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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proliferative retinopathies, such as those complicating prematurity and diabetes, are major causes of blindness. A prominent feature of these retinopathies is excessive neovascularization, which is orchestrated by the hypoxia-induced vascular endothelial growth factor (VEGF) stimulating endothelial cells and the integrin-mediated adhesive interactions of endothelial cells with extracellular matrix components such as fibronectin (FN). Recently, we demonstrated that alpha-defensins interfere with alpha5beta1-FN interactions and dependent endothelial cell functions. Here, alpha-defensins were studied in hypoxia-induced proliferative retinopathy. In vitro, alpha-defensins specifically inhibited alpha5beta1-integrin-dependent migration of bovine retinal endothelial cells (BRECs) to FN, attenuated the VEGF-stimulated increase in endothelial permeability, and blocked BREC proliferation and capillary sprout formation in 3-dimensional fibrin-matrices. An up-regulation of beta1-integrin and FN was observed in the retinal vessels in the mouse model of hypoxia-induced retinal angiogenesis. Systemic and local administration of alpha-defensins reduced retinal neovascularization by 45% and 60%, respectively, and this effect was comparable to the inhibitory effect of alpha5beta1-blocking antibody. alpha-Defensins were detected in human diabetic retinas associated with normal retinal vessels but were absent from proliferative lesions. Together, these data show that alpha-defensins inhibit pathologic retinal neovascularization in vivo and may provide a clinically efficient strategy against proliferative retinopathies.
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PMID:Inhibition of pathologic retinal neovascularization by alpha-defensins. 1612 22

High oxygen tension is a major factor in the genesis of retinopathy of prematurity (ROP). However, clinical and experimental evidence suggests a significant role for high carbon dioxide (CO(2)) tension as well. Along these lines, although ischemia is often considered to be synonymous with an oxygen deficit, it is also associated with a concomitant local elevation of CO(2) that can lead to impaired developmental and ischemic neovascularization. The mechanisms by which hypercapnia induces retinal microvascular degeneration, a critical step which precedes the subsequent proliferative preretinal neovascularization, are not known. Nitrative stress has an important role in microvascular degeneration leading to ischemia in conditions such as ROP. Hypercapnia is a facilitator of nitration in vitro. We hereby present evidence that prolonged exposure to CO(2) impairs developmental retinal neovascularization through a mechanism involving increased endothelial nitric oxide synthase and induction of a nitrative stress; effects of hypercapnia are independent of its hyperaemic effects. Moreover, we demonstrate that an in vivo nitrative stress associated with retinal vasoobliteration results in nitration of arachidonic acids into trans-arachidonic acids (TAAs), which can act as mediators of nitrative stress by causing microvascular degeneration by inducing expression of the antiangiogenic factor thrombospondin-1. These recent findings establish a previously unexplored means by which hypercapnia hinders efficient neovascularization and provide new insight into the molecular mechanisms of nitrative stress on microvascular injury involving TAA, and suggest new therapeutic avenues in the management of nitrative stress disorders such as in ischemic retinopathies (of prematurity and of diabetes) and encephalopathies.
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PMID:Hypercapnia- and trans-arachidonic acid-induced retinal microvascular degeneration: implications in the genesis of retinopathy of prematurity. 1681 71

This study identified the influences of maternal socio-demographic and antenatal factors on stillbirths and neonatal deaths in New South Wales, Australia. Bivariate and multivariate analyses were used to explore the association of selected antenatal and maternal characteristics with stillbirths and neonatal deaths. The findings of this study showed that stillbirths and neonatal deaths significantly varied by infant sex, maternal age, Aboriginality, maternal country of birth, socioeconomic status, parity, maternal smoking behaviour during pregnancy, maternal diabetes mellitus, maternal hypertension, antenatal care, plurality of birth, low birth weight, place of birth, delivery type, maternal deaths and small gestational age. First-born infants, twins and infants born to teenage mothers, Aboriginal mothers, those who smoked during the pregnancy and those of lower socioeconomic status were at increased risk of stillbirths and neonatal deaths. The most common causes of stillbirths were conditions originating in the perinatal period: intrauterine hypoxia and asphyxia. Congenital malformations, including deformities and chromosomal abnormalities, and disorders related to slow fetal growth, short gestation and low birth weight were the most common causes of neonatal deaths. The findings indicate that very low birth weight (less than 2,000 g) contributed 75.6% of the population-attributable risks to stillbirths and 59.4% to neonatal deaths. Low gestational age (less than 32 weeks) accounted for 77.7% of stillbirths and 87.9% of neonatal deaths. The findings of this study suggest that in order to reduce stillbirths and neonatal deaths, it is essential to include strategies to predict and prevent prematurity and low birth weight, and that there is a need to focus on anti-smoking campaigns during pregnancy, optimizing antenatal care and other healthcare programmes targeted at the socially disadvantaged populations identified in this study.
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PMID:The influence of antenatal and maternal factors on stillbirths and neonatal deaths in New South Wales, Australia. 1686 10

