Dermoscopic Evolution of a Congenital Combined Nevus in Childhood

Background. A combined nevus most commonly consists of a blue nevus in combination with a Clark or Spitz nevus. Dermoscopically, combined nevus can mimic melanoma owing to the presence of dermoscopic features common to both types of lesions. Benign clinical and dermoscopic changes can occur in nevi over time, especially in children and young adults.
Objective. To describe the dermoscopic evolution of a congenital combined nevus showing unusual dermoscopic features.
Methods. Digital dermoscopic analysis was performed at the initial visit and after 8 months. The lesion was surgically excised and histopathologically examined.
Results. An asymptomatic plaque with a central blue area and peripheral brown pigmentation located on the back of a 13-year-old boy was diagnosed dermoscopically as combined nevus. Dermoscopic analysis 8 months later showed color changes from steel blue to gray-blue and black in the central area of the lesion, an increased number of blue-black dots or globules, and peripheral irregular streaks. Histopathology revealed typical features of a congenital combined nevus (blue nevus + compound nevus).
Conclusion. Over time, congenital combined nevus may show clinical and dermoscopic changes in size, color, and structure. Surgical excision is recommended when clinical and dermoscopic features are equivocal and the diagnosis of melanoma cannot be ruled out.
ANGELA FERRARI, MD, GIAN PIERO LOZZI, MD, MARIA CONCETTA FARGNOLI, MD, AND KETTY PERIS, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.     

Adrenal function under long-term raloxifene administration.

The aim of the present study was to evaluate the effect of long-term (12 months) administration of raloxifene hydrochloride (60 mg/day) on the steroid production of the adrenal cortex and on the hypothalamic-pituitary-adrenal axis in postmenopausal women. We performed a basal evaluation, a corticotropin releasing factor (CRF) (100 microg i.v. bolus) test and a dexamethasone (DXM) (0.25 mg) suppression-adrenocorticotropic hormone (ACTH) (10 microg i.v. bolus) stimulation test in 11 postmenopausal women, before and after 3, 6 and 12 months of raloxifene treatment. Raloxifene administration significantly modified circulating levels of adrenal steroids, decreasing cortisol (-24%), dehydroepiandrosterone (DHEA) (-36%), and its sulfate (DHEAS) (-41%), and androstenedione (-29%), and increasing circulating allopregnanolone (+39%) levels. Progesterone and 17OH-progesterone levels remained unmodified, while estradiol and estrone levels showed a significant decrease (-51% for estradiol and -61% for estrone). We also observed an increase in circulating ACTH (+58%) and beta-endorphin (+120%). No modifications in the hormonal responses to CRF were observed during the treatment. DXM significantly suppressed circulating steroids at any time with a lower suppression of cortisol from the third month and a higher suppression of DHEA at 12 months. ACTH administration was associated with a significantly blunted cortisol response from the sixth month and a significantly increased response of allopregnanolone from the third month. The present data exclude a raloxifene effect on pituitary sensitivity to CRF and demonstrate a reduced adrenal sensitivity to ACTH, sustained by the opposite changes in basal cortisol and Delta5 androgens, which were reduced, and in ACTH and beta-endorphin, which were increased, as well by the reduced response of cortisol to the direct ACTH stimulus. The reduction of circulating cortisol levels and cortisol response to the ACTH challenge suggests that raloxifene protects against the neurotoxic effects of endogenous glucocorticoids. Furthermore, the progressive increase in basal allopregnanolone and its increased response to ACTH indicate that chronic raloxifene administration exerts direct effects on the pattern of adrenal enzymes, leading to specific changes in the circulating levels of this anxiolytic progesterone metabolite. The important reduction in the circulating levels of estradiol and estrone under long-term raloxifene administration may represent a further mechanism by which this molecule may exert a protective effect against breast and endometrial malignancies.     

Attentional, emotional and hormonal data in subjects of different ages

The differences in attentional style among subjects of different ages and the influence of emotionality on the attentional components were studied for a limited experimental period. Variation in the hormonal data and its relation to behavioural parameters were also evaluated. The subjects enrolled in the study were divided into four age groups (A 18–29, B 30–45, C 46–59, D 60–77 years). The attentional tests involved different types of attention: alert, go/no-go, divided attention and working memory. Emotionality was assessed on the basis of skin conductance, heart rate and frontalis muscle tone. Testosterone (T), free testosterone (fT), non-specifically bound testosterone (NST), sex hormone binding globulin (sHBG), oestradiol, cortisol and adrenocorticotrophic hormone were determined in the plasma. The data were analysed to identify endocrine and behavioural differences related to sex and age. The results showed an influence of age on reaction time (RT) and RT variability. This was particularly evident for groups C and D with respect to A in the simple (alert) and complex RT tests (go/no-go and working memory). Divided attention, with the highest RT, showed a clear distinction between group A and the other groups. The difference in frontalis electromyography (EMG) (test vs control) increased with age, while the autonomic responses (skin conductance and heart rate) did not vary. In most attentional tests, the age-related reduction of RT was associated with increased T, fT and NST and decreased cortisol.     

