Gyrate atrophy of the choroid and retina: Update on diagnosis and treatment.

Gyrate atrophy of the choroid and retina (GACR) is a rare autosomal recessive disease characterised by elevated plasma ornithine levels due to deficiency of the enzyme ornithine aminotransferase (OAT). The accumulation of this amino acid in plasma leads to the development of patches of chorioretinal atrophy in the peripheral retina extending into the macular area. Patients usually present with night blindness followed by constriction of the visual field and, finally, decreased central vision and blindness. The disease is diagnosed by the presence of the characteristic clinical picture, the presence of hyperornithinaemia in plasma and the detection of mutations in the OAT enzyme gene. There is currently no effective gene therapy and the most common therapeutic intervention mainly involves dietary modifications with arginine restriction. This article aims to summarise the pathogenesis, clinical and diagnostic findings and treatment options in patients with GACR.

Lacrimal Puncta Agenesis in Kabuki Syndrome.

Kabuki syndrome (KS) is a rare congenital disorder characterized by multiple systemic anomalies and facial characteristics. Here, the authors present the first case, to the best of the authors' knowledge, of bilateral lacrimal puncta agenesis in a patient with KS.#8232;The proband patient was a 29-year-old woman diagnosed with this syndrome, brought to our office due to recurrent conjunctivitis where agenesia of lacrimal puncta was observed. Therapeutic options were exposed but, as the concomitant medication (topiramate) produced ocular dryness, conservative treatment was decided. Diagnosis of KS is challenging because it is a complex syndrome with many associated findings. The authors recommend taking into account the agenesis of lacrimal points in the differential diagnosis of KS if it is associated with other phenotypic alterations as well as including lacrimal examination in patients with KS diagnosis. The authors emphasize the importance of individualizing treatment since drugs used for the systematic management of these patients can influence tear symptoms.

Capillary Malformations Treated With Sequential Pulsed Dye and Nd:YAG Laser Therapy: A Retrospective Study. / Malformaciones capilares tratadas con aplicación secuencial de láser de colorante pulsado y Nd:YAG: estudio retrospectivo.

INTRODUCTION AND OBJECTIVE: Capillary malformations are the most common vascular malformations in childhood. The current treatment of choice is pulsed dye laser (PDL) therapy, but this frequently does not result in complete resolution. The search for alternative treatment strategies thus continues. In this study we describe our experience with the use of sequential dual-wavelength PDL and Nd:YAG laser therapy in patients with capillary malformations. MATERIAL AND METHODS: We conducted a retrospective, descriptive study of patients with capillary malformations treated with dual-wavelength PDL and Nd:YAG laser therapy between 2006 and 2011. Four dermatologists rated the effectiveness of treatment on a scale of 10 to 0. We also investigated the potential value of the following factors as predictors of better treatment response: sex, malformation size and color, and presence of associated hypertrophy. Adverse effects were also analyzed. RESULTS: We studied 71 patients and most of them experienced a statistically significant improvement after treatment. More favorable responses were observed for violaceous malformations, lesions with associated hypertrophy, and smaller lesions. Adverse effects were reported for 26.76% of patients, and the most common effect was the appearance of isolated areas of skin atrophy. CONCLUSIONS: We consider that sequential dual-wavelength PDL and ND:YAG laser therapy is an effective alternative for treating capillary malformations in selected patients.

Hemangiomas infantiles tratados con aplicación secuencial de láser de colorante pulsado y Nd:YAG: estudio retrospectivo / Infantile Hemangiomas Treated by Sequential Application of Pulsed Dye Laser and Nd:YAG Laser Radiation: A Retrospective Study

