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Biomedical subjects

R Taylor

Publications and source records attributed to R Taylor.

At least 19 recordsLinked to original sources

Immunocytochemical survey of putative neurotransmitters in taste buds from Necturus maculosus.

To investigate synaptic mechanisms in taste buds and collect information about synaptic transmission in these sensory organs, we have examined taste buds of the mudpuppy, Necturus maculosus for the presence of neurotransmitters and neuromodulators. Immunocytochemical staining at the light microscopic level revealed the presence of serotonin-like and cholecystokinin-like (CCK) immunoreactivity in basal cells in the taste bud. Nerve fibers innervating taste buds were immunoreactive for vasoactive intestinal peptide-like (VIP), substance P-like, and calcitonin gene-related peptide-like (CGRP) or compounds closely related to these substances. Immunoreactivity for tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) in the taste cells and nerve fibers was absent. These data suggest that serotonin, CCK, VIP, substance P, and CGRP are involved in synaptic transmission or neuromodulation in the peripheral organs of taste. No evidence was found for cholinergic or adrenergic mechanisms on the basis of the absence of immunocytochemical staining for key enzymes involved in these two transmitter systems.

Animals

Primary malignant melanoma of skin in four regions of New Zealand.

AIMS: to describe the incidence and thickness of a representative collection of melanomas occurring in recent years in New Zealand. METHODS: all pathology reports of primary malignant melanoma of the skin, in defined periods in 1987-9, were collated for four regions of New Zealand. RESULTS: nonMaori incidence rates were 52 and 58 melanomas per 100,000 person years for men and women, respectively. These rates are much higher than the 24 per 100,000 person years for melanoma registrations in 1983-4. The age standardised invasive melanoma rate of 35 per 100,000 person years was higher than those of most Australian states and close to the rate for Queensland in 1986. Preinvasive melanomas comprised 26% of all melanomas. Of invasive melanomas, 58% in men and 55% in women were less than 0.76 mm in thickness; 7% of invasive melanomas in men and 5% in women were at least 3.5 mm thick. CONCLUSIONS: increasingly early detection of malignant melanomas in successive years is likely to have contributed to the recent increase in incidence, perhaps to a major degree, but an environmental cause cannot be excluded.

Adolescent

Validation of 13C NMR measurement of human skeletal muscle glycogen by direct biochemical assay of needle biopsy samples.

Recent developments in 13C nuclear magnetic resonance (NMR) spectroscopy have permitted noninvasive assessment of glycogen concentration in human skeletal muscle. Before these indirect measurements could be accepted as accurate, it was essential that validation should be carried out by comparing the widely used method of muscle biopsy and direct biochemical assay for glycogen concentration with measurement by NMR. Eight normal subjects underwent six NMR scans of gastrocnemius and three biopsies of the same muscle on the same day. The overall mean for muscle glycogen concentration was 87.4 mM by NMR and 88.3 mM by biopsy. There was a close correlation between the pairs of observations on each subject (R = 0.95; P less than 0.0001). The mean coefficient of variation for NMR measurement was 4.3 +/- 2.1% and that for biopsy was 9.3 +/- 5.9%. The performance of the muscle biopsies was accompanied by a small but significant rise in plasma-free fatty acids (529 +/- 157 to 667 +/- 250; P less than 0.01), epinephrine (17 +/- 6 to 25 +/- 8 pg/ml; P less than 0.02), and norepinephrine (318 +/- 119 to 400 +/- 140 pg/ml; P less than 0.02) but no change in plasma glucose, plasma insulin, nor muscle glycogen concentration assessed by NMR. The study demonstrates that in vivo 13C NMR measurement of human muscle glycogen can be regarded as accurate, and the technique is associated with a higher precision that biopsy with direct biochemical assessment.

Biopsy, Needle

Gliclazide: metabolic and vascular effects--a perspective.

Gliclazide is a second-generation sulfonylurea that is widely used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It has been recommended for use on the basis of both its metabolic and nonmetabolic effects. It has a clear beneficial effect on metabolic control in NIDDM. Blood glucose and lipid levels are lowered. The glucose-lowering effects are secondary to both enhanced insulin secretion and a decrease in insulin resistance. The former is due to closure of a K+ adenosine triphosphate (ATP) channel in the beta cell. The mechanism whereby insulin action on the liver and muscle are potentiated remains unknown. It does not appear to involve the insulin receptor, and although glycogen synthase activation is enhanced, this is probably not specific. It has proven difficult to separate the metabolic effects of gliclazide from the effects of improved control. The metabolic actions are probably also shared with other sulfonylureas. Gliclazide also has beneficial effects on platelet behavior and function and on the endothelium, in addition to improving free radical status. These effects should be beneficial for the prevention of diabetic microangiopathy and macroangiopathy. Some evidence has appeared for the prevention of deterioration of diabetic retinopathy, but results are variable and more convincing studies are required. Many of the nonmetabolic effects of gliclazide appear to be unique to this agent. Gliclazide thus appears to be a reasonable choice in the treatment of NIDDM with diet failure, both from the metabolic and nonmetabolic standpoint.

