Interprofessional student teams augmenting service provision in residential aged care.

The aim of this study was to determine the usefulness of student-led interprofessional consultations within residential aged care in augmenting patient care and enhancing student education. Volunteer fourth and final year health-care students conducted interprofessional consultations. In a mixed methods design, residents' health-care changes and perspectives were collected prospectively, and student and educator perceptions were measured by survey and interview. Sixteen aged care residents were consulted by interprofessional teams. Students identified two new health issues and proposed 17 recommendations for referrals and five changes to medication management. At six-weeks follow-up, two recommendations had been acted upon clinically, and two medication changes had been implemented. Reasons for the low uptake of recommendations were determined. Residents, students and educators reported high levels of satisfaction. Residential care facilities offer a useful interprofessional learning environment. Student consultations are positively regarded by patients, students and educators and may augment existing health services.

How do interprofessional student teams interact in a primary care clinic? A qualitative analysis using activity theory.

Practice based interprofessional education opportunities are proposed as a mechanism for health professionals to learn teamwork skills and gain an understanding of the roles of others. Primary care is an area of practice that offers a promising option for interprofessional student learning. In this study, we investigated what and how students from differing professions learn together. Our findings inform the design of future interprofessional education initiatives. Using activity theory, we conducted an ethnographic investigation of interprofessional education in primary care. During a 5 months period, we observed 14 clinic sessions involving mixed discipline student teams who interviewed people with chronic disease. Teams were comprised of senior medicine, nursing, occupational therapy, pharmacy and physiotherapy entry level students. Semi-structured interviews were also conducted with seven clinical educators. Data were analysed to ascertain the objectives, tools, rules and division of labour. Two integrated activity systems were identified: (1) student teams gathering information to determine patients' health care needs and (2) patients either as health consumers or student educators. Unwritten rules regarding 'shared contribution', 'patient as key information source' and 'time constraints' were identified. Both the significance of software literacy on team leadership, and a pre-determined structure of enquiry, highlighted the importance of careful consideration of the tools used in interprofessional education, and the way they can influence practice. The systems of practice identified provide evidence of differing priorities and values, and multiple perspectives of how to manage health. The work reinforced the value of the patients' voice in clinical and education processes.

Prenatal glucocorticoid exposure in the sheep alters renal development in utero: implications for adult renal function and blood pressure control.

Treatment of the pregnant ewe with glucocorticoids early in pregnancy results in offspring with hypertension. This study examined whether glucocorticoids can reduce nephron formation or alter gene expression for sodium channels in the late gestation fetus. Sodium channel expression was also examined in 2-mo-old lambs, while arterial pressure and renal function was examined in adult female offspring before and during 6 wk of increased dietary salt intake. Pregnant ewes were treated with saline (SAL), dexamethasone (DEX; 0.48 mg/h) or cortisol (CORT; 5 mg/h) over days 26-28 of gestation (term = 150 days). At 140 days of gestation, glomerular number in CORT and DEX animals was 40 and 25% less, respectively, compared with SAL controls. Real-time PCR showed greater gene expression for the epithelial sodium channel (α-, ß-, γ-subunits) and Na(+)-K(+)-ATPase (α-, ß-, γ-subunits) in both the DEX and CORT group fetal kidneys compared with the SAL group with some of these changes persisting in 2-mo-old female offspring. In adulthood, sheep treated with dexamethasone or cortisol in utero had elevated arterial pressure and an apparent increase in single nephron glomerular filtration rate, but global renal hemodynamics and excretory function were normal and arterial pressure was not salt sensitive. Our findings show that the nephron-deficit in sheep exposed to glucocorticoids in utero is acquired before birth, so it is a potential cause, rather than a consequence, of their elevated arterial pressure in adulthood. Upregulation of sodium channels in these animals could provide a mechanistic link to sustained increases in arterial pressure in cortisol- and dexamethasone-exposed sheep, since it would be expected to promote salt and water retention during the postnatal period.

