RESUMEN
Clonal hematopoiesis can be identified by the presence of somatic mutations in blood or bone marrow even in individuals without a myeloid malignancy. Advances in DNA sequencing have led to the discovery that clonal hematopoiesis is remarkably common and occurs in a wide variety of settings, each often described by unique acronym. These distinctions can be useful as the implications of clonal hematopoiesis depend almost entirely on the clinical context in which it is identified. However, some generalizations can be made. The prevalence of clonal hematopoiesis increases with age, particularly after the fifth decade of life. Clonal hematopoiesis in normal individuals with very small clones is typically benign, while patients with clinically abnormal hematopoiesis, larger clones and more driver gene mutations appear to be at much greater risk. Understanding the significance of clonal hematopoiesis in the various contexts in which it occurs can influence how physicians assess risk, select therapies and counsel their patients. This concise review examines the implications of clonal hematopoiesis in several settings, including normal aging, aplastic anemia, unexplained cytopenias and patients receiving cytotoxic chemotherapy.
Asunto(s)
Células Clonales/patología , Hematopoyesis/fisiología , Envejecimiento , Humanos , Mutación , Medición de RiesgoRESUMEN
The first report of a 7-month-old male with pseudohypoaldosteronism in which unresponsiveness to mineralocorticoids has been demonstrated in the kidney, colon, and sweat and salivary glands is presented here. This is documented by urinary, salivary, and sweat sodium wasting in the presence of elevated urinary aldosterone excretion, plasma aldosterone concentration, and PRA. There was no mineralocorticoid response in the kidney or salivary or sweat glands to the administration of high doses of 9 alpha-flurocortisol. Furthermore, in this patient, the colonic mucosal cells failed to respond to exogenous aldosterone administration. Repeat evaluation at 25 months of age showed persistence of the sodium wasting and multiple target organ insensitivity to administered mineralocorticoid. Since this patient has defective mineralocorticoid response in the major sodium-conserving organs, the only therapy possible was administration of sodium to compensate for total sodium loss.
Asunto(s)
Aldosterona/deficiencia , Fludrocortisona , Hormona Adrenocorticotrópica , Aldosterona/metabolismo , Corticosterona/sangre , Desoxicorticosterona/sangre , Humanos , Hidrocortisona/sangre , Lactante , Masculino , Potasio/metabolismo , Saliva/metabolismo , Sodio/metabolismo , Sudor/metabolismoRESUMEN
We describe a term newborn with tuberous sclerosis who presented with a neonatal brain tumor, diagnosed as a subependymal giant cell astrocytoma. We compare the various imaging modalities used in the diagnosis of this tumor.
Asunto(s)
Neoplasias del Ventrículo Cerebral/complicaciones , Glioma/complicaciones , Esclerosis Tuberosa/complicaciones , Neoplasias del Ventrículo Cerebral/diagnóstico , Ventrículos Cerebrales/patología , Ventriculografía Cerebral , Glioma/diagnóstico , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
Ninety-seven EEGs from 30 premature infants found to have multifocal white matter necrosis on ultrasound (US) or autopsy were reviewed retrospectively. Twenty infants had intraparenchymal echodensities on US that developed into cystic lesions, a finding consistent with periventricular leukomalacia; 8 had intraparenchymal hemorrhages; and 2 had white matter necrosis at autopsy. Four of these infants had no intraventricular hemorrhage. Positive sharp waves in the central (rolandic) regions (PRS) were identified in 22 of these 30 infants (73%) and in 0 of 30 age-matched controls (p less than 0.001). The presence of PRS on the EEG of the premature infant has a high correlation with white matter necrosis rather than with intraventricular hemorrhage. In all cases, this EEG pattern was present prior to the development of cavitations when echodensities were present on US.
