RESUMEN
HIV-1 infection through vertical transmission provides a good model to evaluate intra-host viral evolution and allows to gain insight into the dynamics of viral populations. Our aim was to assess the diversity and dynamics of X4- and R5-using HIV-1 variants in vertically infected children who presented a switch in SI/ NSI phenotype in MT-2 cell assays during chronic infection. Through molecular cloning and next generation sequencing of the C2-V5 env fragment, we investigated HIV-1 evolution and co-receptor usage based on V3 loop prediction bioinformatic tools of longitudinal samples obtained from 4 children. In all cases, the phylogenetic relationships were assessed by Maximum-Likelihood trees constructed with MEGA 6.0. In two cases, V3 loop sequences predicted exclusively R5-using and or X4-using strains, while in another two a higher degree of concordance was observed between the phenotypic and genotypic characteristics. In 3 of the 4 cases, C2-V5 env sequences from different time points were intermingled in phylogenetic trees, with no segregation neither by time or tropism. In only one case monophyletic clustering defined groups of sequences with different co-receptor usage. Comparison of amino acid frequency between isolates with SI and NSI phenotype allowed the identification of 9 possible genetic determinants in subtype F C2-V5 region of env associated to SI/ NSI phenotype in these patients, one of which had previously been reported for subtype B. Overall, we found a low degree of correlation between phenotypic and genotypic properties of HIV-1 quasispecies in patients under chronic infection. Whether HIV-1 subtype or other factors influence the evolution of HIV-1 in vivo will require further research.
Asunto(s)
Infecciones por VIH/transmisión , VIH-1/clasificación , Transmisión Vertical de Enfermedad Infecciosa , Proteínas Virales/genética , Línea Celular , Niño , Clonación Molecular , Femenino , VIH-1/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Estudios Longitudinales , Masculino , Filogenia , Cuasiespecies , Tropismo ViralRESUMEN
Hypersensitivity reaction to abacavir (ABC hypersensitivity syndrome, AHS) is strongly associated with the presence of the HLA-B*57:01 allele. This study was designed to estimate the prevalence of HLA-B*57:01 allele in Argentinean HIV-1 infected patients. We analyzed the presence of HLA-B*57:01 allele in 1646 HIV-1 infected patients from different regions of Argentina. This allele was detected in 81 patients; most of them corresponded to patients living in the central region of the country. The prevalence of HLA-B*57:01 was 4.9%, similar to other Caucasian populations and higher than other data reported for South American populations. This strongly supports screening for the presence of HLA-B*57:01 in abacavir treatment of HIV-1 in our country.
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Fármacos Anti-VIH/efectos adversos , Didesoxinucleósidos/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/genética , Infecciones por VIH/genética , Antígenos HLA-B/genética , Adulto , Alelos , Fármacos Anti-VIH/administración & dosificación , Argentina , Didesoxinucleósidos/administración & dosificación , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/inmunología , Femenino , Expresión Génica , Frecuencia de los Genes , Pruebas Genéticas , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/inmunología , Antígenos HLA-B/inmunología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIM: This study evaluated the efficacy and safety of ileal diversion, using a tracheal cannula, to protect from a low colorectal anastomosis in patients treated with neoadjuvant chemoradiotherapy. METHOD: Fifty patients who presented with rectal cancer and who had accepted neoadjuvant chemoradiotherapy were included. All underwent a low anterior resection with ileal diversion by either tracheal cannula ileostomy (n = 28) or conventional loop ileostomy (n = 22). Demographics, clinical features and operation data were recorded. RESULTS: Two patients developed anastomotic dehiscence after completion of the cannula ileostomy but neither patient required any further operation. There was no difference in anastomotic dehiscence, peritonitis or requirement for further surgery in patients treated with cannula ileostomy and loop ileostomy. CONCLUSION: Cannula ileostomy is a safe, quick, effective and convenient means of intestinal diversion after low anterior resection. Its obvious advantage over loop ileostomy is a reduced overall hospital stay and avoidance of the need to close the stoma.
