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Biomedical subjects

N Bech-Thomsen

Publications and source records attributed to N Bech-Thomsen.

36 records · Page 2Linked to original sources

A polychromatic action spectrum for photosensitivity to orally administered 8-methoxypsoralen in humans.

The action spectrum for producing minimal phototoxic erythema after oral administration of 8-methoxypsoralen (8-MOP) was determined in the range of 312-368 nm in 12 human volunteers using six different UV radiation sources. The peak sensitivity was found to be at 343 nm. The 8-MOP photosensitivity was at a high level (> or = 0.75 of maximum) between 336 and 355 nm. Conventional UVA radiation sources, like the Philips TL/09R tube, have a high energy output within 335 and 355 nm, and are therefore highly recommended in oral psoralen plus UVA radiation treatment.

Administration, Oral↗

Differences in narrow-band ultraviolet B and broad-spectrum ultraviolet photocarcinogenesis in lightly pigmented hairless mice.

The carcinogenic effect of 4 ultraviolet (UV) sources was studied in lightly pigmented hairless mice. Two narrow-band UV sources, Philips TL01 and Philips TL12 with a Tempax filter, and two broad-spectrum UV sources, Philips TL12 and Bellarium S, were used. Exposure doses were calculated from the CIE erythema action spectrum. Four groups of mice (n = 20) were exposed to a nonerythemogenic dose (low dose), and 4 groups were exposed to an erythemogenic dose (high dose) of each of the 4 UV sources. One group (control) was not irradiated. The mice in the 4 low-dose groups were all exposed to 0.6 basic minimal erythema doses (B-MED) 5 days/week, and all the mice in the high-dose groups to 1.2 B-MED 5 days/week. After 16 weeks of acclimatization, the doses were doubled. Bellarium S and Philips TL12 were equally carcinogenic in the low-dose regimen and the high-dose regimen. Mice exposed to Philips TL12 with a Tempax filter developed tumors significantly earlier compared with Bellarium and Philips TL12. Philips TL01 was more carcinogenic than any of the other UV sources. Equally erythemogenic doses calculated from the CIE erythema action spectrum seem to be more carcinogenic when derived from narrow-band UVB sources than from broad-band UV sources.

Acclimatization↗

A quantitative study of the melanogenic effect of multiple suberythemal doses of different ultraviolet radiation sources.

The melanogenic potential of multiple suberythemogenic doses of 6 different ultraviolet (UV) sources was investigated. The UV sources emitted different amounts of UVA and UVB. The backs of 12 volunteers were exposed to the 6 UV sources 10 times during 4 weeks. Every volunteer was exposed to the same suberythemogenic dose (0.75 basic minimal erythema dose) of each of the UV sources. The changes in pigmentation and minimal erythema dose of the UV exposed test sites were registered during the 10 sessions. Three UVA sources with a low emission in the UVB area (0.2-3.1%) had a high melanogenic potential. Two UVB sources (UVB emission 74.3% and 94.5%) were unable to induce a significant increase in skin pigmentation. The 3 UVA sources with a low UVB output increased skin pigmentation significantly better than a UVA source with a UVB output of 6.9%. All 6 lamps were able to increase photoprotection significantly. The increase in photoprotection was not significantly different between any of the 6 UV sources. This study shows that, if humans are exposed to equally suberythemogenic doses of different types of UV radiation, then radiation obtained from UVA sources greatly enhances melanogenesis, whereas UVB radiation sources are unable to induce pigmentation.

Adult↗

Skin pigmentation as a predictor of minimal phototoxic dose after oral methoxsalen.

BACKGROUND AND DESIGN: Twenty-eight subjects were phototested to determine their erythemal responses to oral methoxsalen with UV-A and UV-B irradiation. Skin pigmentation was measured by skin reflectance at 550 and 660 nm before irradiation. The smallest UV radiation dose to produce erythema (minimal phototoxic dose and minimal erythema dose, respectively) was determined. The serum concentration of methoxsalen was measured at the time of UV-A irradiation. RESULTS: There was a positive correlation between skin pigmentation and both 72-hour minimal phototoxic dose and 24-hour minimal erythema dose. No correlation was demonstrated between methoxsalen serum concentration and minimal phototoxic dose. The combination of skin pigmentation and methoxsalen level did not give a better prediction of minimal phototoxic dose than skin pigmentation alone. CONCLUSIONS: Skin pigmentation measurements can be used to predict the minimal phototoxic and erythema doses. Skin pigmentation measurements are easy to perform and should be included in both phototherapy and photochemotherapy to improve the efficiency and reliability of the treatment.

