Biomedical subjects

G M Ward

Publications and source records attributed to G M Ward.

At least 37 records · Page 2Linked to original sources

PubMed1990

Application of the SAAM modeling program to minimal model analysis of intravenous glucose tolerance test data.

The minimal model approach to analysis of intravenous glucose tolerance tests (IVGTT) yields estimates of parameters representing insulin sensitivity, glucose-mediated glucose disposal and pancreatic responsiveness. The precision of these estimates can deteriorate if the glucose and insulin data lack well-defined structure or freedom from data noise (random error). The precision of parameter estimates can be enhanced if data sets from two or more IVGTTs, obtained under different experimental conditions in the same subject, are analysed together in one data file. Following initial fitting using CONSAM, the conversational version of the modeling program SAAM, those parameters whose estimates remain at the same value under the different experimental conditions are constrained. This effectively reduces the number of adjustable parameters, and their estimates can then be fine-tuned with enhanced precision using the batch version of SAAM.

Animals↗

PubMed1990

Milk distribution and feeding practice data for the PATHWAY model.

Milk is a major source for ingestion of several radionuclides, particularly when it is produced from fresh forage. Estimation of radionuclide ingestion via milk from Nevada Test Site fallout events in the 1950s required information on the sources of milk, feeding practices for cows, and elapsed time between milking and consumption for various geographic areas. These data were essential input to the food-chain model, PATHWAY. A data base was compiled from personal interviews. Milk sources included private cows, local dairies, and regional plants that collected from and distributed to wide geographic areas. Estimates of the contribution of each source were made for communities in a nine-state area. Pasture seasons varied from 3 to 6 mo. Pasture use varied from zero to 80% of the cows' diet. Pasture use declined during the 1950s, as did the number of family cows and local dairy plants. Regional distributors captured a larger portion of the market, and improved technologies increased the shelf life of milk. These factors tended to reduce the human intake of fallout radionuclides from milk in the latter part of the 1950s.

Animals↗

PubMed1990

Effects of prolonged pulsatile hyperinsulinemia in humans. Enhancement of insulin sensitivity.

Prolonged near-physiological pulsatile insulin infusion has a greater hypoglycemic effect than continuous insulin infusion. We have previously shown that continuous hyperinsulinemia induces insulin insensitivity. This study examines the mechanisms responsible for the greater hypoglycemic effect of pulsatile insulin administration, in particular, whether prolonged pulsatile hyperinsulinemia induces insulin insensitivity. Basally and 1 h after cessation of a 20-h pulsatile infusion of insulin (0.5 mU.kg-1.min-1), eight nondiabetic human subjects were assessed for 1) glucose turnover with [3-3H]glucose, 2) insulin sensitivity by minimal-model analysis of intravenous glucose tolerance tests, and 3) monocyte insulin-receptor binding. The time-averaged plasma insulin levels were 30 +/- 5 mU/L (mean +/- SE) during the infusion, which was similar to the levels achieved in our previous continuous hyperinsulinemia study. However, the average rate of glucose infusion to maintain euglycemia was 55% greater than in the previous study. Hepatic glucose production was -5.2 +/- 1.4 mumol.kg-1.min-1 during the infusion but returned to preinfusion levels 1 h after the infusion was stopped. Insulin sensitivity (Sl) and glucose tolerance (rate of glucose disappearance, Kg) showed changes opposite in direction to our previous continuous hyperinsulinemia study (pre- vs. postinfusion Kg 1.5 +/- 0.1 vs. 1.7 +/- 0.2 min-1 x 10(2), NS; pre- vs. postinfusion Sl 8.4 +/- 2.3 vs. 11.8 +/- 3.7 min-1.mU-1.L x 10(4), P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Practical application of methods for in vivo assessment of insulin secretion and action.

