Whole exome trio sequencing reveals a novel LAMP2 mutation found in a male patient with Danon Disease: case report / Secuenciación en trío del exoma revela una nueva mutación LAMP2 encontrada en un paciente masculino con enfermedad de Danon: Reporte de caso

Abstract: Introduction: Danon syndrome was first described by Danon MJ in 1981. This rare disease is a triad consisting of dilated cardiomyopathy, myopathy and mental retardation. The etiology of the disease is associated with mutations in the LAMP2 gene on chromosome X. To date, only mutations in the LAMP2 gene have been associated with the disease. Case presentation: We present the case of a male patient who was initially suspected of being affected by Pompe disease and polymyositis without response to the treatments. He required implantation of pacemakers, and posteriorly a cardioverter defibrillator and isolation of pulmonary veins. Therefore, due to the lack of clarity in the diagnosis, endomyocardial biopsy and genetic studies were performed in order to establish the diagnosis. We found a novel mutation in the LAMP2 gene which had not been reported previously. Discussion: Danon disease is a dominant hereditary syndrome linked to the X chromosome. Danon, specifically is caused by an accumulation of glycogen in muscle cells without alterations in the enzymes responsible for its metabolism. It compromises cardiovascular, muscular and neurological systems, liver and spleen. Cardiac tissue exhibits severe fibrosis, which favors the development of supraventricular and ventricular arrhythmias. As for the diagnosis, the gold standard test is genetic analysis. The treatment is focused on the management of the manifestations that the patient presents, since there is no specific treatment. Conclusions: Danon disease requires further studies in order to obtain epidemiological data for this condition. To date, only mutations in the LAMP2 gene have been documented as the main etiology of Danon disease. We found a single nucleotide deletion in LAMP2 resulting in a frameshift mutation which is the probable cause of Danon disease in this patient.(AU)

Resumen: Introducción: El síndrome de Danon fue descrito por primera vez por MJ Danon en 1981. Esta rara enfermedad es una tríada que consiste en miocardiopatía dilatada, miopatía y retraso mental. La etiología de la enfermedad está asociada con mutaciones en el gen LAMP2 en el cromosoma X. Hasta la fecha, sólo las mutaciones en el gen LAMP2 se han asociado con la enfermedad. Presentación del caso: Presentamos el caso de un paciente masculino que inicialmente se sospechó que estaba afectado por la enfermedad de Pompe y polimiositis sin respuesta a los tratamientos. Requirió la implantación de marcapasos y, posteriormente, un desfibrilador cardioversor y el aislamiento de las venas pulmonares. Entonces, debido a la falta de claridad en el diagnóstico, se realizaron biopsias endomiocardíacas y estudios genéticos para establecer el diagnóstico. Encontramos una nueva mutación en el gen LAMP2 que no se había informado anteriormente. Discusión: La enfermedad de Danon es un síndrome hereditario dominante relacionado con el cromosoma X. Danon, específicamente es causado por una acumulación de glucógeno en las células musculares sin alteraciones en las enzimas responsables de su metabolismo. Compromete los sistemas cardiovascular, muscular y neurológico, el hígado y el bazo. El tejido cardiaco exhibe fibrosis severa, que favorece el desarrollo de arritmias supraventriculares y ventriculares. En cuanto al diagnóstico, la prueba estándar de oro es el análisis genético. El tratamiento se centra en el manejo de las manifestaciones que presenta el paciente, ya que no existe un tratamiento específico. Conclusiones: La enfermedad de Danon requiere más estudios para obtener datos epidemiológicos de esta condición. Hasta la fecha, sólo las mutaciones en el gen LAMP2 se han documentado como la principal etiología de la enfermedad de Danon. Encontramos la eliminación de un solo nucleótido en LAMP2 que resulta en una mutación de cambio de estructura que es la causa probable de la enfermedad de Danon en este paciente.(AU)

Panstrongylus geniculatus and four other species of triatomine bug involved in the Trypanosoma cruzi enzootic cycle: high risk factors for Chagas' disease transmission in the Metropolitan District of Caracas, Venezuela.

