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N Hoggard

Publications and source records attributed to N Hoggard.

At least 19 recordsLinked to original sources
PubMed2006

Sequential dynamic gadolinium magnetic resonance perfusion-weighted imaging: effects on transit time and cerebral blood volume measurements.

PURPOSE: To evaluate if two gadolinium perfusion studies can be performed during the same table occupancy without degradation of the derived data in the second study. MATERIAL AND METHODS: Magnetic resonance (MR) perfusion studies of the whole brain were performed on 12 patients during the administration of two gadolinium boluses separated by 8 min. In six patients, gadolinium was given as two 20-ml administrations of standard 0.5 M chelate (Magnevist), whilst the other six patients received two 10-ml administrations of 1.0 M chelate (Gadovist). RESULTS: There were no significant differences in subjective quality between the time-intensity curves of the first and second perfusion studies using either the 0.5 M or 1.0 M gadolinium chelate. The objective measurements in quality of the time-intensity curves (maximum signal change and full width at half maximum) changed by less than 5% of the original values on the second perfusion study. The first-moment mean transit times did not change significantly on the sequential studies. The regional cerebral blood volume tended to increase on the second study (by 15% on average), but this did not reach statistical significance. CONCLUSION: The results from two sequential dynamic gadolinium-based perfusion studies can be compared in a meaningful manner using the technique described.

Aged↗
PubMed2004

Regulation of adipose tissue leptin secretion by alpha-melanocyte-stimulating hormone and agouti-related protein: further evidence of an interaction between leptin and the melanocortin signalling system.

The central role of the melanocortin system in the regulation of energy balance has been studied in great detail. However, the functions of circulating melanocortins and the roles of their peripheral receptors remain to be elucidated. There is increasing evidence of a peripheral action of melanocortins in the regulation of leptin production by adipocytes. Here we investigate the interaction of alpha-melanocyte stimulating hormone (alpha-MSH) and agouti-related protein (AgRP) in the regulation of leptin secretion from cultured rat adipocytes and examine the changes in circulating alpha-MSH and AgRP in lean and obese rodents after hormonal and energetic challenge. Leptin secretion (measured by ELISA) and gene expression (by real-time quantitative PCR) of differentiated rat adipocytes cultured in vitro were inhibited by the administration of alpha-MSH (EC50=0.24 nM), and this effect was antagonised by antagonists of the melanocortin receptors MC4R and MC3R (AgRP and SHU9119). The presence of MC4R in rat adipocytes (RT-PCR and restriction digest) supports the involvement of this receptor subtype in this interaction. Leptin administered to ob/ob mice in turn increases the release of alpha-MSH into the circulation, suggesting a possible feedback loop between the site of alpha-MSH release and the release of leptin from the adipose tissue. However, the physiological significance of this putative feedback probably depends upon the underlying state of energy balance, since in the fasting state low plasma alpha-MSH is paralleled by low plasma leptin.

Adipocytes↗
PubMed2004

Peripherally administered [Nle4,D-Phe7]-alpha-melanocyte stimulating hormone increases resting metabolic rate, while peripheral agouti-related protein has no effect, in wild type C57BL/6 and ob/ob mice.

