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Biomedical subjects

A F Smith

Publications and source records attributed to A F Smith.

At least 127 records · Page 7Linked to original sources

Monitoring renal transplants: an application of the multiprocess Kalman filter.

The multiprocess Kalman filter offers a powerful general framework for the modelling and analysis of noisy time series which are subject to abrupt changes in pattern. It has considerable potential application to many forms of biological series used in clinical monitoring. In particular, the approach can be used to provide on-line probabilities of whether changes have occurred, as well as to identify the type of change that is involved. In this paper, we extend and illustrate the methodology within the context of a particular case study. The general features of the problem, and the approach adopted, will be seen to have wide application.

Creatinine↗

Two macromolecular complexes between alkaline phosphatase and immunoglobulin A in a patient's serum.

We report the presence of two separate macromolecular complexes between an immunoglobulin and alkaline phosphatase (EC 3.1.3.1) in the serum of a patient with cholestatic liver disease. The complexes were seen as slow-moving bands on electrophoresis on polyacrylamide gel (70 g/L). Estimates of relative molecular mass for the two bands were 785 000 and 490 000 by gel chromatography on Sephacryl S300, and 640 000 and 420 000 by gradient gel-electrophoresis. Inhibitor and heat-inactivation studies showed that the two bands had similar properties, resembling the liver isoenzyme but more heat stable. Immunological studies suggested that both bands consisted of a complex of liver alkaline phosphatase with kappa type immunoglobulin A.

Aged↗

Clinical implications of labile HbA1 as assayed by the electrophoretic method.

The labile fraction of glycosylated haemoglobin (HbA1) was detected using an agar gel electrophoretic method; complete removal of this fraction was obtained by prior incubation of blood for 4 h in isotonic sodium chloride solution at 37 degrees C. Intra-individual variation in pre- and post-incubation HbA1 measurements was considerable, but no greater than would be predicted from methodological imprecision (within-plate CV = 2.8%, between-plate CV = 4.1%). In blood from 13 diabetics with a wide spectrum of glycaemic control, mean labile HbA1 was only 5% of total HbA1 (range -4.4% to + 15.6%); the size of the labile fraction was proportional to total HbA1 and plasma glucose concentrations. Sodium chloride incubation did not affect clinically appropriate classification of results. It is concluded that total HbA1 is adequate for clinical purposes. The colorimetric method was found to be less convenient and less precise.

Blood Glucose↗

The nature of gamma-glutamyltransferase and other hepatocyte plasma membrane enzymes in human bile.

High molecular mass gamma-glutamyltransferase in human bile is converted by physiological concentrations of the bile salts glycocholate and glycochenodeoxycholate to a form with a molecular mass estimated by gel chromatography to be 165,000. A molecule of intermediate molecular mass estimated to be 330,000 is obtained following treatment with the non-ionic detergent Triton X-100. When human bile is centrifuged at 150,000 X g, between 25-73% of gamma-glutamyltransferase activity is recovered in the supernatant. This proportion is increased following prior addition of bile salts to the bile. Analogous results are obtained for the high molecular mass enzymes alkaline phosphatase and leucine aminopeptidase, present in human bile, and also considered to originate from the hepatocyte plasma membrane. From these results it is suggested that these high molecular mass enzymes found in bile may, in part at least, represent artefacts following aggregation of the enzymes in aqueous media containing no bile salts.

Alkaline Phosphatase↗

An ultrastructural and morphometric study of bladder tumours (II).

Bladder tissues from 3 groups of patients were examined, using the light and electron microscopes (LM and TEM). One group of patients had a history of well-differentiated papillary transitional cell carcinomas and specimens were taken from cytoscopically normal areas. In a second group frank papillary carcinoma was biopsied. Finally, patients with no history of urothelial tumours and a normal cytoscopic appearance were biopsied during investigations for various benign conditions and these served as controls. In tissues from the first two groups certain differences were seen when these were compared to the controls and the frequency of these was significant. Light microscopic examination of 0.5 micros toluidine blue stained sections revealed an increased number of immature, small dark cells in the superficial layer of the epithelium (P less than 0.001). Electron microscopic examination showed that in place of the characteristic asymmetric unit membrane of mature superficial cells, the surface was frequently covered with microvilli and the junctional complexes were often atypical. There was an increased number of abnormalities in the basal lamina (P less than 0.001). These features were seen in the absence of cytoscopic and light microscopic changes in three out of eight patients with a history of tumours. It is, therefore, suggested that these are the earliest detectable morphological abnormalities in the pre-neoplastic urothelium.

