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Biomedical subjects

R P Thompson

Publications and source records attributed to R P Thompson.

At least 73 records · Page 4Linked to original sources
PubMed1994

Absorption of iron from ferric hydroxypyranone complexes.

The absorption of 59Fe from preparations of FeSO4 and the ferric hydroxypyranone complexes maltol and ethyl maltol was studied by whole-body counting in normal subjects and patients with Fe deficiency. Fe in the Fe3+ complexes was in general absorbed almost as well as Fe2+. It is concluded that the absorption of Fe3+ from hydroxypyranone complexes is much greater than that from simple Fe3+ salts; this may prove an efficient and less toxic form of Fe for the treatment of deficiency.

Adult↗
PubMed1994

Lipid peroxidation in rats chronically fed ethanol.

Chronic alcohol consumption induces cytochrome P450IIE1, enabling habitual abusers to consume far greater quantities of alcohol than normal subjects. This pathway of metabolism leads to the production of free radical species, which cause tissue damage through peroxidation of cell membranes. Groups of Wistar rats of equal male: female ratio (n = 24) were fed alcohol by gavage twice daily to achieve a dosage of 15 g/kg body weight. Mean peak blood alcohol concentrations of 186 mg% were produced in males and 156 mg% in females. The animals were allowed free access to standard laboratory chow and water. Control animals were pair-fed to the alcoholic group and fed isocaloric glucose by gavage. Groups of animals were killed between 9 and 11 am on consecutive mornings, after nocturnal feeding, since it has previously been shown that fasting rapidly depletes hepatic glutathione concentrations. Hepatic glutathione was measured by a spectrophotometric enzymatic recycling procedure. As a marker of lipid peroxidation hepatic malonaldehyde (MDA) was measured by high performance liquid chromatography. Hepatic MDA was increased in the alcoholic group (p < 0.001), as was total hepatic glutathione (p < 0.0001). Plasma concentrations of alpha-tocopherol were increased in the alcoholic group, but ascorbic acid and superoxide dismutase values were not affected. No sex differences were detected. The increased MDA production in the alcohol group is strong evidence that lipid peroxidation is a mechanism of alcoholic tissue damage. The rise in hepatic glutathione may be an adaptive response to free radical production that protects the rat against tissue damage.

Animals↗
PubMed1994

Resistance of erythrocytes to lipid peroxidation in alcoholic patients.

The ability of erythrocytes to resist lipid peroxidation may be a useful marker of antioxidant status in alcoholic patients, in whom depletion of dietary antioxidants may combine with increased production of free radicals to produce liver damage. There are conflicting reports, however, on the resistance of erythrocytes from alcoholic patients to lipid peroxidation. This study examined the relation between the degree of alcohol induced liver disease and the resistance of erythrocytes to chemically induced lipid peroxidation, measuring lipid peroxidation as malondialdehyde production. Erythrocytes from alcoholic patients with Child's C cirrhosis had significantly increased resistance to lipid peroxidation compared with both controls (p < 0.001) and alcoholic patients with moderate liver disease (p < 0.001). There was no difference between alcoholic patients with moderate liver disease and controls. Increased resistance to free radical initiated lipid peroxidation in alcoholic patients is related to liver damage rather than to alcohol abuse alone. This could arise from changes in the lipid composition of the erythrocyte membranes resulting from abnormal liver function. Tests of antioxidant status based upon the resistance of erythrocytes to free radical stress in vitro may therefore be flawed when such changes in membrane lipid composition can occur.

Adult↗
PubMed1994

Intestinal perfusion of dietary levels of aluminium: association with the mucosa.

An aluminium (93 microM) sulphate solution freshly adjusted to pH 7.0 was perfused through the rat small bowel to mimic the reported physiological conditions that follow dietary aluminium ingestion. One third of this aluminium was taken up from the perfusate, but > 90% of this was then recovered from the intestinal mucus/mucosa and most (> 70%) from the distal third of the small bowel. The fresh perfusate was shown by ultrafiltration to contain largely particulate/colloidal aluminium-hydroxide, and this probably adhered to intestinal mucus which may be an important barrier to the gastrointestinal absorption of aluminium.

Alum Compounds↗
PubMed1994

Gastric telangiectasis: a rare cause of severe blood loss in CREST syndrome.

A 46 year old woman presented with the CREST variety of systemic sclerosis and occult gastrointestinal bleeding due to vascular malformations of her stomach. Partial gastrectomy cured her anaemia. In systemic sclerosis, visceral angiography should be performed early when initial investigations have been negative.

CREST Syndrome↗
PubMed1994

A trial of oral zinc supplementation in psoriasis.

