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Biomedical subjects

T R Hennessy

Publications and source records attributed to T R Hennessy.

17 recordsLinked to original sources
PubMed1996

Measurement of glucose metabolism and insulin secretion during normal pregnancy and pregnancy complicated by gestational diabetes.

Gestational diabetes affects 2-3% of pregnant women and is associated with foetal complications including macrosomia and an increased likelihood of developing diabetes in later life. We have therefore studied seven women with gestational diabetes and five control women both during the third trimester of pregnancy and again 2-3 months post-partum, using the minimal model analysis of the frequently sampled labelled ([6,6-2H2]-glucose) intravenous glucose tolerance test. Glucose tolerance (glucose Kd) was significantly reduced in the women with gestational diabetes compared with the normal pregnant women both in pregnancy (1.16 +/- 0.11 vs 1.78 +/- 0.23%/min; p < 0.05) and post-partum (1.47 +/- 0.22 vs 2.59 +/- 0.43%/min; p < 0.05) and increased significantly in the control women after delivery (p < 0.05). Glucose effectiveness was not significantly different between the women with gestational diabetes and the control group either during or after pregnancy. Insulin sensitivity was significantly lower during pregnancy than after delivery in the women with gestational diabetes (p < 0.05). There was no significant difference in basal insulin secretion in the two groups during pregnancy or post-partum. However, during pregnancy the control subjects significantly increased (p < 0.001) their insulin secretion over a period of 20 min in response to an intravenous glucose tolerance test (96.2 +/- 42.7 pmol/kg) compared with post-partum values (58.3 +/- 25.2 pmol/kg) while in the women with gestational diabetes insulin secretion was similar in pregnancy (65.5 +/- 9.3 pmol/kg) and after delivery (57.7 +/- 15.7 pmol/kg). These data suggest that the glucose intolerance in gestational diabetes compared to normal pregnancy is due to reduced insulin sensitivity and an impaired ability in gestational diabetes to increase insulin secretion in response to glucose.

Adult↗
PubMed1996

Modelling nanoscale fluid dynamics and transport in physiological flows.

The concept of nanotechnology is discussed, and its connection with biomedical engineering is elucidated. For the specific field of nanoscale flow and transport problems of physiological relevance, some typical examples are presented, and their interaction is discussed for some classic biomechanical problems like the flow in arteries with blood-wall coupling. Then, existing computational models are presented and classified according to the length scale of interest, with emphasis on particle-fluid problems. Final remarks address the essential unity of biomedical and engineering behaviour and the possible relevance to small-scale industrial research.

Biological Transport, Active↗
PubMed1995

Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in NIDDM.

We measured the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 (VLDL apoB) using a stable isotope gas-chromatography mass-spectrometry method in six patients with non-insulin-dependent diabetes mellitus (NIDDM) (four males, two females, age 57.5 +/- 2.2 years (mean +/- SEM), weight 88.2 +/- 5.5 kg, glycated haemoglobin (HbA1) 8.5 +/- 0.5%, plasma total cholesterol concentration 5.7 +/- 0.5 mmol/l, triglyceride 3.8 +/- 0.9 mmol/l, high-density lipoprotein (HDL) cholesterol 1.0 +/- 0.1 mmol/l) and six non-diabetic subjects matched for age, sex and weight (four males, two females, age 55.7 +/- 2.8 years, weight 85.8 +/- 5.6 kg, HbA1 6.5 +/- 0.1%, plasma total cholesterol concentration 5.7 +/- 0.5 mmol/l, triglyceride 1.2 +/- 0.1 mmol/l, HDL cholesterol 1.4 +/- 0.1 mmol/l). HbA1, plasma triglyceride and mevalonic acid (an index of cholesterol synthesis in vivo) concentrations were significantly higher in the diabetic patients than in the non-diabetic subjects (p = 0.006, p = 0.02 and p = 0.004, respectively). VLDL apoB absolute secretion rate was significantly higher in the diabetic patients compared with the non-diabetic subjects (2297 +/- 491 vs 921 +/- 115 mg/day, p < 0.05), but there was no significant difference in the fractional catabolic rate of VLDL apoB. There was a positive correlation between VLDL apoB secretion rate and (i) fasting C-peptide (r = 0.84, p = 0.04) and (ii) mevalonic acid concentration (r = 0.83, p < 0.05) in the diabetic patients but not in the non-diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein B-100↗
PubMed1995

Increased hepatic secretion of very-low-density-lipoprotein apolipoprotein B-100 in heterozygous familial hypercholesterolaemia: a stable isotope study.

