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Biomedical subjects

A F Smith

Publications and source records attributed to A F Smith.

At least 109 records · Page 6Linked to original sources
PubMed1987

Hepatic glutathione S-transferase release after halothane anaesthesia: open randomised comparison with isoflurane.

Plasma concentrations of hepatic glutathione S-transferase (GST) are a more sensitive measure of acute hepatic damage than aminotransferase activity. Plasma GST concentrations have been measured by radioimmunoassay in an open randomised study after halothane or isoflurane anaesthesia. The concentration of GST was significantly increased after anaesthesia in patients who received halothane in 30% oxygen/70% nitrous oxide (n = 37) and in patients who received halothane in 100% oxygen (n = 17). The frequency of abnormal GST concentrations, defined as 4 micrograms/l or more, was 35% and 24%, respectively. GST concentrations usually reached a peak 3-6 h after the end of anaesthesia. In 17 patients who received isoflurane in 30% oxygen/70% nitrous oxide, there was no significant rise in GST concentration and no patient had a concentration above 4 micrograms/l. No patient in any of the groups had a significant increase in alanine aminotransferase. In clinically identical situations, anaesthesia with halothane but not isoflurane leads to demonstrable impairment of hepatocellular integrity.

Adult↗
PubMed1987

A two-stage procedure for bioequivalence studies.

A two-stage experimental procedure for bioequivalence studies is proposed. The procedure is based on the idea that information from a first-stage experiment can be used to form a predictive distribution for the outcome of a second-stage experiment, thus permitting an assessment of the probability of a successful overall outcome. A systematic numerical study of a variety of possible strategies results in the identification of procedures that lead to substantial increases in efficiency compared with single-stage studies.

Biometry↗
PubMed1986

In vitro studies upon the release of gamma-glutamyltransferase from human liver.

Samples of human liver have been incubated in different fluids for up to 48 h and the released gamma-glutamyltransferase studied by gel chromatography on Sephacryl S-300 and polyacrylamide gradient gel electrophoresis. When human liver is incubated in serum, most of the released enzyme is of high Mr (greater than 1,000,000). Incubation in hepatic bile, or in a solution of glycochenodeoxycholate, results in the release of enzyme that is hydrophobic in nature and which reaggregates to a varying extent after the removal of bile salts. In contrast, incubation in saline, or in a solution of human albumin results in the release of a hydrophilic low Mr (about 120,000) form of the enzyme. These observations are discussed in relation to possible mechanisms for the release of these multiple forms.

Bile↗
PubMed1986

The measurement of glycosylated albumin by reduction of alkaline nitro-blue tetrazolium.

A method is described for the measurement of glycosylated albumin in human plasma. Purification of albumin is achieved by a simple one-step chromatographic method, adapted for use as a batch analysis technique. The glycosylated albumin fraction is subsequently measured by a modification of the fructosamine assay (alkaline reduction of nitroblue tetrazolium). The method correlates with the plasma fructosamine assay (r = 0.85; p less than 0.001) and with an electrophoretic method for the measurement of HbA1 (r = 0.78; p less than 0.001).

Chromatography↗
PubMed1986

Progression of subclinical polyneuropathy in young patients with type 1 (insulin-dependent) diabetes: associations with glycaemic control and microangiopathy (microvascular complications).

The progression of subclinical polyneuropathy over 2.5 years has been studied in a representative group of 75 young patients with Type 1 (insulin-dependent) diabetes (initial age 16-19 years). The relationships between changes in nerve function, glycaemic control and concurrently developing microvascular complications (retinopathy, microproteinuria) were investigated. Deterioration of motor, sensory and autonomic nerve function, retinopathy and microproteinuria was related to poor glycaemic control. In addition, there was an association between developing neural and microvascular complications which was not diminished when their common relationship to hyperglycaemia was taken into account. These findings suggest that, although poor glycaemic control is an essential permissive factor in the early development of diabetic polyneuropathy, other influences, shared with microvascular complications, must also be important.

Adolescent↗
PubMed1985

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

Quadrant biopsies were taken at cystoscopy from 12 male patients previously diagnosed on light microscopy as having flat carcinoma in situ (CIS) of the urinary bladder. There was also material available from 3 cystectomy specimens with widespread CIS associated with papillary or solid urothelial tumours. Sections of normal ureter from kidney transplant donors and biopsies from two patients investigated for non-malignant bladder conditions severed as controls. The biopsies from 4 patients were classified as mild dysplasia of the urothelium, while those from 11 patients were categorised as CIS. Biopsies categorised as mild dysplasia on light microscopy showed an increase in the number of cells with large nuclei and nucleoli when compared to controls. The number of desmosomes was significantly reduced compared to controls, while the frequency of abnormalities of the basal lamina was increased. These features were more pronounced in the CIS group. Biopsies from the CIS group could be divided into "classical" and "large cell" CIS, the latter showing a higher frequency of ultrastructural abnormalities than the "classical" type. The patients diagnosed as having CIS fell into two clinical categories, the "early onset" and the "late onset" group. The five patients in the former had been diagnosed as having CIS with or without urothelial tumours elsewhere within 3 months of presentation. In the remaining four patients CIS was observed after recurring episodes of papillary or solid tumours during the previous 9 months to 20 years. The biopsies of 3 out of 5 patients with early onset CIS had been classified "large cell" CIS, whereas only one patient out of 4 in the late onset group came into this category. An early appearance of CIS is thought to have a worse prognosis, and it is therefore suggested that "large cell" CIS is a more severe form of the disease.

