Levels of Interleukin‐18 and Endothelin‐1 in Children with Henoch‐Schönlein Purpura: A Study from Northern India

Henoch‐Schönlein purpura (HSP) is an acute systemic vasculitis with unknown etiology, although several studies have found HSP to be related to cytokines such as tumor necrosis factor α, interleukin (IL)‐1, and adhesion molecules. In the present study we determined the levels of cytokines such as IL‐18 and endothelin‐1 (ET‐1) in children with HSP. Subjects were divided into three groups (group 1, 20 subjects with HSP; group 2, 10 subjects belonging to group 1 during their follow‐up 4 to 6 months later; and group 3, 16 controls who were healthy siblings of the subjects). IL‐18 and ET‐1 levels were determined using enzyme immunoassay and expressed as mean ± standard deviation. We observed higher IL‐18 levels in children with HSP (767.6 ± 145.1 pg/mL) than in controls (614.6 ± 66.54 pg/mL, p > 0.05), but IL‐18 levels were found to be significantly lower in subjects with HSP in remission (502.7 ± 60.81 pg/mL) than in those who were in an active phase (1,050 ± 244.5 pg/mL, p < 0.05, n = 10). ET‐1 levels were found to be significantly higher in subjects with HSP (1.93 ± 0.19 pg/mL) than in controls (1.10 ± 0.13 pg/mL, p < 0.05), although no significant difference was observed in ET‐1 levels between subjects in group 1 (1.88 ± 0.30 pg/mL) and group 2 (1.91 ± 0.120, p > 0.05, n = 10). A positive correlation was observed between IL‐18 and ET‐1 levels in subjects with HSP (correlation coefficient [r] = 0.5254, p < 0.01). These results suggest that levels of IL‐18 and ET‐1 are worth monitoring during the clinical course of the disease, but caution must be exercised in extrapolating data based on small study samples.     

Bone mineral metabolism in patients with neurofibromatosis type 1 (von Recklingausen disease)

The neurofibromatosis type 1 (NF1) is characterized by specific cutaneous features (neurofibromas, “café-au-lait” spots of the skin) and alterations of several tissue (nervous, vascular) and bone deformities, such as scoliosis, congenital pseudoarthrosis and bone dysplasia of tibia. Moreover, several studies have shown systemic involvement of bone tissue in NF1 patients, leading to reduced bone mass. The aim of our study was to evaluate some bone mineral metabolism parameters before and after calcium and vitamin D supplementation in NF1 patients. We evaluated in 70 NF1 consecutive patients the mineral metabolism and bone mineral density compared with 40 normal subjects. We showed bone alterations in 35% of patients and the increase of bone formation markers, such as bone isoenzyme of alkaline phosphatase (41.2 ± 15.5 vs. 25.6 ± 8.7 UI; P < 0.05, respectively) and osteocalcin (18.1 ± 5.6 vs. 7.6 ± 1.9 ng/ml; P < 0.05) and reduction of circulating levels of (25OH)-vitamin D (21.8 ± 12.3 ng/ml) with an high percentage of hypovitaminosys D (>60%). Moreover, we revealed a significant reduction of bone mass density at spine (L1–L4) (0.935 ± 0.13 vs. 1.110 ± 0.17 g/cm²; P < 0.001) and femoral neck side (0.765 ± 0.09 vs. 0.839 ± 0.12 g/cm²; P < 0.02), with high prevalence of osteopenia (44%) and osteoporosis (18%). After 12 months of calcium (1,200 mg/die) and cholecalciferol (800 UI/die) supplementation, we found a significant increase of (25) OH-vitamin D level (21.8 ± 12.3 vs. 35 ± 13 ng/ml; P < 0.01), without changes in bone mass density. In conclusion, NF1 patients may present a mineral bone involvement, with vitamin D deficiency; calcium and vitamin D supplementation is necessary to restore these bone mineral metabolic alterations.     

