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R P Thompson

Publications and source records attributed to R P Thompson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Silicic acid: its gastrointestinal uptake and urinary excretion in man and effects on aluminium excretion.

Silicon (Si), as silicic acid, is suggested to be the natural antidote to aluminium (Al) toxicity, and was recently shown to promote the urinary excretion of Al from body stores. The metabolism of Si in man, however, remains poorly investigated. Here we report on the pharmacokinetics and metabolism of Si in healthy volunteers following ingestion of orthosilicic acid (27-55 mg/l Si) in water. We also investigated whether orthosilicic acid promotes the urinary excretion of endogenous Al. Minimum, median uptake of Si from the ingested dose was 50.3% (range: 21.9-74.7%, n = 8) based on urinary analysis following dosing. Significant correlations were observed between creatinine clearance and Si levels in serum or urine (r = 0.95 and 0.99, respectively). Renal clearance of Si was 82-96 ml/min suggesting high renal filterability. These results suggest that orthosilicic acid is readily absorbed from the gastrointestinal tract of man and then readily excreted in urine. There was no significant increase in Al excretion, over 32 h, following ingestion of the orthosilicic acid dose (P = 0.5; n = 5).

Adult↗
PubMed1999

Urinary excretion of essential metals following intravenous calcium disodium edetate: an estimate of free zinc and zinc status in man.

Ethylenediaminetetraacetic acid (EDTA) is a powerful metal chelating agent used in the treatment of lead poisoning. EDTA also binds strongly to other metals. Thus, following intravenous infusion of CaNa2EDTA in healthy subjects the urinary excretion of calcium, copper, iron, magnesium and zinc were assessed. CaNa2EDTA significantly increased the urinary excretion of all metals except magnesium with greatest increases for iron (x 3.8 above baseline) and zinc (x 22). In addition, an in vitro dialysis study with a simplified serum showed that zinc (4.1 X 10(-3) mumol/h) was taken up more rapidly than iron (2.9 X 10(-3) mumol/h) by EDTA. The degree of binding of iron and zinc by EDTA depends on two factors: namely, the affinity of EDTA for Zn2+ and Fe3+, and the levels of unbound hydrated Zn2+ and Fe3+ ('free' ions). Despite differences in the rate of chelation of Zn2+ and Fe3+ by EDTA we show that the measurements of (a) circulating free iron, from routine clinical measurements of transferrin bound iron, and (b) the ratio of zinc:iron excreted in urine could provide an estimate of circulating free zinc, and thereby of zinc status, in man. In addition, EDTA treatment should be evaluated for patients with iron overload.

Adult↗
PubMed1999

Dietary minerals in the gastrointestinal tract: hydroxypolymerisation of aluminium is regulated by luminal mucins.

The regulation of mineral absorption in the gastrointestinal tract is poorly understood. Recent work has identified an intracellular metal-ion transporter but considerable evidence suggests that both soluble and mucosally associated luminal metal-binding ligands regulate initial uptake. Molecules ranging from low molecular weight organic acids to large glycoproteins have been suggested but a definite role for any such species has remained elusive. Here, a series of analytical techniques, allowing for this wide variation in potential binding ligands, was applied to the study of intestinal contents and tissue of rats following different feeding protocols. Aluminium, that has a low endogenous background and maintains a high concentration in the gastrointestinal tract, was investigated as a suitable dietary metal with hydrolytic behaviour similar, for example, to copper, iron and zinc. High resolution nuclear magnetic resonance spectroscopy identified a number of endogenous low molecular weight weak ligands that are secreted into the intestinal lumen. These may slow the rate of hydroxy-polymerisation of hydrolytic metals, allowing their effective donation to less mobile, higher molecular weight binding ligands. Histochemical staining suggested that such species may be soluble mucins as these were consistently associated with luminal aluminium. Significantly, this interaction prevented hydroxy/phosphate precipitation of aluminium, even at supraphysiological levels of the element. This was confirmed with X-ray micro-analysis investigations of ex vivo luminal contents. Nevertheless, from phase distribution experiments, the majority (60-95%) of luminal aluminium was associated with the intestinal solid phase and further histochemistry confirmed this to be gelatinous mucus, chiefly as the mucosally adherent layer. All results suggest a major role for mucus in regulating the gastrointestinal absorption of aluminium. It is proposed that, initially, soluble luminal mucus prevents the hydroxy-precipitation of hydrolytic metals at intestinal pH, allowing their effective donation to the mucus layer. Based on the differing reported metal-mucus interactions, elements that bind well to mucus (Al3+, Fe3+), with kinetically slow rates of ligand exchange (Al3+ < Fe3+) will be less well absorbed than poorly bound elements with kinetically faster rates of ligand exchange (Cu2+, Zn2+ etc.). This mechanism would readily explain many of the reported observations on mineral availability, including the marked variation in absorption of different elements, the differential effects of dietary ligands on mineral uptake and the competition for absorption between different metals.

