Integrating Spirituality Into Outpatient Practice in the Adventist Health System.

OBJECTIVES: We examined Adventist Health System (AHS)-affiliated providers and staff regarding controversial spiritual practices such as praying led by a practitioner, sharing of personal religious beliefs, and encouraging patients' religious beliefs for health reasons. METHODS: Approached were 1082 providers to participate in a project to integrate spirituality into outpatient care. Those who agreed were asked to identify staff in their practice to assist. Providers and staff were asked to complete a baseline questionnaire examining attitudes/practices concerning spiritual activities with patients. Regression models were used to identify predictors. RESULTS: Questionnaires were completed by 520 providers (83% physicians and 17% mid-level practitioners) and 217 nurses and other staff members. A significant proportion of providers and staff (29.6% vs 49.1%) indicated "often/very often" to a statement that healthcare professionals should pray with patients, should initiate an offer to pray (25.7% vs 49.1%), should pray if the patient initiates the request (72.2% vs 79.5%), and should encourage greater religious activity for health reasons (48.9 vs 48.1%). With regard to behaviors, 15.3% of providers and 8.8% of nurses and other staff members currently often or always prayed with patients, 24.2% and 25.1% shared their personal faith, and 28.2% compared with 22.0% encouraged patients to become more active in their religious faith; however, 93.3% had little or no training on how to do so. The strongest and most consistent predictor of religious activity with patients was self-rated religiosity of the health professional. CONCLUSIONS: A significant proportion of Adventist Health System providers and staff favor engaging in spiritual practices with patients. Training is needed to engage appropriately and sensitively in these activities.

Effects of a 12-Month Educational Intervention on Clinicians' Attitudes/Practices Regarding the Screening Spiritual History.

OBJECTIVES: Patients' spiritual values, beliefs, and preferences are identified in outpatient medical settings by the taking of a screening spiritual history (SSH). We report the impact of an educational/training program on the attitudes/practices of physicians (MDs) and midlevel practitioners (MLPs). METHODS: A convenience sample of 1082 MDs or MLPs in outpatient practices was approached to participate in a 12-month educational/training program in this single-group experimental study. Of the 1082 professionals, 48% (427 physicians, 93 MLPs) agreed to complete a questionnaire assessing demographics, practice characteristics, religiosity, and attitudes/practices regarding the SSH. Changes in attitudes/practices over time were examined and baseline predictors identified using mixed-effects regression. RESULTS: Of the 520 participants completing questionnaires at baseline, 436 were assessed at 1 month (83.8%) and 432 were assessed at 12 months (83.1%). The belief that MDs should take a SSH did not significantly change over time (B = -0.022, standard error [SE] 0.028, P = 0.426). However, those who took an SSH often/always increased from 16.7% at baseline to 34.8% at 12-month follow-up (B = 0.328, SE 0.030, P < 0.0001), and perceived patient acceptance/appreciation increased from 72.1% to 80.5% (B = 0.074, SE 0.023, P = 0.001). Predictors of increased SSH taking across time among MDs were older age, female sex, family medicine specialty, prior training, and importance of religion; older age was the only predictor in MLPs. CONCLUSIONS: Although attitudes toward taking an SSH were not affected, taking an SSH increased initially and was sustained over time, as did the sense that patients accepted/appreciated this practice. Educational programs of this type may be used to increase SSH taking by outpatient MDs and MLPs.

The spiritual history in outpatient practice: attitudes and practices of health professionals in the Adventist Health System.

