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R M Wellard

Publications and source records attributed to R M Wellard.

16 recordsLinked to original sources
PubMed2005

Insights into the acute cerebral metabolic changes associated with childhood diabetes.

AIMS: Type 1 diabetes is a prevalent chronic disease in childhood with the commonest single cause of death being cerebral oedema in the context of diabetic ketoacidosis (DKA). The nature of the alterations in cerebral metabolism that may result in vulnerability to neuronal injury remains unknown. The aim of this study was to analyse the magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) brain data from eight children with diabetes following acute presentation with hyperglycaemia with or without ketoacidosis, to determine the nature and timing of any alterations in cerebral structure and metabolism. METHODS: This study used MRI and MRS to investigate regional cerebral abnormalities in a small series of diabetic patients with and without DKA. Changes were compared with the clinical and biochemical features of the patients studied. RESULTS: Our small series of patients all demonstrated abnormal signal changes in the frontal region on fluid attenuated inversion recovery (FLAIR) MR imaging, suggestive of oedema, and spectroscopic abnormalities of increased taurine, myoinositol and glucose levels. The MR abnormalities varied in severity but did not correlate with any clinical or biochemical parameters. CONCLUSIONS: These changes indicate that many diabetic children, particularly at presentation, may have alterations in cerebral metabolism with implications for the pathogenesis and treatment of the cerebral complications of DKA. In addition, our findings suggest that increased taurine may be one of the important differentiating factors in the response of the brain of diabetic children to DKA that may reflect an increase in their vulnerability to cerebral oedema compared with diabetic adults.

Adolescent↗
PubMed2004

Language cortex activation in normal children.

OBJECTIVE: To describe a protocol for use in young children and adolescents for determining language representation. METHODS: We performed 130 fMRI studies in 48 children and 17 adults. Verb generation (VG) and orthographic lexical retrieval (OLR) were used. The localization and lateralization of activation was rated visually. Regional voxel counts measured asymmetry and extent of activation. RESULTS: Activation was predominantly left-lateralized (children 85%, adults 94%), and there was no difference in the localization of activation for either paradigm. Children's typical sites of activation included mesial (96%), inferior (94%) and middle frontal (92%) gyri, the inferior (85%) and superior (65%) temporal cortex, and the cerebellum (67%). Less frequently activated sites were insular (50%) and posterior parietal (48%) cortices. Quantitative asymmetry index scores and visual inspection of laterality were concordant. Greater quantitative asymmetry for VG than OLR occurred in children. Laterality was not related to age, sex, task proficiency, or handedness. Frontal region voxel counts lower in children than adults and left sided counts correlated with task proficiency. CONCLUSIONS: Language fMRI can be performed in young children using resources available to clinical centers. The similarity in frequency of left language lateralization between children and adults suggests that language representation establishes early in development. The reduced amount of frontal region of interest activation in task-specific regions in children may reflect different levels of ability. However, the left-right distribution of activation does not appear to depend on task performance or age. These normative data provide a basis for decisions about language laterality in pediatric patients.

Adolescent↗
PubMed2004

Longitudinal study of MRS metabolites in Rasmussen encephalitis.

This study analyses the evolution of metabolite changes in an 8-year-old boy with focal Rasmussen encephalitis. Five MRI examinations, including magnetic resonance spectroscopy (MRS) were performed over 9 months. Following complex partial status, T2-weighted imaging showed transient dramatic signal increase in the left superior temporal gyrus and mesial temporal structures. Subsequent scans showed resolution of the swelling and signal normalization, with development of slight focal atrophy. MRS after status showed a reduction in N-acetylaspartate, total creatine and trimethylamines. Subsequent scans showed complete resolution of these metabolite abnormalities, followed later by development of further abnormal metabolite values. Lactate and glutamine/glutamate were elevated after status. After surgery, ex vivo high-field (1)H and (31)P MRS confirmed metabolite abnormalities (elevated choline and decreased aspartate, N-acetylaspartate, [(1)H]glutamate together with altered [(31)P]phospholipid ratios. These findings suggested active disease process in the anterior region of the excised superior temporal gyrus. We conclude that Rasmussen encephalitis is a combination of progressive encephalitic damage and fluctuating seizure effects, in which neuronal injury and recovery can occur. MRS measurements at a single time point should consider the fluctuating metabolite profile related to seizure activity.