Administration, Oral↗

Erythema after irradiation with ultraviolet B from Philips TL12 and TL01 tubes.

A trial was conducted to investigate whether the experimentally found erythema caused by irradiation from Philips TL12 (TL12) and Philips TL01 (TL01) tubes corresponded to the expected erythema efficacy calculated from the CIE erythema action spectrum. Using the CIE erythema action spectrum and the emission spectra of the two tubes, the ratio between the calculated erythema efficacy of the two tubes is TL12:TL01 = 1:4.2. Seventeen volunteers were irradiated on previously unexposed buttocks with TL12 and TL01 in doses ranging from 0.8 to 3.3 kJ/m2 and from 3.1 to 18.6 kJ/m2 respectively. The erythema was evaluated clinically and measured by skin reflectance before and 24 h after exposure. Also the pigmentation of the skin was measured before exposure. The erythema efficacy ratio between TL12 and TL01 was found to be 1:2.8. This indicates that TL01 is more or TL12 is less potent than should be expected from the CIE erythema action spectrum and that this should be taken into account when changing from TL12 to TL01 in therapy.

Dose-Response Relationship, Radiation↗

Carcinogenic potential of fluorescent UV tanning sources can be estimated using the CIE erythema action spectrum.

In legislation the CIE human erythema action spectrum is used to assess the risk of UV radiation appliances for household use. The most popular type of UV radiation source for private use is the low pressure 'UVA' radiation source, which mainly emits in the UVA area, but also has some emission in the UVB area. Recently reports have raised doubt whether the CIE erythema action spectrum is a good approximation for the carcinogenic risk. Therefore, it was investigated whether the carcinogenic potential of differing UV tanning sources, which mainly emit in the UVA area, could be assessed by using the CIE erythema spectrum. Two groups of lightly pigmented C3H/Tif mice were initially exposed to broad spectrum UV radiation with a high output of UVB (UVB emission 16.7%) during 84 days, in a daily dose of 4.67 Basic minimal erythema doses (Basic-MED). Subsequently, one group was exposed to Bellarium-S SA-1-12 (UVB emission 6.9%), the other to Philips TL 09R (UVB emission 2.2%), in a daily dose of 1 Basic-MED. The time to occurrence of seven tumour end-points was almost identical in the two groups, p > 0.4. To obtain further information on the relationship between the daily dose of common UV tanning sources measured in Basic-MED and tumour development, we combined the result of this experiment with the results of two others. There existed a negative correlation between the daily exposure dose measured in Basic-MED and the tumour induction time, p < or = 0.05. This inverse relationship was observed both when the UV tanning sources were administered with or without a prior exposure to broad spectrum UV irradiation. Our results indicate that the carcinogenic risk of UV tanning sources in the hairless C3H/Tif mouse can be estimated by the CIE erythema action spectrum.

Animals↗

UV-induced alterations in skin and lymphocytes during a one-week holiday in the Canary Islands in May.

The effect of solar exposure during a one-week sunbathing vacation in May at 29 degrees N latitude was investigated in 22 volunteers. The following end-points were measured before and after the holiday: skin reflectance at 507 nm, transmission of radiation from 289 nm to 448 nm through the epidermis, epidermal thickness, minimal erythema dose (MED), total white cell, neutrophil, lymphocyte, and lymphocyte subpopulation counts in blood, spontaneous DNA synthesis, DNA strand breaks and sister-chromatid exchange in lymphocytes, and the UVC tolerance of lymphocytes. There was a statistically significant decrease in skin reflectance (p < 0.001) and epidermal transmission (p < 0.01) after the holiday, reflecting increased pigmentation and epidermal thickening. There was a statistically significant increase in epidermal thickness (p < 0.001), MED (p < 0.05), spontaneous DNA synthesis (p < 0.01) and DNA strand breaks in lymphocytes (p < 0.02) after the holiday. The other end-points were not significantly changed. We report that changes in skin pigmentation and epidermal thickness occur after one week of UV exposure. It was also observed that a one-week UV exposure increased both spontaneous DNA repair and the amount of DNA strand breaks in the lymphocytes of the volunteers, while no changes in T-cell subsets were detected.

Adult↗

UVA tanning devices interact with solar-simulated UV radiation in skin tumor development in hairless mice.

