 |
|
Pilot Ultrastructural Evaluation of Human Preauricular Skin Before and After High-Energy Pulsed Carbon Dioxide Laser Treatment
Désirée Ratner, MD;
Annie Viron;
Francine Puvion-Dutilleul, PhD;
Edmond Puvion, PhD
Arch Dermatol. 1998;134:582-587.
ABSTRACT
| |
Background Carbon dioxide laser resurfacing has recently come into favor for the treatment of photodamaged skin. While the clinical and histologic effects of high-energy short-pulse carbon dioxide lasers on human skin have been investigated, the ultrastructural effects of these lasers have not been documented. Our objective was to study the ultrastructural effects of a high-energy pulsed carbon dioxide laser on photodamaged human skin.
Observations Before laser surgery, the ultrastructural changes characteristic of photodamaged skin were evident. Immediately after treatment, there was extensive coagulation necrosis of the epidermis and papillary dermis. Thirty days after treatment, there was no evidence of intercellular or intracellular edema, and ordered differentiation of the epidermal keratinocytes, with a loss of keratinocyte dysplasia, was seen. Increased numbers of desmosomes and tonofibrils were noted. New deposition of collagen was present in the papillary dermis. The ultrastructural findings seen at 90 days after treatment were similar to those seen at 30 days, apart from increased organization of collagen fibers in the papillary dermis.
Conclusions Treatment with the high-energy pulsed carbon dioxide laser appears to reverse the epidermal and dermal changes of photoaging on an ultrastructural level. These changes appear morphologically to be consistent with previously described clinical and histologic changes following laser resurfacing.
INTRODUCTION
LONG-TERM exposure to UV radiation produces characteristic clinical and histologic changes in the skin.1-8 Actinically damaged skin tends to develop fine and coarse wrinkling, mottled pigmentation, telangiectases, loss of elasticity, and premalignant and malignant lesions. Histologically, epidermal atrophy, keratinocyte dysplasia, solar elastosis, and increased melanocyte activity are generally evident. The ultrastructural changes seen in photodamaged skin, including epidermal spongiosis, degeneration of basal and suprabasal keratinocytes, vacuolization of the dermoepidermal junction, disorganization of collagen bundles and collagen and elastic fiber degradation in the papillary dermis, and inactive fibroblasts with scant cytoplasm and few organelles, have also been described.8-14
Treatment with  -hydroxy acids and topical tretinoin has been shown to improve the clinical and histologic changes associated with photoaging.15-24 Reversal of the ultrastructural changes seen in photodamaged skin with the use of these topical agents has also been demonstrated.8, 15, 20, 23-24 -Hydroxy acid–treated keratinocytes appear to be connected by fewer desmosomes and exhibit less clumping of tonofibrils. Both -hydroxy acids and topical tretinoin seem to increase the numbers of anchoring fibrils at the dermoepidermal junction of treated photoaged skin.15, 20, 23 Normalization of the structure and organization of papillary dermal collagen, reduction in the amount of degenerated microfibrillar material, and increased activity and numbers of fibroblasts have also been described after treatment with topical tretinoin.20, 24-25
Dramatic clinical and histologic improvement in photoaged skin may also be produced with medium-depth and deep chemical peeling agents and dermabrasion.26-37 When properly performed, both procedures result in architectural and cytologic normalization of the epidermis, as well as an expanded papillary and reticular dermis composed of dense, parallel arrays of collagen bundles, otherwise known as the dermal repair zone. Nelson et al34 were the first to document the ultrastructural changes produced by medium-depth chemical peels on photodamaged facial skin. Three months after a single 35% trichloroacetic acid peel, markedly decreased intracytoplasmic vacuoles within and between keratinocytes were seen, as were activated fibroblasts with increased cytoplasm and organelles and abundant deposition of new collagen with clearly defined cross striations arranged in an orderly parallel fashion. Decreased solar elastosis was also noted within the papillary dermis.
