Remission and relapse of chronic plaque psoriasis treated once a week with clobetasol propionate occluded with a hydrocolloid dressing versus twice daily treatment with clobetasol propionate alone.

BACKGROUND: Many studies have shown the clinical efficiency of occlusion therapy for psoriasis, particularly corticosteroids used under hydrocolloid dressings. However, there are no data from comparative clinical studies evaluating the remission and relapse characteristics of such occlusion therapy compared with orthodox topical steroid monotherapy. METHODS: In a randomised, open-label, parallel group study from three centres, the remission and relapse characteristics were investigated for the use of a hydrocolloid dressing (HCD) over clobetasol propionate 0.05% lotion once a week compared with the same steroid in ointment formulation used unoccluded twice a day in 61 patients with stable chronic plaque psoriasis. RESULTS: There was a pronounced treatment difference in favour of the HCD + clobetasol propionate lotion group with respect to time to clearance, but there was little evidence for a difference with respect to time to relapse. CONCLUSION: The combination of the HCD + clobetasol propionate lotion provides a fast and highly effective remission induction.

Diver's hand: a skin disorder common in occupational saturation diving.

Saturation divers regularly inspect North Sea installations, working at depth for periods of 12-16 days. Diver's hand is a particular problem in saturation diving, and there is no effective protection or treatment available. This paper presents the occurrence of diver's hand and describes the disease in clinical and epidemiological terms. Three studies of diver's hand have been carried out, in 1990, 1994, and 1995. Most long term saturation divers have had diver's hand at some time in their professional career. Diver's hand seems able to occur without any previous skin symptoms, and divers without diver's hand can have several other skin symptoms during a saturation period. It is likely that diver's hand is a specific phenomenon associated with saturation diving.

Pigmentary changes after pulsed dye laser treatment in 125 northern European patients with port wine stains.

We investigated the occurrence of pigmentary changes after flash lamp pumped dye laser treatment in 125 Norwegian patients. Post-treatment hyperpigmentation occurred with equal frequency during summer and winter (23%), and the facial regions did not exhibit higher occurrence than lesions located elsewhere. The patients that achieved hyperpigmented skin were not exposed to any higher fluence than those without this complication. On the contrary, we found that during the summer period from April to September the patients with post-treatment hyperpigmentation had been exposed to a significantly lower dose than those without pigmentary changes. These results indicate that the epidermal melanin content is not the only criterion for obtaining post-treatment hyperpigmentation. There might also be a constitutional disposition. In predisposed individuals the threshold dose for hyperpigmentation might be reduced in summer when the skin is more pigmented.

Laser treatment of port wine stains: therapeutic outcome in relation to morphological parameters.

Thirty patients were treated with a flashlamp-pumped pulsed dye laser, with 0.45 ms pulse width and 585 nm wavelength. Punch biopsies were taken prior to treatment, and the biopsies were examined morphometrically. Three different test sites were exposed to laser light of fluence 5.25, 6.50 and 7.75 J/cm2. The degree of blanching was examined 6-8 weeks after treatment, and each site was retreated four times. Six patients (20%) achieved poor blanching, eight patients (27%) obtained moderate lightening and 16 patients (53%) showed good response. The vessels of the good responders were located significantly more superficially than the vessels of the moderate and poor responders (P < 0.05). The poor responders had significantly smaller vessels than the moderate and good responders (P < 0.01). The moderate responders had deeper, but larger vessels, than the poor responders. Hence, an increasing vessel diameter reduces the negative outcome of increasing vessel depth. The vessel diameter was correlated to the colour (P < 0.01), e.g. the mean vessel diameter was increasing from 16.5 microns in pink lesions to 51.2 microns in purple lesions. The vessel depth was partly reflected in the lesional colour, as the pink and purple lesions had significantly deeper vessels than the red ones (P = 0.02). These results indicate that pink lesions predict poor blanching due to deeply located small vessels, while red lesions predict a good therapeutic result because of more superficially located vessels.