Asunto(s)
Encefalopatías/diagnóstico , Encéfalo/fisiopatología , Hemorragia Cerebral/fisiopatología , Enfermedades del Prematuro/fisiopatología , Encefalopatías/patología , Hemorragia Cerebral/diagnóstico , Electroencefalografía , Humanos , Recién Nacido , Enfermedades del Prematuro/diagnóstico , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
The calcium/calmodulin kinase II (CaMKII) autophosphorylation site is thought to be important for plasticity, learning and memory. If autophosphorylation is prevented by a point mutation (T286A) LTP is blocked in the hippocampus and cortex. Conversely, if the point mutation mimics autophosphorylation (T286D) a range of frequencies that normally produce LTP in wild types cause LTD instead. In order to test whether the alphaCaMKII-T286D mutation increases levels of depression in vivo, we examined the effect of the alphaCaMKII-T286D transgene on plasticity induced in the barrel cortex by whisker deprivation. Surprisingly, the mutation did not affect depression or potentiation. However, in animals reared with the transgene turned on from birth, the surround receptive field responses were greater than normal. This effect may be due to the potentiating action of autophosphorylated CaMKII during early development.
Asunto(s)
Proteínas Quinasas Dependientes de Calcio-Calmodulina/biosíntesis , Corteza Cerebral/enzimología , Plasticidad Neuronal , Privación Sensorial/fisiología , Animales , Ácido Aspártico/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Proteínas Quinasas Dependientes de Calcio-Calmodulina/genética , Corteza Cerebral/fisiología , Regulación del Desarrollo de la Expresión Génica , Ratones , Ratones Transgénicos , Plasticidad Neuronal/genética , Neuronas/enzimología , Mutación Puntual , Transmisión Sináptica/fisiología , Treonina/genética , Vibrisas/enzimología , Vibrisas/fisiologíaRESUMEN
A technique to diagnose subependymal hemorrhage (SEH), intraventricular hemorrhage (IVH), intracerebral hemorrhage, and posthemorrhage hydrocephalus in tiny infants, using real time ultrasound studies of the brain ventricular system, is described. This is a bedside technique that visualizes the brain through the fontanelles and the sutures, in three planes: coronal, sagittal, and horizontal. Excellent visualization of the ventricular system, caudate nuclei, the thalamus, the choroid plexus, the corpus callosum, and the foramen of Monro is obtained. This method has good definition using high frequency transducers since there is no bone interference. The ultrasound diagnosis correlated well with computed tomography (CT) and with direct pathologic studies. This technique was more sensitive in diagnosing small IVH/SEH and organized clots than were CT studies. IVH/SEH were found in 90% of 113 infants less than or equal to 34 weeks of gestation; 49% of the hemorrhages were large and 41% were small. Most hemorrhages were found in the first scan, usually shortly after birth. Twenty-one premature infants who never had perinatal asphyxia or respiratory distress syndrome had IVH/SEH. The hemorrhages were followed until disappearance, usually in one to three months in cases of large hemorrhages.
Asunto(s)
Hemorragia Cerebral/diagnóstico , Enfermedades del Prematuro/diagnóstico , Tomografía Computarizada por Rayos X , Ultrasonografía , Ventrículos Cerebrales , Epéndimo , Humanos , Hidrocefalia/diagnóstico , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , MétodosRESUMEN
Human term labor is thought to be initiated by amniotic and chorionic phospholipase A2, an enzyme that liberates arachidonic acid esters from the phospholipids of these membranes, leading to the synthesis of prostaglandins by the placental membranes. The striking association of premature labor with intrauterine infection or contamination, urinary tract infection, and early neonatal sepsis led us to study the microorganisms present in these infections for phospholipase A2 activity. Activity was found in Bacteroides fragilis, Peptostreptococcus, Fusobacterium necrophorum, Streptococcus viridans, Streptococcus fecalis, Streptococcus A and B, Escherichia coli, Klebsiella, Staphylococcus epidermidis, Pneumococcus, Lactobacillus, and Mycoplasma hominis. Bacteroides fragilis, Peptostreptococcus, Fusobacterium, and S viridans had the highest activities. The specific activities of phospholipase A2 from these organisms were several times higher than that of the membrane phospholipase A2 of the amnion and chorion. We postulate that premature labor may be initiated by microorganisms with phospholipase A2 activity from endocervical and/or intrauterine contamination or infection, producing deacylation of arachidonic acid from amniotic phospholipids with increased concentrations of free arachidonic acid and increased prostaglandin synthesis, which triggers labor.
