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result(s) for
"PHILIPSEN, PETER A."
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A revised action spectrum for vitamin D synthesis by suberythemal UV radiation exposure in humans in vivo
by
Young, Antony R.
,
Morgan, Kylie A.
,
Philipsen, Peter A.
in
Adult
,
Biological activity
,
Biological Sciences
2021
Action spectra are important biological weighting functions for risk/benefit analyses of ultraviolet (UV) radiation (UVR) exposure. One important human benefit of exposure to terrestrial solar UVB radiation (∼295 to 315 nm) is the cutaneous synthesis of vitamin D₃ that is initiated by the photoconversion of 7-dehydrocholesterol to previtamin D₃. An action spectrum for this process that is followed by other nonphotochemical steps to achieve biologically active vitamin D₃ has been established from ex vivo data and is widely used, although its validity has been questioned. We tested this action spectrum in vivo by full- or partial-body suberythemal irradiation of 75 healthy young volunteers with five different polychromatic UVR spectra on five serial occasions. Serum 25-hydroxyvitamin D₃ [25(OH) D₃] levels, as the most accurate measure of vitamin D₃ status, were assessed before, during, and after the exposures. These were then used to generate linear dose–response curves that were different for each UVR spectrum. It was established that the previtamin D₃ action spectrum was not valid when related to the serum 25(OH)D₃ levels, as weighting the UVR doses with this action spectrum did not result in a common regression line unless it was adjusted by a blue shift, with 5 nm giving the best fit. Such a blue shift is in accord with the published in vitro action spectra for vitamin D₃ synthesis. Thus, calculations regarding the risk (typically erythema) versus the benefit of exposure to solar UVR based on the ex vivo previtamin D₃ action spectrum require revision.
Journal Article
Detection of cutaneous malignant melanoma using RNA sampled by tape strips: A study protocol
by
Schmidt, Grethe
,
Tvedebrink, Torben
,
Morling, Niels
in
Biology and life sciences
,
Consent
,
Data collection
2022
Cutaneous malignant melanoma (CMM) is curable if detected in its early stages. However, the clinical recognition of CMM is challenging. An American research group has shown promising results in detecting CMM based on RNA profiles sampled from suspicious lesions with tape strips. We aim to further develop this technique and validate if RNA profiles sampled with tape strips can detect CMM.
This prospective cohort study will include approximately 200 lesions clinically suspected of CMM requiring surgical removal. Tape stripping of the lesions will be performed just before surgical excision. Subsequently, RNA on the tape strips is analyzed using quantitative real-time polymerase chain reaction with TaqMan technology. The results are combined into a binary outcome where positive indicates CMM and negative indicates no CMM. The histopathological diagnosis of the lesions will be used as the gold standard. The main outcome is the results of the RNA test and the histopathological diagnosis, which, combined, provide the sensitivity and specificity of the test.
The accuracy of the clinical examination in CMM diagnostics is limited. This clinical trial will explore the ability to use RNA analysis to improve the management of suspicious lesions by enhancing early diagnostic accuracy. Hopefully, it can reduce the number of benign lesions being surgically removed to rule out CMM and decrease patient morbidity.
The project was approved by The Committee on Health Research Ethics of the Capital Region of Denmark (H-15010559) and registered at the Danish Data Protection Agency (BFH-2015-065).
Journal Article
Sunscreen use optimized by two consecutive applications
by
Torsnes, Linnea R.
,
Heerfordt, Ida M.
,
Philipsen, Peter A.
in
Biology and Life Sciences
,
Medicine and Health Sciences
,
People and places
2018
Sunscreen users are often inadequately protected and become sunburned. This study aimed to investigate how much two consecutive sunscreen applications increased the quantity of sunscreen applied and decreased the skin area left without sunscreen (missed area) compared to a single application. Thirty-one healthy volunteers wearing swimwear were included and applied sunscreen two consecutive times in a laboratory environment. Participants had pictures taken in black light before and after each application. As sunscreens absorb black light, the darkness of the skin increased with increasing amounts of sunscreen applied. We conducted a standard curve establishing a link between change in picture darkness and quantity of sunscreen. The quantity of sunscreen at selected skin sites as well as the percentage of missed area was determined after each application. Participants had missed a median of 20% of their available body surface after a single application. After double application they had missed 9%. The decrease in missed areas was significant for the whole body surface and for each of the body regions separately. The median participant had applied between 13% and 100% more sunscreen at the selected skin sites after double application than after single application. We recommend double application, especially before intense sun exposure.