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Anastomosis Quirúrgica/métodos , Fuga Anastomótica/prevención & control , Quimioradioterapia/métodos , Colon/cirugía , Ileostomía/métodos , Terapia Neoadyuvante/métodos , Neoplasias del Recto/terapia , Recto/cirugía , Adulto , Anciano , Catéteres , Femenino , Humanos , Ileostomía/instrumentación , Tiempo de Internación , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Human immunodeficiency virus (HIV) mother-to-child transmission is a complex event, depending upon environmental factors and is affected by host genetic factors from mother and child, as well as viral genetic elements. The integration of multiple parameters (CD4 cell count, virus load, HIV subtype, and host genetic markers) could account for the susceptibility to HIV infection, a multifactorial trait. The goal of this manuscript is to analyze the immunogenetic factors associated to HIV mother-to-child transmission, trying to unravel the genetic puzzle of HIV mother-to-child transmission and considering the experience in this topic of two research groups from Brazil and Argentina.
Asunto(s)
Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo , Argentina , Brasil , Susceptibilidad a Enfermedades , Femenino , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Humanos , Lactante , Recién Nacido , EmbarazoRESUMEN
Whereas the majority of hot thyroid nodules are caused by somatic TSH-receptor mutations, the percentage of TSH-receptor mutation negative clonal hot nodules (HN) and thus the percentage of hot nodules likely caused by other somatic mutations are still debated. This is especially the case for toxic multinodular goiter (TMNG). 35 HNs [12 solitary hot nodules (SHN), 23 TMNG] were screened for somatic TSHR mutations in the exons 9 and 10 and for Gsα mutations in the exons 7 and 8 using DGGE. Determination of X-chromosome inactivation was used for clonality analysis. Overall TSHR mutations were detected in 14 out of 35 (40%) HNs. A nonrandom X-chromosome inactivation pattern was detected in 18 out of 25 (72%) HNs suggesting a clonal origin. Of 15 TSHR or Gsα mutation negative cases 13 (86.6%) showed nonrandom X-chromosome inactivation, indicating clonal origin. The frequency of activating TSHR and/or Gsα mutations was higher in SHNs (9 of 12) than in TMNGs (6 of 23). There was no significant difference for the incidence of clonality for HNs between TMNGs or SHNs (p: 0.6396). Activating TSHR and/or Gsα mutations were more frequent in SHNs than in TMNG. However, the frequency of clonality is similar for SHN and TMNG and there is no significant difference for the presence or absence of TSHR and/or Gsα mutations of clonal or polyclonal HNs. The high percentage of clonal mutation-negative HNs in SHN and TMNG suggests alternative molecular aberrations leading to the development of TSHR mutation negative nodules.
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Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Mutación/genética , Receptores de Tirotropina/genética , Nódulo Tiroideo/epidemiología , Nódulo Tiroideo/genética , Adulto , Anciano , Animales , Células COS , Chlorocebus aethiops , Células Clonales , Estudios de Cohortes , Femenino , Bocio Nodular/genética , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Prevalencia , Turquía/epidemiología , Adulto JovenRESUMEN
The assessment of tumor vascularization by color flow Doppler sonography (CFDS) has been suggested for the distinction between benign and malignant thyroid nodules. Our objective was to investigate if the CFDS results reflect the percentage of histologically determined microvessels in adenomas (As), adenomatous nodules (ANs), and papillary carcinomas (PCs). Tissue sections from 10 adenomas, 8 ANs and 13 PC and surrounding tissue of 10 PCs and 2 benign nodules were immunostained for CD34. A computerized image analysis was used to determine the microvessel density in four hot spots and ten systematically selected fields. Preoperatively CFDS was performed and classified according to Frates et al. We found a consistent percentage increase of CD34 stained microvessels in PCs (83 and 96%) as compared to adenomas and ANs (38 and 49%) determined by the hot spot analysis and systematic field analysis. A ROC analysis on the basis of the histologically determined number of microvessels demonstrated 70% microvessels as an optimal cut point for the diagnosis of PC with the highest sensitivity of 92% and highest specificity of 89%. The analysis of the CFDS-classification IV for the distinction between PCs and adenomas and ANs showed a sensitivity of 62% with a specificity of 100%. The lower sensitivity of the CFDS classification as compared with the immunohistologic determination of the microvessel density indicates that the CFDS classification detects the pathognomonic intranodular microvessels only incompletely. The higher CFDS specificity is most likely due to the detection of other vascular aspects of malignancy in addition to intranodular microvessels.
