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Biomedical subjects

F G Larsen

Publications and source records attributed to F G Larsen.

At least 19 recordsLinked to original sources
PubMed2002

A new calcipotriol/betamethasone formulation with rapid onset of action was superior to monotherapy with betamethasone dipropionate or calcipotriol in psoriasis vulgaris.

In this study, we compared a new combination ointment containing both calcipotriol and betamethasone dipropionate with betamethasone dipropionate ointment (Diprosone) and calcipotriol ointment (Daivonex) in patients with psoriasis vulgaris; 1106 patients were randomized to twice daily double-blind treatment with combination, betamethasone dipropionate or calcipotriol for 4 weeks. Patients then received twice daily calcipotriol, unblinded, for a further 4 weeks. Mean percentage change in PASI at end of the double-blind phase was -74.4 (combination group), -61.3 (betamethasone group) and -55.3 (calcipotriol group). Mean difference (95% Cl) combination-betamethasone was -13.1 (-16.9 to -9.3, p < 0.001) and for combination-calcipotriol -19.0 (-22.8 to -15.2, p <0.001). The differences in PASI were also statistically significant after 1 week. In the double-blind phase, 8.1% of patients (combination) reported lesional/ perilesional adverse reactions compared to 4.7% (betamethasone) and 12.0% (calcipotriol). In the combination group, mean PASI at the end of the double-blind phase was 2.5, and at end of the unblinded phase 3.6, compared with 3.9 and 4.1 (betamethasone) and 4.4 and 3.7 (calcipotriol). Calcipotriol/betamethasone combination is more effective and has a more rapid onset of action than either active constituent used alone, and is well tolerated. It is safe to transfer patients from combination to calcipotriol, with maintenance of clinical effect.

Administration, Topical↗
PubMed2002

Safety and efficacy of combined high-dose treatment with calcipotriol ointment and solution in patients with psoriasis.

BACKGROUND: In the vast majority of psoriatic patients, psoriatic lesions are localised on the body as well as on the scalp. Therefore, safety data on the combined use of calcipotriol in lotion and calcipotriol in ointment are needed. OBJECTIVE: This study investigated the effect of high-dose treatment with a combination of calcipotriol ointment and scalp solution on calcium metabolism, indices of bone turnover and PASI in patients with extensive psoriasis. METHODS: Following a 2-week wash-out period, 88 patients were randomised to 4 weeks of treatment with either calcipotriol ointment/scalp solution (80-100 g/week and 30-50 ml/week, respectively; n = 41) or with a dithranol/tar regimen (n = 47). Patients were seen at weeks 1, 2 and 4 during treatment and 1 week following cessation of treatment. RESULTS: No significant differences at the end of treatment were found between the 2 groups with respect to 24-hour urinary excretion of calcium (expressed as calcium/creatinine ratio), phosphate or pyridinoline, serum concentrations of calcium (albumin corrected), creatinine, phosphate, parathyroid hormone, 25-hydroxyvitamin D(3), 1,25-dihydroxyvitamin D(3), osteocalcin, alkaline phosphatase (total and bone-specific iso-enzymes) or 1-collagen telopeptide. At the end of treatment, the psoriasis area and severity index had decreased by 57.4% in the calcipotriol group and by 36.1% in the dithranol/tar group (p = 0.004). Investigators' and patients' assessments of overall efficacy also favoured treatment with calcipotriol (p < 0.001). CONCLUSION: The combined use of calcipotriol ointment/scalp solution did not affect the indices of calcium metabolism or bone turnover and was significantly more effective than dithranol/tar in reducing disease severity and extent in patients with extensive psoriasis.

Administration, Topical↗
PubMed2001

Structural asymmetry as a dermatoscopic indicator of malignant melanoma--a latent class analysis of sensitivity and classification errors.