We have measured the hepatic secretion of very-low-density-lipoprotein apolipoprotein B-100 (VLDL apo B) in 6 patients with heterozygous familial hypercholesterolaemia (FH) (4 males, 2 females, age 47.0 +/- 2.7 years (mean +/- S.E.M.), weight 71.0 +/- 5.3 kg) and 6 normocholesterolaemic subjects matched for age, weight and sex (4 males, 2 females, age 47.5 +/- 3.1 years, weight 70.0 +/- 4.4 kg) using a stable isotope method. Each subject received a primed, constant infusion of [I-13C]leucine and isotopic enrichment of VLDL apo B was determined using gas-chromatography mass-spectrometry (GCMS). Mean plasma low-density-lipoprotein (LDL) cholesterol and apo B concentrations in the FH group were more than twice that in the control group (FH, 8.5 +/- 0.5 mmol/l vs. controls, 3.3 +/- 0.2 mmol/l, P < 0.001; and FH, 2.0 +/- 0.1 g/l vs. controls, 1.0 +/- 0.04 g/l, P < 0.0001, respectively). Plasma triglyceride (TG) and high-density-lipoprotein (HDL) cholesterol concentrations were not significantly different between the two groups. Although the fractional secretion rates of VLDL apo B were similar (FH, 14.3 +/- 3.6 pools/day vs. controls, 11.6 +/- 1.7 pools/day, P = 0.53), VLDL apo B pool size and VLDL apo B absolute secretion rates (ASR) were significantly higher in the FH group (FH, 234.2 +/- 27.8 mg vs. controls, 66.3 +/- 13.5 mg, P < 0.001; and FH, 51.4 +/- 17.9 mg/kg per day vs. controls, 9.4 +/- 1.1 mg/kg per day, P < 0.02, respectively). We conclude that FH is associated with increased hepatic secretion of VLDL apo B and that this may contribute to the elevated concentration of LDL-cholesterol. The findings are also consistent with the hypothesis that in FH increased hepatic cholesterol availability (due to increased uptake of LDL-cholesterol via the receptor-independent pathway) stimulates hepatic secretion of VLDL apo B.

Adult↗
PubMed1995

Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in obesity: a stable isotope study.

1. We measured the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 (VLDL apoB) using a stable-isotope gas chromatography-mass spectrometry method in six obese subjects [three males, three females, age 41.5 +/- 3.4 years (mean +/- SEM), weight 105.0 +/- 4.8 kg, plasma total cholesterol concentration 6.2 +/- 0.4 mmol/l, triacylglycerol 2.8 +/- 0.8 mmol/l, high-density lipoprotein cholesterol 1.0 +/- 0.2 mmol/l] and six lean control subjects (three males, three females, age 41.8 +/- 3.7 years, weight 68.2 +/- 4.9 kg, total cholesterol concentration 4.5 +/- 0.3 mmol/l, triacylglycerol 0.8 +/- 0.2 mmol/l, high-density lipoprotein cholesterol 1.3 +/- 0.1 mmol/l). 2. Plasma total cholesterol, triacylglycerol and mevalonic acid (an index of cholesterol synthesis in vivo) concentrations were significantly higher in the obese subjects than in control subjects (P = 0.02, P = 0.03, P = 0.04, respectively). VLDL apoB pool size and absolute secretion rate were significantly higher in the obese subjects than in control subjects (323.4 +/- 99.8 mg versus 53.6 +/- 17.1 mg, P = 0.004; and 42.3 +/- 13.8 mg kg fat-free mass-1 day-1 versus 10.7 +/- 0.4 mg kg fat-free mass-1 day-1, P = 0.01), but there was no significant difference in the fractional catabolic rate of VLDL apoB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A comparison of the effects of IGF-I and insulin on glucose metabolism, fat metabolism and the cardiovascular system in normal human volunteers.

