The psychosocial impact of Klinefelter syndrome and factors influencing quality of life.

Purpose: There is considerable information regarding the medical and cognitive aspects of Klinefelter syndrome yet little research regarding its psychosocial impact. This study investigates the personal impact of Klinefelter syndrome and the influence of age at diagnosis, clinical, social, and demographic factors on adult quality of life outcomes.

Methods: Men from across Australia, diagnosed with KS at different ages, were recruited through multiple sources.

The prevalence and diagnosis rates of Klinefelter syndrome: an Australian comparison.

Objective: To determine the prevalence and diagnosis rates of Klinefelter syndrome (KS) in Victoria, Australia, and compare these to previous international findings.

Design, Setting And Participants: A Victorian population-based descriptive study of all cytogenetic examinations resulting in a diagnosis of KS, including prenatal diagnoses from 1986 to 2006 and postnatal diagnoses from 1991 to 2006.

Main Outcome Measures: Birth prevalence and diagnosis rates of KS.

The anti-inflammatory agent N-acetyl cysteine exacerbates endotoxin-induced hypoxemia and hypotension and induces polycythemia in the ovine fetus.

Background: Lipopolysaccharide (LPS) delivered acutely to the ovine fetus induces cerebral white matter injury and brain inflammation. N-acetyl cysteine (NAC) is potentially neuroprotective as it blocks the production of inflammatory cytokines and increases glutathione levels; however, it is unknown whether NAC affects the physiological status of the fetus already exposed to an inflammatory environment.

Objectives: Our objective was to determine whether NAC influences the physiological effects of LPS exposure in the ovine fetus.

Nephrogenesis and the renal renin-angiotensin system in fetal sheep: effects of intrauterine growth restriction during late gestation.

Previous studies have shown that intrauterine growth restriction (IUGR) can impair nephrogenesis, but uncertainties remain about the importance of the gestational timing of the insult and the effects on the renal renin-angiotensin system (RAS). We therefore hypothesized that induction of IUGR during late gestation alters the RAS, and this is associated with a decrease in nephron endowment. Our aims were to determine the effects of IUGR induced during the later stages of nephrogenesis on 1) nephron number; 2) mRNA expression of angiotensin AT(1) and AT(2) receptors, angiotensinogen, and renin genes in the kidney; and 3) the size of maculae densae.

Intrauterine growth restriction delays cardiomyocyte maturation and alters coronary artery function in the fetal sheep.

There is now extensive evidence suggesting that intrauterine perturbations are linked with an increased risk of developing cardiovascular disease. Human epidemiological studies, supported by animal models, have demonstrated an association between low birth weight, a marker of intrauterine growth restriction (IUGR), and adult cardiovascular disease. However, little is known of the early influence of IUGR on the fetal heart and vessels.

Acute ethanol exposure in pregnancy alters the insulin-like growth factor axis of fetal and maternal sheep.

Maternal ethanol intake during pregnancy impairs fetal growth, but mechanisms are not clearly defined. Reduced IGF abundance or bioavailability in the fetus and/or mother may contribute to this growth restriction. We hypothesized that an episode of acute ethanol exposure, mimicking binge drinking would restrict fetal growth and perturb the maternal and fetal IGF axes.

Chronic endotoxin exposure causes brain injury in the ovine fetus in the absence of hypoxemia.

Objective: Intrauterine infection has been linked to brain injury in human infants, although the mechanisms are not fully understood. We recently showed that repeated acute exposure of preterm fetal sheep to bacterial endotoxin (lipopolysaccharide [LPS]) results in fetal hypoxemia, hypotension, increased systemic proinflammatory cytokines, and brain damage, including white matter injury. However, it is not clear whether this injury is caused by reduced cerebral oxygen delivery or inflammatory pathways independent of hypoxia.

Alveolar epithelial cell differentiation and surfactant protein expression after mild preterm birth in sheep.

As the transition to extrauterine life at birth alters the proportions of type I and II alveolar epithelial cells (AECs), our aim was to determine the effect of mild preterm birth on AECs and surfactant protein (SP) gene expression. Preterm lambs were born at approximately 133 d of gestational age (DGA); controls were born at term (approximately 147 DGA). Lungs were collected from preterm lambs at term-equivalent age (TEA; approximately 2 wk after preterm birth) and 6 wk post-TEA.

Long term consequences of low birthweight on postnatal growth, adiposity and brain weight at maturity in sheep.

Low birth weight (LBW) as a result of restricted fetal growth increases the risk for later metabolic diseases and adiposity. However the relationship between LBW and postnatal growth and adult body composition has not been fully investigated. We have used sheep to determine the effects of LBW on postnatal growth and body composition at maturity.

Effect of lung hypoplasia on birth-related changes in the pulmonary circulation in sheep.

Lung hypoplasia (LH) is a serious cause of neonatal compromise, but little is known of its functional effects on the pulmonary circulation. Our aim was to characterize birth-related changes in the pulmonary circulation of newborn lambs with LH and to compare them with alterations in respiratory function. LH was induced in six ovine fetuses by the creation of a tracheo-amniotic shunt as well as amniotic fluid drainage starting at 105.

Effects of exposure to chronic placental insufficiency on the postnatal brain and retina in sheep.

Chronic placental insufficiency (CPI) has the potential to affect fetal brain development and to cause brain injury. Our aim was to determine the effects of exposure to CPI during late gestation on brain and retinal structure and brain neurotrophin expression 8 weeks after birth. Six fetal sheep were exposed to CPI, induced by umbilico-placental embolization, from 120 days of gestation until term (approximately 147 days) such that fetal arterial oxygen saturation (SaO2) was reduced by approximately 50%.

