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Health care organizations are facing the fallout from inadequate nurse staffing in addition to the emotional and spiritual tolls of the COVID-19 pandemic. Organizations must strategically differentiate themselves by novel methods of recruitment and retention, including care of the nurse as a whole person. Tactical strategies can be implemented by nurse leaders to promote the spiritual well-being of the nursing workforce. These strategies include incorporating spirituality and soft skills into nursing orientation, developing and providing interventions to support spiritual well-being, and implementing methods to provide spiritual care of patients by nurses. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate dermal remodeling effects of crystal-free microdermabrasion on photodamaged skin. DESIGN Biochemical analyses of human skin biopsy specimens following microdermabrasion treatment in vivo. SETTING Academic referral center. PARTICIPANTS Volunteer sample of 40 adults, aged 50 to 83 years, with clinically photodamaged forearms. INTERVENTION Focal microdermabrasion treatment with diamond-studded handpieces of varying abrasiveness on photodamaged forearms and serial biopsies at baseline and various times after treatment. MAIN OUTCOME MEASURES Quantitative polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay were used to quantify changes in inflammatory, proliferative, and remodeling effectors of normal wound healing. Type I and type III procollagen served as the main outcome marker of dermal remodeling. RESULTS Coarse-grit microdermabrasion induces a wound healing response characterized by rapid increase in induction of cytokeratin 16 and activation of the AP-1 transcription factor in the epidermis. Early inflammation was demonstrated by induction of inflammatory cytokines, antimicrobial peptides, and neutrophil infiltration in the dermis. AP-1 activation was followed by matrix metalloproteinase–mediated degradation of extracellular matrix. Consistent with this wound-healing response, we observed significant remodeling of the dermal component of the skin, highlighted by induction of type I and type III procollagen and by induction of collagen production enhancers heat shock protein 47 and prolyl 4-hydroxylase. Dermal remodeling was not achieved when microdermabrasion was performed using a medium-grit handpiece. CONCLUSIONS Microdermabrasion using a coarse diamond-studded handpiece induces a dermal remodeling cascade similar to that seen in incisional wound healing. Optimization of these molecular effects is likely the result of more aggressive treatment with a more abrasive handpiece. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00111254Arch Dermatol. 2009;145(10):1114-1122--

OBJECTIVE To examine clinical and molecular changes after topical fluorouracil treatment of photodamaged human facial skin for actinic keratoses. DESIGN Nonrandomized, open-label 2-week treatment with fluorouracil cream, 5%, followed by clinical and molecular evaluation. SETTING Academic referral center. PATIENTS Twenty-one healthy volunteers, 56 to 85 years old, with actinic keratoses and photodamage. INTERVENTIONS Twice-daily application of fluorouracil cream for 2 weeks and biopsies and clinical evaluation at baseline and periodically after treatment. MAIN OUTCOME MEASURES Gene and protein expression of molecular effectors of epidermal injury, inflammation, and extracellular matrix remodeling 24 hours after fluorouracil treatment; clinical improvement measured by evaluators, photography, and patient questionnaires. RESULTS One day after the final fluorouracil treatment, gene expression of the effectors of epidermal injury (keratin 16), inflammation (interleukin 1β), and extracellular matrix degradation (matrix metalloproteinases 1 and 3) was significantly increased. Types I and III procollagen messenger RNA were induced at week 4 (7-fold and 3-fold, respectively). Type I procollagen protein levels were increased 2-fold at week 24. Actinic keratoses and photoaging were statistically significantly improved. Most patients rated photoaging as improved and were willing to undergo the therapy again. CONCLUSIONS Topical fluorouracil causes epidermal injury, which stimulates wound healing and dermal remodeling resulting in improved appearance. The mechanism of topical fluorouracil in photoaged skin follows a predictable wound healing pattern of events reminiscent of that seen with laser treatment of photoaging.Arch Dermatol. 2009;145(6):659-666--

