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Biomedical subjects

M F Laker

Publications and source records attributed to M F Laker.

At least 91 records · Page 5Linked to original sources
PubMed1989

Intestinal permeability in Crohn's disease.

Crohn's disease may present insidiously, especially in childhood, and diagnosis may be delayed. In addition, the clinical assessment of the extent of disease activity may be inaccurate. Using mannitol and lactulose as probe molecules we have carried out a cross sectional study of intestinal permeability in patients with active Crohn's disease (n = 17) and control subjects (n = 31). Activity was assessed by an activity index score. The lactulose:mannitol urinary excretion ratio was significantly increased in Crohn's disease. Overall sensitivity was 82%, and 92% when activity was moderate or severe. When permeability was compared with the activity index there was a significant correlation among patients. In five patients studied longitudinally a significant correlation was also present. Measurement of intestinal permeability is non-invasive, and may be useful both as a screening test in patients with non-specific symptoms, and for the assessment of the extent of disease activity in patients with Crohn's disease.

Adolescent↗
PubMed1989

Plasma oxalate concentration, oxalate clearance and cardiac function in patients receiving haemodialysis.

Pre-dialysis plasma oxalate concentration was measured in a cross-sectional study of 75 patients receiving maintenance haemodialysis. The aims of this study were to enable formulation of hypotheses regarding the determinants of plasma oxalate concentration and to allow preliminary examination of the possibility that hyperoxalaemia confers an increased risk of cardiac and vascular disease even in the absence of primary hyperoxaluria. Plasma oxalate concentration ranged between 7 and 76 mumol/l, mean (SD) 34.6 (18.1) mumol/l (normal range less than 0.8-2.0 mumol/l). Significant correlations were found between plasma oxalate concentration and plasma creatinine, duration of dialysis, current dose of ascorbic acid, and serum phosphate, and each of these variables retained significance on multiple linear regression. Oxalate clearance across a 1 m2 hollow-fibre Cuprophan dialyser, at 500 ml/min dialysate flow and blood flow between 175 and 225 ml/min, was measured 1 h after commencement of dialysis (n = 19). Mean (SD) clearance was 96.5 (27.0) ml/min. No significant association was found between self-reported maximum walking distance or the occurrence of symptoms of cardiac failure and plasma oxalate concentration. No relationship was found between plasma oxalate concentration and electrocardiographic conduction disturbances (n = 8) 'major' ST/T wave changes (n = 22), 'minor' ST/T wave changes (n = 49). Plasma oxalate was significantly greater in patients with radiologically detectable calcification of medium-sized arteries than in those without calcification, but duration of dialysis was also significantly longer in these patients. Routine haemodialysis results in marked hyperoxalaemia, which may be exacerbated by ascorbate supplementation. Oxalate clearance is similar to that of other small molecules such as creatinine and phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Oxalate retention in chronic renal failure: tubular vs glomerular diseases.

Plasma oxalate concentration was measured using an enzyme/bioluminescent assay in 289 patients (178 males, 111 females) with chronic renal failure (plasma creatinine greater than 200 mumol/l), age (SD) 55.5 (13.8) years. Plasma oxalate ranged between less than 0.8 and 48 mumol/l and showed a positive correlation with plasma creatinine (r = 0.57, p less than 0.0001). The slope of the regression line in 55 patients with glomerulonephritis (GN) was significantly lower than in patients with tubulointerstitial disease (TI); however the intercept was significantly higher in GN than in TI. Analysis of covariance showed no relationship between plasma oxalate concentration and age, duration of renal impairment, or administration of diuretics, vitamin D analogues, or phosphate binders. Longitudinal analysis of plasma oxalate measured 3-monthly in selected patients showed marked variability of oxalate/creatinine and oxalate/urea ratios.

Adolescent↗
PubMed1988

Intestinal permeability during chemotherapy for childhood tumours.

The intestinal permeability to mannitol and lactulose was measured in 29 children receiving treatment for solid tumours. At the time of study they had no gastrointestinal symptoms and appeared clinically well. However, there was a significant reduction in the absorption of mannitol when compared to normal children. This small bowel dysfunction may result in malabsorption of nutrients and drugs. There was a significant correlation between decreased mannitol absorption and low nutritional status.

Adolescent↗
PubMed1988

Effects of the somatostatin analogue SMS 201-995 (sandostatin) on mouth-to-caecum transit time and absorption of fat and carbohydrates in normal man.

