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Biomedical subjects

C A Pennock

Publications and source records attributed to C A Pennock.

At least 19 recordsLinked to original sources

Increases in plasma lysosomal enzymes in type 1 (insulin-dependent) diabetes mellitus: relationship to diabetic complications and glycaemic control.

Lysosomal enzymes degrade membrane glycoconjugates, and increased circulating enzyme activity may be an important mechanism in the pathogenesis of diabetic microangiopathy. We have assayed a profile of seven lysosomal enzyme activities (nmol.h-1.ml-1) in platelet-free plasma from 54 Type 1 (insulin-dependent) diabetic subjects (median age 31 years) and 42 matched normal control subjects. A significant increase in median (interquartile range) enzyme activity was measured in diabetic compared to control subjects for beta-D-glucuronidase, 121 (97.7-171) vs 88.8 (62.8-113), p less than 0.001; beta-D-Nacetylglucosaminidase, 693 (568-799) vs 568 (462-686), p less than 0.001; alpha-D-mannosidase, 23.8 (16.7-28.9) vs 14.5 (10.1-20.0), p less than 0.001; and beta-D-galactosidase, 6.94 (6.11-9.99) vs 6.66 (4.78-8.33), p less than 0.04. In contrast, alpha-L-fucosidase, alpha-D-galactosidase and beta-D-mannosidase activities were similar in diabetic and control subjects. None of the enzyme activities differed significantly (p less than 0.05) between 24 diabetic patients with clinical complications and 30 complication-free diabetic patients with similar glycaemic control which does not support the hypothesis that enzyme increases in diabetes arise simply by leakage from damaged tissues. In the diabetic subjects HbA1, median (interquartile range) 9.10 (7.40-10.60), was significantly related to beta-D-glucuronidase (rs = 0.56, p less than 0.001) and beta-D-Nacetylglucosaminidase (rs = 0.55, p less than 0.001). We have therefore demonstrated in diabetic subjects an increase in certain lysosomal glycosidases, that correlates with glycaemic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase

Measurement of sialic acid in serum and urine: clinical applications and limitations.

Many recent studies have examined the sialic acid content of serum or urine in various pathological states. We have briefly reviewed the substances which contribute to the observed total sialic acid concentration, and given an overview of assay methods used. Three major areas of clinical interest in sialic acid metabolism are discussed. Serum total sialic acid, 'lipid-bound' and 'protein bound' sialic acid have all been proposed as tumour markers; but the usefulness of any of these tests is severely limited by changes due to accompanying inflammatory processes. Serum total sialic acid is not a valuable simple marker of an acute phase response. Urinary free and bound sialic acid measurements should be included in screening protocols for inherited disorders of lysosomal metabolism. Current developments in research and potential applications within the clinical biochemistry laboratory are briefly discussed.

Biomarkers, Tumor

Carrier detection for Sanfilippo A syndrome.

Leukocytes from 21 obligate carriers in 12 Sanfilippo A families and 49 normal controls were assayed for heparan sulphamidase (EC 3.10.1.1) at 55 degrees C. At this assay temperature the results show an absolute distinction between heterozygous carriers and the normal controls.

Clinical Enzyme Tests

Maternal leucocyte zinc deficiency at start of third trimester as a predictor of fetal growth retardation.

Leucocyte zinc concentrations were measured in 70 mothers at the beginning of the third trimester of pregnancy and compared with the weight centiles of their subsequently delivered babies. The median maternal leucocyte zinc concentrations rose progressively with weight centile. Thus the median leucocyte zinc concentration of the mothers delivering babies weighing below the 10th centile was 112 nmol/10(9) leucocytes and that of the mothers with babies weighing above the 90th centile was 229.5 nmol/10(9) leucocytes. A maternal leucocyte zinc concentration less than 120 nmol/10(9) leucocytes strongly predicted a baby weighing below the 10th centile (positive predictive value = 71.9%, negative predictive value = 91.5%, sensitivity = 64.3%, specificity = 81.8%). These findings suggest that maternal zinc concentration might have a role in antenatal screening, but larger studies are required.

Birth Weight

A collaborative study of the measurement of glycosylated haemoglobin by several methods in seven laboratories in the United Kingdom.

