Cutaneous melanoma risk and phenotypic changes in large congenital nevi: a follow-up study of 46 patients.

BACKGROUND: Large congenital melanocytic nevi may undergo malignant transformation. Few prospective studies have evaluated the incidence of melanoma in large congenital nevi or have described how their phenotypic characteristics change over time. OBJECTIVE: We attempted to ascertain the incidence of cutaneous melanoma in a cohort of patients with large congenital nevi and to evaluate the frequency and nature of several morphologic changes over time. METHODS: Forty-six patients with large congenital nevi were prospectively followed up in our Pigmented Lesion Group. Large congenital nevi were defined as those occurring at birth and comprising 5% body surface area or greater in infants, children, and preadolescents and more than 20 cm in adolescents and adults. Information was obtained on location, satellitosis, changes in color and nodularity, and incidence of melanoma. The most atypical histologic findings from those who underwent biopsy were also noted. Standardized morbidity ratios (SMR) and 5-year cumulative risk were calculated and presented with corresponding 95% confidence intervals (CI). RESULTS: Twenty-four male and 22 female patients (age range, 7 days to 36.7 years; mean, 8.4 years) with large congenital nevi were followed up prospectively for a total of 335 person-years (range, 0.17 to 17.5 person-years; mean, 7.3 person-years). Two patients (4.3%) experienced 3 cutaneous melanomas that originated in their primary congenital nevi. We found one case of neurocutaneous melanosis. No satellite, extremity, or extracutaneous melanomas were detected. The majority of nevi in our cohort were located on the posterior trunk, were accompanied by multiple satellite congenital nevi, and became lighter over time. In the 27 patients who underwent biopsies, the most atypical histologic findings included melanoma, atypical melanocytic dysplasia, neurocristic dysplasia, atypical neural crest hamartomas, atypical spindle cell tumors, and congenital nevi with dysplasia. The SMR comparing observed-to-expected melanoma incidence was 148 (95% CI 18, 535; P = .0002) indicating a substantially increased risk of melanoma in patients with large congenital nevi. The cumulative 5-year risk of cutaneous melanoma was 5.7% (95% CI 0%, 13.5%). CONCLUSION: Our findings are consistent with the previously observed increased risk for the occurrence of cutaneous melanoma in patients with large congenital nevi. Although the number of patients with melanoma in this study is small, our observations and those of previous studies suggest that location and age correlates with melanoma risk. The majority of large congenital nevi are located on the trunk and may undergo several clinical changes as these patients age. Additional prospective studies are needed to gain more insight into the natural history and optimal management of large congenital nevi.

Characterization of unmyelinated axons uniting epidermal and dermal immune cells in primate and murine skin.

The present study was undertaken to characterize further the structure and function of cutaneous nerves which we have previously shown to associate with skin immune cells (Hosoi et al., Nature 1993: 363:159). Ultrastructurally, axons were prominent within the superficial dermis and epidermis in neonatal murine skin, but they were inconspicuous in adult murine and primate skin. Immunohistochemical and immunoultrastuctural evaluation of normal adult human and simian skin for neural cell adhesion molecule (N-CAM), however, defined a plexus of axons surrounding superficial dermal mast cells and extending as delicate, vertical branches into the overlying epidermal layer. Antibodies to neuropeptides substance P, calcitonin gene-related peptide, and to nerve cell-specific clathrin (LCb subunit) also reacted with this neural plexus. Double labeling disclosed intimate associations of N-CAM-positive axons with dermal chymase-positive mast cells as well as with epidermal CD1a-positive Langerhans' cells by confocal scanning laser microscopy. Functionally, capsaicin applied to forearm skin revealed by 6 h discharge of mast cell chymase and induction of E-selectin in adjacent microvascular endothelium, events consistent with release of substance P from axons and subsequent stimulation of cytokine-mediated mast cell-endothelial interaction. Identical application of capsaicin to human skin xenografted to immunodeficient mice, and thus experimentally lacking in unmyelinated axons, failed to show similar findings. These results provide additional support to the concept that an elaborate network of cutaneous axons may play a functional role in regulation of skin inflammation and immunity.