Asymmetry of pigmented skin lesions is an important indicator of possible malignant melanoma and contributes substantially to the diagnosis of melanoma in the dermatoscopic ABCD rule for melanocytic lesions and other algorithms. However, it may be observer dependent. Dermatoscopic asymmetry cannot be assessed objectively and no golden standard of asymmetry diagnosis exists. The aim of this study was to assess the sensitivity of axis (a-) symmetry using latent class analysis. We analysed ratings from four experts in dermatoscopy of 232 pigmented lesions by latent class analysis (LCA). Possible ratings were 'no asymmetry', 'asymmetry in one axis' and 'asymmetry in two axes'. A subset of melanocytic lesions (blue naevi excluded) was analysed. Based on LCA, the asymmetry of the singular lesion was determined. The sensitivity of 'no asymmetry' was 40-77%, 40-70% for one-axis asymmetry, and 77-92% for two-axes asymmetry. Overestimation of asymmetry was more common than underestimation. Melanomas were significantly more asymmetric than pigmented naevi, atypical naevi and papillomas, but not basal cell cancers. Analysis of the melanocytic subset gave similar results. The median asymmetry of malignant melanomas (1.67, interquartile range 1.81-1.99) was higher than for melanocytic naevi. In conclusion, asymmetry and symmetry are important criteria for diagnosing or excluding malignant melanoma using the dermatoscopic ABCD rule, risk stratification and other diagnostic rules. Using LCA, we minimized observer dependence in the assessment of axis (a-) symmetry. LCA, besides conceptualizing the diagnostic process, enables the assignment of lesions to their true diagnostic class.

Basal Cell Carcinoma↗
PubMed1999

[Investigation of malignant melanoma in an "open house" setting].

Individuals with a self-evaluated risk of malignant melanoma were invited to an "open house" where trained dermatologists examined suspected lesions. The attendants filled in a short questionnaire relating to skin cancer risk factors. Persons with skin changes suspected for malignancy were referred for excision in the dermatological department. The clinical evaluation included dermatoscopy. Nine hundred and eleven individuals attended. Among 16 individuals referred for excision one malignant melanoma, one lentigo maligna melanoma and two in situ melanomas were histologically verified. Furthermore, 21 basal cell carcinomas were identified clinically. The most frequent clinical diagnoses were melanocytic naevi and seborrhoic keratoses.

Adult↗
PubMed1999

The dermatoscopic ABCD rule does not improve diagnostic accuracy of malignant melanoma.

The dermatoscopic ABCD rule has been suggested to improve diagnostic performance regarding cutaneous malignant melanoma. Using this rule, a total dermatoscopy score is calculated from the presence of various dermatoscopic elements. A total dermatoscopy score above 4.75 signifies possible and 5.45 probable melanoma. We compared the diagnostic accuracy of dermatoscopy with and without the use of the ABCD rule. Furthermore, receiver operating characteristic analysis was performed for the ABCD rule. The area under the receiver operating characteristic curve was 0.854 (range 0.777-0.906) demonstrating that in 85.4% of the cases, cutaneous malignant melanomas were rated higher than the non-melanoma skin lesions. Sensitivity for the melanoma diagnosis was higher for simple dermatoscopy than when the ABCD rule was used (p<0.05). There was no difference in specificity when a total dermatoscopy score of 4.75 was used as cut-off point, but specificity was lower for simple dermatoscopy than when the total dermatoscopy score of 5.45 was used. Diagnostic accuracy was higher for simple dermatoscopy than for the ABCD rule (p<0.01). In conclusion, the dermatoscopic ABCD rule was not superior to simple dermatoscopy, and fewer malignant melanomas were identified with this rule.

Biopsy, Needle↗
PubMed1999

Clinical and dermatoscopic diagnosis of malignant melanoma. Assessed by expert and non-expert groups.

We investigated the nosographic and diagnostic probabilities and likelihood ratios of dermatoscopy in order to evaluate the method's role in decision-making regarding melanoma. Clinical slides and dermatoscopic photos were obtained from 232 patients referred for dermatoscopy. Four dermatoscopy "experts" and 5 "non-experts" assessed the slides. Diagnoses were compared with histopathology. Sensitivity of the clinical assessments was 0.78 vs. 0.69 ("experts" vs. "non-experts"), sensitivity of dermatoscopy assessment was 0.83 vs. 0.69 (p = 0.04). The expert group demonstrated increased specificity (from 0.89 to 0.94) when applying dermatoscopy compared with clinical assessment alone (p=0.03). Positive likelihood ratios were doubled in the "expert group" and the negative likelihood ratios improved 25% with dermatoscopy compared with clinical assessment.

Data Interpretation, Statistical↗
PubMed1998

Urocanic acid isomers in patients with basal cell carcinoma and cutaneous malignant melanoma.