Journal Article
Anatomical Distribution of Ultraviolet Radiation Depends on Phototherapy Unit Design and on Personal Height and Body Mass
by
Heydenreich, Jakob
,
Wulf, Hans Christian
,
Philipsen, Peter A.
in
body irradiance distribution
,
Body mass index
,
body shape
2023
Phototherapy using ultraviolet radiation (UVR) treatment units of various designs is common in dermatology. The anatomical distribution of UVR should be even, regardless of individual body shapes. Using electronic dosimeters, we measured the irradiance at 31 body sites on 12 persons of different heights and body mass (BMI). Five different treatment unit designs were tested: cabinet units with standing patients, units with patients lying down, and a unit where patients rotated in front of flatly arranged UVR tubes. In treatment units with short tubes, persons taller than 170 cm received low irradiance on the face, neck, and shoulders. In cabinet-type units, higher BMI lowered the irradiance on the chest and belly. The relative standard deviation (RSD) of irradiance was smallest for the rotating unit, and for the unit with patients lying down while irradiated from above only. A higher RSD was found in the unit designs where patients stood inside cabinets, and where patients lay down and were simultaneously irradiated from both sides. In general, longer tubes lower the overall RSD. The irradiance of the different body areas is about 60% of the measured calibration values, but to avoid provoking any erythema, the treatment dose can only be increased by 10%.
Journal Article
Combining RNA tape stripping with dermoscopic features for melanoma identification
2025
Background A noninvasive, accurate diagnostic method for melanoma is needed to improve early detection and decrease number of excisions. Gene expression as measured by RNA levels uses tape strips to directly assesses genetic markers from skin lesions. Commercial RNA assays show varying diagnostic accuracy in melanoma detection. Combining dermoscopic features with RNA tape strips could reduce unnecessary removal of benign lesions by increasing specificity. Objectives To test an RNA‐based rule‐out test and integrate dermoscopic features with RNA analysis to improve diagnostic accuracy of malignant melanoma (MM). Furthermore, we explore the association between RNA profiles and dermoscopic features. Methods Seventy patients with pigmented skin lesions suspected of being melanoma were imaged with dermoscopy and tape stripped for RNA analysis before surgical excision. The images were evaluated for seven dermoscopic features, and RNA levels of 11 genes were analyzed. A combined test using both gene expression and dermoscopic features was developed. Associations between RNA profiles and dermoscopic features were explored. Results Histopathology revealed 19 malignant lesions (17 MM and two basal cell carcinomas) and 51 benign lesions. The combined dermoscopy and RNA test identified all malignant lesions (100% sensitivity) based on PRAME expression, blotch and regression structures and patient age. This combined model increased specificity to 35%, compared to 24% with the original RNA rule‐out test, without missing any malignant lesions. Significant differences in RNA profiles were observed for lesions expressing atypical network and regression structures. Conclusions Combining RNA tape stripping with dermoscopic features can reduce the removal of benign lesions by over one‐third while maintaining 100% sensitivity. We found specific RNA profiles to be strongly associated with dermoscopic features, presenting a promising opportunity to integrate molecular and morphological information and provide valuable guidance for dermatologists managing atypical pigmented lesions. RNA tape‐stripping is a simple, non‐invasive way to help detect melano‐ma by collecting RNA from skin cells. This study tested a new method combining RNA analy‐sis with dermoscopy in 70 patients with suspicious pigmented skin lesions. It improved accu‐racy, achieving 100% sensitivity and increasing specificity to 35% (compared to 24% with RNA alone). Certain dermoscopic features closely matched specific RNA patterns. This ap‐proach could cut unnecessary benign lesion removals by over a third while ensuring reliable melanoma detection.
Journal Article
Sunbed Radiation Provokes Cutaneous Vitamin D Synthesis in Humans-A Randomized Controlled Trial
by
Jørgensen, Henrik L.