Adult↗
PubMed1985

Multiple forms of gamma-glutamyltransferase: a clinical study.

We have measured the amounts of different molecular forms of gamma-glutamyltransferase (EC 2.3.2.2), leucine aminopeptidase (EC 3.4.11.2), and alkaline phosphatase (EC 3.1.3.1) in serum of patients with different types of liver disease. A high-molecular-mass (greater than 1 000 000 Da) form of gamma-glutamyltransferase and of each of the other enzymes is present in greatest amounts in patients with jaundice from extrahepatic obstruction. A gamma-glutamyltransferase form of intermediate molecular mass (250 000 to 500 000 Da) is present in the serum from most patients with liver disease and can be separated by electrophoresis into several bands. We found that one of these bands predominated in patients with extrahepatic obstructive jaundice, whereas the others predominated in patients with other liver diseases. Electrophoresis of serum gamma-glutamyltransferase may be of clinical value in distinguishing extrahepatic from intrahepatic causes of jaundice.

Alkaline Phosphatase↗
PubMed1984

Physical properties of gamma-glutamyltransferase in human serum.

Using gel chromatography on Sephacryl S300 we have separated serum gamma-glutamyltransferase into three fractions with estimated relative molecular masses of (a) greater than 1000 000, (b) 250 000-500 000 and (c) about 120 000. Similarly, serum leucine aminopeptidase has been separated into three fractions. We have studied, particularly, the gamma-glutamyltransferase fraction of intermediate relative molecular mass (250 000-500 000) in serum from patients with a number of liver diseases. We have shown, both by polyanion and immuno-precipitation, that it consists significantly of a complex between gamma-glutamyltransferase and high density lipoprotein. The physical properties of this fraction, namely its mass and charge, can be altered by incubating serum with either bile or bile salts.

Alkaline Phosphatase↗
PubMed1984

Myocardial infarction related to coronary artery bypass graft surgery.

Fifty consecutive patients undergoing coronary artery bypass grafting for chronic stable angina were assessed by serial electrocardiography, preoperative and postoperative myocardial scanning with technetium-99m pyrophosphate, gated radionuclide ventriculography, and serial measurement of creatine kinase, aspartate aminotransferase, urea stable lactic dehydrogenase, and creatine kinase isoenzyme (MB) to assess the incidence of perioperative myocardial infarction and identify the most appropriate diagnostic techniques. The correlation between myocardial scanning and the measurement of peak enzyme and isoenzyme activity was excellent in the diagnosis of perioperative infarction, although electrocardiography proved less helpful. There appeared to be no advantage in measuring creatine kinase MB rather than the more routinely measured enzymes. There were two deaths and evidence of myocardial infarction in five other patients, an incidence of 14%. Perioperative infarction was associated with a significant reduction in resting ejection fraction in two cases. In those patients without evidence of perioperative infarction the mean increase in ejection fraction of 7.8% was statistically significant.

Adult↗
PubMed1984

Myocardial infarction related to valve replacement surgery.

Fifty consecutive patients, 25 undergoing aortic valve replacement and 25 mitral valve replacement, were studied by serial electrocardiography, preoperative and postoperative technetium-99m pyrophosphate radionuclide scanning, and serial measurement of enzymes (creatine kinase, aspartate aminotransferase, urea stable lactic dehydrogenase) and the MB isoenzyme of creatine kinase to define the incidence of preoperative myocardial infarction and to identify the most appropriate diagnostic techniques. The use of myocardial scanning and measurement of peak enzyme activity proved to be accurate indicators of myocardial infarction, but the electrocardiogram was of limited value. The measurement of creatine kinase MB isoenzyme had no diagnostic advantage over that of the other enzymes. There were two deaths in the series, one due to acute pancreatitis after aortic valve replacement and the other due to myocardial injury after mitral valve replacement. There were four non-fatal myocardial infarctions after aortic valve replacement, giving an incidence of 16%, and none after mitral valve replacement, giving an incidence of 4%.

Adolescent↗
PubMed1984

A light and electron microscopic study of urothelium from patients with chronic cystitis.