Carbon dioxide laser resurfacing has recently come into favor as a means of treating photodamaged human skin safely and effectively.38-53 Clinical improvement in facial rhytides and photodamage with the new generation of high-energy pulsed carbon dioxide lasers has been well documented.39-48,51-52 The precise control over the extent of tissue vaporization results in minimization of thermal damage to the skin, thereby reducing the potential risks of scarring and hyperpigmentation, while maximizing therapeutic efficacy.39, 49-52
The histologic changes seen after pulsed laser resurfacing have recently been detailed.50-51 Extensive epidermal necrosis and coagulative changes in the superficial papillary dermis are seen 24 hours after laser administration. Partial or complete reepithelialization is usually seen by day 3, although evidence of papillary dermal collagen damage is still seen. By 90 days after laser treatment, the epidermis is completely intact and dysplasia is absent. A papillary dermal repair zone composed of dense compact collagen bundles aligned in a parallel fashion with the epidermal surface is seen. Decreased numbers of thin elastic fibers oriented perpendicular to the dermoepidermal junction are noted in the superficial papillary dermis, with thicker, more haphazardly arranged fibers in the upper reticular dermis. To our knowledge, the ultrastructural changes seen after treatment with the pulsed carbon dioxide lasers have not yet been described. We sought to determine what changes could be seen not only in the epidermis and dermis, but also at the dermoepidermal junction, using a recent study by Cotton et al50 as a model for our work.
PATIENTS AND METHODS
Preauricular skin samples were obtained from 4 patients (3 men and 1 woman), aged 65 to 80 years, who were scheduled to undergo elective laser resurfacing for multiple actinic keratoses. Informed consent was obtained after the nature of the study had been fully explained. There was no preoperative protocol for the patients. The patients did not apply -hydroxy acids or tretinoin cream before laser treatment.
LASER PROTOCOL
A single 2.0 x 2.0-cm preauricular (sun-exposed) area of skin on each of the patients was treated with a high-energy pulsed carbon dioxide laser (Ultrapulse 5000, Coherent Laser Corporation, Palo Alto, Calif) for a total of 2 passes as follows: A collimated handpiece was used to deliver a 3-mm-spot-size beam. The laser was set at 500 mJ and 4 to 6 W. Laser pulses were placed adjacent to one another with less than 10% overlap to minimize char formation. After the first pass with the laser, the residual coagulated skin was wiped away with moistened gauze. The second pass was performed in the same fashion as the first. Immediately after treatment, a topical antibiotic (bacitracin ointment) was applied, followed by a dry sterile dressing. The patient was instructed to remove the dressing after 24 hours and to clean the wound twice daily thereafter with hydrogen peroxide, followed by reapplication of bacitracin ointment and a dry sterile adhesive strip (Band-Aid).
BIOPSY SPECIMENS
One biopsy specimen was obtained from the treated preauricular area of each patient at each time point, ie, before laser treatment, immediately after laser treatment, and at days 30 and 90 after laser treatment, for a total of 4 biopsy specimens per patient. The biopsy site was anesthetized with 1% lidocaine with 1:100000 epinephrine, and a 1.25-mm punch biopsy specimen was obtained using a metal hair transplant punch. After the punch had been inserted to the level of the subcutaneous fat, the punch was withdrawn, leaving a cylindrical column of tissue attached by a pedicle. The pedicle was cut with curved iris scissors, and hemostasis was achieved with pressure or 35% aluminum chloride solution. Each specimen was divided into 2 or 3 small pieces before fixation. Tissue specimens were fixed in 1.6% glutaraldehyde in 0.1-mol/L Sorensen buffer at a pH of 7.3 (98 mL of 27.22-g potassium phosphate per liter of distilled water plus 102 mL of 28.39-g sodium phosphate per liter of distilled water) for 20 minutes. The fixative was then replaced by 0.1-mol/L Sorensen buffer at a pH of 7.3 for 3 rinses of 20 minutes each. The samples were placed into microcentrifuge tubes with positive sealing lids (snap caps) (Eppendorf tubes, Brinkmann, Westbury, NY) filled with Sorensen buffer at a pH of 7.3 and mailed (via Federal Express) to France on ice blocks. The tissue was then postfixed in 1% osmium tetroxide, dehydrated through a graded ethanol series, and embedded in epoxy resin (Epon). Thin sections were cut on an ultramicrotome (Nova microtome, LKB-Produktter AB, Bromma, Sweden), double stained with uranyl acetate–lead citrate, and observed in a transmission electron microscope (Elmiskop I, Siemens Corp, Iselin, NJ).
RESULTS
Three patients (all men) completed the study. One patient (a woman) did not complete the study, as she did not undergo a 90-day biopsy; however, her pretreatment, posttreatment, and 30-day biopsy results were included in our study.