BACKGROUND: A screening spiritual history (SSH) is how health professionals (HP) identify patients' spiritual values, beliefs and preferences (VBPs) in the outpatient setting. We report on attitudes and practices of HPs in the largest Protestant health system in the U.S., the Adventist Health System (AHS). METHOD: Physicians or mid-level practitioners (N = 1082) in AHS-affiliated practices were approached and 513 (47%) agreed to participate. Participants were asked to identify a "spiritual care coordinator" (nurse/staff) and complete a questionnaire that assessed demographics, practice characteristics, religious involvement, and attitudes/practices concerning the SSH. Prevalence and predictors of attitudes/practices were identified. RESULTS: Questionnaires were completed by 427 physicians, 86 mid-level practitioners, and 224 nurses/staff (i.e., spiritual care coordinators). Among physicians, 45% agreed that HPs should take a SSH; of mid-level practitioners, 56% agreed; and of nurses/staff, 54% agreed. A significant proportion (range 31-54%) agreed that physicians should take the SSH. Participants indicated a SSH is appropriate for all outpatients (46-57%), well-visit exams (50-60%), the chronically ill (71-75%) and terminally ill (79-82%). A majority agreed the SSH should be documented in the medical record (67-80%). Few (11-17%) currently took a SSH, although most were at least sometimes willing to take a SSH (87-94%) or review the results thereof (86-98%). Self-rated importance of religion was the strongest predictor of SSH attitudes/practices. CONCLUSIONS: Many in the AHS say a SSH should be done, are willing to do it, and are willing to review the results, although few currently do so. Education, training, and support may help HPs identify and address patients' spiritual VBPs.

Promoting Spiritual Well-Being Among Nurses.

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.

Intraepidermal erbium:YAG laser resurfacing: impact on the dermal matrix.

BACKGROUND: Various minimally invasive treatments enhance the skin's appearance. Little is known about the molecular mechanisms whereby treatments working at the epidermal level might alter the dermis. OBJECTIVE: We sought to quantify the molecular changes that result from erbium:yttrium-aluminium-garnet (Er:YAG) laser microablative resurfacing. METHODS: We performed biochemical analyses after intraepidermal Er:YAG laser resurfacing of 10 patients. Immunohistochemical analysis and polymerase chain reaction technology were utilized to measure key biomarkers. RESULTS: The basement membrane remained intact after intraepidermal microablation, as demonstrated by laminin γ2 immunostaining. Epidermal injury was demonstrated with acute up-regulation of keratin 16. An inflammatory response ensued as indicated by increases in cytokines interleukin 1 beta (IL-1ß) and IL-8 as well as a substantial neutrophil infiltrate. Levels of cJun and JunB proteins, components of the transcription factor AP-1 complex, were also elevated. Up-regulation of extracellular matrix degrading proteinases matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-9 was noted. A transient increase in keratinocyte proliferation, as indicated by staining for Ki67, was observed. Increased expression of type I and type III procollagen was demonstrated. LIMITATIONS: The data presented are those that resulted from a single treatment session. CONCLUSIONS: Although microablation was confined to the uppermost epidermis, marked changes in epidermal and dermal structure and function were demonstrated after Er:YAG laser microablative resurfacing. We demonstrated substantial dermal matrix remodeling, including a degree of collagen production that compares favorably with some more invasive interventions. Dermal remodeling and stimulation of collagen production are associated with wrinkle reduction. Thus these results suggest that the skin's appearance may be enhanced by creating dermal changes through the use of superficially acting treatments.

Retinoic acid 4-hydroxylase inducibility and clinical response to isotretinoin in patients with acne.

