Characterizing the malaria rural-to-urban transmission interface: The importance of reactive case detection.

BACKGROUND: Reported urban malaria cases are increasing in Latin America, however, evidence of such trend remains insufficient. Here, we propose an integrated approach that allows characterizing malaria transmission at the rural-to-urban interface by combining epidemiological, entomological, and parasite genotyping methods. METHODS/PRINCIPAL FINDINGS: A descriptive study that combines active (ACD), passive (PCD), and reactive (RCD) case detection was performed in urban and peri-urban neighborhoods of Quibdó, Colombia. Heads of households were interviewed and epidemiological surveys were conducted to assess malaria prevalence and identify potential risk factors. Sixteen primary cases, eight by ACD and eight by PCD were recruited for RCD. Using the RCD strategy, prevalence of 1% by microscopy (6/604) and 9% by quantitative polymerase chain reaction (qPCR) (52/604) were found. A total of 73 houses and 289 volunteers were screened leading to 41 secondary cases, all of them in peri-urban settings (14% prevalence). Most secondary cases were genetically distinct from primary cases indicating that there were independent occurrences. Plasmodium vivax was the predominant species (76.3%, 71/93), most of them being asymptomatic (46/71). Urban and peri-urban neighborhoods had significant sociodemographic differences. Twenty-four potential breeding sites were identified, all in peri-urban areas. The predominant vectors for 1,305 adults were Anopheles nuneztovari (56,2%) and An. Darlingi (42,5%). One An. nuneztovari specimen was confirmed naturally infected with P. falciparum by ELISA. CONCLUSIONS: This study found no evidence supporting the existence of urban malaria transmission in Quibdó. RCD strategy was more efficient for identifying malaria cases than ACD alone in areas where malaria transmission is variable and unstable. Incorporating parasite genotyping allows discovering hidden patterns of malaria transmission that cannot be detected otherwise. We propose to use the term "focal case" for those primary cases that lead to discovery of secondary but genetically unrelated malaria cases indicating undetected malaria transmission.

Validación del segundo paso de la escalera analgésica de la OMS: ¿es necesario el uso de opioides débiles? / No disponible

Objetivo: Comparar la eficacia, seguridad y tiempo hasta el alivio del dolor por cancer con acetaminofen solo versus acetaminofen mas codeina con el fin de analizar si es necesario el segundo paso de la escalera analgesica de la OMS. Métodos: Se realizo un ensayo clinico controlado, aleatorizado, doble ciego en mayores de 18 anos, con dolor por cancer de intensidad moderada o severa y Karnofsky >= 50/100. Se excluyeron pacientes con antecedentes de drogadiccion, insuficiencia renal o hepatica y embarazo. Se dividieron en dos grupos, uno tratado con acetaminofen y otro con acetaminofen mas codeina. Se realizo una evaluacion inicial y controles diarios durante 7 dias, evaluando analgesia, tiempo hasta el alivio del dolor y efectos colaterales. Se utilizaron las pruebas Chi cuadrado y Fisher para comparar proporciones, T y ANOVA para promedios. La comparacion del tiempo en lograr alivio se realizo mediante una curva de Kaplan-Meier. Resultados: Se asignaron veinte pacientes al grupo de acetaminofen y 16 al de acetaminofen mas codeina. No se presentaron diferencias estadisticamente significativas en la eficacia de los dos tratamientos. El tiempo transcurrido entre la primera dosis y el alivio fue 41 minutos para acetaminofen y 34 minutos para codeina mas acetaminofen (p > 0,05). El grupo de codeina presento mas estrenimiento (p = 0,001). Conclusión: No se presentaron diferencias significativas en eficacia y tiempo hasta el alivio del dolor. El grupo de codeína presentó más estreñimiento que el de acetaminofén (AU)

