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Biomedical subjects

D E Matthews

Publications and source records attributed to D E Matthews.

At least 55 records · Page 3Linked to original sources
PubMed1997

Epinephrine does not impair utilization of exogenous amino acids in humans.

The effect of epinephrine on leucine and phenylalanine kinetics was measured by using the stable isotope amino acid tracers L-[1-(13)C]leucine and L-[phenyl-2H5]-phenylalanine in the postabsorptive state and during the intravenous administration of a standard amino acid solution with respect to the amino acid load. Infusion of epinephrine (plasma concentration: approximately 3600 pmol/L) decreased leucine and phenylalanine and increased ketoisocaproate plasma concentrations and increased the metabolic clearance rate of leucine and phenylalanine. Epinephrine neither influenced leucine or phenylalanine flux nor leucine oxidation or leucine net balance. Hyperaminoacidemia from amino acid infusion reduced endogenous leucine release and stimulated leucine oxidation and nonoxidative disposal of leucine, resulting in a dose-dependent increase in leucine net balance. Epinephrine did not influence any changes in amino acid kinetics during parenteral amino acid administration. Therefore, we conclude that epinephrine had no catabolic effects on amino acid metabolism and no negative effect on the utilization of a parenterally offered amino acid solution in healthy humans.

Adrenergic Agonists↗
PubMed1996

Analysis of blood donor return behaviour using survival regression methods.

The acquisition of a sufficient and safe supply of blood products is required to support modern medical care; in most countries this has meant a reliance on voluntary, nonremunerated blood donors. Recent reported shortages in the United States and elsewhere have highlighted the need for a method to measure and evaluate blood donor return behaviour. This paper describes a framework within which standard time-to-outcome methods can be used to analyse blood donor return behaviour. Survival curves and relative risk estimates derived from a proportional hazards analysis of a large administrative dataset are reported. In addition to assessing the effect of sex, age and other key donor demographic factors on the probability of a subsequent donation attempt, the analysis reveals that the relative risks are time-dependent. This suggests that the likelihood of attempting a subsequent donation may also depend on the time since the index donation attempt. The implications for blood collection agencies and transfusion researchers of this new perspective on donor behaviour are discussed.

Adult↗
PubMed1996

Total-body skeletal muscle mass: evaluation of 24-h urinary creatinine excretion by computerized axial tomography.

A classic body-composition method is estimation of total-body skeletal muscle mass (SM, in kg) from 24-h urinary creatinine excretion (in g). Two approaches of unknown validity have been used to calculate SM from creatinine: one assumes a constant ratio of SM to creatinine, the so-called creatinine equivalence (k), and that SM = k x creatinine; the other suggests a highly variable ratio of SM to creatinine and is based on regression equations of the form SM = b + a x creatinine. We explored these two extreme possibilities by measuring SM with whole-body computerized axial tomography and collecting urinary creatinine during meat-free dietary conditions in 12 healthy adult men. Prediction equations were developed in the men that fit these two models: SM = 21.8 x creatinine (SD and CV of the ratio of SM to creatinine: 1.3 kg and 6.0%, respectively) and SM = 18.9 x creatinine + 4.1 (r = 0.92, P = 2.55 x 10(-5), SEE = 1.89 kg). The validity of each model is reviewed in the context of theoretical aspects of creatine-creatinine metabolism. This first investigation of the method of measuring urinary creatinine excretion to determine SM by using modern techniques raises important practical and basic questions related to SM prediction.

Adipose Tissue↗
PubMed1996

Effects of amino acids on synthesis and degradation of skeletal muscle proteins in humans.

Synthesis and degradation of globular and myofibrillar proteins across arm and leg muscles were examined during stepwise increased intravenous infusion of amino acids (0.1, 0.2, 0.4, and 0.8 g N.kg-1.day-1) to healthy volunteers. Protein dynamics were measured by a primed constant infusion of L-[ring-2H5]phenylalanine and the release of 3-methylhistidine from skeletal muscles. Arterial concentrations and flux of glucose, lactate, and free fatty acids were unchanged despite increasing concentrations of plasma amino acids from 2.6 to 5.7 mM. Plasma insulin, insulin-like growth factor I (IGF-I), and plasma concentrations of IGF-I-binding proteins-1 and -3 remained at fasting levels throughout the investigation. Amino acid infusion caused a significant uptake of the majority of amino acids across arm and leg tissues, except tyrosine, tryptophan, and cysteine, probably due to low concentrations of these amino acids in the formulation. The balance of globular proteins improved significantly (P < 0.01) due to stimulation of synthesis and attenuation of degradation across arm and leg tissues, despite insignificant uptake of tyrosine, tryptophan, and cysteine. Degradation of myofibrillar proteins was uninfluenced by provision of amino acids. The results demonstrate that neither insulin nor circulating IGF-I explained improved protein balance in skeletal muscles after elevation of plasma amino acids. Rather, some amino acids in themselves trigger cellular reactions that initiate peptide formation. Limited availability of some extracellular amino acids was overcome by increased reutilization of the intracellular amino acid.