BACKGROUND: Chagas' disease is caused by the protozoan Trypanosoma cruzi and is autochthonous to the Americas. Its distribution depends on triatomine bugs that are responsible for the transmission of the disease. In 2005, we reported the presence of Panstrongylus geniculatus as a risk for Chagas' disease transmission in Caracas and neighboring areas. Three massive oral outbreaks occurred in the following years. Here we report the results of a 7-year study on triatomine species found in the Metropolitan District of Caracas (MDC), Venezuela. METHODS: Triatomine species collected by inhabitants of Caracas during 7 years were analyzed for parasite infection and blood meal. Triatomines were found in 31 of the 32 parishes surveyed. Traitomines were examined for the presence of blood and parasites in the digestive tract. Molecular techniques were used for the typing of parasites. RESULTS: A total of 3551 triatomines were captured from 31 of the 32 parishes surveyed. The vast majority of these were identified as P. geniculatus (98.96%), followed by Triatoma nigromaculata (0.59%), Triatoma maculata (0.39%) and Rhodnius prolixus (0.06%). Triatomines were always most abundant between April and June, and 2010 showed the highest number. We found that 54% of the specimens were females, 42.5% males and 3.5% nymphs. Overall, 75.2% of the insects were naturally infected with T. cruzi and 48.7% had fed on blood. Analysis of the adult forms showed that 60% of the females and 31.9 % of the males had blood in their stomachs, and 77.5% of the females and 73.3% of the males were naturally infected with T. cruzi. Nearly all, 99.6% of the T. cruzi isolates analyzed belonged to the TcI genotype. CONCLUSIONS: Blood-fed triatomine bugs infected with T. cruzi were distributed throughout Caracas. Four different species of triatomines were identified of which P. geniculatus was by far the most predominant. Our previous report of Eratyrus mucronatus raises the number of triatomine species in the MDC to 5. Dramatic modifications to the surrounding natural habitats have led to the establishment of a T. cruzi urban enzootic cycle, resulting in a high risk for Chagas' disease transmission in this capital city.

Transcatheter aortic valve replacement: techniques, complications, and bailout strategies.

Transcatheter aortic valve replacement has emerged as an alternative option for inoperable or very high-risk patients with severe aortic stenosis-however, there are serious complications associated with the procedure, such as patient mortality, stroke, conduction disturbances, paravalvular regurgitation, and vascular concerns. Our review focuses on the most common complications related to transcatheter aortic valve replacement procedures and potential bailout strategies and techniques.

Molecular epidemiologic source tracking of orally transmitted Chagas disease, Venezuela.

Oral outbreaks of Chagas disease are increasingly reported in Latin America. The transitory presence of Trypanosoma cruzi parasites within contaminated foods, and the rapid consumption of those foods, precludes precise identification of outbreak origin. We report source attribution for 2 peri-urban oral outbreaks of Chagas disease in Venezuela via high resolution microsatellite typing.

Control del vector del dengue utilizando fracciones etéreas de dos plantas (Asteraceae) como larvicidas / Dengue vector control using ether fractions from two plants (Asteraceae) as larvicide

Objetivo Evaluar la actividad larvicida de dos fracciones etéreas de Heli opsisoppositifolia (L.) Drucey Jaegeria hirta (Lag.) Less en larvas de Aedes (Stegomyia) aegypti (L.) de 3-4 ínstar, en el municipio de Armenia, Quindio. Métodos Se realizó la colecta y análisis fitoquímico preliminar de dos especies vegetales, H. oppositifolia y J. hirta. Fueron preparadas fracciones etéreas de las dos especies. Con estas fracciones, fueron evaluadas 11 concentraciones para determinar las concentraciones letales CL50, CL90 y CL95 después de 24 y 48h. Con los resultados de las CL50,CL90 y CL95, se simuló y construyó un modelo que describe la dinámica población-concentración letal. Resultados La marcha fitoquímica preliminar permitió caracterizar en H. oppositifolia y J. hirta la presencia de: Taninos, flavonoides, quinonas, glicósidos cardiotónicos, esteroles, lactonas, terpenos, coumarinas y alcaloides. Las CL, 48 después para J. hirta (CL5024 CL9070 y CL9593 ppm) fueron menores que H. oppositifolia (CL5039, CL9077y CL9594 ppm). El ANOVA factorial confirmó esta tendencia, J. hirta (66 %, F=18.5, p<0.05) y H. oppositifolia (34 %, F=18.5, p<0.05). La simulación matemática sugiere que la aplicación cada 15 días de la CL50, y cada 30 días de las CL90 y CL95 de cualquiera de las dos especies, tienen la misma respuesta que la utilización de las CL90 y CL95 cada 30 días o la CL50 cada 15 días. Conclusión Ambas especies poseen efecto larvicida. Sin embargo, J. hirta se mostró más promisoria como futuro bioinsecticida para el control de estados inmaduros de Ae. aegypti.(AU)