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Microvasos/diagnóstico por imagen , Microvasos/patología , Nódulo Tiroideo/irrigación sanguínea , Nódulo Tiroideo/diagnóstico por imagen , Ultrasonografía Doppler en Color , Antígenos CD34/metabolismo , Humanos , Inmunohistoquímica , Neovascularización Patológica/diagnóstico por imagen , Curva ROC , Nódulo Tiroideo/patologíaRESUMEN
OBJECTIVE: For thyroid tumors increased as well as decreased vessel densities have been reported. Because of different morphometric methods and specificities of previously used antibodies for small and large vessels our objective was to investigate and compare the density of large vessels and microvessels by different morphometric methods and antibodies in hot nodules(HN), cold nodules (CN), papillary carcinoma (PC) and Graves' disease (GD) to try to clarify some of these discrepancies. DESIGN: Tissue sections from 29 HN, 22 CN, 19 PC and 8 GD thyroids were stained with the antibodies for CD34 and alpha-SMA. A computerized image analysis was used to calculate the mean area of endothelium (mEA) and the mean endothelium to tumor epithelial nucleus area ratio (mE/N) in four hot spots and ten systematically selected fields. MAIN OUTCOME: We found a consistent increase of the CD34 stained percentage of microvessels in PC as compared to HN and CN determined by the hot spot analysis and systematic field analysis. This increased microvessel density in PC is of a similar magnitude as in GD, which is characterised by a prominent increase of vascularisation during its active disease stage. Our SMA staining results reveal a kind of mirror image of the CD34 staining results with higher vessel counts in the normal surrounding tissues as compared to HN, CN and PC. CONCLUSIONS: The specific immunohistologic detection of microvessels with the CD34 antibody combined with their specific evaluation is able to clearly differentiate PCs from normal tissue, HN and CN.
Asunto(s)
Adenoma/irrigación sanguínea , Vasos Sanguíneos/metabolismo , Carcinoma Papilar/irrigación sanguínea , Glándula Tiroides/irrigación sanguínea , Neoplasias de la Tiroides/irrigación sanguínea , Actinas/metabolismo , Adenoma/metabolismo , Análisis de Varianza , Antígenos CD34/metabolismo , Vasos Sanguíneos/patología , Carcinoma Papilar/metabolismo , Enfermedad de Graves/metabolismo , Enfermedad de Graves/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Neovascularización Patológica/metabolismo , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Neoplasias de la Tiroides/metabolismoRESUMEN
BACKGROUND: The literature on the involvement of mannose-binding lectin (MBL) in human immunodeficiency virus (HIV) transmission and acquired immunodeficiency syndrome (AIDS) is conflicting. Polymorphisms in the MBL2 gene reduce the level of protein and alter its structure. Thus, we investigated whether MBL2 alleles and plasma concentrations of MBL are associated with perinatal HIV transmission and disease progression. METHODS: Frequencies of MBL2 allelic variants (B, C, D, and X) were estimated among 345 HIV-exposed children and 147 blood donors. AIDS-free time was evaluated for different MBL2 genotypes and MBL plasma levels. The median duration of follow-up was 96.5 months. RESULTS: In the Argentinean population, gene frequencies of MBL2 variants were 18%, 15%, and 3% for the X, B, and D alleles, respectively, with no identified C allele. The haplotype XA/XA was associated with an 8-fold risk of acquiring HIV-1 (P= .054; odds ratio [OR], 8.11 [95% confidence interval {CI}, 0.96-67.86]) and almost a 3-fold risk of progression to pediatric AIDS (P= .026; OR, 2.81 [95% CI, 1.14-7.47]). We also found an independent positive correlation between the rate of AIDS progression and MBL plasma concentration (P= .008; OR, 1.28 [95% CI, 1.07-1.55]). CONCLUSIONS: Our results demonstrate that homozygosity for the MBL2 promoter genotype XA/XA is an important genetic determinant of HIV-1 acquisition through vertical transmission and the pathogenesis of pediatric HIV/AIDS, via a mechanism that remains to be established.