Adult↗
PubMed1996

A comparative study of different means of assessing long-term energy expenditure in humans.

We compared three independent techniques for measurement of total energy expenditure (TEE) in human subjects: 1) weight-maintaining energy intake (dietTEE), 2) 24-h chamber calorimetry (chamberTEE), and 3) differential elimination rates 2H2O and H(2)18O (isotopeTEE). Twenty-three healthy adult in-patients [19 never obese (NO), 2 obese (OB), and 2 formerly-obese (RO); 9 female, 14 malel] ingested a liquid formula diet (40% of calories as fat, 45% carbohydrate, 15% protein), the volume of which was adjusted until body weight was stable for at least 14 days. Body composition was then determined by hydrodensitometry, isotope dilution, and dual photon beam absorptiometry (DXA). The thermic effect of feeding (TEF) and resting energy expenditure [REE; measured before arising (dietREE) and after arising (chamberREE)] were determined by indirect calorimetry. Non-resting energy expenditure (NREE) was calculated as NREE = TEE - (REE + TEF). Subjects then gained or lost 10% of their body weight and were restudied as described above. All measures of TEE were significantly correlated (dietTEE vs. chamberTEE r2 = 0.75; dietTEE vs. isotopeTEE r2 = 0.88; isotopeTEE vs. chamberTEE r2 = 0.73; P < 0.0001). ChamberTEE (mean +/- SE = 2,107 +/- 64 kcal/day) was approximately 20% lower than either dietTEE (2,536 +/- 94 kcal/day, P < 0.0001) or isotopeTEE (2,564 +/- 83 kcal/day, P < 0.0001). When data were normalized to metabolic mass, weight gain of 10% was associated with significant increases in dietTEE (P < 0.005) and isotopeTEE (P < 0.05) but not chamberTEE; weight loss of 10% was associated with significant reductions in dietTEE (P < 0.005) and isotopeTEE (P < 0.05) but not chamberTEE. We conclude that measures of energy expenditure obtained in a highly controlled environment by caloric titration (dietTEE) or differential excretion rates of 2H2O and H(2)18O (isotopeTEE) are not significantly different and that measurements of TEE obtained in a respiratory chamber (chamberTEE) are significantly lower than dietTEE or isotopeTEE, probably largely due to limitations on physical activity in the chamber.

Adult↗
PubMed1995

Unexplained disturbance in body weight regulation: diagnostic outcome assessed by doubly labeled water and body composition analyses in obese patients reporting low energy intakes.

SUBJECTS: Ten patients who had long-term disturbances in body weight regulation, were referred over a 3-year period for obesity evaluation, and reported low energy intakes (< 1,200 kcal/day). OBJECTIVE: To ascertain whether these patients had a low energy expenditure and thus reduced energy requirement, and/or whether they were misreporting their energy intake. DESIGN: Comparison of outcome measures in referred patients and in obese control patients who did not report low energy intakes and disturbances in body weight regulation. MAIN OUTCOME MEASURES: Low energy expenditure was evaluated with serum thyroid hormone levels, resting metabolic rate (RMR), thermic effect of food (TEF), and total energy expenditure (TEE) by doubly labeled water technique. Misreporting of energy intake was evaluated by comparing patients' self-reported energy intake with energy intake estimated by doubly labeled water and body composition analyses over a 14-day period. STATISTICAL ANALYSES PERFORMED: Low energy expenditure was considered present in a patient if RMR or TEE was more than 15% below predicted values according to results from the control group. Patient group TEF was compared with TEF results observed in the control group. RESULTS: All patients had normal serum thyroid hormone levels. Eight patients had RMR and TEE values within 15% of predicted values and were substantially underreporting their energy intake. One patient had low TEE (-19%) and a normal RMR, a finding that implies a low level of physical activity. This patient also underreported energy intake as estimated by the doubly labeled water technique during the study (-38%). The 10th patient had a low RMR (-23.2%) and TEE (-25.0%), the mechanism of which was uncertain. This patient's reported food intake over the 14-day period was accurate but was less than her long-term intake over months or years as suggested by doubly labeled water TEE estimates. The TEF response in patients was not significantly different from that observed in the control group. CONCLUSIONS: Underreporting of energy intake from foods is a frequent finding in patients with disturbances in body weight regulation who are referred for obesity evaluation. Severe underreporting may be detectable by means of screening measures available to most dietitians. Low energy expenditure, due either to physical inactivity or to metabolic factors, is also observed. Modern evaluation methods provide new insights into patients with weight regulatory disturbances and at the same time stimulate important new research questions.

