Which Factors Determine the Development of Late Potentials After First Myocardial Infarction? A Multifactorial Analysis

A multifactorial analysis was performed to study the factors that contributed to the occurrence of late potentials on the signal-averaged electrocardiogram in 106 consecutive patients with a first myocardial infarction. Ninety-three (88%) patients received intravenous thrombolytic therapy within 6 hours of symptom onset. Thirty-two (30%) patients had a late potential on the signal-averaged electrocardiogram on day 6, including 17 of 31 (55%) in whom the infarct-related artery was occluded and 15 of 75 (20%) in whom it was patent (P = 0.0004). Twenty-three variables were analyzed by a multifactorial stepwise regression analysis. Predictors of a late potential were (1) an occluded infarct-related coronary artery (t = -3.653, P = 0.0004) and (2) the extent of myocardial necrosis as indicated by the peak serum lactate dehydrogenase level (t = 3.094, P = 0.0025). The lower incidence of late potentials when the infarct-related coronary artery was patent was independent of left ventricular election fraction and peak enzyme levels after infarction.     

LATE INCREASE IN SERUM 1,25-DIHYDROXYVITAMIN D ONE MONTH AFTER SURGERY FOR ADENOMATOUS HYPERPARATHYROIDISM

This study was designed to follow the evolution of serum 1,25(OH)2D after surgery for primary hyperparathyroidism. Ten patients were studied before and for up to 85 d after removal of a single parathyroid adenoma. Blood and 24 h urine were obtained at various time points, for the measurement of serum or urinary phosphate and calcium indices. Before surgery, serum calcium (2.91 +/- 0.06 mmol/l; mean +/- SEM), parathyroid hormone (354 +/- 47 pg/ml) and 1,25(OH)2D (61.2 +/- 7.8 pg/ml) were elevated while serum phosphate (1.01 +/- 0.07 mmol/l) tended to be low. Relative hypoparathyroidism was evident for up to 5 d after surgery with the lowest value for serum parathyroid hormone (41 +/- 16 pg/ml) on day 1, serum calcium (2.12 +/- 0.06 mmol/l) on day 3 and highest value for serum phosphate (1.41 +/- 0.13 mmol/l) on day 5. As expected, serum 1,25(OH)2D levels decreased to 35.9 +/- 4.2 pg/ml 24 h after surgery. Stabilization of serum and urinary parameters to normal values was seen between day 5 and day 27; the only exception was serum 1,25(OH)2D, which increased again at day 27 to 57.6 +/- 5.0 pg/ml, a value as high as that before surgery. It was still elevated at day 50 (58.3 +/- 4.3 pg/ml), but returned towards normal values in three out of four patients (44 +/- 3.9 pg/ml) by day 80. No variation in 25(OH)D or 24,25(OH)2D was seen throughout the study. 1,25(OH)2D values could be related to serum parathyroid hormone values before surgery (r = 0.659, P less than 0.05) but not after. The secondary increase in serum 1,25(OH)2D could not be related to variations in serum calcium, phosphate, parathyroid hormone or diet. Further studies will be required to explain this phenomenon.     

Sibling Incest

Child sexual abuse has gained national attention within the last decade. The most reported and studied form of intrafamilial child sexual abuse is father-daughter incest However, it is believed that sibling incest may be a more widespread form of intrafamilial sexual abuse. Yet, it has received the least amount of documentation and study. The purpose of this article is to describe sibling incest, including family dynamics. Implications for nursing intervention and research are proposed.     