OBJECTIVE To quantitatively examine the epidermal and dermal cellular and molecular changes that occur after photodynamic therapy of photodamaged human skin. DESIGN Serial in vivo biochemical and immunohistochemical analyses after photodynamic therapy using topical 5-aminolevulinic acid (5-ALA) and pulsed-dye laser treatment. SETTING Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor. PATIENTS A volunteer sample of 25 adults, 54 to 83 years old, with clinically apparent photodamage of the forearm skin. INTERVENTIONS Three-hour application of 5-ALA followed by pulsed-dye laser therapy using non–purpura-inducing settings to focal areas of photodamaged forearms and serial biopsy specimens taken at baseline and various times after treatment. MAIN OUTCOME MEASURES Immunohistochemical analysis was used to assess levels of markers of epidermal proliferation (Ki67), epidermal injury (cytokeratin 16), and photodamage (p53), as well as various markers of dermal collagen production (including prolyl 4-hydroxylase and heat shock protein 47, and type I procollagen). Real-time reverse transcriptase–polymerase chain reaction technology was used to quantify type I and type III collagen. Type I procollagen protein was quantified with enzyme-linked immunosorbent assay. RESULTS Epidermal proliferation was stimulated as demonstrated by increases in Ki67 (more than a 5-fold increase; P < .05) and epidermal thickness (more than a 1.4-fold increase; P < .05). Epidermal injury was produced with increased cytokeratin 16 levels demonstrated (to nearly 70-fold of baseline levels; P < .05). Upregulation of collagen production was demonstrated with increases in procollagen I messenger RNA (2.65-fold; P < .05), procollagen III messenger RNA (3.32-fold; P < .05), and procollagen I protein (2.42-fold; P < .05) levels detected. The baseline epidermal p53 level correlated with cytokeratin 16 levels at acute time points, and the latter were found to correlate with peak collagen production. CONCLUSIONS Photodynamic therapy with the specific treatment regimen employed produces statistically significant quantitative cutaneous molecular changes (eg, production of types I and III collagen) that are associated with improved appearance of the skin. Baseline epidermal p53 immunostaining levels may be predictive of dermal responses to this therapy. Comparison with historical data using pulsed-dye laser therapy alone suggests that use of the photosensitizer may enhance dermal remodeling. The quantitative in vivo molecular data presented herein are in keeping with an evolving model to potentially predict the efficacy of new techniques for the treatment of photoaging.Arch Dermatol. 2008;144(10):1296-1302--

OBJECTIVE To investigate the efficacy, potential limitations, and biological mechanisms of UV-A1 phototherapy for skin sclerosis due to collagen deposition disorders. DESIGN Before-and-after trial of UV-A1 irradiation of sclerotic skin; in vivo biochemical analyses after UV-A1 irradiation of normal skin. SETTING Academic referral center. PARTICIPANTS Patients with morphea/scleroderma or sclerodermoid graft-vs-host disease and volunteers without skin disease. INTERVENTION Sclerotic skin was treated with high-dose (130 J/cm2; n = 12) or medium-dose (65 J/cm2; n = 6) UV-A1 phototherapy 3 times per week for 14 weeks; normal skin was treated with UV-A1 irradiation at various doses and frequencies, with biopsies performed afterwards. MAIN OUTCOME MEASURES In sclerotic skin, induration was clinically assessed using a scoring scale. In normal skin, quantitative polymerase chain reaction was used to assess antifibrotic responses, defined as decreased type I and type III procollagen and increased matrix metalloproteinase levels. RESULTS In patients with sclerotic skin treated with high-dose UV-A1 irradiation, clinical scores for induration modestly decreased. To investigate what factors prevented further improvement (ie, complete clearance), normal skin with light pigmentation was exposed to UV-A1 irradiation (70-150 J/cm2) and was assessed for antifibrotic responses. A single high-dose exposure (110-150 J/cm2) elicited substantial antifibrotic responses and induced skin darkening. This skin darkening attenuated responses to subsequent UV-A1 exposures and was dose dependent. Thus, to minimize skin darkening, additional patients with sclerotic skin were treated with medium-dose UV-A1 phototherapy, which was no less effective than high-dose therapy. CONCLUSION Clinical responses of sclerotic skin to UV-A1 phototherapy were modest because of UV-A1–induced skin darkening, which is photoprotective and attenuates antifibrotic responses. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00129415Arch Dermatol. 2008;144(7):851-858--

