INCA (Peru) Study: Impact of Non-Invasive Cardiac Magnetic Resonance Assessment in the Developing World.

Background Advanced cardiac imaging permits optimal targeting of cardiac treatment but needs to be faster, cheaper, and easier for global delivery. We aimed to pilot rapid cardiac magnetic resonance ( CMR ) with contrast in a developing nation, embedding it within clinical care along with training and mentoring. Methods and Results A cross-sectional study of CMR delivery and clinical impact assessment performed 2016-2017 in an upper middle-income country. An International partnership (clinicians in Peru and collaborators from the United Kingdom, United States, Brazil, and Colombia) developed and tested a 15-minute CMR protocol in the United Kingdom, for cardiac volumes, function and scar, and delivered it with reporting combined with training, education and mentoring in 2 centers in the capital city, Lima, Peru, 100 patients referred by local doctors from 6 centers. Management changes related to the CMR were reviewed at 12 months. One-hundred scans were conducted in 98 patients with no complications. Final diagnoses were cardiomyopathy (hypertrophic, 26%; dilated, 22%; ischemic, 15%) and 12 other pathologies including tumors, congenital heart disease, iron overload, amyloidosis, genetic syndromes, vasculitis, thrombi, and valve disease. Scan cost was $150 USD, and the average scan duration was 18±7 minutes. Findings impacted management in 56% of patients, including previously unsuspected diagnoses in 19% and therapeutic management changes in 37%. Conclusions Advanced cardiac diagnostics, here CMR with contrast, is possible using existing infrastructure in the developing world in 18 minutes for $150, resulting in important changes in patient care.

Síndrome de la cimitarra en resonancia magnética cardiovascular / Scimitar syndrome in a cardiovascular magnetic resonance scan

Resumen El síndrome de la cimitarra es una anomalía parcial del retorno venoso pulmonar de características complejas. Está asociado a múltiples malformaciones cardiovasculares y pulmonares, y representa un diagnóstico diferencial importante en los pacientes con dilatación inexplicada de las cavidades derechas. Se expone el caso de una mujer en la cuarta década de la vida, con un cuadro clínico de dolor torácico, episodios sincopales y deterioro de su clase funcional, que por sus hallazgos en la ecocardiografía fue llevada a resonancia magnética cardíaca que mostró anomalía parcial del retorno venoso pulmonar infracardiaca, hallazgo no visualizado en la ecocardiografía, y confirmó el diagnóstico específico de síndrome de la cimitarra.

Abstract Scimitar syndrome is a partial anomaly, of complex characteristics, of pulmonary venous return. It is associated with multiple cardiovascular and lung malformations, and requires a significant differential diagnosis in patients with an unexplained dilation of the right cavities. The case is presented of a woman, in the fourth decade of life, with a clinical picture of chest pain, syncopal episodes, and a deterioration of her functional class. Due to her findings in the echocardiograph, a cardiac magnetic resonance scan was performed that showed an infra-cardiac partial anomalous pulmonary venous return, a finding that was not observed in the echocardiograph, and confirmed the specific diagnosis of scimitar syndrome.

Anillos vasculares, hallazgos por Resonancia Magnética / Vascular rings, Magnetic Resonance findings

Los anillos vasculares son un espectro de patologías en las que el arco aórtico, la arteria pulmonar o la ramificación de los vasos supraaórticos tienen un origen o trayecto anormal y pueden comprimir la tráquea o el esófago, lo cual genera diferentes síntomas, como los respiratorios, que son lo más comunes. Estas patologías pueden estar asociadas a malformaciones cardiacas, del tracto gastrointestinal y en otros sistemas. Se realiza una revisión de la literatura sobre la embriología, epidemiología, clínica y hallazgos imagenológicos en resonancia magnética de los principales anillos vasculares.

Vascular rings are a spectrum of pathologies where the aortic arch, pulmonary artery and/or the supra-aortic vessels have a different origin or an abnormal course; this may or may not produce tracheal and/or esophageal compression. These entities have a variable clinical presentation, with respiratory symptoms being the most common. They are associated with cardiac, gastrointestinal and other system malformations. We reviewed the available literature about the embryology, epidemiology, clinical and Magnetic resonance imaging findings of the most common vascular rings.