Aluminum↗
PubMed1999

Lansoprazole is superior to ranitidine as maintenance treatment for the prevention of duodenal ulcer relapse.

AIM: To compare lansoprazole 30 mg once daily, lansoprazole 15 mg once daily and ranitidine 150 mg once nightly in the prevention of duodenal ulcer relapse in patients whose duodenal ulcers had been previously healed with lansoprazole 30 mg once daily or ranitidine 300 mg nightly. METHODS: A double-blind, parallel group, randomized multicentre study conducted in 33 centres in the UK, Eire, Sweden and Australia. Two hundred and nineteen patients with a duodenal ulcer were randomized to receive lansoprazole 30 mg and 217 to receive ranitidine 300 mg for 8 weeks. Patients were then re-randomized to receive lansoprazole 30 mg (122 patients), lansoprazole 15 mg (121 patients) or ranitidine 150 mg (116 patients) for 12 months. All patients had an endoscopically-proven duodenal ulcer at baseline and were considered suitable for long-term maintenance therapy to prevent relapse. RESULTS: Significantly more patients were healed on lansoprazole (98%) compared to ranitidine (89%) (P < 0.001, Fisher's exact test). Lansoprazole provided more rapid symptom relief than ranitidine. Lansoprazole 30 mg and lansoprazole 15 mg increased the probability of not relapsing in comparison to ranitidine (P = 0.001 and 0.06, respectively, life-table analysis). Relapse rates over the 12 months were lower in the lansoprazole treatment groups (lansoprazole 30 mg, 5%; lansoprazole 15 mg, 12%; and ranitidine, 21%; lansoprazole 30 mg vs. ranitidine 150 mg, P = 0.002). Symptoms were well controlled in both groups during the maintenance phase. All treatments were well tolerated with no major differences seen in adverse event profiles between treatment groups. CONCLUSIONS: Both doses of lansoprazole (30 mg and 15 mg) were superior to ranitidine 150 mg in the prevention of duodenal ulcer relapse. Lansoprazole was superior to ranitidine in terms of symptom control and duodenal ulcer healing. Both treatments were well tolerated.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

The regulation of mineral absorption in the gastrointestinal tract.

The absorption of metal ions in the mammalian single-stomached gut is fortunately highly selective, and both luminal and tissue regulation occur. Initially, assimilation of metal ions in an available form is facilitated by the intestinal secretions, chiefly soluble mucus (mucin) that retards hydrolysis of ions such as Cu, Fe and Zn. Metal ions then bind and traverse the mucosally-adherent mucus layer with an efficiency M+ > M2+ > M3+. At the mucosa Fe3+ is probably uniquely reduced to Fe2+, and all divalent cations (including Fe2+) are transported by a membrane protein (such as divalent cation transporter 1) into the cell. This minimizes absorption of toxic trivalent metals (e.g. Al3+). Intracellular metal-binding molecules (such as mobilferrin) may be present at the intracellular side of the apical membrane, anchored to a transmembrane protein such as an integrin complex. This mobilferrin would receive the metal ion from divalent cation transporter 1 and, with part of the integrin molecule, transport the metal to the cytosol for safe sequestration in a larger complex such as ferritin or 'paraferritin'. beta 2-Microglobulin and HFE (previously termed human leucocyte antigen H) may be involved in stabilizing metal mobilferrin-integrin to form this latter complex. Finally, a systemic metal-binding protein such as transferrin may enter the antiluminal (basolateral) side of the cell for binding of the sequestered metal ion and delivery to the circulation. Regulatory proteins, such as HFE, may determine the degree of ion transport from intestinal cells to the circulation. Gradients in pH and perhaps pCa or even pNa could allow the switching of ions between the different transporters throughout this mechanism.