Oxidation of thymine to 5-formyluracil in DNA: mechanisms of formation, structural implications, and base excision by human cell free extracts.

Oxidative agents produce several different types of base modifications in DNA, and only a few of these have been properly characterized with respect to mechanisms of formation and biological implications. We have established a procedure using neutral thermal hydrolysis and reverse phase high-performance liquid chromatography to determine the content of the oxidation product 5-formyluracil (5-foU) in DNA. With this method, it is shown that 5-foU residues are formed with high frequency from thymine by quinone-sensitized UV-A photooxidation. Since 5-foU is also induced by ionizing radiation, it appears to be formed under conditions where thymidine radical cations are generated and react with molecular oxygen. It was previously shown that 5-foU is formed directly from [methyl-3H]thymine residues in radioactively labeled DNA by two consecutive transmutations of 3H to 3He. The theoretical basis for the kinetics of such conversion is presented in this paper, and the calculated yields are confirmed experimentally by measuring the content of 5-foU in [methyl-3H]thymine-labeled DNA aged for different time periods. Such DNA contains virtually only 5-(hydroxymethyl)uracil and 5-foU, apart from normal bases, and is therefore very useful for the investigation of repair enzyme activities involved in the repair of 5-foU-containing DNA. Using this substrate, a DNA glycosylase activity was identified in human cell extracts for the removal of 5-foU.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the AlkA enzyme in Escherichia coli.

The alkA gene of Escherichia coli encodes a DNA glycosylase involved in base excision repair of DNA alkylation damage. In an attempt to define the reactions of the AlkA enzyme with methylated DNA, we discovered that the enzyme released substantial amounts of radioactivity from [methyl-3H]thymidine-labeled DNA even without any exposure of the DNA to methylating agents. The excised material was identified by chromatography as two different oxidized derivatives of thymine, 5-hydroxymethyluracil and 5-formyluracil. These products are formed in such DNA by one and two consecutive decays, respectively, of the tritiums of the labeled methyl group. Kinetic analysis showed that both the apparent Km and Vmax values for 5-formyluracil removal are within the same range as found for 3-methyladenine removal, suggesting that this catalytic property of AlkA is also significant under in vivo conditions. Removal of 5-hydroxymethyluracil proceeds at a rate that is 1-3 orders of magnitude slower. Since both 5-formyluracil and 5-hydroxymethyluracil are major products formed in DNA by exposure to ionizing radiation, these results implicate the alkA gene function also in the repair of oxidative DNA damage. Neither of the two other enzymes involved in the repair of oxidative DNA damage in E. coli, i.e. endonuclease III and formamidopyrimidine DNA glycosylase, has any affinity for oxidized unsaturated pyrimidines in DNA.

Elevated expression of human nonpancreatic phospholipase A2 in psoriatic tissue.

In involved psoriatic tissue, which is characterized by chronic inflammation in both epidermis and dermis, elevated levels of arachidonic acid and eicosanoids have been measured. This implies that a phospholipase A2 (PLA2) may be involved in the pathogenesis of psoriasis. The PLA2's are a group of enzymes that release unsaturated fatty acids from the sn2-position of membrane phospholipids. Once released, the fatty acids are converted by various enzymes into biologically very important signaling molecules. Release of arachidonate initiates the arachidonate cascade, leading to the synthesis of eicosanoids such as prostaglandins, thromboxanes, leukotrienes, and lipoxines. Eicosanoids are important in a variety of physiological processes and play a central role in inflammatory mediators, such as lyso-PAF (a precursor for PAF) and other lysophospholipids, may also be formed through the action of a PLA2. We report for the first time the detection of transcripts of nonpancreatic phospholipase A2 (npPLA2, type II) and cytosolic (c) PLA2 in human skin, and overexpression of npPLA2 in involved skin from patients with psoriasis (plaque psoriasis and pustular psoriasis). Limited amounts of npPLA2 enzyme are detected immunologically in the uppermost layers of epidermis from healthy persons. Both involved and uninvolved psoriatic epidermis contain higher levels of npPLA2 than normal skin. Positive cells in dermis showed significantly higher levels of npPLA2 than epidermal cells. In dermis from healthy persons, only weak staining of a few cells could be detected. The two PLA2 enzymes detected in psoriatic skin (cytosolic and nonpancreatic) may both be involved in eicosanoid overproduction in psoriatic tissue, and the npPLA2 may also be involved in potentiating cell activation, especially T cells.