BACKGROUND: The cytochrome P450 (CYP) enzyme CYP26 (retinoic acid [RA] 4-hydroxylase) initiates the catabolism of all-trans RA (tRA) and limits the effects of tRA. The CYP26 enzyme acts specifically on tRA, but not 13-cis RA (isotretinoin), a retinoid used to treat severe acne. However, 13-cis RA can isomerize to tRA, which can then be metabolized by CYP26. OBJECTIVE: In healthy individuals, we assessed the variability of CYP26 enzymatic activity. We then investigated whether response to oral 13-cis RA among patients with acne correlates with variability in CYP26 expression. METHODS: In healthy individuals, we isolated microsomal fractions from the epidermis of keratome biopsy specimens and measured CYP26 enzymatic activity in untreated skin and skin treated with tRA. Enzymatic activity was determined based on rate of formation of 4-hydroxy RA (pg/min/mg microsomal protein). Using real-time polymerase chain reaction we quantified CYP26 messenger RNA induction after tRA application in patients with acne who responded or did not respond to one course of 13-cis RA. RESULTS: In normal-appearing skin (N = 118), CYP26 enzymatic activity was widely variable (1-180 pg/min/mg microsomal fraction; mean 42.7 +/- 3.5). Furthermore, CYP26 enzymatic activity was inducible in a dose-dependent manner in normal-appearing skin after tRA application, but not correlated with age or sex (N = 29). In patients with acne, CYP26 messenger RNA induction after 0.1% tRA application did not differ (P > .05) between patients who responded (N = 8, 587 +/- 325-fold) or did not respond (N = 8, 657 +/- 227-fold) to one course of 13-cis RA. LIMITATIONS: The small number of patients with acne treated with 13-cis RA was a major limitation. CONCLUSION: Factors other than CYP26 activity may determine response to isotretinoin in acne.

Computer-assisted alignment and tracking of acne lesions indicate that most inflammatory lesions arise from comedones and de novo.

BACKGROUND: Inflammatory acne lesions are believed to derive from comedones; however, their evolution has not been rigorously studied. OBJECTIVE: To examine the evolution of facial acne lesions using serial digital photographs and spatial alignment software. METHODS: Six predefined lesion types, including inflammatory lesions, were counted and tracked from photographs taken every 2 weeks for 12 weeks from 25 individuals with untreated facial acne. RESULTS: Closed comedones occurred most frequently (37%), followed by erythematous macules (26%), inflammatory papules (15%), open comedones (12%), pustules (2%), and nodules (1%). Inflammatory lesions were preceded by comedones (54%), normal-appearing skin (28%), erythematous macules (12%), and scars (6%). LIMITATIONS: Lesions could have appeared and resolved within the 2-week intervals and some comedones may have been too small to identify on digital photographs. CONCLUSION: Our results confirm the comedonal origin of the majority of inflammatory acne lesions. However, a sizeable number (28%) appear to arise from normal skin.

Effect of smoking on aging of photoprotected skin: evidence gathered using a new photonumeric scale.

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.

Improvement of naturally aged skin with vitamin A (retinol).

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.

A randomized, controlled, split-face clinical trial of 1320-nm Nd:YAG laser therapy in the treatment of acne vulgaris.

BACKGROUND: There is a need for additional effective treatments for acne vulgaris. Laser therapy has been explored as a therapeutic option for acne, but rigorously designed studies in this area have been limited. OBJECTIVE: We sought to examine the efficacy of an infrared laser in the treatment of acne. METHODS: We conducted a randomized, controlled, single-blind, split-face clinical trial of 46 patients with facial acne. Patients received a series of 3 nonablative laser treatments using a novel neodymium:yttrium-aluminum-garnet (Nd:YAG) laser to half of the face. Serial blinded lesion counts and global acne severity rating of standardized bilateral patient photographs were performed. Sebum production was measured, and patient self-assessment surveys were administered. RESULTS: A transient but statistically significant improvement in lesion counts of open comedones was demonstrated in treated skin as compared with untreated skin. There were no significant differences between treated and control sides of the face in terms of changes in mean papule or pustule counts. Grading of serial photographs revealed no significant differences between treated and untreated skin. Patient surveys indicated that the majority of patients found the treatments to be at least mildly effective for both acne and oiliness. LIMITATIONS: The current study only addresses the efficacy of a single laser system employing a specific treatment regimen. CONCLUSIONS: Infrared laser therapy may improve comedonal acne. Additional work is needed to better define the degree and duration of the effect. Patients appear to positively view such therapy for both acne and oily skin.

