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Biomedical subjects

Susan L Walker

Publications and source records attributed to Susan L Walker.

10 recordsLinked to original sources
PubMed2006

Photoadaptation during narrowband ultraviolet-B therapy is independent of skin type: a study of 352 patients.

Understanding how photoadaptation differs between individuals is important when considering susceptibility to the beneficial and harmful effects of sunlight exposure and when determining optimal phototherapy regimens. Most narrowband UVB (NB-UVB) regimens start with 70% of the minimal erythema dose (MED) with 20% increments at each treatment thereafter. We retrospectively studied 352 skin types I-IV psoriatic patients having twice weekly treatment with this regimen. Patients with high skin types tended to have high MEDs (P<0.001). By session 20 the proportion of patients who had developed erythema was approximately 60% regardless of MED. Among patients who developed erythema, the number of treatments before erythema occurred did not differ between skin types (P=0.33). We conclude that patients with high skin types photoadapt approximately equally per physical unit of UVR in comparison to those with low skin types, but they have greater photoadaptation in absolute terms because they are able to tolerate a higher initial dose of radiation. Differences in skin type or MED are not associated with clinically important differences in tendency to erythema during a standard 70/20% NB-UVB twice-weekly regimen. This regimen is suitable for all skin types I-IV patients regardless of skin type or MED.

Adaptation, Physiological↗
PubMed2005

Azathioprine and UVA light generate mutagenic oxidative DNA damage.

Oxidative stress and mutagenic DNA lesions formed by reactive oxygen species (ROS) are linked to human malignancy. Clinical treatments inducing chronic oxidative stress may therefore carry a risk of therapy-related cancer. We suggest that immunosuppression by azathioprine (Aza) may be one such treatment. Aza causes the accumulation of 6-thioguanine (6-TG) in patients' DNA. Here we demonstrate that biologically relevant doses of ultraviolet A (UVA) generate ROS in cultured cells with 6-TG-substituted DNA and that 6-TG and UVA are synergistically mutagenic. A replication-blocking DNA 6-TG photoproduct, guanine sulfonate, was bypassed by error-prone, Y-family DNA polymerases in vitro. A preliminary analysis revealed that in five of five cases, Aza treatment was associated with a selective UVA photosensitivity. These findings may partly explain the prevalence of skin cancer in long-term survivors of organ transplantation.

Adenine Phosphoribosyltransferase↗
PubMed2005

Measurement of sunscreen immune protection factors in humans: a consensus paper.

It is increasingly accepted that sunscreens should protect against ultraviolet radiation (UVR)-induced immunosuppression, with an index of protection that can be compared with the sun protection factor (SPF). Five groups of immunoprotection researchers met to discuss the status of immune protection factor (IPF) evaluation in human skin in vivo. Current methods rely on a suncreen's inhibition of UVR-induced local suppression of the contact hypersensitivity (CHS) response or the delayed-type hypersensitivity (DTH) response, using either the induction or the elicitation arms of these responses. The induction arm of the CHS response has the advantage of being sensitive to a single sub-erythemal exposure of solar-simulating radiation (SSR) that allows a direct comparison with the SPF. This approach, which necessitates sensitization, requires a large number of volunteers and is too labor intensive and time consuming to become a routine method. The elicitation arm of the CHS or DTH responses exploits prior sensitization to contact or recall antigens and has the advantage of being possible to apply on small groups of volunteers. Some current protocols, however, require repeat SSR exposures, which invalidates a direct comparison with SPF that is based on a single exposure. There is a need for a new simpler method of IPF that will have to be validated against existing models.

Dermatitis, Contact↗
PubMed2004

Species and fetal gender effects on the endocrinology of pregnancy in elephants.