Objective: Compare the analgesic efficacy and tolerability of acetaminophen versus acetaminophen plus codeine in the relief of cancer-related pain. Methods: This 7-day, prospective, double-blind, randomized, parallel-group study was conducted with 36 patients with cancer pain. Outpatients were eligible for the study if they were aged >= 18 years and had moderate to severe cancer-related pain. Eligible patients were randomly assigned to receive acetaminophen or acetaminophen plus codeine. The primary end point was the proportion of patients who achieved pain relief; the second end point was time to achieve relief pain. Results: Of the 36 patients who participated, 20 received acetaminophen and 16 acetaminophen plus codeine. At baseline there were not differences between the groups. None of the between-group differences in response rates were significant (p > 0,05). The most common adverse effect in codeine group was constipation (p = 0,001). Conclusion: Efficacy was comparable between acetaminophen and acetaminophen plus codeine over 7 days of treatment in this patients with moderate or severe cancer-related pain. Codeine was associated with significantly greater constipation (AU)

Trastornos de coagulación en trauma craneoencefálico / Coagulation disorders in cranioencephalic trauma

La comprensión del proceso de la coagulación ha progresado durante la última década, evolucionando a partir del concepto según el cual la producción del coágulo se iniciaba por acción de las plaquetas y la activación de uno de los dos sistemas separados, la vía extrínseca y la vía intrínseca, al concepto actual que hace énfasis sobre la vía común y un sistema proteolítico que da lugar a la degradación de los coágulos formados y a la prevención de la formación indeseada de coágulos. La alteración de este equilibrio cobra especial importancia en los pacientes con trauma craneoencefálico, en quienes -a la luz de los conocimientos actuales- se pueden presentar trastornos de la coagulación que van desde lesiones procoagulantes, en un extremo, hasta lesiones anticoagulantes, en el otro extremo. La meta de los autores es brindar a los clínicos de una guía de evaluación inicial, de seguimiento y, de las posibilidades terapéuticas disponibles en el momento.

The understanding of the coagulation process has progressed during last decade evolving from the concept according to which the production of the clot begins by means of the action of platelets and the activation of one of two separated systems, the extrinsic route and the intrinsic route, to the present concept that makes emphasis on the common route and a proteolytic system that give rise to the degradation of formed clots and to the undesired prevention of the formation of the clot. The alteration of this balance receives special importance in the patients with brain trauma in those who to the light of the present knowledge may present upheavals of the coagulation which can go from procoagulating injuries in one end to anticoagulating injuries in the other. The goal of the authors is to provide a clinical guide with initial evaluation, pursuit and therapeutic possibiliti.es available at the moment.

Enhanced allograft survival and modulation of T-cell alloreactivity induced by inhibition of MMP/ADAM enzymatic activity.

Recent studies have shown significantly increased expression of matrix metalloproteinases (MMP) and disintegrin-type metalloproteinases (ADAM) during allograft rejection. In this regard, our previous studies have demonstrated contrasting roles for MMP-2 and MMP-9 during allograft rejection: MMP-2-deficiency enhanced allograft survival while MMP-9-deficiency decreased allograft survival. The aim of this study was to determine the effect of broad-spectrum MMP/ADAM inhibition on the pathogenesis of allograft rejection. Toward this, heterotopic BALB/c cardiac allografts were transplanted into C57BL/6 recipients treated with MMP/ADAM inhibitors, GM6001 or doxycycline. Systemic MMP/ADAM inhibition significantly enhanced allograft survival. Functioning allografts recovered from MMP/ADAM inhibitor-treated recipients showed lower cellular infiltration and tissue remodeling than rejected allografts recovered from control recipients. In addition, decreased chemotaxis of CD4+ and CD8+ T cells, B cells and macrophages was observed in vitro in the presence of MMP/ADAM inhibitors. Enhanced T-cell alloreactivity was also observed ex vivo in MMP/ADAM inhibitor-treated recipients and in vitro in the presence of MMP/ADAM inhibitors. These observations were associated with enhanced cytokine, chemokine and growth factor production. These results indicate that MMPs and ADAMs play a critical role in the pathogenesis of allograft rejection and may represent novel therapeutic targets for the treatment and/or prevention of this disease.