OBJECTIVE To evaluate the effectiveness of topical retinol (vitamin A) in improving the clinical signs of naturally aged skin. DESIGN Randomized, double-blind, vehicle-controlled, left and right arm comparison study. SETTING Academic referral center. PATIENTS The study population comprised 36 elderly subjects (mean age, 87 years), residing in 2 senior citizen facilities. INTERVENTION Topical 0.4% retinol lotion or its vehicle was applied at each visit by study personnel to either the right or the left arm, up to 3 times a week for 24 weeks. MAIN OUTCOME MEASURES Clinical assessment using a semiquantitative scale (0, none; 9, most severe) and biochemical measurements from skin biopsy specimens obtained from treated areas. RESULTS After 24 weeks, an intent-to-treat analysis using the last-observation-carried-forward method revealed that there were significant differences between retinol-treated and vehicle-treated skin for changes in fine wrinkling scores (−1.64 [95% CI, −2.06 to −1.22] vs −0.08 [95% CI, −0.17 to 0.01]; P<.001). As measured in a subgroup, retinol treatment significantly increased glycosaminoglycan expression (P = .02 [n = 6]) and procollagen I immunostaining (P = .049 [n = 4]) compared with vehicle. CONCLUSIONS Topical retinol improves fine wrinkles associated with natural aging. Significant induction of glycosaminoglycan, which is known to retain substantial water, and increased collagen production are most likely responsible for wrinkle effacement. With greater skin matrix synthesis, retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00272610Arch Dermatol. 2007;143:606-612--

OBJECTIVES To develop a reproducible photonumeric scale to assess photoprotected skin aging and to determine whether health and lifestyle factors, such as smoking, affect skin aging in photoprotected sites. DESIGN Using standard photographs of participants' upper inner arms, we created a 9-point photonumeric scale. Three blinded reviewers used the scale to grade the photographs. Participants answered multiple lifestyle questions. SETTING Academic outpatient dermatology clinic. PARTICIPANTS Eighty-two healthy men and women aged 22 to 91 years. INTERVENTIONS A professional medical photographer took standardized photographs of each participant's upper inner arm. Participants answered standardized health and lifestyle questions. MAIN OUTCOME MEASURES (1) Interobserver agreement and reproducibility using the photonumeric scale and (2) health and lifestyle factors most predictive of the degree of aging in photoprotected skin. RESULTS There was good blinded interobserver agreement as measured by the maximum range of disagreement scores for each participant (mean, 0.91; 95% confidence interval, 0.76-1.06). Results were reproducible. We developed a multiple regression model showing that the best model for predicting the degree of aging in photoprotected skin includes 2 variables: age and packs of cigarettes smoked per day. CONCLUSIONS This photonumeric scale demonstrates good interobserver agreement and good reproducibility. Using this scale, the degree of aging in photoprotected skin was significantly correlated with patient age and a history of cigarette smoking. Additional studies are needed to continue garnering information regarding independent risk factors for aging of photoprotected skin.Arch Dermatol. 2007;143:397-402--

Background:Adapalene is a synthetic retinoid with an established clinical efficacy against acne and good local tolerability. Its effectiveness in the treatment of photodamaged skin has not been studied. Objective:We sought to determine the safety and efficacy of adapalene gel in the treatment of actinic keratoses and solar lentigines. Methods:In a prospective, 2-center, randomized, controlled, investigator-masked, parallel-group study, 90 patients with actinic keratoses and solar lentigines were treated daily with either adapalene gel (0.1% or 0.3%) or its vehicle gel for 4 weeks, followed by twice-daily applications, if tolerated, for up to 9 months. Results:Of the 90 Caucasian patients (69 male, 21 female; mean age 63.1 years) who were enrolled into the study, 83 patients completed 9 months of treatment. With adapalene gel 0.1% and 0.3%, the mean number of actinic keratoses was reduced by 0.5 ± 0.9 (mean ± SE) and 2.5 ± 0.9, respectively. Whereas, with the vehicle gel, there was an increase of 1.5 ± 1.3 (P< .05). After 1 month of treatment, the patients who received adapalene had significant lightening of solar lentigines as compared with the patients who were treated with vehicle gel (P< .05). After 9 months, 57% and 59% of the patients had lighter lesions in the adapalene 0.1% and 0.3% groups, respectively, in comparison with only 36% in the vehicle group (P< .05). Histologic evaluations revealed improved cellular atypia and reduced epidermal melanin in adapalene-, as compared with vehicle-treated group. The differences, however, were not statistically significant. A retrospective evaluation of paired clinical photographs (before and after 9-month treatment) by 2 dermatologists who were treatment-blinded revealed significant improvement in wrinkles and other clinical features of photoaged skin with adapalene as compared with its vehicle. Conclusion:Adapalene gel 0.1% and 0.3% were well tolerated and improved actinic keratoses, solar lentigines, and other features of photodamaged skin. (J Am Acad Dermatol 2003;49:83-90.)