Urocanic acid (UCA) is a major chromophore for ultraviolet (UV) radiation in the skin. On UV exposure, the naturally occurring trans-isomer converts to the cis-isomer in a dose-dependent manner. Accumulating evidence indicates that cis-UCA acts as an initiator of the UV-induced suppression of certain skin immune functions. This immunomodulation is recognized as an important factor in the development of skin cancer. In this study, pigmentation and UCA isomers were measured in 29 patients with previous basal cell carcinoma (BCC), 23 patients with previous cutaneous malignant melanoma (MM), and 32 healthy controls. Measurements were performed on UV-exposed (forehead, upper back) and UV non-exposed (buttock) skin. No significant differences in pigmentation percentage, total UCA concentration, relative (%) or absolute (nmol/cm2) cis-UCA concentration were observed between the groups in any of the body sites studied. The net production of cis-UCA after irradiation with a single test UV dose was evaluated. The relative production of cis-UCA following irradiation was significantly higher in both cancer groups when compared with the control group, while no significant difference was found between the BCC and the MM patients.

Adult↗
PubMed1994

Retinoic acid induces expression of early growth response gene-1 (Egr-1) in human skin in vivo and in cultured skin fibroblasts.

The early growth response gene, Egr-1 (NGFI-A, krox 24, zif 268, TIS 8), is a member of a family of genes with suggested importance in the regulation of cell growth and differentiation. Retinoic acid has been shown to markedly induce Egr-1 gene expression in mouse embryonal carcinoma cells and rat preosteoblastic cells. In this study we demonstrate that treatment of cultured human skin fibroblasts with retinoic acid results in a rapid transient four-fold induction of Egr-1 transcripts, being maximum at 60 min and returning to a basal level by 120 min. However, treatment of cultured human keratinocytes with retinoic acid did not significantly induce Egr-1 transcripts. Expression of Egr-1 message in keratinocytes was observed to be induced by fetal bovine serum and tetra-decanoyl phorbol acetate, whereas calcium, 1,25-dihydroxyvitamin D3, and cyclic adenosine monophosphate caused little or no induction. Topical application of 0.1% retinoic acid cream in vivo resulted in a two- to threefold induction of Egr-1 transcripts following treatment for 24 and 48 h, returning to nearly basal levels by 96 h. Taken together, these data are consistent with the possibility that Egr-1 is a proximal component of an intracellular molecular cascade that may give rise to alterations in cell phenotype in response to retinoic acid.

Blotting, Northern↗
PubMed1994

Retinoic acid induces expression of PA-FABP (psoriasis-associated fatty acid-binding protein) gene in human skin in vivo but not in cultured skin cells.

PA-FABP (psoriasis-associated fatty acid-binding protein) is a new member of a group of low-molecular-weight proteins that are highly up-regulated in psoriatic skin and that share similarity to fatty acid-binding proteins. In this study we demonstrate that PA-FABP transcripts are expressed in human skin in vivo and that topical application of 0.05% retinoic acid (RA) cream results in a rapid induction of PA-FABP transcripts following treatment for 16 hours and persists at increasing levels after 48 and 96 h of RA treatment. The PA-FABP mRNA response to RA was reduced by approximately 50% when patients concurrently were treated with RA and 0.025% clobetasol propionate (CLO) for 48 and 96 h, whereas treatment with CLO alone resulted in PA-FABP transcript levels not significantly different from vehicle-treated skin. When comparing the effects of a well-known irritant, sodium lauryl sulfate (SLS), to those of RA and its vehicle, 0.05% RA cream but not 2% SLS in RA vehicle caused PA-FABP mRNA induction after 16 h. SLS treatment of human skin for 96 h caused a slight increase in PA-FABP transcripts, but markedly less than that observed in response to RA treatment. Incubation of cultured human keratinocytes or skin fibroblasts with RA for up to 48 h did not significantly induce PA-FABP transcripts. Expression of PA-FABP message in keratinocytes was observed to be induced by calcium and fetal calf serum (FCS), while tetra-decanoyl phorbol acetate (TPA) caused little or no induction.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1993

Conversion of acitretin to etretinate in psoriatic patients is influenced by ethanol.