,
Jørgensen, Niklas Rye
,
Philipsen, Peter A.
in
Beds
,
Carcinogenicity
,
Female
2008
We wanted to investigate whether the use of sunbeds with sunlamps emitting mainly UVA and only 0.5% or 1.4% UVB will increase the level of serum 25‐hydroxyvitamin D (25(OH)D). In a randomized, controlled, open study on healthy, Caucasian females (>50 years) sunbed radiation was given as follows: four 6‐min sunbed sessions (days 0, 2, 4 and 7) and four 12‐min sunbed sessions (days 9, 11, 14 and 16 ) with sunlamps emitting 0.5% UVB (n = 20) or with sunlamps emitting 1.4% UVB (n = 15). The controls (n = 21) had no intervention. Serum levels of 25(OH)D were measured on days 0, 9 and 18 in all three groups. The average increase in serum 25(OH)D from day 0 to day 9 was 12 nmol L−1 (SD 11 nmol L−1, P = 0.0002) in the 0.5% UVB group and 27 nmol L−1 (SD 9 nmol L−1, P < 0.0001) in the 1.4% UVB group. From day 9 to day 18 a further but not significant increase in serum 25(OH)D of 3 nmol L−1 (SD 9 nmol L−1, P = 0.2) in the 0.5% UVB group and 0.6 nmol L−1 (SD 18 nmol L−1, P = 0.9) in the 1.4% UVB group was seen. No significant changes were found in the control group. Increasing with UVB dose and exposure time, 37–64% of the sunbed sessions resulted in side effects such as erythema or polymorphic light eruption. The results showed that sunbeds emitting 0.5% and 1.4% UVB increased 25(OH)D serum levels. The increases were dose dependent but reached a plateau after few sessions. Sunbed use as vitamin D source is, however, not generally recommendable due to the well‐known carcinogenicity and high frequency of acute side effects.
Journal Article
Quantification of Urinary Thymidine Dimers in Volunteers After Ultraviolet Radiation Using a New UPLC-MS/MS-based Method
by
HEYDENREICH, JAKOB
,
HERMANSSON, SIGURD
,
LERCHE, CATHARINA M.
in
Biomarkers
,
Calibration
,
Carcinogens
2022
Background/Aim: Solar ultraviolet radiation (UVR) is a carcinogen and irradiation of the skin results in DNA damage. Cyclobutane pyrimidine dimers (CPDs), including thymidine dimers, are among the most frequent forms of DNA damage. When CPDs are formed, the nucleotide excision repair system is activated and CPDs are excreted in the urine. Here, we developed a mass spectrometry-based method to quantify thymidine dimers in the urine and tested the method on a small group of volunteers after whole-body UVR exposure. Patients and Methods: Years of research resulted in a method based on the “dilute-and-shoot” principle and ultra-performance liquid chromatography (UPLC) coupled to mass spectrometry. The whole body of each of eight healthy volunteers was exposed to 1.5-2.0 standard erythema doses (SEDs) of UVR for 3 consecutive days. Morning urine was collected on Day 1 (before irradiation) and on the following 7-9 days. Prior to analysis, sample preparation consisted of a simple dilution. A tandem quadrupole mass spectrometer coupled to UPLC was used for quantitative analysis in the multiple reaction monitoring mode. Results: After 3 consecutive days of 1.5-2 SEDs, the highest level of thymidine dimer excretion occurred on Day 6 (0.7 ng/ml urine). Compared with baseline, significantly more thymidine dimers were excreted every day until Day 8 (p<0.016). Our method quantifies thymidine dimers that are excreted as dimers (i.e., not degraded further) after nucleotide excision repair. Conclusion: This is the first published mass spectrometry-based method for quantifying thymidine dimers in the urine after whole-body UVR exposure.
Journal Article
The effect of vitamin D recommendations on serum 25-hydroxyvitamin D level in patients with erythropoietic protoporphyria
by
Heerfordt, Ida M.
,
Philipsen, Peter A.
,
Lerche, Catharina M.
in
25(OH)D
,
25-Hydroxyvitamin D
,
blood sampling
2022
•Patients with erythropoietic protoporphyria (EPP) experience skin photosensitivity.•Patients with EPP avoid sun exposure and often lack vitamin D.•Danish patients with EPP are in general recommended daily vitamin D supplements all year.•Personal vitamin D counseling was given if vitamin D was low.•We found a positive effect of the recommendations on vitamin D status in patients with EPP.