1. Somatostatin analogues, such as SMS 201-995 (sandostatin), have been suggested as treatment for a variety of disease states including acromegaly, secretory gastrointestinal tumours and diabetes mellitus. 2. Somatostatin-14 has actions to prolong gastro-intestinal transit time and inhibit intestinal absorption, and we have therefore studied the effects of SMS 201-995 on these processes. Five male subjects received a test meal having been given either saline or 50 micrograms of SMS 201-995 subcutaneously 30 min before ingestion. 3. SMS 201-995 caused a delay in mouth-to-caecum transit time for lactulose assessed by breath hydrogen analysis (316 +/- 17 vs 192 +/- 14 min, mean +/- SEM, P less than 0.01), a delay (234 vs 120 min, P less than 0.05) in the plasma peak of the non-metabolizable glucose analogue 3-O-methylglucose and conversion of the expected postprandial rise in serum triglycerides (with saline 1.02 +/- 0.20 to 1.51 +/- 0.28 mmol/l, P less than 0.05) to a decrease below basal values (with SMS 201-995 0.97 +/- 0.80 to 0.79 +/- 0.11 mmol/l, P less than 0.05). 4. After SMS 201-995, an enhancement of the increase in blood glucose (8.2 +/- 0.7 vs 4.7 +/- 0.2 mmol/l, P less than 0.01) and inhibition and postponement of the postprandial rise in insulin (27.6 +/- 6.7 vs 9.9 +/- 2.1 m-units/l, P less than 0.05) occurred. Furthermore, a rise in non-esterified fatty acids, glycerol and 3-hydroxybutyrate, compared with the decline in concentrations of these metabolites after saline, was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1988

Changes in blood acetaldehyde concentrations during acetate haemodialysis.

Hyperacetataemia during acetate haemodialysis has been associated with the development of a variety of unpleasant symptoms, although a direct toxic effect of acetate is hard to prove. Acetaldehyde, which is produced during the metabolism of ethanol to acetate, has various toxic effects including some of those reported during acetate dialysis such as nausea, headache and palpitations. Using a novel, recently developed method we studied blood acetaldehyde concentrations during acetate dialysis in 15 patients and found significant increases in five, with a mean peak value in these patients of 1.36 mumol/l (normal less than 0.4 mumol/l). These five patients also developed high blood acetate concentrations during a subsequent acetate dialysis and showed a significant correlation between blood acetaldehyde and acetate concentrations (r = 0.55, P less than 0.05). Blood acetaldehyde did not change during bicarbonate dialysis in these patients. Our results suggest that significant accumulation of acetaldehyde may occur during acetate dialysis, especially in those patients whose metabolic capacity for acetate is somehow impaired, and that acetaldehyde may contribute to some of the symptoms previously ascribed to 'acetate' intolerance.

Acetaldehyde↗
PubMed1988

Plasma oxalate concentration and secondary oxalosis in patients with chronic renal failure.

To examine the association between hyperoxalaemia and secondary oxalosis, measurement of plasma oxalate concentration was combined with a search for tissue deposition of calcium oxalate crystals in patients with chronic renal disease. Two groups of patients were studied. In the first, samples of the inferior epigastric artery were taken from 35 patients at the time of renal transplantation. In the second, sections taken at necropsy from 23 patients with chronic renal failure in whom plasma oxalate had been measured before death were examined. Though plasma oxalate concentrations ranged between 6 and 116 mumol/l (four to 78 times greater than the upper limit of the reference range), no extrarenal deposits of oxalate were found in either study. Renal deposition of oxalate was associated with a plasma oxalate concentration of greater than 20 mumol/l. This study gives no support to the suggestion that hyperoxalaemia of the degree seen in patients with the type of chronic renal failure that is not due to primary hyperoxaluria confers an appreciable risk of extrarenal oxalosis.

Adolescent↗
PubMed1988

Plasma oxalate in patients receiving continuous ambulatory peritoneal dialysis.

Plasma oxalate has been measured in 125 patients maintained on continuous ambulatory peritoneal dialysis using an enzyme/bioluminescent assay. Values ranged between 6 and 134 mumol/l, with a positively skewed distribution. Multiple linear regression analysis with plasma oxalate as the dependent variable showed highly significant associations with the dose of ascorbic acid, dose of alfacalcidol, and plasma creatinine, and weaker associations with serum phosphate, serum calcium, and body weight. When the presence of other potential risk factors was taken into account, no significant relationship could be found between the presence of clinically evident cardiac or vascular disease and plasma oxalate.

Ascorbic Acid↗
PubMed1987

Passive and active carbohydrate absorption by the ageing gut.