Dramatic medical and technological advances over the past 15 years have resulted in the survival into adulthood of children with chronic health conditions. As this population subset has increased, the demand of caring for these children in the managed care arena has become challenging from a clinical, fiscal, and member satisfaction perspective. A disease management program was designed for children, ages birth through age 18, identified as having special needs at the time of birth or at any point throughout childhood related to disease processes such as diabetes, sickle cell disease, genetic aberrations, or the multiple complications of extreme prematurity. Components of the program included identification of the population, coordinated risk assessment, and ongoing case management interventions. Most important, outcome indicators were tracked to demonstrate program effectiveness. The formulation and function of a dedicated disease management database is also discussed.
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PMID:Caring for children with special healthcare needs in the managed care environment. 1692 94

The success of liver transplantation essentially depends on the prevention and treatment of long term complications, which may be due to surgery, opportunistic infections, organ rejection and relapse of the initial liver disease. The side effects of immunosuppressive drugs--arterial hypertension, glucose intolerance and diabetes, dyslipidemia and obesity, renal failure, osteoporosis, malignancy, and anaemia--should be regularly screened and treated without delay. Surgical procedures in transplanted patients are safe and rarely followed by complications. Although pregnancy in this setting is considered at risk, because of prematurity and low birth weight, overall outcomes are favourable. The yearly influenza vaccination is strongly recommended. The survival and the quality of life of liver transplant patients also depend on a good communication between the general practitioner and the transplantation centre.
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PMID:[Management of patients after liver transplantation]. 1700 50

Neonatal diabetes mellitus is a rare (1/400 000 newborns) but potentially devastating condition, which may be transient or permanent; typical symptoms occur within the first 4 wk of life. The transient form is a developmental insulin production disorder that resolves postnatally. Fifty to 60% of cases can be seen as transient form. Cases that require lifelong insulin therapy can be described as permanent condition. This fraction of cases is less common than the transient form. There are no clinical features that can predict whether a neonate with diabetes mellitus but no other dysmorphology will eventually have permanent neonatal diabetes mellitus (PNDM) or transient neonatal diabetes mellitus. Some metabolic or genetic defects such as complete deficiency of glucokinase or heterozygous activating mutations of KCNJ11, encoding Kir6.2, were found in patients with PNDM. A preterm female infant with a gestational age of 36 wk was admitted to the neonatal intensive care unit in the first hours of life due to prematurity and intra-uterine growth retardation. She was diagnosed as having arthrogryposis multiplex congenita on the first day. Hyperglycemia was detected on the third day of life, and she required insulin treatment. The patient is now 6 yr old with PNDM, arthrogryposis multiplex, neurogenic bladder, immune deficiency, constipation, and ichthyosis. Is this a new form of neonatal diabetes mellitus?
Pediatr Diabetes 2006 Oct
PMID:Permanent neonatal diabetes with arthrogryposis multiplex congenita and neurogenic bladder - a new syndrome? 1705 50