Aplicación clínica de la técnica 4D Flow en la evaluación hemodinámica de cardiopatías congénitas / Clinical Applications of 4D Flow in the Hemodynamic Evaluation of Congenital Heart Diseases

La técnica 4D Flow hace referencia a las imágenes de resonancia magnética (RM) adquiridas mediante una secuencia retrospectiva de angiografía contraste de fase, en la cual se obtienen datos de la velocidad de la sangre en las tres direcciones, en un espacio de 3 dimensiones (3D) y a través de todo el ciclo cardiaco. Con las imágenes obtenidas mediante 4D Flow se puede evaluar de forma cuantitativa la dinámica regional y global del flujo sanguíneo con medidas hemodinámicas, tales como: velocidad promedio, máxima y mínima, flujo latido promedio, flujo de avance y regurgitante, volumen de eyección, y aproximaciones matemáticas a los gradientes de presión y fuerzas de cizallamiento en las paredes de los vasos; además, permite analizar cualitativamente la evolución temporal de los complejos patrones de flujo sanguíneo por medio de líneas de flujo, trazadores de partículas, gráficas de velocidad 3D y vectores; representaciones que describen la trayectoria de la sangre, a través del tiempo, en el sistema cardiovascular. Estas características permiten que la técnica tenga muchas aplicaciones potenciales en la práctica clínica, ya que brindan al especialista información valiosa sobre la función y el estado del sistema cardiovascular del paciente. A continuación se evalúa mediante 4D Flow, en algunas patologías congénitas: estenosis valvular pulmonar, conducto arterioso persistente y estenosis aórtica.

4D Flow technique refers to MR images acquired through a phase contrast angiography retrospective sequence, in which blood velocity data are obtained in three directions, in a 3-dimensional space, and through all of the cardiac cycle. With the 4D flow images, the regional and global dynamics of blood flow can be quantitatively analyzed through hemodynamic measurements, such as: average, maximum and minimum velocity, average flow, forward and regurgitation flow, ejection volume, and mathematical approximations to pressure gradients and shear forces in vessel walls; It also allows analyze qualitatively the temporal evolution of complex blood flow patterns through flow lines, particle tracers, 3D velocity graphs and vectors; representations that describe the trajectory of the blood, over time, in the cardiovascular system. These characteristics make the technique have many potential applications in clinical practice, as it provides information on the function and status of the patient's cardiovascular system. In this study we evaluated with the 4D flow technique some congenital pathologies: pulmonary stenosis, patent ductus arteriosus, and aortic stenosis.

Aftosis compleja idiopática. Diagnóstico diferencial / Idiophatic complex aphthosis. Differential diagnosis

Presentamos el caso de una paciente adolescente, estudiada desde los 11 años por episodios de úlceras genitales asociados a aftas bucales. Tras llevar a cabo un complejo proceso de diagnóstico diferencial, se descartó cualquier tipo de agente causal y se etiquetó el cuadro como una aftosis compleja idiopática, que se resolvió espontáneamente aplicando tratamiento sintomático. A pesar de haberse descartado por el momento una enfermedad de Behçet, la paciente es controlada periódicamente, dada la dificultad diagnóstica de esta entidad sobre todo durante los primeros años de evolución (AU)

We report the case of a teenage patient studied since she was 11 years old by episodes of genital ulcers associated with aphthous stomatitis. After carrying out a complex process of differential diagnosis, any kind of causal agent was ruled out and we got the diagnostic of complex aphthosis idiopathic, which resolved spontaneously applying symptomatic treatment. Although having ruled out Behcet’s disease, the patient is monitored periodically, given the difficulty in diagnosing this entity especially during the first years of evolution (AU)

Cardiomiopatías infiltrativas. presentación de un caso de sarcoidosis cardíaca / Cardiomiopatias infiltrativas. apresentação de um caso de sarcoidose cardíaca / Infiltrative cardiomyopathies. report of a case of cardiac sarcoidosis

La sarcoidosis se caracteriza por la presencia de granulomas no caseificantes y puede afectar cualquier órgano. En el corazón se manifiesta como cardiomiopatía infiltrativa. La frecuencia del compromiso cardíaco es alrededor del 30 %, pero solo el 5 % son sintomáticos. Presentamos el caso de una paciente con sarcoidosis sistémica, diagnosticada por biopsia de un ganglio mediastinal y tratada inicialmente con esteroides. Posteriormente tuvo compromiso del corazón, que se manifestó por falla cardíaca y edema pulmonar. El diagnóstico se hizo por ecocardiografía y resonancia magnética cardíaca. Respondió favorablemente al tratamiento con esteroides y ciclofosfamida.