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Síndrome de Inmunodeficiencia Adquirida/genética , Infecciones por VIH/transmisión , VIH-1 , Transmisión Vertical de Enfermedad Infecciosa , Lectina de Unión a Manosa/genética , Alelos , Preescolar , Estudios de Cohortes , Progresión de la Enfermedad , Predisposición Genética a la Enfermedad , Genotipo , Infecciones por VIH/genética , Humanos , Lactante , Recién Nacido , Lectina de Unión a Manosa/sangre , Oportunidad RelativaRESUMEN
Infestation of corn (Zea mays) by corn earworm (Helicoverpa zea) predisposes the plant to infection by Aspergillus fungi and concomitant contamination with the carcinogenic mycotoxin aflatoxin B1 (AFB1). Although effects of ingesting AFB1 are well documented in livestock and humans, the effects on insects that naturally encounter this mycotoxin are not as well defined. Toxicity of AFB1 to different stages of H. zea (first, third, and fifth instars) was evaluated with artificial diets containing varying concentrations. Although not acutely toxic at low concentrations (1-20 ng/g), AFB1 had significant chronic effects, including protracted development, increased mortality, decreased pupation rate, and reduced pupal weight. Sensitivity varied with developmental stage; whereas intermediate concentrations (200 ng/g) caused complete mortality in first instars, this same concentration had no detectable adverse effects on larvae encountering AFB1 in fifth instar. Fifth instars consuming AFB1 at higher concentrations (1 microg/g), however, displayed morphological deformities at pupation. That cytochrome P450 monooxygenases (P450s) are involved in the bioactivation of aflatoxin in this species is evidenced by the effects of piperonyl butoxide (PBO), a known P450 inhibitor, on toxicity; whereas no fourth instars pupated in the presence of 1 mug/g AFB1 in the diet, the presence of 0.1% PBO increased the pupation rate to 71.7%. Pupation rates of both fourth and fifth instars on diets containing 1 mug/g AFB1 also increased significantly in the presence of PBO. Effects of phenobarbital, a P450 inducer, on AFB1 toxicity were less dramatic than those of PBO. Collectively, these findings indicate that, as in many other vertebrates and invertebrates, toxicity of AFB1 to H. zea results from P450-mediated metabolic bioactivation.
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Aflatoxina B1/toxicidad , Sistema Enzimático del Citocromo P-450/efectos de los fármacos , Lepidópteros/efectos de los fármacos , Animales , Inhibidores Enzimáticos del Citocromo P-450 , Sistema Enzimático del Citocromo P-450/metabolismo , Activación Enzimática , Inhibidores Enzimáticos/toxicidad , Inactivación Metabólica , Resistencia a los Insecticidas , Larva/efectos de los fármacos , Lepidópteros/fisiología , Sinergistas de Plaguicidas/toxicidad , Fenobarbital/farmacología , Butóxido de Piperonilo/toxicidad , Pruebas de ToxicidadRESUMEN
HIV-1 diagnosis of perinatally exposed children is usually performed by molecular biology-based methods, allowing the direct detection of the virus. Thus, HIV-1 genomic variability within and across strains plays a major role in relation to the sensitivity of these tests, often leading to misdiagnosis. We describe the performance of an in-house multiplex nested PCR (nPCR) for early detection of HIV-1 infection in perinatally exposed children born in Argentina, where the percentage of diverse BF recombinants is as high as 80%. After evaluation of 1316 HIV-1 perinatally exposed children collected over a 7-year period, the specificity and sensitivity of the diagnostic nPCR was of 100% and 99.2% respectively, with only two false negative cases indicating a good performance of the diagnostic nPCR in the Argentine pediatric cohort. In search of unusual HIV-1 subtypes among 22 HIV-1 infected cases presenting partial or complete HIV-1 gene amplification failure, we performed phylogenetic and recombination analysis of a vpu-env fragment in addition to gag and env Heteroduplex Mobility Assay screening. The most unusual findings included two subtypes A and a novel BC recombinant, while the majority of the strains were a variety of different BF recombinants. These results indicate the presence of novel and heterogeneous genotypes in our country and the need of continuous viral surveillance not only for diagnostic test optimization but also for the eventual implementation of a successful vaccine.
