The Association between the Level of Advanced Glycation End Products and Objective Skin Quality Parameters.

Advanced glycation end products (AGEs) represent an endogenously produced or exogenously derived group of compounds derived from nonenzymatic glycation. Recent experimental studies are suggesting that AGEs could play an important role in the skin's quality and its aging process. Hence, the aim of this study was to clinically evaluate the AGEs and skin quality parameters across different age groups in the general population. The study included 237 participants. Melanin, erythema, hydration, friction and transepidermal water loss (TEWL) were evaluated using noninvasive probes, while AGEs were evaluated using a skin autofluorescence reader. There was a significant positive correlation between AGEs and the amount of melanin (p < 0.001), erythema (p < 0.001) and TEWL (p < 0.001), while there was a significant negative correlation between AGEs and hydration (p < 0.001) and friction (p < 0.001). After dividing the sample into three groups depending on their age, in all three groups, there was a significant positive correlation between AGEs and the melanin count (p < 0.001) and TEWL (p < 0.001), while there was a significant negative correlation between AGEs and skin hydration (p < 0.001). Multiple linear regression analysis showed that the level of AGEs as a dependent variable retained a significant association with age (p < 0.001), melanin (p < 0.001), erythema (p = 0.005) and TEWL (p < 0.001) as positive predictors. Moreover, AGEs retained a significant association with skin hydration (p < 0.001) and friction (p = 0.017) as negative predictors. These outcomes imply that AGEs could be linked with the complex physiology of the skin and its aging process.

Flow Changes in Orbital Vessels Detected with Color Doppler Ultrasound in Patients with Early Dysthyroid Optic Neuropathy.

Thyroid-associated orbitopathy (TAO) is a common manifestation of Graves' disease. The aim of the study was to assess the six percent of patients with TAO that develop dysthyroid optic neuropathy (DON), which is the most serious complication of TAO. As DON can cause perma-nent damage, it is essential to detect DON early when visual loss is still reversible. Color Doppler ultrasound is a noninvasive diagnostic method, which may be useful in early detection of DON. Thirty-six patients with confirmed Graves' disease and active TAO were included, 21 (58%) of them with early DON (eDON) and 15 (42%) free from any signs of eDON. All study patients underwent Doppler ultrasound examination to determine the blood flow rates in the internal carotid artery, ophthalmic artery, and central retinal artery. Study results showed color Doppler ultrasound examination to have a potential to detect orbital blood flow changes in patients with eDON. Early detection of DON may result in earlier treatment and prevention of permanent optic nerve damage.

RET EXPRESSION AND ITS CORRELATION WITH CLINICOPATHOLOGIC DATA IN PAPILLARY THYROID CARCINOMA.

- The purpose of this study was to analyze the possible prognostic value of RET mutation in papillary thyroid carcinoma and its incidence in the past few decades in our population, due to the increasing incidence of papillary thyroid carcinoma. The present study included 180 patients operated for papillary thyroid carcinoma. The clinical and histopathologic characteristics were analyzed. Paraffin sections of the selected histologic slides were cut again and immunohistochemically stained by the Clone 3F8 P (HIER) from Novocastra (Vision Bio Systems Europe, Newcastle upon Tyne, UK) monoclonal antibody to RET oncoprotein. Univariate analysis indicated sex (p=0.01), histologic subtype (p=0.075) and capsular invasion (p=0.010) to be statistically significant predictors of lymph node metastases, whereas age (p=0.796), tumor size (p=0.556) and intraglandular dissemination (p=0.131) showed no such correlation. The presence of RET mutation (p=0.704) was not a statistically significant predictor of the tumor metastasizing potential. RET mutation (p=0.500) showed no statistically significant correlation with papillary thyroid carcinoma classifed into prognostic groups according to clinicopathologic features either. RET mutation was detected in 30% of 180 papillary thyroid carcinomas. This is the first large study demonstrating that RET mutation incidence in papillary thyroid carcinoma in Croatian population is consistent with the classic distribution of sporadic cases, despite the increased prevalence of papillary thyroid carcinoma in the past few decades.