Aluminum↗
PubMed1999

Development of the cardiac conduction system involves recruitment within a multipotent cardiomyogenic lineage.

The cardiac pacemaking and conduction system sets and maintains the rhythmic pumping action of the heart. Previously, we have shown that peripheral cells of the conduction network in chick (periarterial Purkinje fibers) are selected within a cardiomyogenic lineage and that this recruitment occurs as a result of paracrine cues from coronary arteries. At present, the cellular derivation of other elements of this specialized system (e.g. the nodes and bundles of the central conduction system) are controversial, with some proposing that the evidence supports a neurogenic and others a myogenic origin for these tissues. While such ontological questions remain, it is unlikely that progress can be made on the molecular mechanisms governing patterning and induction of the central conduction system. Here, we have undertaken lineage-tracing strategies based on the distinct properties of replication-incompetent adenoviral and retroviral lacZ-expressing constructs. Using these complementary approaches, it is shown that cells constituting both peripheral and central conduction tissues originate from cardiomyogenic progenitors present in the looped, tubular heart with no detectable contribution by migratory neuroectoderm-derived populations. Moreover, clonal analyses of retrovirally infected cells incorporated within any part of the conduction system suggest that such cells share closer lineage relationships with nearby contractive myocytes than with other, more distal elements of the conduction system. Differentiation birthdating by label dilution using [(3)H]thymidine also demonstrates the occurrence of ongoing myocyte conscription to conductive specialization and provides a time course for this active and localized selection process in different parts of the system. Together, these data suggest that the cardiac conduction system does not develop by outgrowth from a prespecified pool of 'primary' myogenic progenitors. Rather, its assembly and elaboration occur via processes that include progressive and localized recruitment of multipotent cardiomyogenic cells to the developing network of specialized cardiac tissues.

Adenoviridae↗
PubMed1999

Sclerosing mesenteritis involving the pancreas: two cases of a rare cause of abdominal mass mimicking malignancy.

Two patients presented with abdominal pain and weight loss and each was found to have an abdominal mass involving the pancreas and small bowel mesentery. In both cases a malignant process was suspected clinically, radiologically and surgically. Multiple biopsy specimens in both patients showed dense fibrosis, chronic inflammation and fat necrosis with pancreatic infiltration. Histological opinions included the differential diagnosis of retroperitoneal fibrosis but, with the knowledge of the presence of localized masses, these cases were eventually considered to be due to sclerosing mesenteritis. Direct involvement of the pancreas has not previously been highlighted and led to diagnostic difficulty. Both patients have responded to treatment with corticosteroids. Interestingly, one of the patients subsequently developed a tubulo-interstitial nephritis, which has not previously been reported as associated with sclerosing mesenteritis. This has also responded to corticosteroid treatment.

Adult↗
PubMed1998

Activation of nuclear factor kappa B in Crohn's disease.