Basement Membrane↗

Comparison of bupivacaine and prilocaine used in Bier block--a double blind trial.

The value of Bier blocks for the manipulation of fractures and for operations on the upper limb is well recognized. Two anaesthetic agents, bupivacaine and prilocaine, are widely used for this purpose. A prospective double blind trial of 200 patients has been carried out to compare the efficacy of each drug and the incidence of side effects. The study shows that bupivacaine was associated with a greater number of successful fracture reductions than prilocaine with little difference in their analgesic effects, but this was balanced by more minor side effects with bupivacaine. There was little difference in the time from injection to analgesia in the two groups. All intravenous regional analgesia procedures were carried out by junior orthopaedic or accident and emergency doctors. The overall success rate for analgesia was 91 per cent but marked cuff discomfort occurred in 9 per cent of patients. There was a clear association between failure of analgesia and two of the doctors carrying out the procedure.

Adolescent↗

Glycosylated hemoglobin and its temporal relationship to plasma glucose in non-insulin dependent (type 2) diabetes mellitus.

Total glycosylated hemoglobin (HbAI) and random plasma glucose were measured at monthly intervals for 6 mo in 33 non-insulin dependent (type 2) diabetics. The mean HbAI and mean plasma glucose in individual patients over the 6 mo showed a close correlation (p less than 0.001). A significantly higher HbAI (p less than 0.001) for a given plasma glucose was seen in those patients receiving combined chlorpropamide and metformin therapy (n = 14) than in those receiving chlorpropamide alone (n = 19). For each patient correlation coefficients were calculated between plasma glucose and HbAI with time lags of 0.1 and 2 mo. The coefficients with no time lag showed a significant tendency to be positive (p less than 0.01) whereas those with time lags of 1 or 2 mo were not significant. A constant proportional variability of both HbAI and plasma glucose over time was demonstrated, the mean coefficient of variation for HbAI being 8.4 +/- 2.7% and for plasma glucose 22.3 +/- 9.7%. We conclude that HbAI provides an index of plasma glucose control, not during the preceding few months as was previously thought but, during the previous few weeks. In terms of variability from month to month a single HbAI determination was equivalent to approximately the mean of 3 single plasma glucose values.

Blood Glucose↗

Gamma-glutamyltransferases in bile and sera from patients with extrahepatic biliary obstruction.

Gamma-glutamyltransferase has been studied in bile and sera from patients with extrahepatic biliary obstruction. In both fluids gamma-glutamyltransferase activity is found largely in the high molecular mass fraction present in the void volume following G200 gel chromatography and which remains at the origin after 7% polyacrylamide gel electrophoresis. When bile, sera and liver microsomes are treated with deoxycholate, a different form of gamma-glutamyltransferase, with an approximate molecular mass of 157 000 estimated by gel chromatography and of 125 000 by gradient gel electrophoresis, is obtained. After treatment with papain, all three types of specimen gave rise to a form of gamma-glutamyltransferase with a molecular mass of 115 000 estimated by gel chromatography and of 98 000 by gradient gel electrophoresis. The possible relationship between these various forms of gamma-glutamyltransferase, and their relevance to the increases in activity in serum seen in extrahepatic biliary obstruction, are discussed.

Bile↗

Glycosylated haemoglobin concentrations in mothers of large babies.