Cardiovascular Diseases

Etretinate increases carcinoembryonic antigen in palmar scrapings.

BACKGROUND: Retinoids can affect epithelial structure and function. Patients who take etretinate can develop stickiness of their palms and soles. OBJECTIVE: We measured carcinoembryonic antigen, a representative glycoprotein in palmar scrapings, to see whether levels were increased in patients taking etretinate when compared with a variety of controls. METHODS: Carcinoembryonic antigen was measured by a standard immunoassay in scrapings taken from the palm. RESULTS: Carcinoembryonic antigen is increased in palmar scrapings in patients taking etretinate. CONCLUSION: Etretinate usage may affect sweat gland function or possibly adherence of carcinoembryonic antigen to surface keratinocytes. The presence of increased amounts of glycoprotein on the surface of the skin may explain the stickiness often noted by patients taking etretinate.

Carcinoembryonic Antigen

Automation of conformational analysis and other molecular modeling calculations.

A software system has been developed for facilitating modeling calculations on large numbers of molecules. Using the system, it is possible to subject one or more molecules to a series of calculations, each requiring use of a different computer program. No user intervention is required: where necessary, output from one program is used automatically as input to the next. Names are assigned to output files automatically and in a systematic manner. As an example, the system can be used to perform a succession of calculations aimed at identifying the major low-energy conformers of each of a set of molecules, starting only from their chemical connectivities. The reliability of the results has been tested by calculations on 40 molecules taken from the Cambridge Structural Database. The observed crystal structure geometry could be found for the majority of these molecules.

Computer Simulation

Intra-abdominal panniculitis can mimic recurrent stomach carcinoma.

Carcinoma of the stomach is increasingly treated with chemotherapy. We describe two cases of intra-abdominal panniculitis in patients after laparotomy and chemotherapy for stomach carcinoma. Intra-abdominal panniculitis can result in mass lesions in the mesentery and omentum. The diagnosis should be considered in patients who have undergone chemotherapy for stomach carcinoma and who develop abdominal masses.

Abdomen

Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man.

1. Experimental elevation of plasma non-esterified fatty acid concentrations has been postulated to decrease insulin-stimulated glucose oxidation and storage rates. Possible mechanisms were examined by measuring skeletal muscle glycogen synthase activity and muscle glycogen content before and during hyperinsulinaemia while fasting plasma non-esterified fatty acid levels were maintained. 2. Fasting plasma non-esterified fatty acid levels were maintained in seven healthy male subjects by infusion of 20% (w/v) Intralipid (1 ml/min) for 120 min before and during a 240 min hyperinsulinaemic euglycaemic clamp (100 m-units h-1 kg-1) combined with indirect calorimetry. On the control day, 0.154 mol/l NaCl was infused. Vastus lateralis muscle biopsy was performed before and at the end of the insulin infusion. 3. On the Intralipid study day serum triacylglycerol (2.24 +/- 0.20 versus 0.67 +/- 0.10 mmol/l), plasma nonesterified fatty acid (395 +/- 13 versus 51 +/- 1 mumol/l), blood glycerol (152 +/- 2 versus 11 +/- 1 mumol/l) and blood 3-hydroxybutyrate clamp levels [mean (95% confidence interval)] [81 (64-104) versus 4 (3-5) mumol/l] were all significantly higher (all P less than 0.001) than on the control study day. Lipid oxidation rates were also elevated (1.07 +/- 0.07 versus 0.27 +/- 0.08 mg min-1 kg-1, P less than 0.001). During the clamp with Intralipid infusion, insulin-stimulated whole-body glucose disposal decreased by 28% (from 8.53 +/- 0.77 to 6.17 +/- 0.71 mg min-1 kg-1, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid

Kinetics of sodium-lithium countertransport activity in patients with uncomplicated type 1 diabetes.