Adolescent↗
PubMed1995

Effect of cortisol on energy expenditure and amino acid metabolism in humans.

Hydrocortisone was infused overnight into nine normal healthy adults on three occasions at 0, 80, and 200 micrograms.kg-1.h-1, producing plasma cortisol concentrations of 10.6 +/- 1.2, 34.0 +/- 2.0, and 64.9 +/- 4.3 micrograms/dl, respectively. L-[1-13C]leucine, L-[phenyl-2H5]phenylalanine, and L-[2-15N]glutamine were infused during the last 7 h of hypercortisolemia to measure amino acid kinetics. During the last 3.5 h, somatostatin, glucagon, and insulin were infused to reduce the cortisol-induced elevation in plasma insulin to basal. Hypercortisolemia increased plasma glucose, free fatty acid (FFA), and insulin concentrations. Institution of the somatostatin clamp returned insulin to basal but increased glucose and FFA. Acute hypercortisolemia increased protein breakdown 5-20%, as measured by increases in leucine and phenylalanine appearance rates. Normalizing insulin during hypercortisolemia did not alter phenylalanine flux but enhanced leucine appearance rate, the latter result indicating that insulin was affecting leucine metabolism during hypercortisolemia. The fraction of the leucine flux that was oxidized was not significantly increased with hypercortisolemia, but disposal by the nonoxidative route of leucine uptake for protein synthesis was increased. Hypercortisolemia increased cycling of amino acids by increasing protein breakdown and synthesis, but the increase in this process could have increased resting energy expenditure (REE) only 1-2%. Hypercortisolemia increased glutamine flux in a dose-dependent fashion through an increase in de novo synthesis, which presumably reflects increased release from skeletal muscle. Hypercortisolemia increased REE 9-15% at the 80 and 200 micrograms.kg-1.h-1 infusion rates. Respiratory quotient did not rise with cortisol infusion but tended to decrease, suggesting that the increase in REE was fueled by increased oxidation of fat. These data demonstrate that hypercortisolemia increases metabolic rate and may be in part responsible for the hypermetabolic state in injury.

Adult↗
PubMed1995

Oxidation of glutamic acid by the splanchnic bed in humans.

[1,2-13C2]glutamate and [ring-2H5]phenylalanine were infused for 7 h into postabsorptive healthy subjects on two occasions. The tracer infusion was by the intravenous route for 3.5 h and by the nasogastric route for 3.5 h. The order of tracer infusion routes was switched between the two occasions. From the plasma tracer enrichment measurements at plateau during the intravenous and enteral infusion periods, we determined that 33 +/- 3% of the enterally delivered phenylalanine and 96 +/- 1% of the glutamate were removed on the first pass by the splanchnic bed; 78 +/- 3% of the enterally delivered [13C]glutamate tracer was recovered as exhaled CO2 compared with 79 +/- 2% of the intravenously infused tracer. The fraction of the enterally delivered tracer that was sequestered specifically on the first pass by the splanchnic bed was 75 +/- 2%. These results verify the previously reported large uptake of [15N]glutamate by the splanchnic bed [Matthews et al. Am. J. Physiol. 264 (Endocrinol. Metab. 27): E848-E854, 1993] and demonstrate that the uptake of tracer is not due to an artifactual loss of the 15N tracer by reversible transamination but to glutamate uptake for oxidation.

Adult↗
PubMed1995

Metabolic and clinical response to recombinant human insulin-like growth factor I in myotonic dystrophy--a clinical research center study.

