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Notes: Background The immunosuppressant cyclosporin A has been used with success in the treatment of chronic plaque-type psoriasis; little is known about its effect on palmoplantar psoriasis.Subjects and methods Thirty-three patients (12 women, 21 men; mean age = 44.2 years, range 22-68 years) with palmoplantar psoriasis were treated with oral cyclosporin A, (CyA), 2.5 mg/kg/day, which could be increased to 5 mg/kg/day, for 12 weeks. Patients were followed up for a further 4 weeks without CyA treatment. A total of 26 patients completed the 12-week treatment course, an additional six patients were followed up during 4 weeks after premature withdrawal. Efficacy was assessed by calculating the Psoriasis Area and Severity Index (PASl). a Local Psoriasis Severity Index (LPS1), and estimation of the area involved.Results Clinical response, being defined as at least 50% reduction of these parameters at the end of the therapeutic phase compared to baseline before treatment, was reached in 84% of the patients; 61% of the patients showed clinical response after only 6 weeks of treatment. No signs of severe hepatic or renal toxicity were noted during the study period; mild hypertension, which developed in one case, resolved after termination of the treatment. Relapses after treatment never reached the pretreatment baseline levels.Conclusions It is concluded that palmoplantar psoriasis can be treated effectively and safely with oral CyA at the low-dose range of 2.5-5 mg/kg/day. The results demonstrate the necessity for evaluation of a maintenance treatment in this special form of psoriasis, the doses and safety of which remain to be determined in future controlled clinical trials.

Notes: Background A high proportion of those infected with human papilloma virus remain asymptomatic. The co-factors predisposing to the clinical manifestation of condylomata acuminata are unknown. Atopy represents a minimal form of cellular immune deficiency and shows a high association with mucocuta-neous infections. Its role in condylomata acuminata has never been investigated.Objectives To determine the role of atopy in the manifestation of condylomata acuminata.Design The presence of predisposing factors was assessed by clinical data, and serological, microbiological and proctological investigations. Atopy was evaluated by a standardised procedure, and an atopy score calculated and correlated with extent, duration and relapse rate of condylomata acuminata.Subjects Fifty-eight patients with condylomata acuminata were investigated at the Department of Dermatology of the University of Munich.Results A high proportion of patients showed predisposing local factors, such as coexistent infections, anal eczema or haemorrhoids. Many patients showed stigmata of atopy. A positive association was seen between atopy score and relapse of condylomata acuminata. The presence of atopy could be identified as a predisposing factor.Conclusions Atopy is common in patients with condylomata acuminata and may represent a co-factor for the development of clinically evident papillomas in persons infected with HPV, and offer an explanation for the high relapse rate of condylomata acuminata.

