The incidence of basal cell carcinoma is increasing. New aspects of diagnosis and treatment are discussed in this thesis. Interferon can be used for the treatment of BCC. In paper I, 15 patients received 13.5 x 10(6) IU of alfa-2b-interferon intralesionally. Four patients healed completely whereas a 75% reduction was seen in 5 cases. Intralesional alfa-2b-interferon can reduce the number of excisions during Mohs Micrographic Surgery. Topical photodynamic therapy involves the application of ALA on the skin. In tumour cells selectively, formation of the photosensitizer Pp IX occurs. After 4 hours of occlusion of ALA the area is irradiated with light at a wavelength of 630 nm. Tumour cells are selectively destroyed during this procedure. 144/157 SBCC healed in this series and 14/18 Mb Bowen (paper II). The method is only suited for thin BCCs as the result on thicker lesions is poor (2/10 healed). The cosmetic result was generally good or excellent. Another way of utilising the tumour selectivity of Pp IX is for diagnostic purposes. Instead of illuminating with 630 nm, 365, 366 and 405 nm are used to induce a specific fluorescence. In the present paper (III), 50% of facial BCCs with ill-defined borders could be completely visualised and another 23% partly outlined. The technique did not seem to work in 27% of the cases. The critical factor using ALA is probably the relatively poor penetrance through the skin. In paper IV, microdialysis is used for pharmacokinetic studies of ALA for the first time. The concentration of ALA increases rapidly in lesional skin whereas there is virtually no penetration in healthy skin. Also, the blood perfusion in BCCs was investigated by means of laser Doppler Perfusion Imager. The perfusion in skin overlying a BCC was 2.5 fold higher compared to normal skin. For BCCs with ill-defined borders Mohs Micrographic Surgery is generally recommended. Regarding Mohs Micrographic Surgery, Sweden is underserved as only 1% of BCCs are treated with Mohs Micrographic Surgery as opposed to 30% in the US. Consequently, the Swedish cases are probably more severe. The long-term results are reported in paper V. Two hundred and twenty-eight tumours were followed for at least 5 years. The rate of recurrence was 8%. This figure is slightly higher than in international materials but surprisingly low considering the type of tumours.
{"title":"Basal cell carcinoma--new aspects of diagnosis and treatment.","authors":"A M Wennberg","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The incidence of basal cell carcinoma is increasing. New aspects of diagnosis and treatment are discussed in this thesis. Interferon can be used for the treatment of BCC. In paper I, 15 patients received 13.5 x 10(6) IU of alfa-2b-interferon intralesionally. Four patients healed completely whereas a 75% reduction was seen in 5 cases. Intralesional alfa-2b-interferon can reduce the number of excisions during Mohs Micrographic Surgery. Topical photodynamic therapy involves the application of ALA on the skin. In tumour cells selectively, formation of the photosensitizer Pp IX occurs. After 4 hours of occlusion of ALA the area is irradiated with light at a wavelength of 630 nm. Tumour cells are selectively destroyed during this procedure. 144/157 SBCC healed in this series and 14/18 Mb Bowen (paper II). The method is only suited for thin BCCs as the result on thicker lesions is poor (2/10 healed). The cosmetic result was generally good or excellent. Another way of utilising the tumour selectivity of Pp IX is for diagnostic purposes. Instead of illuminating with 630 nm, 365, 366 and 405 nm are used to induce a specific fluorescence. In the present paper (III), 50% of facial BCCs with ill-defined borders could be completely visualised and another 23% partly outlined. The technique did not seem to work in 27% of the cases. The critical factor using ALA is probably the relatively poor penetrance through the skin. In paper IV, microdialysis is used for pharmacokinetic studies of ALA for the first time. The concentration of ALA increases rapidly in lesional skin whereas there is virtually no penetration in healthy skin. Also, the blood perfusion in BCCs was investigated by means of laser Doppler Perfusion Imager. The perfusion in skin overlying a BCC was 2.5 fold higher compared to normal skin. For BCCs with ill-defined borders Mohs Micrographic Surgery is generally recommended. Regarding Mohs Micrographic Surgery, Sweden is underserved as only 1% of BCCs are treated with Mohs Micrographic Surgery as opposed to 30% in the US. Consequently, the Swedish cases are probably more severe. The long-term results are reported in paper V. Two hundred and twenty-eight tumours were followed for at least 5 years. The rate of recurrence was 8%. This figure is slightly higher than in international materials but surprisingly low considering the type of tumours.</p>","PeriodicalId":6960,"journal":{"name":"Acta dermato-venereologica. Supplementum","volume":"209 ","pages":"5-25"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21727358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-01-01DOI: 10.1080/00015550050500040