OBJECTIVES AND DESIGN: The location and degree of activation of nuclear factor kappa (NFkappaB), a primary transcription factor that plays a regulating role in immune and inflammatory responses, was determined in Crohn's disease using full thickness specimens of bowel collected at surgery. MATERIALS AND METHODS: Resected specimens of inflamed and non-inflamed bowel were collected from thirteen patients with Crohn's disease and non-inflamed bowel from eleven control subjects. Prepared frozen sections were immunostained using a monoclonal antibody to the activated form of the p65 subunit of NFkappaB and the number of positive staining cells counted using a Lennox graticule. RESULTS: The number of cells positive for activated NFkappaB was significantly increased (p = 0.001 ) in all layers of inflamed Crohn's disease bowel, compared to non-inflamed bowel from controls. There was also a significant increase ( p = 0.009) in the number of positive cells, when compared to non-inflamed bowel from control subjects, in the submucosa of non-inflamed areas of Crohn's disease bowel. Cells positive for activated NFkappaB were provisionally identified by morphological criteria as mostly macrophages with some lymphocytes. There was no activation in endothelia. CONCLUSION: NFkappaB is activated within large mononuclear cells in all layers of inflamed areas of the bowel in Crohn's disease and may represent key events in the inflammatory process. Increased activation in the submucosa of non-inflamed Crohn's disease bowel provides further evidence of early immunological activation in macroscopically and microscopically uninvolved areas and an underlying abnormal immune system in Crohn's disease.

Adolescent↗
PubMed1998

In vitro mineral availability from digested tea: a rich dietary source of managanese.

Tea is potentially a rich source of some dietary metals and approximately 70 l are drunk per capita per year in the UK. In particular, tea may be an important source of Mn, since leaf tea contains 350-900 micrograms g-1 of this essential element. However, the leaching and bioavailability of Mn from tea have been little studied, so a recently developed in vitro assay was applied to compare the bioavailability of Mn from tea infusions with that of other major and trace essential elements. Analysis of tea infusions before digestion showed that 1.0 l contained 115% of the average daily dietary intake of Mn but < 6% of all other minerals. Samples of these infusions were incubated with human gastric juice (37 degrees C, 1 h) and some were then adjusted to pH 6.5 to simulate intestinal pH. All were centrifuged through ultrafilters with molecular mass cut-offs of 3, 10 and 30 kDa. The percentages of ultrafilterable (< 3 kDa) elements following simulated gastrointestinal digestion were (n = 3; mean +/- s) Ca 47.7 +/- 10.7, Cu 45.3 (n = 1), Fe < 5, Mg 66.4 +/- 1.6, Mn 39.8 +/- 11.4, K 40.3 +/- 2.2, Na 100.0 +/- 5.3 and Zn 33.7 +/- 1.1. Hence the ultrafilterability of elements showed the general trend M+ > M2+ > M3+, which is probably the inverse of the order of their strengths of binding to tea polyphenols. However, Mn was the only element found in significant dietary amounts in tea, and under simulated intestinal conditions was still 40% bioavailable.

Biological Availability↗
PubMed1998

Ferric trimaltol corrects iron deficiency anaemia in patients intolerant of iron.

BACKGROUND: Oral iron supplements, which are usually in the form of ferrous (Fe2+) salts, are toxic to the gastrointestinal mucosa, and so intolerance is common, resulting in poor compliance and failure of treatment. The sugar derivative maltol strongly chelates iron, rendering it available for absorption and stabilized in the less toxic ferric (Fe3+) form. AIM: To test whether ferric trimaltol could correct iron deficiency anaemia in patients intolerant of ferrous sulphate. METHODS: Twenty-three patients were recruited from gastroenterology clinics, of whom 1 5 had inflammatory bowel disease, a group often difficult to treat with oral iron. Patients with iron deficiency anaemia and documented intolerance to ferrous sulphate were given 3 months of treatment with ferric trimaltol. RESULTS: Nineteen of 23 patients completed the treatment and anaemia was fully corrected in 14 of these, mean haemoglobin increased from 106 +/- 15 to 126 +/- 16 g/L, and there was a particularly low incidence of side-effects. Of 11 patients with inflammatory bowel disease who completed the study, nine fully corrected their anaemia. CONCLUSION: The results demonstrate that in patients intolerant of ferrous compounds, ferric trimaltol corrects iron deficiency and has a low incidence of side-effects.

Anemia, Iron-Deficiency↗
PubMed1998

Intraoperative vascular monitoring of ipsilateral vs. contralateral TRAM flaps.

