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Biomedical subjects

M F Laker

Publications and source records attributed to M F Laker.

At least 109 records · Page 6Linked to original sources

The determination of plasma oxalate concentrations using an enzyme/bioluminescent assay.

An enzyme/bioluminescent assay for the determination of oxalate in plasma is described in which NADH, a reaction product of the enzymic degradation of oxalate by oxalate decarboxylase and formate dehydrogenase, is determined using a commercially available bioluminescent system. In contrast to most previously documented methods, this sensitive and specific assay requires minimal sample preparation allowing oxalate concentrations to be determined within 2 h of sample collection. The limit of detection for plasma samples is 0.8 mumol/l. The recovery of oxalate added to plasma averaged 99%. The inter-batch coefficient of variation, calculated by analysis of a plasma sample from a uraemic patient (oxalate concentration = 45.8 mumol/l) on 8 occasions, over a period of 5 wk, was 3.2%. Plasma oxalate concentrations in 35 normal subjects ranged from less than 0.8-1.5 mumol/l, which is in excellent agreement with values obtained by in vivo isotope dilution studies. Plasma oxalate was found to be strikingly elevated in a group of uraemic patients maintained on regular haemodialysis.

Adult↗

Intestinal permeability changes and excretion of micro-organisms in stools of infants with diarrhoea and vomiting.

The relation between diarrhoea and vomiting, the excretion of stool micro-organisms, and the passive intestinal permeability in 20 infants living in a deprived urban area was studied prospectively from birth to age 6 months. Intestinal permeability was measured from the ratio of lactulose to mannitol recovered in the urine of infants receiving feeds containing both markers. Micro-organism excretion was found to occur in both the presence and absence of gastrointestinal symptoms, but a significantly higher mean intestinal permeability was recorded in those infants with symptoms and organisms in the stool than in those with neither. An increased intestinal permeability may be a sign of mucosal damage by intestinal micro-organisms.

Diarrhea, Infantile↗

Factors influencing normal reference intervals for creatinine, urea, and electrolytes in plasma, as measured with a Beckman Astra 8 Analyzer.

In a study of 514 healthy adults, we used a Beckman Astra 8 Analyzer to establish normal reference intervals for plasma creatinine, urea, and electrolytes. For potassium and chloride these were considerably lower and higher, respectively, than previously reported ranges. All of these analytes showed significant sex-related differences; all except chloride showed age-related changes. The relationship of these biochemical indices to fasting, cigarette smoking, alcohol intake, regular exercise, and the contraceptive pill--independent of these age- and sex-related differences--was assessed by multiple linear regression. The effect was significant in each case. Our results underline the importance of regular review of reference values.

Adolescent↗

Effects of isotretinoin on serum lipids and lipoproteins, liver and thyroid function.

Seven patients with severe rosacea were treated with 1 mg/kg per day isotretinoin for 12 wk. There were significant increases in serum triglyceride (p less than 0.001) and cholesterol (p less than 0.001). Triglyceride associated with very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) increased (p less than 0.01), cholesterol in VLDL and LDL increased (p less than 0.01), and levels of HDL cholesterol decreased (p less than 0.01). There were changes in indices of liver function, with increased levels of gamma-glutamyltransferase (GGT) (p less than 0.01), alkaline phosphatase (ALP) (p less than 0.01) and aspartate aminotransferase (AST) (p less than 0.01), and decreased bilirubin levels (p less than 0.05). Although levels of thyroxine and triiodothyronine were lower after treatment (p less than 0.05), there were no changes in basal levels of thyroid-stimulating hormone (TSH), luteinizing hormone (LH) or follicle-stimulating hormone (FSH), and responses to thyrotrophin releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH) were unchanged. These changes may partially be explained by induction of hepatic microsomal enzymes by isotretinoin.

Adult↗

Simplified urinary oxalate determination using an enzyme electrode.

An enzyme electrode for urine oxalate measurement has been produced using acrylamide gel-entrapped oxalate decarboxylase retained over a CO2 sensor. Urine required pre-treatment with EDTA, but oxalate extraction was not necessary and inhibition by phosphate and sulphate was not apparent until after 10-14 days. The linear range was 0-0.2 mmol/l. Analysis of 50 urine specimens diluted 1 in 10 in pH 3.0 glycine buffer showed good correlation with a widely-used colorimetric method (y = 1.101x-0.018, r = 0.955).

Adult↗

Effect of low dose cyproterone acetate on the response of acne to isotretinoin.

Twenty-seven males with severe acne were treated for 12 weeks with 0.05 mg/kg/day isotretinoin (ten patients) or 5 mg daily cyproterone acetate (eight patients) or both drugs together in these doses (nine patients). With isotretinoin, the sebum excretion rate (SER) fell by 45% +/- 9% s.e.m. (P less than 0.0025), lesion count fell by 65% +/- 10% (P less than 0.0005) and median clinical 17% +/- 12% (NS) fall in SER, a 15% +/- 10% (NS) fall in lesion count and the median severity was unchanged. Patients unchanged. Patients treated with both drugs showed a 42% +/- 13% reduction in SER (P less than 0.005), a 68% +/- 11% decrease in lesion count (P less than 0.0005) and a decrease in median severity from 8 to 4 (P less than 0.01) which was no different from the response to isotretinoin alone. Isotretinoin increased serum cholesterol from 4.4 mmol/l +/- 0.3 s.e.m. to 4.7 mmol/l +/- 0.3 s.e.m. (P less than 0.01), serum triglyceride from 0.73 mmol/l +/- 0.07 s.e.m. to 0.96 mmol/l +/- 0.14 s.e.m. (P less than 0.05) and gamma-glutamyltransferase (GGT) from 15.9 i.u./l +/- 2.1 s.e.m. to 19.0 i.u./l +/- 2.4 s.e.m. (P less than 0.01). Comparison of the area under the concentration-time curve for triglyceride and high density lipoprotein (HDL)-cholesterol showed that the changes were smaller when isotretinoin was combined with cyproterone acetate. We conclude that the effect of isotretinoin in acne was not enhanced by the antiandrogen, but the increase in serum triglyceride and decrease in HDL-cholesterol produced by the retinoid were reduced by combination with the antiandrogen.