Haemodynamic characteristics of hypertension induced by prenatal cortisol exposure in sheep.

1. Administration of glucocorticoids to ewes early in pregnancy results in offspring with hypertension in adulthood. The hypertension in female offspring exposed to dexamethasone is associated with increased cardiac output, but whether this is also true in cortisol-exposed offspring is unknown. 2. Systemic haemodynamic variables were measured under basal conditions in castrated male and female adult sheep exposed to cortisol (5 mg/h) or saline (0.19 mL/h) from 26 to 28 days of gestation. To examine the contribution of the autonomic nervous system to maintenance of basal arterial pressure in established hypertension in cortisol-exposed sheep, responses to adrenoceptor blockade (intravenous infusion of 0.15 mg/kg per h phentolamine plus 0.4 mg/kg per h propranolol) and ganglionic blockade (intravenous infusion of 125 mg/h hexamethonium) were examined in castrated male offspring. 3. Mean arterial pressure and calculated systemic vascular resistance were 9% and 17% greater, whereas cardiac output tended to be 8% less, in cortisol-compared with saline-exposed sheep. These effects were not sex dependent. The depressor response to ganglionic blockade and the initial phase of the depressor response to adrenoceptor blockade were greater in cortisol-compared with saline-exposed sheep. 4. These results indicate that hypertension in offspring exposed prenatally to cortisol is associated with increased total peripheral resistance, mimicking observations in human patients with chronic hypertension. Furthermore, the increased vascular resistance appears to be dependent, at least in part, on an increased effect of sympathetic vasomotor drive. Taken together with previous findings, the present observations suggest that prenatal cortisol and dexamethasone programme altered adult cardiovascular function via distinct mechanistic pathways.

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. The aim of this study was to determine the effects of late gestational IUGR on coronary artery function and cardiomyocyte maturation in the fetus. IUGR was induced by placental embolization in fetal sheep from 110 to 130 days of pregnancy (D110-130); term approximately D147; control fetuses received saline. At necropsy (D130), wire and pressure myography was used to test endothelial and smooth muscle function, and passive mechanical wall properties, respectively, in small branches of left descending coronary arteries. Myocardium was dissociated for histological analysis of cardiomyocytes. At D130, IUGR fetuses (2.7 +/- 0.1 kg) were 28% lighter than controls (3.7 +/- 0.3 kg; P = 0.02). Coronary arteries from IUGR fetuses had enhanced responsiveness to the vasoconstrictors, angiotensin II and the thromboxane analogue U46619, than controls (P < 0.01). Endothelium-dependent and -independent relaxations were not different between groups. Coronary arteries of IUGR fetuses were more compliant (P = 0.02) than those of controls. The incidence of cardiomyocyte binucleation was lower in the left ventricles of IUGR fetuses (P = 0.02), suggestive of retarded cardiomyocyte maturation. We conclude that late gestational IUGR alters the reactivity and mechanical wall properties of coronary arteries and cardiomyocyte maturation in fetal sheep, which could have lifelong implications for cardiovascular function.

Atrial electrical and structural abnormalities in an ovine model of chronic blood pressure elevation after prenatal corticosteroid exposure: implications for development of atrial fibrillation.

AIMS: Elevated blood pressure (EBP) is the most prevalent and potentially modifiable risk factor for AF, yet little is known of its atrial effects. We aimed to characterize the atrial electrical and structural changes in a chronic ovine model of EBP after prenatal corticosteroid exposure. METHODS AND RESULTS: Twelve sheep with chronically EBP (mean arterial pressure 94+/-3 mmHg) and six controls (71+/-4 mmHg, P<0.01) underwent acute open chest electrophysiologic and pathologic studies. We measured refractoriness at the atrial appendages at 3 cycle lengths (CL); conduction velocities at Bachmann's bundle, both atrial appendages and free walls at 4 CLs; conduction heterogeneity; atrial wavelength and AF duration. We performed light microscopy (LM) and electron microscopy (EM) and collagen and apoptosis studies. EBP was associated with widespread conduction abnormalities, shortening of atrial wavelength, and increased AF. There was no significant change in refractoriness. LM demonstrated atrial myocyte hypertrophy and myolysis in all EBP sheep and focal scarring in six. EM demonstrated mitochondrial and nuclear enlargement and increased collagen fibrils in EBP sheep, findings not present in any controls. Atrial collagen and apoptosis were increased in EBP animals. CONCLUSION: This study demonstrates that chronically, EBP is associated with significant atrial electrical and structural remodelling. These changes may explain the increased propensity to atrial arrhythmias observed with long-standing EBP.