Objective Evaluating the larvicidal activity of two ether factions from Asteraceae (the aster, daisy or sunflower family, i.e. Heli opsisoppositifolia (L.) Druce (oxeye, sunflower-like) and Jaegeria hirta (Lag.) Less (weed-like)) on Aedes (Stegomyia) aegypti (L.) final third instar or initial fourth instar larvae near the town of Armenia in the Quindío Department in Colombia. Methods H. oppositifolia and J. hirta plants were collected and submitted to phytochemical analysis. Ether fractions were prepared form both species to assess 11 concentrations for determining LC50, LC90 and LC95 lethal concentrations after 24 and 48h. The LC50, LC90 and LC95 results were used to create a mathematical model for describing lethal population-concentration dynamics. Results Phytochemical analysis identified tannins, flavonoids, quinones, cardiac glycosides, sterols, lactones, terpenes, courmarins and alkaloids in H. oppositifolia and J. hirta. LC after 48h regarding J. hirta (LC50 24, LC90 70 and LC95 93ppm) was lower than those for H. oppositifolia (LC50 39, LC90 77 and LC95 94 ppm). A factorial ANOVA test confirmed this trend: 66 %, F=18.5 and p<0.05 for J. hirta and 34 %, F=18.5 and p<0.05 for H. oppositifolia. The mathematical simulation model suggested that using LC50 every 15 days and LC90 and LC95 every 30 days from either of these species led to the same response compared to using LC90 and LC95 every 30 days or LC50 every 15 days. Conclusion Both species had a larvicidal effect. However, J. Hirta turned out to be more promising as an eventual bioinsecticide for controlling A. Aegypti immature states.(AU)

[Dengue vector control using ether fractions from two plants (Asteraceae) as larvicide]. / Control del vector del dengue utilizando fracciones etéreas de dos plantas (Asteraceae) como larvicidas.

OBJECTIVE: Evaluating the larvicidal activity of two ether factions from Asteraceae (the aster, daisy or sunflower family, i.e. Heli opsisoppositifolia (L.) Druce (oxeye, sunflower-like) and Jaegeria hirta (Lag.) Less (weed-like)) on Aedes (Stegomyia) aegypti (L.) final third instar or initial fourth instar larvae near the town of Armenia in the Quindío Department in Colombia. METHODS: H. oppositifolia and J. hirta plants were collected and submitted to phytochemical analysis. Ether fractions were prepared form both species to assess 11 concentrations for determining LC50, LC90 and LC95 lethal concentrations after 24 and 48 h. The LC50, LC90 and LC95 results were used to create a mathematical model for describing lethal population-concentration dynamics. RESULTS: Phytochemical analysis identified tannins, flavonoids, quinones, cardiac glycosides, sterols, lactones, terpenes, courmarins and alkaloids in H. oppositifolia and J. hirta. LC after 48 h regarding J. hirta (LC50 24, LC90 70 and LC95 93 ppm) was lower than those for H. oppositifolia (LC50 39, LC90 77 and LC95 94 ppm). A factorial ANOVA test confirmed this trend: 66 %, F=18.5 and p<0.05 for J. hirta and 34 %, F=18.5 and p<0.05 for H. oppositifolia. The mathematical simulation model suggested that using LC50 every 15 days and LC90 and LC95 every 30 days from either of these species led to the same response compared to using LC90 and LC95 every 30 days or LC50 every 15 days. CONCLUSION: Both species had a larvicidal effect. However, J. Hirta turned out to be more promising as an eventual bioinsecticide for controlling A. Aegypti immature states.

Percutaneous retrograde left ventricular assist support for interventions in patients with aortic stenosis and left ventricular dysfunction.

OBJECTIVES: To evaluate feasibility and technical outcomes in patients with aortic stenosis (AS) who have undergone high-risk procedures with continuous flow left ventricular (LV) assist, with the Impella 2.5 system (Abiomed, Danvers, MA). BACKGROUND: In preparation for transcatheter aortic valve implantation, an increasing number of high-risk patients with severe AS and left ventricular dysfunction are currently considered for percutaneous coronary interventions (PCI) and balloon aortic valvuloplasty (BAV). Hemodynamic support may be required in some patients. METHODS: We reviewed procedural and clinical findings and 30-day outcomes in patients with symptomatic AS who underwent high-risk percutaneous procedures supported by the Impella 2.5 system. All patients carried a high-risk of operative mortality. Impella was used during PCI, BAV, and for hemodynamic support during emergencies. RESULTS: Over a 14-month period, 21 patients with AS underwent insertion of Impella prior to high-risk PCI (n = 3), BAV with subsequent PCI (n = 8), BAV alone (n = 7), or during cardiac arrest immediately following BAV (n = 3). The mean Society of Thoracic Surgeons (STS) predicted mortality risk was 14% (range 7.3-24.7%). Impella was inserted successfully in all patients attempted. Retrograde advancement of two catheters across the aortic valve (for concomitant BAV in 15 patients) was technically feasible. Retrograde continuous flow LV assist produced a reduction in LV end-diastolic pressure and an increase in arterial pressure. Periprocedural complications occurred in 19% (n = 4) patients, with no periprocedural deaths. Mortality at 30 days was 14.2%. CONCLUSION: Our data suggests that continuous flow LV assist with Impella 2.5 can be used in high-risk patients with severe AS who require periprocedural hemodynamic support.