Quantitative and temporal progestin profiles vary during gestation in the elephant, sometimes making it difficult to determine if a pregnancy is progressing normally. The aim of the present study was to determine if circulating progestin variability was related to species or fetal gender effects. A similar comparison also was conducted for secretory profiles of prolactin, relaxin, and cortisol. Overall mean progestin concentrations during gestation in Asian (n = 19) and African (n = 8) elephants were similar; however, the temporal profiles differed (P < 0.001). Concentrations were higher in African elephants during the first half of pregnancy, but then declined to levels below those observed in Asian elephants (P < 0.05). There also was a fetal gender effect in Asian, but not African elephants. Progestin concentrations were higher in Asian cows carrying male calves (n = 9) as compared to those carrying females (n = 10) (P < 0.001). Overall prolactin concentrations were higher in Asian than in African elephants between 8 and 15 months of gestation ( P< 0.001). There were no species differences in the secretory patterns of relaxin. Cortisol was relatively stable until the end of gestation when significant surges were observed, mainly between 8 and 11 days before parturition, and again on the day of birth. In sum, a comparison of progestin patterns between Asian and African elephants identified notable differences related to species and fetal gender. A role for cortisol in the initiation of parturition also was inferred from these data. From a practical standpoint, understanding the factors affecting gestational hormone characteristics and recognizing what the species differences are will help ensure that data used in diagnosing and monitoring elephant pregnancies are properly interpreted.

Analysis of Variance↗
PubMed2004

Comparative endocrinology of cycling and non-cycling Asian (Elephas maximus) and African (Loxodonta africana) elephants.

Up to 14% of Asian and 29% of African elephants in captivity are not cycling normally or exhibit irregular cycles based on progestin profiles. To determine if ovarian acyclicity is related to other disruptions in endocrine activity, serum pituitary, thyroid, adrenal, and ovarian hormones in weekly samples collected for 6-25 months were compared between normal cycling (n=22 each species) and non-cycling (n=6 Asian; n=30 African) elephants. A subset of cycling females (n=4 Asian, 7 African) also were blood sampled daily during the follicular phase to characterize the peri-ovulatory period. In normal cycling females, two leutinizing hormone (LH) surges were observed 3 weeks apart during a normal follicular phase, with the second inducing ovulation (ovLH). Serum FSH concentrations were highest at the beginning of the non-luteal phase, declining to nadir concentrations within 4 days of the ovLH surge. FSH remained low until after the ovLH surge and then increased during the luteal phase. A species difference was noted in prolactin secretion. In the African elephant, prolactin was increased during the follicular phase, but in Asian elephants concentrations remained stable throughout the cycle. Patterns of thyroid hormones (thyroid-stimulating hormone, TSH; free and total thyroxine, T4; free and total triiodothyronine, T3) and cortisol secretion were not affected by estrous cycle stage or season in cycling elephants. In non-cycling elephants, there were no fluctuating patterns of LH, FSH, or prolactin secretion. Overall mean concentrations of all hormones were similar to those in cycling animals, with the exception of FSH, prolactin, and estradiol. Mean serum FSH concentrations were lower due to females not exhibiting normal cyclic increases, whereas serum estradiol was higher overall in most acyclic females. Prolactin concentrations were significantly increased in 11 of 30 non-cycling females, all of which were African elephants. In sum, while there were no consistent endocrine anomalies associated with ovarian acyclicity, hyperprolactinemia may be one cause of ovarian dysfunction. The finding of elevated estrogens in some acyclic females also deserves further investigation, especially determining how it relates to reproductive tract pathologies.

Animals↗
PubMed2004

An optimal method for experimental provocation of polymorphic light eruption.

BACKGROUND: There is controversy about the best method to induce polymorphic light eruption (PLE) experimentally. Objectives To review articles on PLE induction and design a UV radiation protocol that improves success rates with clinically relevant doses of environmentally relevant solar-simulated radiation (SSR). DESIGN AND SETTING: All articles on the experimental provocation of PLE published since 1980 were reviewed. Photoprovocation of lesions was studied in 25 PLE patients. The 24-hour minimal erythemal dose (MED) of SSR was determined. Thereafter, six 4 x 4-cm adjacent sites on previously affected and previously unaffected skin were exposed to 0.25, 0.5, 0.75, 1.0, 1.25, 1.5 MED of SSR for 3 to 4 consecutive days. The study periodwas autumn to spring in London, England (51 degrees north latitude). MAIN OUTCOME MEASURES: Relationship between PLE induction and biological and physical exposure parameters. CONCLUSIONS: The review shows that fractionated erythemally effective UV-A exposures were more successful than single-sunburning UV-B doses. Photoprovocation of PLE was successful in 68% of patients after 2 to 3 SSR exposures that were not necessarily erythemal. There was no difference in success rate between previously affected and previously unaffected skin. Our data indicate that PLE is more likely to be induced when the natural causes of the disease are simulated.