Public awareness and education may lead to the detection of thinner melanomas, which may result in a decrease in morbidity and mortality rates. Which detection patterns, lesion, and patient characteristics are associated with early detection? Using the University of Michigan prospective melanoma database, the detection patterns, lesion characteristics, and patient characteristics of 1515 consecutive patients with in situ or invasive cutaneous melanomas were reviewed. Tumor thickness (measured in millimeters) was evaluated in relationship to detection patterns (patient, physician, spouse), lesion characteristics (change in color, size, shape/elevation, ulceration, bleeding, tenderness, itching), and patient characteristics (gender, skin type, number of atypical and clinically benign nevi, history of sunburn, personal and family history of melanoma). Patient characteristics associated with early detection included female gender, at least one atypical nevus, greater than 20 clinically benign nevi, and/or a personal history of melanoma. Skin types I, II, and III, a history of sunburn, and/or a family history of melanoma were also associated with thinner lesions, but these associations were not statistically significant. Lesion characteristics associated with earlier detection included a change in color, size, shape/elevation, and/or itching. Physician-detected melanomas were significantly thinner than patient or spouse-detected lesions. Educational campaigns should include increasing melanoma awareness in males and educating the public on the early signs and symptoms. Education should be directed at both high and low-risk groups. Physicians should consider performing total skin examinations routinely on patients. Although they detect a relatively small percentage of all melanomas, physicians detect significantly thinner lesions. Cancer 2002;95:1562–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10880

In a double-blind trial, 21 patients with severe plaque psoriasis were randomly assigned to receive oral cyclosporine, 14 mg/kg/d, or its vehicle. After four weeks of therapy the 11 cyclosporine recipients had the following response to treatment: two had total clearing and six improved markedly, two moderately, and one minimally; whereas ten vehicle-treated patients showed no change or minimal improvement. Vehicle-treated patients, after a switch to cyclosporine for four weeks, demonstrated impressive improvement similar to that seen in patients who initially received only cyclosporine. Moderate or marked improvement or total clearing was noted in 17 (81%) of 21 and 20 (95%) of 21 after one and four weeks of therapy, respectively. Mitotic figures and leukotriene B4 levels in lesions decreased 86% and 64%, respectively, after seven days of cyclosporine therapy. Mononuclear (including activated T cells) and polymorphonuclear leukocyte infiltrates were markedly reduced in lesions of all patients after seven days of cyclosporine therapy. These results suggest that (1) psoriasis may have an immunologic basis mediated by activated T cells and/or other immune cells; (2) if a long-term regimen with a favorable efficacy—side effect ratio can be determined, cyclosporine would be a significant advance in the treatment of psoriasis.(JAMA 1986;256:3110-3116)

A conventional stock assessment model is applied to determine the impact of entrainment and impingement at the Monroe Power Plant on the yellow perch stock of the Western basin of Lake Erie. Parameters of the model are estimated using power plant data, biological data available in the literature, and commercial catch data. The model is applied to estimate the age structure and biomass of the perch stock and to estimate the impact of the power plant on abundance of the impingeable stock and abundance and biomass of the exploited stock. The level of impact was examined under a range of mortality conditions. Under the most extreme conditions examined of full pumping, high fishing mortality, and low natural mortality, the fishable biomass is reduced by 1.7%. This impact is not large, but there are several other power plants and many additional water intakes around the Western basin of Lake Erie.

The production of 14CO2in the breath from an intravenous dose of [14C-N-methyl] -erythromycin (the erythromycin breath test [ERMBT]) and the measurement of the ratio of 6-β-cortisol to free cortisol (6-β-F/FF) in the urine have each been proposed as means of measuring hepatic P450IIIA catalytic activity in patients. We found that there was a significant correlation between the results of each test (r = 0.59, p < 0.001) in 47 patients who were without liver disease and who were not taking medications believed to influence P450IIIA catalytic activity. In the 24 of these patients who were subsequently treated with the P450IIIA substrate cyclosporine, the ERMBT result was highly correlated with the mean trough cyclosporine blood level observed; however, there was no correlation between urinary 6-β-F/FF and the cyclosporine blood levels. In a separate study of a patient during the anhepatic phase of liver transplantation surgery, the ERMBT result decreased by greater than 85%, whereas urinary 6-β-F/FF decreased by just 50%. We conclude that the ERMBT and urinary 6-β-F/FF do not always provide similar information about P450IIIA catalytic activity in patients, possibly because of extrahepatic production of 6-β-F. Of the two tests, the ERMBT appears to provide the most relevant information for cyclosporine administration.Clinical Pharmacology and Therapeutics (1992) 52, 265–273; doi:10.1038/clpt.1992.140