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Niño , Femenino , Humanos , Masculino , VIH-1 , Infecciones por VIH/virología , Reacción en Cadena de la Polimerasa/métodos , Recombinación Genética/genética , Argentina , Reacciones Falso Negativas , Genotipo , Análisis Heterodúplex , VIH-1 , Transmisión Vertical de Enfermedad Infecciosa , Infecciones por VIH/diagnóstico , Infecciones por VIH/transmisión , Atención Perinatal , Estudios Retrospectivos , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , Carga ViralRESUMEN
Three isoforms of metallothionein protein induced with Zinc were isolated and purified from housefly larvae, Musca domestica, by gel filtration on Sephadex G-75, G-25 and anion exchange on DEAE-52 chromatography. Among them, one was found to possess antibacterial activity, and was further characterized by SDS-polyacrylamide gel electrophoresis, sulphydryl group determination, enzyme hydrolysis, and spectra property. Our results showed that the novel protein has the characteristics of heat-stable, low-molecular weight (6 kDa), rich-cysteine (approximately 12 cysteine residues in one molecule), metal affinity, and antibacterial activity. This paper was the first to report that metallothionein had antibacterial activity. We expect that this characteristic would give some help to investigate definite physiological functions of metallothionein.
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Antibacterianos/metabolismo , Regulación de la Expresión Génica , Moscas Domésticas , Larva/fisiología , Metalotioneína/metabolismo , Sulfato de Zinc/metabolismo , Animales , Moscas Domésticas/embriología , Moscas Domésticas/metabolismo , Metalotioneína/genética , Pruebas de Sensibilidad Microbiana , Factores de TiempoRESUMEN
AIM: Early diagnosis of the progressive tumor disease and control of the effect of therapy in colorectal carcinoma are most frequently performed by monitoring CEA or CA 19-9 tumor markers. Their clinical application is, however, limited. The aim of our study was to demonstrate the contribution of adhesive molecule assessment to the early diagnosis of progression. We also wanted to find out if changes in the levels of cellular adhesion parameters correlate with the effect of antitumor therapy. MATERIALS AND METHODS: Intercellular cell adhesive molecule-1 (ICAM-1) and Vascular cell adhesive molecule-1 (VCAM-1) were assessed using the ELISA method, and the results were correlated with CEA and CA 19-9 tumor markers. Three hundred and sixty-four patients with colorectal carcinoma in Dukes' stages B-D were monitored. The results were processed with the SAS 6.2. statistical program and Statistica. RESULTS: In 92 patients with first clinical progression (occurrence of distant metastases irrespective of localization), significantly increased ICAM-1 and VCAM-1 values were demonstrated. In ROC evaluation of curves, we also demonstrated high sensitivity of adhesive molecules against both the control healthy group (n =89) and the no evidence of disease group (NED) (n=183). Adhesive molecule levels were closely connected with the type and course of therapy and are presented in the form of case reports. CONCLUSION: Soluble adhesive molecules are a prospective parameter both for the early diagnosis of progression and for control of the effect of therapy. There is a need for a large-scale study, preferably multicentric, which would verify the suitability of introducing cellular adhesion parameter assessment into routine practice.
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Biomarcadores de Tumor/sangre , Adhesión Celular , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/terapia , Moléculas de Adhesión Celular/sangre , Neoplasias Colorrectales/patología , Humanos , Persona de Mediana Edad , Proyectos PilotoRESUMEN
UNLABELLED: Thymidine kinase is involved in nucleic acid synthesis and is, therefore, considered to be an important proliferation tumor marker. For this reason, we monitored this marker in the course of colorectal cancer chemotherapy. MATERIALS AND METHODS: We examined thymidine kinase (TK) levels in 30 patients with colorectal cancer who underwent adjuvant or palliative chemotherapy (CHT schemes). The condition for being included in the study was a minimum of 3 cycles of chemotherapy. TK was always assessed with radio-receptor analysis, before and after every chemotherapy cycle, together with other tumor markers. RESULTS: From the monitored tumor markers, only TK changed typically in the course of chemotherapy. In adjuvant chemotherapy, it was mostly low at the beginning of the cycle and its values usually increased considerably at the end. On the other hand, in palliative chemotherapy the dynamics of TK varied mainly depending on the effect of the therapy. Other tumor markers showed nonstandard behavior and minimal correlation with TK changes. CONCLUSION: Thymidine kinase seems to be a suitable parameter for monitoring the effect of adjuvant and palliative chemotherapy in colorectal cancer.