Reduced renal reserve and increased cardiac output in adult female sheep uninephrectomized as fetuses.

BACKGROUND: Removal of one kidney during the period of nephrogenesis in the sheep leads to offspring with elevated blood pressure and reduced glomerular filtration rate (GFR) at 6 and 12 months of age. The mechanisms underlying the hypertension and the degree of renal impairment are not known. METHODS: Changes in GFR were measured in response to an infusion of amino acids and cardiac output was measured by thermal dilution in female offspring at 2 years of age in eight control (sham-operated) and seven animals that had been unilaterally nephrectomized at 100 days of gestation. RESULTS: Animals uninephrectomized as fetuses had significantly higher blood pressure (91 +/- 2 mm Hg) compared to control animals (86 +/- 2 mm Hg) (P < 0.05). Cardiac output was significantly higher in the uninephrectomized group (148 +/- 10 mL/kg/min) compared to the control group (124 +/- 6 mL/kg/min) (P < 0.05). Heart rate and stroke volume were similar in the two groups although both parameters tended to be higher in the uninephrectomized group. Uninephrectomized animals had a lower basal GFR (P < 0.05). An infusion of amino acids caused a significantly different response in GFR in the two groups (P < 0.01 between the groups) with the uninephrectomized animals having significantly lower GFRs during the infusion period. CONCLUSION: The increased blood pressure observed after fetal uninephrectomy is due to an increase in cardiac output. Thus, formation of a low number of nephrons in utero may predispose an individual to later renal failure and elevated blood pressure.

Fetal renal and blood pressure responses to steroid infusion after early prenatal treatment with dexamethasone.

Maternal infusion of dexamethasone for 48 h early in gestation results in upregulation of mRNA for mineralocorticoid and glucocorticoid (MR and GR) receptors and angiotensin II receptors in ovine fetal kidneys late in gestation. This study sought to determine whether dexamethasone exposure results in changes in renal function and blood pressure responsiveness to infused cortisol or aldosterone in the late-gestation fetus. Merino ewes carrying single fetuses were infused with isotonic saline (Sal; n = 9) or dexamethasone (Dex, 0.48 mg/h; n = 10) for 48 h between days 26 and 28 of gestation (term = 150 days). At 115-122 days, renal function and blood pressure were measured in fetuses during a 4-h infusion of saline, cortisol (100 microg/h), or aldosterone (5 microg/h). Infusions were given in random order at least 2 days apart. Basal blood pressure and renal function were similar in Sal and Dex groups and did not change over the course of saline infusion. Cortisol infusion caused similar increases in blood pressure, urine flow, and glomerular filtration rate (GFR) in the groups. Aldosterone infusion caused a significantly different GFR response between the groups [P(treatment x time) < 0.05], but increase in K excretion and decrease in Na-to-K ratio were similar in the groups. The similar results obtained with cortisol and aldosterone infusion suggest no increased renal functional maturity to those hormones after early prenatal dexamethasone exposure. This suggests that changes in mRNA for MR and GR in kidneys of dexamethasone-exposed fetuses do not result in functional differences and highlights the renin-angiotensin system, as reported previously, as more important in this model.

Kidney development and the fetal programming of adult disease.

