range of concentrations. Also there were no signs of cytotoxicity e.g., leakage of cytoplasmatic lactate dehydrogenase (LDH) caused by anthralin, These data indicate that neutrophil functions may become substantially altered by anthralin. The effective dosages correspond to concentrations obtained in vivo after local application. Danthrone as well as anthralin dimer, known to be clinically ineffective, showed no effects upon PMN function. It is suggested that anthralin via a free radical mechanism alters sensitive sites at or in the cellular membrane including receptors.

Anthracenes↗

Transient absence of C5a-specific neutrophil function in inflammatory disorders of the skin.

Chemotactic migration, production of superoxide anion (O2-), and the release of beta-glucuronidase from azurophilic granules were determined in polymorphonuclear leukocytes (PMN) from 135 patients with infectious (e.g., pyoderma, acne conglobata, erysipelas) as well as noninfectious (psoriasis) skin diseases. Purified C5a and the formylated tripeptide FMLP were used as stimuli. In addition, longitudinal profiles of PMN activities were performed at daily intervals in several patients. There was a complete absence of PMN responses (chemotaxis, O2--production, and enzyme release) specifically induced by C5a in 25 patients suffering from various inflammatory diseases of the skin. In these patients PMN responsiveness for the tripeptide FMLP was either normal or increased. The C5a-dependent defect of PMN was transient and correlated with disease activity. When normal PMN were incubated with sera from C5a-defective patients, no inherent stimulatory or inhibitory activities compared to control sera were seen. Pretreatment of normal PMN in vitro with various concentrations of C5a failed to completely deactivate PMN without affecting FMLP dependent functions. These observations demonstrate the presence of a functional defect in circulating PMN during acute cutaneous inflammation. The in vitro experiments suggest transient blocking of C5a-dependent PMN functions by a cell-bound factor which seems not to be C5a or C5adesarg.

Acne Vulgaris↗

[Porokeratosis plantaris, palmaris et disseminata].

A 74-year-old patient has been affected for about 40 years by hardly discomforting keratotic lesions of the trunk and extremities, especially on the palms and soles. Some of his children and grandchildren have shown similar lesions. Histologically the diagnosis of porokeratosis was established by demonstration of a cornoid lamella. Clinically it appeared to be the rare form of porokeratosis plantaris, palmaris et disseminata, in which mainly the palms and soles are affected by hyperkeratotic papules, but nearly the whole body may be involved. It is discussed how this genodermatosis can be differentiated from other forms of porokeratosis. The family tree of our patient is compatible with autosomal dominant inheritance.

Aged↗

[Therapy of alopecia areata with diphenylcyclopropenone].

Induction and maintenance of contact dermatitis of the scalp has proved effective in producing regrowth of hair in patients with alopecia areata. We observed regrowth of hair in 17 out of 20 patients after local application of the contact allergen, diphenylcyclopropenone. Only 3 patients were treated without success. In 3 patients regrowth of hair was also seen in areas that were not treated with diphenylcyclopropenone, suggesting that this treatment has an additional systemic effect. Patient acceptance of the induced dermatitis was excellent.

Administration, Topical↗