Child↗
PubMed2002

Functional hepatocyte cation compartmentation demonstrated with 133Cs NMR.

This study utilized the large intrinsic chemical shift range of (133)Cs, a potassium congener, in an NMR study of intracellular cation distribution. It demonstrates two distinct intracellular environments in isolated perfused hepatocytes from cesium-fed rats, evident as compartments with different (133)Cs chemical shifts and containing different proportions of total detected cesium. The chemical shifts of the two intracellular compartments were 2.44 +/- 0.07 and 1.21 +/- 0.18 ppm, relative to the cesium signal from the perfusate. The observation of two distinct intracellular cesium signals suggests slow exchange on an NMR chemical shift time-scale (k exchange > 0.02 s). The area of the high-frequency component represented 62 +/- 10% (N = 12) of the total intracellular cesium signal. Manipulation of the intracellular environment using anoxia with aglycemia or digitonin produced changes in the distribution between the two intracellular compartments, showing their dynamic nature. Changes measured in association with metabolic manipulation suggest cytoplasm and mitochondria as the origin of the high and low-frequency intracellular peaks, respectively.

Animals↗
PubMed2001

Hippocampal sclerosis following brief generalized seizures in adulthood.

This report describes a patient who had a first generalized tonic clonic seizure (GTCS) at the age of 18 years. The initial MRI scan was normal on visual and quantitative examination. After a further six GTCS, a second MRI scan showed reduced hippocampal volume and increased hippocampal T2 signal, which was confirmed in a third scan. Therefore, hippocampal sclerosis may be acquired in adulthood after brief GTCS.

Adolescent↗
PubMed1995

133Cs relaxation times in rat tissues.

133Cs relaxation-time studies of tissues from rats into which cesium has been incorporated by dietary loading have been carried out in vivo and in vitro. Whereas tissue T1 values are on the order of seconds, T2 values are as low as a few tens of milliseconds. 133Cs tissue relaxation times are analogous to those of 39K in the same tissues, but are more readily measured because of the greater sensitivity of 133Cs compared with 39K. T1 and T2 data of excised tissue at two resonance frequencies (65.60 and 39.37 MHz) and temperatures (302 and 278K) have been analyzed in terms of a general description of spin-7/2 relaxation. The results are consistent with most of the cesium ions being in a free state, undergoing fast exchange with bound ions having long correlation times located in one or more intracellular compartments.

Animals↗
PubMed1993

NMR measurement of 39K detectability and relaxation constants in rat tissue.

Differences in the NMR detectability of 39K in various excised rat tissues (liver, brain, kidney, muscle, and testes) have been observed. The lowest NMR detectability occurs for liver (61 +/- 3% of potassium as measured by flame photometry) and highest for erythrocytes (100 +/- 7%). These differences in detectability correlate with differences in the measured 39K NMR relaxation constants in the same tissues. 39K detectabilities were also found to correlate inversely with the mitochondrial content of the tissues. Mitochondria prepared from liver showed greatly reduced 39K NMR detectability when compared with the tissue from which it was derived, 31.6 +/- 9% of potassium measured by flame photometry compared to 61 +/- 3%. The detectability of potassium in mitochondria was too low to enable the measurement of relaxation constants. This study indicates that differences in tissue structure, particularly mitochondrial content are important in determining 39K detectability and measured relaxation rates.

Animals↗
PubMed1993

The use of dietary loading of 133Cs as a potassium substitute in NMR studies of tissues.

133Cs NMR chemical shifts and relaxation times have been measured for tissue samples in vitro and in vivo from rats which have been fed on a high cesium, low potassium diet, which leads to a predominantly intracellular distribution of this ion, similar to that of K+. The high sensitivity, large chemical shift range, and narrow linewidths of 133Cs, compared with 39K, allow chemical shift differences to be observed between tissues, and in subcellular organelles such as mitochondria. For example, in vitro tissue chemical shifts, relative to 150 mM CsCl, are 1.06 +/- 0.11 ppm for liver, 0.02 +/- 0.05 ppm for brain, 1.76 +/- 0.20 ppm for erythrocytes, and -0.13 +/- 0.02 ppm for plasma. T1 and spin-echo T2 values range from 1.26 +/- 0.05 s (T1), and 0.028 +/- 0.006 s (T2) for liver, to 6.49 +/- 0.19 s and 1.12 +/- 0.03 s for plasma. 133Cs relaxation times show the same relative trends between tissues as are observed in 39K tissue studies.