The melanocortin system coordinates the maintenance of energy balance via the regulation of both food intake and energy expenditure. Leptin, a key adipogenic hormone involved in the regulation of energy balance is thought to act by stimulating production, in the hypothalamic arcuate nucleus, of alpha-melanocyte stimulating hormone (alphaMSH), a potent agonist of MC3/4 melanocortin receptors located in the paraventricular nucleus of the hypothalamus. Additionally leptin inhibits release of agouti-related protein (AgRP), an MC4R antagonist. During periods of caloric restriction, weight loss is not sustained because compensatory mechanisms, such as reduced resting metabolic rate (RMR) are brought into play. Understanding how these compensatory systems operate may provide valuable targets for pharmaceutical therapies to support traditional dieting approaches. As circulating leptin is reduced during caloric restriction, it may mediate some of the observed compensatory responses. In addition to decreases in circulating leptin levels, circulating AgRP is increased during fasting in rodents while alphaMSH is decreased. As central administration of AgRP depresses metabolism, we hypothesised that the peripheral rise in AgRP might be involved in signalling the depression of RMR during food restriction. We hypothesised that changes in plasma AgRP and alphaMSH may coordinate the regulation of changes in energy expenditure acting through central MC4 melanocortin receptors via the sympathetic nervous system.We show here that acute peripherally administered AgRP at supra-physiological concentrations in both lean (C57BL/6) and obese leptin-deficient (ob/ob) mice does not depress RMR, possibly because it crosses the blood-brain barrier very slowly compared with other metabolites. However, in vitro AgRP can decrease leptin secretion, by approximately 40%, from adipocytes into culture medium and may via this axis have an effect on energy metabolism during prolonged caloric restriction. In contrast, peripheral [Nle4,D-Phe7]-alpha MSH produced a large and sustained increase in resting energy expenditure (0.15 ml O2/min; P < 0.05) with a similar response in leptin-deficient ob/ob mice (0.27 ml O2/min) indicating that this effect is independent of the status of leptin production in the periphery. In both cases respiratory exchange ratio and the levels of energy expended on spontaneous physical activity were unaffected by the administration of peripheral [Nle4,D-Phe7]-alpha MSH. In conclusion, alphaMSH analogues that cross the blood-brain barrier may significantly augment dietary restriction strategies by sustaining elevated RMR.

Agouti-Related Protein↗
PubMed2002

Imaging of haemorrhagic stroke.

Computed tomography (CT) is the reference standard for the imaging of acute non-traumatic intracranial haemorrhage. The sensitivity with which CT detects haemorrhage falls with time and lumber puncture remains mandatory for the exclusion of subarachnoid haemorrhage (SAH). Magnetic resonance (MR) imaging is, however, superior to CT in the subacute and chronic stages after haemorrhage. MR in addition offers pathophysiological information that can help with assessment of both the aetiology of and complications arising from both SAH and intra-parenchymal haemorrhage.

Angiography↗
PubMed2002

Plasma leptin concentration in fetal sheep during late gestation: ontogeny and effect of glucocorticoids.

The ontogeny and developmental control of plasma leptin concentration in the fetus are poorly understood. The present study investigated plasma leptin concentration in chronically catheterized sheep fetuses near term, and in neonatal and adult sheep. The effect of glucocorticoids on plasma leptin in utero was examined by fetal adrenalectomy and exogenous cortisol or dexamethasone infusion. In intact, untreated fetuses studied between 130 and 140 d (term, 145 +/- 2 d), plasma leptin concentration increased in association with the prepartum cortisol surge. Positive relationships were observed between plasma leptin in utero and both gestational age and plasma cortisol. Plasma leptin was also inversely correlated with fetal p(a)O(2). The ontogenic rise in plasma leptin was abolished by fetal adrenalectomy. In intact fetuses at 123-127 d, plasma leptin was increased by infusions of cortisol (3-5 mg kg(-1)d(-1), +127 +/- 21%) for 5 d and dexamethasone (45-60 microg kg(-1)d(-1), +268 +/- 61%) for 2 d. However, the cortisol-induced rise in plasma leptin was transient; by the fifth day of infusion, plasma leptin was restored to within the baseline range. These findings show that, in the sheep fetus, an intact adrenal gland is required for the normal ontogenic rise in plasma leptin near term. Furthermore, fetal treatment with exogenous and endogenous glucocorticoids increases circulating leptin concentration in utero.

Adrenalectomy↗
PubMed2001

Leptin expression in placental and fetal tissues: does leptin have a functional role?

