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Biomedical subjects

C Toothill

Publications and source records attributed to C Toothill.

At least 19 recordsLinked to original sources
PubMed1993

Effect of aluminum mobilization on hemoglobin during the first six months after transplantation.

We prospectively monitored 38 patients for the first six months following successful renal cadaver allograft transplantation. Hemoglobin increased from a mean of 8.2 +/- 0.3 g/dl to 13.4 +/- 0.3 g/dl (SEM), P < 0.001, plasma aluminum decreased from 1.3 +/- 0.2 mumol/liter to 0.46 +/- 0.04 mumol/liter, P < 0.001, and urinary aluminum excretion which peaked at one week post-transplant, 5.5 +/- 1.3 mumol/24 hr decreased to 1.8 +/- 0.3 mumol/24 hr, P < 0.001. Prior to transplantation 22 patients had been prescribed aluminum-containing phosphate binders. Following transplantation this group had persistently greater plasma aluminum and urinary aluminum concentrations which were sustained throughout the study period, compared with those not given aluminum containing medicaments. Hemoglobin and iron status were similar in the two groups prior to transplantation, although red blood cell volume was smaller in those given aluminum-containing phosphate binders, 89 +/- 0.9 fl (fentoliters) versus 95 +/- 1.6 fl, P < 0.05. However, the percentage increase in hemoglobin following transplantation was greater in the group not given aluminum preparations, 34 +/- 4% versus 7 +/- 5% at one month, 69 +/- 7% versus 37 +/- 7% at three months, and 80 +/- 8% versus 56 +/- 8% at six months respectively, all P < 0.05. This study suggests that aluminum mobilization following successful renal transplantation may reduce the rate of hemopoiesis.

Adult↗
PubMed1993

Aluminium mobilization following renal allograft transplantation may have an immunomodulatory role by reducing the incidence of graft rejection.

Urinary aluminium excretion was prospectively monitored during the first year following first cadaver renal allograft transplantation in 79 consecutive patients. Plasma and urinary aluminium concentrations steadily declined with time. Thirty-five patients had 0-1 episodes of acute graft rejection compared to 44 with two or more rejections; more of the former group had been prescribed aluminium-containing phosphate binders (74% versus 56%, P < 0.02), and following transplantation this group had a persistently greater urinary aluminium excretion, suggesting a greater aluminium body burden. There were no significant differences in terms of gender distribution, blood transfusion, or HLA matching between the groups, thus suggesting that either the subsequent mobilization of aluminium body stores following transplantation and/or the accumulation of aluminium in the reticulo-endothelial system prior to transplantation may have had an immunomodulatory effect in reducing the incidence of renal allograft rejection.

Adolescent↗
PubMed1991

Blood lead and platelet aggregation--evidence for a causal association.

Adenosine diphosphate (ADP) and thrombin are agonists of platelet aggregation in which intracellular calcium plays a significant role as a signal transducer. Lead is a well established toxicological agent affecting intracellular mechanisms controlling free ionized calcium concentration in a number of cell lines. This epidemiological study is the first demonstration of a significant relationship between the extent of primary ADP-induced platelet aggregation measured by optical densitometry in platelet rich plasma (PRP) and blood lead concentration. High blood lead levels are associated with decreased aggregation in this population of 2,150 men aged 49-65 years. This is reflected by a negative regression relationship of -0.19% of maximal extent (PRP vs platelet poor plasma) of aggregation per microgram of Pb/dl (T = -3.82, p less than 0.001). In contrast, no relationship is noted between thrombin-induced aggregation and blood lead concentration. Smoking behaviour represents a potential confounder which may be the explanation for the observed relationship. However, because smoking status is simultaneously related to both ADP- and thrombin-induced aggregation, but is simultaneously related to ADP-induced aggregation and blood lead concentration in a different way, the observed relation is likely to be causal. The mechanisms by which ADP and thrombin effect intracellular calcium transduction signals appear to be distinctively different. The findings in this population-based study are not inconsistent with this difference.

Adenosine Diphosphate↗
PubMed1991

A study of adjunctive copper sulphate treatment in patients with rheumatoid arthritis who have relapsed while taking D-penicillamine.

Formation of a D-penicillamine-copper complex may be necessary for the anti-rheumatic effect of D-penicillamine. Thus, depletion of copper stores by D-penicillamine may eventually lead to relapse in D-penicillamine treated patients. Twenty-one patients who relapsed on D-penicillamine were randomised to copper sulphate 20 mg daily (n = 13) or matched placebo (n = 8) in addition to penicillamine daily for 16 weeks. Urinary copper was increased in the copper treated patients but no statistically significant or clinically important improvement occurred in either group.

Adult↗
PubMed1991

Aluminium mobilization following renal transplantation and the possible effect on susceptibility to bacterial sepsis.