Notes: Objectives To investigate the therapeutic efficacy of acitretin + PUVA compared to placebo + PUVA in terms of improvement assessed by the Psoriasis Severity Index (PSI) and total UVA dosage.Design Double-blind, randomized, parallel, multicenter study over 8 weeks.Indication Generalized chronic plaque or exanthematic type of psoriasis severe enough to require PUVA treatment.Targets Decrease of PSI at the end of the study; response defined as improvement of PSI≥ 75% with respect to baseline, total UVA dosage applied and UVA dosage applied up to response.Statistical methods PSI changes (baseline up to end of treatment) in the two groups were compared at the 5% significance level using the Kolmogoroff-Smirnoff test (2-tailed). In addition, descriptive statistics for comparison of response rates (Chi2 test) and total UVA dosage as well as UVA dosage applied up to response (life-table analysis by Kaplan-Meier) were performed.Results Patients Forty patients (36 males. 4 females) in the placebo + PUVA and 43 patients (32 males, 11 females) in the placebo + PUVA group were investigated for efficacy. Twenty-three patients of the acitretin + PUVA group and 25 patients of the placebo + PUVA group ceased treatment prematurely. PSI The median PSI decrease was 24 (89%) score points in the acitretin + PUVA group and 21 (83%) in the placebo + PUVA group (P 〉 0.05, Kolmogoroff-Smirnoff test). The response rate was 34 out of 40 (85%; 95% CI 70-94%) in the acitretin + PUVA group and 26 out of 43 (60%; 95% CI 44–75%) in the placebo + PUVA group (P= 0.013. Chi2 test: descriptive). Complete remission The clinical outcome as assessed by the investigator was complete remission in 28 patients of the acitretin + PUVA group and 19 patients of the placebo + PUVA group. Premature discontinuation of treatment due to complete remission was possible in 16 patients of the acitretin + PUVA group and 11 patients of the placebo + PUVA group. UVA dosage The total UVA dose applied was 77.6 J/cm2 (SEM = 9.2 J/cm2) in the acitretin + PUVA group and 73.0 I/cm2 (SEM = 7.2 J/cm2) in the placebo + PUVA group. The median UVA dose up to response was 52.0 J/cm2 in the acitretin + PUVA group and 74.5 J/cm2 in the placebo + PUVA group. Tolerability In both treatment groups, adverse events were frequent. Mucocutaneous adverse events, such as dry lips, mouth and nose and dryness and scaling of the skin, were the most common complaints in both groups, but more pronounced in the acitretin + PUVA group. Treatment of adverse events included mainly indifferent ointments, non-steroidal, anti-inflammatory drugs and anti-puritic agents and tranquilizers. Treatment had to be discontinued due to adverse events in three patients of each group. In the acitretin + PUVA group, the reasons were acral-bullous photodermatosis due to PUVA, increased liver enzymes and increased triglycerides, respectively. In the placebo + PUVA group, one patient developed sensori-neural loss of hearing, one stomach pain, nausea and colics of the upper abdomen and one increased triglycerides, cholesterol and liver enzymes.Conclusions Difference in improvement of the PSI was not statistically significant between the acitretin + PUVA and the placebo + PUVA groups. However, the response rates (75% PSI decrease) and complete remission as assessed by the investigator for acitretin + PUVA was superior to PUVA alone. The UVA-saving effect could not be confirmed although the UVA dose applied up to response was less in the acitretin + PUVA group. Overall, acitretin was found to enhance the therapeutic efficacy of PUVA in patients with severe psoriasis.

Notes: Abstract:  Hurpin was identified by differential display analysis studying UV-repressible genes in the keratinocyte cell line HaCaT. We have previously reported that hurpin mRNA is overexpressed in psoriatic skin compared to non-lesional or normal skin; hurpin inhibits cathepsin L and that, after overexpression in keratinocytes, hurpin decreases UV-induced apoptosis. To further study the expression of hurpin, we have isolated monoclonal antibodies against hurpin and analyzed its expression in normal and diseased skin by immunohistochemistry (IHC). In the epidermis of normal skin, we found hurpin to be mainly expressed in the stratum basale. In contrast, we found an enhanced expression of hurpin in the stratum spinosum and stratum granulosum in the majority of diseased skin samples. Within the dermis of normal and diseased skin, hurpin was detected in sebaceous and sweat glands, hair follicles, and endothelial cells of blood vessels. Hurpin was localized in the cytoplasm in normal and diseased skin. Additionally to IHC, we analyzed hurpin expression in selected skin diseases by semiquantitative reverse-transcription polymerase chain reaction. We found overexpression of hurpin mRNA in psoriasis, squamous cell carcinoma (SCC), and actinic keratosis. In contrast, expression of hurpin in melanoma and basal cell carcinoma was comparable to that in normal skin. Overall, the strongest overexpression was observed in SCC and psoriasis. Individual differences in hurpin expression between patients were observed. The increased expression and redistribution of hurpin in diseased skin suggests its possible involvement in inflammatory processes or the regulation of endogenous or pathogen-derived proteinase activity. Additional studies will elucidate the physiological role of hurpin.