Total aorto-ostial chronic occlusion of the right coronary artery successfully recanalized via retrograde approach.

Chronic total occlusions remain a technical challenge for interventional cardiologists. This group of lesions carries a decreased rate of success and continues to be an important reason for surgical revascularization. Recently, retrograde percutaneous coronary intervention of total occlusions via epicardial and septal perforators was introduced as an alternative approach when a previous antegrade attempt has failed. We describe a unique case where retrograde approach was used as the initial recanalization technique in the absence of a right coronary ostium.

Hemodynamic support with impella 2.5 during balloon aortic valvuloplasty in a high-risk patient.

Aortic stenosis (AS) has been considered an exclusion criterion for the use of the Impella 2.5 catheter. We describe a case in which the Impella catheter was successfully implanted and used for hemodynamic support during balloon aortic valvuloplasty in a high-risk patient of severe AS with a calculated aortic valve area of 0.59 cm2 .

Outcome and cost-effectiveness of cardiopulmonary resuscitation after in-hospital cardiac arrest in octogenarians.

CONTEXT: Octogenarians are the fastest growing segment of the population and little is known about the results of cardiopulmonary resuscitation (CPR) after in-hospital cardiac arrest in this population. OBJECTIVE: We sought to investigate the clinical benefit and cost-effectiveness of CPR after in-hospital cardiac arrest in octogenarians. MAIN OUTCOME MEASURE: Years of life saved. DESIGN: Effectiveness data were obtained from a review of 91,372 hospital discharges from January 1st, 1993 until June 30th, 1996. Cardiac arrest was reported in 956 patients. The study group consisted of 474 patients > or = 80 years old. CPR costs included equipment and training, physician and nursing time and medications. Post-CPR expenses included in-hospital true cost, repeat hospitalizations, physician office visits, nursing home, rehabilitation, and chronic care hospital costs. Life expectancy of the patients who were still alive at the end of the study was estimated from census data. A utility of 0.8 was used to calculate quality-adjusted-life years saved (QALYS). We used a societal perspective for analysis. RESULTS: The study population was 86 +/- 4.8 years old (range 80-103), and 42% were male. Fifty-four patients (11%) were discharged alive, 35 to a chronic care facility and 19 to their home. Assuming that a cardiac arrest without CPR has 100% mortality, 12 octogenarians required treatment with CPR in order to save one life to hospital discharge. Similarly, 29 octogenarian patients with cardiac arrest have to be treated with CPR to net one long-term survivor (mean survival 21 months, with a range from 9 to 48 months). The cost-effectiveness ratio, after estimating the life expectancy of octogenarian survivors, was USD 50,412 per year of life saved, and USD 63,015 per QALYS. However, a utility of 0.5 yielded a cost of USD 100,825 per QALYS. CONCLUSION: In comparison with other life-saving strategies, CPR in octogenarians is effective. The favorable cost-effectiveness ratio is highly dependent on the patients' preference for quality rather than quantity of life, as expressed by the utility assumptions.

Amiloidosis primaria con compromiso oseo a nivel de columna vertebral, hepatomegalia y polineuropatía

Describimos el caso de una paciente con amiloidosis sistémica adquirida, quien presentó compromiso de la columna lumbar con lesiones líticas y fracturas de cuerpos vertebrales por invasión amiloide, polineuropatía documentada por electromiografía y hepatomegalia evidenciada por gamagrafía y examen físico. El compromiso directo de hueso se corroboró por biopsia de L4. La paciente se ha manejado con colchicina fundamentalmente y en la actualidad tiene supervivencia de 12 años y se encuentra en buen estado general. Es el primer caso en la literatura médica confirmado de affeción de columna lumbar por amiloidosis.

Angeítis y granulomatosis alérgica (Síndrome de Churg-strauss). Presentación de un caso sin asma

Se presenta un caso comprobado de síndrome de Churg-Strauss, el tercero que se aplica en el país, con dos características clínicas interesantes: ausencia de asma bronquial y atopia y compromiso predominate a nivel del aparato gastrintestinal. Se hace notar que la ausencia de asma no excluye el diagnóstico.