Capillary Malformation in CLAPO Syndrome Successfully Treated with Pulsed Dye Laser. / Malformación capilar del síndrome CLAPO exitosamente tratado con láser de colorante pulsado.

CLAPO syndrome (Capillary vascular malformation of the lower lip, Lymphatic malformations of the head and neck, Asymmetry and Partial/generalized Overgrowth) is a recently described entity, with very few published cases in the literature, and no standardized treatment. The objective of our study was to assess the efficacy and safety of PDL in patients with this syndrome. Seven patients were treated with two to four sessions of PDL at 595-nm wavelength. Laser therapy was performed using a spot size of 7 to 10 mm, a pulse duration of 0,5 to 1,5 ms and a fluence from 6 to 8 J/cm2. Clinical photographs were taken before treatment and 3 weeks after procedure. Clearance of the erythema was > 75% in 4 patients. Transient purpura was present in all patients for about 2 weeks and 1 patient presented post inflammatory hypopigmentation. In conclusion we consider that PDL seems to be a safe and effective treatment for capillary malformations of the CLAPO syndrome. A marked reduction in erythema was achieved in all patients with a low incidence of side effects.

Interobserver variability in the classification of childhood maculopapular cutaneous mastocytosis.

BACKGROUND: Maculopapular cutaneous mastocytosis (MPCM) in children is classified in two variants: (i) monomorphic variant, presenting with the small macules or papules typically seen in adult patients; and (ii) polymorphic variant with larger lesions of variable size and shape, typically seen in children. The definition of polymorphic and monomorphic variants is mostly intuitive, and a validation of this classification has not been done. OBJECTIVE: To study interobserver variability in the classification of MPCM in two groups of observers: mastocytosis experts and general dermatologists. MATERIALS AND METHODS: Nineteen cases of childhood MPCM were shown blindly, for classification as monomorphic or polymorphic type, to 10 independent observers (eight dermatologists, one allergist and one haematologist) from Europe and North America with a vast experience in the management of paediatric mastocytosis. Also, the same cases were shown on a screen to 129 general dermatologists attending a meeting; their votes were registered by remote controls. The interobserver variability kappa coefficient (with 95% confidence interval) was calculated to measure the reliability of the correlation. RESULTS: The value of kappa interobserver variability coefficient for the group of 10 experts (95% confidence interval) was 0.39 (0.18-0.63), which is considered as 'fair'. The value of kappa interobserver variability coefficient for the group of 129 general dermatologists (95% confidence interval) was 0.17 (0.06-0.39), which is considered as 'slight'. A complete agreement of all 10 experts was achieved in only four of 19 cases (21.1%) The most voted choice was concordant between the two groups in only 11 of the 19 cases. CONCLUSIONS: We failed to validate the classification system of childhood MPCM in monomorphic and polymorphic types. While the rate of agreement was low for mastocytosis experts, it was nearly the agreement expected by chance in general dermatologists.

Usefulness of ultrasound for treatment and follow-up of cutaneous leishmaniasis.

PURPOSE: Local therapy is the preferred option of treatment for most cutaneous leishmaniasis (CL); however, local therapy could be challenging, depth and size of the skin lesions are not always clinically evident and treatment response evaluation could occasionally be misleading. High frequency ultrasound is a non-invasive imaging tool which allows initial depth assessment ultrasound-guided infiltrations and ultrasound monitoring until resolution. METHODS: We present two cases of CL treated with ultrasound-guided infiltrations and ultrasound monitoring until resolution. RESULTS: Ultrasound imaging allowed a more accurate diagnosis of CL, defining more precisely the depth and size of the skin lesions. During follow-up, progressive decrease in dermal involvement, marked attenuation of the echogenicity of subcutaneous cellular tissue and a decrease in vascularization in the color Doppler mode was observed, which aided in evaluation of treatment response. Hypodermal inflammation observed through sonography was addressed with image-guided infiltration. CONCLUSION: We would like to highlight the usefulness of skin ultrasound (both B-mode and color Doppler mode) in the diagnosis, depth assessment, imaging guided treatment, and follow-up in CL.

Tryptophan depletion affects compulsive behaviour in rats: strain dependent effects and associated neuromechanisms.