Muscle weakness and wasting in myotonic dystrophy (MyD) are believed to be due to a decrease in muscle protein synthesis, secondary to insulin resistance. A 4-month, randomized, double blind, placebo-controlled trial was undertaken to assess whether recombinant human insulin-like growth factor I (rhIGF-I) may overcome the insulin resistance. Patients received either 5 mg rhIGF-I (n = 7) or placebo (n = 9), sc, twice daily. Glucose metabolism was assessed by stable label iv glucose tolerance test, amino acid metabolism by L-[13C] leucine turnover, body composition by dual energy x-ray absorptiometry and N excretion, and muscle response by manual muscle strength and neuromuscular function. In the treated group, the insulin sensitivity index, insulin action, and glucose disposal all increased (P < 0.05). Leucine flux and leucine incorporation into protein increased (P < 0.05), and the rate of leucine oxidation to leucine turnover decreased (P < 0.05), findings indicative of increased protein synthesis. Body weight and lean body mass increased, whereas percent body fat decreased (P < 0.05). An increase in manual muscle strength of 0.42 +/- 0.30 (P < 0.02) and in neuromuscular function of 17.5 +/- 11.7 (P < 0.02) occurred in the four patients who received a rhIGF-I dose greater than 70 micrograms/kg, whereas a more modest response occurred in the three patients who received a dose less than 70 micrograms/kg. Two patients showed dramatic improvement. Long term rhIGF-I therapy appears to cause metabolic and muscle improvement in optimally treated MyD patients.

Adult↗
PubMed1995

Impact of 2H and 18O pool size determinations on the calculation of total energy expenditure.

Measurement of total energy expenditure using [2H,18O] water requires both accurate and precise determination of the rates of disappearance of 2H and 18O from body water over time and determination of the 2H and 18O pool sizes. However, the impact of the isotopic determination of body water upon the determination of energy expenditure is often overlooked. For measurement of total body water per se, the delay after administration before sampling body fluids becomes important, and saliva sampling can be used to resolve the timing of early samples for body water determination. For energy expenditure measurement per se, linear regression can be used to define the initial dilution. Because the hydrogen tracer dilutes into a pool significantly larger than body water pool per se due to the presence of labile hydrogens, a correction to the isotope pool size must be applied. The theoretical calculations of the exchangeable hydrogen pool presented here suggest that the hydrogen pool size is < 3% greater than the body water pool and data are provided to support this idea. Finally, the two approaches used to define the body water pool space contribution to the calculation of energy expenditure using 2H2(18)O are reviewed. Using a pool size based upon the average of the two pool spaces limits the effect of pool size error in the calculation of energy expenditure.

Body Composition↗
PubMed1994

Arthroscopic suture fixation of displaced tibial eminence fractures.

The purpose of this article is to describe a technique for arthroscopic reduction and suture fixation of avulsion fractures of the tibial eminence involving the anterior cruciate ligament (ACL). Six patients (five type III, one type II) with tibial eminence fractures underwent arthroscopic evaluation when closed reduction after aspiration failed to yield an anatomic reduction. The study population was composed of five males and one female. Average age was 24 years (range 16-36). One fracture (type II) was easily reduced after manipulating the interposed anterior horn of the lateral meniscus. In five patients the fragment was stabilized with multiple sutures. The technique involved arthroscopic placement of multiple sutures of 2-0 polydioxanone suture (PDS) into the base of the ACL pulled through a tibia drill hole and tied onto a 4.5-mm screw post. Patients were placed in a standard postoperative ACL protocol. All fractures demonstrated radiographic healing by 8 weeks, and no patients had subjective complaints of instability at 1 year. All patients obtained full extension intraoperatively, and only one patient lost 2 degrees of terminal extension at latest follow-up. Arthroscopic reduction and suture fixation of avulsion fractures of the tibial eminence restores the length of the ACL, provides stable fixation promoting early motion with minimal morbidity, and does not require a second operation for metal removal.

Adolescent↗
PubMed1994

Insulin selectively attenuates breakdown of nonmyofibrillar proteins in peripheral tissues of normal men.