M. Kaštelan, F. Gruber, E. Čečuk, V. Kerhin-Brkljačić, L. Brkljačić-Šurkalović, Andrija Kaštelan
In common with most autoimmune diseases, psoriasis is associated with some HLA antigens. We studied the distribution of HLA antigens in Croatian patients with psoriasis: 108 patients were divided into groups according to family history and age of disease onset. HLA antigens were analyzed serologically and HLA-C alleles were analyzed using polymerase chain reaction. We found significant increases in HLA-A2, -B17, -B37 and -B13 antigens and highly significant increases in HLA-Cw*0602 and DR7 antigens in psoriatic patients compared with controls. Patients with type I psoriasis (early onset, positive family history) showed highly significant associations with Cw*0602 [p < 0.00001; relative risk (RR) = 14.45] and DR7 (p < 0.00001; RR = 15.09) antigens. Patients with type II psoriasis (late onset, no family history) had a significant association with Cw*03 antigen (p = 0.008; RR = 0.17). In conclusion, HLA-B13, -B17, Cw*0602 and -DR7 antigens are associated with a significant risk of psoriasis in the Croatian population and the Cw*0602 allele has the strongest association, especially for type I psoriasis.
{"title":"Analysis of HLA antigens in Croatian patients with psoriasis.","authors":"M. Kaštelan, F. Gruber, E. Čečuk, V. Kerhin-Brkljačić, L. Brkljačić-Šurkalović, Andrija Kaštelan","doi":"10.1080/00015550050500040","DOIUrl":"https://doi.org/10.1080/00015550050500040","url":null,"abstract":"In common with most autoimmune diseases, psoriasis is associated with some HLA antigens. We studied the distribution of HLA antigens in Croatian patients with psoriasis: 108 patients were divided into groups according to family history and age of disease onset. HLA antigens were analyzed serologically and HLA-C alleles were analyzed using polymerase chain reaction. We found significant increases in HLA-A2, -B17, -B37 and -B13 antigens and highly significant increases in HLA-Cw*0602 and DR7 antigens in psoriatic patients compared with controls. Patients with type I psoriasis (early onset, positive family history) showed highly significant associations with Cw*0602 [p < 0.00001; relative risk (RR) = 14.45] and DR7 (p < 0.00001; RR = 15.09) antigens. Patients with type II psoriasis (late onset, no family history) had a significant association with Cw*03 antigen (p = 0.008; RR = 0.17). In conclusion, HLA-B13, -B17, Cw*0602 and -DR7 antigens are associated with a significant risk of psoriasis in the Croatian population and the Cw*0602 allele has the strongest association, especially for type I psoriasis.","PeriodicalId":6960,"journal":{"name":"Acta dermato-venereologica. Supplementum","volume":"42 1","pages":"12-3"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86017797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-01-01DOI: 10.1080/000155500750042835
S Engström, K Ekelund, J Engblom, L Eriksson, E Sparr, H Wennerström
This contribution summarises the results from a number of investigations undertaken in the spirit of the Domain Mosaic Model proposed by Forslind in 1994. Atomic Force Microscopy (AFM) studies on the two-dimensional phase behaviour of some stratum corneum lipids revealed phase separation of the lipids in the typical case and the ability of cholesterol to reduce the line tension between phases. A theoretical model was developed describing the response of an oriented stack of polar lipid bilayers in the presence of a gradient in water chemical potential (water solution to humid air). The gradient gives rise to an inhomogeneous water swelling, and presumably to a liquid crystal-to-gel transition in the lamellar region closest to humid air. Skin penetration enhancers such as Azone and oleic acid cause phase transformations in lipid bilayer systems which may be relevant in the context of skin permeation.