Body measurements and body weights of special-fed Holstein veal calves.

Changes in various body dimensions of special fed veal calves were measured and correlated with body weight (BW) at three specific times during the growth period as contemporaries and over the entire feeding period as noncontemporaries. The calves (n = 826) were weighed and measured for body length, heart girth, wither height, and hip width at 2, 8, and 16 wk after arrival at the veal farms. Each of the four measurements, expressed as ratios to BW, decreased over the feeding period; decline in the ratio of hip width to BW was less than the decreases in the other ratios. Linear models to predict contemporary BW within each age group based on all body measurements were developed; R2 values for models for 2, 8, and 16 wk were 0.72, 0.77, and 0.76, respectively. Within each of the three age classes, a model including linear, quadratic, and cubic terms of heart girth yielded the highest R2 values of any single measurement (0.46, 0.63, and 0.67 for data for 2, 8, and 16 wk, respectively). The addition of heart girth as a second linear measurement to three-term models containing only one other measurement increased the R2 more than did the addition of any other single linear expression, except for the equation based on body length. When all records on all calves were combined and the observations were treated as noncontemporaries, the R2 was 0.97 for a linear model that included all four measurements. However, this R2 was essentially the same as the R2 from a three-term model using only heart girth. The cubic models in descending order of R2 values were heart girth, body length, hip width, and wither height. These results suggest that BW can be predicted accurately in a group of noncontemporary male veal calves ranging from 2 to 16 wk after the start of the feeding period. However, the BW of calves within contemporary groups (2, 8, and 16 wk) cannot be predicted accurately according to R2 values.

Effects of live animal performance and hemoglobin level on special-fed veal carcass characteristics.

Growth and carcass characteristics were measured on 975 Holstein bull calves raised on four commercial veal farms (nine feeding groups). Average values for blood hemoglobin (Hb), live weight and gain, dressing percentage (DP; hide-on and hide-off), visual muscle color score, rib-eye-area (REA), and carcass conformation score were 7.8 g/dl, 187.1 kg, 1.46 kg/d, 67.4%, 60.4%, 1.42, 42.0 sq cm, and 11.7, respectively. Carcass weights averaged 127.6 and 112.4 kg for hide-on and hide-off, respectively. There were few significant correlations of Hb with growth performance, carcass weight or DP. Pre-slaughter Hb was correlated 0.54 (P < 0.01) with flank muscle color score. Calves which were either heavier or which gained weight more rapidly tended to have slightly lower muscle color scores, larger REA and higher carcass conformation scores. Results from this study suggest that pre-slaughter Hb levels are higher than previously reported in specialfed veal, and there is no apparent relationship of Hb value, red blood cell count or mean corpuscular hemoglobin with growth performance traits. Although final Hb values were moderately predictive of muscle color score (accounting for 29% of the within-group variance), apparently there are other factors both within and between farms which influence muscle color in special-fed veal carcasses.

Blood, growth, and other characteristics of special-fed veal calves in private cooperator herds.