The metabolic and cardiovascular effects of recombinant human IGF-I were compared to insulin in six normal subjects. Subjects were studied twice and intravenously received an infusion of [6,6-2H2]glucose (0-480 min) and in random order either IGF-I 20 micrograms kg-1 h-1 (43.7 pmol kg-1 min-1 or insulin 0.5 mU kg-1 min-1 (3.4 pmol kg-1 min-1) with an euglycaemic clamp. One subject was withdrawn following a serious adverse event. During the IGF-I infusion glucose appearance rate (Ra) decreased from 1.79 +/- 0.13 at baseline (150-180 min) to 0.35 +/- 0.26 mg kg-1 min-1 (P < 0.01) at 360 min, and glucose utilization rate (Rd) increased from 1.79 +/- 0.28 to 4.17 +/- 0.84 mg kg-1 min-1 (P < 0.01). There was no change in free fatty acids (FFA) and an increase (percentage change from pre-infusion mean) in cardiac output +l37.3% +/- 9% (P < 0.01), heart rate +13% +/- 2% (P < 0.01) and stroke volume +21% +/- 7% (P < 0.05). During the insulin infusion glucose Ra decreased from 1.89 +/- 0.13 to 0.34 +/- 0.33 mg kg-1 min-1 (P < 0.01) and FFA from 0.546 mmol l-1 to 0.198 mmol l-1 (P < 0.01), glucose Rd increased from 1.89 +/- 0.18 to 5.41 +/- 1.47 mg kg-1 min-1 (P < 0.01) and there were no significant changes in the cardiovascular variables.

Adult↗
PubMed1995

Acute hyperinsulinemia decreases the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in NIDDM.

In a randomized crossover study, we measured the hepatic secretion rate of very-low-density lipoprotein (VLDL) apolipoprotein B-100 (apoB) in seven patients with well-controlled non-insulin-dependent diabetes mellitus (NIDDM) (HbA1 8.4 +/- 0.4% [mean +/- SE]) on two occasions: during a 13-h hyperinsulinemic (plasma insulin concentration 586 +/- 9.7 pmol/l) euglycemic (plasma glucose concentration 5.2 +/- 0.1 mmol/l) clamp; and during a 13-h saline (control) infusion. After 5 h of the hyperinsulinemic euglycemic clamp (or saline infusion) when a new steady state of apoB turnover was reached, [1-(13)C]leucine was administered by a primed (1 mg/kg), constant 8-h infusion (1 mg.kg-1. h-1). VLDL apoB isotopic enrichment was determined with gas chromatography-mass spectrometry, and a monoexponential model was used to calculate the fractional secretion rate of VLDL apoB. VLDL apoB secretion rate was significantly reduced during the hyperinsulinemic euglycemic clamp compared with the saline study (12.2 +/- 3.6 vs. 24.5 +/- 7.1 mg.kg-1.day-1, P = 0.001), but there was no change in the fractional catabolic rate of VLDL apoB. Concomitantly, plasma concentrations of nonesterified fatty acids (NEFAs), glycerol, and triglycerides (TGs) were significantly lower during the hyperinsulinemic euglycemic clamp compared with the saline study (NEFAs, P < 0.001; glycerol, P = 0.005; TGs P = 0.004). We conclude that acute hyperinsulinemia decreases the hepatic secretion rate of VLDL apoB in NIDDM, probably in part due to reduction in the delivery of NEFA and glycerol substrate to the liver.

Apolipoprotein B-100↗
PubMed1994

Use of a leucine clamp to demonstrate that IGF-I actively stimulates protein synthesis in normal humans.