BACKGROUND AND DESIGN: The efficacy of topical tretinoin (all-trans-retinoic acid) in treating photoaging is well established. Questions that remain are (1) whether irritation causes all or part of the improvement; (2) the concentration of tretinoin that maximizes clinical response with minimal side effects; and (3) the effects of long-term treatment on components of the cutaneous immune system. To address these issues, 99 photoaged patients completed a 48-week study using 0.1% tretinoin cream (n=32), 0.025% tretinoin (n=35), or vehicle (n=32) once daily in a double-blind manner. Before and after treatment, we assessed histologic features, keratinocyte expression of HLA-DR and intercellular adhesion molecule-1, numbers of epidermal Langerhans' cells and epidermal and dermal T lymphocytes, and vascularity as measured by dermal endothelial cell area. RESULTS: Both 0.1% and 0.025% tretinoin produced statistically significant overall improvement in photoaging of the face compared with vehicle; there were no clinically or statistically significant differences in efficacy between the two concentrations of tretinoin. After 48 weeks, 0.1% and 0.025% tretinoin produced similar statistically significant epidermal thickening (by 30% and 28%, respectively) compared with vehicle (11% decrease) and increased vascularity (by 100% and 89%, respectively) compared with vehicle (9% decrease). By various analyses, irritant side effects (erythema and scaling) were statistically significantly greater with 0.1% tretinoin than with 0.025% tretinoin. No significant changes occurred in any immunologic markers when tretinoin and vehicle treatments were compared. CONCLUSIONS: Tretinoin 0.1% and 0.025% produce similar clinical and histologic changes in patients with photoaging, despite significantly greater incidence of irritation with the higher concentration. The separation between clinical improvement and irritation suggests that mechanisms other than irritation dominate tretinoininduced repair of photoaging in humans.(Arch Dermatol. 1995;131:1037-1044)

BACKGROUND: Cyclosporine therapy is highly effective in the treatment of psoriasis. To minimize side effects, the lowest effective dosage for maintenance therapy should be sought. METHODS: We selected 61 patients who had achieved clearing or near-clearing of psoriasis during an induction phase of cyclosporine therapy. We then randomly assigned them in a double-blind fashion to receive one of two dosages of cyclosporine (1.5 or 3 mg/kg per day) or placebo for maintenance treatment. For each patient, the time to relapse was the time from the start of maintenance therapy until the patient showed a two-point worsening of psoriasis on a seven-point scale, up to a maximum of 4 months, when the study ended. RESULTS: Sixty patients completed the maintenance study. The mean time to relapse was significantly longer in the 3-mg/kg group (12± 1 weeks) than in the 1.5-mg/kg group (9±1 weeks; P=.04) and the placebo group (7± 1

• BACKGROUND AND DESIGN.— To avoid systemic side effects, topical and intralesional administration of cyclosporine has been used; however, only intralesional administration has been successful. To understand more about the dosing requirements and resultant tissue levels of intralesional cyclosporine, we injected psoriasis plaques in a double-blind fashion with three different concentrations of cyclosporine (17 mg/mL in seven patients, 10 mg/mL in 13 patients, and 2.5 mg/mL in 11 patients) or matching vehicle three times weekly for 4 weeks. RESULTS.— Statistically significant improvement was observed in plaques treated with 17 mg/mL (P =.003) compared with vehicle-treated plaques; the improvements in plaques treated with 10 mg/mL (P=.078) and 2.5 mg/mL (P=.054) achieved marginal statistical significance compared with vehicle treatment. Four weeks after discontinuation of ther

• In an 8-week double-blind trial of sulfasalazine for the treatment of moderate-to-severe psoriasis, 23 and 27 patients received the active and placebo tablets, respectively. At the end of the double-blind phase, there were 17 assessable patients receiving sulfasalazine; 7 (41%) had marked improvement, 7 (41%) had moderate improvement, and 3 (18%) demonstrated minimal change. Only 1 patient receiving placebo demonstrated moderate improvement, whereas the rest had minimal improvement or worsening of psoriasis. When the randomization code was broken, patients receiving sulfasalazine were allowed to continue therapy for an additional 4 weeks in an open manner, while those using placebo left the study. Six of 23 patients discontinued sulfasalazine therapy during the double-blind phase because of side effects, 4 due to the development of a cutaneous eruption and 2 due to nausea. Fourteen of 17 patients, who were assessable at the end of the 8-week double-blind phase, completed the additional 4 weeks of sulfasalazine therapy. Of these 14 patients, marked improvement occurred in 8 (57%), moderate improvement in 2 (14%), and minimal improvement in 4 (29%), compared with pretherapy. The low incidence of severe side effects makes sulfasalazine a consideration for oral therapy in patients whose disease severity does not justify use of methotrexate, etretinate, or psoralen plus UV-A, but whose disease severity is too widespread for safe and practical use of topical corticosteroids.(Arch Dermatol. 1990;126:487-493)