Prior to laser surgery, ultrastructural findings characteristic of photodamaged skin were noted. There was marked epidermal disorganization, as well as prominent intercellular edema with loss of desmosomal connections and intracellular vacuolization of epidermal keratinocytes (Figure 1). On higher magnification, epidermal atypia was clearly evident (Figure 2). Prominent nucleoli were seen, surrounded by a nucleoplasmic area containing highly dispersed chromatin, reflective of heightened nuclear synthetic activity (Figure 2). Condensed chromatin clumps were rare. Sparse tonofibrils were found within the keratinocytes of the stratum spinosum, and the cytoplasm had a cytolytic appearance, reflective of organellar degradation (Figure 2). The dermoepidermal junction exhibited a flattened contour, as relatively few "footlike" processes of the basal cells were seen (Figure 3). Melanocytes were rarely identified. In the superficial dermis, amorphous material consistent with degraded collagen and elastic tissue was seen (Figure 3). Disorganization of the papillary dermal collagen was present (Figure 3). Inactive fibroblasts with relatively few organelles were occasionally seen.
|
|
|
|
Figure 1. Suprabasal (S) and basal (B) keratinocytes before laser resurfacing. Intracytoplasmic and perinuclear vacuoles (v), widened intercellular spaces (V), and a paucity of desmosomes (d) are present. Papillary dermis (D) is seen at the base of the micrograph (uranyl acetate–lead citrate, original magnification x9000).
|
|
|
|
|
|
|
Figure 2. Keratinocytes of stratum spinosum before laser resurfacing. Sparse tonofibrils (T) are noted within the cytoplasm (C). Scattered mitochondria (m) are seen. The nucleus (N) contains a prominent nucleolus (Nu) and is surrounded by highly dispersed chromatin (c). Few desmosomes (d) occupy intercellular spaces (I) (uranyl acetate–lead citrate, original magnification x9000).
|
|
|
|
|
|
|
Figure 3. Dermoepidermal junction (dej) of photodamaged skin. Intracellular vacuoles (v) are seen within disorganized basal (B) keratinocytes. Disorganized papillary dermal collagen (c) and clumps of amorphous material (a) consistent with degraded collagen and elastic tissue are present in the dermis (D) (uranyl acetate–lead citrate, original magnification x9000).
|
|
|
Immediately after laser treatment, there was extensive epidermal coagulation necrosis as well as coagulative change in the superficial papillary dermis (Figure 4). The reticular dermis did not exhibit coagulation necrosis.
|
|
|
|
Figure 4. Photodamaged skin immediately after laser resurfacing. Coagulation necrosis is noted in the epidemis (E) and papillary dermis (P). The reticular dermis (R), composed of densely packed collagen bundles (c), does not exhibit coagulative change. A single fibroblast (F) is seen in the dermis (uranyl acetate–lead citrate, original magnification x7500).
|
|
|
Thirty days after treatment, marked changes were seen in both the dermis and the epidermis. The keratinocytes were arrayed in a more organized fashion, and widened intercellular spaces were no longer evident (Figure 5). On higher magnification, innumerable desmosomes filled the intercellular spaces between keratinocytes (Figure 5, inset). Numerous, tightly organized bundles of tonofibrils were uniformly distributed throughout the cytoplasm of all keratinocytes (Figure 6). Atypical keratinocytes were no longer evident, and keratinocyte nuclei exhibited abundant condensed chromatin and less prominent nucleoli. Intracytoplasmic vacuoles were no longer seen. The basal cells were precisely aligned along the dermoepidermal junction, with convolution of the junction due to the increased numbers of footlike processes of the basal cells (Figure 7). Scattered normal-appearing melanocytes were identified in the suprabasal and basal layers. The basement membrane zone exhibited newly prominent anchoring fibrils (Figure 7, inset). New deposition of collagen fibers organized in parallel arrays was present in the papillary dermis (Figure 7). A decreased amount of amorphous degraded material was seen in the papillary dermis. Fibroblasts exhibited increased numbers of organelles, most notably rough endoplasmic reticulum and mitochondria.
|
|
|
|
Figure 5. Spinous (S) and basal (B) layers 30 days after laser resurfacing. No vacuolar changes are present. Intercellular spaces are packed with desmosomes (d). A single melanocyte (M) is seen. Organized collagen bundles (c) are noted in the dermis (D) (original magnification x6000). Inset, Innumerable desmosomes (arrows) are present in the intercellular spaces (uranyl acetate–lead citrate, original magnification x30000).
