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Biomedical subjects

H G Parkes

Publications and source records attributed to H G Parkes.

At least 19 recordsLinked to original sources
PubMed2004

A comparison of bile composition from heart-beating and non-heart-beating rabbit organ donors during normothermic extracorporeal liver perfusion: experimental evaluation using proton magnetic resonance spectroscopy.

BACKGROUND: Organs retrieved from marginal and non-heart-beating donors (NHBDs) have sustained variable degrees of preretrieval damage that result in an increased incidence of complications. Normothermic extracorporeal liver perfusion (NELP) provides an opportunity to evaluate and resuscitate such organs. The aim of this study was to identify markers of ischemic injury in bile during perfusion of livers from heart-beating donors (HBDs) and NHBDs. METHODS: Livers were retrieved from New Zealand white rabbits. The HBD group (n=4) had no in situ warm ischemia before retrieval and the NHBD group (n=4), 45 minutes of in situ warm ischemia before liver retrieval. After 40 minutes of postretrieval cold ischemia, all livers were dual vessel reperfused, normothermically with oxygenated buffer solution supplemented with rabbit red blood cells, for 6 hours. Bile was collected and examined with 1HMRS. RESULTS: Perfusion bile from HBD group showed an increased concentration of bile acids, lactate, glucose, and phosphatidylcholine, but a decreased concentration of acetate as compared to retrieval bile. This trend was further enhanced in NHBD group. The mean +/- SD (in micromol/L) were bile acids (10.48 +/- 2.8 vs 26.05 +/- 12.1 vs 44.5 +/- 44.5), lactate (10.66 +/- 4.5 vs 14.66 +/- 5.2 vs 13.22 +/- 1.8), glucose (5.37 +/- 2 vs 21.2 +/- 5.0 vs 29.09 +/- 15.3), phosphatidylcholine (0.21 +/- 0.02 vs 5.57 +/- 1.7 vs 6.42 +/- 0.3), and acetate (1.8 +/- 0.5 vs 0.39 +/- 0.1 vs 0.38 +/- 0.09) for retrieval bile, HBD perfusion bile, and NHBD perfusion bile, respectively. One animal from each group did not produce any bile during perfusion. CONCLUSIONS: 1HMRS of biliary constituents revealed differences with the type of ischemia. These indices may be potential markers of the extent of warm ischemic injury and the functional activity of an extracorporeally perfused liver.

Animals↗
PubMed2003

High resolution MRI of the brain at 4.7 Tesla using fast spin echo imaging.

Over recent years, high field MR scanners (3 T and above) have become increasingly widespread due to potential advantages such as higher signal-to-noise ratio. However, few examples of high resolution images covering the whole brain in reasonable acquisition times have been published to date and none have used fast spin echo (FSE), a sequence commonly employed for the acquisition of T(2) weighted images at 1.5 T. This is mostly due to the increased technical challenges associated with uniform signal generation and the increasingly restrictive constraints of current safety guidelines at high field. We investigated 10 volunteers using an FSE sequence optimized to the 4.7 T environment. This sequence allows the acquisition of 17- and 34-slice data sets with an in-plane resolution of approximately 500 microm x 500 microm and a slice thickness of 2 mm, in 5 min 40 s and 11 min 20 s, respectively. The images appear T(2) weighted, although the contrast is due to the combined effects of chosen echo time, magnetization transfer, direct radio frequency saturation and diffusion as well as the T(1) and T(2) relaxation times of the tissue. The result is an excellent detailed visualization of anatomical structures, demonstrating the great potential of 4.7 T MRI for clinical applications. This paper shows that, with careful optimization of sequence parameters, FSE imaging can be used at high field to generate images with high spatial resolution and uniform contrast across the whole brain within the prescribed power deposition limits.

Adult↗
PubMed2001

Proton nuclear magnetic resonance analysis of hepatic bile from donors and recipients in human liver transplantation.

