Search PubMed⌕ Search

Biomedical subjects

J H Shaw

Publications and source records attributed to J H Shaw.

At least 91 records · Page 5Linked to original sources
PubMed1987

Energy and protein metabolism in sepsis and trauma.

Energy and protein metabolism in septic and trauma patients has been extensively studied over the past 30 years. Despite this, a number of inconsistencies are present in the literature and it is difficult to formulate a clear global picture of this complex series of metabolic events. Conclusions from human studies have often been hampered by the utilization of small numbers of patients, and data from animal models of sepsis or trauma are often difficult to interpret. Over the past 5 years, the authors have performed a series of isotopic infusions in normal volunteers, and in patients with either sepsis or trauma, in order to gain a clearer understanding of energy and protein metabolism in severely stressed patients. This review summarizes the findings.

Animals↗
PubMed1987

Glucose and urea kinetics in patients with early and advanced gastrointestinal cancer: the response to glucose infusion, parenteral feeding, and surgical resection.

We isotopically determined rates of glucose turnover, urea turnover, and glucose oxidation in normal volunteers (n = 16), patients with early gastrointestinal (EGI) cancer (n = 6), and patients with advanced gastrointestinal (AGI) cancer (n = 10). Studies were performed in the basal state, during glucose infusion (4 mg/kg/min), and during total parenteral feeding (patients with AGI cancer only). Patients with early stages of the disease were also studied 2 to 3 months after resection of the cancer. Basal rates of glucose turnover were similar in volunteers and in patients with EGI cancer (13.9 +/- 0.3 mumol/kg/min and 13.3 +/- 0.2 mumol/kg/min, respectively) but were significantly higher in patients with AGI cancer (17.6 +/- 1.4 mumol/kg/min). Glucose infusion resulted in significantly less suppression of endogenous production in both patient groups than that seen in the volunteers (76% +/- 6% for EGI group, 69% +/- 7% for AGI group, and 94% +/- 4% for volunteers). The rate of glucose oxidation increased progressively in proportion to the tumor bulk. In the volunteers the percent of VCO2 from glucose oxidation was 23.9% +/- 0.7%, and in EGI and AGI groups the values were 32.8% +/- 2.0% and 43.0% +/- 3.0%, respectively. After curative resection of the cancer, glucose utilization decreased significantly (p less than 0.05). The rate of urea turnover was significantly higher in the AGI group (8.4 +/- 1.0 mumol/kg/min) in comparison with the volunteer group value of 5.9 +/- 0.6 mumol/kg/min (p less than 0.03). Glucose infusion resulted in a significant suppression of urea turnover in the volunteers (p less than 0.02), but in the AGI group glucose infusion did not induce a statistically significant decrease. We conclude from these studies that the presence of even a small, potentially curable gastrointestinal cancer is associated with a loss of the normal host-regulatory mechanisms designed to conserve body resources; this effect is more marked as the tumor bulk increases; increasing tumor bulk effects a progressive increase in glucose utilization and in protein breakdown.

Aged↗
PubMed1987

The effect of extradural blockage upon glucose and urea kinetics in surgical patients.

We have determined the metabolic effects induced by the use of extradural blockage with 0.5 per cent bupivacaine hydrochloride in a group of surgical patients. Turnover rates of glucose and urea were determined isotopically using radioisotopes and studies were performed both in the basal state and during total parenteral nutrition. In the basal state, extradural blockade resulted in a decrease in the turnover rates of both glucose and urea. In addition, when extradural blockade was instituted while the patients were receiving total parenteral nutrition, there was also a significant fall in glucose turnover. We conclude that the use of extradural blockade is effective as a means of conserving bodily resources in surgical patients both in the basal state and during total parenteral nutrition.

Adult↗
PubMed1986

Effect of epinephrine infusion and adrenergic blockade on glucose oxidation in conscious dogs.

The effect of combined alpha- and beta-adrenergic blockade, and the effect of epinephrine infusion, on the rate of glucose oxidation has been tested in conscious dogs. The dogs were prepared seven to ten days before the experiment with chronic catheters and tracheostomy. Glucose oxidation was measured by means of the primed-constant infusion of U-14C-glucose and indirect calorimetry. Six experimental groups were tested. In all groups, insulin and glucagon concentrations were held constant throughout by the inhibition of their secretion with somatostatin and intraportal replacement at basal rates. All experiments consisted of two two-hour periods. In half of the experiments, combined alpha- and beta-adrenergic blockade was administered in the second period, and in the other experiments, epinephrine was infused in the second period. The adrenergic blockade or epinephrine infusion (E) was performed in three different groups. In one, free fatty acid (FFA) levels were allowed to change spontaneously in response to blockade or E; in a second group, liposyn and heparin were infused throughout periods 1 and 2 in order to maintain FFA levels at high, constant levels; and in a third group, FFA levels were maintained at a constant low level in periods 1 and 2 by means of an infusion of nicotinic acid. In all cases tested, epinephrine infusion caused an increase in the rate of glucose oxidation. Adrenergic blockade also caused an increase in glucose oxidation when FFA levels were allowed to spontaneously fall; but when FFA levels were held constant (either high or low), there was no effect on glucose oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Glucose, fatty acid, and urea kinetics in patients with severe pancreatitis. The response to substrate infusion and total parenteral nutrition.