|
|
|
|
|
|
|
Figure 6. Spinous layer 30 days after laser resurfacing. Many desmosomes (d) are seen in the intercellular spaces. Innumerable bundles of tonofibrils (T) are distributed throughout the cytoplasm. The nuclei exhibit condensed chromatin (c) at their periphery (uranyl acetate–lead citrate, original magnification x9000).
|
|
|
|
|
|
|
Figure 7. Thirty days after laser resurfacing. Basal keratinocytes (B) with prominent "footlike" processes (arrows) are aligned at the dermoepidermal junction. A mast cell (m), several fibroblasts (F), new collagen deposition (c), and decreased amorphous material (a) are seen in the dermis (original magnification x9000). Inset, Prominent anchoring fibrils (arrows) are present in the basement membrane zone (uranyl acetate–lead citrate, original magnification x30000).
|
|
|
By 90 days after treatment, the epidermal keratinocytes were still arrayed in an organized fashion (Figure 8). Their intercellular spaces were not as tightly packed with desmosomes, although bundles of tonofibrils were uniformly distributed within their cytoplasm. Intracytoplasmic vacuolization of the keratinocytes was not seen. The basal cells were precisely aligned at the dermoepidermal junction, and prominent footlike processes were again noted. Occasional normal-appearing melanocytes were seen. Prominent anchoring fibrils were identified in the basement membrane zone, comparable in quantity to those seen at 30 days. An even more highly organized network of collagen and elastic fibers was present in the papillary dermis, and amorphous degraded material was absent (Figure 8). Fibroblasts with increased numbers of organelles were noted in the dermis.
|
|
|
|
Figure 8. Ninety days after laser resurfacing. The dermoepidermal junction exhibits no vacuolar change. The basal cells (B) are precisely aligned. Two melanocytes (M) are seen. Highly organized collagen (c) is present in the papillary dermis. Amorphous degraded material is absent (uranyl acetate–lead citrate, original magnification x7500).
|
|
|
COMMENT
In recent years, high-energy short-pulse carbon dioxide lasers have grown in popularity for the treatment of photoaged facial skin, both for the treatment of actinic damage and rhytides. The clinical and histologic effects of these lasers have been studied, and it has been shown that the histologic effects of laser resurfacing are microscopically similar to those of phenol peeling, such that, at 90 days after laser treatment, epidermal atypia and dysplasia are corrected and epidermal polarity is restored, the epidermis being then "indistinguishable from that of younger, normal skin."51 The presence of a subepidermal repair zone consisting of new subepidermal collagen at 3 months after laser treatment, comparable to that seen after medium-depth chemical peels or dermabrasion, has also been described.50-51 The ultrastructural changes seen in our small group of patients at 30 and 90 days after laser resurfacing appear to correlate with these histologic findings.
It is known that ablation of photodamaged epidermis and upper dermis, whether by chemical or physical means, allows reepithelialization from deeper, less photodamaged cells, resulting in the restored structural and functional integrity of epidermal keratinocytes.26-38,50 The increased number and organization of the tonofibrils in epidermal keratinocytes that we have seen at 30 and 90 days after laser treatment appears therefore to be significant, as these findings correlate with the normalization of keratinocyte differentiation from the basal layer to the stratum corneum seen histologically after laser resurfacing. Additionally, the loss of intracellular and intercellular epidermal vacuolization and the presence of folded and tightly apposed intercellular spaces of adjacent keratinocytes studded at intervals with innumerable desmosomes 30 and 90 days after treatment appear to be significant, as these findings are characteristically seen in normal squamous epithelium.54
Clinical studies have revealed a measurable and reproducible decrease in fine wrinkling and improvement in skin texture after laser resurfacing, but the mechanism by which these changes occur is not yet clear.39-48 Fitzpatrick et al39 have postulated that, when the carbon dioxide laser interacts with tissue, 3 zones of tissue damage are produced: a vaporized zone, a zone of irreversible thermal necrosis, and a zone of reversible thermal damage, in which collagen shrinkage is thought to take place. It has been documented that thermal damage to collagen itself results in shrinkage, but it is not clear how great a role this shrinkage plays in generating clinical improvement in wrinkles.55-57 It is also thought that repair of this layer during healing may account for tightening of sagging skin and improvement of creases.39, 46-47 The clinically evident tightening of sagging skin after laser surfacing may be in part due to the formation of new collagen, the decrease in the amount of amorphous debris in the papillary dermis, and the increased activity and number of fibroblasts that have been documented histologically and ultrastructurally after laser and other resurfacing procedures.26-36,38, 50
Nelson et al34 have in fact found that collagen's striation periodicity is reduced after medium-depth chemical peels, resulting in a more compact architecture, and that the diameter of individual fibrils is more variable, consistent with recent production of collagen by activated fibroblasts. Precise quantitative studies will be required to substantiate whether compression of the collagen bundles occurs immediately after laser resurfacing and whether the striation periodicity of the collagen is immediately changed after treatment. If, in fact, the striation periodicity of the collagen in the papillary dermis is reduced at 30 and 90 days after treatment, this may partially explain the clinical perception of tighter, smoother skin in patients treated with resurfacing lasers. The new deposition of dermal collagen that we have seen ultrastructurally after laser resurfacing seems to correspond to the papillary dermal repair zone described by others, but will need to be further characterized, both ultrastructurally and biochemically. While it does appear that the papillary dermal collagen is more organized after 90 days than after 30 days after laser resurfacing, and that individual collagen fibrils may exhibit more variability in diameter at 30 days than at 90 days after laser resurfacing, it is important to realize that these are subjective impressions and that these findings must be documented both qualitatively and quantitatively when future studies of larger numbers of patients are performed.