Introducción: Los hemangiomas infantiles son los tumores benignos más frecuentes en la infancia, presentando una fase proliferativa, una fase de involución y una fase residual. En muchas ocasiones no precisan de un tratamiento activo. No obstante, en algunos pacientes se impone la necesidad de un tratamiento. Entre las posibilidades terapéuticas ha demostrado utilidad, durante todas las fases evolutivas de la lesión, el tratamiento con láser. Comunicamos nuestra experiencia con el láser dual secuencial de colorante pulsado (LCP) y Nd:YAG. Material y métodos: Se efectuó un estudio retrospectivo y descriptivo de los pacientes con hemangiomas infantiles en diversas fases evolutivas tratados con el láser dual de LCP y Nd:YAG. Cuatro dermatólogos valoraron el grado de efectividad en una escala del 10 al 0. Se recogieron los efectos adversos e incidencias relativas al tratamiento. En el análisis se utilizó para los valores descriptivos la mediana y el rango intercuartílico y la prueba de Wilcoxon para la comparación pre y postratamiento. Resultados: Se recogieron 22 pacientes con hemangiomas en distintos estadios evolutivos, obteniéndose una mejoría estadísticamente significativa tanto en el conjunto de todos los pacientes como en los distintos subgrupos. Cuatro pacientes presentaron incidencias postratamiento: edema y ulceración, atrofia cutánea e hiperpigmentación. Conclusiones: Consideramos que el láser dual de LCP y Nd:YAG puede ser una alternativa para el tratamiento de hemangiomas infantiles cuando las terapias consideradas de primera línea se muestran ineficaces o están contraindicadas (AU)

Background and objectives: Infantile hemangiomas are the most common benign tumor in children. They have 3 phases of development: a proliferative phase, an involuting phase, and involution. Although active treatment is often not required, it is necessary in some cases. Of the possible treatments for hemangiomas, lasers have been shown to be effective in all phases of development. We report our experience with dual-wavelength sequential pulses from a pulsed dye laser and an Nd:YAG laser. Material and methods: This was a retrospective, descriptive study of patients with infantile hemangioma in different phases of development treated with pulsed dye laser pulses followed by Nd:YAG laser pulses. Four dermatologists assessed the effectiveness of treatment on a scale of 10 to 0. Adverse effects and incidents related to treatment were recorded. The median and interquartile range were calculated as descriptive statistics. Pretreatment and posttreatment comparisons were performed using the Wilcoxon test. Results: Twenty-two patients with hemangiomas in different phases of development were included. A statistically significant improvement was obtained both for the entire group and for different subgroups. Posttreatment events were reported in 4 patients, and included edema and ulceration, skin atrophy, and hyperpigmentation. Conclusions: We believe that treatment with dual-wavelength light from a pulsed dye laser and a Nd:YAG laser is a viable treatment option for infantile hemangiomas when first-line therapies are ineffective or contraindicated (AU)

Infantile hemangiomas treated by sequential application of pulsed dye laser and Nd:YAG laser radiation: a retrospective study.

BACKGROUND AND OBJECTIVES: Infantile hemangiomas are the most common benign tumor in children. They have 3 phases of development: a proliferative phase, an involuting phase, and involution. Although active treatment is often not required, it is necessary in some cases. Of the possible treatments for hemangiomas, lasers have been shown to be effective in all phases of development. We report our experience with dual-wavelength sequential pulses from a pulsed dye laser and an Nd:YAG laser. MATERIAL AND METHODS: This was a retrospective, descriptive study of patients with infantile hemangioma in different phases of development treated with pulsed dye laser pulses followed by Nd:YAG laser pulses. Four dermatologists assessed the effectiveness of treatment on a scale of 10 to 0. Adverse effects and incidents related to treatment were recorded. The median and interquartile range were calculated as descriptive statistics. Pretreatment and posttreatment comparisons were performed using the Wilcoxon test. RESULTS: Twenty-two patients with hemangiomas in different phases of development were included. A statistically significant improvement was obtained both for the entire group and for different subgroups. Posttreatment events were reported in 4 patients, and included edema and ulceration, skin atrophy, and hyperpigmentation. CONCLUSIONS: We believe that treatment with dual-wavelength light from a pulsed dye laser and a Nd:YAG laser is a viable treatment option for infantile hemangiomas when first-line therapies are ineffective or contraindicated.

Venous malformations treated with dual wavelength 595 and 1064 nm laser system.

