ABSTRACT
INTRODUCTION: Malnutrition is common in children with congenital heart disease (CHD). Medical treatment and surgical interventions contribute improving the nutritional status of these children. OBJECTIVE: To describe nutritional recovery in children with CHD and associated factors after surgery. PATIENTS AND METHOD: Longitudinal study. 46 Children under 18 years old admitted for CHD surgery between April 2015 and April 2016 were recruited. The following CHD were included: Ventricular septal defect (VSD), Atrial septal defect (ASD), Hypoplastic left heart syndrome (HLHS), Tetralogy of Fallot (TOF), and Transposition of great arteries (dTGA). Children with genetic syndromes and other diseases that could compromise nutritional status were excluded. We obtained demographic, CHD, nasogastric tube use (NGT), nutritional evaluation, and weight and height data at the time of admission and one, three and six months after surgery and. Z-score to assess anthropometric measu res were calculated according to WHO standards. RESULTS: Median age was 8 months (IQR: 3,26), 24 (52%) male, 6 (13%) preterm and 12 (26,1%) small for gestational age (SGA). CHD diagnosis were: 9 (19,6%) VSD, 8 (17,4%) ASD, 12 (26,1%) HLHS, 9 (19,6%) TOF and 8 (17,4%) dTGA. The mean weight-for-heigth-BMI-for-age-z-score (W/H-BMI/AZ) was 0,6 ± 1,5 SD, (28.3% of undernutri tion). The mean heigth-for-age-z-score (H/AZ) was -0,86 ± 1.3sd (21.7% of short stature). We found differences between each CHD and age, use of NGT and been under nutritional follow-up. There was an improvement between H/AZ at admission and 3rd month (p = 0,02), and W/H-BMI/AZ at 3th (p = 0,046) and 6th month (p = 0,001). Use of NGT decreased from admission to 6th month (19 vs 3) (p = 0,0016). We found correlation between admission W/H-BMI/AZ and nutritional recovery (r = -0,7; p < 0,001). CONCLUSION: There is a high prevalence of prematurity, SGA, undernutrition and short stature use of with weight recovery but not in heigth after cardio-surgery.
Subject(s)
Heart Defects, Congenital/surgery , Malnutrition/etiology , Adolescent , Child , Child, Preschool , Female , Heart Defects, Congenital/complications , Humans , Infant , Infant, Newborn , Longitudinal Studies , Male , Malnutrition/diagnosis , Malnutrition/epidemiology , Prospective Studies , Treatment OutcomeABSTRACT
Resumen: Introducción: La desnutrición es frecuente en niños con cardiopatía congénita (CC). El manejo mé dico e intervenciones cardioquirúrgicas contribuyen a mejorar el estado nutricional en estos niños. Objetivo: Describir la recuperación nutricional posterior a cirugía de CC y sus factores asociados. Pacientes y Método: Estudio longitudinal. Se reclutaron 46 sujetos menores de 18 años ingresados para cirugía de CC entre abril de 2015 y abril de 2016. Se incluyeron las siguientes CC: comunica ción interventricular (CIV), comunicación interauricular (CIA), hipoplasia de ventrículo izquierdo (HVI), Tetralogía de Fallot (TOF) y transposición de grandes arterias (dTGA). Se excluyeron los síndromes genéticos y pacientes con otra enfermedad con compromiso nutricional. Se obtuvo al ingreso y los meses 1, 3 y 6 postquirúrgico los datos demográficos, de su CC, uso de sonda naso- gástrica (SNG), control nutricional, peso y talla. Los valores Z de indicadores antropométricos se calcularon según estándares de la OMS. Resultados: La mediana de edad de los pacientes reclutados fue de 8 meses (RIC 3,26); 24 (52%) varones; 6 (13%) prematuros y 12 (26,1%) pequeños para edad gestacional (PEG). Las CC fueron: 9 (19,6%) CIV; 8 (17,4%) CIA; 12 (26,1%) HVI; 9 (19,6%) TOF y 8 (17,4%) dTGA. ZP/T-IMC/E promedio -0,6 (± 1,5DE), 28,3% malnutrición por déficit. ZT/E promedio -0,86 (± 1,3 DE), 21,7% talla baja. Se encontraron diferencias según CC para edad, uso de SNG y tener control nutricional. Hubo una mejoría de ZT/E entre ingreso y tercer mes (p = 0,02) y de ZP/T-IMC/E al tercer (p = 0,046) y sexto mes (p = 0,001). Se disminuyó el uso de SNG, 19 al ingreso y 3 al sexto mes (p = 0,0016). Se encontró una correlación entre ZP/T-IMC/E de ingreso y una recuperación nutricional (r = -0,7; p < 0,001). Conclusiones: En este estudio se encontró una alta prevalencia de prematurez, PEG, malnutrición por déficit y talla baja, con recuperación de peso, pero no de talla post cardiocirugía.