RATIONALE: Compulsive behaviour, present in different psychiatric disorders, such as obsessive-compulsive disorder, schizophrenia and drug abuse, is associated with altered levels of monoamines, particularly serotonin (5-hydroxytryptamine) and its receptor system. OBJECTIVES: The present study investigated whether 5-HT manipulation, through a tryptophan (TRP) depletion by diet in Wistar and Lister Hooded rats, modulates compulsive drinking in schedule-induced polydipsia (SIP) and locomotor activity in the open-field test. The levels of dopamine, noradrenaline, serotonin and its metabolite were evaluated, as well as the 5-HT2A and 5-HT1A receptor binding, in different brain regions. METHODS: Wistar rats were selected as high (HD) or low (LD) drinkers according to their SIP behaviour, while Lister hooded rats did not show SIP acquisition. Both strains were fed for 14 days with either a TRP-free diet (T-) or a TRP-supplemented diet (T+) RESULTS: The TRP depletion diet effectively reduced 5-HT levels in the frontal cortex, amygdala and hippocampus in both strains of rats. The TRP-depleted HD Wistar rats were more sensitive to 5-HT manipulation, exhibiting more licks on SIP than did the non-depleted HD Wistar rats, while the LD Wistar and the Lister Hooded rats did not exhibit differences in SIP. In contrast, the TRP-depleted Lister Hooded rats increased locomotor activity compared to the non-depleted rats, while no differences were found in the Wistar rats. Serotonin 2A receptor binding in the striatum was significantly reduced in the TRP-depleted HD Wistar rats. CONCLUSIONS: These results suggest that alterations of the serotonergic system could be involved in compulsive behaviour in vulnerable populations.

Therapeutic antidepressant potential of a conjugated siRNA silencing the serotonin transporter after intranasal administration.

Major depression brings about a heavy socio-economic burden worldwide due to its high prevalence and the low efficacy of antidepressant drugs, mostly inhibiting the serotonin transporter (SERT). As a result, ~80% of patients show recurrent or chronic depression, resulting in a poor quality of life and increased suicide risk. RNA interference (RNAi) strategies have been preliminarily used to evoke antidepressant-like responses in experimental animals. However, the main limitation for the medical use of RNAi is the extreme difficulty to deliver oligonucleotides to selected neurons/systems in the mammalian brain. Here we show that the intranasal administration of a sertraline-conjugated small interfering RNA (C-SERT-siRNA) silenced SERT expression/function and evoked fast antidepressant-like responses in mice. After crossing the permeable olfactory epithelium, the sertraline-conjugated-siRNA was internalized and transported to serotonin cell bodies by deep Rab-7-associated endomembrane vesicles. Seven-day C-SERT-siRNA evoked similar or more marked responses than 28-day fluoxetine treatment. Hence, C-SERT-siRNA (i) downregulated 5-HT1A-autoreceptors and facilitated forebrain serotonin neurotransmission, (ii) accelerated the proliferation of neuronal precursors and (iii) increased hippocampal complexity and plasticity. Further, short-term C-SERT-siRNA reversed depressive-like behaviors in corticosterone-treated mice. The present results show the feasibility of evoking antidepressant-like responses by selectively targeting neuronal populations with appropriate siRNA strategies, opening a way for further translational studies.

RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis.

Current antidepressants, which inhibit the serotonin transporter (SERT), display limited efficacy and slow onset of action. Here, we show that partial reduction of SERT expression by small interference RNA (SERT-siRNA) decreased immobility in the tail suspension test, displaying an antidepressant potential. Moreover, short-term SERT-siRNA treatment modified mouse brain variables considered to be key markers of antidepressant action: reduced expression and function of 5-HT(1A)-autoreceptors, elevated extracellular serotonin in forebrain and increased neurogenesis and expression of plasticity-related genes (BDNF, VEGF, Arc) in hippocampus. Remarkably, these effects occurred much earlier and were of greater magnitude than those evoked by long-term fluoxetine treatment. These findings highlight the critical role of SERT in serotonergic function and show that the reduction of SERT expression regulates serotonergic neurotransmission more potently than pharmacological blockade of SERT. The use of siRNA-targeting genes in serotonin neurons (SERT, 5-HT(1A)-autoreceptor) may be a novel therapeutic strategy to develop fast-acting antidepressants.

Atopy and serum eosinophil cationic protein in 110 white children with vernal keratoconjunctivitis: differences between tarsal and limbal forms.