Asunto(s)
Bacterias/enzimología , Trabajo de Parto Prematuro/metabolismo , Fosfolipasas A/análisis , Fosfolipasas/análisis , Vagina/microbiología , Animales , Técnicas Bacteriológicas , Bioensayo/métodos , Venenos Elapídicos , Femenino , Humanos , Macaca mulatta , Fosfolipasas A/aislamiento & purificación , Fosfolipasas A2 , EmbarazoRESUMEN
Amnion and chorion from premature and term placentas after both spontaneous labor and elective cesarean section were assayed for phospholipids and fatty acid composition by 2-dimensional thin-layer chromatography and gas-liquid chromatography. In preterm placental phospholipids, phosphorus concentrations were higher in amnion than in chorion, whereas at term the membranes were similar owing to an increase in phospholipid concentration in the chorion late in gestation. PHosphatidylcholine (PC) accounted for 47% of the total phospholipid phosphorus, followed by sphingomyelin at 20%, phosphatidylethanolamine (PE) at 15%, phosphatidylserine (PS) at 12%, and phosphatidylinositol (PI) at 5%. These percentages were similar for amnion and chorion and they did not change during gestation. The percentage of arachidonic acid (AA) was higher in PS (40 to 65%) than in PE (30 to 53%) and PC (10 to 13%). The percentage of AA was significantly higher in PC, PE, and PS from the amnion in premature pregnancies than in those of the premature chorion. At term, these amnionic and chorionic phospholipids had similar concentrations of AA owing to a significant increase in AA in the chorion late in gestation. Amnionic PE from term and preterm elective cesarean section had a significantly higher percentage of AA than that from preterm and term labor. These data suggest that AA is consumed during labor and that amnionic phospholipids, particularly PE, may be its principal source. The amnion seems to be more important for the storage of AA than the chorion, particularly in preterm pregnancies in which the concentrations of phospholipids and the percentages of AA in PC, PE, and PS were significantly higher than in the chorion.
Asunto(s)
Amnios/análisis , Corion/análisis , Ácidos Grasos/análisis , Glicerofosfatos/análisis , Trabajo de Parto Prematuro/metabolismo , Ácidos Araquidónicos/análisis , Cromatografía en Capa Delgada , Femenino , Humanos , Embarazo , Tercer Trimestre del EmbarazoRESUMEN
Eleven preterm infants (gestational ages 27-35 weeks) with echogenic paraventricular white matter identified shortly after birth were studied with serial echoencephalograms to fully delineate the sonographic findings characterizing the pathologic stages of white-matter necrosis. Echoencephalograms were compared with autopsy findings and CT scans. Cerebral function was assessed by electroencephalograms and later by neurodevelopmental evaluations. Echogenic areas were observed in the paraventricular white matter in the acute stage. Microscopically, the echogenic white matter consisted of vascular congestion and petechial hemorrhages, but not always with foci of necrosis. Anechoic areas, which characterized the chronic stage, corresponded to cavitary lesions, and these generally appeared within 2 weeks of birth. However, six infants had anechoic lesions by day 4, suggesting that the onset of white-matter damage was antenatal. CT showed mildly decreased attenuation when paraventricular echogenic areas alone or in association with small anechoic areas were observed. Markedly decreased attenuation on CT scans corresponded to large anechoic areas. Resolution of the sonographic and CT findings did not indicate normalization of the white matter since all surviving infants were neurologically abnormal at 1 year. Electroencephalograms with central (rolandic) positive sharp waves were associated with echogenic white matter alone or with evolving anechoic areas. All patients with positive sharp waves on electroencephalograms had large anechoic areas in later studies. Early and serial echoencephalograms are necessary to evaluate white-matter necrosis in preterm infants. When echogenic white matter is identified, electroencephalography can suggest the presence of white-matter necrosis.