A controlled double-blind study of oral zinc supplementation was performed in twenty-five patients with chronic plaque psoriasis over twelve weeks to assess changes in both psoriasis (using the psoriasis area and severity index) and neutrophil zinc content. There were no statistically significant differences in the psoriasis area and severity index during the trial between the placebo- and zinc-treated group, nor in the zinc levels. There was therefore no evidence of a benefit from zinc supplementation in patients with this disease.

Administration, Oral↗
PubMed1993

Comparison of serum procollagen III peptide concentrations and PGA index for assessment of hepatic fibrosis.

In early hepatic fibrosis, increased amounts of type III collagen are deposited. Persistently high serum concentrations of aminoterminal type III procollagen propeptide (PIIIP) correlate with the activity of the fibrogenic process. Another index for the detection of fibrosis, the PGA index, combines the prothrombin time, gamma-glutamyl transpeptidase activity, and serum apolipoprotein A1 concentration (the latter falls with progressive fibrosis). We compared PIIIP measurements and PGA index in patients with various histological forms of alcoholic liver disease (104), primary biliary cirrhosis (38), and chronic B virus hepatitis (27), and in healthy age-matched controls (30). The ability of each test to identify correctly patients with fibrosis or cirrhosis was assessed with receiver operating curves. The PGA index was much higher in all groups of patients with alcoholic liver disease than in controls (p < 0.0001). PIIIP concentrations were also substantially higher than in controls (p < 0.05 for fatty liver, p < 0.0001 for all other groups), especially in the group with alcoholic hepatitis and cirrhosis. For the detection of cirrhosis the PGA was 91% sensitive and 81% specific and the PIIIP concentration was 94% sensitive and 81% specific. The two tests combined had 85% sensitivity, but 93% specificity. Among patients with primary biliary cirrhosis, both PGA index and PIIIP concentration correlated well with the severity of the disease, determined by the Mayo score (r = 0.72 and 0.66 respectively). The combined tests were 96% sensitive for the detection of fibrosis. All patients with chronic B virus hepatitis had raised PGA and PIIIP values in comparison with controls (p < 0.0001) but there were no differences between subgroups. Substantially raised PIIIP concentrations thus identify the subgroup of alcoholic patients with both hepatitis and cirrhosis. The combination of PGA index and PIIIP concentration may be useful for targeting treatment with antifibrotic drugs and to reduce the need for liver biopsy.

Apolipoprotein A-I↗
PubMed1993

Expression of homeobox genes Msx-1 (Hox-7) and Msx-2 (Hox-8) during cardiac development in the chick.

The vertebrate homeobox genes Msx-1 and Msx-2 are related to the Drosophila msh gene and are expressed in a variety of tissues during embryogenesis. We have examined their expression by in situ hybridisation during critical stages of cardiac development in the chick from stages 15+ to 37. Msx-1 expression is apparent in a number of non-myocardial cell populations, including cells undergoing an epithelial to mesenchymal transformation in the atrioventricular and the outflow tract regions that play an integral role in heart septation and valve formation. Msx-2 expression is restricted to a distinct subpopulation of myocardial cells that, in later stages, coincides morphologically with the cardiac conduction system. The timing of Msx-2 expression suggests that it plays a role in conduction system tissue formation and that it identifies precursor cells of this specialised myocardium. The pattern of Msx-2 expression is discussed with reference to current models of conduction tissue development.

Animals↗
PubMed1993

Developmental anatomy of HNK-1 immunoreactivity in the embryonic rat heart: co-distribution with early conduction tissue.

To investigate the origin and development of the cardiac conduction system, the distribution of HNK-1 immunoreactivity in embryonic rat hearts was studied in histological sections and in three-dimensional computer reconstructions. Earliest HNK-1 reactivity was found along the endocardial surface of the fusing tubular heart at 9.5 embryonic days (ED) and subsequently within individual myocytes scattered widely along the looped tubular heart. Immunopositive myocytes appeared along the earliest ventricular trabeculae as they coalesced to form the developing interventricular septum during day 11, spreading to either side to give rise to the right and left bundle branches in the 12.5 ED heart. In the venous pole of the heart, primordia of the sinus node, and of the transient left sinus node, appeared immunopositive from 12.5 ED, coalescing during ED 13 along the anterior wall of the right sinus horn or developing coronary sinus, respectively. In the atria, several distinct tracts of immunoreactive myocytes were defined by 14.5 ED, ramifying from the sinoatrial junction to the atrial appendages or to the atrio-ventricular (AV) junction near the AV node. The timing and distribution of these immunostaining patterns suggest that ventricular conduction tissue develops within the earliest trabecular and septal myocardium, and is distinct from later immunopositive atrial tracts and extracardiac cell populations, such as neural crest, that appear to contribute to formation of the sinus node and autonomic innervation of the heart.