The carcinogenic effect of three UVA tanning sources was studied in lightly pigmented hairless mice. The three tanning sources (Bellarium-S SA-1-12, Philips TL 09R and Philips TL 10R) have different emission spectra, and emit different amounts of UVB. Radiation from the tanning sources was administered for 20 min/day, 5 day/week in daily doses equivalent to those used in suntan salons. The radiation was given alone or after 12 weeks of exposure to solar-simulated UV radiation (SOLAR UV) (10 min/day, 4 day/week; daily dose, 19.5 kJ/m2 UVA and 3.9 kJ/m2 UVB). Irradiation with Bellarium-S SA-1-12 for 47 weeks and Philips TL 09R for 74 weeks induced skin tumours in 20/20 and 13/20 of the animals, respectively. When irradiation with Bellarium-S SA-1-12 and PHilips TL 09R was administered after 12 weeks of SOLAR-UV exposure, a strong enhancement of SOLAR-UV-induced photocarcinogenesis was observed (p < 0.001). Irradiation with Philips TL 10R was only slightly carcinogenic, and during 85 weeks of irradiation only one skin tumor appeared in a group of 20 mice. However, when irradiation with Philips TL 10R was administered after 12 weeks of exposure to SOLAR UV, an enhancement of SOLAR-UV-induced carcinogenesis was observed (p < 0.001). Our results suggest that the hazards of exposure to commercial tanning devices are increased when they are used after a period of natural sun exposure. Even tanning sources with a low carcinogenic potential are able to increase SOLAR-UV-induced carcinogenesis significantly.

Animals↗

The influence of food on 8-methoxypsoralen serum concentration and minimal phototoxic dose.

Ten adult volunteers were given three oral doses of 0.46-0.56 mg/kg body weight of 8-methoxypsoralen (8-MOP) in a liquid formulation under fasting conditions, and after ingestion of a low-fat or fat-rich breakfast. 8-MOP serum levels and photosensitivity were measured 0.5-4 h after drug ingestion. The 1-h 8-MOP serum levels and photosensitivity were significantly higher in fasting conditions than after ingestion of a low-fat or fat-rich meal (intra-individual median difference in photosensitivity 7.5 J/cm2). On 12 of 20 occasions when the drug was taken after food ingestion, the 1-h 8-MOP serum concentration was below 30 ng/ml. A survey of 43 out-patients undergoing regular PUVA treatment showed that the frequency of erythemal reactions was significantly higher when 8-MOP was ingested with a > 50% smaller quantity of food than usual (P < 0.005). This study demonstrated food-induced variations in 8-MOP photosensitivity both in an experimental situation and in an out-patient survey. In order to optimize the therapeutic effect of PUVA, the quantity of food taken before 8-MOP should remain constant, and the timing of UVA irradiation should be adjusted according to the preceding food intake.

Adult↗

Xeroderma pigmentosum lesions related to ultraviolet transmittance by clothes.

Xeroderma pigmentosum is associated with severe actinic degeneration of the skin. Our patient with xeroderma pigmentosum showed increasing actinic damage in some areas covered by clothes. We therefore performed a complete evaluation of the patient's exposure to ultraviolet radiation. This included transmission measurements of the patient's clothes, glasses, and car windows. The transmission of UVB (280 to 320 nm) by the clothes varied from none to 17.8%. The transmitted UVB radiation was proportional to the clinical manifestations of xeroderma pigmentosum. The patient's wardrobe was changed, and UVA-blocking film was applied to the windows of the car and house. A decline in manifestations was seen after 18 months of improved ultraviolet protection.

Adult↗

Photocarcinogenesis in hairless mice induced by ultraviolet A tanning devices with or without subsequent solar-simulated ultraviolet irradiation.

The carcinogenic effect of 3 commercially available ultraviolet A (UVA) tanning sources was studied in lightly pigmented hairless mice. The tanning sources (Bellarium-S SA-1-12 and Philips TL 09R and TL 10R) have different emission spectra and emit different quantities of UVB. The tanning sources were administered either alone, or before irradiation with solar-simulated UV (solar UV). All 3 UVA tanning sources were able to induce skin tumors when administered in daily doses resembling those used in tanning salons (20 min/d, 5 d/week). Irradiation with Bellarium-S during 32 weeks induced skin tumors in all mice; a similar response was seen after 66 weeks of irradiation with Philips TL 09R. Irradiation with Philips TL 10R during 98 weeks induced tumors in 6 of 20 mice. Nine groups of 20 mice were pretreated 20 min/d, 5 d/week during 13 weeks with one of the UVA tanning sources. Three groups were irradiated with Bellarium-S, 3 groups with Philips TL 09R and 3 groups with Philips TL 10R in daily doses ranging from 0.2 to 1.8 minimum erythema doses (MED). The highest daily doses were equivalent to the doses received during one session in a commercial solarium. Subsequently all 9 groups were irradiated with 3.1 MED/d solar UV 10 min/d, 4 d/week until all mice had died. Time to first tumor was compared. All groups pretreated with Bellarium-S and Philips TL 09R showed an enhanced tumor development compared with a group irradiated with solar UV only. Pretreatment with Philips TL 10R did not enhance the carcinogenic effect of solar UV.

