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Biomedical subjects

J J Powell

Publications and source records attributed to J J Powell.

At least 55 records · Page 3Linked 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

Lichen sclerosus.

Lichen sclerosis is a chronic inflammatory skin disease that causes substantial discomfort and morbidity, most commonly in adult women, but also in men and children. Any skin site may be affected (and, rarely, the oral mucosa) but lichen sclerosus is most common in the anogenital area, where it causes intractable itching and soreness. In children, the disorder may be confused with changes seen in sexual abuse. Progression to destructive scarring is common. There is increased risk of developing vulval cancer, and there are links with penile cancer. Patients should be kept under long-term review. Lichen sclerosus can occur without symptoms, and the exact prevalence is uncertain. It occurs most commonly in women at times of low sex hormone output. The underlying cause is unknown, but there seems to be a genetic susceptibility and a link with autoimmune mechanisms. The wart virus and the spirochaete borrelia have been suggested but not substantiated as infective triggers. The Koebner phenomenon is known to occur (lichen sclerosus occurs in skin already scarred or damaged), so trauma, injury, and sexual abuse have been suggested as possible triggers of symptoms in genetically predisposed people. The treatment of choice for anogenital lichen sclerosus is potent topical corticosteroid ointment for a limited time. Circumcision may be indicated in men, and surgery may be considered in women, to relieve effects of scarring or to treat coexisting carcinoma. Current research aims to identify a treatable cause of lichen sclerosus, to identify patients at risk of scarring and of malignant disorders, and to find target pathways for therapeutic intervention.

Carcinoma, Squamous Cell↗
PubMed1999

Accumulation of aluminium by the freshwater crustacean Asellus aquaticus in neutral water.

This study examined the accumulation of aluminium (Al), mostly as the insoluble (Al(OH)(3)) species, by the freshwater crustacean Asellus aquaticus at neutral pH. Animals were exposed to a range of Al concentrations (5-356 microg l(-1)) in three experiments. The first two were of 30 and 50 days duration, respectively, followed by transfer of the A. aquaticus to water containing no Al for 20 days. The third used live and dead animals in order to investigate the contribution made by surface adsorption of Al to the total accumulated. Significant accumulation of Al in the whole tissues occurred by day 10 in all animals in the 30- and 50- day experiment. Peak concentrations of Al were measured in animals between days 10 and 20 with high concentration factors ranging from 1.4 x 10(4) to 5.5 x 10(3). By day 30, accumulated Al had fallen but was still significantly greater than the control in the 50- day exposure experiment. This 30- day increase followed by decreased accumulation of Al was repeated over the remaining exposure period (i.e. 30-50 days) although rates of uptake and loss and peak tissue levels of Al were higher. Proportionality between environmental (water) and tissue concentrations of Al occurred at day 20 but not at day 45. Significantly more Al was accumulated by dead animals than live animals at all Al exposure concentrations. These results suggest that Al is available to the crustacean at neutral pH and that the cuticle may provide an important site of uptake.

Journal Article↗
PubMed1999

Folliculitis decalvans including tufted folliculitis: clinical, histological and therapeutic findings.

In a series of 18 patients with folliculitis decalvans attending the Oxford hair clinic, eight were found to have areas of tufted folliculitis either at presentation or follow-up. There was no difference between these two groups in their presentation, clinical course, growth of causative organism (Staphylococcus aureus) or investigations including histology. We suggest that these two entities form part of a spectrum of a single disease. We performed lymphocyte staining on affected scalp biopsies, including CD4: CD8 and T-cell/B-cell ratios, but found no evidence of local immune suppression or failure which would explain the abnormal host response to a common pathogen in this rare condition. We introduced a new treatment regimen for these patients, oral rifampicin and oral clindamycin together for 10 weeks. Ten of the 18 patients have responded well with no evidence of recurrence 2-22 months after one course of treatment, and 15 of the 18 responded after two or three courses.

Adolescent↗
PubMed1999

Survey of antibiotic prophylaxis in acute pancreatitis in the UK and Ireland.