Insulin-like growth factor I (IGF-I) is thought to mediate the anabolic action of growth hormone. A glucose and amino acid clamp technique was used to investigate the effects of a 3-h intravenous infusion of either 43.7 pmol.kg-1.min-1 (20 micrograms.kg-1.h-1) IGF-I or 3.4 pmol.kg-1.min-1 (0.5 mU.kg-1.min-1) insulin on whole body leucine turnover in five normal human volunteers. During the IGF-I infusion, IGF-I levels increased (P < 0.01; 26.6 +/- 2.8 to 88.9 +/- 14.2 nmol/l) and insulin levels fell (P < 0.05; 0.096 +/- 0.018 to 0.043 +/- 0.009 nmol/l). During the insulin infusion, insulin levels increased (P < 0.01; 0.057 +/- 0.013 to 0.340 +/- 0.099 nmol/l), and there was no change in IGF-I. There was no significant change in leucine production rate (Ra; a measure of protein degradation) during the IGF-I infusion (2.23 +/- 0.17 to 2.13 +/- 0.2 mumol.kg-1.min-1), but there was an increase (P < 0.03) in nonoxidative leucine disposal rate (Rd; a measure of protein synthesis; 1.83 +/- 0.15 to 2.05 +/- 0.21 mumol.kg-1.min-1). In contrast, insulin reduced (P < 0.02) leucine Ra (1.81 +/- 0.24 to 1.47 +/- 0.24 mumol.kg-1.min-1) and had no effect on nonoxidative leucine Rd (1.44 +/- 0.25 to 1.41 +/- 0.22 mumol.kg-1.min-1). We conclude that IGF-I, under conditions of adequate substrate supply, directly increases protein synthesis in contrast to insulin, which exerts its anabolic action by reducing proteolysis.

Adult↗
PubMed1992

Incomplete suppression of hepatic glucose production in non-insulin dependent diabetes mellitus measured with [6,6-2H2]glucose enriched glucose infusion during hyperinsulinaemic euglycaemic clamps.

We have minimized methodological errors in the isotope dilution technique by using stable isotope, [6,6-2H2]glucose, thus avoiding the problem of contamination of tritiated glucose tracers and, by maintaining a constant plasma tracer enrichment have reduced error due to mixing transients. Using these modifications we have calculated hepatic glucose production in 20 patients with non-insulin-dependent diabetes mellitus during low (1 mU kg-1 min-1) and high (8 mU kg-1 min-1) dose insulin infusions. Mean fasting hepatic glucose production was 14.2 +/- 0.8 mumol kg-1 min-1. This suppressed by only 68% to 4.6 +/- 0.8 mumol kg-1 min-1 during the low-dose insulin infusion (plasma insulin 0.85 +/- 0.05 nmol l-1) and did not suppress further during the high-dose insulin infusion (plasma insulin 14.55 +/- 0.83 nmol l-1). Hepatic glucose production was significantly higher than zero throughout the study. Thus, we have found that minimization of known errors in the isotope dilution technique results in physiologically plausible and significantly positive values for hepatic glucose production indicating that the liver is resistant to insulin in patients with non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1990

Venous air embolism in swine: transport of gas bubbles through the pulmonary circulation.

The assumption that the lung is an effective filter for gas bubbles is of importance for certain occupations (e.g., divers, astronauts) as well as in the accomplishment of several medical procedures. The filtering capacity was tested in pigs by use of continuous air infusion into the right ventricle and a transesophageal echocardiographic transducer for detection of air in the left atrium. Twenty pigs, anesthetized with pentobarbital sodium and mechanically ventilated, were divided into groups that received air at infusion rates of 0.05 (group 1a, n = 7), 0.10 (group 2, n = 6), and 0.20 (group 3, n = 5) ml.kg-1.min-1. Two pigs served as controls. The breakthrough incidence was 0, 67, and 100%, respectively. Group 1a received a second infusion of 0.10 ml.kg-1.min-1 (group 1b, n = 7), and spillover of bubbles occurred in only 14% of these pigs. Infusion of gas caused a maximum increase in mean pulmonary arterial pressure (PAP) of 129 +/- 9% to 39.2 +/- 1.3 (SE) mmHg, with no significant difference between the groups. Breakthrough was observed only in animals with a dramatic reduction in mean arterial pressure and a PAP that returned to almost-normal values at spillover time. Our results suggest that the threshold value for breakthrough of air bubbles in pigs is reduced compared with that in dogs. The hemodynamic consequences at a given infusion rate are, however, greatly enhanced.