Intellectual disability: population‐based estimates of the proportion attributable to maternal alcohol use disorder during pregnancy

Aim The aim of this study was to examine the association between maternal alcohol use disorder and intellectual disability in children. Method All mothers with an International Classification of Diseases (ICD) 9 and/or 10 alcohol‐related diagnosis, a proxy for alcohol use disorder, recorded on the Western Australian health, mental health, and drug and alcohol data sets were identified through the Western Australian Data Linkage Unit (n=5614 non‐Aboriginal; n=2912 Aboriginal). A comparison cohort of mothers without an alcohol‐related diagnosis was frequency matched on maternal age within maternal Aboriginal status and year of birth of their children. Linkage with the Western Australian Midwives Notification System (1983–2001) identified all births to these mothers (n=10 664 and 7907 respectively). Linkage to the Western Australian Intellectual Disability Database and Register of Developmental Anomalies identified cases of intellectual disability with no identified genetic origin (intellectual disability) (n=1487) and fetal alcohol syndrome (n=66). Odds ratios (ORs) and 95% confidence intervals (CIs) for intellectual disability were calculated using logistic regression incorporating generalized estimating equations and used to estimate population‐attributable fractions. Results At least 3.8% (95% CI 2.84–4.89%) of cases of intellectual disability could be avoided by preventing maternal alcohol use disorder: 1.3% (95% CI 0.81–1.86%) in non‐Aboriginal and 15.6% (95% CI 10.85–20.94%) in Aboriginal children. We observed a three‐fold increase in the adjusted odds of intellectual disability in children of mothers with an alcohol‐related diagnosis recorded during pregnancy (non‐Aboriginal OR 2.89, 95% CI 1.62–5.18; Aboriginal OR 3.12, 95% CI 2.13–4.56), with a net excess proportion of 3.7% and 5.5% respectively. One‐third (32%) of children diagnosed with fetal alcohol syndrome had intellectual disability. Interpretation Maternal alcohol use disorder is the leading known risk factor for intellectual disability with no identified genetic origin.     

Inhibition of tissue factor pathway inhibitor by the aptamer BAX499 improves clotting of hemophilic blood and plasma

Summary. Background: Tissue factor pathway inhibitor (TFPI) is the major inhibitor of tissue factor‐initiated coagulation, making it an interesting and novel therapeutic target in hemophilia treatment. The aptamer BAX499 (formerly ARC19499) is designed to improve hemostasis by specifically inhibiting TFPI. Objectives: The aim of the study was to examine the concentration‐dependent augmentation of clotting by BAX499. Methods: Whole blood clot formation was quantified by rotational thromboelastometry and thromboelastography, and thrombin generation in platelet‐poor plasma was assessed with the calibrated automated thrombogram, in samples from patients with congenital hemophilia A (N = 55) and B (N = 11), patients with acquired hemophilia A (N = 1), and healthy controls (N = 37). Results: BAX499 significantly improved clotting of samples from hemophilic patients in a concentration‐dependent manner, resulting in clotting profiles in samples from patients with severe hemophilia that were similar to those of healthy controls. Conclusion: BAX499 improved ex vivo clotting parameters in blood and plasma from patients with hemophilia A and B with different severity of disease, and also in a patient with acquired hemophilia. These results further support the contention that anti TFPI strategies may be an effective treatment for hemophilic patients.     

Autonomic Regulation of Voltage-Gated Cardiac Ion Channels

Altering voltage-gated ion channel currents, by changing channel number or voltage-dependent kinetics, regulates the propagation of action potentials along the plasma membrane of individual cells and from one cell to its neighbors. Functional increases in the number of cardiac sodium channels (Na_V1.5) at the myocardial sarcolemma are accomplished by the regulation of caveolae by β adrenergically stimulated G-proteins. We demonstrate that Na_V1.5, Ca_V1.2a, and K_V1.5 channels specifically localize to isolated caveolar membranes, and to punctate regions of the sarcolemma labeled with caveolin-3. In addition, we show that Na_V1.5, Ca_V1.2a, and K_V1.5 channel antibodies label the same subpopulation of isolated caveolae. Plasma membrane sheet assays demonstrate that Na_V1.5, Ca_V1.2a, and K_V1.5 cluster with caveolin-3. This may have interesting implications for the way in which adrenergic pathways alter the cardiac action potential morphology and the velocity of the excitatory wave.