Mothers who have big babies may have had abnormal glucose tolerance during pregnancy. Glycosylated haemoglobin (HbA1) concentrations were measured on the first or second day after delivery in 50 women who had had babies weighing over the 95th centile for gestational age and in 50 women who had had normal-sized babies (controls). Nine of the mothers of big babies but only one of the controls had an HbA1 concentration above the normal range. All the women had normal glucose tolerance and HbA1 concentrations six weeks after delivery. Measuring HbA1 concentration in the first two days after delivery in mothers of large babies may identify gestational diabetics.

Birth Weight↗

Diabetic control in patients treated with once or twice-daily insulin injections, including a comparison of conventional beef and highly purified pork insulins.

Twenty patients were changed from a single daily injection of beef insulin (a mixture of soluble and protamine zinc insulin) to two daily injections (mixtures of soluble and isophane insulins). This was associated with a reduction, one month later, in the concentration of glycosylated haemoglobin (HbA1) and in the degree of late evening glycosuria. A reduction was shown 6 months later in antibody binding of beef and pork insulin by serum. Subsequent conversion to a twice daily regime of highly purified pork insulin was not associated with further improvement in diabetic control, but was associated after 1 month with a reduction in daily insulin dose, and after 5 months with a further reduction in antibody binding of beef and pork insulin by serum. Patients failing to show a C-peptide response to intravenous glucagon had a fall in HbA1 after conversion from a once to a twice daily insulin regime, which correlated inversely with insulin antibody binding estimated at the beginning of the study.

Adolescent↗

Hypercholesterolemia in diabetics with clinically unrecognised primary thyroid failure.

Forty-nine diabetics with primary thyroid failure, as indicated by an elevated TSH concentration (TSH 38.0 +/- 5.4 mU/L, T4 63.0 +/- 4.0 nmol/L), without overt clinical evidence of hypothyroidism, had a higher (p less than 0.025) mean plasma cholesterol concentration (6.8 +/- 0.2 nmol/L vs 6.0 +/- 0.2 nmol/L) than 49 euthyroid diabetics (TSH 3.16 +/- 0.2 mU/L, T4 99.1 +/- 2.81 nmol/L) of equivalent age, sex, weight, diabetic treatment and duration of diabetes. No significant difference in triglyceride concentration was observed between the two groups of diabetics. Thyroxine replacement therapy in 18 diabetics with subnormal T4 concentrations was associated with a reduction (p less 0.01) in mean plasma cholesterol concentration to 5.8 +/- 0.3 nmol/L, but no significant change in triglyceride concentration. Clinically unrecognised thyroid failure may contribute to the high mortality from ischaemic heart disease observed in diabetics by virtue of accompanying, reversible hypercholesterolemia.

Cholesterol↗

Relationship of glycosylated haemoglobin to C-peptide secretory status and antibody binding of insulin in insulin-dependent diabetes.

Diabetic control, assessed by measuring the concentration in venous blood of total glycosylated haemoglobin (HbA1), endogenous insulin secretion, as estimated by the C-peptide response (delta C-P) to intravenous glucagon, and serum beef insulin antibody binding were measured in 50 juvenile onset insulin dependent diabetics (IDDM) receiving a single daily injection of soluble and protamine zinc insulin. The delta C-P correlated inversely with duration of diabetes (tau = -0.27, p less than 0.01) and daily insulin requirement (tau = -0.22, p less than 0.05) in the 50 IDDM studied of whom 28 exhibited a measurable delta C-P. In C-peptide nonresponders, but not in the C-peptide responders, and inverse regression (t = 2.19, p less than 0.05) was observed between beef insulin antibody and HbA1. In the 25 IDDM having the lowest insulin antibody binding, and inverse correlation (tau = 0.36, p less than 0.02) was observed between delta CP and HbA1, which was not found (tau = 0.05) in the remaining 25 IDDM who had the highest insulin antibody binding. These findings suggest that, in the absence of endogenous insulin secretion, diabetic control in IDDM receiving a single daily injection of conventional beef insulin is better in patients with high beef insulin antibody binding. Conversely, in patients with low beef insulin antibody binding, diabetic control appears to be better in those with persisting endogenous insulin secretion.

Adolescent↗