Animals↗
PubMed1993

Echocardiographic and anatomic correlation of ventricular septal defect morphology in newborn Yucatan pigs.

With the use of a Yucatan micropig strain with a high incidence of ventricular septal defects (VSDs), results of two-dimensional and color-flow Doppler echocardiography of VSD morphology in newborn piglets were correlated with autopsy findings. A spectrum of perimembranous, muscular outlet, and doubly committed subarterial VSDs was found. Echocardiography was performed in 29 piglets weighing 1.2 to 4.4 (mean 2.8) kg, studied at age 4 to 18 (mean 8) days. VSD was diagnosed by means of echocardiography in 16 of 29 subjects; morphologic findings included perimembranous defects in 12, muscular outlet in two, and doubly committed subarterial defect in two. At autopsy the presence and location of defects were confirmed in all pigs. No additional defects were found. VSD diameters were 1.0 to 5.0 (mean 3.94) mm on echocardiography and 1.0 to 6.0 (mean 2.84) mm at autopsy. After aortic valve diameter was used as an internal control for tissue shrinkage during fixation, echocardiography/color Doppler imaging tended to overestimate VSD diameter by 21% (0.6 mm). In conclusion, echocardiography/Doppler imaging accurately identified the presence, morphology, and size of even the smallest VSDs in newborn Yucatan micropigs. Echocardiographic classification of VSD morphology in vivo will facilitate future research on specific types of VSDs in this animal model.

Animals↗
PubMed1993

Histologic study of chronic catheter cryoablation of atrioventricular conduction in swine.

To evaluate the efficacy of catheter cryoablation, we studied histologic changes of the atrioventricular (AV) junction in eight pigs 6 weeks after cryoablation of central conducting tissue. Cryothermia at -60 degrees C was applied to the AV junction through an 8F or 11F cryocatheter with no electrode and was maintained for 3 minutes after complete AV block was obtained. Six weeks later, gross inspection revealed a distinct, oval-shaped scar 5 to 8 mm in length along or above the septal leaflet of the tricuspid valve in each animal. Microscopically, ablated sites were discrete and were replaced by dense connective tissue with no signs of chronic inflammation. Neovascularization was often seen in scar tissue, and small branches of coronary vasculature within lesions appeared patent with mild intimal proliferation. Ablated lesions involved a small area of the summit of the muscular interventricular septum in three animals, but lesions were never found in the base of the aortic wall or aortic valve. The proximal AV conduction system, either the penetrating bundle or a portion of the AV node, was ablated in all five animals with complete AV block. Three animals that did not maintain complete AV block showed scar formation in the atrial septum above the AV node or penetrating bundle; two of these lesions had small islands of viable atrial myocardium embedded within scar tissue. Catheter cryoablation can produce lesions as effectively as those created during open-heart surgery and is a possible procedure for treatment of intractable supraventricular tachycardia. Improvements in technique or in the cryocatheter may be needed to create more reliably located and homogeneous scar.

Animals↗
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↗
PubMed1993

Effect of thyroidectomy and adrenalectomy on changes in liver glutathione and malonaldehyde levels after acute ethanol injection.

At low concentrations ethanol is metabolized largely by alcohol dehydrogenase to acetaldehyde, while at higher concentrations a microsomal ethanol oxidising system (MEOS) is involved, namely cytochrome P450 IIE1, which also probably generates free radical species. In hyperthyroidism hepatic glutathione stores are depleted and net superoxide anion production occurs. In contrast, in hypothyroidism hepatic glutathione may be increased and thus renders the liver less sensitive to alcohol generated free radical production. Steroid hormones inhibit lipid peroxidation. Sixty male Wistar rats either underwent thyroidectomy, adrenalectomy, or sham procedures. Twenty control animals were pair fed with thyroidectomized animals, whilst another twenty fed ad libitum. An intraperitoneal injection of alcohol (75 mmol/kg) was given 2.5 h prior to sacrifice to half the animals in each group, the remainder receiving saline. The total hepatic glutathione contents of the pair fed and the ad libitum groups were not different, but were significantly increased by thyroidectomy (p = < 0.001). This effect was significantly reduced by alcohol (p < 0.01). The sham procedures and dietary restrictions had no effect. The ethanol alone reduced total hepatic glutathione, but this only reached statistical significance in the thyroidectomized and sham-adrenalectomized groups. Hepatic malonaldehyde (MDA) levels were significantly reduced in the thyroidectomy group but alcohol had no effect on them. We conclude that hypothyroidism increased hepatic glutathione status, presumably by reducing radical production by enzyme systems, which would otherwise consume this important scavenger. Long term exposure to ethanol with induction of MEOS is probably required for it to generate toxic levels of free radical species.

Adrenal Glands↗