We investigated the effects of advanced age, hospitalization and poor nutrition on passive and active carbohydrate absorption using the probe molecules lactulose and mannitol (passive absorption), and 3-O-methylglucose (active absorption). We studied five groups of subjects; healthy controls aged 20-30 years, 40-50 years and over 65 years, respectively, together with long-stay patients and elderly in-patients being investigated for malnutrition. Each subject undertook two separate studies ingesting a drink containing 5 g lactulose, 2 g mannitol and 2.5 mg 3-O-methylglucose (3-O-MG), on one occasion in isotonic solution and in the second study in hypertonic solution, following overnight fast. Urinary recovery of all three probe molecules declined significantly with age (P less than 0.02) and was reduced in malnourished elderly subjects compared to healthy elderly controls (P less than 0.05). Correction of urinary recoveries for renal function on the basis of creatinine clearance abolished significant differences between groups. Thus passive absorption of carbohydrate is not impaired with advanced age in healthy elderly subjects or long-stay hospital patients. The ratio of the percentage recovery of 3-O-MG to the percentage recovery of mannitol was significantly reduced in the healthy elderly subjects compared to middle-aged and young controls in the hypertonic study; similar changes did not occur in the long-stay and malnourished elderly patients, interpretation of this finding is thus difficult. If confirmed, this impairment would suggest a possible defect in active sugar transport in the elderly.

3-O-Methylglucose↗
PubMed1987

Isotretinoin and serum lipids: studies on fatty acid, apolipoprotein and intermediary metabolism.

Thirteen patients with severe acne were treated for 16 weeks with 1.0 mg/kg/day isotretinoin. There were significant increases in serum cholesterol (P less than 0.02), triglycerides (P less than 0.02) and apolipoprotein B (P less than 0.02). No changes were found in serum apolipoprotein A-1, non-esterified fatty acids (NEFA), carnitine, lactate, pyruvate, glycerol, alanine, beta-hydroxybutyrate, glucose or insulin. We therefore found no evidence that the hyperlipidaemia of isotretinoin therapy is due to increased fluxes of NEFA from adipose tissue to the liver, although we cannot exclude the possibility that there are changes in the proportion of NEFA being esterified to triglyceride or undergoing beta-oxidation. We suggest that the hyperlipidaemia induced by isotretinoin may be due to an increase in circulating lipoprotein from increased production or impaired catabolism.

Acne Vulgaris↗
PubMed1987

Cardiovascular and acid-base effects of acetate and bicarbonate haemodialysis.

Cardiovascular and acid-base changes were studied in 18 adult haemodialysis patients during a single dialysis against acetate or bicarbonate dialysate. Tachycardia was significantly greater with acetate but, otherwise, blood pressure and peripheral resistance fell and cardiac output increased to a similar degree with the two types of dialysate. Arterial PCO2 increased with bicarbonate and fell slightly with acetate, while hypoxaemia was significantly worse during acetate dialysis. Arterial acetate concentrations increased in 2 of 12 patients during bicarbonate dialysis. No differences in patient symptomatology or hypotensive episodes were noted with acetate or bicarbonate. Any beneficial effects of bicarbonate dialysis are more likely to be related to preservation of arterial PO2 than to the absence of adverse cardiovascular effects of acetate.

Acetates↗
PubMed1987

Haemodialysis-induced respiratory changes.

Eight patients receiving maintenance haemodialysis were studied under six different dialysis protocols, comprising Cuprophan and polyacrylonitrile (PAN 15) membranes, each used with dialysate containing 40 mmol/l acetate, 30 mmol/l acetate or bicarbonate (35 mmol/l), all other constituents being identical. Blood and expired gas determinations as well as transfer factor (DLCO) measurements, serum acetate concentrations, and WBC counts were performed. Rapid reductions in arterial oxygen (PaO2) were observed with Cuprophan (P less than 0.001), and with both strengths of acetate. Polyacrylonitrile used with acetate also demonstrated reductions in PaO2 but these were less severe than those observed with Cuprophan. Bicarbonate buffer resulted in a reduction in the severity of hypoxaemia, but failed to totally eliminate its occurrence. Hypoventilation was observed with both strengths of acetate dialysates, but not with bicarbonate. The respiratory exchange ratio decreased by 25% as a result of decreases in lung CO2 excretion when using acetate. Transfer factor declined by 40% for Cuprophan compared with 14% with polyacrylonitrile (P less than 0.01). Leucopenia was more severe with Cuprophan than with polyacrylonitrile. We conclude that amelioration of hypoxaemia may be achieved by the use of bicarbonate, but its cause is multifactorial, with contributions from hypoventilation secondary to dialyser CO2 losses and pulmonary dysfunction due to leucostasis. These observations suggest that the treatment of patients who have compromised cardiovascular function is most optimal with the use of biocompatible membranes which induce minimal leucopenia, used in conjunction with dialysate that utilises bicarbonate as the base replacement.

Blood Gas Analysis↗
PubMed1987

Critical evaluation of a commercial enzyme kit (Sigma) for determining oxalate concentrations in urine.