Sarcoidosis is characterized by the presence of non-caseating granulomas that may affect any organ. Heart involvement manifests as cardiomyopathy. Frequency of cardiac involvement in sarcoidosis is around 30 %, but only 5 % of such cases are symptomatic. We report the case of a patient with systemic sarcoidosis diagnosed by means of biopsy of a mediastinal lymph node. Initial treatment was with steroids. She later had cardiac involvement manifested by heart failure and pulmonary edema. Diagnosis was established by echocardiography and cardiac magnetic resonance. Response to treatment with steroids and cyclophosphamide was favorable.

A sarcoidose se caracteriza pela presença de granulomas não caseificantes e pode afetar qualquer órgão. No coração se manifesta como cardiomiopatia infiltrativa. A frequência do compromisso cardíaco é ao redor de 30 %, mas só 5 % são sintomáticos. Apresentamos o caso de uma doente com sarcoidose sistémica, diagnosticada por biopsia de um gânglio mediastinal e tratada inicialmente com esteroides. Posteriormente teve compromisso do coração, que se manifestou por falha cardíaca e edema pulmonar. O diagnóstico se fez por ecocardiografia e ressonância magnética cardíaca. Respondeu favoravelmente ao tratamento com esteroides e ciclofosfamida.

Sarcoidosis cardíaca. Estado del arte / Cardiac sarcoidosis. State of the art / Sarcoidose cardíaca. Estado da arte

La sarcoidosis es una enfermedad infrecuente de etiología desconocida, descrita hace más de 80 años, y caracterizada por un trastorno multisistémico con presencia de lesiones granulomatosas no caseificantes. El compromiso cardíaco es variable según la región estudiada, peroen general se acepta que 5 % de los pacientes con sarcoidosis sistémica tienen infiltración cardíaca con evidencia clínica; sin embargo, estudios de autopsia indican que hasta 20 % a 30 % de los pacientes con sarcoidosis tienen afectación miocárdica. Se han propuesto factores ambientales, ocupacionales e infecciosos como los disparadores del proceso en individuos con predisposición genética. La sarcoidosis cardíaca puede tener un amplio espectro de presentaciones e incluso puede ser asintomática; las manifestaciones más frecuentes son por falla cardíaca, alteraciones del ritmo cardíaco y arritmias ventriculares letales. El tratamiento incluye medicamentos para la falla cardíaca, esteroides e inmunosupresores, tratamiento de las arritmias letales con ablación y/o cardiodesfibrilador implantable y, en casos avanzados, el trasplante cardíaco.

Sarcoidosis is a rare disease of unknown etiology, described over 80 years ago. It is a multisystemic disorder characterized by the presence of granulomatous lesions without caseation. Cardiac involvement varies according to the region, but it is generally accepted that 5 % of patients with systemic sarcoidosis have cardiac infiltration with clinical evidence; however, autopsy studies indicate that up to 20 % to 30 % of patients with sarcoidosis have myocardial involvement. Several factors -environmental, occupational and infectious- have been proposed as triggers of the process in individuals with genetic predisposition. Cardiac sarcoidosis may have a wide range of presentations and may even be asymptomatic; the most common manifestations are heart failure, abnormal heart rhythm and lethal ventricular arrhythmias. Treatment includes medications for heart failure, steroids and immune-suppressants, management of lethal arrhythmias with ablation and/or implantable cardioverter defibrillator and cardiac transplantation in severe cases.

