Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have suggested that postoperative bleeding is decreased in pediatric heart operations if fresh whole blood instead of blood component therapy is used for postoperative transfusions. Because this is in contrast to our practice to use whole blood for only the priming of the cardiopulmonary bypass circuit and then to use blood components for additional transfusion requirements, it was our interest to analyze the bleeding complications and the use of blood products after heart operations in infants. The patient records of the 73 infants operated on in 1992 were reviewed. The chest tube drainage varied from 3 to 51 ml/kg per 6 hours (mean 10 ml/kg) and it did not correlate with any of the tested clinical or laboratory parameters. One infant underwent reoperation because of surgical bleeding. Disseminated intravascular coagulation developed in another patient. Sixty-eight patients (93%) needed red blood cell supplementation. Sixty-eight percent of patients between 1 month and 1 year old could be treated without any other postoperative transfusion except for red blood cell supplementation. In contrast, in the neonates, platelet concentrates or fresh frozen plasma, or both, were used in 61% of the patients. In addition to the known immaturity of the hemostatic system, the increased need for platelet concentrates in the neonates was attributed to longer cardiopulmonary bypass time, deeper hypothermia in association with circulatory arrest, larger dosages of heparin, and more extensive plasma dilution during cardiopulmonary bypass. In conclusion, a low rate of bleeding complications and acceptably low general blood loss can be achieved postoperatively with blood component therapy.
J Thorac Cardiovasc Surg 1995 Mar
PMID:Bleeding and use of blood products after heart operations in infants. 787 14

The effects of diltiazem, a sarcolemmal Ca2+ channel blocker, and ryanodine, an inhibitor of sarcoplasmic reticulum function, were investigated in isolated newborn rabbit hearts (2 to 5 days old) subjected to ischemia and reperfusion. After cardioplegic arrest with St. Thomas' Hospital solution, global ischemia was induced at 37 degrees C (normothermia) for 45 minutes or at 20 degrees C (hypothermia) for 180 minutes. The hearts were then reperfused at 37 degrees C for 30 minutes. Diltiazem or ryanodine, at concentrations that have minimal to moderately negative inotropic effects under nonischemic conditions, was added to the cardioplegic solution. After normothermic ischemia, reperfusion of untreated hearts resulted in recovery of left ventricular developed pressure to 52.9% +/- 2.5% of the preischemic level. In hearts treated with diltiazem, recovery of left ventricular developed pressure was significantly improved (84.2% +/- 2.9% at 3 x 10(-8) mol/L; p < 0.01). Comparable improvement was achieved with ryanodine (90.5% +/- 4.1% at 10(-9) mol/L; p < 0.01). Creatine kinase leakage and structural derangement of mitochondria were also reduced by both agents. With hypothermic ischemia, left ventricular developed pressure recovered in untreated hearts to 72.7% +/- 3.3% of preischemic values. Treatment with diltiazem improved the recovery of left ventricular developed pressure to 96.9% +/- 3.5% at 3 x 10(-8) mol/L and reduced creatine kinase leakage and mitochondrial damage. Ryanodine also improved the recovery of left ventricular developed pressure and attenuated ultrastructural damage. These findings suggest that Ca2+ handling by the sarcoplasmic reticulum, like transsarcolemmal Ca2+ influx, plays an important role in the pathogenesis of myocardial ischemia-reperfusion injury in the neonatal heart despite the morphologic and functional immaturity of the sarcoplasmic reticulum in the neonate.
J Thorac Cardiovasc Surg 1993 Jul
PMID:Protective effects of diltiazem and ryanodine against ischemia-reperfusion injury in neonatal rabbit hearts. 832 Oct 5