Animals↗

Pretreatment with long-wave ultraviolet light inhibits ultraviolet-induced skin tumor development in hairless mice.

The carcinogenic effects of long-wave ultraviolet radiation (UV-A) (320 to 400 nm) irradiation followed by exposure to broad-spectrum ultraviolet (UV) irradiation were studied in 200 lightly pigmented, hairless, hr/hr C3H/Tif mice. No skin tumors were observed in the group irradiated with UV-A for four weeks (total dose, 4050 kJ/m2, observed for 57 weeks). Ultraviolet exposure induced skin tumors in a dose-dependent manner. In a group exposed to UV irradiation for 13 weeks, 35% of the mice had developed tumors after 57 weeks. Twenty-six weeks of exposure resulted in 88% of the animals being affected. In contrast it was found that treatment with UV-A irradiation (four weeks, total dose up to 4200 kJ/m2) preceding exposure to UV irradiation (13 or 26 weeks) resulted in a significantly delayed tumor development. Exposure with UV-A induced no visible changes of the skin, and subsequent microscopic examination revealed no measurable changes in epidermal thickness or melanin content. Our results suggest that, depending on the exposure schedule, UV-A in addition to previously reported carcinogenic properties also may act as an antitumor agent.

Animals↗

Detection by ELISA of IgG-subclass-specific antibodies in primary respiratory syncytial (RS) virus infections.

The IgG-subclass specific antibody response was investigated in primary RS-virus infections in infants and small children by using an ELISA with monoclonal antibodies against the four human IgG subclasses. When 78 serum samples obtained from 21 patients during the first 3-4 mo following the onset of illness were studied, only IgG-1 and IgG-3 antibodies could be detected. Both of these subclass specific antibodies appeared during the second week following the beginning of illness. Approximately 4 wk after the onset of illness, IgG-1 antibodies reached maximum levels, which persisted during the following months. Approximately 3 wk after the onset of illness, IgG-3 antibodies reached maximum levels, which decreased during the following months. Both IgG-1 and IgG-3 antibodies showed neutralizing capacity.

Acute Disease↗

Detection of RS-virus IgG-subclass-specific antibodies: variation according to age in infants and small children and diagnostic value in RS-virus-infected small infants.

The variation according to age of RS-virus IgG-subclass specific antibodies was investigated by ELISA in 140 acute phase sera from 140 infants and children 1-47 mo of age who were hospitalized with acute respiratory disease. Sixty-nine of these serum samples were obtained from patients with RS-virus infections. Mean OD values of IgG-1 antibodies decreased corresponding to the decrease in maternal antibodies. In patients with RS-virus infections, the mean IgG-1 OD values increased in children who were 3 yr old, but in patients without RS-virus infections this increase was observed in children at 1 yr of age. RS-virus IgG-3 antibodies were detected only in children 1-3 yrs of age, and only in 18% of samples from children without RS-virus infections. The concept of the transient nature of RS-virus IgG-3 antibodies as compared with RS-virus IgG-1 antibodies is supported by these results. RS-virus subclass specific antibodies were studied in paired serum samples from 12 infants 1-5 mo of age with acute lower RS-virus disease. IgG-1 antibodies developed in six infants, but only in one of six infants aged 1-3 mo. IgG-3 antibodies developed in nine infants, including four of six infants who were 1-3 mo old. These results suggest that in small infants with RS-virus infections the detection of IgG-3 antibodies is of higher diagnostic value than the detection of IgG-1 antibodies.

Acute Disease↗

Two-day trimethoprim-sulfamethoxazole treatment of pharyngeal gonorrhea.