A sarcoidose é uma doença infrequente de etiologia desconhecida, descrita há mais de 80 anos, e caracterizada por um transtorno multissistêmica com presença de lesões granulomatosas não caseificantes. O compromisso cardíaco é variável segundo a região estudada, mas em geral se aceita que 5 % dos pacientes com sarcoidose sistémica têm infiltração cardíaca com evidência clínica; porém, estudos de autopsia indicam que até 20 % a 30 % dos pacientes com sarcoidose têm afetação miocárdica. Se há proposto fatores ambientais, ocupacionais e infecciosos como os disparadores do processo em indivíduos com predisposição genética. A sarcoidose cardíaca pode ter um amplo espectro de apresentações e incluso pode ser assintomática; as manifestações mais frequentes são por falha cardíaca, alterações do ritmo cardíaco e arritmias ventriculares letais. O tratamento inclui medicamentos para a falha cardíaca, esteroides e imunossupressores, tratamento das arritmias letais com ablação e/ou cardiodesfibrilador implantável e, nos casos avançados, o transplante cardíaco.

Schwannoma benigno retroperitoneal gigante: diagnóstico incidental en paciente con masa pélvica sospechosa de cáncer de ovario / Benign giant retroperitoneal schwannoma: incidental diagnosis in a patient with pelvic mass mimicking ovarian cancer

Las tumoraciones del compartimento sacro son poco frecuentes (1:40.000 ingresos hospitalarios), siendo los tumores benignos más infrecuentes. Los schwannomas son tumores benignos compuestos por células de Schwann con crecimiento lento, permaneciendo las pacientes asintomáticas durante gran parte de su historia natural. Se expone el caso de una paciente de 82 años, sin antecedentes de interés, que presenta masa pélvica y marcadores tumorales negativos, con diagnóstico de sospecha radiológico de cáncer de ovario, filiada como schwannoma benigno retroperitoneal gigante tras estudio anatomopatológico definitivo. Tras tratamiento quirúrgico óptimo, la paciente se encuentra libre de enfermedad tras 5 años de seguimiento (AU)

Sacral tumors are rare (1:40,000 hospital admissions) and benign sacral tumors are even more uncommon. Schwannomas are slow-growing benign tumors composed of Schwann cells and remain asymptomatic for much of their natural history. We report the case of an 82-year-old woman with no relevant medical history and a pelvic mass and negative tumor markers. The presumptive radiological diagnosis was ovarian cancer but the definitive pathological diagnosis was benign giant retroperitoneal schwannoma. After successful surgical treatment, the patient is disease-free after 5 years of follow-up (AU)

Assessment of cardiac volumes using an isotropic whole-heart dual cardiac phase sequence in pediatric patients.

PURPOSE: To evaluate the accuracy of a three-dimensional dual phase (3D DP) whole-heart technique for cardiac volumetric assessment in pediatric patients with cardiac abnormalities. MATERIALS AND METHODS: The institutional approved this study, and informed consent was obtained from patients or their guardians. This prospective study involved 31 pediatric patients (mean age, 7.9 years; range, 15 days to 15 years) for the assessment of cardiac abnormalities using cardiovascular MR. A standard protocol was performed for assessing cardiac anatomy and function. For evaluating the 3D DP technique, statistical comparison with a 2D cine multi-slice technique (2D steady-state free-precession [SSFP]) was performed using linear regression, intraclass correlation coefficient, and Bland Altman plots. RESULTS: Left (LV) and right (RV) ventricular cardiac volumes obtained with the 3D DP technique were in strong agreement with those obtained with the 2D SSFP technique for small and large ventricular volumes. The intraclass correlation coefficients (ICC) between both techniques were 0.992 for the LV end-diastolic volume (EDV), 0.983 for the LV end-systolic volume (ESV), 0.952 for the LV-systolic volume (SV), 0.992 for the RV-EDV, 0.992 for the RV-ESV, 0.928 for the RV-SV. Interobserver analysis indicated good reproducibility for both the 2D SSFP and the 3D DP techniques. CONCLUSION: The 3D DP technique provides as accurate cardiac volumes as the 2D SSFP technique in the pediatric population, but with the added benefits of easier data acquisition and detailed anatomical information of the whole heart and great vessels in a single free-breathing scan.

Spanish Menopause Society position statement: use of tibolone in postmenopausal women.