Abstract: Introduction: Malnutrition is common in children with congenital heart disease (CHD). Medical treatment and surgical interventions contribute improving the nutritional status of these children. Objective: To describe nutritional recovery in children with CHD and associated factors after surgery. Patients and Method: Longitudinal study. 46 Children under 18 years old admitted for CHD surgery between April 2015 and April 2016 were recruited. The following CHD were included: Ventricular septal defect (VSD), Atrial septal defect (ASD), Hypoplastic left heart syndrome (HLHS), Tetralogy of Fallot (TOF), and Transposition of great arteries (dTGA). Children with genetic syndromes and other diseases that could compromise nutritional status were excluded. We obtained demographic, CHD, nasogastric tube use (NGT), nutritional evaluation, and weight and height data at the time of admission and one, three and six months after surgery and. Z-score to assess anthropometric measu res were calculated according to WHO standards. Results: Median age was 8 months (IQR: 3,26), 24 (52%) male, 6 (13%) preterm and 12 (26,1%) small for gestational age (SGA). CHD diagnosis were: 9 (19,6%) VSD, 8 (17,4%) ASD, 12 (26,1%) HLHS, 9 (19,6%) TOF and 8 (17,4%) dTGA. The mean weight-for-heigth-BMI-for-age-z-score (W/H-BMI/AZ) was 0,6 ± 1,5 SD, (28.3% of undernutri tion). The mean heigth-for-age-z-score (H/AZ) was -0,86 ± 1.3sd (21.7% of short stature). We found differences between each CHD and age, use of NGT and been under nutritional follow-up. There was an improvement between H/AZ at admission and 3rd month (p = 0,02), and W/H-BMI/AZ at 3th (p = 0,046) and 6th month (p = 0,001). Use of NGT decreased from admission to 6th month (19 vs 3) (p = 0,0016). We found correlation between admission W/H-BMI/AZ and nutritional recovery (r = -0,7; p < 0,001). Conclusion: There is a high prevalence of prematurity, SGA, undernutrition and short stature use of with weight recovery but not in heigth after cardio-surgery.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Malnutrition/etiology , Heart Defects, Congenital/surgery , Prospective Studies , Longitudinal Studies , Treatment Outcome , Malnutrition/diagnosis , Malnutrition/epidemiology , Heart Defects, Congenital/complicationsABSTRACT
INTRODUCCIÓN: Los niños con cardiopatía congénita (CC) presentan alto porcentaje de malnutrición por déficit, siendo difícil la interpretación de su estado nutricional. OBJETIVO: Describir el estado nutricional de lactantes con CC utilizando dos clasificaciones antropométricas y realizar una comparación entre ellas. PACIENTES Y MÉTODO: Estudio de cohorte no concurrente. Se estudiaron menores de 12 meses sometidos a cirugía de CC. Se excluyeron prematuros, pequeños para la edad gestacional, portadores de síndrome genético u otra enfermedad con compromiso nutricional. Se registraron datos demográficos, diagnóstico de CC, peso y talla de ingreso. Se realizó evaluación nutricional comparando estándares OMS según clasificación norma ministerial (CNM) y una Clasificación Antropométrica Integrada (CAI) que define desnutrición si (ZT/E)≤-2 y/o (ZP/T)≤-2, riesgo de desnutrición ZP/T entre -1 a -1,9, eutrofia ZP/T entre -0,9 a +0,9, sobrepeso entre +1 a +1,9 y obesidad ZP/T≥+2. RESULTADOS: Se incluyeron 387 intervenciones, 219 (56,6%) varones, mediana de edad 3,1 meses (RIC:0,4;6,4). Un 26,4% tenían talla baja. Utilizando CNM 55 sujetos presentaron dos diagnósticos por superposición de ZP/E y ZP/T, con CAI no hubo superposición. Al comparar CNM con CAI se encontró diferencia en desnutrición 28,9% versus 38,5%(p = 0,001), riesgo de des nutrición 27,4% versus 16,3%(p = 0,01) y obesidad 4,9% versus 3,3%(p = 0,03) respectivamente. Se encontró correlación entre ZP/E y ZP/T, r = 0,6(p < 0,001) y entre ZP/E y ZT/E, r = 0,6(p < 0,001). Conclusiones: Los niños con CC presentan alto porcentaje de desnutrición y talla baja. Utilizando las mismas mediciones antropométricas CAI no presentó superposición de diagnósticos y detectó más desnutrición. El P/E es útil como tamizaje, pero insuficiente en malnutrición crónica.
