Late-onset and long-lasting neutropenias in the young: A new entity anticipating immune-dysregulation disorders.

This study identifies a new chronic form of immune neutropenia in the young with or without detectable indirect anti-neutrophil antibodies, characterized by mild/moderate neutropenia low risk of severe infection (14%), tendency to develop autoimmune phenomena over the course of the disease (cumulative incidence of 58.6% after 20 years of disease duration), leukopenia, progressive reduction of absolute lymphocyte count and a T- and B-cell profile similar to autoimmune disorders like Sjogren syndrome, rheumatoid arthritis, and systemic lupus erythematosus (increased HLADR+ and CD3 + TCRγδ cells, reduced T regulatory cells, increased double-negative B and a tendency to reduced B memory cells). In a minority of patients, P/LP variants related to primary immuno-regulatory disorders were found. This new form may fit the group of "Likely acquired neutropenia," a provisional category included in the recent International Guidelines on Diagnosis and Management of Neutropenia of EHA and EUNET INNOCHRON ACTION 18233. The early recognition of this form of neutropenia would help clinicians to delineate better specific monitoring plans, genetic counseling, and potentially targeted therapies.

The P2X7 receptor is a key modulator of the PI3K/GSK3ß/VEGF signaling network: evidence in experimental neuroblastoma.

Neuroblastoma (NB) is an aggressive pediatric tumor, responsible for 15% of cancer-related deaths in childhood, lacking an effective treatment in its advanced stages. The P2X7 receptor for extracellular ATP was associated to NB cell proliferation and recently emerged as a promoter of tumor engraftment, growth and vascularization. In an effort to identify new therapeutic options for neuroblastoma, we studied the role of P2X7 receptor in NB biology. We first analyzed the effect of P2X7 activation or down-modulation of the main biochemical ways involved in NB progression: the PI3K/Akt/GSK3ß/MYCN and the HIF1α/VEGF pathways. In ACN human NB cells, P2X7 stimulation enhanced PI3K/Akt, while decreasing GSK3ß activity. In the same model, P2X7 silencing or antagonist administration reduced the activity of PI3K/Akt and increased that of GSK3ß, leading to a decrease in cellular glycogen stores. Similarly, P2X7 downmodulation caused a reduction in HIF1α levels and vascular endothelial growth factor (VEGF) secretion. Systemic administration of two different P2X7 antagonists (AZ10606120 or A740003) in nude/nude mice reduced ACN-derived tumor growth. An even stronger effect of P2X7 blockade was obtained in a syngeneic immune-competent neuroblastoma model: Neuro2A cells injected in AlbinoJ mice. Together with tumor regression, treatment with P2X7 antagonists caused downmodulation of the Akt/HIF1α axis, leading to reduced VEGF content and decreased vessel formation. Interestingly, in both experimental models, P2X7 antagonists strongly reduced the expression of the probably best-accepted oncogene in NB: MYCN. Finally, we associated P2X7 overexpression with poor prognosis in advanced-stage NB patients. Taken together, our data suggest that P2X7 receptor is an upstream regulator of the main signaling pathways involved in NB growth, metabolic activity and angiogenesis, and a promising therapeutic target for neuroblastoma treatment.

Criptococosis meníngea asociada al SIDA. Análisis de los pacientes varones HIV (+) con criptococosis meníngea internados en la Sala 11 del Hospital Francisco J Muñiz / Meningeal cryptococcosis associated with AIDS. Analysis of male HIV (+) patients with internal meningeal cryptococcosis in Room 11 of Francisco J Muñiz Hospital

La criptococosis es una micosis sistémica oportunista con distribución universal causada por una levadura capsulada. El Cryptococcus neoformans (C. neoformans). C. neoformans infecta al hombre y a animales susceptibles por vía inhalatoria, provocando en huéspedes inmunocompetentes una primoinfección asintomática. Crece preferentemente en ambientes ricos con componentes nitrogenados, principalmente a partir de las excretas desecadas de las palomas que son ricas en nitrógeno y creatinina, con alto contenido en sales y pH alcalino, cualidades que facilitan la supervivencia del hongo. La diseminación hematógena del agente causal provoca múltiples localizaciones, las cuales se hacen clínicamente evidentes en pacientes con deterioro de la inmunidad mediada por células. A partir de la eclosión del SIDA se produjo un aumento significativo del número de casos, transformándose esta última condición en la causa predisponente más importante de esta micosis. La mayoría de los pacientes con SIDA y criptococosis del SNC presentan signos y síntomas de meningitis o meningoencefalitis subagudas como cefalea, fiebre, parálisis de nervios craneales, letargo, coma o amnesia de varias semanas de evolución. La anfotericina B es el pilar terapéutico del tratamiento. En nuestro estudio analizamos las características demográficas, epidemiológicas, clínicas, el líquido cefalorraquídeo, el diagnóstico micológico y el tratamiento empleado en los pacientes hospitalizados en Sala 11 con diagnóstico de criptococosis meníngea. En la criptococosis meníngea asociada al SIDA, el diagnóstico puede realizarse por el análisis de distintos tipos de especímenes biológicos, siendo los principales el examen microscópico directo del LCR con tinción de tinta china y el cultivo.