Leptin is expressed in the placenta and in certain fetal tissues; however, little is known with regard to the function of this hormone in these tissues. To date, most evidence suggests that placental and/or fetal leptin acts as a fetal growth factor, but this is far from clear. Leptin may also have physiological effects on the placenta, including angiogenesis, growth and immunomodulation. The effects of placental leptin, if any, on the mother may contribute to endocrine-mediated alterations in energy balance, such as the mobilization of maternal fat, which occurs during the second half of pregnancy. In this review we will address these and other issues related to the expression of both placental and fetal leptin.

Animals↗
PubMed2001

The imaging of ischaemic stroke.

Stroke is a clinical syndrome of a rapidly developing focal neurological deficit that may be classified for practical purposes into ischaemic and haemorrhagic. The role of imaging is to exclude mimics of ischaemic stroke or intracranial haemorrhage and confirm the presence of an ischaemic stroke. Computed tomography (CT) remains the investigation of choice to exclude acute intracranial haemorrhage but diffusion weighted magnetic resonance (MR) has proved to be a sensitive method of detecting early ischaemic infarction. Perfusion weighted MR allows further assessment at the same examination that could help guide the clinician in the risk/benefit analysis of treatment with thrombolytics or neuroprotective agents under evaluation. This can also be achieved with CT. This review article discusses the imaging of ischaemic stroke, relating the pathophysiology of stroke to it. It deals separately in more detail with these newer MR techniques.

Aged↗
PubMed2001

Leptin secretion to both the maternal and fetal circulation in the ex vivo perfused human term placenta.

The contribution of placental leptin, if any, to both the fetal and maternal circulation and its role in pregnancy remains to be determined. In an experiment to investigate this, 27 placentae from term pregnancies were perfused ex vivo (gestational age=39.5 s.d. 1.2; range=38-42 weeks: fetal weight=3285 s.d. 482; range=2480-4420; birthweight centile range=4th to the 98th) at both the maternal and fetal interface. Placental leptin was exported into both the maternal and fetal circulations. The log leptin production by the maternal side of the placenta was significantly greater (P=0.001) than that for the fetal side (5.193 s.d.1.049 versus 4.387 s.d. 0.768 ng/placenta/min). There was no significant relationship between maternal and fetal log leptin production and maternal body mass index, birthweight, birthweight centile, ponderal index or gestational age or with cord blood pO(2), pCO(2) and pH. There was however, a significant increase in the maternal log leptin production with increasing fetal to placental weight ratio (P=0.017; r(2)=20.7 per cent) but no corresponding relationship for fetal leptin production. It is proposed that such a mechanism would allow the placenta to modulate fat supply to the fetus in response to the fetal demand relative to placental supply.

Body Mass Index↗
PubMed2001

Detection of subarachnoid haemorrhage with magnetic resonance imaging.

OBJECTIVES: To measure the sensitivity and specificity of five MRI sequences to subarachnoid haemorrhage. METHODS: Forty one patients presenting with histories suspicious of subarachnoid haemorrhage (SAH) were investigated with MRI using T1 weighted, T2 weighted, single shot fast spin echo (express), fluid attenuation inversion recovery (FLAIR), and gradient echo T2* sequences, and also by CT. Lumbar puncture was performed in cases where CT was negative for SAH. Cases were divided into acute (scanned within 4 days of the haemorrhage) and subacute (scanned after 4 days) groups. RESULTS: The gradient echo T2* was the most sensitive sequence, with sensitivities of 94% in the acute phase and 100% in the subacute phase. Next most sensitive was FLAIR with values of 81% and 87% for the acute and subacute phases respectively. Other sequences were considerably less sensitive. CONCLUSIONS: MRI can be used to detect subacute and acute subarachnoid haemorrhage and has significant advantages over CT in the detection of subacute subarachnoid haemorrhage. The most sensitive sequence was the gradient echo T2*.

Adult↗
PubMed2001

Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: effects on placental leptin and fetal growth.