We monitored urinary aluminium excretion in 60 renal allograft recipients for the first 6 months following transplantation. Plasma and urinary aluminium values steadily decreased during the study period. Patients who suffered two or more bacterial infections during this period excreted more urinary aluminium than those with only one or no infections. Twenty patients experienced a two-fold or greater sudden unexpected increase in urinary aluminium excretion: 14 of these patients (60 per cent) had evidence of infection (10 bacterial and four viral), at this time. Both urinary aluminium and fractional aluminium excretion were greater in the 10 patients with bacterial infection than in the other 10 patients. Thus, patients who suffered bacterial infections had higher base-line urinary aluminium excretion, suggesting a higher body burden of aluminium. In addition, bacterial sepsis was associated with aluminium release from tissue stores with an associated increase in urinary aluminium excretion. This implies that patients with an increased body burden of aluminium are more prone to bacterial sepsis, and that aluminium excretion is increased during sepsis.

Adult↗
PubMed1990

Urinary aluminium excretion following renal transplantation and the effect of pulse steroid therapy.

Urinary aluminium was measured in 48 patients with primary graft function for 14 days following renal transplantation. The plasma aluminium prior to transplantation was greater in those prescribed aluminium-containing phosphate binders (1.7 +/- 0.2 vs 0.6 +/- 0.2 mumol/L, P less than 0.05) and correlated with the duration of dialysis therapy (r = 0.42, P less than 0.008). After an initial reduction the plasma aluminium returned to pre-transplant values by the fifth day. The 24 h urinary aluminium excretion, aluminium clearance and fractional aluminium excretion all increased during the first week to a maximum around the sixth postoperative day, thereafter returning to values obtained during the first postoperative days, suggesting an early 'wash-out' of a readily accessible aluminium pool followed by a lower steady state determined by the rate of release of aluminium from tissue stores. For the whole group, aluminium excretion, at this steady state, was five times that of urinary aluminium excretion in normal subjects. Acute allograft rejection was diagnosed in 25 patients, who were treated with pulsed methyl prednisolone. Apart from improving graft function, no additional effect was observed on aluminium excretion, suggesting that the readily accessible aluminium pool does not come from lysosomal release, but probably from aluminium bound to small molecular weight protein.

Adolescent↗
PubMed1988

Blood pressure and blood lead in surveys in Wales.

The association between blood pressure and blood lead level was examined in two population surveys in Wales. In a survey of 1,721 male and female subjects throughout the principality, there was evidence of a marked relation of blood pressure with age, but when this was removed no residual association with blood lead remained. In a survey of 1,164 older men in Caerphilly, there was no evidence of an association between blood lead and either resting blood pressure or the rise in blood pressure during a cold pressor test.

Adult↗
PubMed1988

Two Welsh surveys of blood lead and blood pressure.

The relationship between blood pressure and blood lead was examined in two population samples. One of these consisted of 1137 men aged 49 to 65 years, the other of 865 men and 856 women aged 18 to 64 years. Neither population had any known important exposure to lead, and the 95% ranges of blood lead levels were 6 to 26 micrograms/100 mL and 6 to 23 micrograms/mL in the men and 5 to 18 micrograms/100 mL in the women. No significant relationship between blood pressure and blood lead was detected in either of the population samples, and the regression coefficients suggest that if there were a real effect, then the mean difference in blood pressure per 10 micrograms difference in blood lead is likely to be 0.7 mm Hg in both systolic and diastolic pressures. In the survey of 1137 men, the rise in blood pressure was measured during the cold pressor test. This test is likely to be affected if lead were to affect neurogenic mediators of blood pressure. The mean change in systolic pressure was 24 mm Hg and the 95% range was -6 to 60 mm Hg, but there was no evidence of any association with blood lead level.

Aged↗
PubMed1987

Inorganic phosphate transport across the red blood cell membrane: the effect of exposure to hyperoxia.

Red cell structure and function were examined in rats exposed to 80% oxygen: 20% nitrogen for five days and compared with red cells from air-breathing animals. Evidence of red cell destruction was noted in the animals exposed to hyperoxia. Osmotic fragility was found to be reduced in red cells from oxygen exposed rats (p less than 0.05), also, red cell haemolysis in hydrogen peroxide was noted to be greater (p less than 0.001) in these animals. Inorganic phosphate ion transport was significantly reduced (p less than 0.001) in the red cells from rats receiving oxygen for 5 days. The results demonstrate a decreased ability of the red cell to transport anions and suggest an impairment of the normal movement of water across the membrane following exposure to oxygen.

Animals↗
PubMed1987

Tissue responses to hyperoxia. Biochemistry and pathology.

An animal model was established to study the toxic effects of hyperoxia and the consequent changes in intracellular antioxidant status. Superoxide dismutase, catalase and glutathione peroxidase activities were measured in erythrocytes, liver and lung, in addition to cellular glutathione concentrations and its associated metabolism. Overt cellular damage was assessed biochemically by measurement of lipid peroxidation, hydrogen peroxide-induced haemolysis and osmotic fragility. Pathological changes were assessed by light and electron microscopy. Up to 11 days exposure of rats to 80% oxygen was not lethal, but resulted in overt cellular damage to red blood cells (haemoglobin concentration decreased from 13.8 +/- 1.4 (SD) g dl-1 to 12.4 +/- 0.5 g dl-1; hydrogen peroxide-induced haemolysis increased from 7.7 +/- 1.6% to 75.1 +/- 13.5% after 11 days of hyperoxia) and to cells of lung (4-fold increase in lipid peroxidation) as well as a biochemical adaptation to the increased concentration of oxygen metabolites (superoxide dismutase increased 3-fold, catalase 5-fold and glutathione peroxidase 2-fold). It is suggested that red cell hydrogen peroxide-induced haemolysis and reduced glutathione concentration may be useful indicators of oxidant stress in the clinical situation.