BACKGROUND & OBJECTIVE: Venous malformations (VM) represent a localized error in the embryological development of the venous branch of the circulation. The management of VM is complex and challenging. The aim of this study was to assess the efficacy and safety of combined sequential pulsed dye laser (PDL)-Nd:YAG laser in patients with cutaneous or mucosal VM. METHODS: Thirty patients (age from 8 to 65 years) with cutaneous or mucosal VM treated with dual wavelength PDL-Nd:YAG laser were retrospectively analyzed. Laser parameters were 10 mm spot size with 10 ms pulse and 8-10 J/cm(2) of PDL, followed with a second delay by Nd:YAG with 15 or 20 ms at 35-70 J/cm(2); or 7 mm spot size with 10 ms pulse and 5-10.5 J/cm(2) of PDL, followed with a second delay by Nd:YAG with 15 or 20 ms at 50-100 J/cm(2). Laser sessions were repeated approximately every 2-6 months. Air cooling was applied during treatment. Three dermatologists evaluated treatment effectiveness by means of photographs of the patients before and after laser treatment (scale from 0 to 4). Differences in the degree of clinical improvement between patients with cutaneous or mucosal VM were also assessed. Adverse events were registered. Patient satisfaction was also assessed in 19 cases (scale from 0 to 10). RESULTS: Mean global improvement was rated as 3.37. Mean improvement in patients with cutaneous VM was 3.35 and 3.38 in patients with mucosal VM. No significant difference between both groups was observed (P = 0.53). Long-lasting side effects included partial epilation of the eyelashes in one patient, ulceration in two patients and permanent scarring in three patients. Mean patient satisfaction was 8.55. CONCLUSIONS: Our study concludes that dual wavelength PDL-Nd:YAG laser was effective for treatment of the superficial component of cutaneous and mucosal VM.

Ablative fractional yttrium-scandium-gallium-garnet laser for scarring residual haemangiomas and scars secondary to their surgical treatment.

BACKGROUND: Infantile haemangiomas are benign self-involuting tumours. They have a characteristic clinical course marked by early proliferation and followed by spontaneous involution. However, residual evidence with scar formation, fibrofatty residua, atrophic wrinkling, yellowish discoloration and telangiectasias is usually seen after involution. OBJECTIVE: The aim of this study was to assess the efficacy and safety of ablative fractional yttrium-scandium-gallium-garnet (YSGG) laser in patients with residual haemangiomas or with scarring after their surgery. METHODS: Twelve patients with atrophic scar or fibrofatty tissue secondary to residual hemangiomas or with scarring after surgery of haemangioma were treated with one or two sessions of ablative fractional YSGG laser at 2.790-nm wavelength. Laser therapy was performed using a spot size of 300 µm, a pulse width of 600 ms, a fluence range between 120 and 200 mJ per microspot and a density level of 3. Treatment with PDL at 595-nm or with combined sequential 595 nm PDL and 1064 nm Nd:YAG was applied if telangiectasias or a residual vascular component were present. Three dermatologists evaluated treatment effectiveness by means of photographs of the patients before starting and 3 months after finishing the therapy; the degree of improvement was rated from 0 to 4. Parents' satisfaction was also assessed (scale from 0 to 10). RESULTS: Improvement was rated as 3 in two patients, 2 in four patients, 1 in five patients and no improvement in only one patient. Mean improvement was 1.58. Degree of parents' satisfaction ranged from 0 to 10. Mean satisfaction was 6.75. A discrete punctuate pattern was seen in three patients as the only long-lasting side-effect. CONCLUSION: We consider that ablative fractional YSGG laser could be an interesting option for the treatment of selected patients with atrophic wrinkling or scarring residual haemangiomas and scars secondary to their surgical treatment.

Keratosis pilaris rubra and keratosis pilaris atrophicans faciei treated with pulsed dye laser: report of 10 cases.

BACKGROUND: Keratosis pilaris rubra (KPR) and keratosis pilaris atrophicans faciei (KPAF) are both keratinization disorders characterized by erythema and keratotic follicular papules usually located on cheeks, forehead, chin and eyebrows. Topical keratolytics, vitamin D3 analogues, antibiotics, topical and oral retinoids have been used with limited results. As this condition can be socially very limiting, the need for an effective treatment has led to the use of other technologies such as pulsed dye laser (PDL) or intense pulsed light. OBJECTIVE: The aim of this study was to assess the efficacy and safety of PDL in patients with KPR or KPAF. METHODS: Ten patients with KPR or KPAF were treated with two to seven sessions of PDL at 595-nm wavelength. Laser therapy was performed using a spot size of 7 or 10mm, a pulse duration of 0.5 or 1.5ms and a fluence from 5 to 9J/cm(2) . Two dermatologists evaluated treatment effectiveness by means of photographs of the patients before starting and after finishing the therapy. RESULTS: Complete resolution of erythema was achieved in three patients; clearance of erythema was >75% in the other seven patients. Transient purpura was present in all patients for about 2weeks and one patient presented postinflammatory hyperpigmentation for 7months. CONCLUSION: We consider that PDL is a good option for the treatment of KPR and KPAF. A marked reduction in erythema is achieved in all patients with a low incidence of side effects.