Transverse rectus abdominis musculocutaneous (TRAM) flap breast reconstruction has become an increasingly common procedure in the 1990s. The original description of the procedure was that of an ipsilaterally based pedicled procedure. However, because of concerns about potential folding of the pedicle with possible compromise of the vascular supply, with full muscle harvest the contralateral flap soon became the flap of choice. Subsequently there have been several large clinical series of pedicled TRAM flaps reported showing a relatively high complication rate related to problems with flap vascularity. These findings resulted in many centers favoring free TRAM flap breast reconstruction, despite an increased resource utilization and negligible differences in complication rates. Ipsilateral pedicled TRAM flap breast reconstruction is not a commonly reported procedure, and is reserved for patients in whom scars preclude use of the contralateral pedicle. The ease of flap shaping and lack of tension on the pedicle is recognized by some, and the ipsilateral procedure has become the flap of choice for these surgeons. The authors hypothesized that ipsilateral TRAM flaps have less compromise of venous outflow as a result of the rotational tension effect of transposing the flap to the mastectomy site. To determine if the vascularity of the pedicled TRAM procedure is influenced by pedicle choice, an intraoperative clinical study was designed to compare intravascular pressures in the deep inferior epigastric artery and vein pedicle at various times from pedicle division to flap insetting. Ten consecutive ipsilateral TRAM flaps were compared with eight contralateral flaps. The deep inferior epigastric pedicle was cannulated with both an arterial and venous catheter, and pressures were monitored from the time of division of the inferior pedicle through to the time of flap insetting. The venous pressures of the contralateral flaps were significantly higher at flap rotation and flap insetting compared with the ipsilateral group (p = 0.014 and p = 0.022 respectively). Perfusion pressures showed a greater decrease in the contralateral group from the time of pedicle division to the point of flap rotation and flap insetting compared with the ipsilateral group (p = 0.081 and p = 0.055). The authors conclude that pedicle tension in contralateral TRAM flaps is more common and results in greater venous resistance and decreased perfusion pressures. Versatility in flap shaping, improved maintenance of the IMF, and lack of disruption of the natural xyphoid hollow gives ipsilateral TRAM flaps additional advantages.

Abdominal Muscles↗
PubMed1998

Preparation of urine samples for trace metal determination: a study with aluminium analysis by inductively coupled plasma optical emission spectrometry.

Urinary analysis of trace metals forms a significant role in clinical chemistry, but the optimal preparation and analysis of urine samples has not been investigated. Human urine is generally supersaturated with dissolved solids. Therefore, samples often precipitate following collection. X-ray microanalysis showed that this precipitate was predominantly rich in calcium and phosphorus but could include some trace metals from urine, potentially lowering their concentrations in solution. Hence, the precipitate must be fully redissolved for accurate analysis of trace metals in urine. Methods are emphasized for the best collection and preparation of urine samples for subsequent trace metal analysis; in this work inductively coupled plasma optical emission spectrometry (ICPOES) was used for the analysis of aluminium. For optimal accuracy, peak profiles were collected over 396.147 nm-396.157 nm. Urinary aluminium levels were investigated from 10 healthy volunteers and concentrations were obtained using either aqueous, pooled or individual urine-based standard curves. Since urine has a highly variable matrix, individual sample-based standards, which are unique to that particular sample, gave the most accurate results. However, where sample size is small or sample numbers are unfeasibly large, pooled sample-based standards give good approximations to within 15% and, with appropriate validation, other elements as internal standards could also be used for approximations. Aqueous standards should be avoided. Spike-recovery experiments confirmed these data since individual sample based standards showed optimal recovery [99.3 (4.4)%], while pooled sample-based standards were a close proxy [101.6 (9.2)%] but aqueous standards were inappropriate [137.4 (12.8)%]. Postprandial urinary aluminium levels of the 10 volunteers were [7.2 (3.7)micrograms/L] after analysis using individual sample-based standard curves.

Aluminum↗
PubMed1997

Characterization of a sphingomyelinase activity in Saccharomyces cerevisiae.