BACKGROUND AND DESIGN: Stretch marks are disfiguring lesions usually caused by excessive stretching of skin. We investigated the response of early, clinically active stretch marks to topical 0.1% tretinoin (retinoic acid) cream. In a double-blind, randomized, vehicle-controlled study, 22 patients applied either 0.1% tretinoin (n=10) or vehicle (n=12) daily for 6 months to the affected areas. Patients were evaluated by physical examination monthly and by analysis of biopsy specimens of stretch marks obtained before and at the end of therapy in comparison with untreated normal skin. RESULTS: After 2 months, patients treated with tretinoin had significant improvement in severity scores of stretch marks compared with patients who received vehicle (P&lt;.05). After 6 months, eight (80%) of the 10 tretinointreated patients had definite or marked improvement compared with one (8%) of the 12 vehicle-treated patients (P=.002). Targeted stretch marks in patients treated with tretinoin had a decrease in mean length and width of 14% and 8%, respectively, compared with an increase of 10% (P&lt;.001) and 24% (P=.008), respectively, in patients who received vehicle. There were no significant differences in various measures of quality and quantity of dermal collagen and elastic fibers in stretch marks when tretinoin and vehicle treatments were compared. CONCLUSIONS: Topical application of tretinoin significantly improves the clinical appearance of early, active stretch marks. The processes that are responsible for the clinical improvement remain unknown.(Arch Dermatol. 1996;132:519-526)

BACKGROUND AND DESIGN: The ability of superficial dermabrasion to improve clinical features of photoaged skin is well known, but the specific biological mechanisms involved are poorly understood. The so-called repair zone, as visualized by routine histologic examination, has been attributed to new collagen formation within the papillary dermis and may be responsible for clinical improvement following dermabrasion. We investigated molecular and histologic events occurring in dermabraded skin and correlated them with clinical improvement. Ten photoaged patients (mean age, 59 years) underwent facial dermabrasion to the level of the papillary dermis. Clinical severity of photoaging was graded in a blinded manner at baseline and 12 weeks after dermabrasion. Biopsy specimens obtained at baseline and 3 and 12 weeks after dermabrasion were analyzed histologically and by in situ hybridization for fibroblast procollagen I mRNA, immunohistologically and by Western blotting with a monoclonal antibody specific for the aminoterminal cleavage site of procollagen I. RESULTS: Masson's trichrome staining demonstrated an increase in collagen from baseline (as an upper dermal band in the dermabrasion ''repair zone'') at 3 and 12 weeks' postdermabrasion. Immunohistologic examination demonstrated papillary dermal fibroblast staining for procollagen I at baseline that increased by threefold at 3 weeks' postdermabrasion and by 1.5-fold at 12 weeks' postdermabrasion. Western blotting demonstrated an average-fold increase in pN collagen I of 4.2± 1.5 at 3 weeks and of 2.7±0.7 at 12 weeks. By in situ hybridization, baseline levels of procollagen I mRNA in papillary dermal fibroblasts increased sixfold at weeks 3 and 12 postdermabrasion. Increase in procollagen I mRNA correlated with clinical improvement, ie, reduction in wrinkling. CONCLUSION: Superficial dermabrasion clinically improves photoaged skin, and this improvement correlates strongly with increased collagen I gene expression.(Arch Dermatol. 1994;130:1136-1142)

BACKGROUND AND DESIGN: Melasma is an acquired, masklike, facial hyperpigmentation. The pathogenesis and treatment of melasma in black (African-American) patients is poorly understood. We investigated the efficacy of topical 0.1% all-trans-retinoic acid (tretinoin) in the treatment of melasma in black patients. Twenty-eight of 30 black patients with melasma completed a 10-month, randomized, vehicle-controlled clinical trial in which they applied either 0.1% tretinoin or vehicle cream daily to the entire face. They were evaluated clinically (using our Melasma Area and Severity Index), colorimetrically, and histologically. RESULTS: After 40 weeks, there was a 32% improvement in the Melasma Area and Severity Index score in the tretinoin treatment group compared with a 10% improvement in the vehicle group. Colorimetric measurements showed lightening of melasma after 40 weeks of tretinoin treatment vs vehicle. Lightening of melasma, as determined clinically, correlated well with colorimetric measurements. Histologic examination of involved skin revealed a significant decrease in epidermal pigmentation in the tretinoin group compared with the vehicle group. Side effects were limited to a mild ''retinoid dermatitis'' occurring in 67% of tretinoin-treated patients. Among the patients in this study in comparison with comparably recruited white patients, melasma was reported to have begun at a later age and was more likely to be in a malar distribution.Conclusions: This controlled study demonstrates that topical 0.1% tretinoin lightens melasma in black patients, with only mild side effects.(Arch Dermatol. 1994;130:727-733)