Patients with erythropoietic protoporphyria (EPP) avoid sun exposure owing to photosensitivity. For decades, sun-avoiding Danes have been recommended daily vitamin D supplements all year. We offered our EPP patients serum 25-hydroxyvitamin D (25(OH)D) monitoring, and counseling if their level was low. We aimed to investigate the effect of the general recommendation and counseling on 25(OH)D status in patients attending our clinic. Additionally, the 25(OH)D status of our EPP patients was compared to that of British patients with EPP not taking vitamin D supplements and with that of the general Danish population.
Forty-six Danish patients with EPP had 25(OH)D measured in 721 blood samples collected between 2003 and 2021. Dates of individual counseling were noted. Data on British patients with EPP and the general Danish population were extracted from previous publications.
Our patients had higher 25(OH)D levels than British patients with EPP not taking vitamin D supplements, but the recommendations did not elevate their 25(OH)D levels to that of the general Danish population. Overall, 17.5% of the 25(OH)D measurements in our EPP patients were below 30 nmol/L (deficiency) and 29.4% were between 30 and 50 nmol/L (insufficiency). Patients were monitored for a median of 11 y. Thirty-one patients had a total of 74 vitamin D counseling sessions, providing an increase in 25(OH)D of about 18 nmol/L the year after. However, many patients repeatedly developed insufficiency.
This study documents the positive effect of vitamin D recommendations on serum 25(OH)D in patients with EPP. Follow-up on vitamin D status and recommendations is essential to increase 25(OH)D levels.
Journal Article
Vitamin D Production after UVB Exposure Depends on Baseline Vitamin D and Total Cholesterol but Not on Skin Pigmentation
by
Bogh, Morten K.B.
,
Wulf, Hans C.
,
Philipsen, Peter A.
in
Adolescent
,
Adult
,
Biological and medical sciences
2010
UVB radiation increases serum vitamin D level expressed as 25-hydroxyvitamin-D3 (25(OH)D), but the influence of skin pigmentation, baseline 25(OH)D level, and total cholesterol has not been well characterized. To determine the importance of skin pigmentation, baseline 25(OH)D level, and total cholesterol on 25(OH)D production after UVB exposure, 182 persons were screened for 25(OH)D level. A total of 50 participants with a wide range in baseline 25(OH)D levels were selected to define the importance of baseline 25(OH)D level. Of these, 28 non-sun worshippers with limited past sun exposure were used to investigate the influence of skin pigmentation and baseline total cholesterol. The participants had 24% of their skin exposed to UVB (3 standard erythema doses) four times every second or third day. Skin pigmentation and 25(OH)D levels were measured before and after the irradiations. Total cholesterol was measured at baseline. The increase in 25(OH)D level after UVB exposure was negatively correlated with baseline 25(OH)D level (P<0.001) and positively correlated with baseline total cholesterol level (P=0.005), but no significant correlations were found with constitutive or facultative skin pigmentation. In addition, we paired a dark-skinned group with a fair-skinned group according to baseline 25(OH)D levels and found no differences in 25(OH)D increase after identical UVB exposure.
Journal Article
Thickness of Actinic Keratosis Does Not Predict Dysplasia Severity or P53 Expression
by
Heerfordt, Ida M.
,
Nissen, Christoffer V.
,
Poulsen, Thomas
in
692/4028/67/1813/1352
,
692/53/2422
,
Biopsy
2016
The severity of dysplasia and expression of p53 in actinic keratosis (AK) is of importance for the transformation to squamous cell carcinoma. It is assumed that it is most important to treat thick AKs as they are believed to be more dysplastic than thin AKs. However, a relation between AK thickness and dysplasia or the expression of p53 has never been demonstrated. The aim of this study was to investigate this possible relation. Sixty-six AKs were included for clinical and histological examination. Prior to performing a punch biopsy, the clinical thickness of each AK was measured objectively using two scale bars with a thickness of 0.5 mm and 1 mm. Subsequently, the thickness of the epidermis, the severity of dysplasia and the expression of p53 were assessed histologically. We found a strong and significant positive correlation between measured clinical thickness of the AKs and the histological thickness of epidermis (p < 0.0001). However, the clinical thickness did not correlate with either the severity of dysplasia (p = 0.7) or the expression of p53 (p = 0.5). In conclusion, thin AKs show the same severity of dysplasia and expression of p53 as thicker AK lesions. Consequently, clinical thickness cannot predict aggressiveness.
Journal Article