Animals↗
PubMed1984

U.K. deep diving trials.

Using a breathing medium of 40 kPa oxygen, remainder helium, 18 volunteer subjects participated in a series of 15 exposures to pressures equivalent to depths of 180-540 m s.w. The time of exposure at these pressures was mostly 2 days, except for the 540 m s.w. exposure, when 6 days were spent at full pressure. Compression procedures, based upon placing 'stages' at 60 m s.w. intervals, evolved with experience and proved to be a highly successful way of achieving acceptable pressure-time courses. Decompression combined slow linear release of pressure with overnight halts for sleep. On one occasion a depth of 660 m s.w. was reached by breathing 40 kPa oxygen, 10% nitrogen, remainder helium. Throughout all exposures, teams of investigators followed the changes in cardiovascular, respiratory, haematological, neurophysiological and metabolic status, and mental performance of the volunteers. Some major findings were that the neurophysiological and behavioural changes could be assigned to the motor, or vestibular, or cerebral, or autonomic systems, and were mainly first observed during compression. The subjects suffered, apparently from severe nitrogen narcosis, when breathing 10% (by volume) nitrogen in oxygen-helium at 420 m s.w. Lung ventilation was remarkably adaptable to the oxygen requirements of exercise at all depths, but cardiac output was adversely affected at 540 m s.w., particularly for heavier workloads. Ventilatory responses to carbon dioxide were significantly elevated after diving. Thermal balance was seen to be precarious, but nevertheless it was achieved by the normal subjective assessments of comfort. Water loss was affected by diminished evaporation from the skin. Skin temperature sensitivity was changed and took many days after the dives to return to normal. Energy requirements increased for work purposes, but basal metabolic rate was undisturbed. Body chemistry altered at pressures in excess of 300 m s.w., for example thyroid hormone and nitrogen balances were affected. No decompression sickness was encountered until the pressures were low, but marked haematological changes could occur during decompression. Every change that occurred during these dives reverted to normal, mostly before the end of the decompression. It is concluded that diving with oxygen-helium breathing mixtures to depths as great as 540 m s.w. can be effective and safe. An attempt is made to assess the physiological significance of the principal findings.

Adult↗
PubMed1977

Converting standard air decompression tables for no-stop diving from altitude or habitat.

Using the phase equilibration theory of Hills (1966), as modified by Hennessy and Hempleman (1977), it is possible to predict formulas for converting standard air decompression tables for no-stop diving at altitude or from a normoxic habitat, breathing air. For diving following equilibration at altitude, the Royal Navy, Royal Naval Physiological Laboratory, and Haldane-type rules appear to be too conservative, with the opposite result for diving after excursion to altitude. Predictions in the latter case are in fair agreement with the Swiss (Boni, Schibli, Nussberger, and Bühlmann 1976) no-stop altitude tables. In the case of habitats, close agreement is found between the Hamilton, Kenyon, Freitag, and Schreiner (1973) normoxic tables for no-stop downward excursions and indefinite dive upward-excursions on air. In the case of flying directly after no-stop diving, the US Navy rule of using repetitive group D appears to be conservative for dives less than 50 fsw, and possibly unsafe for dives over 50 fsw. It is concluded that for no-stop diving a single tissue and single safe ascent pressure formula are all that is necessary to generate equivalent air dives. This enforces the hypothesis that it is the volume of gas released on ascent that governs marginal type I bends, and that in a no-stop ascent, all excess dissolved gas is released in the worst case.

Aerospace Medicine↗