1. Increased erythrocyte sodium-lithium countertransport activity has been reported to be associated with nephropathy in type 1 diabetes and linked to a family history of essential hypertension. 2. This study aimed to determine the mechanism of increased sodium-lithium countertransport activity. Sodium-lithium countertransport kinetics were measured in uncomplicated and hyperlipidaemic type 1 diabetic patients. 3. In the nine out of 31 uncomplicated type 1 diabetic patients who had high sodium-lithium countertransport activity, the sodium affinity (Km) was normal but the maximum velocity (Vmax) was increased. 4. Hyperlipidaemia, when present in diabetic patients, was associated with increased sodium-lithium countertransport activity, but could not explain the high activity in uncomplicated type 1 diabetic patients in whom plasma lipid concentrations were normal. 5. Sodium-lithium countertransport activity is increased in type 1 diabetes by a mechanism different to that in essential hypertension, where the mechanism is a low Km (increased sodium affinity). Hence familial hypertension cannot explain the raised sodium-lithium countertransport activity in type 1 diabetes.

Adult

Changes in erythrocyte sodium-lithium countertransport kinetics in diabetic nephropathy.

1. It has been proposed that raised erythrocyte sodium-lithium countertransport activity in type 1 diabetic patients is associated with an increased risk of developing diabetic nephropathy. Diabetic patients with established nephropathy would therefore be expected to have high activity. 2. Standard sodium-lithium countertransport activity, sodium affinity (Km) and maximum velocity (Vmax) were measured in type 1 diabetic patients at different stages of diabetic nephropathy and in appropriately matched uncomplicated diabetic patients and normal control subjects. 3. A small proportion (15%) of patients with nephropathy had standard sodium-lithium countertransport activity higher than the control range. However, mean standard sodium-lithium countertransport activity in the diabetic patients with nephropathy [mean +/- SEM, 0.26 +/- 0.12 mmol of Li+ h-1 (l of cells)-1] was not significantly higher than in the uncomplicated diabetic patients [0.27 +/- 0.03 mmol of Li+ h-1 (l of cells)-1] or in the normal control subjects [0.25 +/- 0.02 mmol of Li+ h-1 (l of cells)-1]. 4. There were marked changes in the kinetic characteristics of the sodium-lithium countertransport in the diabetic patients with nephropathy so that there were decreases in both Km and Vmax. 5. These kinetic changes could not be attributed to an effect of either renal failure per se or the duration of diabetes. 6. The characteristic kinetic changes in sodium-lithium countertransport may indicate underlying alterations in membrane function with the onset of nephropathy in type 1 diabetes.

Antiporters

Dietary intake, exercise, obesity and noncommunicable disease in rural and urban populations of three Pacific Island countries.

Dietary intake surveys of rural and urban communities in three Pacific Island countries were conducted using an adjusted 24-hour dietary recall method. Dietary survey samples were drawn from noncommunicable disease surveys of Melanesians and Indians in Fiji, Micronesians in Kiribati and Melanesians in Vanuatu. Comparisons of total energy and macronutrient intakes and of obesity, hypertension, diabetes mellitus, serum cholesterol and physical activity levels revealed similar rural/urban trends. Urban subjects were more obese than rural ones, had higher prevalence rates of diabetes and hypertension, and generally had higher cholesterol levels. Rural subjects were leaner, suffered less from diabetes and hypertension, and had greater total energy intakes than urban dwellers. Rural people ate a greater proportion of carbohydrates, while urban subjects ate proportionally more protein and fat, apart from the outer Kiribati atolls with high coconut intakes. Rural subjects in all three studies had higher levels of physical activity. These studies provide persuasive evidence that exercise as well as diet has a significant effect on rural/urban differentials in obesity and noncommunicable disease, and that energy intake reflects energy expenditure.

Diet

Heparin management protocol for cardiopulmonary bypass influences postoperative heparin rebound but not bleeding.

A group of 63 adult patients undergoing cardiac surgical procedures requiring cardiopulmonary bypass (CPB) were studied to examine the relationship between heparin doses administered and postoperative bleeding. Patients were randomly assigned either to receive heparin 200 U/kg and additional heparin as needed to reach and maintain an activated clotting time (ACT) greater than 400 s for CPB (group A, n = 30), or to receive heparin 400 U/kg and additional heparin as needed to reach and maintain a whole blood heparin concentration greater than 4.0 U/ml for CPB (group H, n = 33). Groups were compared for the amount of postoperative bleeding, heparin rebound, homologous transfusion requirements, and standard laboratory coagulation tests. In the last 33 patients studied, additional tests of platelet aggregation and plasma levels of beta thromboglobulin (BTG), antithrombin III, and several markers of fibrinolysis were measured and compared by group. The mean heparin dose was 28,000 +/- 4,800 U for group A and 57,000 +/- 10,700 U for group H (P less than 0.05 for group A vs. group H). At 8 and 24 h postoperatively, mediastinal drainage did not differ significantly between groups (mean 24-h drainage +/- SD = 901 +/- 414 ml in group A, 1035 +/- 501 ml in group H), nor did the incidence of transfusion with homologous blood products.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

General anesthesia and exhaled breath hydrogen peroxide.