The current shortage of donor organs in liver transplantation has led experienced transplant centers to use more "marginal" grafts. The development of a reliable technique of bile collection gives access to hepatic bile from donors and recipients for bile analysis to characterize the grafts. Proton nuclear magnetic resonance analysis has been applied to the study of bile for more than 30 years, showing encouraging results. This is the first study where proton nuclear magnetic resonance analysis has been applied to hepatic bile from selected liver grafts to evaluate its potential role in graft assessment. Hepatic bile was collected from eight liver donors (four with normal and four with steatotic grafts) during organ retrieval and four transplant recipients (two with good early graft function and two with primary dysfunction) immediately after graft reperfusion. A Varian Unity+ NMR spectrometer, operating at 11.7 Tesla (500 MHz for 1H), was used to obtain the proton nuclear magnetic resonance spectra. The results showed that the hepatic bile from steatotic grafts collected before transplantation had more intense phosphatidylcholine head group resonance than bile from normal grafts. It also showed slower clearance of University of Wisconsin solution in grafts with subsequent primary graft dysfunction, suggesting a slower recovery of bile secretion. These preliminary findings suggest that proton nuclear magnetic resonance analysis might help to differentiate the characteristics of bile acids and biliary lipids from normal and steatotic grafts. The monitoring of the resonance signal of University of Wisconsin solution washout, bile acid, and biliary lipid secretion may help to predict the development of primary graft dysfunction and avoid the need for retransplantation.

Adolescent↗
PubMed2000

A new system for the metabolic investigation of the isolated, perfused rat heart.

NMR spectroscopy is an invaluable technique in metabolic investigations of isolated, perfused hearts. Most studies employ global perfusion methods together with an NMR coil that surrounds the heart and thus detects signals from its entirety. The present report describes the construction and testing of a novel, two surface-coil probe, in combination with a dual-perfused heart preparation, that enables spectra to be collected independently from the two coronary beds of the rat heart.(31)P NMR spectra of perfused rat hearts in which the septum and right ventricle have been made ischaemic, while the free left ventricular wall is fully perfused, demonstrate the powerful potential of this new system.

Animals↗
PubMed1999

Altered brain metabolism in the C57BL/Wld mouse strain detected by magnetic resonance spectroscopy: association with delayed Wallerian degeneration?

In the C57BL/Wld(s) (Wld) mouse strain, both PNS and CNS axonal disintegration during Wallerian degeneration is dramatically slowed, with isolated axons being able to conduct compound action potentials (CAPs) for several weeks post-transection. The ability to conduct a CAP signifies the presence of an intact plasma membrane, normal ion gradients, and functioning ion channels. In neurons, ion homeostasis is primarily regulated by the Na(+)-K(+)-ATPase, which utilizes approximately 50% of neuronal energy output. To investigate the possibility that the Wld mutation prolongs axonal degeneration by conferring a more favorable energetic status to neurons or alters metabolism, we used 31P and 1H magnetic resonance spectroscopy (MRS) to compare the cerebral and muscle energy metabolism, membrane phospholipid contents, and water-soluble metabolites of Wld and wild-type (C57BL/6J [6J], and BALB/c) mouse strains. We first demonstrate that, with advancing age, transected Wld CNS nerves degenerate faster, paralleling previous findings in the PNS. We found significantly decreased phosphocreatine and phosphomonoester concentrations in the brains of Wld mice at 1- and 2-months of age compared to both 6J and BALB/c mice, but we failed to find differences in the adenylate (ATP, ADP, or AMP) or phospholipid concentrations. In another excitable tissue, skeletal muscle, no differences in energy-containing metabolites were detected. High resolution 1H MRS indicated that at 1 month of age, Wld brains have cytosolic levels of glutamate and phosphocholine that are significantly decreased, relative to total N-acetyl aspartate content. Our results demonstrate that delayed Wallerian degeneration in the C57BL/Wld mouse strain is associated with altered cerebral metabolism, although these changes may be secondary to the mutation.

Action Potentials↗
PubMed1997

PET and NMR dual acquisition (PANDA): applications to isolated, perfused rat hearts.