{"title":"The skin barrier from a lipid perspective.","authors":"S Engström, K Ekelund, J Engblom, L Eriksson, E Sparr, H Wennerström","doi":"10.1080/000155500750042835","DOIUrl":"https://doi.org/10.1080/000155500750042835","url":null,"abstract":"<p><p>This contribution summarises the results from a number of investigations undertaken in the spirit of the Domain Mosaic Model proposed by Forslind in 1994. Atomic Force Microscopy (AFM) studies on the two-dimensional phase behaviour of some stratum corneum lipids revealed phase separation of the lipids in the typical case and the ability of cholesterol to reduce the line tension between phases. A theoretical model was developed describing the response of an oriented stack of polar lipid bilayers in the presence of a gradient in water chemical potential (water solution to humid air). The gradient gives rise to an inhomogeneous water swelling, and presumably to a liquid crystal-to-gel transition in the lamellar region closest to humid air. Skin penetration enhancers such as Azone and oleic acid cause phase transformations in lipid bilayer systems which may be relevant in the context of skin permeation.</p>","PeriodicalId":6960,"journal":{"name":"Acta dermato-venereologica. Supplementum","volume":"208 ","pages":"31-5"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/000155500750042835","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21727354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-01-01DOI: 10.1080/00015550050500077
P. Pigatto
The allergen-specific IgE antibody was determined in 20 men and 120 women with psoriasis and the results were correlated with a history of current and previous allergic disease. Allergic disease was reported in 21% of the patients, but a positive RAST test was obtained in 44%. In chronic plaque-type psoriasis a positive RAST test was significantly more common (58%) than in active psoriasis (22%). Grass pollen and house dust mite were the most prevalent sensitizing allergens, with frequencies of 64% and 53%, respectively in the sensitized subjects. Sensitization increased with age and polysensitization was common. Contact dermatitis was verified with patch tests in 12 men and 20 woman, of whom 10 had chronic plaque-type psoriasis and 22 active psoriasis. Tar, nickel sulphate, corticosteroid mixture and thiomersal were the most common allergens. No irritant reactions were seen at the concentrations used. Atopic allergic diseases and contact sensitization were therefore common among our psoriatic patients.
{"title":"Atopy and contact sensitization in psoriasis.","authors":"P. Pigatto","doi":"10.1080/00015550050500077","DOIUrl":"https://doi.org/10.1080/00015550050500077","url":null,"abstract":"The allergen-specific IgE antibody was determined in 20 men and 120 women with psoriasis and the results were correlated with a history of current and previous allergic disease. Allergic disease was reported in 21% of the patients, but a positive RAST test was obtained in 44%. In chronic plaque-type psoriasis a positive RAST test was significantly more common (58%) than in active psoriasis (22%). Grass pollen and house dust mite were the most prevalent sensitizing allergens, with frequencies of 64% and 53%, respectively in the sensitized subjects. Sensitization increased with age and polysensitization was common. Contact dermatitis was verified with patch tests in 12 men and 20 woman, of whom 10 had chronic plaque-type psoriasis and 22 active psoriasis. Tar, nickel sulphate, corticosteroid mixture and thiomersal were the most common allergens. No irritant reactions were seen at the concentrations used. Atopic allergic diseases and contact sensitization were therefore common among our psoriatic patients.","PeriodicalId":6960,"journal":{"name":"Acta dermato-venereologica. Supplementum","volume":"167 1","pages":"19-20"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86735925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-01-01DOI: 10.1080/00015550050500059
Larisa Prpić, N. Strbo, V. Sotošek, F. Gruber, E. Podack, D. Rukavina
There are very few data concerning the role played by cell-mediated cytotoxicity, particularly at the molecular level, in the course of psoriasis. Both cytotoxic T lymphocytes (CTL) and natural killer cells contain in their granules the cytolytic protein perforin, a mediator in cell-mediated cytotoxicity reactions. The aim of this study was to analyze perforin expression in various sets and subsets of perforin-positive peripheral blood lymphocytes in 17 patients with chronic psoriasis vulgaris in the exacerbation phase. The results were compared with those of an age- and sex-matched healthy control group (n = 21). Perforin (intracellular antigen) and cell surface antigens were detected using the simultaneous double-staining method. We found a significant increase in perforin (P) expression in the patient group for CTL (CD3+P+ cells), which are located mostly in the CD8+ population of T lymphocytes (CD8+P+).
