RESUMO
Mutations in the genes encoding calcium/calmodulin dependent protein kinase II (CAMK2) isoforms cause a newly recognized neurodevelopmental disorder (ND), for which the full clinical spectrum has yet to be described. Here we report the detailed description of a child with a de novo gain of function (GoF) mutation in the gene Ca/Calmodulin dependent protein kinase 2 beta (CAMK2B c.328G > A p.Glu110Lys) who presents with developmental delay and periodic neuropsychiatric episodes. The episodes manifest as encephalopathy with behavioral changes, headache, loss of language and loss of complex motor coordination. Additionally, we provide an overview of the effect of different medications used to try to alleviate the symptoms. We show that medications effective for mitigating the child's neuropsychiatric symptoms may have done so by decreasing CAMK2 activity and associated calcium signaling; whereas medications that appeared to worsen the symptoms may have done so by increasing CAMK2 activity and associated calcium signaling. We hypothesize that by classifying CAMK2 mutations as "gain of function" or "loss of function" based on CAMK2 catalytic activity, we may be able to guide personalized empiric treatment regimens tailored to specific CAMK2 mutations. In the absence of sufficient patients for traditional randomized controlled trials to establish therapeutic efficacy, this approach may provide a rational approach to empiric therapy for physicians treating patients with dysregulated CAMK2 and associated calcium signaling.
RESUMO
BACKGROUND: Listeria monocytogenes is a food-borne pathogen that primarily affects pregnant women. Cardiac involvement is an uncommon complication of infection. We present a case of a gravida with Listeria bacteremia at 36 weeks of gestation. CASE: Two of a patient's blood cultures grew L monocytogenes after she experienced chills, headache, myalgia, and diarrhea. The patient was treated with antibiotics for 48 hours, and then labor was induced, resulting in a normal delivery with a healthy neonate. On day 5 postpartum, the patient developed progressive heart block, resulting in a third-degree block, which required a pacemaker. An electrocardiogram done 30 days after hospital discharge demonstrated an atrial-sensed, ventricularly paced rhythm, which indicated that the heart block had not resolved. CONCLUSION: Heart block is a rarely reported and possibly overlooked complication of listeriosis. Mothers with listerial infection should be screened for cardiac complications to avoid unexpected decompensation.
Assuntos
Bloqueio Cardíaco/microbiologia , Listeriose/complicações , Complicações Infecciosas na Gravidez/etiologia , Transtornos Puerperais/microbiologia , Adulto , Feminino , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/terapia , Humanos , Listeriose/diagnóstico , Listeriose/terapia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/terapia , Transtornos Puerperais/diagnóstico , Transtornos Puerperais/terapiaRESUMO
OBJECTIVE: The purpose of this study was to compare the accuracy of transabdominal sonography and magnetic resonance imaging (MRI) for prenatal diagnosis of placenta accreta. METHODS: A historical cohort study was undertaken at 3 institutions identifying women at risk for placenta accreta who had undergone both sonography and MRI prenatally. Sonographic and MRI findings were compared with the final diagnosis as determined at delivery and by pathologic examination. RESULTS: Thirty-two patients who had both sonography and MRI prenatally to evaluate for placenta accreta were identified. Of these, 15 had confirmation of placenta accreta at delivery. Sonography correctly identified the presence of placenta accreta in 14 of 15 patients (93% sensitivity; 95% confidence interval [CI], 80%-100%) and the absence of placenta accreta in 12 of 17 patients (71% specificity; 95% CI, 49%-93%). Magnetic resonance imaging correctly identified the presence of placenta accreta in 12 of 15 patients (80% sensitivity; 95% CI, 60%-100%) and the absence of placenta accreta in 11 of 17 patients (65% specificity; 95% CI, 42%-88%). In 7 of 32 cases, sonography and MRI had discordant diagnoses: sonography was correct in 5 cases, and MRI was correct in 2. There was no statistical difference in sensitivity (P = .25) or specificity (P = .5) between sonography and MRI. CONCLUSIONS: Both sonography and MRI have fairly good sensitivity for prenatal diagnosis of placenta accreta; however, specificity does not appear to be as good as reported in other studies. In the case of inconclusive findings with one imaging modality, the other modality may be useful for clarifying the diagnosis.
