The influence of patient age and argon laser therapy on port-wine stains (PWS) was studied quantitatively in 16 patients aged 15-64 years using a spectrophotometer and computer graphics/statistics program. Normalized reflectance curves revealed a 10-20% decrease with age in the reflectance of normal skin from 400 nm to 650 nm, with an even more pronounced reflectance decrease in the region of peak deoxyhemoglobin absorption at approximately 555 nm. In each patient, PWS reflectance was less than that in the normal skin, as expected, and the average discrepancy increased with age from approximately 25% to 50%, with further reduction at 555 nm. The data suggest that with advancing age, both normal skin and PWS have a greater total hemoglobin content and an increased proportion of deoxyhemoglobin, consistent with increasing vascular dilation and tortuosity; and that the age-associated changes in PWS are an exaggeration of those in normal skin. Laser-treated PWS in both young and old patients had reflectance curves indistinguishable from those of untreated PWS in young patients. This implies, contrary to published clinical impressions, that in the absence of scarring the results of argon laser therapy are the same in young and old patients, but that only older patients experience a significant color shift in the lesion.

Twenty-three patients with facial port wine stains were studied to determine whether chilling lesional skin at the time of treatment could improve the outcome of argon laser therapy and whether this effect could be attributed to increased hemoglobin content of chilled sites, as hypothesized on clinical grounds. Each patient was biopsied in two representative and clinically identical sites, once at room temperature and once immediately after application of ice to the skin surface for 2 to 3 minutes. Two additional identical sites were treated with an argon laser in the same manner. Histologic sections of the port wine stain after application of ice tended to have a higher percentage of erythrocyte-filled vessels, but the effect of chilling on the dermal vasculature varied greatly among patients and was not statistically significant. In contrast, chilling of lesional skin prior to laser therapy resulted in a significantly better average outcome (p = 0.0002), with 57 percent of chilled sites superior to the paired room temperature control and none inferior. In nearly all instances of differential response, the site treated at room temperature manifested scarring, while the chilled site did not. Overall, after an average evaluation period of 4.8 months, 65 percent of the patients achieved a good or excellent result in the control site, and 87 percent achieved this result in the chilled site. These data establish the potential benefit of lesional modification prior to argon laser therapy and suggest that in the case of port wine stain chilling, this benefit is due to reduced heat injury of nonvascular elements in the skin.

Patients undergoing maintenance hemodialysis were asked to complete a questionnaire to define further the nature of uremic pruritus. Of the 237 respondents, 87 (37%) reported "prolonged bothersome itchiness" at the time surveyed, and an additional 97 (41%), not affected at that time, had experienced this problem in the past. Of the 184 patients who reported pruritus in either the past or present, discomfort occurred only during or soon after dialysis in 46 (25%) patients and was most severe at those times in an additional 78 (42%) patients. Topical emollients and orally administered antipruritic agents provided relief in only 33 (18%) and 31 (17%) patients, respectively. These data provide the first statistical basis for certain clinical impressions concerning uremic pruritus and suggest it is not as common among patients who are undergoing dialysis as has been previously implied.

Using a serum‐free system, we have investigated the influence of human fibronectin (HFN) and selected growth factors (GF) on the attachment and growth of normal human keratinocytes in vitro. Single‐cell suspensions of keratinocytes from near‐confluent primary plates, plated on 5–10 μg/cm 2 HFN, showed approximately 30–40% attachment after 2–24 hours of incubation at 37°C, compared with 4–6% attachment on uncoated platic plates. Percentage of attached cells was independent of seed density, tissue donor age, in vitro culture age, or medium composition, while subsequent cellular proliferation was strongly dependent on these factors. Keratinocytes grown on an adequate HFN matrix in a previously described hormone‐supplemented medium (Maciag et al., 1981a) achieved four to eight population doublings over 7–12 days at densities ≥ 10 4 cell/cm 2 . Removal of most GF individually from the medium had little or no effect on growth, while removal of epidermal growth factor (EGF) alone reduced growth by 30–35% and removal of bovine brain extract (BE) alone reduced growth by approximately 90%. Conversely, EGF alone in basal medium supported approximately 10% control growth, BE alone supported 30–40% control growth, and the combination of EGF and BE approximately 70%. In addition to its major effect on proliferation in this system, BE was necessary to preserve normal keratinocyte morphology and protein production. These findings expand earlier observations that HFN facilitates keratinocyte attachment in vitro and that a brain‐derived extract can exert a major positive influence on cultured keratinocytes.