Clinical Trials as Topic↗
PubMed2004

Ultraviolet-radiation-induced erythema and suppression of contact hypersensitivity responses in patients with polymorphic light eruption.

Ultraviolet-radiation suppresses cell-mediated immunity in healthy humans. It has been postulated that, in the short term, this immunosuppression prevents autoimmune responses to ultraviolet-radiation damaged skin. Patients with polymorphic light eruption (PLE) demonstrate abnormal responses to ultraviolet-radiation suggestive of an immune response to an ultraviolet-radiation-induced antigen. We investigated whether PLE patients (n=22) were resistant to ultraviolet-radiation-induced immunosuppression compared to skin-type, aged-matched controls (n=23). Groups of patients and controls (six subjects per group) received a single dose of solar-simulated ultraviolet-radiation of either 0, 0.6, 1 or 2 minimal erythema doses (MED). Erythema was quantified using a reflectance meter and all volunteers were sensitised on the irradiated site with dinitrochlorobenzene. Contact hypersensitivity responses (CHS) to dinitrochlorobenzene were quantified after challenge using ultrasound. Ultraviolet-radiation-induced erythema was comparable in patients and controls. CHS was comparable in unirradiated patients and controls. UVR-induced a dose-dependent suppression of CHS in all volunteers but patients were more resistant to immunosuppression after 1MED. Exposure to 1MED suppressed CHS by 78% in controls but induced less suppression in patients (44%, p < 0.01). Our data suggest that PLE patients have a flaw in their immunoregulatory response to ultraviolet-radiation it is only apparent over a narrow dose range around 1 MED.

Adult↗
PubMed2003

A commercial sunscreen's protection against ultraviolet radiation-induced immunosuppression is more than 50% lower than protection against sunburn in humans.

Ultraviolet radiation (280-400 nm)-induced suppression of cutaneous cell-mediated immunity plays an important part in the development of skin cancer. Sunscreens are widely advocated to protect against skin cancer but if they offer insufficient protection against immunosuppression they may inadvertently increase skin cancer risk. This human study evaluated immunoprotection afforded by a commercial sunscreen preparation (labeled sun protection factor 15) offering primarily ultraviolet B (280-320 nm) protection. Indirectly, it also investigated whether ultraviolet A (320-400 nm) plays a part in ultraviolet radiation-induced immunosuppression. Healthy white-skinned volunteers were used (n=119). Ultraviolet radiation exposures were on previously unexposed buttock skin with an ultraviolet radiation source that complied with European recommendations for sunscreen testing. Ultraviolet radiation dose-response curves for sunburn/erythema and suppression of the contact hypersensitivity response were generated either with or without sunscreen in vivo and protection factors were derived for both end-points. The ultraviolet radiation wavelengths transmitted by the sunscreen were determined in vitro and showed that the sunscreen was primarily an ultraviolet B absorber, with relatively poor absorption in the ultraviolet A region. The sun-screen protected against both erythema and immunosuppression but protection against immunosuppression (IPF=4.9, 95% confidence interval: 2.3-10.6) was less than half that for erythema (Ery-PFg=14.2, 95% confidence interval: 10.2-19.8). Failure of the sunscreen to afford comparable protection against both end-points was probably due to immunosuppression by ultraviolet A, a part of the solar spectrum that does not readily cause sunburn. The sunscreen protected against both end-points, which supports the use of sunscreens to reduce immunosuppression but protection against immunosuppression may be improved if sunscreens are formulated to offer equivalent protection against ultraviolet B and ultraviolet A.

Adolescent↗
PubMed2002

Effects of solar simulated radiation on the human immune system: influence of phototypes and wavebands.

We have shown that skin-types I/II are much more susceptible to UVR-induced suppression of the induction phase of contact hypersensitivity than skin-types III/IV. Studies with a UVB sunscreen have provided indirect evidence that UVA is more immunosuppressive than it is erythemogenic. Overall, our studies show a lack of direct correlation between erythema and immunosuppression.

Humans↗