Gestational diabetes mellitus (GDM) results from an interaction between susceptibility genes and the diabetogenic effects of pregnancy. During pregnancy, mice heterozygous for the lepin receptor (db/+) gain more weight, are glucose intolerant, and produce macrosomic fetuses compared with wild-type (+/+) mothers, suggesting that an alteration in leptin action may play a role in GDM and fetal overgrowth. To investigate whether leptin administration or pair-feeding can reduce adiposity and thereby prevent GDM and neonatal overgrowth, we examined energy balance, glucose and insulin tolerance, and fetal growth in pregnant db/+ and +/+ mice treated with recombinant human leptin-IgG during late pregnancy. Leptin reduced food intake and adiposity in pregnant db/+ mice to levels similar to pregnant +/+ mice and significantly reduced maternal weight gain. Maternal glucose levels were markedly lower during glucose and insulin challenge tests in leptin-treated db/+ mice relative to db/+ and pair-fed controls. Despite reduced energy intake and improved glucose tolerance, leptin administration did not reduce fetal overgrowth in offspring from db/+ mothers. Fetal and placental leptin levels were 1.3- to 1.5-fold higher in offspring from db/+ mothers and remained unchanged with leptin administration, whereas leptin treatment in +/+ mothers or pair-feeding decreased placental leptin concentration and reduced fetal birth weight. Our results provide evidence that leptin administration during late gestation can reduce adiposity and improve glucose tolerance in the db/+ mouse model of spontaneous GDM. However, fetal and placenta leptin levels are higher in db/+ mothers and are subject to reduced negative feedback in response to leptin treatment. These data suggest that alterations in placenta leptin may contribute to the regulation of fetal growth independently of maternal glucose levels.

Animals↗
PubMed2001

Circulating leptin during ovine pregnancy in relation to maternal nutrition, body composition and pregnancy outcome.

This study examined the pattern of circulating leptin in age-matched sheep during adolescent pregnancy, and its relationship with maternal dietary intake, body composition and tissue expression of the leptin gene. Overfeeding the adolescent pregnant ewe results in rapid maternal growth at the expense of the placenta, leading to growth restriction in the fetus, compared with normal fed controls. Our results demonstrate that, in the adolescent ewe, overfeeding throughout pregnancy was associated with higher maternal leptin concentrations, when compared with moderately fed controls (P<0.05), with no peak in circulating leptin towards the end of pregnancy. There was a close correlation between indices of body composition and circulating leptin levels at day 104 of gestation and at term (P<0.03). Further, when the dietary intake was switched from moderate to high, or high to moderate, at day 50 of gestation, circulating leptin levels changed rapidly, in parallel with the changes in dietary intake. Leptin mRNA levels and leptin protein in perirenal adipose tissue samples, taken at day 128 of gestation, were higher in overfed dams (P<0.04), suggesting that adipose tissue was the source of the increase in circulating leptin in the overnourished ewes. Leptin protein was also detected in placenta but leptin gene expression was negligible. However, leptin receptor gene expression was detected in the ovine placenta, suggesting that the placenta is a target organ for leptin. A negative association existed between maternal circulating leptin and fetal birth weight, placental/cotyledon weight and cotyledon number. In conclusion, in this particular ovine model, hyperleptinaemia was not observed during late pregnancy. Instead, circulating leptin concentrations reflected increased levels of leptin secretion by adipose tissue primarily as a result of the increase in body fat deposition, due to overfeeding. However, there appears to be a direct effect of overfeeding, particularly in the short term. In the nutritional switch-over study, circulating leptin concentrations changed within 48 h of the change in dietary intake. The presence of leptin protein and leptin receptor gene expression in the placenta suggests that leptin could be involved in nutrient partitioning during placental and/or fetal development.

Adipose Tissue↗
PubMed2001

Cerebral arteriovenous malformations: comparison of novel magnetic resonance angiographic techniques and conventional catheter angiography.