Increasing evidence implicates periodontitis, a chronic inflammatory disease of the tooth-supporting structures, as a potential risk factor for increased morbidity or mortality for several systemic conditions including cardiovascular disease (atherosclerosis, heart attack, and stroke), pregnancy complications (spontaneous preterm birth [SPB]), and diabetes mellitus. Cross-sectional, case-control, and cohort studies indicate that periodontitis may confer two- and up to sevenfold increase in the risk for cardiovascular disease and premature birth, respectively. Given the recently acquired knowledge that systemic inflammation may contribute in the pathogenesis of atherosclerosis and may predispose to premature birth, research in the field of periodontics has focused on the potential of this chronic low-grade inflammatory condition to contribute to the generation of a systemic inflammatory phenotype. Consistent with this hypothesis clinical studies demonstrate that periodontitis patients have elevated markers of systemic inflammation, such as C-reactive protein (CRP), interleukin 6 (IL-6), haptoglobin, and fibrinogen. These are higher in periodontal patients with acute myocardial infarction (AMI) than in patients with AMI alone, supporting the notion that periodontal disease is an independent contributor to systemic inflammation. In the case of adverse pregnancy outcomes, studies on fetal cord blood from SBP babies indicate a strong in utero IgM antibody response specific to several oral periodontal pathogens, which induces an inflammatory response at the fetal-placental unit, leading to prematurity. The importance of periodontal infections to systemic health is further strengthened by pilot intervention trials indicating that periodontal therapy may improve surrogate cardiovascular outcomes, such as endothelial function, and may reduce four- to fivefold the incidence of premature birth. Nevertheless, further research is needed to fully discern the underlying mechanisms by which local chronic infections can have an impact on systemic health, and in this endeavor periodontal disease may serve as an ideal disease model.
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PMID:Low-grade inflammation in chronic infectious diseases: paradigm of periodontal infections. 1719 71

Morbidity and mortality due to vaccine-preventable diseases are high among persons with underlying medical conditions. Thus, inactivated influenza and pneumococcal polysaccharide vaccines are recommended for individuals with cardiac disease, diabetes mellitus, chronic obstructive pulmonary disease, immunosuppression, and other chronic illnesses. Inactivated influenza vaccine is recommended for pregnant women and for persons with asthma and neuromuscular disease. Palivizumab, a respiratory syncytial virus immunoglobulin preparation, is recommended for certain infants with prematurity and chronic lung disease. Health care workers are at high risk for acquiring and transmitting hepatitis B, pertussis, measles, varicella, and influenza; hence, vaccination against these diseases is recommended. A signed declination is recommended for health care workers who refuse influenza vaccination.
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PMID:Vaccines for persons at high risk, 2007. 1727 Jan 9

Developmental origins of health and disease (DOHaD) focuses on the earliest stages of human development, and provides a novel paradigm to complement other strategies for lifelong prevention of common chronic health conditions. The 3 International Congress on DOHaD, held in 2005, retained the most popular features from the first two biannual Congresses, while adding a number of innovations, including increased emphasis on implications of DOHaD for the developing world; programs for trainees and young investigators; and new perspectives, including developmental plasticity, influences of social hierarchies, effects of prematurity, and populations in transition. Emerging areas of science included, first, the controversial role of infant weight gain in predicting adult obesity, diabetes, and cardiovascular disease. Second, in the era of epidemic obesity, paying attention to the over-nourished fetus is as important as investigating the growth retarded one. Third, environmental toxins appear to have abroad range of long-lasting effects on the developing human. Fourth, epigenetic mechanisms could unite several strands of human and animal observations, and explain how genetically identical individuals raised in similar postnatal environments can nonetheless develop widely differing phenotypes. Improving the environment to which an individual is exposed during development may be as important as any other public health effort to enhance population health world wide.
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PMID:Meeting report on the 3rd International Congress on Developmental Origins of Health and Disease (DOHaD). 1741 66

Diabetic pregnancy is a precarious situation, both for mother and fetus, because it increases the risk of prematurity and respiratory distress. We report 3 cases of severe acute complications following antenatal betamethasone treatment in mothers presenting with severe diabetes. Corticosteroids are strongly recommended to prevent prematurity complications in newborns. We highlight the high risk profile of theses pregnancies, the effect of this treatment on the mother and the child, and question the real benefit of corticotherapy for these fragile newborns. The metabolic and blood pressure balance is dangerously disturbed in such pregnancies by this treatment. This brings the question of how justified are corticosteroids in such cases?
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PMID:[Antenatal betamethasone during pregnancy with severe diabetes: is better worse than good?]. 1745 75


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