INTRODUCTION: Children with congenital heart disease (CHD) present a high percentage of undern utrition and the interpretation of their nutritional assessment is difficult. OBJECTIVE: To describe the nutritional status of infants with CHD using two anthropometric classifications and compare them. PATIENTS AND METHOD: Non-concurrent cohort study. We studied children under 12 months under going cardiac surgery. We excluded preterm infants, small for gestational age, carriers of genetic syndrome or other disease with nutritional compromise. Demographic data, type of CHD, weight and height were recorded. Nutritional assessment was performed using WHO standards per health ministry criteria (HMC) and per an Integrated Anthropometric Classification (IAC), which defines undernutrition if height-for-age Z-score (ZT/E)≤-2 and/or weight-for-height (ZP/T)≤-2, risk of un dernutrition as ZP/T between -1 to -1,9, normal as ZP/T between -0.9 to +0.9, overweight as ZP/T between +1 to +1.9 and obesity as ZP/T≥+2. RESULTS: 387 interventions were included, 219 (56.6%) were males, median age 3.1 months (IQR:0.4;6.4). A 26.4% presented short stature. Using HMC classification 55 subjects presented two diagnoses by overlap of ZP/E and ZP/T, although with IAC there was no overlap. Comparing HMC with IAC, a difference was found in undernutrition, 28.9% versus 38.5% (p = 0.001), risk of undernutrition 27.4% versus 16.3%(p = 0.01) and obesity 4.9% ver sus 3.3% (p = 0.03) respectively. Correlation was found between ZP/E and ZP/T, r = 0.6(p < 0.001) and between ZP/E and ZT/E, r = 0.6 (p < 0.001). CONCLUSIONS: Children with CHD have a high per centage of undernutrition and short stature. Using the same anthropometric measurements IAC did not present overlapping diagnoses and detected more undernutrition. P/E is useful as screening, but insufficient in chronic undernutrition.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Nutrition Assessment , Malnutrition/diagnosis , Growth Disorders/diagnosis , Heart Defects, Congenital/complications , Cohort Studies , Malnutrition/etiology , Malnutrition/epidemiology , Growth Disorders/etiology , Growth Disorders/epidemiology , Heart Defects, Congenital/surgeryABSTRACT
INTRODUCTION: Children with congenital heart disease (CHD) present a high percentage of undern utrition and the interpretation of their nutritional assessment is difficult. OBJECTIVE: To describe the nutritional status of infants with CHD using two anthropometric classifications and compare them. PATIENTS AND METHOD: Non-concurrent cohort study. We studied children under 12 months under going cardiac surgery. We excluded preterm infants, small for gestational age, carriers of genetic syndrome or other disease with nutritional compromise. Demographic data, type of CHD, weight and height were recorded. Nutritional assessment was performed using WHO standards per health ministry criteria (HMC) and per an Integrated Anthropometric Classification (IAC), which defines undernutrition if height-for-age Z-score (ZT/E)≤-2 and/or weight-for-height (ZP/T)≤-2, risk of un dernutrition as ZP/T between -1 to -1,9, normal as ZP/T between -0.9 to +0.9, overweight as ZP/T between +1 to +1.9 and obesity as ZP/T≥+2. RESULTS: 387 interventions were included, 219 (56.6%) were males, median age 3.1 months (IQR:0.4;6.4). A 26.4% presented short stature. Using HMC classification 55 subjects presented two diagnoses by overlap of ZP/E and ZP/T, although with IAC there was no overlap. Comparing HMC with IAC, a difference was found in undernutrition, 28.9% versus 38.5% (p = 0.001), risk of undernutrition 27.4% versus 16.3%(p = 0.01) and obesity 4.9% ver sus 3.3% (p = 0.03) respectively. Correlation was found between ZP/E and ZP/T, r = 0.6(p < 0.001) and between ZP/E and ZT/E, r = 0.6 (p < 0.001). CONCLUSIONS: Children with CHD have a high per centage of undernutrition and short stature. Using the same anthropometric measurements IAC did not present overlapping diagnoses and detected more undernutrition. P/E is useful as screening, but insufficient in chronic undernutrition.