Sphingomyelinases (SMase), which hydrolyze sphingolipids to yield ceramide, participate in signal transduction pathways in mammalian cells. Although yeast express many homologs of mammalian signaling proteins, SMase activity had not been previously demonstrated in yeast. In this study, we used an in vitro assay to characterize yeast SMase activity. Activity was detected in yeast membranes at both acid and neutral pH. The enzyme exhibited a requirement for magnesium or manganese, and was sensitive to detergents. The pI of the enzyme was approximately 5.9. SMase was separable from phospholipase D (PLD) activity, and was expressed at normal levels in yeast lacking expression of PLD1. While sphingosine and phytosphingosine inhibited growth, other sphingolipid metabolites had no effect on yeast growth. Intact yeast generate ceramide from exogenous sphingomyelin. These studies demonstrate that yeast express a membrane-localized neutral SMase activity.

Animals↗
PubMed1997

Randomised double blind controlled study of recurrence of gastric ulcer after treatment for eradication of Helicobacter pylori infection.

OBJECTIVE: To determine whether eradication of Helicobacter pylori infection reduces recurrence of benign gastric ulceration. DESIGN: Randomised, double blind, controlled study. Patients were randomised in a 1:2 ratio to either omeprazole 40 mg once daily for eight weeks or the same treatment plus amoxycillin 750 mg twice daily for weeks 7 and 8. A 12 month untreated follow up ensued. SETTING: Teaching and district general hospitals between 1991 and 1994. SUBJECTS: 107 patients with benign gastric ulcer associated with H pylori. MAIN OUTCOME MEASURES: Endoscopically confirmed relapse with gastric ulcer (analysed with life table methods), H pylori eradication, and healing of gastric ulcers (Mantel-Haenszel test). RESULTS: 172 patients were enrolled. Malignancy was diagnosed in 19; 24 were not infected with H pylori; four withdrew because of adverse events; and 18 failed to attend for start of treatment, leaving 107 patients eligible for analysis (35 omeprazole alone; 72 omeprazole plus amoxycillin). In the omeprazole/amoxycillin group 93% (67/72; 95% confidence interval 84% to 98%) of gastric ulcers healed and 83% (29/35; 66% to 94%) in the omeprazole group (P = 0.103). Eradication of H pylori was 58% (42/72; 46% to 70%) and 6% (2/35; 1% to 19%) (P < 0.001) and relapse after treatment was 22% (16/72) and 49% (17/35) (life table analysis, P < 0.001), in the two groups, respectively. The recurrence rates were 7% (3/44) after successful H pylori eradication and 48% (30/63) in those who continued to be infected (P < 0.001). CONCLUSIONS: Eradication of H pylori reduces relapse with gastric ulcer over one year. Eradication rates achieved with this regimen, however, are too low for it to be recommended for routine use.

Amoxicillin↗
PubMed1997

Retinoic acid directs cardiac laterality and the expression of early markers of precardiac asymmetry.

Formation of the left/right body axis is a critical early step in embryogenesis. The heart loop is one of the first clearly recognizable morphological asymmetries, and the molecular pathway which dictates this laterality is now beginning to be understood. We report here that the left and right precardiac fields of chick differ in their sensitivity to retinoic acid (RA); while RA applied to the right precardiac field at gastrulation randomizes heart looping, left side treatment induces situs inversus only at high RA concentrations. We identified two extracellular matrix proteins, the heart-specific lectin-associated matrix protein-1 (hLAMP1) and the fibrillin-related protein recognized by the antibody JB3, which are distributed asymmetrically within the precardiac fields at the head process stage. In normal embryos, JB3 expression is enhanced within the right precardiac field, and hLAMP-1 is enriched within the left. RA treatment predictably altered the expression of these proteins in a manner consistent with subsequent heart laterality: RA treatments which randomize heart loop direction also equalized or reversed the left/right JB3 and hLAMP-1 distribution prior to heart tube fusion. The existence of asymmetrically expressed extracellular matrix proteins within precardiac regions suggests that interactions between cardiocytes and their environment may contribute to heart laterality determination and looping.

Animals↗