Urothelial tissues from two groups of patients were examined by light and transmission electron microscopy. Group A (n = 7) had no evidence of clinical or morphological abnormality. Group B (n = 9) consisted of patients with recurrent bacterial and abacterial cystitis. 6 of the 9 patients in group B showed hyperplastic urothelium in their biopsy specimens. The superficial cells contained a significantly greater number of immature cells when compared to controls (p less than 0.001). As it has been shown that bacteria attach more easily to immature cells, it is possible that their persistent presence among the luminal cells of the bladder epithelium is a contributory factor to the recurrence of cystitis.

Chronic Disease↗
PubMed1984

Long-term effects of cold cardioplegic myocardial protection in the rat.

The long-term histologic effects of the use of two cold cardioplegic solutions (St. Thomas' and saline) were studied and compared in a model of heterotopic cardiac transplantation in rats of isogeneic strain. After cold cardioplegic arrest, hearts were stored for varying times ("minimal," 30, or 90 minutes) in one of the solution prior to transplantation, giving a total of six groups (five animals in each group). Early assessment of myocardial injury 48 hours after transplantation was by the uptake of technetium 99m pyrophosphate and by measurement of serum creatine kinase activity. Late assessment of myocardial injury at 3 months after transplantation was by quantitative histologic examination. The findings indicated that significant myocardial fibrosis occurred in hearts stored in both solutions for the longest storage period (90 minutes) and that St. Thomas' cardioplegic formula conferred better myocardial protection after 90 minutes' storage than did cold saline, as judged by the degree of histologic injury at 3 months (p less than 0.025). Significant correlation was found between long-term histologic changes at 3 months and the uptake of technetium 99m pyrophosphate (p less than 0.001) and serum creatine kinase activity (p less than 0.05) assessed at 48 hours. Uptake of technetium 99m pyrophosphate and increased serum creatine kinase activity was demonstrated 48 hours after injury in animals having no detectable histologic injury at 3 months. These observations indicate that there may be technetium 99m pyrophosphate uptake and enzyme release from reversibly damaged myocardial cells.

Animals↗
PubMed1983

Detection of renal allograft rejection by computer.

A computer program incorporating an adaptation of a statistical method, the multiprocess Kalman filter, was used to detect changes in trends of plasma creatinine and urea concentrations. In 28 recipients of renal allografts a definite deterioration in renal function was identified retrospectively on 32 occasions by an experienced renal physician independently of the statistical analysis. The computer identified 31 of these 32 episodes using creatinine and urea results, and 29 using creatinine alone. Dysfunction was identified by the computer significantly earlier (p less than 0.05) than by the clinician and a median of one day earlier (p less than 0.02) than treatment was actually initiated. The computer identified dysfunction on 11 out of 1259 days when the clinician did not suspect rejection. These 11 episodes may have had a pathological importance, though no clinical diagnosis was made. This computer method is useful for immediate analysis of incoming results and for timing events either prospectively or retrospectively.

Computers↗
PubMed1983

Mathematical and statistical aids to evaluate data from renal patients.

The monitoring of renal patients and the making of many decisions during their management involves consideration of sequences of numerical data. Renal function results after renal transplantation were used as an example of how graphical presentations, simple mathematical transforms, statistical evaluation and adjustments to the data, to take into account other biological and technical sources of error, can all contribute to better understanding. Experience with a statistical technique, the 4-state Kalman filter not often used in the biological sciences, was summarized and its use suggested as a method to quantitate some traditionally subjective decisions about individual patients, for example, the onset of allograft rejection. The method has identified in retrospect and in prospect events after transplantation earlier than did experienced clinicians. Other statistical techniques to set the sensitivity and specificity of monitoring methods, to detect change points and to quantitate rhythmic sequences of clinical data were discussed, with examples, and with increasing access to computers, these can be used more easily by nephrologists, transplant surgeons, and others.

Computers↗
PubMed1983

A study of cold cardioplegic myocardial protection in rats: an experimental model using the uptake of technetium 99m pyrophosphate and enzyme activity as parameters of injury.

This study compares the use of St Thomas' cardioplegia and cold saline cardioplegia at 4 degrees C for protection against global myocardial ischaemia in a model of heterotopic cardiac transplantation in rats of isogeneic strain. The parameters of myocardial injury applied were the uptake of Technetium 99m pyrophosphate (Tc 99m Pyp) in the transplanted heart and the measurement of serum total creatine kinase (CK) and creatine kinase MB (CK:MB) isoenzyme activity. The findings indicate that St Thomas' cardioplegic solution confers improved myocardial protection compared with normal saline as judged by statistically significant differences between: (a) the uptake of Tc 99m Pyp between the two solutions at 30 min storage: and (b) the peak total serum creatine kinase enzyme activity at 90 min storage. Excellent correlation was present between the uptake of Tc 99m Pyp and peak total serum creatine kinase activity. Further application of this model is described.

Animals↗