Subject(s)
Growth Disorders/diagnosis , Heart Defects, Congenital/complications , Malnutrition/diagnosis , Nutrition Assessment , Cohort Studies , Female , Growth Disorders/epidemiology , Growth Disorders/etiology , Heart Defects, Congenital/surgery , Humans , Infant , Infant, Newborn , Male , Malnutrition/epidemiology , Malnutrition/etiologyABSTRACT
Background: Congenital anomalies of coronary implantation are unfrequent, only 1 percent of congenital cardiopathies. The anomalous origin of left coronary artery from the pulmonary artery (alcapa) is far more frequent and its manifestations usually arise from myocardial ischemia. Case-report: A male infant 2 month-old that was admitted at our unit with cardiogenic shock and severe metabolic acidosis. The chest X-ray showed cardiomegaly and the echocardiography found diastolic left ventricular dysfunction, with left ventricular shortening fraction of 13 percent, evidence of dilated cardiomyopathy and anomalous insertion of left coronary artery in the left postero-lateral side of pulmonary artery trunk. Connected to mechanical ventilation, he received crystalloids, hemoderivatives, inotropic hemodynamic support, furosemide and calcium continuous infusión. Modérate hypothermia appeared the second and third day after admission. He developed multiorgan dysfunction with cardiogenic shock and non-oliguric renal failure. At the fifth day, he was stable enough to try surgical repair. Coronary transference from pulmonary artery trunk to aorta was performed without serious adverse events. Finally, a month after his admission, he was discharged home. An ambulatory evaluation 3 months after showed normal cardiac function. Comment: Myocardial ischemia is the main manifestation of alcapa. Its signs and symptoms usually start at the end of the first gestational trimester, according to the lower pulmonary vascular resistance. The clinician must be aware in every patient with cardiogenic shock and dilated cardiomyopathy. Surgical repair must be done, although good outcomes can be achieved only with early and reliable diagnosis.
Introducción: Las anomalías de implantación de las arterias coronarias constituyen menos del 1 por ciento de las cardiopatías congénitas. La implantación anómala de la arteria coronaria izquierda (IAACI) es la más frecuente y se presenta habitualmente con manifestaciones de isquemia miocárdica. Caso clínico: Comunicamos un lactante de 2 meses de edad, sexo masculino, quién ingresó con shock cardiogénico y acidosis metabólica grave. Radiografía de tórax con cardiomegalia marcada, ecocardiograma reveló disfunción sistólica ventricular izquierda grave con FAVI 13 por ciento), evidencias de miocardiopatía dilatada y sospecha IAACI (cara posterolateral izquierda tronco arteria pulmonar). Recibió ventilación mecánica, expansores de volumen, transfusión de hemoderivados, drogas inotrópicas, infusión furosemida, hipotermia moderada e infusión de calcio continua. Evolucionó con disfunción orgánica con: shock cardiogénico y falla renal no oligúrica. Al quinto día se logra estabilización y se somete a resolución quirúrgica, efectuándose transferencia coronaria desde tronco de arteria pulmonar a aorta. Fue dado de alta a su domicilio al mes de ingresado. Control ambulatorio a los tres meses con función cardíaca normal. Comentario: IAAC se manifiesta por isquemia miocárdica y los síntomas aparecen habitualmente al ocurrir el descenso de la resistencia vascular pulmonar. El resultado a largo plazo es bueno, si se realiza la revascularización en forma temprana. Su sospecha y búsqueda debe de ser acuciosa, contando con el valioso rol de la evaluación ecocardiográfica, en todo paciente que curse con shock cardiogénico y miocardiopatía dilatada.