OBJECTIVE: To investigate the potential of novel magnetic resonance (MR) angiographic techniques for the assessment of cerebral arteriovenous malformations. METHODS: Forty patients who were about to undergo stereotactic radiosurgery were prospectively recruited. Three-dimensional, sliding-slab interleaved ky (SLINKY), time-of-flight acquisition was performed, as was a dynamic MR digital subtraction angiography (DSA) procedure in which single thick slices (6-10 cm) were obtained using a radiofrequency spoiled Fourier-acquired steady-state sequence (1 image/s). Sixty images were acquired, in two or three projections, during passage of a 6- to 10-ml bolus of gadolinium chelate. Subtraction and postprocessing were performed, and images were viewed in an inverted cine mode. SLINKY time-of-flight acquisition was repeated after the administration of gadolinium. Routine stereotactic conventional catheter angiography was performed after MR imaging. All images were assessed (in a blinded randomized manner) for Spetzler-Martin grading and determination of associated vascular pathological features. RESULTS: Forty-one arteriovenous malformations were assessed in 40 patients. Contrast-enhanced (CE) SLINKY MR angiography was the most consistent MR imaging technique, yielding a 95% correlation with the Spetzler-Martin classification defined by conventional catheter angiography; MR DSA exhibited 90% agreement, and SLINKY MR angiography exhibited 81% agreement. CE SLINKY MR angiography provided improved nidus delineation, compared with non-CE SLINKY MR angiography. Dynamic information from MR DSA significantly improved the observation of early-draining veins and associated aneurysms. CONCLUSION: CE SLINKY MR angiographic assessment of cerebral arteriovenous malformations offers significant advantages, compared with the use of non-CE SLINKY MR angiography, including improved nidus demonstration. MR DSA shows promise as a noninvasive method for dynamic angiography but is presently restricted by limitations in both temporal and spatial resolution.

Adult↗
PubMed2001

In vivo measurement of cerebral blood flow: a review of methods and applications.

This article reviews the concepts of cerebral blood flow for the clinician involved in the management of patients with carotid stenosis and/or ischaemic stroke. Methods of assessing cerebral blood flow in vivo using nuclear medicine, magnetic resonance and X-ray computed tomography are described. Applications of magnetic resonance and X-ray computed tomographic methods are reviewed and illustrated by examples from the authors' radiological practice.

Blood Flow Velocity↗
PubMed2001

Multimodality MR imaging depiction of hemodynamic changes and cerebral ischemia in subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is a common and serious neurologic emergent condition. We tested the hypothesis that multimodality MR imaging depicts changes in cerebral blood flow SAH, before any surgical or endovascular intervention, and that the frequency of these changes increases with time after ictus. METHODS: We prospectively examined 37 patients with suspected SAH and three with symptoms of acute stroke but who subsequently had SAH. Routine CT and multimodality MR imaging were performed within 18 h of presentation. Standard MR imaging, diffusion-weighted MR imaging, time-of-flight MR angiography, and dynamic first-pass gadolinium-enhanced MR perfusion imaging were performed. Images were reviewed for abnormalities in cerebral blood flow, ischemia, and infarction. Nine patients did not have SAH at CT and CSF investigations. Of 31 patients with proved SAH, 13 were examined during the acute stage (within 4 d of ictus) and 18, during the subacute stage (4-14 d after ictus). RESULTS: MR imaging showed alteration in cerebral blood flow parameters in 16 of 31 patients before surgery or endovascular treatment. The frequency of blood flow changes and associated complications increased with worsening clinical grade and increasing time after ictus. CONCLUSION: Multimodality MR imaging provides information not available from CT in patients with SAH. MR imaging shows oligemic and ischemic areas in SAH before surgery or endovascular treatment. MR imaging is a simple noninvasive method of assessing cerebral blood flow and its complications in SAH. It can be performed in a clinical environment.

Adult↗