Asunto(s)
Encefalomalacia/patología , Leucomalacia Periventricular/patología , Ultrasonografía , Ecoencefalografía , Electroencefalografía , Estudios de Seguimiento , Hemorragia/etiología , Humanos , Hidrocefalia/etiología , Recién Nacido , Recien Nacido Prematuro , Leucomalacia Periventricular/complicaciones , Leucomalacia Periventricular/diagnóstico , Leucomalacia Periventricular/fisiopatología , Tomografía Computarizada por Rayos XRESUMEN
Real-time ultrasonography is being used increasingly to establish the diagnosis of and serially assess intraventricular hemorrhage and hydrocephalus in neonates. The procedure requires an open fontanel because scatter from the bone occurs from direct application of the transducer to the skull and bone density precludes satisfactory imaging. With an adult, under circumstances where a bone flap is left out after intracranial procedures and the patient's clinical status is such that the patient cannot be transferred for computed tomographic scanning, real-time ultrasonography allows a safe, noninvasive, bedside demonstration of ventricular size, degree of shift of midline structures, and intraparenchymal and intraventricular lesions.
Asunto(s)
Lesiones Encefálicas/diagnóstico , Cráneo/cirugía , Ultrasonografía , Adulto , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/cirugía , Hemorragia Cerebral/etiología , Femenino , Hematoma/etiología , Humanos , Síndrome de Dificultad Respiratoria/complicacionesRESUMEN
A 7-year-old girl presented with the physical and endocrinological stigmata of Cushing's disease. An adrenocorticotropic hormone (ACTH)-producing pituitary microadenoma was excised. Three weeks after trans-sphenoidal adenomectomy, the patient developed benign intracranial hypertension. Although ACTH levels had decreased to normal, the serum cortisol had fallen to subnormal levels. The child responded to exogenous steroid therapy, which was gradually tapered and discontinued after 5 months. Normal pituitary and adrenal functions persist 2 years later.
Asunto(s)
Adenoma/cirugía , Hormona Adrenocorticotrópica/metabolismo , Síndrome de Cushing , Neoplasias Hipofisarias/cirugía , Seudotumor Cerebral/etiología , Adenoma/metabolismo , Hormona Adrenocorticotrópica/sangre , Niño , Síndrome de Cushing/tratamiento farmacológico , Femenino , Humanos , Neoplasias Hipofisarias/metabolismo , Hueso EsfenoidesRESUMEN
The experience of the Special Care Nursery of the University of California Medical Center, San Diego, in the management of the high risk newborn with progressive ventricular enlargement is reviewed, and the physiopathological basis of progressive ventricular enlargement is analyzed.
Asunto(s)
Hemorragia Cerebral/complicaciones , Hidrocefalia/cirugía , Enfermedades del Prematuro/cirugía , Hemorragia Cerebral/diagnóstico , Ventrículos Cerebrales/cirugía , Derivaciones del Líquido Cefalorraquídeo , Ecoencefalografía , Humanos , Hidrocefalia/diagnóstico , Recién Nacido , Enfermedades del Prematuro/diagnóstico , Peritoneo , Pronóstico , Riesgo , Tomografía Computarizada por Rayos XRESUMEN
Real time echoencephalography (RTE) was used to diagnose and serially follow intracranial pathological conditions in the posterior fossa of infants with a gestational age of less than 34 weeks. The posterior fossa was studied in four planes (coronal, modified coronal, sagittal, and parasagittal) with a sector scanner equipped with a high frequency transducer that was placed on the fontanelles and the sutures. Hemorrhagic complications were easily differentiated from normal anatomy. RTE diagnosis was confirmed with computed tomographic scans (5 patients) and postmortem examination of the brain (18 infants). RTE is a precise and noninvasive technique to visualize hemorrhagic and other forms of abnormalities in the infratentorial compartment.