Hair care practices and structural evaluation of scalp and hair shaft parameters in African American and Caucasian women

How African American hair fragility relates to hair care practices and biologic differences between races is not well understood. To assess the differences between perceptions of hair health, hair care practices, and several biologic hair parameters between Caucasian and African American women. A questionnaire on perceptions of hair health and hair care practices was administered. Biological and structural parameters of hair shaft and scalp, including growth, density, diameter, cycle, breakage, and scalp blood flow were also assessed in this case–control study. Significant differences between the Caucasian and African American women were observed in the questionnaire and biologic study data. Regarding self‐reported perceptions of hair health, there were differences in the following: hair shaft type (P < 0.001), hair breakage (P = 0.040), and desire to change hair (P = 0.001). Regarding self‐reported hair care practices, there were differences in the following: location of haircutting (P = 0.002) and washing (P = 0.010), washing frequency (P < 0.001), chemical relaxer use (P < 0.001), hooded hair dryer use (P < 0.001), and hair shaft conditioner use (P = 0.005). The two groups had similar practices in regard to the use of hair color, frequency of hair color use, chemical curling agents, and handheld blow dryer use. Regarding biological and structural parameters, there were differences in the following: hair growth rate (P < 0.001), density (P = 0.0016), diameter (P = 0.01), number of broken hairs (P < 0.001), and blood flow (P = 0.03). There was no significant difference in hair cycle parameters.The differences in hair care practices and hair fiber morphology among African American women may contribute to clinically observed variation in hair fragility and growth.     

Nonattendance in a dermatology clinic – a large sample analysis

Background Previous studies have described factors determining non‐attendance at dermatology appointments in small sample sizes. Objective To perform an analysis of factors associated with non‐attendance in a dermatology clinic in a larger sample. Methods Factors determining non‐attendance were examined in 52 604 consecutive first‐time visits to a dermatology clinic over a period of 44 months. Results Non‐attendance proportion was 27.6%. Among children, non‐attendance was associated with waiting for an appointment < 7 days [odds ratio (OR), 1.44], Bedouin sector (OR, 1.30), rural Jewish sector (OR, 0.45) and the treating physician. Among adults, non‐attendance was associated with female gender (OR, 1.08), age < 55 years (OR, 1.65), waiting time for an appointment < 7 days (OR, 1.44), timing of the appointment between 1 and 4 pm (OR, 1.13), Bedouin sector (OR, 1.63), rural Jewish sector (OR, 0.46) and the treating physician. Conclusion Non‐attendance is common among Bedouins, adult female patients and young adults and is more likely as waiting times become longer. Strategies to reduce non‐attendance are needed.     

An observational analysis of low-dose thalidomide in recalcitrant prurigo nodularis

Thalidomide has been used as an effective treatment for prurigo nodularis (PN) with a median dose of 200 mg, but the risk of peripheral neuropathy precludes long-term use. We analysed the efficacy of low-dose thalidomide (< 100 mg) in 17 patients with recalcitrant PN. Patients were initiated on thalidomide 50 mg on alternate days, and the dose was increased (doubled) in a stepwise manner, if needed, until a ≥ 50% reduction in score (partial response; PR) on a visual analogue scale (VAS) was achieved. Thalidomide then was continued at the same dose for 4 weeks to achieve ≥ 90% decrease in VAS score; if this was not achieved, the dose was increased to a maximum of 100 mg and continued until complete resolution of lesions (complete response; CR). Four patients discontinued thalidomide due to adverse effects. Four patients achieved PR, while 9 patients (n = 2 with 50 mg, n = 7 with 100 mg) achieved CR. No patient developed neuropathy. In addition, complete responders achieved an earlier ≥ 50% reduction in VAS score. Two patients relapsed after 12 months but responded to thalidomide 50 mg.     

Increased peripheral Th17 in patients with pustulosis palmaris et plantaris

Pustulosis palmaris et plantaris (PPP) is a chronic recurrent dermatitis characterized by intraepidermal pustules with erythematous scaling on the palms and soles. PPP shares many characteristics with psoriasis, but has a different genetic background. T helper 17 cells (Th17) have an important role in the pathogenesis of psoriasis. In psoriasis, regulatory T cells (Treg) are dysfunctional and circulating Th17 are increased. Whether Th17 are involved in PPP, however, is unclear. Therefore, we examined the Th17 population in peripheral blood mononuclear cells (PBMC) of patients with PPP. Foxp3⁺ Treg was also analyzed. We examined circulating Th17 and Treg in the peripheral blood of PPP patients. PBMC were obtained from healthy volunteer controls (n = 26, mean ± SD age 33.11 ± 9.80 years) and PPP patients (n = 24, age 55.00 ± 12.26 years). The proportion of Th17 among the PBMC was 2.52 ± 0.811% (mean ± SD) in healthy controls and 3.23 ± 1.45% in PPP patients. The proportion of Th17 in the PPP patients was significantly higher than that in the healthy controls (p < 0.05, Student’s t test). PPP patients had significantly fewer Treg (5.69 ± 1.86%) than healthy controls (7.10 ± 1.78%). Th17 was inversely correlated with Treg.     