In vivo measurement of insulin sensitivity can be made using the glucose clamp technique or the intravenous glucose tolerance test (IVGTT) with minimal model analysis. The glucose clamp provides a direct, readily understandable measure of insulin action but is more demanding for investigators and subjects. Assessment of insulin secretion must be made by a separate test. The IVGTT is easier to perform but the data are more difficult to analyse and the value for insulin sensitivity is a derived rather than direct measure. As well as insulin sensitivity, glucose mediated glucose disposal and insulin secretion are measured by the IVGTT. In fact the IVGTT technique relies on adequate endogenous insulin secretion whereas the glucose clamp does not. The choice between these two techniques depends on the study to be performed and the available laboratory facilities.

Animals↗

PubMed1989

Effects of short-term pulsatile and continuous insulin delivery on glucagon secretion and insulin secretion and action.

In six normal nonobese subjects, hyperinsulinemic euglycemic clamps were performed during paired sequential two-hour intravenous (IV) insulin infusions separated by an hour washout period. Each infusion was either 32 mU/kg/h of continuous insulin (CI) or 75% of this dose as 40-second pulses delivered every 13 minutes (PI). Six studies were performed with each of the following sequences in random order: PI-CI, CI-PI, and CI-CI. Based on the initial infusions, the insulin-dependent fractional glucose disappearance rate (X) during pulsatile insulin delivery (3.0 +/- 0.4 min-1 X 10(2), n = 6) was 73% of that of the continuous infusions (4.1 +/- 0.3 min-1 X 10(2), n = 12). This ratio was similar to that of the measured time-averaged plasma insulin areas (PI = 24.7 +/- 3.8 v CI = 31.4 +/- 3.5 mU/L). There was an average 23% enhancement of insulin's hypoglycemic effect during the second 12 CI infusions compared with the 12 initial CI infusions (X = 5.1 +/- 0.5 v 4.1 +/- 0.3 min-1 X 10(2), P less than .05). There was no significant difference between the enhancing effects of PI and CI infusions on insulin action in the subsequent CI's (X = 4.9 +/- 0.9 for PI-CI v X = 5.3 +/- 0.2 min-1 X 10(2) for CI-CI). First infusion PI significantly (P less than .05) decreased plasma C-peptide levels (0.34 +/- 0.05 to 0.20 +/- 0.06 mumol/L), whereas CI did not (0.33 +/- 0.02 to 0.32 +/- 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Assessment of milk transfer coefficients for use in prediction models of radioactivity transport.

The transfer coefficient (Fm) which is widely used to predict the fraction of ingested radionuclides found in milk is an important parameter for modelling. The accuracy of estimates can be improved by considering the following factors that influence the Fm; (1) the physical-chemical form of the radionuclide in the feed of cows, (2) the hay to concentrate ratio of cows diets and (3) correcting for a steady state situation for feed intake and milk concentrations. Factors such as stable element intake, soil intake, milk production rate, metabolic rate and inhalation do not appear to have significant effects upon the transfer coefficient.

Accidents↗

PubMed1989

Technetium metabolism by lactating goats.

The goat milk transfer coefficients of 99mTc, 95mTc and 99Tc, administered as pertechnetate (TcO4-), were 1.5 x 10(-4), 8.5 x 10(-4) and 1.1 x 10(-2) d L-1, respectively. The differences between the goat milk transfer coefficients of the three Tc isotopes administered as TcO4- were significant (p less than 0.05). The milk transfer coefficients of Tc were affected by chemical form and specific activity. Reduced 99mTc produced a transfer coefficient 17 times lower than that of 99TcO4- in the same goats. Reduction of pertechnetate in the rumen was evaluated to explain the low and variable transfer coefficients.

Administration, Oral↗

PubMed1989

Transfer of 137Cs to milk and meat in Hungary from Chernobyl fallout with comparisons of worldwide fallout in the 1960s.