To study the role of free radical formation on the impairment of pulmonary function seen with general anesthesia, we measured the hydrogen peroxide (H2O2) concentration in the exhaled breath condensate of 27 patients. Patients were divided into three study groups: a healthy patient group (group 1, n = 15) consisting of ASA physical status 1 and 2 patients undergoing elective noncardiothoracic surgery; a specific anesthetic event group (group 2, n = 6) composed of patients undergoing cardiopulmonary bypass (CPB); and a positive control group (group 3, n = 6) consisting of patients with the adult respiratory distress syndrome (ARDS). The exhaled breath condensate was collected by diverting exhaled breath through a glass condensation coil submerged in an ice/salt water bath. The exhaled breath condensate samples were then assayed using a spectrophotometric method. In group 1, samples were collected before and after the induction of general anesthesia with intravenous drugs, and before and after the administration of the inhalational anesthetics isoflurane (1.5%) (n = 7) or N2O (70%) (n = 8). In group 2, samples were collected pre- and post-CPB, and in group 3, when specific diagnostic criteria for ARDS were met. There was no significantly detectable H2O2 (not significantly different from zero) in any of the samples from the group 1 patients. Similarly, group 2 patients had exhaled breath H2O2 concentrations near zero except for one patient who was positive for the lupus anticoagulant. Group 3 patients had a mean (+/- SE) exhaled breath H2O2 concentration of 0.55 (+/- 0.08) microM, which was significantly greater than zero (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General

Insulin sensitivity and secretion in healthy elderly human subjects with 'abnormal' glucose tolerance.

Glucose tolerance deteriorates dramatically with advancing age. It is not known whether the underlying pathophysiology is different in older subjects. We employed a two step hyperinsulinaemic euglycaemic glucose clamp with [6(14)C] glucose infusion to compare peripheral and hepatic insulin sensitivity in eight elderly (EAGT) with eight young (YAGT) subjects with abnormal (matched) glucose tolerance and nine elderly subjects with normal glucose tolerance (ENGT). There was no difference in basal HGO (EAGT 14.5 +/- 0.9, YAGT 15.3 +/- 1.1 mumol kg-1 min-1). Glucose turnover was similar in both groups at step 1 (EAGT 13.2 +/- 0.8, YAGT 13.4 +/- 0.8 mumol kg-1 min-1) and step 2 (EAGT 25.1 +/- 3.1, YAGT 27.2 +/- 2.7 mumol kg-1 min-1). HGO was lower in the EAGT subjects at step 1 (2.3 +/- 0.4 vs. 4.3 +/- 0.6 mumol kg-1 min-1 P = 0.01). Incremental serum insulin response to oral glucose was comparable (EAGT 66.8 +/- 11.6 YAGT 57.8 +/- 12.2 mU l-1.h). Compared to the ENGT group the EAGT group was insulin resistant with a lower MCR of glucose at step 1 (2.03 +/- 0.28 vs. 3.23 +/- 0.44 ml kg-1 min-1 P = 0.04) and at step 2 (6.18 +/- 0.83 vs. 9.64 +/- 0.38 ml kg-1 min-1 P = 0.004) and had a lower early insulin response (AUC 0-30 min 5.9 +/- 1.1 vs. 9.8 +/- 1.4 mU l-1.h P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Five year audit of peripartum blood glucose control in type 1 diabetic patients.

An audit was conducted of the degree of blood glucose control achieved during labour using a simple glucose/insulin infusion regimen. Records were examined of 40 pregnancies in 37 women over a 5-year period. Mean blood glucose was 5.2 +/- 2.2 (SD) mmol-1 7 h before delivery and 4.7 +/- 1.8 mmol-1 1 h before delivery. Four women experienced mild symptomatic hypoglycaemia before delivery and two during the 6 h after delivery. Seven neonates had blood glucose levels of 2.2 mmol-1 or less recorded at any time, but there was no relationship between neonatal hypoglycaemia and maternal hyperglycaemia during labour in the range of achieved maternal blood glucose levels. The mean HbA1 at booking was 8.4 +/- 1.2% (non-diabetic range 5.0-7.5%) and fell to a steady plateau from 12 weeks gestation to delivery averaging 7.5% (2SD above the non-diabetic mean). These data demonstrate the practical applicability of a simple regimen for control of blood glucose during labour in insulin-dependent diabetic women and suggest that less stringent aims of blood glucose control than originally adopted may be appropriate.

Adult