Determination of ellagic acid in oak leaves and in sheep ruminal fluid by ion-pair RP-HPLC.

An isocratic ion-pair high-performance liquid chromatography (IP-RP-HPLC) method with UV detection was developed to identify and quantify ellagic acid (EA). This phenolic compound is widely distributed in the plants and is often present in the diet of ruminants. The method was validated and validation parameters were: linearity range 5-100 mg/L; correlation coefficient, 0.9995; mean recoveries (99.94 and 101.07%) and detection limit 1.4 mg/L. Method was applied for the determination of ellagic acid in oak leaves and in ruminal fluid from to a vitro ruminal system. The proposed method proved to be rapid and accurate and can be successfully used in ruminant nutrition studies.

The discovery of moriniafungin, a novel sordarin derivative produced by Morinia pestalozzioides.

A novel sordarin derivative, moriniafungin (1), containing a 2-hydroxysebacic acid residue linked to C-3' of the sordarose residue of sordarin through a 1,3-dioxolan-4-one ring was isolated from the fungus Morinia pestalozzioides. Isolation of moriniafungin employed a highly specific bioassay consisting of a panel of Saccharomyces cerevisiae strains containing chimeric eEF2 for Candida glabrata, Candida krusei, Candida lusitaniae, Crytpococcus neoformans, and Aspergillus fumigatus as well as wild type and human eEF2. Moriniafungin exhibited an MIC of 6 microg/mL versus Candida albicans and IC(50)'s ranging from 0.9 to 70 microg/mL against a panel of clinically relevant Candida strains. Moriniafungin was shown to inhibit in vitro translation in the chimeric S. cerevisae strains at levels consistent with the observed IC(50). Moriniafungin has the broadest antifungal spectrum and most potent activity of any natural sordarin analog identified to date.

Cultura organizacional: hacia un nuevo enfoque de la misión del administrador

Describe tanto la trascendencia de la cultura en el análisis de las organizaciones, como la nueva visión que del término cultura organizacional deberá tener el administrador del próximo milenio.

Antimicrobial activity of ergokonin A from Trichoderma longibrachiatum.

AIMS: Natural fungal products were screened for antifungal compounds. The mode of action of one of the hits found and the taxonomy of the producing organism were analysed. METHODS AND RESULTS: An extract from a Trichoderma species showed a more potent activity in an agar-based assay against the null mutant fks1::HIS strain than against the wild-type strain, suggesting that it could contain a glucan synthesis inhibitor. The active component was identified as the known compound ergokonin A. The compound exhibited activity against Candida and Aspergillus species, but was inactive against Cryptococcus species. It induced alterations in the hyphal morphology of Aspergillus fumigatus. The identification of the producing isolate was confirmed by sequencing of the rDNA internal transcribed spacers and comparison with the sequences of other Trichoderma species. The analysis showed that the producing fungus had a high homology with other strains classified as Trichoderma longibrachiatum and its teleomorph Hypocrea schweinitzii. CONCLUSIONS: The antifungal activity spectrum of ergokonin A and the morphology alterations induced on A. fumigatus are consistent with glucan synthesis as the target for ergokonin A. The production of ergokonin A is not uncommon, but is probably restricted to Trichoderma species. SIGNIFICANCE AND IMPACT OF THE STUDY: The discovery that ergokonin A could be an inhibitor of glucan synthesis, having a structure very different to other inhibitors, increases the likelihood that orally active agents with this fungal-specific mode of action may be developed.

Arundifungin, a novel antifungal compound produced by fungi: biological activity and taxonomy of the producing organisms.