BACKGROUND: A predominance of Th2 response has been suggested in vernal keratoconjunctivitis (VKC), and a high prevalence of IgE-sensitized (IgE-S) patients has been reported (positive skin prick test or serum-specific-IgE). Palpebral and bulbar VKC are considered to be expressions of the same disease and only occasional racial and histopathological differences are described between the two forms. Tear levels of eosinophil cationic proteins have been correlated with the severity of ocular symptoms; however, there is no published study that demonstrates the presence of serum markers of disease activity. OBJECTIVE: This study was performed to evaluate the prevalence of IgE-sensitization in palpebral, bulbar and mixed VKC and to determine possible useful markers of disease activity in peripheral circulation. METHODS: A total of 110 white VKC patients (mean age 8.3 years, range 3.2-18 years) were evaluated for ocular score in the active phase of the disease. Skin prick tests and serum-specific IgE for common allergens, serum-total IgE, peripheral blood eosinophil counts (PBECs) and serum eosinophil cationic protein (s-ECP) were determined. Fifteen age-matched non-IgE-S control children underwent the same determinations. RESULTS: s-ECP, PBECs and s-total IgE were significantly higher in IgE-S than in non-IgE-S VKC patients and in non-IgE-S VKC patients than in controls. A lower prevalence of IgE-S patients was found in bulbar vs. tarsal (P = 0. 050) or mixed forms (P = 0.002). The score of giant papillae was strongly correlated with s-ECP levels (P < 0.001) and with PBECs (P = 0.001). CONCLUSIONS: Our data suggest that an overall eosinophilic response is present in VKC independently of IgE-sensitization; bulbar forms, unlike tarsal and mixed forms, were associated with a low prevalence of IgE-sensitization. Serum ECP was a useful marker of disease activity in tarsal and mixed forms.

Changes in refraction in anisomyopic patients.

PURPOSE: The purpose of this study was to investigate the evolution of refraction and visual function in patients with myopic anisometropia. DESIGN: A retrospective study on a selected population. METHODS: Forty-six anisomyopic patients underwent a complete ophthalmologic examination (cycloplegic refraction, visual acuity, ocular movement and fundus examination). RESULTS: The results show two different patterns of changes in refraction between the two eyes; in the same patient, the less myopic eye tends to get more myopic, while the more ametropic eye shows a more stable refraction. Furthermore, a recovery of binocular vision and amblyopia can be obtained by occlusion and full-time refractive correction. CONCLUSIONS: The evolution of refraction seems to be different in eyes with anisometropia and it is still to be understood whether it is fixation or reduced fixation that leads to a myopic shift.

[Electrophysiological studies in amblyopia]. / Badania elektrofizjologiczne w niedowidzeniu.

The authors describe the methods of recording the visual evoked potentials and of their utilization for investigations in amblyopia. The characteristics of VEP have been analyzed in an amblyopic and a normal eye; analyzed further on were the reciprocal dependencies between an uniocular and binocular records, the phenomenon of suppression and sensitivity to contrast. The authors confirm the suitability of the VEP for objective evaluation of the progress of treatment and for elucidation of the physiopathology of amblyopia.

[Placoid pigment epitheliopathy: a parallel study between automatized perimetry and fluorescence angiography]. / Epithéliopathie en plaques: parallèle entre la périmétrie automatisée et l'angiographie en fluorescence.

This report concerns a patient whom, on the basis of clinical data and instrumental findings, we diagnosed as suffering from Acute Multifocal Posterior Pigment Epitheliopathy (AMPPE). We found the comparison of the angiographic findings and of the automated perimetry performed with the Octopus quite interesting since the literature does not contain reports of such comparisons. The results of perimetry were also of considerable interest. The test revealed serious impairment of retinal luminous sensitivity. The comparison of angiography and automated perimetry of the lesions of the pigmented epithelium was quite useful for providing a better clinical picture and understanding of the functional state.

[Elevation in adduction. Relation to congenital strabismus and other types of ocular motility disorders]. / L'élévation en adduction. Rapports avec le strabisme congénital et avec d'autres types de troubles de la motilité oculaire.

This retrospective study shows the clinical data of 81 patients with elevation in adduction. The relationships between the elevation in adduction and various ocular anomalies, such as horizontal deviations, refractive errors, nystagmus, torticollis, superior oblique muscle paralysis and dissociated vertical deviation, have been studied in order to specify the clinical characteristics of this phenomenon. The age of onset of the elevation in adduction and of the dissociated vertical deviation has also been considered, and a typical temporal progression of these symptoms has been found. In this sequence, we first noticed the onset of the horizontal deviation, then the appearance of the elevation in adduction, and finally the appearance of the dissociated vertical deviation. Although the elevation in adduction is frequently found in association with the complex syndromic pattern of congenital esotropia, this phenomenon may also accompany other types of anomalies of ocular motility.