In premature, very-low-birth-weight (VLBW) neonates, complex cardiac malformations can be successfully repaired under conditions of cardiopulmonary bypass. However, due to the immaturity of organ systems, these patients are exposed to a specific risk resulting from noxious effects of extracorporeal circulation, especially on the central nervous system. Two premature neonates with low and very low birth weight of 1160 g and 1650 g, were operated on using cardiopulmonary bypass for severe pulmonary artery stenosis and truncus arteriosus communis type II, respectively. The neonate with pulmonary valve stenosis survived, but at 2-year-follow-up examination motoricity retardation as a result of cerebral immaturity-related changes was evident. The other neonate died suddenly on the fifth postoperative day of a massive intracranial haemorrhage. Due to the fact that the natural history of VLBW children is a priori characterized by a high incidence of major neurological handicaps, open heart surgery may by improving survival chances contribute to an increased incidence of mentally handicapped children.
Thorac Cardiovasc Surg 1997 Oct
PMID:Open heart interventions in premature low- and very-low-birth-weight neonates: risk profile and ethical considerations. 940 63

Perturbations of the trans-sarcolemmal and sarcoplasmic Ca2+ transport contribute to the abnormal myocardial activity provoked by anoxia and reoxygenation. Whether Ca2+ pools of the extracellular compartment and sarcoplasmic reticulum (SR) are involved to the same extent in the dysfunction of the anoxic-reoxygenated immature heart has not been investigated. Spontaneously contracting hearts isolated from 4-day-old chick embryos were submitted to repeated anoxia (1 min) followed by reoxygenation (5 min). Heart rate, atrioventricular propagation velocity, ventricular shortening, velocities of contraction and relaxation, and incidence of arrhythmias were studied, recorded continuously. Addition of verapamil (10 nM), which blocks selectively sarcolemmal L-type Ca2+ channels, was expected to protect against excessive entry of extracellular Ca2+, whereas addition of ryanodine (10 nM), which opens the SR Ca2+ release channel, was expected to increase cytosolic Ca2+ concentration. Verapamil (a) had no dromotropic effect by contrast to adult heart, (b) attenuated ventricular contracture induced by repeated anoxia, (c) shortened cardioplegia induced by reoxygenation, and (d) had remarkable antiarrhythmic properties during reoxygenation specially. On the other hand, ryanodine potentiated markedly arrhythmias both during anoxia and at reoxygenation. Thus despite its immaturity, the SR seems to be functional early in the developing chick heart and involved in the reversible dysfunction induced by anoxia-reoxygenation. Moreover, Ca2+ entry through L-type channels appears to worsen arrhythmias especially during reoxygenation. These findings show that the Ca2+-handling systems involved in irregular activity in immature heart, such as the embryonic chick heart, may differ from those in the adult.
J Cardiovasc Pharmacol 1998 Feb
PMID:Effects of verapamil and ryanodine on activity of the embryonic chick heart during anoxia and reoxygenation. 947 60

In order for ABO-incompatible organ transplantation to be performed successfully, the antibody response must be targeted. Aggressive strategies are usually required both to remove pre-existing antibodies directed at donor A/B antigens and to suppress further production of antibodies. If this can be accomplished in the short-term, graft accommodation of ABO-incompatible transplants may develop upon eventual re-accumulation of antibodies as the graft acquires resistance to antibody-mediated damage. In contrast to mature individuals, very young infants lack isohemagglutinins due to a natural lag in development of immunity to T cell-independent polysaccharide antigens. This delay in maturation permits a window of safety during which infants can receive ABO-incompatible grafts without the requirement for aggressive immunosuppressive strategies. We have recently demonstrated that ABO-incompatible heart transplantation performed during this stage of immaturity is followed by the spontaneous development of donor-specific B cell tolerance rather than graft accommodation, and that tolerance in this setting occurs by a cellular mechanism of antigen-specific B cell elimination. This finding is strikingly similar to the original descriptions of neonatal T cell tolerance in mice. Our data provide compelling justification that every effort should be made to include juvenile recipients routinely as subjects in tolerance research. Through understanding the mechanisms underlying tolerance in this setting, as with murine models of neonatal tolerance originally described by Medawar and colleagues, it may be possible to expand the potential applications of tolerance strategies to older patient populations.
Curr Drug Targets Cardiovasc Haematol Disord 2005 Jun
PMID:Targeting antibody-mediated rejection in the setting of ABO-incompatible infant heart transplantation: graft accommodation vs. B cell tolerance. 1597 36