Acitretin has recently been introduced to replace etretinate in the treatment of severe psoriasis due to a considerable shorter terminal half-life. The previously recommended 2-month anticonceptive period after acitretin treatment has been extended to 2 years after the detection of etretinate in certain acitretin recipients. In the present study, 10 patients with severe psoriasis were treated with 30 mg acitretin daily for 3 months. Seven patients had detectable mean steady-state plasma etretinate concentrations in the range of 2.5 to 56.7 ng/ml. Four of the patients showed teratogenic levels of plasma etretinate. Consumption of alcohol appeared to be an important contributing factor for the formation of etretinate. As judged from the dose- and body-weight-normalized AUC values (AUCcor) there was a great inter-individual variation (sixfold) in the systemic availability of acitretin. After discontinuation of therapy, the rate of elimination of both acitretin (t1/2 range 1.0 to 25.4 d) and 13-cis-acitretin (t1/2 range 1.5 to 25.7 d) was found to be related to the observed mean steady-state level of etretinate as evidenced by a longer terminal t1/2 of patients with high levels of etretinate in plasma. A mean terminal elimination half-life of etretinate was found to be 45.7 d +/- 10.6 (mean +/- SD; range 27.0 to 59.3 d). The risk of metabolic formation of etretinate in acitretin recipients makes it impossible to draw any definite conclusion with regard to recommendation of length of anticonceptive period following acitretin therapy in psoriatics. Monitoring of plasma etretinate levels in acitretin-treated fertile women is advisable.

Acitretin↗
PubMed1992

Pharmacokinetics and therapeutic efficacy of retinoids in skin diseases.

The retinoids are a class of compounds that includes the natural forms and synthetic analogues of vitamin A. Isotretinoin, often referred to as a first generation retinoid, may be of considerable benefit to patients with severe, recalcitrant acne. Etretinate and acitretin, 2 aromatic compounds representing the second generation, have found their major success in the treatment of psoriasis, particularly in combination with more traditional therapies. Retinoid therapy is associated with a distinctive adverse effect profile typical of hypervitaminosis A; thus, it is especially important that fertile women undergoing retinoid therapy adhere to a contraceptive regimen. These drugs are extensively metabolised and only traces of unchanged drugs are eliminated in urine. The terminal elimination half-lives of isotretinoin, etretinate and acitretin after long term treatment are up to 20h, 120 days and 48h, respectively. Because of lack of definite correlation between plasma concentration and desired pharmacological effects, in conjunction with the very pronounced inter- and intraindividual variation in systemic availability (15 to 90%) after oral administration of these drugs, initial dosages in individual patients can only be roughly judged on the basis of the general pharmacokinetics of the agents. Later dosage adjustments should be made on the basis of monitoring of both plasma drug (and possible metabolite) concentrations, and the efficacy and tolerability of the drugs.

Drug Interactions↗
PubMed1992

A double-blind comparison of acitretin and etretinate in the treatment of Darier's disease.

The objective of this double-blind study was to compare the therapeutic effects of acitretin with those of etretinate in patients with Darier's disease. Twenty-six patients (10 males and 16 females) were included in the study. Patients were treated with 30 mg daily for the first 4 weeks and with an individually adjusted dose (10-50 mg/day) for the subsequent 12 weeks. Remission or marked improvement was obtained in 10 of the 13 acitretin-treated patients and in 8 of the 11 etretinate-treated patients who completed the 16-week treatment. The usual mucocutaneous adverse reactions of retinoids were observed in all but one patient. There were no significant differences between treatment groups with regard to the incidence of these reactions.

Acitretin↗
PubMed1992

Oral acitretin in psoriasis: drug and vitamin A concentrations in plasma, skin and adipose tissue.

The purpose of the present study was to determine the concentrations of acitretin and its main metabolite, 13-cis acitretin, in epidermis, subcutis and plasma in twelve psoriatic patients treated with 30 mg acitretin orally daily for 6 months. In addition, endogenous concentrations of vitamin A were monitored. Blood samples and biopsies from normal appearing skin were obtained prior to therapy, after 1 and 6 months of treatment and finally 1 month after cessation of therapy. Using a highly sensitive liquid chromatography method concentrations of synthetic retinoids and endogenous retinoid (retinol, 3,4-didehydroretinol) were analysed in hydrolyzed tissue samples and plasma. Steady-state concentration of acitretin in epidermis (17 +/- 9 ng/g) was reached within 1 month of therapy. There was a significant correlation between the individual plasma trough value and the epidermal concentration of acitretin after 1 month of therapy. The acitretin concentrations in subcutis varied from 15 to 1437 ng/g, but the mean values at 1 and 6 months of therapy were similar (177 and 227 ng/g, respectively). After stopping therapy the acitretin level was below the detection limit in both epidermis and serum within 1 month in 9 out of 12 patients. In contrast, only 3 of the patients were negative for acitretin in subcutis biopsies obtained 1 month after stopping therapy. The occurrence of a presumed tissue contaminator with characteristics similar to 13-cis acitretin prevented quantitation of this metabolite in many subcutis samples. The epidermal, subcutis and serum composition of retinol and 3,4-didehydroretinol remained unchanged during therapy, indicating no or only minimal interaction between acitretin and endogenous vitamin A metabolism.