BACKGROUND: Current surgical practice with regards to antibiotic prophylaxis in acute pancreatitis in the UK and Ireland was overviewed. METHODS: The 1103 members of the Association of Surgeons of Great Britain and Ireland were surveyed by postal questionnaire. A total of 528 replies were received (48 per cent). Following exclusion of surgeons not treating patients with acute pancreatitis, analysis was carried out on 429 replies. RESULTS: Respondents treated a median of 12 (interquartile range (i.q.r.) 10-20) patients per year with acute pancreatitis. Prophylactic antibiotic therapy was used by 88 per cent of responding surgeons, of whom 24 per cent used it in all cases. For surgeons professing selective use of antibiotics, the most common indication for use was in patients with prognostically severe disease. A cephalosporin was prescribed in 72 per cent of patients; cefuroxime was the single most common antibiotic. Combination therapy with metronidazole was used in 48 per cent of attacks. The median duration of antibiotic therapy was 5 (i.q.r. 5-7) days. An adverse drug reaction attributable to the use of prophylactic antibiotics was reported by 11 per cent of respondents. CONCLUSION: This study has established that a significant body of clinicians charged with the responsibility of treating acute pancreatitis use antibiotic prophylaxis in the initial treatment of patients with predicted severe disease.

Acute Disease↗
PubMed1999

Two polymorphisms of the tumour necrosis factor gene do not influence survival in pancreatic cancer.

Polymorphisms of the tumour necrosis factor (TNF) gene have been related to TNF production and outcome in a variety of inflammatory and malignant diseases. Proinflammatory cytokines and the inflammatory state appear to affect outcome in pancreatic cancer. Thus, the present study examined the TNFB and TNF-308 polymorphisms for their relationship to the inflammatory state and survival in pancreatic cancer. Sixty-four patients with advanced pancreatic cancer and 101 healthy subjects were genotyped for each polymorphism. Serum concentrations of the two TNF receptors and C-reactive protein (CRP) were measured in 45 of the cancer patients with no evidence of infection or jaundice, 1 month after surgical intervention. There was no difference in distribution of genotypes between the patient and control groups. There was no association between any genotype and concentrations of any of the measured inflammatory mediators. While those with an elevated CRP concentration had significantly poorer survival, there was no association between either TNF genotype and survival. This study found no association between TNF genotype and the inflammatory state or survival in advanced pancreatic cancer. Other cytokines may be more important than TNF in determining the inflammatory state and disease progress in pancreatic cancer.

Adult↗
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

Evidence for the role of environmental agents in the initiation or progression of autoimmune conditions.

The concordance of autoimmune disease among identical twins is virtually always less than 50% and often in the 25-40% range. This observation, as well as epidemic clustering of some autoimmune diseases following xenobiotic exposure, reinforces the thesis that autoimmune disease is secondary to both genetic and environmental factors. Because nonliving agents do not have genomes, disease characteristics involving nonliving xenobiotics are primarily secondary to host phenotype and function. In addition, because of individual genetic susceptibilities based not only on major histocompatibility complex differences but also on differences in toxin metabolism, lifestyles, and exposure rates, individuals will react differently to the same chemicals. With these comments in mind it is important to note that there have been associations of a number of xenobiotics with human autoimmune disease, including mercury, iodine, vinyl chloride, canavanine, organic solvents, silica, l-tryptophan, particulates, ultraviolet radiation, and ozone. In addition, there is discussion in the literature that raises the possibility that xenobiotics may also exacerbate an existing autoimmune disease. In this article we discuss these issues and, in particular, the evidence for the role of environmental agents in the initiation or progression of autoimmune conditions. With the worldwide deterioration of the environment, this is a particularly important subject for human health.

Anilides↗
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

Antibiotic prophylaxis in the initial management of severe acute pancreatitis.

BACKGROUND: The role of antibiotic prophylaxis in the initial management of patients with acute pancreatitis is an area of major controversy. Contrary to earlier clinical trials, recent experimental and clinical studies have accrued evidence that warrants reappraisal of current clinical practice. This article reviews these recent advances in knowledge. METHODS: All papers derived from a Medline search for the years 1990-1997 inclusive using the text words 'acute', 'pancreatitis', 'antibiotic' and 'antibiotics' were studied. Additional papers were derived from reference lists within papers identified by the Medline search. Only experimental and clinical papers relevant to the issue of prophylactic antibiotic therapy in acute pancreatitis are included in the review. RESULTS AND CONCLUSION: Current experimental evidence favours the use of prophylactic antibiotics in severe acute pancreatitis. The results of contemporary randomized clinical trials restricted to patients with prognostically severe acute pancreatitis have demonstrated improvement in outcome associated with antibiotic treatment.

Acute Disease↗
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↗