Asunto(s)
Hemorragia Cerebral/diagnóstico , Ecoencefalografía , Enfermedades del Prematuro/diagnóstico , Fosa Craneal Posterior , Humanos , Recién Nacido , Hemorragia Subaracnoidea/diagnósticoRESUMEN
Fifty-three low birth weight high risk newborns who developed progressive hydrocephalus despite a trial period of intermittent lumbar punctures underwent cribside ventriculoperitoneal shunt placement. They all weighed less than 2000 g at the time of shunting (mean, 1308.6 g +/- 398.2 SD). The operative procedures were performed at a mean age of 31.5 days +/- 16.1 (SD). There were no deaths in this series. During the nursery stay, 14 patients required operative revisions for obstruction. The most common problem was infection, which occurred in 13 (24.5%) after the primary intervention and in another 5 of the 14 (35.7%) patients who required revision. The overall infection rate/patient was 26.9%. Shunt removal and intensive antibiotic therapy cured the infection in all but 1 patient. Premature, low birth weight newborns may undergo ventriculoperitoneal shunting, but close follow-up for complications such as infection and shunt obstruction is always required.
Asunto(s)
Derivaciones del Líquido Cefalorraquídeo , Hidrocefalia/cirugía , Recién Nacido de Bajo Peso , Antibacterianos/uso terapéutico , Derivaciones del Líquido Cefalorraquídeo/efectos adversos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Cavidad Peritoneal , Reoperación , Riesgo , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/etiología , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/etiologíaRESUMEN
Fifty preterm infants (mean birth weight, 1266 +/- 303 g; mean gestational age, 30 +/- 2 weeks) who required a ventriculoperitoneal (VP) shunt for posthemorrhagic hydrocephalus (92% with Grade III or IV hemorrhage) were followed for neurodevelopmental problems. VP shunts were placed at a median age of 29 days (range, 18 to 87 days) after serial lumbar punctures failed to control progressive and symptomatic ventriculomegaly. A total of 34 infants (68%) required one shunt revision or more, and the overall infection rate per patient was 50%. Seven infants died, 2 from shunt infections. The infants were evaluated with audiological, ophthalmological, and neurodevelopmental examinations. Of the survivors, 11 (28%) have severe visual loss and 10 (24%) have hearing impairment. Of the infants, 21 (49%) have severe motor handicaps and 19 (38%) have seizure disorders. Developmental and motor scores were obtained using the Bayley or Knobloch-Gesell scales. Seven infants (18%) have normal developmental outcomes; 26 (60%) have multiple handicaps. Grade IV hemorrhage or the occurrence of seizures was a predictor of poor neurodevelopmental outcome. We conclude that progressive posthemorrhagic hydrocephalus in low birth weight infants is associated with multiple handicaps despite early VP shunt placement.
Asunto(s)
Hemorragia Cerebral/complicaciones , Derivaciones del Líquido Cefalorraquídeo , Hidrocefalia/cirugía , Recién Nacido de Bajo Peso , Desarrollo Infantil , Femenino , Estudios de Seguimiento , Pérdida Auditiva , Humanos , Recién Nacido , Masculino , Parálisis , Cavidad Peritoneal , Complicaciones Posoperatorias , Convulsiones , Trastornos de la VisiónRESUMEN
Data organization has become a strategic target for biologists due to the increasing volume of genomic data available for them. For this purpose, we need a complete knowledge model for representing biological system. In this paper, we deal with both processes for the creation and integration of shareable, reusable domain models within biology, which is a critical issue. In particular, this work introduces a new cooperative development approach for biology ontologies. This approach is based on the integration of the ontologies supplied by different human experts. Two experiments in biological domains are presented and their results discussed.