Left ventricular systolic asynchrony: an important sign for cardiac involvement in plaque‐type psoriasis

Psoriasis is associated with cardiovascular diseases (CVD). The purpose of this study was to evaluate the relationship between Left Ventricular (LV) asynchrony and psoriasis. Asynchrony was assessed in 31 patients with psoriasis without evidence of CVD and 25 healthy subjects. All the patients and controls were subjected to tissue synchronization imaging (TSI), and conventional and tissue Doppler echocardiography. The time to regional peak systolic tissue velocity (Ts) in LV by the six‐basal‐six‐midsegmental model was measured on ejection phase TSI images, and four TSI parameters of systolic asynchrony were computed. C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels in psoriatic patients were measured. All TSI parameters of LV asynchrony increased in psoriatic patients compared to the controls: the standard deviation (SD) of the 12 LV segments Ts (37.3 ± 14.8 vs. 24.6 ± 11.1, P = 0.002); the maximal difference in Ts between any two of the 12 LV segments (112.7 ± 39.8 vs. 83.1 ± 38.1, P = 0.01), the SD of the six basal LV segments (36.2 ± 17.3 vs. 23.2 ± 14.5, P = 0.008); and the maximal difference in Ts between any two of the six basal LV segments (91.3 ± 43.5 vs. 60.5 ± 37.3, P = 0.01). LV asynchrony was observed in 67.7% of psoriatic patients. Higher CRP (1.9 ± 1.3 vs. 0.92 ± 1.4, P = 0.04) and ESR (34.8 ± 17.3 vs. 20 ± 15.3, P = 0.03) levels were determined in patients with LV asynchrony. Regression analysis showed LV systolic asynchrony (P = 0.02), Tei index (P = 0.03), EF (P = 0.04), and E/A ratio (P = 0.04) were independently associated with psoriasis. LV asynchrony firstly described in patients with psoriasis may be an important finding of cardiac involvement in psoriasis.     

Mongolian Spots—A Prospective Study

To determine the frequency and clinical presentation of Mongolian spots (MS) and assess their evolution with age, this study was conducted in three phases. The first phase examined 2,313 babies born at Jawaharlal Institute of Postgraduate Medical Education and Research between October and December 2010 for the number, size, shape, color, and distribution of MS. Babies with MS were followed up at 6 months and 1 year, in the second and third phases, respectively, to note the evolution of the patches. Of 2,313 babies, 1,524 (65.9%) had MS. The majority had a single patch (n = 790), measuring less than 5 cm (n = 932), with an irregular shape (n = 981) and a blue‐green color (n = 577). The most common site was sacral (n = 1,203), and the most common extrasacral site was a lower extremity (n = 156). A single case of superimposed MS was recorded. Male sex and prematurity were significantly associated with MS (p < 0.05). At 6 months, 73 of 634 babies (11.5%) showed fading and 83 (13.1%) showed complete disappearance. At 1 year, 90 (14.2%) showed fading and 268 (42.3%) showed complete disappearance. Multiple MS (p < 0.05), extrasacral position (p < 0.05), size larger than 10 cm (p < 0.05), and dark‐colored lesions (blue/blue‐black) (p < 0.05) were significantly associated with persistence beyond 1 year. Seven hundred ninety babies (51.8%) had a single MS. More than 40% of MS disappeared by 1 year. Multiple patches, extrasacral position, size larger than 10 cm, and dark‐colored lesions were markers of persistence beyond 1 year.     