The relationship of actinically-induced "premature aging" to chronologic aging was studied in paired fibroblast cultures obtained from the habitually sun-exposed (lateral) and nonexposed (medial) aspects of the arm of eight male donors, aged 41 to 80 years. In each case, the fibroblast strain derived from the medial, nonexposed aspect of the arm underwent more cumulative population doublings than did the paired strain from the lateral sun-exposed aspect, and this discrepancy increased with donor age and severity of clinical aging changes. Hence, chronic sun exposure does accelerate aging in human skin by at least one established in vitro criterion: it decreases the lifespan of cultured fibroblasts. The data underline the difficulty of distinguishing environmental effects from intrinsic aging changes.

The relation between chronic renal failure and the clinical and histological findings in normal-looking skin was studied in twenty-seven patients with minimum to marked rises of serum creatinine; eleven of these were on maintenance hæmodialysis, and three were successful renal transplant recipients. Clinical findings, including pruritus and xerosis which affected 48% and 60%, respectively, of the patients overall, correlated strongly with severity of renal failure. Histological examination revealed endothelial cell activation and/or necrosis, basement membrane zone thickening, and reduplication of the basal lamina involving both venules and arterioles in all specimens. The microangiopathy was severe in 18 of 24 (75%) of the uræmic specimens, but severity correlated poorly with serum creatinine level, hæmodialysis status, or known duration of renal failure, except that it was less severe in the first 2 years (p<0·02). In contrast, the microangiopathy was very much less severe in the transplant recipients than in hæmodialysed patients (p<0·2) and, in the patient studied both before and after transplantation, changes regressed from severe to moderate within 2 months of transplantation. Other histological findings present in many specimens did not correlate with vessel changes. The findings establish the existence of a potentially reversible microangiopathy in normal-looking skin of patients with chronic renal failure. Further study is needed to determine if it reflects the same pathological process that underlies the development of accelerated atherosclerosis responsible for about half the deaths among patients on maintenance haemodialysis.

Repeated exposure to mid-range ultraviolet light (UVB) can dramatically relieve the pruritus associated with uremia. The efficacy of UVB phototherapy in uremic pruritus has been established in a controlled trial; experience with 38 patients suggests that 80 to 90% of those receiving 6 to 8 exposures respond favorably within the treatment period (2 to 5 weeks). Treatment frequency appears not to influence the remission rate, although patients on more intensive schedules experience relief sooner than those treated once weekly. Remissions are long-lasting in many patients, sometimes longer than 2 years. Patients with recurrent pruritus respond to phototherapy at least as well as previously untreated patients and tend to improve more rapidly. UVB phototherapy appears to exert its beneficial effect systemically rather than locally, but its mechanism of action is otherwise unknown.

Gerontology and geriatrics are areas of increasing importance in medicine today. Although changes in the appearance and behavior of human skin have long been noted to accompany aging, physicians have only recently begun to consider the impact of such an age-associated change on the manifestations of dermatologic disease and on the dermatologic management of elderly patients. Gerontologic studies in such fields as immunology, epidermal cell kinetics, DNA damage and repair, and therapeutics are potentially of great relevance to the practicing dermatologist and deserve increased emphasis within our specialty.