Cáncer de seno y hormonoterapia. Estado actual / Breast cancer and hormone therapy. Current state of knowledge

El manejo del cáncer de seno es multidisciplinario e involucra la cirugía, la quimioterapia, la radioterapia y la hormonoterapia. La hormonoterapia es un tratamiento muy antiguo para el manejo efectivo del cáncer de seno hormono-sensible. Cerca de 75 porciento de las pacientes expresan receptores hormonales en el tumor y el estándar de manejo ha sido con antiestrógenos como el tamoxifeno, que se viene usando desde hace más de 25 años en ensayos clínicos con buena respuesta, mejorando la supervivencia libre de enfermedad (SLE) y la supervivencia total (ST) de las pacientes, tanto en mujeres premenopáusicas como postmenopáusicas; por los efectos secundarios sobre endometrio y coagulación, se han venido desarrollando nuevas drogas llamadas inhibidores de aromatasa, que han sido comparados con el tamoxifeno en el estado metastásico y en adyuvancia, con mejores resultados de supervivencia libre de enfermedad con menos efectos secundarios sobre endometrio y menos eventos trombóticos, aunque aumentan el riesgo de osteoporosis y fracturas con su uso prolongado.

Determinación de anomalías cromosómicas y secuencias de ADN amplificadas en cáncer de mama / Establishment Of Chromosomic Abnormalities And Amplified Dna Sequences In Breast Cancer

El cáncer de mama en Colombia, es la tercera causa de muerte en la población en general y la segunda en mujeres. En el año 2002 el 40.5% de los casos se presentaron en mujeres menores de 50 años (Pardo, et al. 2003). El cáncer de mama resulta de múltiples factores, entre los que se incluyen cambios sucesivos en el genoma de células epiteliales originalmente normales, que pueden conducir a la activación de oncogenes, inactivación de genes supresores de tumor y pérdida de función de genes reparadores de daños al ADN. Estas alteraciones pueden también ser producto de anomalías cromosómicas tales como monosomías, trisomías, translocaciones, inversiones, pérdida de material genético y amplificaciones que también afectan la expresión de genes (1) (2) (3) (4). Sin embargo, el orden de aparición de los diferentes eventos no está completamente dilucidado. En este estudio se determinaron las anomalías cromosómicas y secuencias de ADN amplificadas en pacientes con cáncer de mama, tanto en muestras de sangre periférica como de tumor de mama de 30 pacientes. En las dos líneas celulares analizadas se observó una alta frecuencia de monosomías principalmente de los cromosomas X, 6, 7, 9, 17, 19 y 22. Hay una asociación entre las monosomías de los cromosomas 17 y 22 con el estado negativo para los receptores de estrógenos y progestágenos (p=0.027, p=0.050). También se encontró asociación entre la monosomía del cromosoma 19 con edad avanzada (p=0.034), observándose formas más agresivas de la enfermedad cuando ésta estuvo presente. Las monosomías fueron características de carcinomas ductales infiltrantes de todos los grados. En los demás tipos de carcinoma su frecuencia fue más baja. En el presente estudio se encontró una asociación significativa entre algunas anomalías cromosómicas y la enfermedad, no reportadas anteriormente, como fueron algunas monosomías, fragilidades y roturas cromosómicas y cromatídicas. La alta frecuencia de fragilidades encontradas tanto en sangre periférica (fra 9q12 p=0.001 y fra 3p14 p= 0.38) como de fragilidades expresadas espontáneamente (no inducidas por el uso de reactivos específicos) en muestras de tumor de mama (fra 1p11 p= 0.001, fra 2q11 p= 0.002), pueden ser el reflejo de una alta inestabilidad cromosómica en el genoma de estos pacientes, mostrando la utilidad de los estudios de fragilidad en la determinación de individuos en alto riesgo de desarrollar cáncer de mama. En ensayos de FISH no se observaron amplificaciones de los genes ERBb2 y c-myc en los pacientes analizados. Esto concuerda con lo encontrado en la literatura en donde se ha reportado, para este tipo de tumores, una sobre expresión de la proteína sin amplificación del gen, explicada por desregulación de la expresión del gen, a su vez posiblemente debida a mutaciones en la región promotora o a alteraciones, que conducen a un aumento de la tasa de transcripción (5) (6) (7). Los resultados obtenidos, aunque preliminares, aportan nuevos marcadores cromosómicos que pueden orientar el diagnóstico, pronóstico y tratamiento de esta patología.