Acne Vulgaris↗

Intestinal permeability in the newborn.

Passive intestinal permeability in 33 newborn babies was studied using feeds containing lactulose and mannitol. Each marker is thought to pass across the gut wall by a different route; lactulose by a paracellular and mannitol by a transcellular pathway. Neither is metabolised and both are wholly and solely excreted by the kidney; urinary recovery is a measure of the intestinal uptake. Babies born before 34 weeks' gestation exhibited a higher intestinal permeability to lactulose than more mature babies, and all preterm babies showed an appreciable decline in lactulose absorption during the first week of oral feeds. Babies of 34 to 37 weeks' gestation achieved a 'mature' intestinal permeability to lactulose within four days of starting oral feeds. These findings may reflect the immaturity of the gut of the preterm baby rather than a process essential to adaptation to enteral nutrition.

Gestational Age↗

Enhanced intestinal permeability in preterm babies with bloody stools.

During a study of the intestinal permeability of newborn babies, three exhibited a sudden increase in lactulose absorption in association with the passage of bloody stools. An enhanced intestinal permeability may be an expression of the disruption of mucosal integrity in necrotising enterocolitis.

Humans↗

Small bowel function in acute lymphoblastic leukaemia.

Small bowel function before, during, and after treatment for acute lymphoblastic leukaemia was studied in 26 children. A significant impairment of D-xylose absorption was found during treatment. Permeability studies showed a significant decrease in mannitol and a significant increase in lactulose concentrations; five of 20 children tested had evidence of lactose malabsorption, three of whom were symptomatic. Intestinal function abnormalities were greater in children whose methotrexate treatments were separated by 7 day than by 16 day intervals. Only five (19%) children had no abnormal tests. Abnormalities of small bowel function may be treatment induced and this has implications for morbidity from gastrointestinal symptoms, impairment of the mucosal barrier, and malabsorption of both nutrients and drugs leading to malnutrition and suboptimal drug concentrations.

Adolescent↗

The implications of assaying external quality control sera under 'special conditions'.

Two identical series of Wellcome quality control specimens were analysed by different procedures. One series was entered into the laboratory in the same way as patients' specimens while the other was analysed under special favourable conditions. This involved assaying the samples in replicate in different batches, omitting transcription errors and outliers, and placing the sample in a position following a calibration standard or an internal control. It was found that a significantly higher position in overall league ranking was achieved by assaying the control under 'special conditions'.

Blood Chemical Analysis↗

Comparative study of the sodium salts of iodamide and iothalamate in clinical urography.

In a comparative urographic study of the sodium salts of iodamide (Uromiro 300 Sodium) and iothalamate (Conray 420) the following conclusions have been made. (i) In subjects with radiologically normal kidneys and a creatinine clearance greater than 70 ml/min, nephrogram scores were significantly higher with iodamide (P less than 0.02). There were differences between the media in respect of total urogram scores and pyelogram scores but they were not statistically significant. (ii) In patients with radiologically normal kidneys and a spectrum of normal and abnormal renal function, performance scores for iothalamate showed no significant relationship with creatinine clearance. Results for iodamide, however, showed some relationship with creatinine clearance (nephrogram score r = 0.46, pyelogram score r = 0.38, total urogram score r = 0.49). A possible mechanism for this is proposed. (iii) Side-effects encountered in the study were mild and there were no significant differences between the contrast media in either the incidence or severity of the side-effects. (iv) Blood-pressure and pulse-rate profiles following iodamide were not significantly different from those following iothalamate. (v) Cardiac arrhythmias were mild and uncommon.

Adult↗

[Blood phosphate and calcium metabolism in bicarbonate dialysis of chronic stable hemodialysis patients].

Leucocyte count, blood pH and gases, plasma concentrations of total and ionised calcium, of phosphate and PTH were studied in 11 stable patients on chronic haemodialysis alternatively, the sequence being randomised, during acetate (AHD) and bicarbonate (BHD). Initial leucopenia and its subsequent correction were comparable with both dialysis types whereas pO2 and pCO2 transitory decreased only in AHD so that the mechanism of hypoxemia with AHD does not seem to be related to the pulmonary leucostatis but rather to the reflex hypoventilation secondary to the decrease of pCO2 into the acetate dialysis. As regards the bone metabolism, no difference was observed between HDA and HDB considering the increase of total and ionised calcium, the decrease of plasma phosphate and the absence of decrease of PTH, the initial levels of which being however only slightly elevated. However blood pH was significantly (but slightly) higher before the subsequent dialysis in the case of BHD. This more sustained correction of acidosis would be the only theoretical advantage of BHD for the prevention of bone demineralisation.

Acetates↗