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To compare the pregnancy outcomes in all T1DMP attending at combined (diabetes-obstetric) outpatients clinics in three university teaching hospitals in Dublin from 1995 to 2006 with a non-diabetic control population (C) attending at antenatal outpatient clinics at the same hospitals over the same period.T1DMP (n = 600) were compared with control non-diabetic pregnancies (n = 142,498).The spontaneous abortion rate was 15% in T1DMP versus 8% in C (p0.0001). Perinatal mortality rate was 3.3% in T1DMP compared to 0.9% in C (p0.001). The incidence of foetal macrosomia was 29% in T1DMP versus 16% in C (p0.001).Pregnancy outcomes in T1DMP remain worse than in the general population despite management of T1DMP in combined obstetric/diabetes clinics in a single centre using similar management protocols. These outcomes in our study population of T1DMP in Dublin appear better than some previously reported studies.

We have previously shown that when tested in the morning, older men and women, pretreated with metyrapone to block endogenous cortisol synthesis, exhibit delayed suppression of plasma ACTH in response to cortisol infusion. To confirm this finding and to determine whether aging-related changes in feedback responsiveness are exaggerated near the time of the circadian nadir in adrenocortical secretion, we performed a similar study in the evening. Healthy young (20-35 yr, n = 22) and old (>65 yr, n = 21) men and women were administered metyrapone orally (750 mg) at 1600 and 1900 h, followed by a cortisol infusion of 0.06 mg/kg/h for 150 min. Blood samples were taken at 15-min intervals for 4 h following infusion onset for measurement of plasma ACTH, cortisol, 11-deoxycortisol, and corticosteroid binding globulin. When corrections were made for differences in circulating cortisol concentrations achieved among age and gender subgroups, feedback inhibition of ACTH was found to be significantly greater in young than in old subjects of both genders. Our studies support the hypothesis that glucocorticoid responses to stress in aging individuals are likely to be prolonged due to blunted and delayed inhibition of ACTH secretion, thus increasing the total exposure to glucocorticoids.

Differences in hypothalamic-pituitary-adrenal (HPA) axis responsiveness to lumbar puncture (LP) stress were studied in normal elderly subjects and Alzheimer's disease (AD) patients of both genders. Elderly normal subjects had larger peak cortisol and ACTH responses than AD patients. These results contrast with some previous reports of increased HPA-axis responsivity associated with AD and suggest that AD-related changes in HPA responsiveness depend on the type of stressor involved and are mediated 'upstream' to the final common pathway to ACTH secretion. HPA-axis responsiveness also differed by gender, with higher peaks and prolonged elevations in elderly female subjects than in elderly males.

Central nervous system (CNS) adrenergic systems are involved in regulation of behavior and blood pressure. The effects of Alzheimer's disease (AD) and normal aging on resting CNS adrenergic activity were estimated by measuring cerebrospinal fluid (CSF) epinephrine (EPI) concentrations in 74 persons with AD, 42 cognitively normal healthy older persons, and 54 healthy young persons. The responsiveness of CSF EPI to the alpha-2 adrenergic antagonist yohimbine and the alpha-2 adrenergic agonist clonidine was measured in smaller subject groups. Resting CSF EPI was higher in AD than in older or young subjects, and increased with dementia severity in AD subjects. There was no relationship between resting CSF EPI and blood pressure. CSF EPI increased following yohimbine in AD and older subjects but not in young subjects. CSF EPI was unaffected by clonidine in all subject groups. The agitation increase following yohimbine was substantially greater in AD subjects than in older or young subjects. CNS adrenergic activity seems increased in AD, may further increase as AD progresses, and may be involved in the pathophysiology of agitation.

To assess the effects of aging on hypothalamic-pituitary-adrenal (HPA) axis responsivity, we compared the plasma cortisol and adrenocorticotropin (ACTH) responses to hypertonic saline infusion between normal older and young human volunteers. We administered a 90 min hypertonic saline infusion (5% sodium chloride at 0.06 ml/kg/min) and a 90 min placebo infusion (0.9% sodium chloride at 0.06 ml/kg/min) to normal young subjects (n = 13, age = 29 +/- 2 years) and normal older subjects (n = 8, age = 63 +/- 3 years). Plasma cortisol, ACTH, osmolality and arginine vasopressin (AVP) were measured before and at 30 min intervals during the infusions. The rate of increase in plasma osmolality and AVP induced by hypertonic saline infusion was similar between groups. The plasma cortisol increase during hypertonic saline infusion was greater in normal older subjects than in young subjects (p = .03), but a stimulatory effect of hypertonic saline infusion on plasma ACTH was not apparent in either older or young subjects. These results suggest increased sensitivity with human aging to stimulation of cortisol release by hypertonic saline infusion at the adrenocortical level of the HPA axis.