Asunto(s)
Inteligencia Artificial , Fenómenos Fisiológicos Celulares , Biología Computacional/métodos , Bases de Datos Factuales , Almacenamiento y Recuperación de la Información/métodos , Modelos Biológicos , Biología de Sistemas/métodos , Sistemas de Administración de Bases de Datos , Proteoma , Integración de SistemasRESUMEN
Schizencephaly is a regional disturbance of cerebral hemisphere formation occurring at 3-5 months gestation; neonatal presentation is uncommon. Three neonates with schizencephaly were evaluated with cranial ultrasonography (US), unenhanced computed tomography (CT), and magnetic resonance imaging (MRI) examinations. Common findings in US, CT, and MRI include parasylvian and midline clefts, size asymmetries of the basal ganglia and thalamus, cerebral parenchymal volume loss, ventriculomegaly, ventricular diverticula, and absence of the septum pellucidum. MRI and CT were superior to US in detecting calcification, gyral and sulcal abnormalities, and parasylvian clefts. MRI alone demonstrated homolateral absence of the sylvian vasculature, small medullary pyramids, low position of the fornix, and the thinning of the corpus callosum. Although US appears adequate as a screening test, MRI best defines the precise pathoanatomic findings of neonatal schizencephaly and allows for the prediction of neurologic outcomes in affected newborns.
Asunto(s)
Encéfalo/anomalías , Diagnóstico por Imagen , Epilepsias Parciales/congénito , Hemiplejía/congénito , Discapacidad Intelectual/diagnóstico , Encéfalo/patología , Ecoencefalografía , Epilepsias Parciales/diagnóstico , Femenino , Estudios de Seguimiento , Hemiplejía/diagnóstico , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos XRESUMEN
Encephalocraniocutaneous lipomatosis is a rare hamartomatosis involving the craniofacial region and the central nervous system. The most prominent clinical features are large areas of scalp alopecia, soft subcutaneous craniofacial masses, lipomas, connective tissue nevi of the eyelids and surrounding areas, pterygium-like choriostoma of the ocular conjunctiva, mental retardation, motor deficit, and seizures. Of the eight patients reported previously, three had spinal cord evaluations and two had evidence of lipomatosis. We report the third patient with this association, review the literature of encephalocraniocutaneous lipomatosis, and stress the importance of spinal cord evaluation during the newborn period.
Asunto(s)
Neoplasias Encefálicas/congénito , Lipomatosis/congénito , Neoplasias Cutáneas/congénito , Neoplasias de la Médula Espinal/congénito , Adolescente , Desarrollo Infantil , Humanos , Masculino , MielografíaRESUMEN
The control of the right application of medical protocols is a key issue in hospital environments. For the automated monitoring of medical protocols, we need a domain-independent language for their representation and a fully, or semi, autonomous system that understands the protocols and supervises their application. In this paper we describe a specification language and a multi-agent system architecture for monitoring medical protocols. We model medical services in hospital environments as specialized domain agents and interpret a medical protocol as a negotiation process between agents. A medical service can be involved in multiple medical protocols, and so specialized domain agents are independent of negotiation processes and autonomous system agents perform monitoring tasks. We present the detailed architecture of the system agents and of an important domain agent, the database broker agent, that is responsible of obtaining relevant information about the clinical history of patients. We also describe how we tackle the problems of privacy, integrity and authentication during the process of exchanging information between agents.
Asunto(s)
Inteligencia Artificial , Automatización , Protocolos Clínicos , Seguridad Computacional , Sistemas de Computación , Comunicación , Sistemas de Información en Hospital , HumanosRESUMEN
A premature infant with nonbacterial endocardial thrombosis and embolization of the cerebral circulation is presented. The patient was born at 32 weeks with a birthweight of 1480 g. Pregnancy was complicated by toxemia and placental infarctions. Echocardiographic examination by 12 hours after birth revealed a large mass in the right atrium compatible with endocardial thrombus. Follow-up echocardiograms showed a small mass in the left atrium and a decrease of the right atrial mass by day 7. Echoencephologram studies were normal on day 1. An echodense area in the subcortical white matter was seen by day 2. Other echodensities were detected by day 10. Computerized tomography studies showed areas of decreased attenuation in both hemispheres. Lung perfusion scan and renal-liver ultrasound studies were normal. All these cerebral and cardiac lesions were asymptomatic. Real-time ultrasonography is useful to diagnose asymptomatic endocardial thrombosis and its cerebral complications in premature infants.