Animals↗
PubMed1991

Factors affecting 39K NMR detectability in rat tissue.

In this study we have found that NMR detectability of 39K in rat thigh muscle may be substantially higher (up to 100% of total tissue potassium) than values previously reported of around 40%. The signal was found to consist of two superimposed components, one broad and one narrow, of approximately equal area. Investigations involving improvements in spectral parameters such as signal-to-noise ratio and baseline roll, together with computer simulations of spectra, show that the quality of the spectra has a major effect on the amount of signal detected, which is largely due to the loss of detectability of the broad signal component. In particular, lower-field spectrometers using conventional probes and detection methods generally have poorer signal-to-noise and worse baseline roll artifacts, which make detection of a broad component of the muscle signal difficult.

Animals↗
PubMed1989

Effect of magnesium depletion and potassium depletion and chlorothiazide on intracellular pH in the rat, studied by 31P NMR.

1. Both dietary magnesium depletion and potassium depletion (confirmed by tissue analysis) were induced in rats which were then compared with rats treated with chlorothiazide (250 mg/kg diet) and rats on a control synthetic diet. 2. Brain and muscle intracellular pH was measured by using a surface coil and [31P]-NMR to measure the chemical shift of inorganic phosphate. pH was also measured in isolated perfused hearts from control and magnesium-deficient rats. Intracellular magnesium status was assessed by measuring the chemical shift of beta-ATP in brain. 3. There was no evidence for magnesium deficiency in the chlorothiazide-treated rats on tissue analysis or on chemical shift of beta-ATP in brain. Both magnesium and potassium deficiency, but not chlorothiazide treatment, were associated with an extracellular alkalosis. 4. Magnesium deficiency led to an intracellular alkalosis in brain, muscle and heart. Chlorothiazide treatment led to an alkalosis in brain. Potassium deficiency was associated with a normal intracellular pH in brain and muscle. 5. Magnesium depletion and chlorothiazide treatment produce intracellular alkalosis by unknown mechanism(s).

Acid-Base Equilibrium↗
PubMed1988

Problems in the assessment of magnesium depletion in the rat by in vivo 31P NMR.

Prior in vitro studies, utilizing 31P nuclear magnetic resonance (31P NMR) to measure the chemical shift (sigma) of beta-ATP and lengthening of the phosphocreatine spin-spin (T2) relaxation time, suggested an assessment of their efficacy in measuring magnesium depletion in vivo. Dietary magnesium depletion (Mg2+ decreases) produced markedly lower magnesium in plasma (0.44 vs 1.13 mmol/liter) and bone (130 vs 190 mumol/g) but much smaller changes in muscle (41 vs 45 mumol/g, P less than 0.01), heart (42.5 vs 44.6 mumol/g), and brain (30 vs 32 mumol/g). NMR experiments in anesthetized rats in a Bruker 7-T vertical bore magnet showed that in Mg2+ decreases rats there was a significant change in brain beta-ATP shift (16.15 vs 16.03 ppm, P less than 0.05). These chemical shifts gave a calculated free [Mg2+] of 0.71 mM (control) and 0.48 mM (Mg2+ decreases). In muscle the change in beta-ATP shift was not significant (Mg2+ decreases 15.99 ppm, controls 15.96 ppm), corresponding to a calculated free Mg2+ of 0.83 and 0.95 mM, respectively. Phosphocreatine T2 (Carr-Purcell, spin-echo pulse sequence) was no different with Mg2+ decreases in muscle in vivo (surface coil) (Mg2+ decreases 136, control 142 ms) or in isolated perfused hearts (Helmholtz coil) (control 83, Mg2+ decreases 92 ms). 31P NMR is severely limited in its ability to detect dietary magnesium depletion in vivo. Measurement of beta-ATP shift in brain may allow studies of the effects of interaction in group studies but does not allow prediction of an individual magnesium status.

Animals↗
PubMed1987

Water depletion, not oral sodium loading, increases levels of sodium, potassium-dependent adenosine triphosphatase inhibitors in rat plasma.