Epidemiology of tuberculosis in immigrant patients hospitalised in Infectious Diseases Units in Italy: multicentric study

In order to retrospectively evaluate the prevalence of immigrant patients affected by active tuberculosis, we analysed the clinical data of 2255 immigrant patients hospitalised during 2002 in ordinary admission or in Day Hospital in 48 Clinics of Infectious Diseases. In all, 303 patients were affected by active tuberculosis (13.4% of the total immigrant hospitalised patients); 30 patients (9.9%) were also HIV-positive. There was a considerable male gender bias (62.5%); the mean age was 29.7 years; 144 patients were from Africa (47.5%), 72 (23.7%) from Asia, 47 (15.5%) from eastern Europe and 40 (13.2%) from South America. The clinical variants were: pulmonary (57.7%), lymph node (15.8%), meningitis (13.8%), intestinal (4.2%), bone (3.3%), pleurical (2.3%), peritoneal (2.3%) and renal (0.6%). We conclude that tuberculosis is a very frequent disease among immigrants, especially of African origin. The high percentage is due to several factors, such as no vaccine prophylaxis and poor, overcrowded living conditions. It is fundamental to focus on the need to provide better health support for all subjects by setting up screening plans to estimate the real incidence of this pathology and ensure medical treatment to prevent the spread of this infection among immigrants and the local host population.     

Vascular endothelial growth factor and neo-angiogenesis in H. pylori gastritis in humans

Host response plays a major role in the pathogenesis of Helicobacter pylori-induced gastroduodenal disease including adenocarcinoma of the distal stomach. Vascular endothelial growth factor (VEGF) is an important modulator of gastric mucosal repair and is overexpressed in gastric cancer. The present study sought to evaluate the expression of VEGF in the gastric mucosa of H. pylori-infected and H. pylori-non-infected dyspeptic patients. Fifteen H. pylori-infected and 15 H. pylori-non-infected dyspeptic patients were studied. Diagnosis of H. pylori infection was based on rapid urease test and histology. VEGF protein expression was assessed by western blotting. VEGF mRNA expression was assessed by RT-PCR. VEGF localization in the gastric mucosa and neo-angiogenesis were determined by immunohistochemistry. VEGF protein and mRNA expression was significantly greater in H. pylori-infected than in non-infected patients. Immunohistochemistry showed that VEGF expression was more intense in the gastric gland compartment of H. pylori-infected mucosa than in the non-infected mucosa. The increase in VEGF expression was associated with a significant increase in neo-angiogenesis as assessed by determination of CD34-positive micro-vessels. H. pylori gastritis is therefore associated with up-regulation of VEGF expression, which parallels the increased formation of blood vessels in the gastric mucosa. It is postulated that increased VEGF expression and neo-angiogenesis may contribute to H. pylori-related gastric carcinogenesis.     

Endogenous levels of mRNA for IFNs and IFN-related genes in hepatic biopsies of chronic HCV-infected and non-alcoholic steatohepatitis patients

To investigate the intra-hepatic activation of the IFN system in patients affected by chronic HCV-infection in comparison with that observed in a non-infectious liver disease such as non-alcoholic steatohepatitis, we measured the liver steady state mRNA levels of interferon-alpha, interferon-beta and interferon-gamma as well as of IFN-related genes (IFNAR-1, STAT1alpha, PKR, 2-5 AS, IRF-1, ICE and IL-18). In HCV-infected subjects, possible correlations of these parameters with viral load and liver injury were also analyzed. Twenty-four chronic untreated HCV-infected subjects and seven patients with non-alcoholic steatohepatitis were enrolled in the study. Liver biopsies were graded according to Knodell scores. Intra-hepatic mRNA levels of IFNs and related genes were assessed by semi-quantitative RT-PCR. In comparison with non-alcoholic steatohepatitis, in HCV-infected subjects IFN-alpha and -beta mRNA levels were significantly lower, whereas IFN-gamma, IFNAR-1, STAT1alpha IRF-1, and IL-18 mRNA were upregulated. Moreover, IFN-gamma mRNA steady state levels were correlated positively with those of IFNAR-1, IRF-1, and IL-18, suggesting a coordinated induction of these genes. Although plasma viral load was correlated inversely with IL-18-specific mRNA, viral load was not related to liver injury. IFN-gamma and IRF-1 mRNA levels were correlated positively with ALT, but not with the grading or staging. Conversely, IFN-alpha and -beta mRNA levels were higher in livers with lower staging scores. These findings support the hypothesis that in chronic HCV infection there is an imbalance between an upregulated IFN-gamma system and a downregulated IFN-alpha and -beta system, probably due to a mixed effect exerted by HCV-specific and inflammatory non-specific factors.     

Identification of four novel melanocortin 1 receptor (MC1R) gene variants in a Mediterranean population

The melanocortin 1 receptor (MC1R) gene is a major determinant of human pigmentation and specific allelic variants have been associated with red hair and sun sensitive skin types as well as increased skin cancer risk in Caucasian individuals. We screened for allelic variants the entire MC1R coding region of 100 unrelated individuals sampled from an Italian population who has darker pigmentary traits than populations analyzed to date. Twenty MC1R variants were identified, eighteen located at non-synonymous sites and two at synonymous sites. We report four novel MC1R allelic variants: C35Y (g.104G>A), V38M (g.112G>A), L44V (g.130C>G) and I120T (g.359T>C).