Tibolone is a drug with complex tissue-specific action that exhibits a combination of estrogenic, progestogenic, and slight androgenic activity. Its variable profile explains its clinical effects, depending on the target tissue where it is metabolized, its metabolites' affinity for and potency in hormone receptors, and probable enzymatic activity modulation.In recent reviews and clinical trials, the effectiveness of tibolone in alleviating different hot flush menopause symptoms, mainly in mood and sexuality disorders, has been noted. In Spain, tibolone is the most prescribed hormonal treatment, and one of the most common complaints among postmenopausal women is change in sexual drive. For such reason, a panel of experts from the Spanish Menopause Society met to develop usage recommendations based on the best evidence available.

[Preimplantatory genetic diagnosis and ″saviour sibling″: ethical criteria found in the biomedical and bioethics literature]. / Diagnóstico Genético Preimplantatorio y el ″Bebé Medicamento″: Criterios Éticos Encontrados en la Literatura Biomédica y Bioética.

UNLABELLED: A bibliographic review on <> was performed in order to find out the ethical criteria put forward by the authors on this issue. 23 biomedical and 10 bioethical journals were reviewed and authors for and against the procedure were found. In the Biomedical journals, the main arguments for this issue are that nobody should be hurt and that there is an ethical imperative that is to save a life and that this is preferable to abortion. Those against, believe that an inadequate discrimination against women is being exerted on one hand by subjecting them to a complex, inefficient and dangerous procedure, and on the other, against embryos when many healthy ones are rejected because they are not compatible, or because of the dangers to the embryo, and also the psychological problems for the sick child as well as the donor. In the bioethical journals, we found a higher proportion of papers that are in its favor than in biomedical journals. The arguments are similar to those of the bioethical ones, but there are some particular arguments such as that the autonomy of parents must be respected; that it is a success of the common sense; that it is not an invasive process as it is considered; that it only involves blood donation not a solid organ; that the child that donates will feel accompanied by the saved one and he/she will feel the satisfaction of since having helped someone to live because without this procedure, the baby child would probably not have been born. The arguments against are the discrimination women undergo when they are subjected to this procedure with potential risks for her, the embryos and children. IN CONCLUSION: a) the morality of <> medicine not has been debated in the bioethics and biomedical community before its implementation b) in both communities the majority of authors consider it to be ethically licit; c) paradoxically there is a greater relative percentage of authors who are critical of it within the biomedical field than in bioethics; d) from a personalist bioethics perspective a human embryo is endowed with the dignity of a person and as such must be respected, this technique being an positive eugenics practice, in which, after previous selection health embryos are deprived of their right to exist.

Uso de sedación profunda asistida por un anestesiólogo en resonancia magnética para población pediátrica / The use of profound sedation assisted by the anesthesiologist in pediatric patients undergoing MRI

Introducción. Para la obtención de imágenes con calidad diagnóstica en la población pediátrica por medio de la resonancia magnética es necesario usar la sedación profunda asistida por un anestesiólogo, dado que ésta garantiza la inmovilidad completa del paciente para el adecuado desarrollo del examen. Objetivo. Describir el uso de sedación profunda asistida por un anestesiólogo en los estudios de resonancia magnética para población pediátrica. Métodos. Estudio observacional de serie de casos; se eligieron aleatoriamente 113 exámenes de resonancia magnética asistida por anestesiólogo en pacientes menores de 15 años de edad, atendidos en la Fundación Instituto de Alta Tecnología Médica de Antioquia en el 2009; y para la concordancia entre observadores se evaluaron 84 exámenes con sus respectivas series de imágenes. Resultados. Los tiempos promedio de sedación de las resonancias magnéticas más comunes fueron: cráneo simple, 45,2 ± 12,4 minutos; cráneo contrastado, 46,3 ± 16,7 minutos; cardiaca, 96 ± 24,1 minutos; angio de cráneo, 60 ± 16,8 minutos, y cráneo-columna total, 76,3 ± 32 minutos. Al ajustar por sexo no se hallaron diferencias significativas (p > 0,05). Los medicamentos sedantes empleados para estos exámenes fueron: midazolam, ketamina, propofol, hidrato de cloral y fentanyl. Respecto a la fiabilidad de las series de imágenes de los pacientes con sedación profunda, se halló una excelente concordancia entre observadores (Kappa > 0,9). Conclusión. Se considera la sedación asistida por un anestesiólogo un procedimiento con baja tasa de complicaciones, el cual puede ser usado con mayor frecuencia en la población pediátrica para la obtención de imágenes con calidad diagnóstica en pacientes con comorbilidades y en procedimientos de resonancia magnética complejos.