Asunto(s)
Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/enzimología , Cuidados Paliativos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/enzimología , Timidina Quinasa/metabolismo , HumanosRESUMEN
This presentation is based on our experience with tumor marker monitoring of surgery therapy and chemotherapy effects. The control of chemotherapy is one of the most important problems in oncological practice. The correlation between the clinical status of the patient and tumor size changes, based on the results of different imaging methods, has been the most important and most frequently used method. However, the therapy effect has been recently assessed by markers of the biological activity of the tumor. Using tumor markers for the assessment of the effect of surgery therapy is already part of routine practice in many different types of cancer. Pre-operative and post-operative values of tumor markers are essential for a proper evaluation. However, tumor marker monitoring of the effect of radiotherapy and chemotherapy has been used very rarely, mostly only for research purposes. Besides monitoring by classical tumor markers, monitoring by markers of angiogenesis and apoptosis seem to be promising for the assessment of chemotherapy effect. Measurement of circulating cancer cells by means of mRNA also seems to be intriguing for therapy effect control and monitoring of the course of disease. Unfortunately, the routine use of these methods has been applied in only a few institutes worldwide. A completely different situation has been observed in palliative treatment. In most cases, changes of serum levels of tumor markers correlate with therapy effect. Thus, the effect of treatment on tumor proliferation can be successfully estimated by decreasing tumor marker levels.
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Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Humanos , Proyectos PilotoRESUMEN
El tratamiento antirretroviral de alta eficacia (TAAE) modificó la morbilidad y mortalidad de la infección HIV. Con el objetivo de determinar el efecto del TAAE en la evolucón clínica, virológica e inmunológica y los factores que inciden en dicha respuesta, se realizó este estudio. Métodos: estudio prospectivo, incluyó 228 niños con infección HIV con TAAE desde 01/1998 a 12/2003 seguidos en el hospital. Se calcularon las tasas de incidenica (TI) por 100 pacientes/año de eventos incluídos en las categorías clínicas del CDC y se analizó el efecto sobre la respuesta al TAAE de la edad al inicio del tratamiento, presencia de SIDA, carga viral y % de CD4 basales. A través de las curvas de Kaplan Meir se determinó el efecto de los predictores sobre la ocurrencia de eventos. Resultados: la mediana de edad al inicio del TAAE fue 53 meses, 62% presentaban SIDA. La TI de eventos categoría B pre-TAAE fue de 28,6 por 100 pacientes/año mientras que post-TAAE fue de 20 por 100 pacientes-año (p<0.0001). La TI de eventos C pre -TAAE fue 11.6 por 100 pacientes/año y posterior fue de 1.9 por 100 pacientes/año(p<0.0001). La respuesta de CD4 a los 6 meses fue el predictor más potente de reducción de eventos B y C. La tasa de mortalidad fue de 6% a los 60 meses de TAAE. Conclusiónes: El TAAE se asoció con una marcada reducción de la morbilidad de la infección HIV. Dicha respuesta clínica estuvo asociada a la disminución de la carga viral y la restauración de la función inmunológica.
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Niño , VIH , Infecciones , Terapia Antirretroviral Altamente Activa , Interpretación Estadística de Datos , Estudios ProspectivosRESUMEN
La transmisión vertical es el modo de adquisición más frecuente de la infección HIV en los niños. Desde el año 1997 se encuentra en vigencia en nuestro país el programa de prevención de la transmisión perinatal. Con el objetivo de analizar las características de los niños con diagnóstico reciente de infección HIV y evaluar factores relacionados con el fallo de la prevención realizamos el presente estudio. Estudio retrospectivo. Población: niños expuestos al virus HIV en forma vertical que concurrieron al hospital para descartar el diagnóstico. Período enero 2002- julio 2003. Se analizaron los datos demográficos, estadío clínico-inmunológico, lugar de procedencia y antecedentes maternos. Se incluyeron 222 niños, en 64 de ello se confirmó la infección. La edad en el momento del diagnóstico fue 38 meses (mediana) en los niños con infección HIV versus 2 meses en aquellos no infectados. El 64 por ciento de los infectados nació en el período 1998-2003, luego de la incorporación de las recomendaciónes para la prevención de la transmisión vertical y tuvieron en promedio 1.6 internaciones previas con diagnósticos relacionados con la infección HIV. El 78 por ciento de las madres infectadas recibió atención prenatal. Sin embargo solo el 18% de la madres de niños infectados conocía el diagnóstico de HIV en el embarazo. Se observó que 27/64 (42 por ciento) de los niños infectados se encontraban en un estadio clínico inmunológico avanzado en el momento del diagnóstico. El diagnóstico en los niños fue tardio aunque tenían internaciones previas por enfermedades relacionadas al HIV. Es fundamental: implementar acciones para optimizar el programa de prevención de transmisión vertical y mejorar la sospecha diagnóstica de infección HIV en pediatría.