Decreased suppression of CD8+ and CD4+ T cells by peripheral regulatory T cells in generalized vitiligo due to reduced NFATC1 and FOXP3 proteins

Regulatory T cells (Tregs) are involved in the suppression of activated T cells in generalized vitiligo (GV). The study was aimed to investigate Tregs functional defects in Treg:CD8⁺ and Treg:CD4⁺ T cells' co-culture systems of 55 GV patients and 45 controls. CD8⁺ and CD4⁺ T-cell proliferation was assessed by BrdU assay; production of IL-10, TGF-β and IFN-γ cytokines was assessed by ELISA; and FOXP3, CD25, NFATC1 and CD44 proteins were measured by flow cytometry. Generalized vitiligo patients showed reduced suppression of CD8⁺ and CD4⁺ T cells (P = .0384, P = .0084), increased IFN-γ (P < .0001, P = .0019), decreased IL-10 and TGF-β (P < .0001) and decreased FOXP3, CD25 and NFATC1 proteins (P < .0001). Active vitiligo (AV) patients showed reduced suppression of CD8⁺ & CD4⁺ T cells (P = .006, P = .015), increased IFN-γ (P = .036, P = .045), decreased IL-10 (P = .009, P = .021), FOXP3 (P = .0244) and NFATC1 (P = .019). Severe GV (50%-75% VASI) patients showed reduced suppression of CD8⁺ and CD4⁺ T cells (P = .0003, P = .001), increased IFN-γ (P = .0029, P < .0001), decreased IL-10 (P = .0057, P = .0017), FOXP3 (P = .002) and NFATC1 (P = .0347). VASI score was positively correlated with the suppression of CD8⁺ and CD4⁺ T cells (P = .0006, P < .0001), IL-10 (P = .0096, P = .029), FOXP3 (P = .0008) and NFATC1 (P = .043), whereas it was negatively correlated with IFN-γ (P = .0029, P = .0017). Early age of onset patients' Tregs demonstrated decreased suppression of CD8⁺ and CD4⁺ T cells (P = .0156, P = .0074), decreased TGF-β (P = .0212, P = .0083) and NFATC1 (P = .0103). NFATC1 was positively correlated with FOXP3 in Tregs (P < .0001). Our results suggest impaired Tregs suppressive function in GV patients due to decreased NFATC1, FOXP3, CD25, IL-10 and TGF-β resulting into increased CD8⁺ and CD4⁺ T-cell proliferation and IFN-γ production. For the first time, decreased NFATC1 levels were correlated with decreased FOXP3, thereby altering Treg cell function in GV patients. Additionally, decreased Treg cell function also affected onset, activity and severity of GV.     

Autologous serum skin test response in chronic spontaneous urticaria and respiratory diseases and its relationship with serum interleukin-18 level

Autologous serum skin test (ASST) is mostly used in chronic spontaneous urticaria (CSU) to show autoreactivity. Interleukin-18 (IL-18) has also been shown to be involved in autoimmune conditions. To investigate the role of autoreactivity assessed by ASST in CSU and respiratory diseases and to investigate whether this autoreactive state is related to IL-18 level or other clinical covariates. Fifty-five patients with CSU (mean age: 40.3 ± 12.3 years), 70 patients with persistent asthma (mean age: 43.7 ± 9.6 years), 21 patients with seasonal allergic rhinitis (SAR) (mean age: 35.5 ± 11.8 years) and 20 normal controls (mean age: 37.7 ± 9.8) were included. All subjects underwent a laboratory examination and skin prick test. ASST was performed and serum IL-18 levels were measured in all subjects. Positive response to ASST and serum IL-18 levels were higher in CSU patients than those with respiratory diseases (asthma and SAR) (P = 0.034 and 0.002, respectively) and normal controls (P = 0.004 and 0.031, respectively). Considering all patients, IL-18 levels were higher in patients with positive ASST (301.8 ± 194.4 vs. 241.8 ± 206.3 pg/ml, P = 0.036) than ASST negative patients. ASST response was associated with disease severity in CSU (P = 0.037) and asthma patients (P = 0.001). Multivariate analysis showed that positive response to ASST was significantly associated with diagnosis of CSU (OR: 3.13, 95% CI: 1.25–7.87) and female gender (OR: 3.98, 95% CI: 1.19–13.38). ASST response could be related with activity of the disease. A positive ASST response found in respiratory diseases patients suggests that it may occur as a result of some inflammatory events during the diseases’ process.     