Animals↗
PubMed1986

Further evidence of a fall in blood lead levels in Wales.

Random samples of residents in North Wales, some of whom had been seen in 1976 and others in 1981, were seen again in 1984. Blood lead estimations indicated that there had been a fall of about 5% per year. This is similar to the fall we estimated from two previous studies in Wales and is comparable to changes described in the USA and New Zealand.

Follow-Up Studies↗
PubMed1986

Effects of blood storage on red cell antioxidative systems.

The activities of the antioxidative enzymes superoxide dismutase, catalase and glutathione peroxidase and the concentration of reduced glutathione were determined in CPD-adenine blood stored at 4 degrees C for up to 20 days. Superoxide dismutase activity was found to be significantly reduced with storage beyond 10 days. The clinical significance of this finding is discussed.

Blood Specimen Collection↗
PubMed1985

Lead levels on traffic-less islands.

Surveys were conducted on three traffic-less islands: Tory and Aran, off the coast of Ireland, and Sark, one of the Channel Islands off the coast of France. Identical methods were used in surveys in three other areas, all of which have heavy gasoline driven traffic. These were Jersey, another of the Channel Islands, Ebbw Vale--a mixed industrial area, and Cardiff--the capital city of Wales. Environmental lead levels were very low in two of the traffic-less islands, but on the third, house dust lead levels were comparable with levels found throughout Wales. Blood lead levels on one of the islands were similar to those which have been reported for unaccultured remote tribes, but on the other two traffic-less islands blood lead levels were comparable with those of areas on the mainland of Wales.

Adult↗
PubMed1984

Vegetable consumption and blood lead concentrations.

Women resident in an area heavily contaminated by spoil from old lead mining have blood lead concentrations that are about 50% higher (p less than 0.001) than those of women living in a "control" area some distance away. Blood lead concentrations were related to the consumption of home grown produce. Those with the highest consumptions had blood lead concentrations that were 28% higher (p less than 0.001) than those of women who consumed no locally grown vegetables. Nevertheless, in the total population in the area this effect seemed likely to account for only about 5% of the population mean blood lead concentration. The data suggested that an increase in soil lead of 1000 micrograms/g is associated with an increase in blood lead of about 0.20 microM/1 (4.2 micrograms/dl).

Adult↗
PubMed1983

Urinary coproporphyrin in lead intoxication: a study in the rabbit.

Lead acetate was administered to adult New Zealand White rabbits in their drinking water. Their mean blood lead level rose to 4.5 mumol/l within a week and then remained relatively constant. The rabbits developed a marked coproporphyrinuria. Plasma levels of coproporphyrin increased but not in proportion to the urine excretion. Thus the renal clearance of coproporphyrin rose from a mean of 1.8 ml/min to 32.2 ml/min whilst creatinine clearance remained constant. The concentration of coproporphyrin in renal venous blood from control rabbits was found to be slightly lower than that in arterial blood. In the lead intoxicated rabbits the concentration of coproporphyrin in renal venous blood was approximately three times higher than the arterial concentration. Significantly higher levels of lead, porphobilinogen, uroporphyrin, coproporphyrin and protoporphyrin were found in renal tissue than in brain, heart or liver. Renal tissue homogenates from control rabbits were able to synthesize porphobilinogen, uroporphyrin, coproporphyrin and protoporphyrin when incubated with 5-aminolaevulinic acid. Renal tissue from lead intoxicated rabbits was also able to synthesize these haem precursors although at a reduced rate. Three enzymes from the haem biosynthetic pathway were assayed in renal mitochondria. Compared with those from controls, mitochondria from lead intoxicated rabbits showed no significant difference in ferrochelatase activities, but the activities of coproporphyrinogen oxidase were decreased, and those of 5-aminolaevulinate synthase were increased. It was concluded that a large portion of the excess coproporphyrin excreted by the lead intoxicated rabbits was of renal origin.

Animals↗
PubMed1983

Hardness of domestic water and blood lead levels.

The effect on the blood lead levels of residents in an area in which a soft plumbo-solvent water was hardened is examined. Water lead levels fell after hardening was introduced whereas there was a small rise in water lead levels in a control area monitored over the same time. The blood lead levels of residents fell after hardening and the fall was slightly greater than would have been predicted on the basis of the change in water lead levels. This suggests that lead is less well absorbed from hard water than from soft water. Following hardening there was a significant fall in mean blood lead level of subjects living in houses which had initially had negligible amounts of lead in the water. This suggests that hard water may interfere with the absorption of lead from sources other than water.

Humans↗