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Lactante , Niño , VIH , Transmisión Vertical de Enfermedad Infecciosa , Atención Prenatal , Diagnóstico Precoz , Control de Enfermedades Transmisibles , Dados Estadísticos , Estudios RetrospectivosRESUMEN
The authors of this study are concerned with the analysis of optimal criteria for the selection of referential groups in the statistical evaluation of tumor markers for early detection of recurrent disease. Although criteria for the selection of optimal referential groups have already been published on a number of occasions (EGTM recommendation), these criteria are not followed in daily routine, which leads to a false interpretation of results and the impossibility of comparing individual studies. The commonest problem is an incorrect determination of cut-off, caused by not following the recommended specificities at 95%, which results in an incorrect assessment of tumor marker sensitivities. Other faulty interpretations happen in consequence of inaccurate and not clearly defined referential groups, which differ from each other by, for example, stage of the disease, length of the follow-up and so on. Comparing tumor marker results still remains a problem, since they are assessed with diagnostic kits from different manufacturers which may misrepresent the final value of the results, and thus imitate remission or progression of the tumor disease. Similarly, mutual comparison of results from prospective and retrospective studies without standardization of clinical conditions leads to an unreliable interpretation. The authors show, through concrete examples, the possibility of a completely different interpretation of the results in identical referential groups in consequence of their inaccurate characteristics.
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Biomarcadores de Tumor/sangre , Neoplasias/diagnóstico , Neoplasias Colorrectales/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Valores de Referencia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
In order to evaluate the frequency distributions of CCR5-Delta 32 and CCR2-64I polymorphisms in an Amerindian population, we tested a total of 42 Chiriguanos individuals that are aboriginal inhabitants of the north west of Argentina. Only one carried the CCR5-Delta 32 allele (0.0238), while 17 out of 35 carried the CCR2-64I mutation, including one homozygous for the mutated allele (0.2571). Although the cohort studied is considered highly endogamic, the HLA genotyping revealed that 8 out of 42 subjects had a gene flow from Caucasian populations. The only heterozygous CCR5+/Delta 32 found and three heterozygous CCR2+/64I belonged to the admix group. In conclusion, the protective deletion CCR5-Delta 32 is practically absent in Chiriguanos whereas the CCR2-64I allele is highly frequent.
Asunto(s)
Indígenas Sudamericanos/genética , Receptores CCR5/genética , Alelos , Argentina , Genotipo , Humanos , Polimorfismo Genético , Receptores CCR2 , Receptores de Quimiocina/genéticaRESUMEN
The role of neutrophils in mediating host inflammation was examined in mice vaccinated with living third-stage infective hookworm larvae (L3). Mice were vaccinated by oral immunization with 500 L3 (Ancylostoma caninum) once every 2 weeks for a total of three immunizations. The vaccinated mice were then challenged intraperitoneally with 2000 L3) 1 week after the final immunization. To stimulate peritoneal production of neutrophils, 2 ml of 2% glycogen were injected intraperitoneally at 16 h prior to the challenge infection. Neutrophils were found to comprise 85% of the peritoneal cell population. L3 from the challenge infection were collected and then examined at timed intervals by inverted light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Greater than a fivefold increase in the total numbers of peritoneal cells was noted in the vaccinated mice as compared to unvaccinated mice. In the peritoneal cavity of vaccinated mice, the neutrophils adhered to the L3 within 2 h, and over 55% of the L3 were surround by clusters of neutrophils to form a sausage-like sheath 4 h later. At 24-72 h after challenge, almost all of the L3 recovered from the vaccinated mice were covered with thick clusters of cells. Both SEM and TEM demonstrated extensive ultrastructural damage to the L3. In contrast, the L3 recovered from the unvaccinated mice appeared to be unaffected by neutrophils. These studies suggest that neutrophils, like macrophages, can have an important role as effector cells in L3-vaccinated mice.