† BACKGROUND AND DESIGN.— The assessment of the severity of cutaneous photodamage and its response to treatment is an impractical consideration for most practitioners without extensive experience or recourse to high-quality, standardized, baseline photographs. To address this problem, a ninepoint photonumeric standard scale was developed using photographs of subjects representing grades of photodamage from none to severe. This scale was formally tested in a side-by-side comparison with a conventional and widely used written descriptive scale. A panel of seven graders used both scales to score two sets of 25 photographs of photodamaged individuals, and the intergrader agreement and repeatability for the scales were calculated. RESULTS.— The photonumeric scale demonstrated significantly greater agreement between graders than did the descriptive scale (chance-corrected agreements of 0.31 and 0.11, respectively, P&lt;.0001) with no significant difference in repeatability between the two methods. CONCLUSIONS.— This study demonstrates that the photonumeric standard scale is superior to existing methodology in the accurate assessment of cutaneous photodamage and would be a useful adjunct to studies of the efficacy of skin repair agents for this indication.(Arch Dermatol. 1992;128:347-351)

• A histologic study was designed to evaluate the pilosebaceous unit of the scalp in nonpustular patch- and plaque-stage psoriasis. Punch biopsy specimens from involved and uninvolved areas of 28 patients were sectioned in a horizontal plane for qualitative and quantitative study. All samples were evaluated in a blind mode, and data were analyzed for statistical significance. There was no evidence for alopecia of any type. Sebaceous gland atrophy was a frequent concomitant in the psoriatic lesion, with probable down-sizing of the hair follicle and thinner hair shafts. Paradoxical sebaceous gland atrophy and down-sized hair follicles in psoriasis may be due to possible inhibiting effects of yet unidentified factors produced by the epidermal lesion.(Arch Dermatol. 1989;125:639-642)

† Findings from an eight-week fish oil-supplemented diet given to 13 psoriatic patients demonstrated that eicosapentaenoic acid (20:5,n3 [EPA]) and docosahexaenoic acid (22:6,n3 [DCHA]) are rapidly incorporated into the sera, neutrophils, and epidermis of participating patients, and that the incorporation of EPA and DCHA into epidermal lipids increased with weeks of supplementation with minimal alteration of arachidonic acid (AA) in the epidermal lipids. Global clinical evaluation showed that eight patients demonstrated mild to moderate improvement in their psoriatic lesions. Improved clinical response correlated with high EPA/DCHA ratios attained in epidermal tissue specimens. These findings underscore the need for further investigations into the role of dietary n3 fatty acids, particularly the possibility of pentaenoic acid as a potential protective agent and/or therapeutic adjunct for the clinical management of psoriasis.(Arch Dermatol 1986;122:1277-1282)

• The HLA type of patients with various kinds of immune reactions to bovine collagen implants were evaluated to determine a possible genetic basis for such responses. All patients suffering adverse clinical reactions to bovine collagen implants were lacking the HLA-DR4 antigen. All patients who received multiple bovine collagen injections without having adverse clinical reactions were lacking HLA-B5 and HLA-DR5 and had a significantly increased incidence of HLA-DR4. Combinations of histocompatibility antigens may influence immune response to bovine collagen implants.(Arch Dermatol 1986;122:650-654)

In a 16-week randomized, double-blind, vehicle-controlled study of topical tretinoin in the treatment of photoaging, all patients applied topical tretinoin to one forearm and vehicle cream to the other. Half of the patients received tretinoin to the face, and half received vehicle cream. All 30 patients who completed the study showed statistically significant improvement in photoaging on the tretinoin-treated forearms, but not on the vehicle-treated forearms. Fourteen of the 15 patients who received tretinoin to the face had improvement in photoaging, whereas none of the vehicle-treated patients' faces improved, a statistically significant difference in response between the two groups. Statistically significant histologic changes were seen in forearm skin treated with tretinoin, but not with vehicle cream. Side effects were limited to irritation of tretinoin-exposed skin.(JAMA 1988;259:527-532)