It has been postulated that increased numbers of anchoring fibrils may help to produce increased adherence of the epidermis to the dermis, resulting in a pulling, or "tenting," that may decrease wrinkling, as seen in patients treated with tretinoin and -hydroxy acids.15, 23, 25 While increased convolution of the dermoepidermal junction and increased numbers of anchoring fibrils may play a role in the increased smoothness and tautness of the skin seen clinically in patients treated with laser resurfacing, further studies will be needed to verify and quantitate any true increase in the number of anchoring fibrils. It is possible that such a phenomenon may somehow also contribute to the clinical improvement in superficial rhytides after laser resurfacing.
It is impossible to draw any conclusions about the ultrastructural effects of laser resurfacing on melanocytes at this time. Very few melanocytes were seen in our pretreatment specimens, but it is probable that this paucity of melanocytes was a result of sampling error. While normal-appearing melanocytes were seen in the basal layer of the epidermis at 30 and 90 days after treatment, it would be premature to make any generalizations regarding melanocyte activity or number at this time. This will be an important area of future study, especially given the recent reports of delayed hypopigmentation occurring after laser resurfacing.58
Despite the small size of our study, it appears that treatment with the high-energy pulsed carbon dioxide laser appears to reverse epidermal and dermal photoaging changes on an ultrastructural level. These changes appear morphologically to be consistent with previously described clinical and histologic changes following laser resurfacing. Further studies will be necessary to correlate more precisely the clinical, histologic, and ultrastructural changes that result from laser resurfacing. Such studies will undoubtedly provide us with a wealth of useful information.
AUTHOR INFORMATION
Accepted for publication January 5, 1998.
We would like to acknowledge the financial support of the Center for Surgical Dermatology, Lutherville, Md, during the early stages of this study.
Presented in poster form at the 24th Annual Clinical and Scientific Meeting of the American Society for Dermatologic Surgery, Boston, Mass, May 8-11, 1997.
We thank Craig Thomas, MS, for his assistance in the preparation of the manuscript for this article.
Reprints: Désirée Ratner, MD, Department of Dermatology, Columbia-Presbyterian Medical Center, 161 Fort Washington Ave, New York, NY 10032.
From the Department of Dermatology, Columbia-Presbyterian Medical Center, New York, NY (Dr Ratner), and the Department of Electron Microscopy, Institut de Recherches sur le Cancer, Villejuif, France (Ms Viron and Drs Puvion-Dutilleul and Puvion).
REFERENCES
| |
1. Kligman LH. Skin changes in photoaging: characteristics, prevention and repair. In: Balin A, Kligman A, eds. Aging and the Skin. New York, NY: Raven Press; 1989:331-346.
2. Taylor DR, Stern RS, Leyden JJ, Gilchrest BA. Photoaging/photodamage and photoprotection. J Am Acad Dermatol. 1990;22:1-15.
ISI
| PUBMED
3. Lavker RM. Structural alterations in exposed and unexposed aged skin. J Invest Dermatol. 1979;73:59-66.
FULL TEXT
|
ISI
| PUBMED
4. Kligman AM. Early destructive effects of sunlight on human skin. JAMA. 1969;210:2377-2380.
FREE FULL TEXT
5. Smith JG, Davidson EA, Sams WM, Clark RD. Alterations in human dermal connective tissue with age and chronic sun damage. J Invest Dermatol. 1962;39:347-350.