Low incorporation of dUMP by some thermostable DNA polymerases may limit their use in PCR amplifications.

Incorporation of dUMP instead of dTMP is frequently used to control carryover contamination during PCR amplifications. We have tested four thermostable DNA polymerases for their ability to utilize dUTP as a substrate in PCR. Amplification of products in the presence of dUTP instead of dTTP was good with Thermus aquaticus DNA polymerase but highly inefficient with three other thermostable DNA polymerases. The latter was due to: (a) lower incorporation of dUMP relative to dTMP, (b) increased proofreading toward dUMP in DNA, (c) relative termination at dUMP residues as verified by sequencing reactions in the presence of dUTP, (d) thermostable dUTPase activity in the commercial enzyme preparation. The last point only applies to Pyrococcus furiosus DNA polymerase. This study demonstrates that various thermostable DNA polymerases utilize dTTP and dUTP with highly different efficiencies and thus the choice of DNA polymerase may be critical for amplification of DNA.

Consensus sequences for good and poor removal of uracil from double stranded DNA by uracil-DNA glycosylase.

We have purified uracil DNA-glycosylase (UDG) from calf thymus 32,000-fold and studied its biochemical properties, including sequence specificity. The enzyme is apparently closely related to human UDG, since it was recognised by a polyclonal antibody directed towards human UDG. SDS-PAGE and western analysis indicate an apparent M(r) = 27,500. Bovine UDG has a 1.7-fold preference for single stranded over double stranded DNA as a substrate. Sequence specificity for uracil removal from dsDNA was examined for bovine and Escherichia coli UDG, using DNA containing less than one dUMP residue per 100 nucleotides and synthetic oligonucleotides containing one dUMP residue. Comparative studies involving about 40 uracil sites indicated similar specificities for both UDGs. We found more than a 10-fold difference in rates of uracil removal between different sequences. 5'-G/CUT-3' and 5'-G/CUG/C-3' were consensus sequences for poor repair whereas 5'-A/TUAA/T-3' was a consensus for good repair. Sequence specificity was verified in double stranded oligonucleotides, but not in single stranded ones, suggesting that the structure of the double stranded DNA helix has influence on sequence specificity. Rate of uracil removal appeared to be slightly faster from U:A base pairs as compared to U:G mis-matches. The results indicate that sequence specific repair may be a determinant to be considered in mutagenesis.

[Effective treatment of chronic inflammatory skin diseases. Once a week occlusion therapy with clobetasol propionate and Duoderm]. / Effektiv behandling av kronisk inflammatoriske hudsykdommer. Okklusjonsbehandling med klobetasol propionat og Duoderm en gang ukentlig.

The lesions of 161 patients with chronic skin diseases that were unresponsive to therapy were treated once a week with clobetasol propionate lotion left under the completely occlusive patch Duoderm. The lesions completely resolved after a period of nine days to four weeks in 148 patients, while partial remission was observed in the remaining 13. The following diseases responded favourably: chronic plaque psoriasis, psoriasis on palms and soles, palmoplantar pustulosis, skin lesions related to Reiter's syndrome, chronic lichenified eczema, neurodermatitis, breast eczema, discoid lupus erythematosus, lichen planus, sarcoidosis, lichen sclerosus et atrophicus and lymphocytic infiltrate of Jessner. Relapses were infrequent when complete histological remission had been achieved. Other diseases which improved with this treatment were pompholyx, necrobiosis lipoidica, granuloma annulare and pretibial myxoedema.