Positron emission tomography and nuclear magnetic resonance spectroscopy are non-invasive techniques that allow serial metabolic measurements to be obtained in a single subject. Significant advantages could be obtained if both types of scans could be acquired with a single machine. A small-scale PET scanner, designed to operate in a high magnetic field, was therefore constructed and inserted into the top half of a 7.3 cm bore, 9.4 T NMR magnet and its performance characterized. The magnetic field did not significantly affect either the sensitivity (approximately 3 kcps/MBq) or the spatial resolution (2.0 mm full width at half maximum, measured using a 0.25 mm diameter line source) of the scanner. However, the presence of the PET scanner resulted in a small decrease in field homogeneity. The first, simultaneous 31P NMR spectra (200, 80 degrees pulses collected at 6 s intervals) and PET images (transverse, mid-ventricular slices at the level of the mitral value) from isolated, perfused rat hearts were acquired using a specially designed NMR probe inserted into the bottom half of the magnet. The PET images were of excellent quality, enabling the left ventricular wall and interventricular septum to be clearly seen. In conclusion, we have demonstrated the simultaneous acquisition of PET and NMR data from perfused rat hearts; we believe that the combination of these two powerful techniques has tremendous potential in both the laboratory and the clinic.

Adenosine Triphosphate↗
PubMed1997

High resolution 1H NMR investigations of the reactivities of alpha-keto acid anions with hydrogen peroxide.

The chemical reactivity of various alpha-keto acid anions (beta-hydroxypyruvate, beta-phenylpyruvate, 2-ketobutyrate and 2-ketoglutarate) with hydrogen peroxide (H2O2) was investigated at physiological pH (7.4) and a temperature of 25 degrees C. The initial concentration of the alpha-keto acid anions was kept constant at 1.00 mM whilst that of added H2O2 was varied from 0.25 to 1.00 mM, and the rate and extent of these reactions was evaluated using 1H NMR spectroscopy. At all H2O2 concentrations utilised, the order of reactivity of the alpha-keto acid anions was beta-hydroxypyruvate > beta-phenylpyruvate > 2-ketobutyrate > 2-ketoglutarate. The results obtained are in agreement with a proposed mechanism for these reactions, involving nucleophilic attack of the mono-deprotonated peroxide species (HO2-) at the C-2 carbonyl group carbon centre. The antioxidant capacity of such alpha-keto acids is discussed in terms of their potential use as therapeutic agents in clinical conditions where H2O2 has been shown to play a critical role in the disease process, i.e., those involving 'oxidative stress'.

Butyrates↗
PubMed1996

An in vivo and in vitro H-magnetic resonance spectroscopy study of mdx mouse brain: abnormal development or neural necrosis?

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder primarily affecting young boys, often causing mental retardation in addition to the well-known progressive muscular weakness. Normal dystrophin expression is lacking in skeletal muscle and the central nervous system (CNS) of both DMD children and the mdx mouse model. The underlying biochemical lesion causing mental impairment in DMD is unknown. 1H-magnetic resonance spectroscopy (1H-MRS) detects choline-containing compounds, creatine and N-acetyl aspartate (NAA) in vivo. NAA is commonly used as a chemical marker for neurons, and a decline in NAA is thought to correlate with neuronal loss. Control mice were compared to mdx using a combination of in vivo and in vitro 1H-MRS methods to determine whether neural necrosis or developmental abnormalities occur in dystrophic brain. NAA levels were normal in mdx brain compared to controls suggesting minor, if any, neuronal necrosis in dystrophic brain. In contrast, choline compounds and myo-inositol levels were increased, indicative of gliosis or developmental abnormalities in dystrophic brain.

Animals↗
PubMed1996

Effects of n-3 fatty acids on the NMR profile of plasma lipoproteins.