In order to define a physiological role for circulating inhibitors of sodium, potassium-dependent adenosine triphosphatase (Na+,K+-ATPase), plasma was obtained from control, water deplete, water repleted, sodium deplete and sodium loaded rats. The effect of this plasma on Na+,K+-ATPase activity, and its transport equivalent 86Rb uptake, was measured in separated guinea pig renal cortical tubules. Plasma from water deplete rats had a raised plasma osmolality and sodium concentration and a significant inhibitory effect on Na+,K+-ATPase (14%) and 86Rb uptake (24%) compared with control or water repleted rats. Inhibition of Na+,K+-ATPase and 86Rb transport was not seen with plasma from rats after dietary sodium loading (urine sodium 5.2 +/- 0.9 mmol/day) compared with low sodium diet controls (urine sodium 0.41 +/- 0.08 mmol/day). Des-amino arginine vasopressin in vivo produced no inhibition of Na+,K+-ATPase or Rb transport. These studies suggest, that in terms of common homoeostatic insults, circulating inhibitors of Na+,K+-ATPase are more responsive to water depletion than to oral sodium loading. The inhibitors may fulfil a physiological role in increasing sodium excretion to maintain osmolality after dehydration.

Animals↗
PubMed1986

Aromatic L-amino acid decarboxylase: histochemical localization in rat kidney and lack of effect of dietary potassium or sodium loading on enzyme distribution.

Utilizing a mono-specific antiserum produced in rabbits to hog kidney aromatic L-amino acid decarboxylase (AADC), the enzyme was localized in rat kidney by immunoperoxidase staining. AADC was located predominantly in the proximal convoluted tubules; there was also weak staining in the distal convoluted tubules and collecting ducts. An increase in dietary potassium or sodium intake produced no change in density or distribution of AADC staining in kidney. An assay of AADC enzyme activity showed no difference in cortex or medulla with chronic potassium loading. A change in distribution or activity of renal AADC does not explain the postulated dopaminergic modulation of renal function that occurs with potassium or sodium loading.

Animals↗
PubMed1984

Renal potassium adaptation in the rat: role of glucocorticoids and aldosterone.

This study examines the role of adrenocortical hormones in the kaliuresis following an acute intragastric KCl load in conscious control (CK) and high potassium diet (HK) rats. Adrenalectomy, 1 day before test, reduced K+ excretion by 35% in CK and 60% in HK rats, leading to minimal differences in K excretion between CK and HK. By contrast, spironolactone inhibited K excretion by only 10%. Glucocorticoids (dexamethasone 3-10 micrograms/100 g) increased K+ excretion in adrenalectomized CK and to a greater extent in adrenalectomized HK rats. Aldosterone (3 micrograms/100 g) alone had a variable effect on urinary potassium excretion in adrenalectomized rats. A combination of dexamethasone (3 micrograms/100 g) and aldosterone (3 micrograms/100 g) in adrenalectomized rats induced potassium excretion equivalent to that in intact rats. Adrenalectomized HK rats had a greater kaliuretic response to dexamethasone and aldosterone than CK rats. These results 1) demonstrate a role for glucocorticoids in K+ excretion in HK rats and 2) illustrate the importance of the increased responsiveness to both glucocorticoids and mineralocorticoids in potassium adaptation.

Adaptation, Physiological↗
PubMedDate not supplied

Inhibition of guinea-pig renal [Na + K]-ATPase by normotensive human plasma: effects of a high sodium diet.

The effect of plasma taken from normotensive humans, while on a low and high sodium diet, on [Na + K]-ATPase and 3H-ouabain binding was measured in tubules from guinea-pig kidneys. Plasma from the high sodium, compared to the low sodium, diet period: (a) inhibited [Na + K]-ATPase activity; (b) decreased 3H-ouabain affinity for binding sites; (c) increased the number of available 3H-ouabain binding sites; (d) decreased [Na + K]-ATPase turnover (activity/3H-ouabain binding sites). The inhibition of [Na + K]-ATPase suggests an increase in a (possible) natriuretic factor. The decreased affinity of 3H-ouabain binding suggests an endogenous ouabainoid, which may be the natriuretic factor.

Adult↗