{"title":"Assessment of perforin expression in peripheral blood lymphocytes in psoriatic patients during exacerbation of disease.","authors":"Larisa Prpić, N. Strbo, V. Sotošek, F. Gruber, E. Podack, D. Rukavina","doi":"10.1080/00015550050500059","DOIUrl":"https://doi.org/10.1080/00015550050500059","url":null,"abstract":"There are very few data concerning the role played by cell-mediated cytotoxicity, particularly at the molecular level, in the course of psoriasis. Both cytotoxic T lymphocytes (CTL) and natural killer cells contain in their granules the cytolytic protein perforin, a mediator in cell-mediated cytotoxicity reactions. The aim of this study was to analyze perforin expression in various sets and subsets of perforin-positive peripheral blood lymphocytes in 17 patients with chronic psoriasis vulgaris in the exacerbation phase. The results were compared with those of an age- and sex-matched healthy control group (n = 21). Perforin (intracellular antigen) and cell surface antigens were detected using the simultaneous double-staining method. We found a significant increase in perforin (P) expression in the patient group for CTL (CD3+P+ cells), which are located mostly in the CD8+ population of T lymphocytes (CD8+P+).","PeriodicalId":6960,"journal":{"name":"Acta dermato-venereologica. Supplementum","volume":"97 1","pages":"14-6"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86218411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-01-01DOI: 10.1080/00015550050500022
W. Salmhofer, H. Maier, H. Soyer, H. Hönigsmann, S. Hödl
A double-blind, randomized clinical study was conducted to compare the efficacy and tolerability of twice-daily topical calcipotriol treatment with a combination treatment of calcipotriol once a day in the morning and diflucortolone valerate in the evening. Sixty-three patients with a clinical diagnosis of chronic plaque psoriasis and comparable psoriatic lesions on both sides of the body were included. After a washout phase of 1 week, psoriatic lesions were treated for 4 weeks with calcipotriol ointment twice daily on one side of the body and a combination of calcipotriol and diflucortolone valerate ointment on the other side. The treatment period was followed by a period of 4 weeks without any treatment. The psoriasis area and severity index (PASI) was used to compare the 2 groups. Furthermore, the overall therapeutic results were assessed independently by the investigators and by the patients. Both treatment regimens showed a significant, nearly identical, reduction in PASI. The mean PASI for calcipotriol alone was 5.7 at baseline, 1.9 after 4 weeks of treatment and 3.8 at the end of the follow-up period. For combination therapy, these values were 5.7, 1.8 and 3.8, respectively. There was a statistically significant advantage in favor of combined calcipotriol and diflucortolone valerate treatment at weeks 1 and 2 (p < 0.05); however, at the end of the treatment phase the difference between the 2 therapies was not significant. Subjective evaluation of efficacy by both the investigators and the patients revealed no difference between the 2 treatments. The frequency of side effects (e.g. irritation) was low in both groups. In conclusion, both therapies were effective for the treatment of chronic plaque-type psoriatic lesions. The combination of calcipotriol and a topical steroid appeared to produce a more rapid clinical response and was shown to be as effective as calcipotriol therapy alone.
{"title":"Double-blind, placebo-controlled, randomized, right-left study comparing calcipotriol monotherapy with a combined treatment of calcipotriol and diflucortolone valerate in chronic plaque psoriasis.","authors":"W. Salmhofer, H. Maier, H. Soyer, H. Hönigsmann, S. Hödl","doi":"10.1080/00015550050500022","DOIUrl":"https://doi.org/10.1080/00015550050500022","url":null,"abstract":"A double-blind, randomized clinical study was conducted to compare the efficacy and tolerability of twice-daily topical calcipotriol treatment with a combination treatment of calcipotriol once a day in the morning and diflucortolone valerate in the evening. Sixty-three patients with a clinical diagnosis of chronic plaque psoriasis and comparable psoriatic lesions on both sides of the body were included. After a washout phase of 1 week, psoriatic lesions were treated for 4 weeks with calcipotriol ointment twice daily on one side of the body and a combination of calcipotriol and diflucortolone valerate ointment on the other side. The treatment period was followed by a period of 4 weeks without any treatment. The psoriasis area and severity index (PASI) was used to compare the 2 groups. Furthermore, the overall therapeutic results were assessed independently by the investigators and by the patients. Both treatment regimens showed a significant, nearly identical, reduction in PASI. The mean PASI for calcipotriol alone was 5.7 at baseline, 1.9 after 4 weeks of treatment and 3.8 at the end of the