Recent evidence, from both epidemiological and animal experimental studies, suggest that the very first environment, the intrauterine, is extremely important in determining the future health of the individual. Genetic and 'lifestyle' factors impinge on, and can exacerbate, a 'programming' effect of an adverse fetal environment. In this review, we present compelling evidence to suggest that one of the major organs affected by an unfavourable prenatal environment is the kidney. Many of the factors that can affect fetal renal development (i.e. exposure to excess glucocorticoids, insufficient vitamin A, protein/calorie malnutrition (in rats) and alterations in the intrarenal renin angiotensinogen system), also produce hypertension in the adult animal. When nephron number is compromised during kidney development, maladaptive functional changes occur and can lead, eventually, to hypertension and/or renal disease. Surprisingly, it is during the very earliest stages of kidney development that the vulnerability to these effects occurs.

Programming effects of short prenatal exposure to dexamethasone in sheep.

Recent studies have linked fetal exposure to a suboptimal intrauterine environment with adult hypertension. The aims of the present study were to see whether prenatal dexamethasone administered intravenously to the ewe between 26 to 28 days of gestation (1) resulted in high blood pressure in male and female offspring and whether hypertension in males was modulated by testosterone status, and (2) altered gene expression for angiotensinogen and angiotensin type 1 (AT1) receptors in the brain in late gestation and in the adult. Basal mean arterial pressure (MAP) at 2 years of age was significantly higher in wethers exposed to prenatal dexamethasone (group D; 106+/-5 mm Hg, n=9) compared with the control group (group S; 91+/-3 mm Hg, n=8; P<0.01). Infusion of testosterone for 3 weeks had no effect on MAP in either treatment group. At 130 days of gestation, dexamethasone administered between 26 to 28 days of gestation (group DF; n=8), resulted in an increased expression of angiotensinogen in hypothalamus (in arbitrary units: 2.5+/-0.3 versus 1.3+/-0.3 in the saline group [group SF], n=10; P<0.05). In addition, there was higher expression of the AT1 receptors in medulla oblongata in group DF (2.6+/-0.6 versus 1.1+/-0.2 in group SF; P<0.01). This effect of prenatal dexamethasone treatment was still evident in females at 7 years of age (group DA; n=5; 2.6+/-0.5 versus 1.1+/-0.2 in group SA; n=6, P<0.05). In conclusion, brief prenatal exposure of the pregnant ewe to dexamethasone leads to hypertension in adult animals of both sexes. Most interestingly, the mechanism leading to programming of hypertension might be linked with the brain angiotensin system.

Programmed hypertension: kidney, brain or both?

The results from numerous epidemiological studies suggested that there was a link between low birth weight (low for gestational age) and development of high blood pressure in adulthood. More recently, it has been shown that one important determinant is the early exposure of the developing fetus to excess glucocorticoid (GC). Hypertension develops in adult sheep and rats that are exposed to excess GC at a stage in gestation when both kidney and brain are still extremely primitive organs. Here, we propose that permanent changes in gene expression and function of these two organs could be crucial in the development of adult-onset hypertension as a result of prenatal GC exposure.

Fetal uninephrectomy leads to postnatal hypertension and compromised renal function.

It has been proposed that the number of nephrons an individual has may be inversely related to his or her blood pressure. In this study using female ovine fetuses, nephron number was reduced by performing a fetal uninephrectomy during the period of active nephrogenesis (100 days of gestation, term=150 days). Lambs were born at term and grew at a similar rate. At 5 months of age, ovaries were removed and the carotid artery exteriorized into a fold of skin. Blood pressure and renal function were studied at 6 and 12 months of age. At 6 months of age, uninephrectomized lambs had significantly higher mean arterial blood pressure than sham-operated lambs (89+/-2 versus 82+/-2 mm Hg, P<0.05) when measured over a 3-day period. Heart rate was not different between the groups. Urine flow rate was similar, but glomerular filtration rate was significantly lower in uninephrectomized animals (P<0.05). Urinary concentrations and excretion rates of sodium tended to be higher in uninephrectomized animals but were similar for chloride and potassium. There was no evidence of proteinuria in the uninephrectomized lambs. Similar differences were observed in blood pressure and renal function at 12 months of age. Plasma renin concentrations at this age were lower in the uninephrectomized lambs (P<0.05). An oral salt load for 10 days did not increase blood pressure significantly in either group at 12 months of age, nor were there differences in the responsiveness to graded doses of angiotensin II. These results suggest that formation of a low nephron number in utero, may result in elevated blood pressure and compromised renal function in later life.