Long‐term changes in nail fold capillary abnormalities and serum fibroblast growth factor 23 levels in dermatomyositis patients with anti‐melanoma differentiating antigen 5 antibody

Nail fold videocapillaroscopy (NVC) abnormalities are a characteristic finding of microangiopathy in dermatomyositis (DM). The aim of the present study was to examine long‐term changes in NVC abnormalities and serum fibroblast growth factor 23 (FGF23) and vascular endothelial growth factor (VEGF) levels in DM patients with anti‐melanoma differentiation‐associated gene 5 (MDA5) antibody (Ab). Serum levels of FGF23 and VEGF were measured by enzyme‐linked immunosorbent assay. NVC abnormalities were evaluated by capillaroscopy in 11 DM patients with anti‐MDA5 Ab at baseline and after treatment. NVC abnormalities included irregularly enlarged capillaries, reduced capillaries, hemorrhages, capillary ramifications, disorganization of the vascular array, loss of capillaries and giant capillaries. Serum FGF23 levels were significantly decreased in patients with anti‐MDA5 Ab (0.3 ± 0.3 pmol/L) compared with healthy controls (1.0 ± 0.6 pmol/L, P < 0.01). Serum FGF23 levels significantly increased after treatment (0.3 ± 0.3 vs 1.0 ± 0.7 pmol/L, P < 0.005), but serum VEGF levels were comparable between at baseline and after treatment. At baseline, irregularly enlarged capillaries were observed in 10 of 11 patients, but after treatment, they were significantly reduced in only two (91% vs 18%, P < 0.001). Hemorrhages were observed in all 11 patients at baseline, but disappeared in all after treatment (100% vs 0%, P < 0.001). These results suggest that NVC abnormalities are reversible by treatment and that serum FGF23 levels reflect the degree of microvascular damage in DM patients with anti‐MDA5 Ab.     

Pigmented skin lesions displaying regression features: Dermoscopy and reflectance confocal microscopy criteria for diagnosis

Melanomas and nevi displaying regression features can be difficult to differentiate. To describe reflectance confocal microscopy features in benign and malignant pigmented skin lesions characterized by regression features in dermoscopy. Observational retrospective study. Inclusion criteria were presence of dermoscopic features of regression; availability of clinical, dermoscopic and RCM imaging; definite histopathologic diagnosis. The study sample comprised 217 lesions; 108 (49.8%) melanomas and 109 were benign lesions, of which 102 (47.0%) nevi and 7 (3.2%) lichen planus‐like keratosis (lplk). Patients with melanoma were significantly older than those with benign lesions (61.9 ± 15.4 vs 46.1 ± 14.8; P < 0.001) and a higher proportion of melanomas displayed dermoscopic regression structures in more than 50% of lesion surface (n = 83/108; 76.9%; P < 0.001). On RCM examination, pagetoid cells were significantly more reported in melanoma group, than in benign lesions (86.1% vs 59.6%; P < 0.001) and were more frequently widespread distributed (65.6% vs 20.0%; P < 0.001) and both dendritic and roundish (36.6% vs 15.4%; P < 0.001) in shape. Aspecific architecture at the dermo‐epidermal junction (DEJ) was more commonly seen among melanomas than benign lesions (23.1% vs 11.9%; P = 0.002) with higher presence of dendritic and both dendritic and roundish atypical cells at the DEJ (28.7% vs 18.3% and 19.4% vs 3.7%; P < 0.001, respectively). Focal pagetoid infiltration and ringed or clod patterns were more commonly seen in benign lesion. In conclusion, the correct interpretation of regressing lesions remains a challenge, assessing carefully the extent and characteristics of architectural and cytologic atypia on RCM is an additional piece of the complex puzzle of melanoma diagnosis.     