We report the case of a 3-day-old male baby, weighing 1.6 kg with severe aortic coarctation and associated cardiac anomalies and extracardiac defects. We adopted an extra-anatomical conduit running from the left carotid artery to the descending aorta after laceration of the distal aortic arch due to extreme tissue fragility and baby immaturity.
J Cardiovasc Med (Hagerstown) 2009 Jun
PMID:Aortic arch laceration during aortic coarctation repair in a low-weight neonate and use of an extra-anatomical conduit. 1935 96

A best evidence topic (BET) in cardiac surgery was written according to a structured protocol. The question addressed was whether ABO-incompatible (ABO-I) heart transplant recipients have a similar survival rate as an ABO-compatible (ABO-C) transplant in the pediatric population <1 year of age. Altogether more than 112 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. Generally, ABO-I transplantation has been associated with the neonatal population because of the relative immaturity of the immune system for the first year of life. In the BET the search-term 'pediatric' was used as a method to ensure retrieval all relevant papers. However, the vast majority of the patients reviewed were <1 year of age with specific techniques undertaken to modulate preoperative, intraoperative and postoperative isohemagglutinin titer levels with rejection monitoring. Therefore, the BET conclusions should not be applied to the pediatric group as a broad age classification. Two large series are of particular interest. Patel et al. reviewed all primary heart transplantation recipients < or =1 year of age in the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) registry (ABO-I=35 vs. ABO-C=556). There was no difference in 30-day mortality (ABO-I=5.9% vs. ABO-C=8.8%; P=0.55); one-year mortality (ABO-I=16.6% vs. ABO-C=14.7%; P=0.77); graft rejection (ABO-I=1 vs. ABO-C=0); and graft failure (ABO-I=24% vs. ABO-C=24%; P>0.99). Three-year Kaplan-Meier survival was 70% (P=0.85). Propensity score adjusted analysis did not implicate ABO-I as a predictor of mortality [hazard ratio (HR)=3.6, confidence interval (CI): 0.2-49.0; P=0.33]. The ABO-I group demonstrated an increased need for pacemaker (ABO-I=3.1% vs. ABO-C=0.4%; P=0.03) and higher stroke rate (ABO-I=12.9% vs. ABO-C=1.3%; P<0.0001). Dipchand et al. published the results of the Toronto cohort from 1992 to 2006 (ABO-I=16 vs. ABO-C=38). The median age at transplantation (ABO-I=88 days vs. ABO-C=84 days; P=0.82) and the number of neonatal transplant recipients (ABO-I=17% vs. ABO-C=22%; P=0.59) was similar. The freedom from post-transplantation death or retransplantation was equivalent at one year (ABO-I=77% vs. ABO-C=84%) and seven years (ABO-I=74% vs. ABO-C=74%; P=0.87). No significant difference was observed for the five-year freedom from: rejection (ABO-I=60% vs. ABO-C=45%; P=0.41); renal dysfunction (ABO-I=67% vs. ABO-C=72%; P=0.70); allograft vasculopathy (ABO-I=87% vs. ABO-C=78%; P=0.45); and post-transplantation lymphoproliferative disorder (PTLD) (ABO-I=87% vs. ABO-C=86%; P=0.93). We conclude that ABO-I transplantation is comparable to ABO-C transplantation, with several retrospective papers concluding there is no difference in mortality, morbidity or graft failure in the pediatric population <1 year of age.
Interact Cardiovasc Thorac Surg 2010 Jun
PMID:Does ABO-incompatible and ABO-compatible neonatal heart transplant have equivalent survival? 2030 66