Transfer coefficients for 137Cs from the Chernobyl accident were determined for milk (Fm) and meat (Ff) of cows and sheep in Hungary. Fm and Ff for both cows and sheep fed forage harvested within 1 mo of the accident were lower than results reported for worldwide fallout from weapons tests. Forage harvested 60 d or later after the accident produced an Fm similar to results from feeding soluble 134Cs. The results are interpreted to indicate three distinct categories of Fm about 2.0 X 10(-3), 4.0 X 10(-3) and 1.4 X 10(-2) d L-1, respectively, for Chernobyl fallout, worldwide fallout and soluble Cs isotopes or 137Cs contained in plants from soil uptake.

Accidents↗

PubMed1989

Chronic renal failure and growth.

Growth was assessed in 38 prepubertal children with chronic renal failure for a mean (range) of 2.3 (1-4) years. At first clinic visit their mean (range) glomerular filtration rate was 17 (7-35) ml/min/1.73 m2, their mean (range) age was 3.4 (0.2-9.1) years, and 23 (61%) were greater than two standard deviations below the mean for height. After intensive medical management of their chronic renal failure, half of the children who presented before 2 years of age showed appreciable catch up growth. Only a slow improvement in growth occurred in most children presenting over 2 years of age. At final assessment, the mean (range) glomerular filtration rate was 15 (6-42) ml/min/1.73(2) and 20 (53%) were greater than two standard deviations below the mean for height. There was no correlation between glomerular filtration rate and growth. There remained a group of children who continued to grow poorly. Many of these were of low birth weight, and had dysplastic kidneys.

Body Height↗

PubMed1989

Fenfluramine increases insulin action in patients with NIDDM.

These studies examined the effect of fenfluramine on insulin action and insulin secretion in healthy subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). In the first study, a double-blind crossover design was used in healthy subjects to compare the effect of short-term fenfluramine therapy (60 mg orally for 3 days) with placebo. Insulin secretion and whole-body insulin sensitivity (determined by frequently sampled intravenous glucose tolerance tests with analysis by the minimal-model method) were unchanged by fenfluramine. In the second study, involving patients with NIDDM inadequately controlled on submaximal to maximal doses of oral hypoglycemic agents, a double-blind crossover strategy was used to compare baseline studies (conducted after a run-in period) with fenfluramine (60 mg orally) or placebo for 4 wk. There was a significant fall in fasting blood glucose after therapy with fenfluramine compared with the baseline study period (13.0 +/- 1.2 vs. 8.4 +/- 0.89 mM, mean +/- SE, P less than .01) with no significant fall in fasting serum insulin (20 +/- 2 vs. 24 +/- 3 microU/ml) or C-peptide (1.3 +/- 0.2 vs. 1.3 +/- 0.1 nM). During euglycemic-hyperinsulinemic (1 mU.kg-1.min-1) clamp studies there was a significant increase in insulin action from 12.7 +/- 2.3 to 17.3 +/- 1.8 min-1.10(3) microU.ml-1 (P less than .05), although clamp insulin levels were lower after fenfluramine treatment (136 +/- 14 vs. 96 +/- 9 microU/ml, P less than .02), reflecting an enhanced metabolic clearance rate for insulin (12.7 +/- 1.5 vs. 20.1 +/- 2.1 ml.kg-1.min-1, P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Recent research involving the transfer of radionuclides to milk.

The radionuclides in milk, which result from exposure of dairy cows to radioactive fallout, are a major factor in assessment of internal radiation of humans. To evaluate the radionuclide intake of people from fallout-contaminated milk requires information about feed sources and milk distribution. Pasture intake and the shelf-life of milk are important factors in the case of a short-lived radionuclide like 131I. Large-scale human radiation assessment studies are underway, all of which consider the dairy food chain as a critical component. These include retrospective studies of fallout from nuclear weapons testing at the Nevada site in the 1950s and the impact of the Chernobyl accident on April 26, 1986.

Accidents↗

PubMed1988

A specific activity effect in the metabolism of Tc.