Análisis de la producción científica nacional e internacional de los dermatólogos españoles (1988-2000)

ObjectiveTo compare the scientific production in articles published in Actas Dermo-Sifiliográficas (AD) with papers published by Spanish dermatologists in international journal (IJ) included in Medline data base between 1988 and 2000. The main features studied were: type and extension of document, subject, authors’ place of work, speciality and geographical distribution.Material and methodsData were obtained by consulting the articles published in the journal AD. Also Spanish papers in dermatology were retrieved from Medline data base.ResultsA total of 1,864 articles were published in AD and 1,645 papers were retrieved from IJ. The extension of documents in AD was higher (4.46 ± 2.57) than in IJ (3.29 ± 2.33). In the journal AD there is a predominance of topics related to oncology (13.3 % vs 9.0 %) (< 0.001), pediatrics (12.7% vs 8.7%) (p < 0.001) and surgery (2.4 % vs 0.9%) (p = 0.001) compared to the papers published in IJ. In IJ there was a predominance of topics related to contact dermatitis (14.6% vs 4.5%) (p < 0.001), physiopathology (4% vs 2.3%) (p = 0.001), drug-induced reactions (6.6 % vs 4.3%) (p = 0.001) and dermatopathology (18.7 % vs 16.1 %) (p = 0.01). Andalucía (16.4% vs 8.6 %) (p < 0.001), Aragón (3.9 % vs 0.7 %) (p < 0.001), Asturias (2.1 % vs 0.2 %) (p < 0.001), Castilla-León (8.5 % vs 3.6 %) (p < 0.001), and Madrid (37.1% vs 30.6%) (p < 0.001) published more in AD than in IJ. However, Cataluña (26.3% vs 9.6 %) (p < 0.001), Navarra (5.6 % vs 1.8%) (p < 0.001) and País Vasco (4.2% vs 2.0%) (p < 0.001) published more in IJ.ConclusionWe have observed differences in the topics and the geographical distribution of papers published by Spanish researchers in dermatology.     

The important role of radiation treatment in the management of Merkel cell carcinoma

Merkel cell carcinoma is an aggressive, radiosensitive cutaneous neuroendocrine tumour. In this review, the roles of radiation therapy and chemoradiation in the management of Merkel cell carcinoma are described and discussed, and guidelines for patient management are presented. Radiation treatment may be indicated for definitive (> 55 Gy) or adjuvant (> 50 Gy) treatment of the primary tumour site and for prophylactic (> 50 Gy), adjuvant (> 50 Gy) or definitive (> 55 Gy) treatment of the regional lymph node field. If a patient presents with positive margins after initial biopsy or resection, definitive radiation therapy or chemoradiation may be an alternative to further surgery and, importantly, results in less delay than re‐resection followed by adjuvant radiation treatment. Given the rarity of this tumour, patients should be enrolled on prospective databases and clinical trials, and managed in a multidisciplinary clinical setting wherever possible.     

Melanocytic Nevi in Children of Southern Italy: Dermoscopic,Constitutional, and Environmental Factors

The objective was to estimate the prevalence of melanocytic nevi (MN) in children and to determine their dermoscopic characteristics and relationship with anatomic location and environmental and constitutional factors. The population was a randomly selected sample of 144 children who attended primary schools in Naples, Italy. Before physical examination of the children, standardized interviews were conducted with their parents. Follow‐up interviews of both the children and parents were conducted 1 year later. Photographic and dermoscopic images were obtained. Boys had more MN than girls; 465 MN (55.6%) were observed in boys and 371 (44.4%) in girls (p < 0.05). The trunk and neck were the most common locations of MN (p < 0.001). The main dermoscopic feature of all MN observed was a globular pattern (p < 0.001). A significant correlation between duration of sunbathing and MN counts was revealed (p < 0.05). At 1‐year follow‐up, 118 new MN were identified in 66 children. The trunk and neck areas were the most common regions involved in the appearance of new MN (n = 68, 57.6% of all new MN, p < 0.001). The new MN count was significantly higher in children who reported more sunbathing (p < 0.001). Changes in the dermoscopic pattern were observed in 45 persistent MN, demonstrating more MN with a reticular‐globular pattern, especially on the trunk, neck, and upper extremities (p < 0.001). MN development in early life is the result of complicated relationships between nevus evolution, anatomic location, and environmental and constitutional factors.     