Neurotrophin expression in the hippocampus and cerebellum is affected by chronic placental insufficiency in the late gestational ovine fetus.

Our aim was to determine the effects of chronic placental insufficiency (CPI) during late gestation on the expression of neurotrophic factors and their receptors in the hippocampus and cerebellum in the near-term fetus. Structural alterations were also assessed in these brain regions. CPI was induced in eight fetal sheep by umbilicoplacental embolization (UPE) from 120 to 140 days of gestation (term approximately 147d) such that fetal arterial O2 saturation (SaO2) was maintained at approximately 50% of pre-UPE values.

Effects of umbilical cord occlusion in late gestation on the ovine fetal brain and retina.

Objective: Previous studies on the effects of umbilical cord occlusion (UCO) on the fetal brain have focused on short-term alterations, and in most cases have used only subjective techniques to evaluate brain injury. Our aim was to assess quantitatively the persistent consequences of UCO on the developing brain; we also examined the retina.

Methods: We subjected fetal sheep to a single episode of UCO at 126 days of gestation (term approximately 147 days) to induce at least 10 minutes of isoelectric fetal electrocorticogram (ECoG).

Pulmonary elastin synthesis and deposition in developing and mature sheep: effects of intrauterine growth restriction.

Hypoxia and nutrient restriction during gestation restrict fetal growth and alter lung development. As elastin is intimately involved in lung development, our aim was to assess pulmonary elastin synthesis and deposition following intrauterine growth restriction (IUGR) induced by umbilicoplacental embolization (UPE). Pulmonary tropoelastin expression and elastin content were examined at 128 days (5 days UPE) and 140 days (20 days UPE) of the 147- days gestation and at 8 weeks and 2.

Nephron endowment and filtration surface area in the kidney after growth restriction of fetal sheep.

Low birth weight is associated with adult-onset diseases including hypertension and renal disease; altered renal development after intrauterine growth restriction (IUGR) may underlie such prenatal programming. Our aim was to investigate nephron endowment and renal filtration surface area in fetal sheep in which IUGR resulted from late gestational umbilico-placental embolization (UPE) or natural twinning. UPE was performed between 120 and 140 d of gestation (term approximately 147 d).

Fetal growth restriction has long-term effects on postnatal lung structure in sheep.

We have previously shown that fetal growth restriction (FGR) during late gestation in sheep affects lung development in the near-term fetus and at 8 wk after birth. In the present study, our aim was to determine the effects of FGR on the structure of the lungs at 2 y after birth; our hypothesis was that changes observed at 8 wk after birth would persist until maturity. FGR was induced in sheep by umbilicoplacental embolization, which was maintained from 120 d until delivery at term (approximately 147 d); birth weights of FGR lambs were 41% lower than in controls.

Chronic placental insufficiency and foetal growth restriction lead to long-term effects on postnatal retinal structure.

The aim of this study was to determine the effects of foetal growth restriction on the retina after birth. Foetal growth restriction (FGR) was induced via umbilico-placental embolization (UPE) in ewes from 120 days of pregnancy until term (term approximately 147 days); controls were not exposed to UPE. Lambs were delivered and raised until 2 years of age when retinas were collected and processed for structural and neurochemical analysis.

White matter injury after repeated endotoxin exposure in the preterm ovine fetus.

Intrauterine infection has been linked to neurologic injury in preterm infants. However, a reproducible model of white matter injury in the preterm fetus in a long gestation species that can be monitored in utero is currently unavailable. Thus, our objective was to determine the effects of bacterial endotoxin (lipopolysaccharide, LPS) on physiologic and inflammatory responses and brain structure in the preterm ovine fetus.

Relation between oligohydramnios and spinal flexion in the human fetus.

Background: Oligohydramnios, a severe reduction in the volume of amniotic fluid, is associated with fetal lung hypoplasia but underlying processes are unclear. Studies in sheep suggest that oligohydramnios may lead to lung hypoplasia by causing increased flexion of the fetal spine, but this has not been demonstrated in the human, which has a different uterine anatomy.

Aims: Our aims were to quantify spinal flexion in the human fetus and to determine the relationship between oligohydramnios and the degree of spinal flexion.

Influence of intrauterine growth restriction on airway development in fetal and postnatal sheep.

Epidemiologic studies suggest that intrauterine growth restriction (IUGR) can lead to impaired lung function, yet little information exists on the effects of IUGR on airway development. Our objectives were to characterize morphometrically effects of IUGR on airway structure in the fetus and to determine whether alterations persist into postnatal life. We used two groups of sheep, each with appropriate controls; a fetal group was subjected to IUGR by restriction of placental function from 120 to 140 d (term approximately 147 d), and a postnatal group, killed 8 wk after birth, was subjected to IUGR from 120 d to birth at term.

Fetal responses to intra-amniotic endotoxin in sheep.

Objective: Our aim was to determine the acute physiologic effects of intra-amniotic endotoxin administration in fetal sheep, and in particular, to determine whether intra-amniotic endotoxin causes an increase in fetal cortisol that could underlie the functional maturation of the fetal lungs previously reported in this model.

Methods: As in our previous experiments, ewes were randomly assigned to receive a single intra-amniotic injection of either endotoxin (20 mg, Escherichia coli [055:B5], n = 5) or saline (n = 5). Between 0.