ISI
| PUBMED
6. Bernstein EF, Chen YQ, Kopp JB, et al. Long-term sun exposure alters the collagen of the papillary dermis. J Am Acad Dermatol. 1996;34:209-218.
FULL TEXT
|
ISI
| PUBMED
7. Gilchrest BA, Blog FB, Szabo G. Effects of aging and chronic sun exposure on melanocytes in human skin. J Invest Dermatol. 1979;73:141-143.
FULL TEXT
|
ISI
| PUBMED
8. Mitchell RE. A light and electron microscopical study of collagen degeneration. Aust N Z J Surg. 1967;36:310-318.
PUBMED
9. Yamamoto O, Bhawan J, Hara M, Gilchrest BA. Keratinocyte degeneration in human facial skin: Documentation of new ultrastructural markers for photodamage and their improvement during topical tretinoin therapy. Exp Dermatol. 1995;4:9-19.
FULL TEXT
| PUBMED
10. Mitchell RE. Chronic solar dermatosis: an electronmicroscopic study of the epidermis. Australas J Dermatol. 1969;10:75-91.
PUBMED
11. Matsuta M, Kunimoto M, Kosegawa G, Akasaka T, Kon S. Electron microscopic study of the colloid-like substance in solar elastosis. J Dermatol. 1989;16:191-195.
PUBMED
12. Braverman IM, Fonferko E. Studies in cutaneous aging, I: the elastic fiber network. J Invest Dermatol. 1982;78:434-443.
FULL TEXT
|
ISI
| PUBMED
13. Braverman IM, Fonferko E. Studies in cutaneous aging, II: the microvasculature. J Invest Dermatol. 1982;78:444-448.
FULL TEXT
|
ISI
| PUBMED
14. Mitchell RE. Chronic solar dermatosis: a light and electron microscopic study of the dermis. J Invest Dermatol. 1967;48:203-220.
ISI
| PUBMED
15. Ditre CM, Griffin TD, Murphy GF, Sueki H, Telegen B. Effects of alpha-hydroxy acids on photoaged skin: a pilot clinical, histologic, and ultrastructural study. J Am Acad Dermatol. 1996;34:187-195.
FULL TEXT
|
ISI
| PUBMED
16. Griffin TD, Murphy GF, Sueki H, Telegen B, Johnson WC. Increased factor XIIIa transglutaminase expression in dermal dendrocytes after treatment with alpha-hydroxy acids: potential physiologic significance. J Am Acad Dermatol. 1996;34:196-203.
FULL TEXT
|
ISI
| PUBMED
17. Weinstein GD, Nigra TP, Pochi PE, et al. Topical tretinoin for treatment of photodamaged skin: a multicenter study. Arch Dermatol. 1991;127:659-665.
FREE FULL TEXT
18. Bhawan J, Gonzales-Serva A, Nehal K, et al. Effects of tretinoin on photodamaged skin: a histologic study. Arch Dermatol. 1991;127:666-672.
FREE FULL TEXT
19. Weiss JS, Ellis CN, Headington JT, Tincoff T, Hamilton TA, Voorhees JJ. Topical tretinoin improves photoaged skin: a double-blind vehicle-controlled study. JAMA. 1988;259:527-532.
FREE FULL TEXT
20. Ellis CN, Weiss JS, Hamilton TA, Headington JT, Zelickson AS, Voorhees JJ. Sustained improvement with prolonged topical tretinoin (retinoic acid) for photoaged skin. J Am Acad Dermatol. 1990;23:629-637.
ISI
| PUBMED
21. Griffiths CEM, Russman AN, Majmudar G, Singer RS, Hamilton TA, Voorhees JJ. Restoration of collagen formation in photodamaged human skin by tretinoin. N Engl J Med. 1993;329:530-535.
FREE FULL TEXT
22. Tavakkol A, Griffiths CEM, Keane KM, Palmer RD, Voorhees JJ. Cellular localization of mRNA for cellular retinoic acid-binding protein II and nuclear retinoic acid receptor gamma-1 in retinoic-acid treated human skin. J Invest Dermatol. 1992;99:146-150.