Objetive. Obtaining diagnostic quality images in the pediatric population using magnetic resonance imaging, requires the use of deep sedation assisted by the anesthesiologist to ensure the totalimmobility of the patient for an adequate examination. Objective. To describe the use of deep sedation assisted by an anesthesiologist in magnetic resonance studies for the pediatric population. Methodos. Observational study of a series ofcases. 113 randomly selected MRI scans, with assisted sedation by an anesthesiologist in pediatric patients aged less than 15, treated at the Fundación Instituto de Alta Tecnología Médica de neAntioquia in 2009. The inter-observer consistency was evaluated in 84 examinations with their corresponding series of images.Results. Average sedation time for the most common MRIs were are follows: cerebral MRI, 45.2 ± 12.4 minutes; cerebral with contrast, 46.3 ± 16.7 minutes; cardiac, 96 ± 24.1 minutes; cerebral angiography, 60 ± 16.8 minutes and cerebral-total spine, 76.3 ± 32 minutes. No significant gender-adjusted differences were found (p > 0.05). The sedatives used for these examinations were: midazolam, ketamine, propofol, chloral hydrate and fentanyl. Excellent inter-observer consistency was found in terms of the reliability of the series of images of deep sedation patients (Kappa > 0.9).Conclusions. Sedation assisted by an anesthesiologist is considered a procedure with a low rate of complications that can be used more often in the pediatric population for obtaining diagnostic quality images in patients with co-morbidities and in complex MRI procedures.

Origen anómalo de la arteria coronaria izquierda en la arteria coronaria derecha y curso ínter-arterial / Anomalous origin of the left coronary artery arising from the right coronary arter

El origen del tronco coronario principal izquierdo a partir de la arteria coronaria derecha o del seno de Valsava opuesto, es una anomalía extremadamente rara con un riesgo potencial de mortalidad. En este informe se describe el caso de una paciente con esta anomalía, inicialmente detectada por coronariografía y posteriormente confirmada mediante resonancia magnética cardiaca.

The left main coronary artery arising from the opposite sinus of Valsalva or from the right coronary artery is an extremely rare condition with a potential risk of mortality. This report describes the case of a female patient with this coronary artery anomaly, initially detected by coronariography and subsequently confirmed by cardiac magnetic resonance.

Fibrosarcoma pericárdico primario: reporte de caso / Pericardial fibrosarc oma primary: case report

En este artículo se presenta el caso de un joven de 14 años de edad, quien presentó un derrame pericárdico masivo y fiebre. Se diagnosticó una masa de implantación pericárdica, que fue resecada quirúrgicamente y confirmada, mediante un estudio histológico e inmunohistoquímico, como un fibrosarcoma de alto grado. Se demostraron las características de esta lesión en diferentes modalidades diagnósticas (ultrasonido, radiografía convencional, tomografía y resonancia magnéticaEn este artículo se presenta el caso de un joven de 14 años de edad, quien presentó un derrame pericárdico masivo y fiebre. Se diagnosticó una masa de implantación pericárdica, que fue resecada quirúrgicamente y confirmada, mediante un estudio histológico e inmunohistoquímico, como un fibrosarcoma de alto grado. Se demostraron las características de esta lesión en diferentes modalidades diagnósticas (ultrasonido, radiografía convencional, tomografía y resonancia magnética).

Male, 14 years, presents massive pericardial effusion and fever. It is diagnosed as a pericardial mass which is surgically excised and then confirmed by histology and immunohistochemestry as a high grade fibrosarcoma. We will demonstrate the features of this uncommon lesion, in different diagnostic modalities (ultrasound, conventionalradiography, tomography and magnetic resonance imaging).