The effects of fish oil supplementation (14.5 g n-3 fatty acids/day) on plasma lipoprotein particles in healthy volunteers were assessed by high resolution 13C and 1H nuclear magnetic resonance (NMR) spectroscopy. Resonances not previously observed in the 13C and 1H spectra of plasma and isolated lipoproteins were detected after fish oil ingestion. The 13C resonances, centered at 14.3, 127.1, and 131.6 ppm, have been assigned to specific carbon groups (CH3-CH2-CH = CH-, CH3-CH2-CH = CH-CH2-, CH3-CH2-CH = CH-CH2-, respectively) in eicosapentaenoic acid (C20:5n-3) and docosahexaenoic (C22:6n-3) DHA. The new lipid resonance observed in the 1H spectra of plasma (0.941 ppm) is consistent with the incorporation of these n-3 fatty acids into lipoprotein particles. The presence of increased EPA and DHA in plasma lipids was confirmed by gas-liquid chromatography. A marked reduction in the intensity of the methylene signal from very low density lipoproteins (VLDL) was also observed with fish oil. This reduction arises from a decrease in plasma triglyceride concentration (ca. 18%) and a reduction in the number of VLDL particles. Transverse relaxation studies of isolated VLDL and low density lipoprotein (LDL) showed significant elevation in the T2 of the -(CH2)n- and CH3- signals from non-n-3 fatty acids. The relaxation characteristics and signal intensity of the novel 1H peak (0.941 ppm) point to the existence of n-3 enriched microenvironments within lipoprotein particles. These findings suggest that incorporation of EPA and DHA into VLDL and LDL, after fish oil ingestion, leads to significant alteration in the molecular architecture of lipoprotein particles.

Adult↗
PubMed1995

In vitro determination by 1H-NMR studies that bile with shorter nucleation times contain cholesterol-enriched vesicles.

Although biliary vesicles are considered to be the primary source of cholesterol found in cholesterol gallstones, difficulties in quantitatively separating the different cholesterol transport modes in bile still remain. Proton nuclear magnetic resonance spectroscopy (1H-NMR) offers an alternative approach. Investigations were carried out on both model biles and human gallbladder bile samples: (i) to follow the effect of increasing sodium glycocholate concentrations on the 1H-NMR spectra of arachidonic acid rich-phospholipid, and cholesterol-lecithin vesicles, (ii) to compare the concentrations of total phospholipids in bile determined enzymatically with those obtained by integration of the phospholipid choline head group resonance peak, and (iii) to examine the relationship between biliary cholesterol nucleation time (NT) and the areas of the biliary lipid 1H-NMR peaks. It was found that the molecular motions of vesicle phospholipid, as determined by 1H-NMR, were restricted by saturation with cholesterol. In bile from patients with cholesterol gallstones, the reduced NMR fluidity of the phospholipid choline-head group indicated that the proportion of cholesterol-phospholipid vesicles containing more than 50% cholesterol, on a molar basis, was increased. The ratios of the N+(CH3)3 and = CH proton resonance peaks showed no overlap between samples with cholesterol gallstones and shorter NT and those with either no gallstones or pigment stones and longer NT. 1H-NMR spectroscopy indicates in a non-invasive manner those biles which are prone to cholesterol crystal formation.

Arachidonic Acid↗
PubMed1993

Gastro-intestinal availability of aluminium from tea.

The in vitro speciation of aluminium (Al) in black tea infusion (pH 4.8) was assessed using 3000, 10,000 and 30,000 Da cut-off ultrafilters, and the effect of adding human gastric juice (pH 2.3) and then raising the pH to 6.5 were also studied. 78% Al in the tea infusion passed through the 3000-Da ultrafilter; this percentage increased to more than 90% with the addition of gastric juice at pH 2.3, but then reduced to approximately 5% when the incubate was adjusted to pH 6.5. The breakdown of tea-derived polyphenols to low molecular weight phenols in vivo was measured using high-resolution 1H nuclear magnetic resonance spectroscopic analysis of ileostomy effluent, but there was no evidence of low molecular weight breakdown products from the polyphenols of ingested tea in this effluent. These results suggest that only a small proportion of Al in tea is potentially available for absorption throughout the small bowel. It may be misleading to estimate systemic Al absorption from tea drinking simply from total urinary aluminium excretion as has been done previously.