Breast cancer is the third cause of death in the general population and the second one in Colombian women. In 2002, 40.5% of the cases were of women younger than 50. Breast cancer originates as a result of multiple and consecutive changes in the genome of normal epithelial cells, such as mutations, oncogene activation, inactivation of tumor suppression genes and of DNA damage repairing genes. The latter, can have its origin in chromosomal abnormalities such as monosomies, trisomies, translocations, inversions, loss of genetic material and amplifications, which may lead to over-expression of oncoproteins related with a greater risk of tumor progression (1) (2) (3) (4). However, very little is known about the sequence in which the different types of alterations of the genome appear. In the present study, the chromosomal abnormalities and amplified DNA sequences were established in breast cancer patients in both samples of peripheral blood and of tissue from the breast tumor of 30 patients. A high frequency of monosomies, specially those of the chromosomes X, 6, 7, 9, 17, 19 and 22 were observed, with statistically meaningful differences between the monosomies of the chromosomes 17 and 22 and the negative STATE for the estrogen and progesterone receptors (p=0.027, p=0.050) and between the monosomy of the chromosome 19 with an advanced age (p=0.034), indicating more aggressive forms of the disease. The monosomies were characteristic of ductal infiltrating carcinomas of any stage and they were observed in a low frequency in other types of carcinomas. Although relationship between the monosomies, fragilities and BREAKINGS of the chromosome 9 with breast cancer has not been reported by previous studies, these chromosomal abnormalities were found in our study in a representative manner and this finding could constitute a new risk marker in this type of cancer. The high frequency and significance of the fragilities found in peripheral blood and (fra 9q12 p=0.001 y fra 3p14 p= 0.38) those of fragilities spontaneously expressed (not induced by the use of specific REACTIVOS) in breast tumor samples (fra 1p11 p= 0.001, fra 2q11 p= 0.002) may somehow confirm the high chromosomal instability in the genome of these patients, probably allowing these fragility tests to be useful in the early determination of the individuals with a high risk of developing breast cancer. Amplification of the ERBb2 and c-myc genes was not observed in FISH assays in any of the analyzed patients; this agrees with related research, in which an over-expression of the protein without an adequate amplification of the gene has been found in this type of tumors, probably due to mutations in the promoter region and an increase in the transcription rate without there being an amplification of the gene (5) (6) (7). The obtained results, although preliminary, are important due to the fact that they contribute to the search of new chromosomal markers and are also important to the orientation of the diagnosis, prognosis and treatment of this disease.

Effects of drugs acting on adrenergic and adenosine receptors on the intraocular pressure and the activity of adenylyl cyclase in ciliary processes and their sensitivity to pertussis toxin.

The effects of the selective alpha2-adrenergic agonist p-aminoclonidine, the nonselective adrenergic agonist epinephrine, the selective beta2-adrenergic agonist fenoterol and the adenosine A1 agonist R-PIA on intraocular pressure were studied in control and pertussis toxin-pretreated rabbits. Pretreatment of rabbits with pertussis toxin decreased the ocular hypotensive effects of p-aminoclonidine and epinephrine, did not influence the same effects of fenoterol or R-PIA and markedly potentiated the initial ocular hypertensive effects of epinephrine and R-PIA. As far as the action on adenylyl cyclase in ciliary processes is concerned, isoproterenol stimulated its activity in control rabbits and epinephrine exerted dual, i.e. stimulatory and inhibitory effects on the activity of this enzyme. The data obtained with epinephrine and p-aminoclonidine confirm the view that their ocular hypotensive effects are associated with their inhibitory action on adenylyl cyclase and contradict the opinion that the hypotensive action of adrenergic drugs depends on adenylyl cyclase activation.

Differences in response to activation of adenylyl cyclase by various stimulants in human myocardium.

The response of adenylyl cyclase complex in human atrial tissue removed at corrective surgery of normoxemic and hypoxemic congenital heart defects in children to various stimulants was evaluated and related to the oxygenation state of the myocardium. When comparing response to stimulation in normoxemic and hypoxemic atria a higher basal as well as stimulated adenylyl cyclase activity was found in hypoxemic atria; an insignificant stimulatory effect of isoprenaline in normoxemic hearts became significant in the atria of hypoxemic patients. Hypoxemic samples also showed two times higher activity when the total catalytic activity was evaluated by the stimulation with forskolin. Higher stimulatory effect of Gpp/NH/p was also observed in hypoxemic than in normoxemic state. Increased adenylyl cyclase activity might represent one of adaptive mechanisms to hypoxemia in patients with congenital heart defects.