Effects of a 12-month educational intervention on outpatient clinicians' attitudes and behaviors concerning spiritual practices with patients.

OBJECTIVE: We report here the impact of an educational training program on attitudes and practices of physicians (MDs) and mid-level practitioners (MLPs) toward controversial spiritual practices, such as practitioner-led prayer, sharing personal religious beliefs, and encouraging patients' religious beliefs. METHODS: In this single-group experimental study, 427 physicians and 93 MLPs affiliated with the Adventist Health System agreed to complete a questionnaire assessing demographics, practice characteristics, religiosity, and attitudes and behaviors at baseline, 1 month, and 12 months. Changes in attitudes and practices over time were examined and baseline predictors were identified using mixed-effects regression models. RESULTS: For the most part, attitudes regarding praying with patients, sharing faith with patients, and encouraging patients' own religious faith did not change much during the 12-month educational training program. However, significant increases were found in frequency of praying with patients (MDs and MLPs), willingness to pray with patients (MDs), sharing their faith with patients (MDs), and encouraging patient's own religious faith (MDs and MLPs). Among physicians, predictors of praying with patients across time were older age, Christian affiliation, and importance of religion, and among MLPs, they were older age, non-White race, and importance of religion. No interaction between time and religiosity was found. CONCLUSION: Although attitudes toward these mostly controversial practices were largely unaffected, the frequency of praying with patients, sharing faith, and supporting patient's own religious faith increased over time in both religious and nonreligious clinicians. Educational programs of this type may be important in changing clinicians' behaviors regarding appropriate and sensitive engagement in such activities with patients.

Prevalence of psychotropic medication use among cosmetic and medical dermatology patients: a comparative study.

BACKGROUND: Little is known about the psychologic status of cosmetically oriented dermatology patients. OBJECTIVE: We sought to determine the prevalence of psychotropic medication use among such patients to offer insight into the rates of psychopathology in this group. METHODS: We conducted a retrospective chart review of patients seeking consultation at a cosmetic dermatology practice, recorded patients' use of psychotropic medicines, and compared this with data from a control group of medical dermatology patients. RESULTS: Both groups reported rates of psychotropic medication use above those expected in the general population. There was no statistically significant difference in the prevalence of psychotropic drug use between cosmetic (18%) and medical (17%) dermatology patients. LIMITATIONS: There is not a one-to-one correspondence between psychotropic medication use and the presence of psychopathology. Data are based on patient health histories and, thus, may be subject to underreporting. CONCLUSIONS: There is a relatively high rate of psychotropic drug use among all patients seeking care from dermatologists, but this does not appear to be more common among patients interested in undergoing cosmetic procedures.

The effects of laser-mediated hair removal on immunohistochemical staining properties of hair follicles.

BACKGROUND: The mechanisms involved in laser-mediated hair removal remain unclear. One means of reducing hair growth is alteration of follicular stem cells. OBJECTIVE: We sought to examine the effects of laser hair removal on the immunohistochemical staining properties of human hair follicles, including the putative stem cells of the bulge region. METHODS: Treatment of unwanted axillary hair was performed on one side using an 800 nm-wavelength diode laser and on the other side using a 1064 nm-wavelength neodymium:yttrium-aluminum-garnet laser. Serial skin samples were obtained at baseline and various times after treatment and stained using immunohistochemical techniques. RESULTS: Hair shafts were thermally altered, but the immunostaining properties of much of the follicle, including the bulge region, remained generally unchanged. LIMITATIONS: This study only addressed the acute immunohistochemical changes found after a single treatment using specific laser parameters. CONCLUSIONS: Laser-mediated hair removal does not appear to work by frank destruction of follicular stem cells. Other mechanisms including functional alteration of these cells may underlie the clinical efficacy of the procedure.

Microdermabrasion with and without aluminum oxide crystal abrasion: a comparative molecular analysis of dermal remodeling.