Cryptococcosis is a fungal opportunistic infection systemic who has universal distribution, caused by capsulated yeast, Cryptococcus neoformans. C. neoformans infects humans and susceptible animals by inhalation, causing an asymptomatic primary infection in immunocompetent hosts. It grows preterentially in rich environments with nitrogen components, mainly from dried excreta of pigeons that are rich in nitrogen and creatinine, with a high salt content and alkaline pH, qualities which facilitate the survival of the fungus. Haematogenous dissemination of the causative agent leads to multiple locations, which are clinically evident in patients with impairment of cell-mediated immunity. Since the emergence of AIDS, it was a significant in crease in the number of cases, who becomes in the most important predisposing cause of this mycosis. Most patients with AIDS and CNS cryptococcosis have signs and symptoms of subacute meningitis or meningoencephalitis as headache, fever, cranial nerve palsy, lethargy, coma or amnesia of several weeks of evolution. Amphotericin B therapy is the mainstay of treatment. We analyzed the demographic, epidemiological, clinical, cerebrospinal fluid, mycological diagnosis and treatment used for hospitalized patients in the unit 11 of the Infectious Disease Hospital Muñiz with the diagnosis of meningeal cryptococcosis. In meningeal cryptococcosis associated with AIDS, the diagnosis can be performed by the analysis of different types of biological specimens, mainly direct microscopic examination of CSF with India ink staining and culture.

[Disseminated tuberculosis with cutaneous manifestations in AIDS patients. Presentation of 4 cases]. / Tuberculosis diseminada con manifestaciones cutáneas en pacientes con SIDA. A propósito de 4 observaciones.

BACKGROUND: Acute cutaneous miliary tuberculosis is a rare form of Mycobacterium tuberculosis infection which has been described in only 25 published cases in the last 15 years. The appearance of serious disseminated forms of tuberculosis is enhanced by the severe immunodeficiency which characterizes AIDS. METHODS: Four cases are described of disseminated tuberculosis with cutaneous localization clinically described as the acute miliary form. Patients had AIDS and CD4 lymphocyte levels of < 100 cells/mm3. Diagnosis was established in all cases by scraping of cutaneous lesions and direct examination with Ziehl-Neelsen coloration. RESULTS: The 4 patients presented signs and symptoms of disseminated tuberculosis with cutaneous manifestations, without a definite pattern and with localization predominantly on the thorax. Three had BAAR-positive sputum. Multiresistant strains of Mycobacterium tuberculosis were confirmed by antibiogram. One patient infected by a strain sensitive to first-line drugs responded favorably to conventional treatment for disseminated tuberculosis. In the remaining three with multiresistant strains, the evolution of the disease was rapid and unfavorable. CONCLUSIONS: Abrupt appearance of cutaneous lesions in a patient with disseminated tuberculosis and advanced HIV-disease should raise the suspicion of its etiology. Scraping and direct examination using Ziehl-Neelsen coloration is practical, economical and non-invasive diagnostic method.

Micobacterias atípicas: estudio clínico-epidemiológico en 14 pacientes con SIDA / Atypical mycobacterium: clinical-epidemiological study in 14 patients with AIDS

La incidencia de la infección por Micobacterias Atípicas en pacientes con SIDA se ha incrementado en los últimos años. La demora en el diagnóstico, el estadio avanzado de la enfermedad debida al VIH-1, y la elevada resistencia a los agentes antimicrobianos de primera línea hacen que la respuesta al tratamiento sea habitualmente pobre. Se presentan 14 pacientes con SIDA, atendidos en el pabellón 22 del Hospital F.J. Muñiz; 12 presentaron enfermedad por complejo MAI (2 con localización pulmonar y 10 con formas diseminadas) y en dos pacientes se identificó al M.kansasii (uno con enfermedad pulmonar y el otro con enfermedad diseminada). Los criterios de inclusión fueron: para la enfermedad pulmonar, el hallazgo de la micobacteria en dos o más muestras de esputo o LBA, con cuadro clínico compatible; y para la diseminada, el desarrollo de microorganismos en líquidos o tejidos habitualmente estériles. Se describen las características clínicas y epidemiológicas, patrón radiológico y sensibilidad a los antibióticos observadas en los 14 pacientes

Neumonía cavitaria crónica por Rhodococcus equi en dos pacientes con síndrome de inmunodeficiencia adquirida / Pneuromia caavitaria chronic by Rhodococcus equi in two patients with acquired immunodeficiency syndrome

Se comunican dos casos de pacientes seropositivos para el Virus de la Inmunodeficiencia Humana, con diagnóstico de neumonía cavitaria crónica por Rhodococcus equi, que presentan los primeros casos de esta patología registrados en la bibliografía latinoamericana de acuerdo con nuestra búsqueda. Se resumen las diferencias en las formas de presentación en pacientes inmunocompetentes e inmunocomprometidos, con una revisión de los casos reportados en la literatura internacional. Uno de los pacientes permitió evaluar la eficiencia terapéutica del tratamiento indicado

Psychological needs underlying the creative process.

The 25-year follow-up study of the motivation underlying creativity of 10 highly creative women indicated that they create primarily to satisfy inner psychological needs for self-understanding, control, and mastery.

A twenty-five year follow-up study of ten exceptionally creative adolescent girls.

A 25-yr. follow-up of 10 women identified as highly creative during adolescence indicated that most believed they had actualized their creative potential to a moderately high degree. However, only one woman stated that creative expression was a dominant life theme and primary commitment. Factors that facilitate and inhibit creativity over a lifetime are discussed.