The daily dose of cyclosporine required to attain a desired blood level can vary greatly among patients. Because elimination of cyclosporine depends on its metabolism in the liver by an enzyme (cytochrome P-450IIIA) that also demethylates erythromycin, we reasoned that the ability of patients to demethylate a test dose of erythromycin might be useful in estimating their appropriate daily doses of cyclosporine. Accordingly, the [14C-N-methyl] erythromycin breath test was administered to 32 patients before they received 3.0, 5.0, or 7.5 mg/kg/day cyclosporine to treat psoriasis. We found that a simple mathematical equation incorporating just the 14CO2production, the age of the patient, and the daily dose of cyclosporine accounted for almost 80% (R2= 0.78) of the interpatient variability in cyclosporine blood levels we observed. Our data indicate that P-450IIIA activity largely accounts for the relationship between dose of cyclosporine and blood levels for an individual patient. We conclude that the erythromycin breath test may be a convenient guide for cyclosporine dosing.

Long-term sun exposure (UV-A and -B light) results in characteristic clinical changes of the skin (eg, wrinkles, lentigines, elastosis, roughness, and sallowness) collectively known as photodamage.1 We observed that a number of our patients have asymmetrical facial photodamage, with the left side of the face appearing more severely photodamaged than the right side. We postulated that this perceived left-sided predominance of severe photodamage may have arisen from exposure to UV light while driving a left-hand-drive automobile. We performed a study designed to test this hypothesis. METHODS. A total of 120 patients (age range, 43 to 81 years; mean, 62 years; 105 female and 15 male subjects) were recruited through the mail using a questionnaire that obtained the following information: age, sex, occupation, percentage of time spent as an automobile driver, number of years as a driver, number of hours driven per week, and the percentage of time driving with

TO THE EDITOR.— In the July 1985 issue of the Archives, we reported reduction of antibody-dependent cell-mediated cytotoxicity (ADCC) of polymorphonuclear leukocytes obtained from patients during etretinate therapy for psoriasis.1 To further examine the immunomodulatory effect of the retinoid, we also monitored natural killing (NK) activity of lymphocytes and ADCC of monocytes obtained from the same study patients, comparing the activities with those of control subjects.Lymphocytes for the NK cell cytotoxicity assay were isolated by collecting nonadherent monocytes after Ficoll-Hypaque density centrifugation. A human myeloid cell line (K562) was used as the target cell. Radioactive labeling of K562 cells by sodium chromate Cr 51 was accomplished as previously described.2 For the assay, lymphocyte effector cells were incubated with the K562 target cells at three effector-to-target ratios (10:1, 5:1, and 2:1). The rest of the assay procedure and calculation of the percent of cytotoxicity were identical to methods

IN REPLY.— We fully acknowledge that the chance-corrected intergrader agreement coefficient (ie, generalized κ) of .31 for the photonumeric scale does not demonstrate a high level of agreement among graders when assessing varying degrees of photodamaged skin. However, what we have shown is that a grading scale anchored by representative photographs can significantly improve the level of intergrader agreement achieved with a conventional scale. Whether or not this is an "acceptable" level of agreement is not the issue. An improvement is still an improvement, regardless of the size of the increment; until a superior method is devised, we feel the photonumeric scale represents a preferable alternative.Regarding intraobserver agreement (repeatability), the methods employed to test and summarize our data were appropriate and not unduly influenced by limited power or nonnormality.The speculation that the level of intergrader agreement from a photonumeric scale would be especially unsuited when used by less experienced workers is

In Reply.—In answer to Dr Pazmiño, laboratory and drug absorption studies were not done in our study because of the known safety of topical tretinoin.Plasma levels of tretinoin were undetectable after applications of 0.025% tretinoin cream to the arms, legs, and back twice daily for 28 days or 1.0% tretinoin cream once to the entire body.1Any minimal absorption of tretinoin through intact skin and any prostaglandins in the skin (which are metabolized locally) would be unlikely to affect the kidney directly. Based on our experience with retinoids2,3 and on 17 years of safe use of tretinoin without reported vasculitis or effects on kidney function (E. G. Thorne, MD, Ortho Pharmaceutical Company, oral communication, March 1988), we conclude that it is unnecessary to perform kidney function measurements in patients using tretinoin topically.Day-to-day variation and laboratory or collection errors could account for some of the findings