A collaborative study compared methods for measuring glycosylated haemoglobin in seven laboratories in the United Kingdom. No satisfactory standard for general use was found. Satisfactory internal quality control systems were in use for each assay which allowed the maintenance of a normal range in each participating laboratory. No satisfactory quality control system suitable for general use could be identified. Costs and convenience of the assays are reported. The technical problems with each type of assay and precautions for their use were identified, such as the need for standardization in incubation times, the practicability of automation of colorimetric assays, and the precision of pH needed for buffers in column separation methods. The relevance of the technical problems to interpretation of measurements is also considered. It is concluded that laboratories measuring glycosylated haemoglobin should maintain a normal range, use 'in-house' quality controls to monitor assay performance and keep clinical colleagues informed of the findings and of any changes in methodology that might affect the interpretation of results.

Autoanalysis

Mannosidosis in two brothers: prolonged survival in the severe phenotype.

Two cases of mannosidosis are reported in brothers, one aged 41 years at death, the other aged 40 years and still alive. These patients are the oldest reported in the literature. Prolonged survival has previously been associated with the milder Type II phenotype. In addition to the characteristic clinical and radiological features of mannosidosis, both had severe joint destruction, which may be related to abnormal lysosomal enzymes in cartilage. The activity of acidic alpha-mannosidase was markedly reduced in plasma, leucocytes and fibroblasts, and the altered kinetic and physical properties are described.

Adult

Impact of home blood glucose monitoring on childhood diabetes.

Ninety diabetic children each provided at least one 24-hour blood glucose profile at home using an impregnated filter paper strip. The mean 24-hour blood glucose level correlated significantly with urine control, height velocity, and Hb A1. The correlation coefficient for individual blood glucose values (r = 0.61) and for mean 24-hour blood glucose values (r = 0.73) repeated within 14 days showed an acceptable degree of reproducibility for the blood glucose profiles. Mean 24-hour blood glucose values fell significantly overall (11.4 to 9.8 mmol/l; 205 to 176 mg/100 ml) in 47 children who had repeated profiles more than 2 weeks apart. Unrecognised nocturnal hypoglycaemia (less than 3.0 mmol/l; 54 mg/100 ml) was found in 19% of children on twice-daily Semitard insulin. The study shows that children over age 7 years manage home blood glucose monitoring without difficulty. It shows that the results are reproducible and correlate with other indices of control, and that it provides a practical basis for the improvement of diabetic control.

Blood Glucose

A comparison of three methods for the estimation of capillary blood glucose in filter paper spots.

A comparison has been made between three methods for measuring capillary blood glucose collected on filter paper, including a new method using a Beckman glucose analyser 2. The methods are suitable for use with capillary blood spots collected onto filter paper for monitoring the control of diabetic patients. Their accuracy, precision, and recovery of glucose were similar. Glucose measurement with the Beckman glucose analyser 2 involves elution of the dried blood spots with 2% trichloroacetic acid and injection of a fraction of the eluate into the analyser. The method provides a simple and rapid alternative procedure for laboratories that do not have a heavy workload for this type of assay.

Autoanalysis

Brain gangliosides: an improved simple method for their extraction and identification.

Total ganglioside extracts prepared from brain tissue were concentrated either by dialysis against Carbowax or by employing Millipore filter cones. Thin-layer chromatography was then carried out using silica gel plates. After location of the various fractions quantitation was effected by direct densitometry. The methods that have been adopted are rapid and suitable for the study of brain gangliosides in post mortem and biopsy material in a clinical chemistry laboratory.

Animals

Keratan sulphate excretion in a patient with Kniest dysplasia.

The clinical and radiological features of a patient with Kniest dysplasia, a form of metatropic dwarfism, are described. The patient excreted glycosaminoglycans (mucopolysaccharides) in normal amounts during infancy but subsequently showed abnormal keratan sulphate excretion. The significance of these findings and the possibility that Kniest dysplasia represent another mucopolysaccharidosis are discussed.

Abnormalities, Multiple

Abnormal keratan sulphate excretion.

Simple methods for the detection of keratan sulphate in urine have been applied to over 300 urine samples collected from children and adults with bone and cartilage dysplasias with or without mental retardation. Abnormal keratan sulphate excretion, which is a feature of type IV mucopolysaccharidosis (Morquio syndrome), is found in patients with that condition only during childhood. Abnormal excretion is also a feature of Kniest dysplasia and GM1 gangliosidosis and may be present in a number of other bone and cartilage dysplasias of unknown aetiology.

Adolescent