Assuntos
Imageamento por Ressonância Magnética/métodos , Placenta Acreta/diagnóstico por imagem , Diagnóstico Pré-Natal/métodos , Ultrassonografia/métodos , Estudos de Coortes , Feminino , Humanos , Gravidez , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Estados UnidosRESUMO
BACKGROUND: Myocardial infarction (MI) is uncommon during pregnancy. As the average maternal age increases and assisted reproductive technology allows for very advanced maternal ages, so too may the incidence of MI during pregnancy. Percutaneous transluminal coronary angioplasty (PTCA) with stent placement is an attractive option for treatment of MI in pregnancy when revascularization is required. CASE: We present a gravida with an ST elevation MI during the third trimester, who was treated with emergent PTCA, stent placement, and platelet inhibitors, and we discuss the patient's subsequent obstetric and anesthetic management. CONCLUSION: Percutaneous transluminal coronary angioplasty with stent placement may be used during the third trimester with successful outcome.
Assuntos
Angioplastia Coronária com Balão/métodos , Infarto do Miocárdio/terapia , Complicações Cardiovasculares na Gravidez/terapia , Stents , Adulto , Terapia Combinada , Feminino , Humanos , Idade Materna , Infarto do Miocárdio/complicações , Inibidores da Agregação Plaquetária/uso terapêutico , Gravidez , Resultado da Gravidez , Terceiro Trimestre da GravidezRESUMO
OBJECTIVES: Recent studies have found dysregulation in circulating levels of a number of angiogenic factors and their soluble receptors in preeclampsia. In this study, we examined the mechanism of production of soluble Tie2 (sTie2) and its potential connection to the failure of vascular remodeling in preeclamptic pregnancies. DESIGN/SETTING/PATIENTS: Serum samples were collected prospectively from 41 pregnant subjects at five different time points throughout pregnancy. Five of these subjects developed preeclampsia. For a second study, serum and placental samples were collected at delivery from preeclamptic and gestational age-matched controls. We examined serum sTie2 levels, and angiopoietin 1, angiopoietin 2, and Tie2 mRNA expression and localization in placental samples from the central basal plate area. We also examined the effects of vascular endothelial growth factor (VEGF) and a matrix metalloproteinase (MMP) inhibitor on proteolytic shedding of Tie2 in uterine microvascular endothelial cells. RESULTS: Serum sTie2 levels were significantly lower in preeclamptic subjects starting at 24-28 wk of gestation and continued to be lower through the time of delivery. In culture experiments, VEGF treatment significantly increased sTie2 levels in conditioned media, whereas the MMP inhibitor completely blocked this increase, suggesting that VEGF-induced Tie2 release is MMP dependent. CONCLUSIONS: Our data suggest, for the first time, an interaction between VEGF and Tie2 in uterine endothelial cells and a potential mechanism for the decrease in circulating sTie2 levels in preeclampsia, likely through inhibition of VEGF signaling. Further studies on VEGF-Tie2 interactions during pregnancy should provide new insights into the mechanisms underlying the failure of vascular remodeling in preeclampsia and other pregnancy complications.
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Células Endoteliais/metabolismo , Pré-Eclâmpsia/metabolismo , Receptor TIE-2/sangue , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Células Cultivadas , Meios de Cultivo Condicionados , Células Endoteliais/citologia , Feminino , Humanos , Metaloproteinases da Matriz/metabolismo , Gravidez , Útero/citologia , Útero/metabolismoRESUMO
OBJECTIVE: To explore angiogenic factor differences in preeclamptic patients according to the absence or presence of underlying vascular disease. METHODS: We prospectively compared serum soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin, and placental growth factor (PlGF) from 41 normal-risk and 32 high-risk (preexisting conditions) subjects at serial gestational ages. RESULTS: Median sFlt1 was lower at delivery in preeclamptic patients with underlying chronic hypertension and/or chronic proteinuria (5115 pg/ml) compared with normal risk preeclamptic patients (16375 pg/ml). PlGF was consistently low in patients who developed preeclampsia. CONCLUSIONS: Effects of sFlt1 may be contextual, varying according to the health or disease state of vascular endothelium.