BACKGROUND: Microdermabrasion is a popular method of superficial skin resurfacing with effects on dermal remodeling. OBJECTIVE: The purpose of this study was to evaluate the relative importance of the two components of microdermabrasion, negative pressure and abrasion, in stimulating expression of key genes involved in dermal remodeling. METHODS: Ten subjects were treated with a microdermabrasion machine using focal crystal abrasion and negative pressure or negative pressure alone for 3 seconds. Serial biochemical analyses were performed. Reverse transcriptase real-time polymerase chain reaction assays were used to evaluate changes in transcription factor activator protein-1, primary cytokines (interleukin 1beta, tumor necrosis factor-alpha), and matrix metalloproteinases (MMP-1, MMP-3, MMP-9). RESULTS: Significant increases in gene expression of the c-Jun component of activator protein-1, interleukin 1beta, tumor necrosis factor-alpha, MMP-1, MMP-3, and MMP-9 were found with crystal abrasion combined with negative pressure. Negative pressure alone resulted in increased gene expression of MMP-1 and MMP-3 but of a quantitatively reduced magnitude when compared with negative pressure with crystal abrasion. LIMITATIONS: It is unclear that molecular changes seen with these treatments can result in clinical effect. CONCLUSION: The abrasive component of microdermabrasion is necessary for stimulating expression of key genes involved in dermal remodeling.

Long-term treatment of photoaged human skin with topical retinoic acid improves epidermal cell atypia and thickens the collagen band in papillary dermis.

BACKGROUND: Risk of photocarcinogenesis and the relevance of collagen in wrinkle effacement are two issues related to prolonged use of retinoic acid (RA) that have not been fully addressed. OBJECTIVE: Our purpose was to investigate the degree of epidermal cellular atypia and the thickness of papillary dermal collagen in photoaging after long-term use of RA. METHODS: Thirty-four subjects with photoaged skin were treated daily with 0.05% RA for at least 6 months. Epidermal cellular atypia was graded by means of a semiquantitative scale. Thickness of collagen band was measured by using image-analysis software. RESULTS: Compared with pretreatment findings, melanocytic and keratinocytic atypia was significantly reduced and the collagen band thickness doubled. LIMITATIONS: This was an open-label study. CONCLUSION: Improvement in epidermal cellular atypia is consistent with the ability of RA to act as a chemopreventive agent in epithelial carcinogenesis. Prolonged use also significantly increased collagen matrix deposition in dermal repair zones, which most likely contributes to wrinkle effacement by RA.

Microdermabrasion: a molecular analysis following a single treatment.

BACKGROUND: Microdermabrasion is a popular method of superficial skin resurfacing. It is unclear if dermal remodeling actually occurs. OBJECTIVE: To rigorously investigate the molecular alterations observed following a single microdermabrasion treatment. METHODS: Forty-nine subjects received a single microdermabrasion treatment to buttock skin. Serial in vivo biochemical and immunohistological analyses were performed. Reverse transcriptase real-time polymerase chain reaction and immunohistochemistry assays were used to evaluate changes in transcription factors (AP-1, NF-kappaB), primary cytokines (interleukin-1beta, tumor necrosis factor-alpha), matrix metalloproteinases (MMP-1, MMP-3, MMP-9), barrier repair enzymes (acetyl-coenzyme A carboxylase, 3-hydroxy-3-methylglutaryl coenzyme A reductase), and type I procollagen. Results Elevation of transcription factors, primary cytokines, and matrix metalloproteinases occurs rapidly after a single microdermabrasion treatment. Two of 11 subjects also demonstrated increased type I procollagen messenger RNA and protein levels 14 days after treatment. No alteration in stratum corneum thickness was detected. CONCLUSION: Microdermabrasion activates a dermal remodeling/wound healing cascade with minimal epidermal disruption. Evidence now exists to further study manipulation of variables such as number and timing of microdermabrasion sessions.

