Vitamin-D analogues and renal function.
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Biomedical subjects
Publications and source records attributed to M F Laker.
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Recent work suggests that rising arterial acetate levels occur in some patients undergoing hemodialysis and that they may be responsible for some dialysis problems, particularly cardiovascular instability. Blood acetate levels and acetate flux rates have been determined in 20 adult and 4 pediatric patients during hemodialysis as well as in 4 patients with combined renal and hepatic failure. Rising acetate levels occurred in 25% of the adult patients, although they were stable in the children and the patients with renal and hepatic failure. The occurrence of hypotension during dialysis was unrelated to a high blood acetate level.
Bone tissue was examined in 21 patients who had undergone jejuno-ileal bypass for obesity between 1971 and 1974. 10 patients had osteomalacia with evidence of secondary hyperparathyroidism. Clinical symptoms and biochemical and radiological investigations were often unreliable in diagnosing bone disease, although plasma-25-hydroxyvitamin-D and plasma-phosphate concentrations were significantly lower and plasma-parathyroid-hormone concentrations were significantly higher in the patients with bone disease. The presence of osteomalacia was unrelated to age, length of time since bypass, or post-bypass weight-loss, and plasma-25-hydroxyvitamin-D levels did not correlate closely with bone histological changes. It is concluded that osteomalacia is common after jejuno-ileal bypass and that factors other than simple vitamin-D deficiency may contribute to its development.
A method of acetate determination by gas phase chromatography using a porous polymer stationary phase is reported that is suitable for use with aqueous and plasma samples. It is linear up to 100 mmol/l and has a coefficient of variation of less than 4% for acetate values of greater than 1 mmol/l. The recovery of acetate from plasma is 92% and sample retention time is 3 minutes. The reference range of plasma acetate in a group of 40 apparently healthy subjects was from less than 0.1 to 0.35 mmol/l. The frequently encountered problem of absorption and ghosting of volatile fatty acids is overcome without the addition of formic acid vapour to the carrier gas.
1. A simple oral loading technique involving the ingestion of solutions containing lactulose is described. Timed urinary excretion of lactulose, which is non-metabolizable, is used as an indicator of intestinal permeability, and measured by quantitative paper chromatography. 2. This technique has been used to investigate the intestinal permeability of apparently healthy adults following the ingestion of solutions made hypertonic by the addition of the solutes sucrose, glucose, mannitol, glycerol, urea and sodium chloride. 3. These experiments show that intestinal permeability to lactulose increases as the solute concentration in the ingested solution is increased. Susceptibility to this effect, though consistent for each individual, shows considerable variation between subjects. 4. Factors thought to be pernitent to the enhancement of intestinal permeability by hypertonic solutions, and some possible implications of this, are discussed.
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The contrasting effects of natural versus cow's milk formula (CMF) on upper gastrointestinal development in the newborn were studied. The passive intestinal permeability of neonatal human infants and guinea pigs was measured using the nonmetabolisable markers lactulose and mannitol. Mucosal morphology was examined in guinea pigs by light microscopy. Nineteen full-term human infants and 63 guinea pigs were studied during the 1st week of extrauterine life. The naturally fed infants showed a decline in intestinal permeability to lactulose following the onset of feeding. This was not shared by those fed CMF. The CMF-fed guinea pigs showed a persistently higher intestinal permeability than the naturally fed animals throughout the 1st week of life. No differences were observed in the villous heights or crypt depths between feeding groups, but both showed an increase in intraepithelial lymphocyte number during the 1st week. Cow's milk formula may cause a persistently higher intestinal permeability, or natural feeding may promote a decline in permeability in the enterally fed newborn.
The association between plasma fibrinogen levels, fibrinogen genotype, and the development of macrovascular disease was studied in 100 patients with non-insulin dependent diabetes mellitus (NIDDM). The mean plasma fibrinogen levels in patients with macrovascular disease was higher than those without, although the difference was not statistically significant (3.67 g l-1, and 3.43 g l-1, respectively). The frequency of the rare allele of the fibrinogen gene DNA polymorphism detected with the restriction enzyme Bc1I was slightly higher in the group of patients with disease, but the difference was not statistically significant (0.20 vs 0.16). The frequency of the TaqI polymorphism rare allele was the same in both groups (0.30 vs 0.31). However, the Bc1I polymorphism was strongly associated with plasma fibrinogen levels, with those patients heterozygous for the rare allele having mean levels 16 per cent higher than those lacking the allele (3.81 g l-1 vs 3.28 g l-1, p < 0.05). This data demonstrates that variation at the fibrinogen locus is involved in determining fibrinogen levels in patients with NIDDM, and suggests the possibility that fibrinogen genotype and plasma fibrinogen levels could be one of the factors making a small contribution to the development of macrovascular disease in diabetic patients.
Several studies have demonstrated an association between variation in the apolipoprotein (apo) B gene, principally as detected by the XbaI and EcoRI restriction fragment length polymorphisms (RFLPs), and lipoprotein levels or cardiovascular disease. We have examined the frequency of the EcoRI and XbaI RFLPs of the apoB gene in 95 white Type 2 diabetic patients aged between 45 and 80 years in order to ascertain whether variation in this gene may be influencing the development of Type 2 diabetes and associated atherosclerosis through obesity. Neither of the two RFLPs had a significant association with clinically defined cardiovascular disease or with body mass index in our sample. However, while XbaI displayed no association with circulating levels of lipids, lipoproteins or apolipoproteins, the presence of the rare (R2) alele of EcoRI (absence of cutting site) was associated with significantly higher levels of circulating triglycerides. Furthermore, the EcoRI R2 allele was over-represented in the diabetic sample when compared to a healthy control group. Our findings support previous studies which have shown an effect of variation at the apoB gene on circulating lipid levels; additionally, variation in this gene may contribute to the development of Type 2 diabetes mellitus.