A study of transfer to milk of three isotopes of Tc indicated different results for 99mTcO4-, 95mTcO4-, and 99TcO4-. When the three isotopes were given orally to lactating goats in separate experiments, the milk transfer coefficients increased with decreasing specific activity. Gut absorption of Tc administered as pertechnetate (TcO4-) was decreased by reduction of TcO4- in the rumen. The rate of reduction of TcO4- in the rumen was greater for higher specific activity doses of Tc. These results suggest that the specific activity of a radioisotope may significantly influence the estimated dose to humans from contaminated milk and, probably, other food products.

Animals↗

PubMed1988

Transfer coefficients of selected radionuclides to animal products. I. Comparison of milk and meat from dairy cows and goats.

The diet-milk transfer coefficient, Fm (Bq L-1 output in milk divided by Bq d-1 intake to the animal) was studied for eight radionuclides that previously had been given little attention. The Fm values for cows and goats, respectively, were: 2.3 X 10(-5) and 1.5 X 10(-4) for 99mTc, 1.4 X 10(-4) and 8.5 X 10(-4) for 95mTc, 1.1 X 10(-2) for 99Tc (goats only); 1.7 X 10(-3) and 9 X 10(-3) for 99Mo; 4.8 X 10(-4) and 4.4 X 10(-3) for 123mTe; 4.8 X 10(-4) and 4.6 X 10(-3) for 133Ba; 5.5 X 10(-7) and 5.5 X 10(-6) for 95Zr; and 4.1 X 10(-7) and 6.4 X 10(-6) for 95Nb. The goat/cow transfer coefficient ratios for milk were approximately 10, but the goat/cow ratios for meat varied by three orders of magnitude.

Animals↗

PubMed1988

Transfer coefficients of selected radionuclides to animal products. II. Hen eggs and meat.

Transfer coefficients to eggs and meat were determined after acute oral doses of 95mTc, 99Mo, 123mTe, 133Ba, 131I, 95Zr and 95Nb to laying hens. The mean values (in units of d kg-1) to eggs and hen meat were, respectively, 3.0 and 0.03 for Tc, 0.87 and 0.18 for Mo, 5.1 and 0.60 for Te, 0.87 and 9.2 X 10(-3) for Ba, 3.2 and 0.01 for I, 2 X 10(-4) and 6 X 10(-5) for Zr, and 1 X 10(-3) and 3 X 10(-4) for Nb. For the same radionuclides administered in the same chemical form, transfer coefficients for eggs are about one to two orders of magnitude higher than for cow's milk, while the transfer coefficients for hen meat are several orders of magnitude higher than for beef.

Animals↗

PubMed1987

The influence of energy intake and percentage of body fat on the reproductive performance of nonpregnant mares.

Sixty mares in transition from winter anestrus to normal cyclicity were assigned to a 3 x 2 factorial experiment to determine the effect of energy intake and percentage of body fat on the interval to first ovulation. The factors were 1) percentage of body fat--thin (<11.5), good (11.5 to 15), or fat (>15); and 2) energy intake--maintenance (100% of National Research Council (NRC) digestible energy requirement for maintenance) or high energy (150% of NRC digestible energy requirement for maintenance). Percentage of body fat was estimated by ultrasonographic scanning of rump fat thickness. Energy treatments began on April 2 and ended on June 4. Mares were teased daily with a stallion and their ovaries were palpated per rectum daily or every third day. A high energy intake was effective in hastening ovulation for mares in the thin group (P < 0.05) but not for mares in the moderate or fat groups. Mares in the fat group had a shorter (P < 0.05) interval from April 2 to ovulation (26.4 +/- 4.2 d) than those in the good or high energy-thin groups (48.7 +/- 2.8 and 49.1 +/- 4.2 d, respectively). Duration of the initial estrus was shorter (P < 0.05) for mares in the fat group (16.2 +/- 5.7 d) compared with mares in the good group (34.7 +/- 3.9 d) and tended (P<0.12) to be shorter than mares in the high energy-thin group (29.0 +/- 5.7 d).