We determined whether transient tachypnoea of the newborn (TTN) is more common in macrosomic versus normal weight infants and in those delivered by caesarean section versus vaginally, in a retrospective cohort analysis of 212 type 1 diabetes pregnancies. Caesarean section and macrosomia were both associated with higher TTN rates.

National governments worldwide work to improve education and health outcomes for children and youth and influence their behaviours. Also heavily engaged are national non-governmental organisations (NGOs) in the voluntary and non-profit sector. While individual agencies and non-profit organisations are often concerned with specific issues of interest related to their charge, constituency or membership, they often develop allegiances with like-minded groups to accomplish broader goals. Two such collaborations in the United States are the focus of this discussion, the National Co-ordinating Committee on School Health and Safety (NCCSHS) and the Friends of School Health (hereafter, "the Friends"). This article reviews these two significant partnerships of public health and education NGOs and outlines successful strategies and lessons learned from the development of these large-scale partnerships. NCCSHS is a collaboration of 64 NGOs and six U.S. government departments representing both the fields of public health and education. Nearly all major NGOs working in fields related to school health are represented, and the six primary governmental agencies all have at least some responsibility for students' health and safety. The group is the primary intersection of NGOs and the Federal government related to school health at the national level. The Friends of School Health ("the Friends") is the primary school health advocacy coalition at the national level in the United States. Sixty-one education and public health NGOs participate. The coalition serves as a communication mechanism and venue for collaborative action on issues before the U.S. Congress and state legislatures that relate to school health. Since the coalition advocates to legislators and other decision makers, no government agencies participate. The paper describes the strategies relating to the initial development of the collaboratives and their ongoing operation. A common theme in development of both of these examples of large-scale partnerships is trust. Like any partnership, the ability to work and grow is dependent on the level of trust among the partners. Both the National Coordinating Committee on School Health and Safety and the Friends of School Health work together successfully within and across their collaborations, to improve health and educational outcomes for children and youth. While both experience challenges, and neither would indicate that its work is near completion, they provide important insight into how these collaboratives can initially develop and subsequently operate productively while providing important contributions to the promotion of healthy schools, and ultimately, healthy nations.

PUBLISHED, Homozygosity for the T allele of the C677T polymorphism of the gene encoding the folate dependent enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is a risk factor for neural tube defects.1 Both the homozygous (TT) and heterozygous (CT) genotypes are associated with lower tissue concentrations of folate, higher homocysteine concentrations, and lower enzyme activity than the wild type (CC) genotype; these effects are more marked in homozygotes. Low folate and raised homocysteine levels in early pregnancy are risk factors for neural tube defects.2 We investigated the possibility that the CT genotype would also increase the risk of these malformations.

Background: The resting cerebrospinal fluid (CSF) norepinephrine concentration is unchanged or even increased in patients with Alzheimer's disease (AD). These in vivo findings appear to be inconsistent with the postmortem locus ceruleus neuronal loss that is reported in patients with AD. Methods: The effects of AD and advanced age on central nervous system noradrenergic status were estimated by comparing CSF norepinephrine concentrations following the administration of yohimbine hydrochloride, clonidine hydrochloride, and placebo in outpatients with AD and older and young normal subjects. Levels of yohimbine, its metabolite 11-hydroxy-yohimbine, and clonidine were measured in CSF and plasma samples. Behavioral responses were quantified by rating the Tension, Excitement, and Anxiety items on the Brief Psychiatric Rating Scale. Results: Yohimbine-induced increases of CSF norepinephrine concentrations were greater in both patients with AD and normal older subjects than in normal young subjects. Clonidine-induced decreases of CSF norepinephrine concentrations did not differ among groups. Behavioral arousal following the administration of yohimbine was greater in patients with AD than in the other groups. Conclusions: Central nervous system noradrenergic responsiveness is enhanced in normal older subjects, and this age effect is retained in patients with AD. Behavioral sensitivity to increased central nervous system noradrenergic activity is enhanced in patients with AD.

Intraventricular hemorrhage (IVH) is the most common brain lesion documented at autopsy in 40% to 50% of preterm infants with birth weights less than 1,500 g (Papile, Burstein, Burstein, & Kofler, 1978). The incidence of IVH remains high in the very low birth weight preterm population because of improved survival rates of infants with increasingly shorter gestations in whom IVH insult can be expected (Shinnar, Molteni, Gammon, D’Souva, Altman, & Freeman, 1982). Ultrasonographic studies conducted within 2 to 10 days of preterm birth can detect IVH in approximately one-third of infants of very low birth weight (less than 1,500 g) (Ahmann, Lazzara, Dykes, Brann, & Schwartz, 1978; Papile et al., 1978).