FULL TEXT
|
ISI
| PUBMED
23. Woodley DT, Zelickson AS, Briggaman RA, et al. Treatment of photoaged skin with topical tretinoin increases epidermal-dermal anchoring fibrils: a preliminary report. JAMA. 1990;263:3057-3059.
FREE FULL TEXT
24. Yamamoto O, Bhawan J, Solares G, Tsay AW, Gilchrest BA. Ultrastructural effects of topical tretinoin on dermoepidermal junction and papillary dermis in photodamaged skin: a controlled study. Exp Dermatol. 1995;4:146-154.
FULL TEXT
| PUBMED
25. Zelickson AS, Mottaz JH, Weiss JS, Ellis CN, Voorhees JJ. Topical tretinoin in photoaging: an ultrastructural study. J Cutan Aging Cosmetic Dermatol. 1988;1:41-47.
26. Brodland DG, Roenigk RK. Trichloroacetic acid chemexfoliation (chemical peel) for extensive premalignant actinic damage of the face and scalp. Mayo Clin Proc. 1988;63:887-896.
ISI
| PUBMED
27. Monheit GD. The Jessner's + TCA peel: a medium-depth chemical peel. J Dermatol Surg Oncol. 1989;15:945-950.
ISI
| PUBMED
28. Brody HJ, Hailey CW. Medium-depth chemical peeling of the skin: a variation of superficial chemosurgery. J Dermatol Surg Oncol. 1986;12:1268-1275.
ISI
| PUBMED
29. Brodland DG, Cullimore KC, Roenigk RK, Gibson LE. Depths of chemexfoliation induced by various concentrations and application techniques of trichloroacetic acid in a porcine model. J Dermatol Surg Oncol. 1989;15:967-971.
ISI
| PUBMED
30. Brody HJ. Variations and comparisons in medium-depth chemical peeling. J Dermatol Surg Oncol. 1989;15:953-963.
ISI
| PUBMED
31. Stegman SJ. A comparative histologic study of the effects of three peeling agents and dermabrasion on normal and sun-damaged skin. Aesthetic Plast Surg. 1982;6:123-138.
FULL TEXT
|
ISI
| PUBMED
32. Kligman AM, Baker TJ, Gordon HC. Long-term histologic follow-up of phenol face peels. Plast Reconstr Surg. 1985;75:652-659.
FULL TEXT
|
ISI
| PUBMED
33. Baker TJ, Gordon HL, Mosienko P, Seckinger DL. Long-term histological study of skin after chemical face peeling. Plast Reconstr Surg. 1974;53:522-525.
FULL TEXT
|
ISI
| PUBMED
34. Nelson BR, Fader DJ, Gillard M, Majmudar G, Johnson TM. Pilot histologic and ultrastructural study of the effects of medium-depth chemical facial peels on dermal collagen in patients with actinically damaged skin. J Am Acad Dermatol. 1995;32:472-478.
FULL TEXT
|
ISI
| PUBMED
35. Nelson BR, Majmudar G, Griffiths CEM, et al. Clinical improvement following dermabrasion of photoaged skin correlates with synthesis of collagen I. Arch Dermatol. 1994;130:1136-1142.
FREE FULL TEXT
36. Benedetto AV, Griffin TD, Benedetto EA, Humenink HM. Dermabrasion: therapy and prophylaxis of the photoaged face. J Am Acad Dermatol. 1992;27:439-447.
ISI
| PUBMED
37. Winton GR, Salasche SJ. Dermabrasion of the scalp as a treatment for actinic damage. J Am Acad Dermatol. 1986;14:661-668.
ISI
| PUBMED
38. Fitzpatrick RE, Tope WD, Goldman MP, Satur NM. Pulsed carbon dioxide laser, trichloroacetic acid, Baker-Gordon phenol, and dermabrasion: a comparative clinical and histologic study of cutaneous resurfacing in a porcine model. Arch Dermatol. 1996;132:469-471.
FREE FULL TEXT
39. Fitzpatrick RE, Goldman MP, Satur NM, Tope WD. Pulsed carbon dioxide laser resurfacing of photoaged facial skin. Arch Dermatol. 1996;132:395-402.
FREE FULL TEXT
40. Fitzpatrick RE, Goldman MP. Advances in carbon dioxide laser surgery. Clin Dermatol. 1995;13:35-47.
FULL TEXT
|
ISI
| PUBMED
41. Lowe NJ, Lask G, Griffin ME, Maxwell A, Lowe P, Quilada F. Skin resurfacing with the Ultrapulse carbon dioxide laser: observations on 100 patients. Dermatol Surg. 1995;21:1025-1029.