Short-contact treatment at home with Micanol.

The efficacy of home treatment of psoriasis with a new dithranol formulation, Micanol, was investigated in three studies. They were carried out according to a randomized, within-patient comparison design. In a 4-week pilot study Micanol was compared with placebo (10 patients) and in two 6-week studies Micanol was compared with dithranol 1% in petrolatum (33 patients) and with dithranol 1% in Amitase stick (16 patients). Micanol was found to be effective and well suited for treatment at home in all studies. The vehicle itself did not improve the psoriasis plaques. The rate of clinical improvement was faster for dithranol in petrolatum and Amitase stick than for Micanol. The prevalence and severity of erythema, burning and staining of skin and clothing were far less for Micanol. Approximately half the number of patients preferred dithranol in petrolatum or Amitase stick and the other half preferred Micanol.

Successful treatment of therapy-resistant atopic dermatitis with clobetasol propionate and a hydrocolloid occlusive dressing.

During recent years, 48 patients with therapy-resistant chronic skin lesions of atopic dermatitis have been treated once a week with clobetasol propionate lotion left under Duoderm occlusive patches. They had previously failed to respond, or responded only sparsely, to topical corticosteroids. The lesions resolved completely in 44 patients, while partial remission was observed in the remaining 4. The mean time needed to obtain complete remission was, for lichenifications, 2 weeks; pruriginous lichenoid papules, 12 days; chronic hand eczema, 2.5 weeks; nummular eczema, 8 days; perioral eczema, 11 days, and breast eczema, 10 days. Adverse experiences were mild and infrequent. The amount of topical corticosteroid required was reduced to at most one-twentieth and to as little as one-hundredth of the amount of common topical steroid treatment needed. We conclude that clobetasol propionate and Duoderm once a week is the best treatment for resistant lesions of atopic dermatitis.

Successful treatment of chronic skin diseases with clobetasol propionate and a hydrocolloid occlusive dressing.

The lesions of 141 patients with chronic skin diseases unresponsive to therapy were treated once a week with clobetasol propionate lotion left under the completely occlusive patch Duoderm. In 131 patients the lesions resolved completely, while partial remission was observed in the remaining 10. The mean interval to complete remission was: for chronic plaque psoriasis, 12 days; psoriasis on palms and soles, 2.5 weeks; palmoplantar pustulosis, 2.2 weeks; skin lesions of Reiter's syndrome, 3 weeks; chronic lichenified eczema, 2.0 weeks; neurodermatitis, 3.1 weeks; breast eczema, 9 days; discoid lupus erythematosus, 3.7 weeks; lichen planus, 2.8 weeks; sarcoidosis, 4 weeks; and lichen sclerosus et atrophicus, 2 weeks. Other conditions benefitting from the treatment were pompholyx, necrobiosis lipoidica, granuloma annulare and pretibial myxedema. The amount of topical corticosteroids needed was reduced to at most 1/20 and to as little as 1/100, compared with common topical steroid preparations.

[Dermatological laser treatment]. / Dermatologisk laserbehandling.

This article reviews the different lasers used in dermatology. Special emphasis is placed on the treatment of naevus flammeus ("portwine stain") where lasers are the treatment of choice. Argon laser and pulsed dye laser are the main lasers used in vascular skin diseases, and the article focuses on these two types. Copper vapour laser, neodymium-YAG-laser and CO2-laser are also presented. Information is provided about the availability of laser technology in the different health regions in Norway.

[Local sunscreening agents--why, when, how and where?]. / Lokale solbeskyttelsesmidler--hvorfor, når, hvordan og hvor?