Programming effects of short prenatal exposure to cortisol.

Recent studies have linked fetal exposure to a suboptimal intrauterine environment with adult hypertension. The aims of this study were twofold: 1) to see whether cortisol treatment administered to the ewe for 2 days at 27 days of gestation (term approximately 150 days) resulted in high blood pressure in offspring; 2) to study the effect of the same treatment on gene expression in the brain at 130 days of gestation and in lambs at 2 months of age. Mean arterial pressure was significantly higher in the adult female and male offspring of sheep treated with cortisol than in the control group (females: 89+/-2 mmHg vs. 81+/-2; P<0.05 and males: 102+/-4 mmHg vs. 91+/-3; P<0.05). Prenatal cortisol treatment led to up-regulation of angiotensinogen, AT1, MR, and GR mRNA in the hippocampus in fetuses at 130 days of gestation but not in the animals at 2 months of age. This is the first evidence that short prenatal exposure to cortisol programmed high blood pressure in the adult female and male offspring of sheep. Altered gene expression in the hippocampus could have a significant effect on the development of the hippocampus, and on postnatal behavior.

Effect of early glucocorticoid treatment on MR and GR in late gestation ovine kidney.

BACKGROUND: The ontogeny of the renal mineralocorticoid (MR) and glucocorticoid (GR) receptors in the ovine fetus, and the effects of early exposure to synthetic or natural glucocorticoids on the expression of these genes in late gestation were examined. METHODS: A partial cDNA sequence for the ovine MR was cloned and used to generate primers and probes to measure MR mRNA expression by real-time polymerase chain reaction (PCR). GR mRNA was also measured. Kidneys were collected from ovine fetuses at various stages of gestation (days 60 to 140), twin ovine fetuses at 130 days, from ewes treated at days 26 to 28 with either saline, dexamethasone or cortisol, and adult sheep. Ligand binding was used to determine both GR and MR protein levels in all 130-day-old fetuses and adults. RESULTS: No significant changes in the expression of either renal MR or GR were detected throughout gestation. Cytosolic protein levels were higher in the fetal kidneys than in the adult. There was a significant increase in both fetal MR and GR mRNA expression, but not protein levels in kidneys from ewes pretreated with dexamethasone. CONCLUSIONS: MR and GR mRNA are expressed throughout development in ovine fetal kidneys. Dexamethasone treatment resulted in increased expression of MR and GR mRNA but not protein levels. The dissociation between fetal mRNA and protein levels, relative to adult kidneys, suggests that it may be confounding to draw conclusions based on mRNA levels alone.

No evidence for HPA reset in adult sheep with high blood pressure due to short prenatal exposure to dexamethasone.

Exposure of pregnant ewes to dexamethasone, for only 2 days (term approximately 150 days) at 27 days of gestation (group D), results in adult offspring with high blood pressure. In this study, hemorrhage stress has been used to see whether in these animals the responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis is altered. In addition, we studied mineralocorticoid (MR) and glucocorticoid (GR) receptor gene expression in the hippocampus and GR gene expression in the hypothalamus using real-time PCR. Calculated areas under the adrenocorticotropin, arginine vasopressin, and cortisol plasma concentration curves in response to hemorrhage were similar between the control and group D. In addition, there was no significant difference in the expression of MR and GR in the hippocampus or GR in the hypothalamus between the control and group D. Taken together, it is unlikely that reset in the HPA axis plays a major role in this particular model of "programmed" hypertension.