Synthesis and structure-activity relationships of azamacrocyclic C-X-C chemokine receptor 4 antagonists: analogues containing a single azamacrocyclic ring are potent inhibitors of T-cell tropic (X4) HIV-1 replication.

Bis-tetraazamacrocycles such as the bicyclam AMD3100 (1) are a class of potent and selective anti-HIV-1 agents that inhibit virus replication by binding to the chemokine receptor CXCR4, the coreceptor for entry of X4 viruses. By sequential replacement and/or deletion of the amino groups within the azamacrocyclic ring systems, we have determined the minimum structural features required for potent antiviral activity in this class of compounds. All eight amino groups are not required for activity, the critical amino groups on a per ring basis are nonidentical, and the overall charge at physiological pH can be reduced without compromising potency. This approach led to the identification of several single ring azamacrocyclic analogues such as AMD3465 (3d), 36, and 40, which exhibit EC(50)'s against the cytopathic effects of HIV-1 of 9.0, 1.0, and 4.0 nM, respectively, antiviral potencies that are comparable to 1 (EC(50) against HIV-1 of 4.0 nM). More importantly, however, the key structural elements of 1 required for antiviral activity may facilitate the design of nonmacrocyclic CXCR4 antagonists suitable for HIV treatment via oral administration.

[Lack of biological exchange in assisted reproductive techniques]. / Carencias de la comunicación biológica en las técnicas de reproducción asistida.

There is a clear dividing line in the group of actions aimed at solving sterility, and the techniques aimed at generating embryos to be transferred to a womb. The dividing line is now clearly established by science. The growing alarm among paediatricians raised by the higher risk of malformations and diseases in children when generated in vitro, with respect to those normally engendered, is leading to the need to clearly establish the consequences of in vitro technologies and informing society in an honest way. Two types of lack of exchange of information, cellular and molecular, cause the detected defects. In the fi rst place it is clear that both gametes should recognize each other when adequately mature and in the appropriate natural environment. In vitro technologies force these conditions and either one or both gametes might be impaired and consequently negative effects for the child might be caused. In the second place both embryo and maternal womb are deprived of that early mother-child communication facilitating implantation.

Quality by design case study: an integrated multivariate approach to drug product and process development.

To facilitate an in-depth process understanding, and offer opportunities for developing control strategies to ensure product quality, a combination of experimental design, optimization and multivariate techniques was integrated into the process development of a drug product. A process DOE was used to evaluate effects of the design factors on manufacturability and final product CQAs, and establish design space to ensure desired CQAs. Two types of analyses were performed to extract maximal information, DOE effect & response surface analysis and multivariate analysis (PCA and PLS). The DOE effect analysis was used to evaluate the interactions and effects of three design factors (water amount, wet massing time and lubrication time), on response variables (blend flow, compressibility and tablet dissolution). The design space was established by the combined use of DOE, optimization and multivariate analysis to ensure desired CQAs. Multivariate analysis of all variables from the DOE batches was conducted to study relationships between the variables and to evaluate the impact of material attributes/process parameters on manufacturability and final product CQAs. The integrated multivariate approach exemplifies application of QbD principles and tools to drug product and process development.

Usos de la resonancia magnética en la valoración posquirúrgica en pacientes con tetralogía de Fallot / Uses of Magnetic Resonance in Post-Surgical Evaluation of Patients with Tetralogy of Fallot

El número de pacientes con tetralogía de Fallot que sobreviven a la cirugía reparativa completa es cada vez mayor. Por este motivo, las complicaciones tardías de este procedimiento -como insuficiencia pulmonar, disfunción ventricular derecha, arritmias, estenosis de ramas pulmonares o pseudoaneurismas del tracto de salida- son cada vez mas frecuentes en la práctica clínica. La resonancia magnética es el método de imagen de elección para la valoración integral de estos pacientes por su capacidad de valorar la morfología, cuantificación de la función del VD y caracterización de la anatomía y función de la válvula pulmonar. El conocimiento de la embriopatología y anatomía de esta cardiopatía, así como las diferentes intervenciones, correctivas o paliativas y sus complicaciones son indispensables para la adecuada interpretación de las imágenes y contribuyen en la toma de decisiones terapéuticas.