MRI and comparison mammography: a worthy diagnostic alliance for breast microcalcifications?

BACKGROUND: There is a lack of data concerning diagnostic performance of magnetic resonance imaging (MRI) in patients with new or increasing microcalcifications. PURPOSE: To evaluate suspicious microcalcifications by using comparison mammography, MRI, and a combination of both methods. MATERIAL AND METHODS: Our study group consisted of 55 patients with mammographically detected BI-RADS (Breast Imaging Reporting and Data System) 3-5 microcalcifications for whom comparison mammograms were available. All patients underwent breast MRI before SVAB (stereotactic vacuum-assisted biopsy). Diagnostic performances of comparison mammography and MRI were evaluated, as well as the combination of the respective imaging findings. RESULTS: Of the 55 microcalcification cases, 35 showed progression and 20 were stable between interval screenings. The negative predictive value (NPV) of comparison mammography was 100%, whereas the NPV of MRI was 92%. However, the specificity of combination of findings was 97%, significantly higher than the 42% specificity of comparison mammography (P < 0.001). Additionally, the positive predictive value of combination of findings was 93% versus 44% of comparison mammography (P = 0.001). CONCLUSION: A biopsy is recommended when MRI positive lesion corresponding the area of new or increasing mammographic microcalcifications is detected. Patients with stable microcalcifications can continue follow-up mammography, regardless of MRI result.

The Event-related Potential P300 in Patients with Migraine.

OBJECTIVE: Recording of event-related potentials by using oddball paradigm of auditory P300 has yielded conflicting results in migraine. The aim of this study was to demonstrate that migraine patients have reduced P300 amplitude and prolonged P300 latency, suggesting alterations of the cognitive-evaluative component. METHODS: We recruited 29 migraine patients (24 females; median age 40 years) and 29 healthy age- and gender-matched participants. Participants were subjected to the same testing procedures of auditory P300 by discrimination the target auditory stimulus from the frequent stimulus, and analyzing P300 target/frequent stimulus amplitudes, and P300 target/frequent stimulus latencies. RESULTS: Patients with migraine don't have prolonged P300 target stimulus latency, but have a longer P300 frequent stimulus latency for 17.5ms. Out of 29 participants with migraine 8 had pathological P300 target stimulus amplitude, and 19 had pathological P300 frequent stimulus amplitude. CONCLUSION: People with migraine have altered the P300 which indicates the presence of cognitive dysfunction in these patients and importance of early diagnosis and intervention to preventing any deterioration in cognitive functions.

Matrix metalloproteinases and E-cadherin immunoreactivity in different basal cell carcinoma histological types.

The immunohistochemical staining of matrix metalloproteinases (MMPs) and E-cadherin in tumor epithelial and stromal cells was analyzed in a group of solid, superficial spreading and cystic tumors and in a group of morpheaform and recurrent basal cell carcinomas (BCC) in order to determine whether any of these factors possibly contribute to tumor therapy resistance. Tumor tissues of 64 patients were obtained by complete excisional or curettage biopsy of BCC and these were immunohistochemically stained for MMP-1, MMP-2, MMP-9, MMP-13 and E-cadherin. In the morpheaform and recurrent BCC, MMP-9 expression significantly increased in the stroma, while E-cadherin expression was negative in epithelial cells. Odds ratio for development of morpheaform and recurrent BCC was 6.2 for positive MMP-1 immunostaining in epithelial tumor cells, 5.8 for positive MMP-9 immunostaining in tumor stroma, 3.2 for positive MMP-13 immunostaining in tumor stroma, and 4.5 for negative E-cadherin in epithelial tumor cells. Our results suggest that MMP-1 immunostaining in tumor cells, MMP-9 expression in stromal cells, and absence of E-cadherin expression are associated with morpheaform and recurrent BCC.

Vitiligo and glaucoma - an association or a coincidence? A pilot study.

