Reconstrucción de neoglande con colgajo uretral para el tratamiento quirúrgico de calcifilaxis peniana

ResumenIntroducciónLa arteriolopatía urémica calcificante, también conocida como calcifilaxis, es una entidad caracterizada por la presencia de áreas de necrosis isquémica junto con extensas calcificaciones de la capa media de las arteriolas de la piel; la etiopatogenia es compleja, las formas de presentación y evolución son diversas. La calcifilaxis del pene es una entidad muy rara. El dolor y la ulceración del glande es una de sus manifestaciones clínicas iniciales, el diagnóstico en estas etapas es difícil de establecer y el manejo debe ser integral. El tratamiento médico seguido del manejo quirúrgico se establecerá de acuerdo a la etapa y evolución de la enfermedad.La reconstrucción aislada del glande se recomienda tras una amputación traumática o quirúrgica por alguna enfermedad benigna o maligna. El objetivo es conseguir una apariencia estética razonable, permitir una micción fisiológica y tratar de conservar la mayor cantidad de tejido eréctil. En pacientes con calcifilaxis peniana, el manejo quirúrgico convencional es radical y consiste en falectomía parcial o total según sea el caso. El manejo conservador ha sido reportado mediante la desbridación de las lesiones ulcerosas en pene, tratamiento local y vigilancia.Caso clínicoSe presenta el caso de un paciente masculino de 59 años de edad con insuficiencia renal crónica en tratamiento con hemodiálisis, hospitalizado por cuadro de 5 días de evolución con úlcera dolorosa en glande, refractaria a manejo analgésico. Se realizó biopsia escisional de la lesión con estudio histopatológico confirmando calcifilaxis. Se plantea a paciente falectomía parcial la cual rechaza por lo que se ofrece reconstrucción en un tiempo como opción terapéutica.ConclusiónUtilizar injertos o colgajos de piel para realizar la reconstrucción del pene en pacientes con calcifilaxis no representa una opción viable. Por su gran aporte vascular, la uretra representa una buena opción de reconstrucción en pacientes con calcifilaxis en etapa inicial. La selección y evaluación de los pacientes debe ser muy cautelosa para que los resultados estéticos y funcionales sean aceptables.AbstractIntroductionCalcific uremic arteriolopathy, also known as calciphylaxis, is an entity characterized by areas of ischemic necrosis with extensive calcifications of the middle layer of the skin arterioles. Its etiopathogenesis is complex and its forms of presentation and progression are diverse. Calciphylaxis of the penis is an extremely rare entity. Pain and ulceration of the glans penis are initial clinical manifestations and diagnosis at these stages is difficult. Management should be comprehensive. Medical treatment, followed by surgical management, is established according to disease stage and progression.Isolated reconstruction of the glans penis is recommended when there is traumatic amputation or a surgical one due to benign or malignant disease. The goal is to obtain a reasonably esthetic appearance, to have physiologic micturition, and to spare the greatest amount of erectile tissue possible. Conventional surgical management in patients with penile calciphylaxis is radical and consists of partial or total phallectomy, depending on the case. Conservative management through ulcerous penile lesion debridement, local treatment, and surveillance has been reported.Case reportA 59-year-old man with chronic renal insufficiency in hemodialysis treatment was hospitalized for symptoms of 5-day progression of a painful ulcer on the glans penis that was refractory to analgesics. An excisional biopsy of the lesion was taken and the histopathologic study confirmed calciphylaxis. Partial phallectomy was suggested to the patient, but he rejected it, and so single stage reconstruction was offered as a therapeutic option.ConclusionThe use of skin grafts or flaps for penile reconstruction in patients with calciphylaxis is not a viable option. Because of its large blood supply, the urethra is a good reconstruction option in patients with initial-stage calciphylaxis. Patient selection and evaluation must be carried out with great care in order to have acceptable functional and esthetic results

Behavioral Responses of a Parasitoid Fly to Rapidly Evolving Host Signals

Animals eavesdrop on signals and cues generated by prey, predators, hosts, parasites, competing species, and conspecifics, and the conspicuousness of sexual signals makes them particularly susceptible. Yet, when sexual signals evolve, most attention is paid to impacts on intended receivers (potential mates) rather than fitness consequences for eavesdroppers. Using the rapidly evolving interaction between the Pacific field cricket, Teleogryllus oceanicus, and the parasitoid fly, Ormia ochracea, we asked how parasitoids initially respond to novel changes in host signals. We recently discovered a novel sexual signal, purring song, in Hawaiian populations of T. oceanicus that appears to have evolved because it protects the cricket from the parasitoid while still allowing males to attract female crickets for mating. In Hawaii, there are no known alternative hosts for the parasitoid, so we would expect flies to be under selection to detect and attend to the new purring song. We used complementary field and laboratory phonotaxis experiments to test fly responses to purring songs that varied in many dimensions, as well as to ancestral song. We found that flies strongly prefer ancestral song over purring songs in both the field and the lab, but we caught more flies to purring songs in the field than reported in previous work, indicating that flies may be exerting some selective pressure on the novel song. When played at realistic amplitudes, we found no preferences–flies responded equally to all purrs that varied in frequency, broadbandedness, and temporal measures. However, our lab experiment did reveal the first evidence of preference for purring song amplitude, as flies were more attracted to purrs played at amplitudes greater than naturally occurring purring songs. As purring becomes more common throughout Hawaii, flies that can use purring song to locate hosts should be favored by selection and increase in frequency