Subject(s)
Humans , Male , Infant , Coronary Vessel Anomalies/complications , Coronary Vessel Anomalies/diagnosis , Heart Defects, Congenital/complications , Heart Defects, Congenital/diagnosis , Shock, Cardiogenic/etiology , Ventricular Dysfunction, Left/etiology , Echocardiography , Radiography, ThoracicABSTRACT
INTRODUCTION: The treatment of Parkinson's disease (PD) is based on the use of levodopa and/or dopaminergic agonists. This treatment is associated with motor complications in around 50% of the patients over 5 years of treatment. Numerous risk factors have been related to the onset of this motor complications. AIM: To describe the prevalence and risk factors associated with the occurrence of motor complications in our population. PATIENTS AND METHODS: PD patients in control in a movement disorders center were consecutively recruited. Using a multivariate logistic regression model the risk factors associated with the onset of MC were determined. RESULTS: 124 patients were evaluated. Mean age was 66,2 +/- 10,1 years, the years of PD evolution were 8,1 +/- 5,2 years, the on UPDRS score was 27,7 +/- 14,8 points. A 62% of the patients presented at least one motor complication, a 52% with wearing off and a 47,2% dyskinesias. Both motor complications were present in 39%. The multivariate analysis showed that that female sex and the dose of levodopa equivalents were the risk factors for the occurrence of dyskinesias. For the wearing off the main risk factor were the years of evolution of the PD. CONCLUSIONS: This study shows that the time of evolution of the PD is the main risk factor for the wearing off and the female sex and the dose of levodopa equivalents are the risk factor for the development of dyskinesias. These results are in agreement with the previously reported in the literature for other populations.
Subject(s)
Movement Disorders/etiology , Parkinson Disease/complications , Aged , Antiparkinson Agents/adverse effects , Chile , Disease Progression , Dopamine Agonists/adverse effects , Female , Humans , Levodopa/adverse effects , Middle Aged , Movement Disorders/physiopathology , Multivariate Analysis , Parkinson Disease/drug therapy , Parkinson Disease/physiopathology , Risk FactorsABSTRACT
Introducción. El tratamiento de la enfermedad de Parkinson (EP) se basa principalmente en el uso de levodopa y/o agonistas dopaminérgicos. Este tratamiento se asocia con complicaciones motoras aproximadamente en el 50% de los pacientes a los cinco años. Existen diversos factores de riesgo para el desarrollo de estas complicaciones descritos en otras poblaciones. Objetivo. Describir la prevalencia y factores de riesgo para la aparición de complicaciones motoras en nuestra población de portadores de EP. Pacientes y métodos. Consecutivamente se reclutaron portadores de EP. Mediante un modelo de regresión logística multivariada se determinaron los factores de riesgo asociados con el desarrollo de las complicaciones motoras. Resultados. Se evaluaron 124 pacientes, con una edad media de 66,2 ± 10,1 años, tiempo medio de evolución de la EP de 8,1 ± 5,2 años, y estado motor on mediante UPDRS-III de 27,7 ± 14,8 puntos. Un 62% presentó alguna complicación motora, un 52% deterioro de fin de dosis, un 47,2% discinesias y un 39% ambas complicaciones motoras. El análisis multivariado mostró que el sexo femenino y la dosis de equivalentes de levodopa son los principales factores de riesgo para la aparición de discinesias, mientras que el tiempo de evolución lo es para el desarrollo de deterioro de fin de dosis. Conclusiones. El tiempo de evolución de la EP es el principal factor de riesgo para el desarrollo de deterioro de fin de dosis, mientras que la dosis de fármacos dopaminérgicos y el sexo femenino son los principales para el desarrollo de discinesias. Estos resultados obtenidos en nuestra población son similares a los comunicados en otras series