follow-up period. For combination therapy, these values were 5.7, 1.8 and 3.8, respectively. There was a statistically significant advantage in favor of combined calcipotriol and diflucortolone valerate treatment at weeks 1 and 2 (p < 0.05); however, at the end of the treatment phase the difference between the 2 therapies was not significant. Subjective evaluation of efficacy by both the investigators and the patients revealed no difference between the 2 treatments. The frequency of side effects (e.g. irritation) was low in both groups. In conclusion, both therapies were effective for the treatment of chronic plaque-type psoriatic lesions. The combination of calcipotriol and a topical steroid appeared to produce a more rapid clinical response and was shown to be as effective as calcipotriol therapy alone.","PeriodicalId":6960,"journal":{"name":"Acta dermato-venereologica. Supplementum","volume":"5 1","pages":"5-8"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81987553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-01-01DOI: 10.1080/000155500750042817
D J Moore, M E Rerek
In order to gain some insight into the molecular organization of lipids in the skin barrier we used Fourier transform infrared (FTIR) spectroscopy to investigate models of the stratum corneum (SC) containing deuterated hexadecanoic acid, cholesterol, and ceramide 2 or ceramide 5. In both models there is clear evidence of separate conformationally ordered domains of ceramide and fatty acids. In addition, these chains are packed in orthorhombic subcells at physiological temperatures. The ceramide headgroup behavior indicates distinct hydrogen bonding patterns between the ceramide 2 and ceramide 5 models. In the ceramide 2 model the amide I mode is split into two components suggesting strong transverse intermolecular hydrogen bonding between headgroups. In contrast, no amide splitting is observed for ceramide 5 although the amide frequencies are indicative of strong hydrogen bonding. These observations on the molecular organization of SC lipids are discussed in terms of skin barrier function.
{"title":"Insights into the molecular organization of lipids in the skin barrier from infrared spectroscopy studies of stratum corneum lipid models.","authors":"D J Moore, M E Rerek","doi":"10.1080/000155500750042817","DOIUrl":"https://doi.org/10.1080/000155500750042817","url":null,"abstract":"<p><p>In order to gain some insight into the molecular organization of lipids in the skin barrier we used Fourier transform infrared (FTIR) spectroscopy to investigate models of the stratum corneum (SC) containing deuterated hexadecanoic acid, cholesterol, and ceramide 2 or ceramide 5. In both models there is clear evidence of separate conformationally ordered domains of ceramide and fatty acids. In addition, these chains are packed in orthorhombic subcells at physiological temperatures. The ceramide headgroup behavior indicates distinct hydrogen bonding patterns between the ceramide 2 and ceramide 5 models. In the ceramide 2 model the amide I mode is split into two components suggesting strong transverse intermolecular hydrogen bonding between headgroups. In contrast, no amide splitting is observed for ceramide 5 although the amide frequencies are indicative of strong hydrogen bonding. These observations on the molecular organization of SC lipids are discussed in terms of skin barrier function.</p>","PeriodicalId":6960,"journal":{"name":"Acta dermato-venereologica. Supplementum","volume":"208 ","pages":"16-22"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/000155500750042817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21727352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M S Agren, W H Eaglstein, M W Ferguson, K G Harding, K Moore, U K Saarialho-Kere, G S Schultz
The pathogenesis of venous leg ulcers is multifactorial. In this review article new physiological, molecular and cellular abnormalities in venous ulcers related to the chronic inflammation are presented and discussed. Venous hypertension causes disturbed microcirculation and pathological changes of the capillaries, which eventually locks the condition in a self-amplifying, detrimental cascade with persistent elevated levels and activities of pro-inflammatory cytokines and proteases preventing progress into a healing phase. As a consequence fibroblasts senescence and become less responsive to growth factors the older the ulcers become. Current data imply there is no deficiency but rather an unfavorable distribution of growth factors in venous ulcers. An imbalance in proteolytic enzymes and their endogenous inhibitors is a common finding in chronic venous leg ulcers. Variation in disease severity and concomitant ailments in this heterogeneous patient group may explain the contradictory results in the literature. Thus, to advance the areas of research further, longitudinal studies involving larger number of patients are required to identify the major pathogenic factors.