Quantitative analysis of α1(I) and α1(III) procollagen mRNA expression in systemic sclerosis skin tissue – an in situ hybridization study

Abstract Human α1(I) and α1(III) procollagen mRNA expression in skin tissue from 15 systemic sclerosis (SSc) patients and from 7 normal control subjects was quantitatively analyzed using in situ hybridization. The grains accumulating in each area, representing procollagen mRNA expression per cell, were counted. To normalize the results from each subject, the number of cells and the number of grains per cell were divided by the area of the skin specimen (in square millimeters). The number of cells per square millimeter expressing α<1(I) and α1(III) procollagen mRNA in SSc skin was significantly elevated compared with normal control skin (both P < 0.01). The number of grains per cell per square millimeter expressing α1(III) procollagen mRNA in SSc skin was also significantly elevated compared with normal control skin (P < 0.01). The relationship between procollagen mRNA expression and the histological findings in SSc was also studied. The numbers of cells and grains per cell per square millimeter expressing α1(I) procollagen mRNA in fibrotic zone SSc skin were significantly elevated compared with normal control skin (both P < 0.01). The numbers of cells and grains per cell per square millimeter expressing α1(III) procollagen mRNA in SSc skin were significantly elevated compared with normal control skin (both P < 0.01) and with border zone SSc skin (number of cells P < 0.01, number of grains P < 0.05). These results indicate an increase in the number of cells showing elevated expression of α1(I) and α1(III) procollagen mRNA, and a close relationship between α1(I) and α1(III) procollagen mRNA expression and the histological findings in SSc. Received: 24 February 1999 / Received after revision: 20 May 1999 / Accepted: 16 August 1999     

Serum‐Level Changes of Vascular Endothelial Growth Factor in Children with Infantile Hemangioma after Oral Propranolol Therapy

Oral propranolol is the first‐line therapy for infantile hemangioma (IH), but its mechanism of action remains unclear. The aim of this study was to evaluate the change in serum vascular endothelial growth factor (VEGF) levels in patients with IH who underwent propranolol treatment. The study included 22 patients with IH receiving propranolol treatment. At three time points—before treatment and 1 and 3 months after treatment—blood samples were examined by enzyme‐linked immunosorbent assay for serum VEGF expression. The mean serum VEGF concentration in children with proliferative hemangiomas was 395.0 ± 176.7 pg/mL, approximately twice as high as in patients with venous malformations (mean 170.7 pg/mL) and in healthy controls (204.8 pg/mL, p = 0.006). After 1 month of propranolol treatment, the level had fallen 21.6% (p = 0.003), although the downward trend was less obvious after 3 months of treatment (18.0%, p = 0.63). VEGF expression correlated significantly with the lesion size (correlation coefficient [R] = 0.43, p = 0.046), whereas no correlation was observed with age (R = 0.13, p = 0.56). Serum VEGF levels were higher in patients with IH and fell after 1 month of oral propranolol treatment. Similar results, although less pronounced, were found after 3 months of treatment. Lesion volume and serum level of VEGF were significantly correlated.     

The relative contribution of α- and β-adrenergic sweating during heat exposure and the influence of sex and training status

While human eccrine sweat glands respond to adrenergic agonists, there remains a paucity of information on the factors modulating this response. Thus, we assessed the relative contribution of α- and β-adrenergic sweating during a heat exposure and as a function of individual factors of sex and training status. α- and β-adrenergic sweating was assessed in forty-eight healthy young men (n = 35) and women (n = 13) including endurance-trained (n = 12) and untrained men (n = 12) under non–heat exposure (temperate, 25°C; n = 17) and heat exposure (hot, 35°C; n = 48) conditions using transdermal iontophoresis of phenylephrine (α-adrenergic agonist) and salbutamol (β-adrenergic agonist) on the ventral forearm, respectively. Adrenergic sweating was also measured after iontophoretic administration of atropine (muscarinic receptor antagonist) or saline (control) to evaluate how changes in muscarinic receptor activity modulate the adrenergic response to a heat exposure (n = 12). α- and β-adrenergic sweating was augmented in hot compared with temperate conditions (both P ≤ .014), albeit the relative increase was greater in β (~5.4-fold)- as compared to α (~1.5-fold)-adrenergic-mediated sweating response. However, both α- and β-adrenergic sweating was abolished by atropinization (P = .001). Endurance-trained men showed an augmentation in α- (P = .043) but not β (P = .960)-adrenergic sweating as compared to untrained men. Finally, a greater α- and β-adrenergic sweating response (both P ≤ .001) was measured in habitually active men than in women. We show that heat exposure augments α-and β-adrenergic sweating differently via mechanisms associated with altered muscarinic receptor activity. Sex and training status modulate this response.