Introduction. The treatment of Parkinsons disease (PD) is based on the use of levodopa and/or dopaminergic agonists. This treatment is associated with motor complications in around 50% of the patients over 5 years of treatment. Numerous risk factors have been related to the onset of this motor complications. Aim. To describe the prevalence and risk factors associated with the occurrence of motor complications in our population. Patients and methods. PD patients in control in a movement disorders center were consecutively recruited. Using a multivariate logistic regression model the risk factors associated with the onset of MC were determined. Results. 124 patients were evaluated. Mean age was 66,2 ± 10,1 years, the years of PD evolution were 8,1 ± 5,2 years, the on UPDRS score was 27,7 ± 14,8 points. A 62% of the patients presented at least one motor complication, a 52% with wearing off and a 47,2% dyskinesias. Both motor complications were present in 39%. The multivariate analysis showed that that female sex and the dose of levodopa equivalents were the risk factors for the occurrence of dyskinesias. For the wearing off the main risk factor were the years of evolution of the PD. Conclusions. This study shows that the time of evolution of the PD is the main risk factor for the wearing off and the female sex and the dose of levodopa equivalents are the risk factor for the development of dyskinesias. These results are in agreement with the previously reported in the literature for other populations
Subject(s)
Male , Female , Humans , Parkinson Disease/complications , Motor Skills Disorders/epidemiology , Chile/epidemiology , Dyskinesias/epidemiology , Risk Factors , Levodopa/adverse effects , Dopamine/adverse effects , Sex FactorsABSTRACT
BACKGROUND: There are changes in inspiratory breath sound intensity in patients with airway obstruction. Airway narrowing may change sound spectral characteristics. AIM: To define the characteristics of lung sounds at standardized air flow during methacholine challenge and to compare acoustic changes with transcutaneous oxygen tension (PtcO2) during induced airway narrowing. PATIENTS AND METHODS: Forty asthmatic children (20 male) aged 5.2 +/- 1 years and 40 normal children (18 male), aged 5.6 +/- 1 years were studied. All patients were free of respiratory tract infections one month before the study. A methacholine challenge from 0.06 to 8 mg/ml was performed; the test was ended when a fall in PtcO2 of > 20% from baseline was observed or if the final concentration was reached. Subjects breathed through a pneumotachograph aiming at flows of 0.4 to 0.6 l/s. Respiratory sounds were recorded using contact sensors at the suprasternal notch and at the posterior right lower lobe. From average spectra, power at low (100-200 Hz = P1) and high frequencies (400-2000 = P2) was calculated. Frequencies below which 50% (F50) and 99% (SEF90) of the spectral power between 100 and 2000 Hz was contained, were also calculated. RESULTS: In asthmatics, the metacholine concentration at which a 20% fall in PtcO2 was observed, was lower than in normal children (p < 0.05). There was an increase in P1 (p < 0.01) and a reduction in P2 (p < 0.01) during inspiration, in subjects that experienced a 20% reduction in PtcO2. Also, there was an increase in F50 and SEF99 during inspiration in lung sounds, but not over the trachea. CONCLUSIONS: Lung sounds analysis can be useful for the assessment of airway reactivity in asthmatic children.
Subject(s)
Asthma/diagnosis , Bronchoconstrictor Agents , Methacholine Chloride , Respiratory Sounds/diagnosis , Signal Processing, Computer-Assisted , Auscultation/methods , Blood Gas Monitoring, Transcutaneous , Bronchial Provocation Tests , Child , Child, Preschool , Female , Humans , MaleSubject(s)
Pesticides/poisoning , Strychnine/poisoning , Animals , Child , Chile , Dogs , Humans , Male , Poisoning/therapyABSTRACT
Genetic studies have shown that grim is a central genetic switch of programmed cell death in Drosophila; however, homologous genes have not been described in other species, nor has its mechanism of action been defined. We show here that grim expression induces apoptosis in mouse fibroblasts. Cell death induced by grim in mammalian cells involves membrane blebbing, cytoplasmic loss and nuclear DNA fragmentation. Grim-induced apoptosis is blocked by both natural and synthetic caspase inhibitors. We found that grim itself shows caspase-dependent proteolytic processing of its C-terminus in vitro. Grim-induced death is antagonized by bcl-2 in a dose-dependent manner, and neither Fas signalling nor p53 are required for grim pro-apoptotic activity. Grim protein localizes both in the cytosol and in the mitochondria of mouse fibroblasts, the latter location becoming predominant as apoptosis progresses. These results show that Drosophila grim induces death in mammalian cells by specifically acting on mitochondrial apoptotic pathways executed by endogenous caspases. These findings advance our knowledge of the mechanism by which grim induces apoptosis and show the conservation through evolution of this crucial programmed cell death pathway.