Notes: Cellular responses to platelet-derived growth factor, which affects all phases of the wound healing process, are dependent on the interaction of the growth factor with its cell surface receptors. Recently, we have shown that the platelet-derived growth factor-receptor was not expressed in uninjured human skin. In acute human wounds healing by secondary intention, both platelet-derived growth factor-receptor subunits were coordinately expressed, whereas no expression was found after reepithelialization at day 47. Even though impaired wound healing may be due to uncoordinated expression or the failure to express platelet-derived growth factor-receptor subunits, little is known regarding their expression in chronic ulcers. We studied the localization of platelet-derived growth factor-receptor expression in chronic venous leg ulcers of 15 patients with a median age of 73 years. Cryostat sections of biopsy specimens were immunostained with the use of antibodies against the α- and the β-platelet-derived growth factor subunits. RNA was extracted from biopsy specimens and subjected to Northern blot analysis with the use of oligolabeled complementary DNA for the platelet-derived growth factor-receptor. Platelet-derived growth factor-receptor α- and β-subunit expression was found in fibroblast-like cells within the wound bed and in cells beneath the epidermis of the wound edge. Platelet-derived growth factor-receptor β-subunit expression was detected in endothelial cells of the vessels, in the granulation tissue, and the wound edge, whereas platelet-derived growth factor-receptor α-subunit was not expressed in endothelial cells of the uninjured skin. This finding suggests that the platelet-derived growth factor α-subunit may be involved in vessel formation during tissue repair. Both platelet-derived growth factor-receptor subunits were expressed at the messenger RNA level indicating that the synthesis is at least partly regulated at a pretranslational level. As the cellular responsiveness to growth factors depends on their specific receptors, our finding that both platelet-derived growth factor-receptor subunits are expressed in chronic venous ulcers substantiates the concept of therapeutic trials with recombinant platelet-derived growth factor.

Notes: Dapsone yielded excellent therapeutic results in certain forms of lupus erythematosus (LE), whereas discoid lesions and the maculo-papular rash of the systemic and disseminated chronic forms of discoid LE remained uninfluenced by the drug. On the basis of these observations, we suggest the following indications for dapsone treatment in LE:〈list xml:id="l1" style="custom"〉1Vasculitic urticaria2Oral ulceratino3Non-scarring form of chronic LE4Chloroquine intolerance.

Notes: Abstract Directed migration of keratinocytes and fibroblasts is a fundamental prerequisite in wound healing. Cation-dependent affinity changes of integrins are responsible for cell adhesion to and deadhesion from extracellular matrix proteins and have been implicated in driving cell migration. The specific requirements for divalent cations in the integrin-dependent migration of human dermal fibroblasts and human epidermal keratinocytes to various extracellular matrix proteins have been studied in vitro using blindwell Boyden chambers. The migration of the tested cells to collagen type I was mediated by the α2β2 integrins, to fibronectin by the combined action of the α3β2 and the α5β1 integrin, and the migration of fibroblasts to laminin dependent both on the α2β1 and the α6β1 integrins. No migration of keratinocytes to laminin was detected. Mg2+ alone induced cell migration with an optimum at 2 mM for fibroblasts and at 10 mM for keratinocytes. Ca2+ alone at 2 mM only marginally enhanced fibroblast and keratinocyte migration. At higher concentrations Ca2+ suppressed the stimulatory Mg2+ effect. 2 mM Ca2+ combined with 2 mM Mg2+ showed an additive stimulatory effect on the migration of fibroblasts to fibronectin. These data suggest that extracellular divalent cations differentially influence the integrin-mediated cell migration. A concentration gradient of Mg2+/Ca2+, as reported in tissue injury, thus may play a regulatory role in cell migration required for tissue remodelling.

Notes: Abstract  Malignant melanomas frequently show loss of alleles on the long arm of chromosome 10. The PTEN (MMAC1) gene has been identified as a tumour suppressor gene at 10q23.3 that is mutated in various types of advanced human cancers. We have investigated a series of 40 sporadic melanomas from 37 patients (15 primary cutaneous melanomas and 25 melanoma metastases) for allelic losses on chromosome 10, as well as for deletion and mutation of the PTEN gene. Microsatellite analysis revealed loss of heterozygosity at loci located on 10q in tumours from 15 of 34 patients investigated (44%). Somatic PTEN mutations were identified in melanomas from 4 of 37 patients (11%), all of whom had metastatic disease. In two of these patients, the tumours had additionally lost one PTEN allele, indicating complete loss of wild-type PTEN in the tumour cells. Our findings corroborate that loss of heterozygosity on chromosome 10 is a frequent aberration in malignant melanomas and implicate PTEN as a tumour suppressor gene inactivated by somatic mutation in a fraction of these tumours.