The role of insulin to control protein synthesis and degradation in the human leg and forearm was investigated in eight healthy individuals. The glucose clamp technique with simultaneous infusion of crystalline amino acids were used to create hyperinsulinemia (100-120 mU/l) in combination with euglycemia and elevated plasma concentrations of amino acids (> 4 mmol/l). A primed constant infusion with L-[U-14C]tyrosine and L-[phenyl-2H5]phenylalanine was used for simultaneous measurements of the disposal (protein synthesis) and the release (protein degradation) of tyrosine and phenylalanine, respectively, across the leg and forearm before and during hyperinsulinemia. The balance of 3-methylhistidine was also determined as a measure of muscle breakdown. Insulin stimulated tissue glucose and net amino acid uptake across the arm and leg tissues, whereas the disposal of both tyrosine and phenylalanine (protein synthesis) was not stimulated across the arm and the leg during hyperinsulinemia. The release of tyrosine and phenylalanine was significantly decreased from both leg and arm tissues (protein degradation) in response to insulin. However, the release of 3-methylhistidine from skeletal muscles was totally unaffected by hyperinsulinemia. We conclude that it is unlikely that insulin contributes to the normal stimulation of protein synthesis during feeding in humans and that insulin has no effect on breakdown of the large myofibrillar protein pool in skeletal muscles in unstressed individuals.

Adult↗
PubMed1994

Whole body and splanchnic leucine, phenylalanine, and glucose kinetics during endotoxemia in humans.

To examine the whole body and splanchnic tissue substrate handling during endotoxemia, an intravenous bolus of endotoxin was given to six healthy volunteers during primed, continuous infusions of [1-13C]leucine, [ring-2H5]phenylalanine, and [6,6-2H2]glucose. Whole body protein breakdown, based on whole body Leu and Phe appearance rates (Ra), increased in response to endotoxin given at time 0 (RaLeu 77 +/- 2 mol.kg-1 x h-1, t = 0 h; 88 +/- 6, t = 4 h; P < 0.05) (RaPhe 39 +/- 2 mol.kg-1 x h-1, t = 0; 46 +/- 3, t = 4 h; P < 0.05). Splanchnic amino acid balance (Bal) increased (BalLeu 7 +/- 4 mol.kg-1 x h-1, t = 0; 21 +/- 5, t = 2 h; P < 0.05) (BalPhe 3 +/- 2 mol.kg-1 x h-1, t = 0; 16 +/- 4, t = 2 h; P < 0.05) and can be accounted for by increased splanchnic uptake (Rd) of Phe and Leu (RdLeu 21 +/- 3 mol.kg-1 x h -1, t = 0; 37 +/- 7, t = 120 min; P < 0.05) (RdPhe 10 +/- 3 mol.kg-1 x h-1, t = 0; 24 +/- 5, t = 120 min; P < 0.05). Splanchnic conversion of Leu to ketoisocaproate increased with endotoxin administration (0.7 +/- 0.6 mol.kg-1 x h-1, t = 0; 8 +/- 3, t = 360 min; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗
PubMed1993

A multivariate example of case-cohort analysis: neonatal mortality in Switzerland, 1979-81.

A study of all births in Switzerland during the years 1979-81 is used to illustrate the advantages of the case-cohort design for this epidemiologic analysis of neonatal mortality. The example shows that familiar associations between infant mortality and explanatory variables such as sex and weight at birth can be precisely estimated using only a sample from the full cohort.

Birth Rate↗
PubMed1993

Increased energy expenditure in a patient with diencephalic syndrome.

Total energy expenditure, measured in an infant with diencephalic syndrome with doubly labeled water, was 30% to 50% higher than that reported for other healthy infants whose energy expenditure was measured by the same technique and 13% higher than the patient's energy intake. This result suggests that the weight loss and cachexia of the diencephalic syndrome are the result of abnormally increased energy expenditure.

Astrocytoma↗
PubMed1993

The donation cycle: a framework for the measurement and analysis of blood donor return behaviour.

The donation cycle represents a new framework for the measurement of blood donor return behaviour. Because it is based on the interval between successive donation attempts, it is more efficient than previously reported methods and the resulting data can be analysed using the statistical techniques for interval data. To illustrate the merits of this quantitative approach to the study of blood donor behaviour, the donation cycle framework is used to analyse the interval between the first and second donation attempts in a random sample (n = 5,183) of type 0, whole blood donors from the Gulf Coast Regional Blood Center. Simple statistical tools such as the log-rank test are employed to describe and to evaluate relative differences in the return behaviour of Rh-negative and Rh-positive donors. The analysis indicates that Rh-negative donors are significantly (p < 0.001) more likely than Rh-positive donors to attempt to donate on a second occasion. Kaplan-Meier estimates of the survival function of these first-time donors reveal marked elevations in the rate of return exactly 52 weeks after the initial donation. The donation cycle paradigm provides transfusion researchers with quantitative tools which are essential for designing statistically efficient, prospective intervention studies. By using the knowledge which such studies could provide, blood banks might be better able to manage donor return behaviour and thereby the safety of the blood supply.

Blood Donors↗