Stem cell therapy is an emerging therapeutic approach for the treatment of cardiovascular diseases. Experimental studies have demonstrated that different types of stem cells, including bone marrow-derived cells, mesenchymal stem cells, skeletal myoblasts, and cardiac progenitor cells and embryonic stem cells, can improve cardiac function after myocardial injuries. Nevertheless, the potential proarrhythmic risk after stem cell transplantation remains a major concern. Several mechanisms, including the immaturity of electrical phenotypes of the transplanted cardiomyocytes, poor cell-cell coupling and cardiac nerve sprouting, may contribute to arrhythmogenic risk after stem cell transplantation. This review summarizes the potential theoretical arrhythmogenic mechanisms associated with different types of stem cells for the treatment of cardiovascular diseases. Nevertheless, current experimental and clinical data on the proarrhythmic risk for different types of stem cell transplantation are limited, and await further experimental and clinical investigation.
Expert Rev Cardiovasc Ther 2011 Dec
PMID:The proarrhythmic risk of cell therapy for cardiovascular diseases. 2210 78

Intraplaque hemorrhages are mainly related to inward neoangiogenesis, initiated from the adventitia by lipid-dependent outwardly convected signals, and by the immaturity of these neovessels, allowing leaks and hemorrhages. Repeated intraplaque hemorrhages play a major role in the evolution of thrombotic occlusive disease, similar to the role of intraluminal thrombus in the progression of abdominal aortic aneurysm toward rupture. Red blood cells (RBCs) are an important source of unesterified cholesterol, because their membranes are particularly cholesterol rich. This unesterified cholesterol is rapidly organized in cholesterol crystals, highly toxic for cell and membranes. Oxidized cholesterol and LDL provoke the irreversible covalent aggregation of proteins, including hemoglobin, forming ceroids, which are also highly toxic. Hemoglobin play a major role of prooxydant molecules in this context, by its ability to release heme and iron, the main catalyser of oxidative reaction. In the context of type 2 diabetes, the oxidative potential of intraplaque-free hemoglobin play a predominant role in the progression of atherothrombotic disease toward clinical expression. Associated to RBC, intraplaque hemorrhages convey leukocyte, mainly neutrophils in human, and plasma zymogen that are the main source of proteases, including coagulation proteases, activation of the fibrinolytique system, release of leukocyte serine proteases and cathepsins and activation of MMPs. These proteases concentrate in the hemorrhagic/necrotic core rendered plaque highly vulnerable. An adaptive immune response takes place in the adventitia, in regard of hemorrhagic plaques, in relation to outwardly convected oxidized or proteolyzed neoantigens, and chemokinic signals. Finally, intraplaque hemorrhages and thrombi are the site of weak pathogen entrapment, which promote all these oxydative and proteolytic phenomenons.
J Cardiovasc Med (Hagerstown) 2012 Oct
PMID:From intraplaque haemorrhages to plaque vulnerability: biological consequences of intraplaque haemorrhages. 2292 66

Calcium (Ca(2+)) is an important intracellular messenger, regulating myocyte contraction via excitation-contraction (EC) coupling and gene transcription underlying hypertrophy in the heart. Although the mechanisms of EC coupling in the immature heart are believed to be different from those in the adult heart because of the structural immaturity of the sarcoplasmic reticulum in the young heart, the details of these mechanisms are not completely understood. Neuronal Ca(2+) sensor-1 (NCS-1) is an EF-hand Ca(2+)-binding protein that is highly expressed in young hearts; however, little is known about its cardiac functions. In this review, we summarize our recent findings indicating that NCS-1 acts as a novel regulator enhancing Ca(2+) signals in the heart and hence promoting contraction in the immature heart and hypertrophy in the adult heart. Possible signal transduction pathways are also discussed.
Trends Cardiovasc Med 2012 Jan
PMID:Role of neuronal calcium sensor-1 in the cardiovascular system. 2294 25


1 2 Next >>