FULL TEXT
|
ISI
| PUBMED
42. Waldorf HA, Kauvar ANB, Geronemus RG. Skin resurfacing of fine to deep rhytides using a char-free carbon dioxide laser in 47 patients. Dermatol Surg. 1995;21:940-946.
FULL TEXT
|
ISI
| PUBMED
43. Lowe NJ, Lask G, Griffin ME. Laser skin resurfacing: pre- and post-treatment guidelines. Dermatol Surg. 1995;21:1017-1019.
FULL TEXT
|
ISI
| PUBMED
44. Lask G, Keller G, Lowe N, Gormley D. Laser resurfacing with the SilkTouch flashscanner for facial rhytides. Dermatol Surg. 1995;21:1021-1024.
FULL TEXT
|
ISI
| PUBMED
45. David LM, Sarne AJ, Unger WP. Rapid laser scanning for facial resurfacing. Dermatol Surg. 1995;21:1031-1033.
FULL TEXT
|
ISI
| PUBMED
46. Hruza GJ, Dover JS. Laser skin resurfacing. Arch Dermatol. 1996;132:451-455.
FREE FULL TEXT
47. Dover JS. CO2 laser resurfacing: why all the fuss? Plast Reconstr Surg. 1996;98:506-509.
ISI
| PUBMED
48. Alster TA, Garg HA. Treatment of facial rhytides with the Ultrapulse high-energy carbon dioxide laser. Plast Reconstr Surg. 1996;98:791-794.
ISI
| PUBMED
49. Kauvar AN, Geronemus RG, Waldorf HA. Charfree tissue ablation: a comparative histopathological analysis of new carbon dioxide (CO2) laser systems. Lasers Surg Med. 1995;16(suppl 7):50.
50. Cotton J, Hood AF, Gonin R, Beeson WH, Hanke CW. Histologic evaluation of preauricular and postauricular human skin after high-energy, short-pulse carbon dioxide laser. Arch Dermatol. 1996;132:425-428.
FREE FULL TEXT
51. Stuzin JM, Baker TJ, Baker TM, Kligman AM. Histologic effects of the high-enery pulsed CO2 laser on photoaged facial skin. Plast Reconstr Surg. 1997;99:2036-2050.
ISI
| PUBMED
52. Fitzpatrick RE, Ruiz-Esparza J, Goldman MP. The depth of thermal necrosis using the CO2 laser: a comparison of the superpulsed mode and conventional mode. J Dermatol Surg Oncol. 1991;17:340-344.
ISI
| PUBMED
53. Smith KJ, Graham JS, Skelton HG, Hurst CG. Additional observations using a pulsed carbon dioxide laser with a fixed pulse duration. Arch Dermatol. 1997;133:105-106.
FREE FULL TEXT
54. Breathnach AS. An Atlas of the Ultrastructure of Human Skin. London, England: J & A Churchill; 1971:116-125.
55. Stringer H, Parr J. Shrinkage temperature of eye collagen. Nature. 1964;204:1307.
ISI
| PUBMED
56. Allain JC, Lous LE, Cohen-Solal L, Bagin S, Maroteaux P. Isometric tension developed during the hydrothermal swelling of rat skin. Connect Tissue Res. 1980;7:127-133.
ISI
| PUBMED
57. Thompson VM, Seiler T, Durrie DS, Cavanaugh TB. Holmium: YAG laser thermokeratoplasty for hyperopia and astigmatism: an overview. Refract Corneal Surg. 1993;9(suppl):S134-S137.
58. Bernstein LJ, Kauvar ANB, Grossman MC, Geronemus RG. The short- and long-term side effects of carbon dioxide laser resurfacing. Dermatol Surg. 1997;23:519-525.
FULL TEXT
|
ISI
| PUBMED
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Expression and Targeting of Human Fibroblast Activation Protein in a Human Skin/Severe Combined Immunodeficient Mouse Breast Cancer Xenograft Model
Tahtis et al.
Molecular Cancer Therapeutics 2003;2:729-737.
ABSTRACT
| FULL TEXT
Nonablative Laser and Light Rejuvenation: The Newest Approach to Photodamaged Skin
Kelly et al.
Arch Facial Plast Surg 2001;3:230-235.
FULL TEXT
|