Echinocandins, the lipopeptide class of glucan synthase inhibitors, are an alternative to ergosterol-synthesis inhibitors to treat candidiasis and aspergillosis. Their oral absorption, however, is low and they can only be used parenterally. During a natural product screening program for novel types of glucan synthesis inhibitors with improved bioavailability, a fungal extract was found that inhibited the growth of both a wild-type Saccharomyces cerevisiae strain and the null mutant of the FKS1 gene (fks1::HIS). The mutant strain was more sensitive to growth inhibition, suggesting that the fungal extract could contain an inhibitor of glucan synthesis. A novel acidic steroid, named arundifungin, was purified from a fungal extract obtained from a liquid culture of Arthrinium arundinis collected in Costa Rica. Arundifungin caused the same pattern of hallmark morphological alterations in Aspergillus fumigatus hyphae as echinocandins, further supporting the idea that arundifungin belongs to a new class of glucan synthesis inhibitors. Moreover, its antifungal spectrum was comparable to those of echinocandins and papulacandins, preferentially inhibiting the growth of Candida and Aspergillus strains, with very poor activity against Cryptococcus. Arundifungin was also detected in nine other fungal isolates which were ecologically and taxonomically unrelated, as assessed by sequencing of the ITS1 region. Further, it was also found in two more Arthrinium spp from tropical and temperate regions, in five psychrotolerant conspecific isolates collected on Macquarie Island (South Pacific) and belonging to the Leotiales, and in two endophytes collected in central Spain (a sterile fungus belonging to the Leotiales and an undetermined coelomycete).

The discovery of enfumafungin, a novel antifungal compound produced by an endophytic Hormonema species biological activity and taxonomy of the producing organisms.

In a screening of natural products with antifungal activity derived from endophytic fungi, we detected a potent activity in a culture belonging to the form-genus Hormonema, isolated from leaves of Juniperus communis. The compound is a new triterpene glycoside, showing an antifungal activity highly potent in vitro against Candida and Aspergillus and with moderate efficacy in an in vivo mouse model of disseminated candidiasis. The agent is especially interesting since its antifungal spectrum and its effect on morphology of Aspergillus fumigatus is comparable to that of the glucan synthase inhibitor pneumocandin B,,, the natural precursor of the clinical candidate MK-0991 (caspofungin acetate). An additional search for other Hormonema isolates producing improved titers or derivatives resulted in the isolation of two more strains recovered from the same plant host showing identical activity. The producing isolates were compared with other non-producing Hormonema strains by DNA fingerprinting and sequencing of the rDNA internal transcribed spacers. Comparison of rDNA sequences with other fungal species suggests that the producing fungus could be an undetermined Kabatina species. Kabatina is a coelomycetous genus whose members are known to produce Hormonema-like states in culture.

Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors.

The increasing incidence of life-threatening fungal infections has driven the search for new, broad-spectrum fungicidal agents that can be used for treatment and prophylaxis in immunocompromised patients. Natural-product inhibitors of cell wall (1,3)-beta-D-glucan synthase such as lipopeptide pneumocandins and echinocandins as well as the glycolipid papulacandins have been evaluated as potential therapeutics for the last two decades. As a result, MK-0991 (caspofungin acetate; Cancidas), a semisynthetic analogue of pneumocandin B(o), is being developed as a broad-spectrum parenteral agent for the treatment of aspergillosis and candidiasis. This and other lipopeptide antifungal agents have limited oral bioavailability. Thus, we have sought new chemical structures with the mode of action of lipopeptide antifungal agents but with the potential for oral absorption. Results of natural-product screening by a series of newly developed methods has led to the identification of four acidic terpenoid (1,3)-beta-D-glucan synthase inhibitors. Of the four compounds, the in vitro antifungal activity of one, enfumafungin, is comparable to that of L-733560, a close analogue of MK-0991. Like the lipopeptides, enfumafungin specifically inhibits glucan synthesis in whole cells and in (1,3)-beta-D-glucan synthase assays, alters the morphologies of yeasts and molds, and produces a unique response in Saccharomyces cerevisiae strains with point mutations in FKS1, the gene which encodes the large subunit of glucan synthase.

Screening of basidiomycetes for antimicrobial activities.

As a part of a screening programme developed to evaluate the antimicrobial activity of basidiomycetes, 317 isolates representing 204 species collected in Spain were screened against a range of human clinical pathogens and laboratory controls. Extracts from 45% of the isolates, representing 109 species, showed antimicrobial activity. Antibacterial activity was more pronounced than antifungal activity. The proportion of extracts from basidiomycetes showing antimicrobial activity was similar to or above that obtained for representative orders of Ascomycetes, such as Pezizales and Xylariales, but lower than that produced by members of the orders Diaporthales, Eurotiales, Hypocreales, Leotiales and Sordariales. Suprageneric taxa (orders and families) did not show pronounced differences in their antimicrobial activities though such differences were observed at the genus level, suggesting that the ability to produce these bioactive compounds is not homogenously distributed amongst the basidiomycetes. Isolates from some species showed large differences in their ability to produce metabolites with antimicrobial activity, possibly reflecting genetic differences at the infraspecific level.