Journal Article↗

PubMed1987

The insulin receptor concept and its relation to the treatment of diabetes.

The initial step in insulin action is binding to specific receptors. Two covalent receptor modifications possibly involved in producing pharmacodynamic effects as a result of insulin receptor binding are autophosphorylation and disulphide insulin binding. Insulin receptor numbers are 'down regulated' by insulin, but this effect may be minimised by pulsatile insulin secretion. Insulin receptor affinity is modulated rapidly by fasting, exercise and dietary composition. In non-insulin-dependent diabetes coupling of receptor binding to bioeffects is impaired. Binding is also reduced in those subjects with hyperinsulinaemia and non-insulin-dependent diabetes. Insulin-dependent diabetics have reduced insulin sensitivity, which is only partially reversed by conventional insulin therapy. 'Post-binding defects' in some diabetics could be related to defective covalent receptor modifications resulting from genetic receptor defects. High carbohydrate diets improve diabetes control through effects on the binding and coupling defects. In addition to stimulating insulin secretion, oral hypoglycaemics stimulate post-binding insulin action in vivo and in vitro. Insulin therapy in diabetes also tends to reverse post-binding defects. Pulsatile insulin delivery is more effective in lowering blood sugar than continuous administration, and produces less 'down regulation' of receptors. Combined insulin and sulphonylurea drugs reduce insulin requirements only in insulin-dependent diabetics with some endogenous insulin secretion, whereas metformin reduces insulin requirement in C-peptide negative insulin-dependent diabetes mellitus.

Diabetes Mellitus↗

PubMed1986

An anomalous postprandial increase in erythrocyte insulin receptor affinity associated with hyperinsulinemia.

Whereas the expected decrease in the binding of 125I-insulin to erythrocytes 4.5 h after a standard mixed breakfast was seen in six young nonobese normoglycemic controls (delta % bound/free = 2.0 +/- 0.5 SEM), 10 obese hyperglycemic subjects showed an increase (0.54 +/- 0.43) and eight obese normoglycemic subjects of similar age and weight, no change in binding (0 +/- 0.31), both being significantly different from the controls (p less than 0.05) but not from each other. Of the total 18 obese subjects, the 11 with fasting hyperinsulinemia (23 +/- 1.4 mU/l) showed an increase in binding of 0.82 +/- 0.40, significantly different (p less than 0.05) from the decrease of 0.30 +/- 0.25 shown by the seven normoinsulinemic (11 +/- 1.4 mU/l) subjects, despite their similar age, weight, and blood glucose concentrations. These changes in binding were explained by alterations in receptor affinity. Thus, an anomalous postprandial increase in erythrocyte insulin receptor affinity occurs in some obese subjects with or without diabetes, and is related to hyperinsulinemia rather than hyperglycemia.

Adult↗

PubMed1986

Structure of the human erythrocyte insulin receptor.

The structure of the insulin receptor in intact human erythrocytes was defined using the techniques of disuccinimidyl suberate (DSS) cross-linking of 125I-insulin and surface [125I]iodination followed by receptor immunoprecipitation. In contrast to a recent report, we found the erythrocyte insulin receptor to be similar in structure to that in classic target tissues for insulin, consisting of at least three species of molecular weight approximately 295,000, 265,000, and 245,000, containing disulfide-linked subunits of molecular weight approximately 130,000 and 95,000. The interconversion of the three oligomeric forms could mediate changes in receptor affinity as postulated in other tissues. The 95,000 subunit was detected by immunoprecipitation only if surface iodination was performed in a Tris/Hepes buffer using lodogen and not if phosphate-buffered saline or lactoperoxidase iodination was used. These findings indicate that the lack of a bioeffect of insulin in erythrocytes is not explained by a gross defect in the structure of their insulin receptors. The apparent identity of the insulin receptor structure in erythrocytes and insulin target tissues provides a firmer basis for the use of erythrocytes in some circumstances to reflect insulin receptor status.

Adult↗