Efficacy and safety of flexible-dose oral sildenafil citrate (Viagra((R))) in the treatment of erectile dysfunction in Brazilian and Mexican men

A 12-week, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of flexible-dose sildenafil citrate (Viagra((R))) treatment (25, 50 or 100 mg) in Brazilian and Mexican men with erectile dysfunction (ED) of broad-spectrum etiology. Efficacy was assessed on the basis of responses to the 15-item International Index of Erectile Function (IIEF) questionnaire, completed at baseline and after 12 weeks of treatment. At end point, mean scores for all IIEF domains of sexual function (erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction) were significantly (P < 0.0001) higher in the sildenafil group (n = 109) than in the placebo group (n = 105). These findings confirm the significant increases in frequency of penetration and frequency of maintained erections reported previously. Sildenafil treatment was well tolerated. the most common adverse events were headache and flushing. in conclusion, sildenafil is a well-tolerated and effective treatment for ED of broad-spectrum etiology in Latin American men.Hosp Albert Einstein, BR-01250000 São Paulo, BrazilTorre Hosp Angeles del Pedregal, Consultorio 827, MexicoFac Ciencias Med Santa Casa, Porto Alegre, RS, BrazilHosp Clin Cuiritiba, Curitiba, Parana, BrazilUniv Estadual Campinas, Fac Ciencias Med, Campinas, SP, BrazilClin Rio Claro, Rio Claro, SP, BrazilUniv Estadual Rio de Janeiro, Fac Med, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilHosp Servidor Publ Estadual, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilWeb of Scienc

Further clinical and molecular delineation of the 15q24 microdeletion syndrome

Background Chromosome 15q24 microdeletion syndrome is a rare genomic disorder characterised by intellectual disability, growth retardation, unusual facial morphology and other anomalies. To date, 20 patients have been reported; 18 have had detailed breakpoint analysis. Aim To further delineate the features of the 15q24 microdeletion syndrome, the clinical and molecular characterisation of fifteen patients with deletions in the 15q24 region was performed, nearly doubling the number of reported patients. Methods Breakpoints were characterised using a custom, high-density array comparative hybridisation platform, and detailed phenotype information was collected for each patient. Results Nine distinct deletions with different breakpoints ranging in size from 266 kb to 3.75 Mb were identified. The majority of breakpoints lie within segmental duplication (SD) blocks. Low sequence identity and large intervals of unique sequence between SD blocks likely contribute to the rarity of 15q24 deletions, which occur 8-10 times less frequently than 1q21 or 15q13 microdeletions in our series. Two small, atypical deletions were identified within the region that help delineate the critical region for the core phenotype in the 15q24 microdeletion syndrome. Conclusion The molecular characterisation of these patients suggests that the core cognitive features of the 15q24 microdeletion syndrome, including developmental delays and severe speech problems, are largely due to deletion of genes in a 1.1-Mb critical region. However, genes just distal to the critical region also play an important role in cognition and in the development of characteristic facial features associated with 15q24 deletions. Clearly, deletions in the 15q24 region are variable in size and extent. Knowledge of the breakpoints and size of deletion combined with the natural history and medical problems of our patients provide insights that will inform management guidelines. Based on common phenotypic features, all patients with 15q24 microdeletions should receive a thorough neurodevelopmental evaluation, physical, occupational and speech therapies, and regular audiologic and ophthalmologic screenin

Mechanisms of Assortative Mating in Speciation with Gene Flow: Connecting Theory and Empirical Research

The large body of theory on speciation with gene flow has brought to light fundamental differences in the effects of two types of mating rules on speciation: preference/trait rules, in which divergence in both (female) preferences and (male) mating traits is necessary for assortment, and matching rules, in which individuals mate with like individuals on the basis of the presence of traits or alleles that they have in common. These rules can emerge from a variety of behavioral or other mechanisms in ways that are not always obvious. We discuss the theoretical properties of both types of rules and explain why speciation is generally thought to be more likely under matching rather than preference/trait rules. We furthermore discuss whether specific assortative mating mechanisms fall under a preference/trait or matching rule, present empirical evidence for these mechanisms, and propose empirical tests that could distinguish between them. The synthesis of the theoretical literature on these assortative mating rules with empirical studies of the mechanisms by which they act can provide important insights into the occurrence of speciation with gene flow. Finally, by providing a clear framework we hope to inspire greater alignment in the ways that both theoreticians and empiricists study mating rules and how these rules affect speciation through maintaining or eroding barriers to gene flow among closely related species or populations

Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844–848

Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000–3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons—Leu844, Cys845, Ala846, Leu847, and Gly848—located in the cysteine-serine-rich domain (CSRD). Collectively, these recurrent missense mutations affect ∼0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. Major superficial plexiform neurofibromas and symptomatic spinal neurofibromas were more prevalent in these individuals compared with classic NF1-affected cohorts (both p < 0.0001). Nearly half of the individuals had symptomatic or asymptomatic optic pathway gliomas and/or skeletal abnormalities. Additionally, variants in this region seem to confer a high predisposition to develop malignancies compared with the general NF1-affected population (p = 0.0061). Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. A genotype-phenotype correlation at the NF1 region 844–848 exists and will be valuable in the management and genetic counseling of a significant number of individuals

Role of deficits in pathogen recognition receptors in infection susceptibility

This work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 to A.C. and SFRH/BPD/96176/2013 to C.C.