The objectives of this study were to determine the mean values for mortality, blood, and growth traits and the correlations among blood and growth traits on privately owned farms producing special-fed veal. Mortality percentages were available on 13 groups of special-fed veal calves (n = 1403) from four farms; growth and some blood traits were available on 9 groups from four farms (n = 975). Mean mortality percentages for periods 0 to 2, 2 to 7, and 7 to 16 wk, and over 16 wk were 1.0, 1.0, 1.0, and 3.1%, respectively. Means for average daily gain for 2 to 7 wk were 1.37 +/- .008 kg and for 7 to 16 wk were 1.52 +/- .001 kg. When calves arrived at the veal farm, total plasma protein averaged 6.2 +/- .05 g/dl. Examination of total plasma protein upon arrival of calves indicated that 81% of the calves had received colostrum. The base level indicating colostral deficiency was < 5.5 g/dl of total plasma protein; 51% of the calves had total plasma protein > 6.0 g/dl at arrival. Mean hemoglobin concentrations at arrival and at 2, 7, and 16 wk were 11.1 +/- .15, 10.6 +/- .18, 9.2 +/- .14, and 7.8 +/- .13 g/dl, respectively. Means for hemoglobin were generally higher than previously reported for special-fed veal calves reared in individual stalls. Hemoglobin and red blood cell counts were correlated positively with 16-wk average daily gain and body weight, and midtrial white blood cell counts were correlated negatively with average daily gain and body weight from 2 to 7 wk; there were no other significant relationships between blood traits and growth performance measures.

Effects of different doses of zeranol on growth, hemoglobin, and carcass traits in veal calves.

Effects of different doses of zeranol on ADG, hemoglobin (Hb), feed efficiency (FE), and carcass traits were evaluated in special-fed veal calves in two trials. On d 0, calves were implanted subcutaneously in the middle third of the ear with either 0 (control, placebo pellet), 12, 24, 36, or 48 mg of zeranol. Trial 1 was conducted from February through May 1990 with 120 Holstein bull calves (17 to 21 d of age on d 0) and Trial 2 was conducted from May through August 1991 with 100 Holstein bull calves (24 to 28 d of age d 0). Calves were fed on an individual calf basis. Calves in Trial 1 that were implanted with 48 mg of zeranol had improved FE (P < .05) and ADG (P < .05) during Period 1 (0 to 43 d). No significant differences in ADG or FE were observed among treatments in Trial 2. Hemoglobin levels at slaughter averaged 7.88 +/- .096 and 8.19 +/- .149 g/dL over all treatments for Trials 1 and 2, respectively. The only postslaughter trait affected by zeranol dose was testicular weight. In both trials, testicular weight at slaughter decreased (P < .05) with increasing doses of zeranol. Dressing percentage tended to be higher for 48-mg implants than for controls but the difference was not significant. There were no significant zeranol dose effects on longissimus muscle area, flank color, carcass conformation, or percentage of fore- vs hind-quarter weight. These results indicated that higher doses of zeranol improved ADG and FE during the first 6 wk after the trial period (to 8 wk of age), decreased testicular weight, and increased hide-on carcass dressing percentage for calves implanted with 48 mg of zeranol compared with those that received 0 mg of zeranol.

Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide.

Several observations suggest interactions between the immune and nervous systems. Psoriasis and atopic dermatitis may worsen with anxiety and have been associated with anomalous neuropeptide regulation. Neurotransmitters affect lymphocyte function and lymphoid organs are innervated. Calcitonin gene-related peptide (CGRP) is a neuropeptide and vasodilator that modulates some macrophage functions, including antigen presentation in vitro. CGRP is associated with Langerhans cells (LC) in oesophageal mucosa, particularly during inflammation, is present in epidermal nerves and is associated with Merkel cells. We examined the ability of CGRP to modulate LC antigen-presenting function and asked if CGRP-containing nerves impinge on LC. We report here that CGRP-containing nerve fibres are intimately associated with LC in human epidermis and CGRP is found at the surface of some LC. In three functional assays CGRP inhibited LC antigen presentation. These findings indicate that CGRP may have immunomodulatory effects in vivo and suggest a locus of interaction between the nervous system and immunological function.

Phytophotodermatitis: a visit to Margaritaville.

Phytophotodermatitis is a phototoxic eruption following contact with photosensitizing compounds and long-wave ultraviolet light. The most common phototoxic compounds are the furocoumarins contained in a wide variety of plants, especially of the Umbelliferae, Rutaceae, and Moracea families. Commonly occurring photosensitizing plants include citrus fruits such as limes and oranges and many vegetables, notably celery, parsnip, parsley, carrots, and dill.