The Sigma reagent kit for urinary oxalate determination is reportedly simple, rapid, and specific for oxalate. We evaluated the kit and identified a number of shortcomings. Our investigations suggest that the recommended time for chromophore development is too short and should be doubled. Oxalate recovery during the extraction procedure depends strongly on urine pH. For complete extraction, urine should be acidified to pH 1.8-2.4. We also observed positive interference from ascorbate in urine. This interference was substantial, absorbances produced from ascorbate standards being approximately 80% of those obtained from oxalate standards of similar concentration. Our investigations also indicate the presence of a substance on the Sigma adsorbent that is eluted during the extraction procedure and interferes in the color reaction. These interferences represent potentially major sources of imprecision in the assay.

Adsorption↗
PubMed1986

Serum calcium status in health and disease: a comparison of measured and derived parameters.

The relationship of serum ionised calcium to total calcium was investigated in three series of experiments, each using different ion-selective electrodes. In the first, total and ionised calcium were measured in healthy and patient groups to compare the predictive value of each estimation. In the second and third studies, measured ionised calcium was compared with ionised calcium calculated using 5 different formulae, and with total calcium, both uncorrected, and adjusted for varying protein content using eight formulae. In 144 of 149 healthy subjects, serum ionised calcium and total calcium were normal. There were discrepancies between serum ionised calcium and total calcium in 135 of 572 patients with conditions associated with abnormal calcium metabolism. Correction of total calcium, or calculation of ionised calcium did not significantly improve this figure. Thus, corrected or derived calcium values will not substitute for ionised calcium determination in patients with abnormal calcium metabolism.

Arthritis, Rheumatoid↗
PubMed1986

Lipogenesis in isolated human sebaceous glands.

Lipogenesis in isolated human sebaceous glands from [U-14C]glucose, [U-14C]leucine, [U-14C]isoleucine, and [U-14C]valine has been determined by thin-layer chromatography. Total lipogenesis from 2 mmol/l [U-14C]glucose was 114.8 +/- 22.3 pmol/gland per h (mean +/- SE), with 53.8% being incorporated into triglycerides, 20.2% into squalene, 12.8% into phospholipids, 2.1% into cholesterol and 7.1% into wax monoester and cholesterol ester and 5% into di- and monoglycerides and free fatty acids. Total lipogenesis from 2 mmol/l [U-14C]leucine, 2 mmol/l [U-14C]isoleucine, and 2 mmol/l [U-14C]valine in the presence of 2 mmol/l glucose was 26, 29 and 9%, respectively, of that seen with 2 mmol/l glucose alone. The pattern of 14C distribution in the various lipid classes from the three U-14C-labelled branched-chain amino acids was not significantly different from that seen with [U-14C]glucose.

Carbon Radioisotopes↗
PubMed1986

Effect of guar on second-meal glucose tolerance in normal man.

Whole body glucose turnover and absorption of a 50 g glucose drink was studied in six healthy volunteers on two occasions, 4 h after a 'breakfast' of 50 g of glucose, mixed on one occasion with 20 g of guar gum. Plasma glucose concentrations were significantly reduced with guar gum compared with those obtained without guar gum (P less than 0.0001). Whole body glucose turnover studied by an intravenous primed dose constant infusion technique using D-[3-3H]glucose showed no significant difference between the two groups: 353 +/- 15 mmol with guar and 350 +/- 9 mmol without guar. Total oral glucose absorption, followed with a D-[1-14C]glucose tracer, was significantly decreased by guar treatment, being 219 +/- 3 mmol with guar and 239 +/- 5 mmol without guar (P less than 0.05). Serum insulin levels were lowered by guar treatment (P less than 0.05) while those of C-peptide, gastric inhibitory polypeptide, glucagon, cortisol and pancreatic polypeptide did not differ significantly. Blood lactate concentrations were raised in the guar treated group (P less than 0.05) whereas pyruvate, alanine, glycerol and 3-hydroxybutyrate concentrations did not differ significantly. These results support the suggestion that guar improves second-meal tolerance to glucose by decreasing absorption.

Adult↗
PubMed1986

Neonatal intestinal lactase activity.

The sequential changes in intestinal lactase activity of 40 neonates were measured indirectly from the differential uptake and excretion of lactose and the non-metabolisable disaccharide lactulose contained in formula feeds. A daily decline in urinary lactose:lactulose excretion ratios, reflecting a rise in intestinal lactase activity, followed formula feeding. Percentage decline was related directly to gestation: full term infants displayed a fivefold greater decline in lactosuria than infants with a gestation of 28 weeks during the first 10 days of milk feeding. The difference between lactose:lactulose ingestion and excretion ratios suggests that within five days of starting feeds intestinal hydrolysis of lactose exceeds 98% efficiency, even in very preterm infants.

Aging↗