Acitretin↗
PubMed1991

The pharmacokinetics of acitretin and its 13-cis-metabolite in psoriatic patients.

The synthetic retinoic acid derivative acitretin has recently been introduced for the treatment of severe psoriasis. Hitherto, the use of the carboxylic acid ester analogue, etretinate, has been hampered by an extremely long elimination half-life of up to 120 days for this drug. In the presented study, 12 patients with severe psoriasis were treated with 30 mg acitretin daily for a period of 6 months. The maximum plasma concentration of the drug occurred within about 0.9 to 4.6 hours with an apparent absorption half-life ranging from 0.2 to 1.7 hours and with half-lives of the distribution phase within the range of 1.2 to 3.5 hours. After stopping therapy, the terminal elimination half-life of acitretin varied between 16.5 and 111.1 hours (mean: 47.1 hr +/- 29.8 SD), whereas that for the 13-cis-metabolite varied between 36.5 and 249.4 hours (mean: 119.4 hr +/- 73.4 SD). Suction blister fluid concentrations of both the parent drug and metabolite were lower than plasma concentrations. The mean concentration of serum triglycerides was significantly elevated during the course of therapy, but still remained within the normal range. Saliva concentrations of drug and metabolite at steady-state were below 1 ng/mL. It is not possible from the observed half-lives of acitretin and its 13-cis-metabolite to draw any definite conclusion with regard to the anticonceptional period after acitretin therapy in psoriatic patients.

Acitretin↗
PubMed1991

A hydrocolloid occlusive dressing plus triamcinolone acetonide cream is superior to clobetasol cream in palmo-plantar pustulosis.

The purpose of this study was to compare the therapeutic efficacy of a hydrocolloid dressing (Actiderm) over a medium strength corticosteroid (triamcinolone acetonide (TAA) 0.1% cream) with that of a highly potent corticosteroid (clobetasol propionate 0.05% cream) in palmo-plantar pustulosis and localized pustular psoriasis. It was a randomized, open, prospective, right-left comparative trial in 19 patients. The Actiderm dressing and the TAA cream were applied every third day, whereas the clobetasol cream was applied twice daily for 4 weeks. Both treatments resulted in a significant improvement. On completion of treatment, complete clearance was found in 13 patients (63%) with Actiderm plus TAA, but in only 3 patients (21%) with clobetasol (p = 0.001). Four weeks after stopping therapy, the clinical parameters had returned to their pre-treatment level, except for erythema on the Actiderm plus TAA treated lesions (p less than 0.05). No clinically important adverse effects were reported or observed; in particular there was no sign of skin atrophy at the end of study. The results of this study demonstrate that Actiderm applied over a medium strength corticosteroid every third day is highly effective against palmoplantar pustulosis and localized pustular psoriasis. However, it is necessary to develop treatment regimens to maintain the improvement achieved.

Adolescent↗
PubMed1990

Interaction of etretinate with methotrexate pharmacokinetics in psoriatic patients.

Combined treatment of psoriasis with methotrexate and etretinate may be associated with hepatoxicity. This study investigated the potential effects of steady state etretinate administration on methotrexate pharmacokinetics in six psoriatic patients. When compared with a matched group a significantly higher mean value for the maximum plasma concentration Cmax (992 nmol/L +/- 94 SE vs 721 nmol/L +/- 35 SE) for methotrexate was found (P less than .05) after intramuscular administration of 0.2 mg/kg body weight of the drug. In accordance with this finding mean values of the time (tmax) to reach Cmax, half-life of the absorption (t1/2ka) and the apparent volume of distribution at steady state Vss were also lower than in the control groups but did not deviate significantly. Total clearance differed very little and insignificantly between the two groups. Absorption and disposition rates of etretinate during combined treatment with methotrexate were not significantly altered compared with previous results in psoriatic patients only receiving etretinate. Overall, these results indicate that the apparently increased risk for developing hepatotoxic reactions during coadministration of methotrexate and etretinate cannot be explained by drug accumulation due to pharmacokinetic interaction. A possible influence on potential hepatotoxicity of an increase of Cmax for methotrexate cannot be excluded.

Drug Interactions↗