Sunscreens are used primarily to protect against sunburn. The cosmetic benefits of sunscreens have been widely accepted with the recent indictment of photoaging as a major cause of wrinkles. It is not so well known that sunscreens also protect against the development of carcinomatous processes in the skin. It is important to protect against UV-A as well as against UV-B because UV-A has an additional effect and can also itself initiate cancer. We advocate use of sunscreens with a high sun protection factor. It is of utmost importance to protect children against the deleterious effects of the sun to prevent development of skin cancer later in life. The article includes an overview of the most common active sunfilter compounds. Allergy to these compounds does occur but is rare. Certain textiles provide good but varying protection against the sun.

The production of tumour necrosis factor, tissue thromboplastin, lactoferrin and cathepsin C during lipopolysaccharide stimulation in whole blood.

The release of tumour necrosis factor (TNF), lactoferrin (LF) and cathepsin C (CC) into plasma and production of thromboplastin (TPL) in monocytes were studied in lipopolysaccharide (LPS) stimulated heparinized whole blood from 10 healthy donors. The influence of dextran 70, haemaccel and methylprednisolone on levels of these parameters were examined. TNF concentration in plasma 5 min after the addition of LPS (0 h) was 250 pg/ml (median), 520 pg/ml after 1 h and 1300 pg/ml after 3 h. The addition of dextran 70 to the blood in addition to LPS at the same intervals gave significantly higher values of 740 pg/ml and 1800 pg/ml after 1 h and 3 h respectively. Unstimulated cells had no TPL but after 1 h with LPS, the TPL activity in incubated cells was 2.3 mU/10(6) monocytes and after 3 h, 2.7 mU/10(6) monocytes. LPS induced the secretion of LF from granulocytes (PMN) and the levels 5 min after the addition of LPS (0 h) were 2.1 mg/l (control 0.2 mg/l) and after 1 h, 5.3 mg/l (control 1.3 mg/l) in plasma after LPS stimulation. Haemaccel enhanced the LPS-induced generation of TPL in monocytes and production of CC. The LPS-induced secretion of LF was, to a small extent, influenced by the three reagents tested. Methylprednisolone (1 mmol/l) reduced the production and appearance of TNF in plasma and the generation of TPL activity in monocytes. This model for stimulating heparinized whole blood is suitable for examination of the production and appearance of cellular factors and the influence of drugs on this production.

[Malignant melanoma--a warning. How to reduce mortality?]. / Malignt melanom--et varsko. Hvordan redusere dødeligheten?

Incidence of malignant melanoma of the skin has risen rapidly during the last decades. Mortality rates are also rising, although not so much as incidence rates. There is strong evidence that exposure to sunlight is a major factor in the etiology of melanomas. There appears to be no direct cumulative dose-response relationship, except in the case of lentigo maligna melanoma. Episodes of sunburn among children and young individuals seem to be more important as an etiologic factor for melanoma than chronic exposure to the sun. Very high risk of melanoma exists in persons with dysplastic nevus syndrome. Persons with giant congenital nevi are also at increased risk. However, many melanomas arise de novo. It is our intention to reduce mortality by screening families at risk, by early detection and treatment of melanomas, and by education.

Ultraviolet radiation at high latitudes and the risk of skin cancer.

Solar irradiance in the spectral region 280 to 800 nm was measured with a double monochromator at 2 locations in Norway, Tromsø (69.7 degrees N) and Longyearbyen (78.2 degrees N). During the observational (midnight sun) period in Longyearbyen, the maximum UVB irradiance recorded was less than 0.3 W/m2, and no radiation was detected for wavelengths below 300 nm. Such low levels are believed to be a consequence of the low solar elevation angle and the high ozone content of the Arctic ozone layer, which absorbs the incident UV light. With levels between 280 and 350 DU over the period of study, Tromsø and Longyearbyen recorded only one-ninth of the calculated UVB radiation at the equator. There is therefore a considerably higher risk of radiation damage to the skin in equatorial regions (controlling for skin type), a finding that agrees with the statistical evidence for a 7-8 times higher rate of skin cancer in the white population of equatorial countries.