The efficacy of three different regimens of oral medication for pharyngeal gonorrhea was examined in a study of 119 patients. Of 34 patients treated with 1.4 g of pivampicillin plus 1.0 g of probenecid, both taken once a day for five days, 33 (97.1%) were cured. The other two regimens consisted of tablets containing sulfamethoxazole (400 mg) and trimethoprim (80 mg). Of 36 patients treated with a single ten-tablet dose on the first day, two five-tablet doses on the second day, and two three-tablet doses for the next three to five days, 35 (97.2%) were cured. Of 49 patients treated with a single ten-tablet dose on the first day and two five-tablet doses on the second day, 44 (89.8%) were cured. The cure rates for the three regimens were not significantly different (P greater than 0.05). Therefore, we conclude that a two-day trimethoprim-sulfamethoxazole regimen is quick, inexpensive, and reliable in the treatment of pharyngeal gonorrhea.

Adult↗

Treatment with topical khellin in combination with ultraviolet A or solar-simulated radiation is carcinogenic to lightly pigmented hairless mice.

Khellin is used together with either UVA irradiation or sun exposure in the treatment of vitiligo. The purpose of this study was to investigate the carcinogenic effect of topically applied khellin together with UVA or solar simulated radiation (SSR) in lightly pigmented C3H/Tif mice. For comparison purposes a 0.1% 8-methoxypsoralen (8-MOP) cream was also tested in combination with SSR. Fifty microliters of a 5% khellin cream, a 0.1% 8-MOP cream, or a cream without active substances were spread uniformly on the back of the mice 30 minutes before UVA or SSR irradiation. All mice were irradiated 3 times a week until age or skin tumor development necessitated killing. Treatment with topical khellin and UVA irradiation was carcinogenic to lightly pigmented hairless mice, time to 50% of the mice had developed one tumor (t50) was 507 days. This indicates that the combination of topical khellin and UVA radiation, formerly expected to be rather innocuous, is carcinogenic to mice. Also the combination of khellin and SSR (t50 = 268 days) enhanced skin tumor development significantly compared with control cream and SSR (t50 = 330 days), P < 0.05. In addition, the combination of khellin and SSR was found to have the same carcinogenic effect as treatment with 0.1% 8-MOP and SSR (t50 = 262 days). This study shows that topically applied khellin increases the carcinogenic effect of both UVA and sunlight.

Administration, Topical↗

Photoprotection due to pigmentation and epidermal thickness after repeated exposure to ultraviolet light and psoralen plus ultraviolet A therapy.

Tanning and thickening of the epidermis are cardinal defensive responses of human skin to ultraviolet (UV) radiation that lead to increased photoprotection. Earlier studies have shown that skin pigmentation can be used to predict minimal erythema dose and minimal phototoxic dose. In this study it was calculated how much of the increase in photoprotection after 4 weeks of repeated exposure to suberythemogenic doses of either UVA or UVB radiation sources or psoralen plus UVA (PUVA) therapy that was attributable to melanogenesis. The backs of 12 volunteers were exposed to 6 different UVA and UVB radiation sources 9 times during 4 weeks. Skin pigmentation was assessed by skin reflectance measuring. Photoprotection was determined from the minimal erythema dose. Melanogenesis accounted for 63-95% of the increase in photoprotection after 4 weeks of exposure to UVA radiation. Exposure to two UVB sources induced a significant increase in photoprotection but not in pigmentation. Melanogenesis accounted only for 6-11% of the increase in photoprotection after 4 weeks of UVB exposure. The pigmentary and photoprotective responses to PUVA therapy were followed in 14 patients. After 2 weeks of exposure, the increase in photoprotection was significantly higher than predicted from the increase in skin pigmentation. After 4 weeks, melanogenesis accounted for only 36% of the increase in photoprotection. This study shows that melanogenesis accounts for the increased photoprotection after 2 weeks of exposure to UVA radiation, but after 4 weeks other protective mechanisms occur. During suberythemal UVB exposure and during PUVA therapy the importance of skin pigmentation in the overall photoprotection gradually decreases during a 4-week irradiation period.

Adult↗

Sunbathers' application of sunscreen is probably inadequate to obtain the sun protection factor assigned to the preparation.

The sun protection factor (SPF) is a ratio that estimates the protective efficacy of a sunscreen against sunburn. The generally accepted methods used to determine the SPF of a sunscreen require that the formulation be applied in a thickness of 1.5 mg/cm2 (Deutsches Institut für Normung) or 2 mg/cm2 (US Food and Drug Administration). The applied thickness of a sunscreen is important for the degree of photoprotection. Forty-two volunteers on a beach applied their own sunscreen all over the body. The amount of the applied sunscreen was on average 0.5 mg/cm2. This indicates that the labelled SPF is probably considerably higher than the obtained degree of protection against sunburn.

Adolescent↗