Dermal matrix remodeling after nonablative laser therapy.

OBJECTIVE: Nonablative laser therapy is widely practiced for cutaneous rejuvenation. We sought to quantify dermal molecular changes after exposure of photodamaged skin to nonablative laser energy. METHODS: Nonablative laser therapy of forearm skin using either a 585-nm wavelength pulsed dye laser or a 1320-nm wavelength neodymium:yttrium-aluminum-garnet laser was performed. Serial biopsy specimens were obtained at baseline and various times after treatment. RESULTS: Statistically significant increases in type I procollagen messenger RNA expression occurred after exposure of photodamaged skin to each laser. Induction was 47% (P < .05) and 84% (P < .05) above baseline levels 1 week after laser therapy among those treated with the pulsed dye and neodymium:yttrium-aluminum-garnet lasers, respectively. Substantial induction of type III procollagen, various matrix metalloproteinases, and primary cytokines was also demonstrated. Responses with respect to all molecules studied were highly variable. LIMITATIONS: This study addresses molecular changes after a single laser exposure whereas clinically, serial treatments are often provided. CONCLUSIONS: Nonablative laser therapy may result in quantifiable alterations in molecules associated with remodeling of the dermal matrix, although responses vary greatly among patients.

Analysis of the Nature of IRB Contingencies Required for Informed Consent Document Approval.

The University of Michigan Human Research Protection Program formed a six-member committee to analyze the nature of Institutional Review Board (IRB) staff and board contingencies for the approval of informed consent documents. Of the 100 studies examined, 87% had one or more informed consent contingencies. "Omissions" in documentation (40%) and "better clarity" (24%) accounted for the majority, while "word-smithing" accounted for only 10%. This is one of the first studies to examine the nature of IRB contingencies as they relate to informed consent documents. Educational efforts targeting completeness in documentation and clarity on the part of study teams, and discouraging "word-smithing" on the part of IRBs, could reduce the number of informed consent contingencies and expedite the IRB approval process.

Connective tissue remodeling induced by carbon dioxide laser resurfacing of photodamaged human skin.

OBJECTIVE: To quantitatively examine the dynamics of molecular alterations involved in dermal remodeling after carbon dioxide (CO(2)) laser resurfacing of photodamaged human skin. DESIGN: Serial in vivo biochemical analyses after laser therapy. SETTING: Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor. Subjects Volunteer sample of 28 adults, 48 to 76 years old, with clinically evident photodamage of the forearms. Intervention Focal CO(2) laser resurfacing of photodamaged forearms and serial biopsies at baseline and various times after treatment. MAIN OUTCOME MEASURES: Reverse transcriptase real-time polymerase chain reaction technology and immunohistochemistry were used to assess levels of type I and type III procollagens; matrix metalloproteinases (MMPs) 1, 3, 9, and 13; tropoelastin; fibrillin; primary cytokines interleukin 1beta and tumor necrosis factor alpha; and profibrotic cytokine transforming growth factor beta1. RESULTS: Production of type I procollagen and type III procollagen messenger RNA peaked at 7.5 and 8.9 times baseline levels, respectively, 21 days after treatment and remained elevated for at least 6 months. Increases in messenger RNA levels of several cytokines (interleukin 1beta, tumor necrosis factor alpha, and transforming growth factor beta1) preceded and/or accompanied changes in collagen levels. Marked increases in messenger RNA levels of MMP-1 (39 130-fold), MMP-3 (1041-fold), MMP-9 (75-fold), and MMP-13 (767-fold) were noted. Levels of fibrillin and tropoelastin rose in a delayed fashion several weeks after treatment. CONCLUSIONS: The biochemical changes seen after CO(2) laser resurfacing proceed through a well-organized and highly reproducible wound healing response that results in marked alterations in dermal structure. These quantitative changes may serve as a means for comparison as other therapeutic modalities meant to improve the appearance of photodamaged skin are evaluated.