{"title":"Causes and effects of the chronic inflammation in venous leg ulcers.","authors":"M S Agren, W H Eaglstein, M W Ferguson, K G Harding, K Moore, U K Saarialho-Kere, G S Schultz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The pathogenesis of venous leg ulcers is multifactorial. In this review article new physiological, molecular and cellular abnormalities in venous ulcers related to the chronic inflammation are presented and discussed. Venous hypertension causes disturbed microcirculation and pathological changes of the capillaries, which eventually locks the condition in a self-amplifying, detrimental cascade with persistent elevated levels and activities of pro-inflammatory cytokines and proteases preventing progress into a healing phase. As a consequence fibroblasts senescence and become less responsive to growth factors the older the ulcers become. Current data imply there is no deficiency but rather an unfavorable distribution of growth factors in venous ulcers. An imbalance in proteolytic enzymes and their endogenous inhibitors is a common finding in chronic venous leg ulcers. Variation in disease severity and concomitant ailments in this heterogeneous patient group may explain the contradictory results in the literature. Thus, to advance the areas of research further, longitudinal studies involving larger number of patients are required to identify the major pathogenic factors.</p>","PeriodicalId":6960,"journal":{"name":"Acta dermato-venereologica. Supplementum","volume":"210 ","pages":"3-17"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21726662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-01-01DOI: 10.1080/00015550050500068
I. Bartenjev, M. R. Butina, M. P. Nik, I. Bartenjev
Epidemiological evidence implicates bacterial infection as a common triggering stimulus for psoriasis. Recent studies suggest that continuing, subclinical streptococcal and staphylococcal infections might be responsible not only for relapse of acute guttate psoriasis but also for a new episode of chronic plaque psoriasis. In this study 195 patients suffering from a severe form of chronic plaque psoriasis hospitalized between 1996 and 1998 were examined. The presence of subclinical microbial infection of the upper respiratory tract was studied by the cultivation of pathogens from this area. Patients with other provoking factors, such as a positive history of taking any drugs that may exacerbate psoriasis, endocrine and metabolic factors, alcohol abuse, trauma, dental focus and clinically evident bacterial infection, were excluded. Subclinical streptococcal and/or staphylococcal infections were detected in 68% of tested patients and in only 11% of the control group. The results of this study indicate that subclinical bacterial infections of the upper respiratory tract may be an important factor in provoking a new relapse of chronic plaque psoriasis. Searching for, and eliminating, microbial infections could be of importance in the treatment of psoriasis.
{"title":"Subclinical microbial infection in patients with chronic plaque psoriasis.","authors":"I. Bartenjev, M. R. Butina, M. P. Nik, I. Bartenjev","doi":"10.1080/00015550050500068","DOIUrl":"https://doi.org/10.1080/00015550050500068","url":null,"abstract":"Epidemiological evidence implicates bacterial infection as a common triggering stimulus for psoriasis. Recent studies suggest that continuing, subclinical streptococcal and staphylococcal infections might be responsible not only for relapse of acute guttate psoriasis but also for a new episode of chronic plaque psoriasis. In this study 195 patients suffering from a severe form of chronic plaque psoriasis hospitalized between 1996 and 1998 were examined. The presence of subclinical microbial infection of the upper respiratory tract was studied by the cultivation of pathogens from this area. Patients with other provoking factors, such as a positive history of taking any drugs that may exacerbate psoriasis, endocrine and metabolic factors, alcohol abuse, trauma, dental focus and clinically evident bacterial infection, were excluded. Subclinical streptococcal and/or staphylococcal infections were detected in 68% of tested patients and in only 11% of the control group. The results of this study indicate that subclinical bacterial infections of the upper respiratory tract may be an important factor in provoking a new relapse of chronic plaque psoriasis. Searching for, and eliminating, microbial infections could be of importance in the treatment of psoriasis.","PeriodicalId":6960,"journal":{"name":"Acta dermato-venereologica. Supplementum","volume":"14 1","pages":"17-8"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91241450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The thesis opens with review chapters concerning theoretical and practical aspects of the investigation of drug contents in the skin. A discussion of the advantages and limitations of the established methods as well as the relatively new sampling method of microdialysis, which is employed in the experimental section, is given. Factors influencing the barrier function of the normal human skin are described as are the alterations in skin barrier function found in diseased and experimentally barrier perturbed skin. The microdialysis technique consists of introducing an ultra thin, semipermeable tube, a so-called probe, in the dermis. The tube is connected to a precision pump, which provides a steady flow of a tissue-compatible fluid through the probe at a very low flow. Smaller molecules in the tissue, among them the non-protein bound fraction of the drug content in the extracellular