Both aging and sun exposure have well-documented effects on the human melanocyte system. Paired biopsies of habitually exposed and nonexposed skin from adjacent anatomic sites were obtained from 8 donors aged 28 to 80 yr in order to study the combined effect of chronic actinic irradiation and chronologic aging. Density of dopa-positive melanocytes was roughly twofold higher in the exposed than in the nonexposed skin at all ages, suggesting an irreversible effect of sun exposure. Melanocyte density declined approximately 6 to 8% of the surviving population per decade in both sites. Dopa-positivity of individual melanocytes was consistently greater in the chronically exposed skin than in the nonexposed skin of the same subject and did not vary with age. These data strengthen and expand earlier observations of age-related melanocyte changes, and explain the apparent paradox of a generalized increase in pigmentation and simultaneous decrease in melanocyte density which frequently accompany advancing age. In addition, the present study suggests that the principal effect of chronic sun exposure on the human pigmentary system is not premature "aging" as currently recognized histologically, but rather activation and/or proliferation of the exposed melanocytes.

The relationship of actinically-induced "premature aging" to chronological aging was studied in paired keratinocyte cultures obtained from the habitually sun-exposed (lateral) and nonexposed (medial) aspects of the arm of 5 male donors, aged 41 to 80 yr. In all cases, the number of cell generations in vitro was greater for cultures derived from sun-exposed skin, and this discrepancy increased with donor age and the severity of clinical aging changes. Hence, chronic sun exposure does accelerate aging in human skin by at least one previously established in vitro criterion: it decreased the lifespan of cultured keratinocytes. Plating efficiency was 11- to 32-fold higher for keratinocytes from chronically sun-exposed skin than nonexposed controls, perhaps reflecting the recognized carcinogenic potential of actinic radiation. Keratinocyte cultures appear to be as amenable to gerontologic studies as the already widely used human fibroblast cultures.

The cutaneous manifestations of mycosis fungoides have been successfully treated in nine patients for 16 to 28 months with oral methoxsalen and subsequent irradiation with longwave ultraviolet light. The efficacy of this therapy was confirmed in one patient, who showed complete clearing of generalized plaques after 1 month (12 treatments) except for a shielded control area which worsened during this period. Methoxsalen photochemotherapy may prove a valuable addition to therapies currently available for mycosis fungoides and may obviate some of the problems associated with conventional management of this disorder.

The beneficial effect of sunburn-spectrum ultraviolet (UVB) phototherapy on uremic pruritus was studied. Seven patients were treated twice weekly for 4 weeks with UVB to one half of the body and placebo phototherapy to the other half. All patients noted generalized improvement without localization of benefit to the UVB side, suggesting a systemic effect of UVB. A comparison of three schedules varying from one to three treatments weekly showed that the percentage of patients responding was not influenced by frequency of UVB exposure, although patients treated more intensively improved faster. In three patients, improvement was delayed until 2 weeks after completion of a course of six treatments over 2 weeks, indicating a delayed onset of benefit in at least some patients. Overall 32 of 38 patients improved after a course of six or eight UVB exposures. Pruritus has recurred in 15 patients after a mean remission of 3 months. Sixteen patients are known to remain in remission for a mean of at least 10.6 months after the first or second course of treatment. The present evidence indicates a systemic mechanism of action for the long-lasting relief of uremic pruritus afforded by UVB phototherapy.

We studied the effect of ultraviolet-light phototherapy on severe persistent pruritus in 18 adult patients on hemodialysis. Patients were randomly assigned to one of two light sources. The experimental group received conventional sunburn-spectrum light in gradually increasing doses. The control group received time-matched exposures to long-wave ultraviolet light. All patients received eight exposures to the entire skin surface over a four-week treatment period. Nine of 10 patients in the sunburn-spectrum group reported marked decrease in pruritus as opposed to two of eight in the placebo group (P less than 0.01). of those responding to sunburn-spectrum light, improvement usually occurred two to three weeks into treatment. Mild sunburn, noted by some patients in this group, was the only side effect. The response to phototherapy was unaffected by the presence of secondary hyperparathyroidism. Ultraviolet phototherapy is a safe, convenient, inexpensive and effective treatment for uremic pruritus.