Aluminum↗
PubMed1992

Nuclear magnetic resonance spectroscopy to determine the micellar cholesterol in human bile.

The cholesterol of gallstones comes from the vesicular rather than the micellar phase of bile. Progress in this field has been limited because conventional analytical methods disturb the distribution of cholesterol between the two phases. The resonance of the cholesterol C6 proton occurs at a chemical shift of 5.4 ppm, to be shown by 2D NMR to be specific for biliary cholesterol, and arises only from the micellar mode. Thus integration of the C6 proton resonance peak area provides a direct non-invasive determination of the cholesterol distribution in human bile.

Bile↗
PubMed1991

Oxidative damage to hyaluronate and glucose in synovial fluid during exercise of the inflamed rheumatoid joint. Detection of abnormal low-molecular-mass metabolites by proton-n.m.r. spectroscopy.

Proton Hahn spin-echo n.m.r. spectroscopy was employed to detect abnormal metabolites present in rheumatoid synovial fluid that are derived from the deleterious generation of reactive oxygen radical species during exercise of the inflamed rheumatoid joint. A resonance attributable to a low-molecular-mass N-acetylglucosamine-containing oligosaccharide formed by the oxygen-radical-mediated depolymerization of synovial-fluid hyaluronate was clearly demonstrable when subjects with inflammatory joint disease were exercised. Moreover, formate, which may be derived from the attack of OH.radical on synovial-fluid carbohydrates, was also readily detectable in these samples. gamma-Radiolysis of rheumatoid synovial fluid samples and aqueous solutions of hyaluronate also gave rise to the production of the low-molecular-mass hyaluronate-derived oligosaccharide species and markedly elevated concentrations of (non-protein-bound) formate in the biological fluids. As expected, corresponding spectra of gamma-irradiated blood serum samples obtained from normal volunteers did not contain the signal attributable to the low-molecular-mass oligosaccharide species, but the formate resonance (barely detectable in non-irradiated normal serum samples) became clearly visible. Additionally, a curious increase in the effective concentration of non-protein-bound low-molecular-mass metabolites such as acetate, citrate, lactate and glutamine was observed after gamma-radiolysis of all biological fluids studied. The hyaluronate-derived low-molecular-mass oligosaccharide species and formate are suggested as novel markers of reactive oxygen radical activity in the inflamed rheumatoid joint during exercise-induced hypoxic/reperfusion injury.

Adult↗
PubMed1989

Mortality in the British rubber industry 1946-85.

The mortality experienced by a cohort of 36,691 rubber workers during 1946-85 has been investigated. These workers were all male operatives first employed in any one of the 13 participating factories in 1946-60; all had worked continuously in the industry for a minimum period of one year. Compared with the general population, statistically significant excesses relating to cancer mortality were found for cancer of the pharynx (E = 20.2, O = 30, SMR = 149), oesophagus (E = 87.6, O = 107, SMR = 122), stomach (E = 316.5, O = 359, SMR = 113), lung (E = 1219.2, O = 1592, SMR = 131), and all neoplasms (E = 2965.6, O = 3344, SMR = 113). Statistically significant deficits were found for cancer of the prostate. (E = 128.2, O = 91, SMR = 71), testis (E = 11.0, O = 4, SMR = 36), and Hodgkin's disease (E = 26.9, O = 16, SMR = 59). Involvement of occupational exposures was assessed by the method of regression models and life tables (RMLT). This method was used to compare the duration of employment in the industry, the duration in "dust exposed" jobs, and the duration in "fume and/or solvent exposed" jobs of those dying from causes of interest with those of all matching survivors. Positive associations (approaching formal levels of statistical significance) were found only for cancers of the stomach and the lung. The results of the RMLT analysis are independent of those from the SMR analysis, and the study continues to provide limited evidence of a causal association between the risks of stomach cancer and dust exposures, and the risks of lung cancer and fume or solvent exposures in the rubber industry during the period under study.

Adolescent↗