Our aim was to draw attention of clinicians, dermatovenereologists and ophthalmologists to the possible association of vitiligo and ocular findings characteristic of primary open angle glaucoma (POAG). According to our clinical experience, POAG is relatively often diagnosed or previously diagnosed in patients treated for vitiligo. We found no literature report directly connecting vitiligo and POAG. The articles mentioning glaucoma, i.e. increased intraocular pressure (IOP), are mainly based on secondary type of glaucoma as a direct consequence of vitiligo treated by corticosteroids. On the other hand, there is a substantial number of articles elaborating the association of vitiligo with ocular findings in known clinical syndromes. During a 2-year period, from May 2007 to May 2009, 42 patients with vitiligo were examined at University Department of Dermatology and Venereology and referred for previously appointed ophthalmologic examination at University Department of Ophthalmology, Split University Hospital Center. All patients with vitiligo underwent complete ophthalmologic examination including visual field analysis, in order to treat and follow up or diagnose newly discovered POAG. Of 42 patients with vitiligo suspect of glaucoma, POAG was confirmed in 24 (57%) patients. Age median of all vitiligo patients was 56 (range 19-82) years. In patients with vitiligo and glaucoma, the duration of vitiligo was twofold that recorded in patients with vitiligo alone, the difference being statistically significant (z=3.3; P<0.001). The risk of developing glaucoma in vitiligo patients was 4.4-fold in >56 age group versus <56 age group and 3.5-fold in patients with >13 year versus patients with <13 year duration of vitiligo. Multivariate logistic regression for glaucoma development according to vitiligo duration (< or =13 years vs. > or =13 years) and patient age (< or =56 years vs. > or =56 years) pointed to the association of glaucoma development and age and yielded a 92% probability for the association of glaucoma development and vitiligo duration. Therefore, we believe that patients treated for vitiligo should regularly undergo complete ophthalmologic examination with special attention paid to POAG irrespective of age, sex, severity, localization and duration of the disease. Although performed in a relatively small sample and over short period of time, the results of this pilot study demonstrated that this association was not accidental. Additional studies in a greater sample of vitiligo patients and POAG are expected to provide definitive answers and conclusion on the association of these two diseases.

Fractionated illumination improves the outcome in the treatment of precancerous lesions with photodynamic therapy.

Photodynamic therapy (PDT) is a noninvasive therapy for non-melanoma skin cancer. The aim of this study was comparison of efficacy between fractioned versus single dose illumination in photodynamic therapy (PDT) of actinic keratosis (AK) and Bowen's disease (BD). Fifty-one patients (36 AK and 15 BD) were treated with PDT They were randomly arranged in two treatment groups. Group one included 26 patients (20 AK and 6 BD) that, after five hours of incubation with 20% 5-ALA, were treated with a single illumination of 100 Jcm(-2) at fluence rate of 30 mWcm(-2). Group two included 25 patients (16 AK and 9 BD) that, after 16 hours of incubation with 20% 5-ALA, were treated with two light fractions (50 plus 50 Jcm(-2)) at same fluence rate with dark interval of two hours between fractions. Twenty-four weeks later, a treated area was incubated for four hours again with 5-ALA in order to detect occult areas of abnormal skin with possible remaining tumor tissue. In case of fluorescence, histological examination was performed. In the group one, fluorescence at the end of the session was absent in 19 (73%) or very weak in 7 (27%). Residual tumor was found in 15 (75%) AK and in 4 (66.6%) BD. In the group two, fluorescence at the end of second session was more intense; in one patient (4%) was absent, very weak in 5 (20%) and weak in 19 (76%) of patients. In this group histology revealed remaining tumor tissue in only 2 (12.5%) AK and 2 (22.2%) BD. Among the patients in the first group, the remaining tumor tissue was significantly bigger (p=0.005). The treatment response with clearing of tumor tissue was significantly higher in fractionated illumination than in a single dose illumination group. Fractionated illumination scheme with 16 hours of incubation separated by two hours dark interval significantly improves the therapeutic outcome in tumor eradication.