fluid, will passively diffuse across the surface of the membrane and thus enter the flow of the perfusate, which is sampled at regular intervals and analysed. Microdialysis is used for the determination of drug levels in the skin after topical as well as systemic drug delivery in the experimental part of the thesis. The method is not applicable to the investigation of all drugs or compounds, as we have shown that it is not feasible to sample highly protein-bound drugs or very lipophilic drugs by microdialysis without further development of the method. The investigation of topical drug administration consists of 2 studies of cutaneous penetration of a model drug, salicylic acid, initially investigated in hairless rats and subsequently in human volunteers. In both studies, barrier perturbation of the skin was undertaken by physical (removal of the stratum corneum by repeated tape stripping) or chemical (treatment with acetone) methods or by provocation of irritative dermatitis (by application of sodium lauryl sulphate, a detergent). Prior to the penetration experiment, the barrier damage inflicted was quantified by non-invasive measurements of transepidermal, water loss and erythema. The penetration of salicylic acid, applied in an ethanol solution in chambers glued to the skin in the barrier perturbed areas, was measured by microdialysis sampling of the drug level in the underlying dermis. At the end of the experiment, probe depth in the dermis and skin thickness were measured by ultrasound scanning. In humans and hairless rats alike, the cutaneous drug penetration was highly increased in tape stripped skin (157- and 170-fold increased, respectively, in comparison to the penetration in unmodified skin) and in skin with irritative dermatitis (46- and 80-fold increased). Delipidization by acetone led to a doubling of the penetration in humans but had no effect on penetration in hairless rats. In both studies a close correlation between the measurements of barrier perturbation by non-invasive methods and the cutaneous drug penetration in the same area was found. In the huma
{"title":"In vivo microdialysis for the investigation of drug levels in the dermis and the effect of barrier perturbation on cutaneous drug penetration. Studies in hairless rats and human subjects.","authors":"E. Benfeldt","doi":"10.1080/00015555206159","DOIUrl":"https://doi.org/10.1080/00015555206159","url":null,"abstract":"The thesis opens with review chapters concerning theoretical and practical aspects of the investigation of drug contents in the skin. A discussion of the advantages and limitations of the established methods as well as the relatively new sampling method of microdialysis, which is employed in the experimental section, is given. Factors influencing the barrier function of the normal human skin are described as are the alterations in skin barrier function found in diseased and experimentally barrier perturbed skin. The microdialysis technique consists of introducing an ultra thin, semipermeable tube, a so-called probe, in the dermis. The tube is connected to a precision pump, which provides a steady flow of a tissue-compatible fluid through the probe at a very low flow. Smaller molecules in the tissue, among them the non-protein bound fraction of the drug content in the extracellular fluid, will passively diffuse across the surface of the membrane and thus enter the flow of the perfusate, which is sampled at regular intervals and analysed. Microdialysis is used for the determination of drug levels in the skin after topical as well as systemic drug delivery in the experimental part of the thesis. The method is not applicable to the investigation of all drugs or compounds, as we have shown that it is not feasible to sample highly protein-bound drugs or very lipophilic drugs by microdialysis without further development of the method. The investigation of topical drug administration consists of 2 studies of cutaneous penetration of a model drug, salicylic acid, initially investigated in hairless rats and subsequently in human volunteers. In both studies, barrier perturbation of the skin was undertaken by physical (removal of the stratum corneum by repeated tape stripping) or chemical (treatment with acetone) methods or by provocation of irritative dermatitis (by application of sodium lauryl sulphate, a detergent). Prior to the penetration experiment, the barrier damage inflicted was quantified by non-invasive measurements of transepidermal, water loss and erythema. The penetration of salicylic acid, applied in an ethanol solution in chambers glued to the skin in the barrier perturbed areas, was measured by microdialysis sampling of the drug level in the underlying dermis. At the end of the experiment, probe depth in the dermis and skin thickness were measured by ultrasound scanning. In humans and hairless rats alike, the cutaneous drug penetration was highly increased in tape stripped skin (157- and 170-fold increased, respectively, in comparison to the penetration in unmodified skin) and in skin with irritative dermatitis (46- and 80-fold increased). Delipidization by acetone led to a doubling of the penetration in humans but had no effect on penetration in hairless rats. In both studies a close correlation between the measurements of barrier perturbation by non-invasive methods and the cutaneous drug penetration in the same area was found. In the huma","PeriodicalId":6960,"journal":{"name":"Acta dermato-venereologica. Supplementum","volume":"92 1","pages":"1-59"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79992343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}