Rates of glucose turnover and oxidation in normal volunteers (N = 16) and in severely ill patients with pancreatitis (N = 9) were isotopically determined. Glucose turnover was determined using primed constant infusions of either 6-3H-glucose or 6-d2-glucose, and glucose oxidation with either U-14C-glucose or U-13C-glucose after appropriate priming of the bicarbonate pool. Urea kinetics were determined using primed constant infusions of either (15N2)-urea or U-14C-urea, whereas free fatty acid (FFA) kinetics were determined by the constant infusion of 1,2-13C palmitate. Basal rates of glucose production and plasma glucose clearance were significantly higher in the patients than in the volunteers. During glucose infusion (4 mg/kg/min) endogenous glucose production was virtually totally suppressed in the volunteers (94 +/- 4%). There was significantly less suppression in the patients, however (44 +/- 1%). In addition, the percentage of available glucose oxidized (i.e., percentage of uptake oxidized) was significantly less in the patients than in the volunteers. The basal rate of urea production was significantly higher in the patients; however, in both patients and volunteers, glucose infusion resulted in a significant decrease. The rate of FFA turnover was similar in the patients and volunteers, and the patients and volunteers were equally sensitive to the suppressive effects of glucose infusion. When the patients were studied during total parenteral nutrition (TPN), there was no further suppression of endogenous glucose turnover than that seen during 2 hours of glucose infusion, and the mean rate of urea turnover measured during TPN (7.0 +/- 1.9 mumol/kg/min) was also not significantly different than the value determined during glucose infusion (8.9 +/- 1.8 mumol/kg/min). It was concluded from these studies that patients with pancreatitis are metabolically similar to septic patients, have an impairment in their ability to oxidize infused glucose when compared with normal volunteers, have an elevated rate of net protein catabolism, and have FFA kinetics similar to those seen in normal humans.

Acute Disease↗
PubMed1986

Determinations of glucose turnover and oxidation in normal volunteers and septic patients using stable and radio-isotopes: the response to glucose infusion and total parenteral feeding.

Rates of glucose turnover and oxidation were isotopically determined in normal volunteers (n = 16) and in severely septic patients (n = 10). Glucose turnover was determined using primed constant infusions of either 6-3H- or 6,6-d-glucose and glucose oxidation with either U-14C-glucose or U-13C-glucose after appropriate priming of the bicarbonate pool. Basal rates of glucose turnover, oxidation, and plasma clearance were significantly higher in the septic patients than in the volunteers. During glucose infusion (4 mg/kg.min) endogenous glucose production was virtually abolished in the volunteers (94 +/- 4% suppression). There was significantly less suppression in the septic patients (39 +/- 7%); (P less than 0.01). In addition, the percentage of available glucose oxidized (i.e. the percentage of glucose uptake oxidized) was significantly less in the septic patients. When the patients were studied during total parenteral nutrition (at a similar rate of glucose infusion) there was no further suppression of endogenous glucose production compared with that seen during 2 h of glucose infusion. However, the percentage of available glucose oxidized increased significantly. From these studies it is concluded that septic patients continue to have ongoing consumption of host tissue despite receiving either glucose infusion or total parenteral nutrition, and septic patients are less able to oxidize glucose than normal volunteers when infused for only 2 h. However, adaptation occurs with the longer infusion time used in total parenteral nutrition (TPN).

Adult↗
PubMed1986

Early vascularization of syngeneic, allogeneic and xenogeneic skin grafts.

The vascularization of syngeneic, allogeneic and xenogeneic skin grafts 3-4 days after grafting was studied in inbred rats by injecting hosts with 51Cr labelled red cells on the third day and counting graft radioactivity on the fourth day. Vascularization as determined by this method was quantitatively similar in syngeneic, allogeneic and mammalian xenogeneic grafts, while the vascularization of non-mammalian xenografts was significantly inferior. For any one donor-host combination, full-thickness grafts contained relatively more blood than did split-thickness grafts, presumably because of the large vessels in the deep part of the dermis in full-thickness grafts. Full-thickness neonatal grafts were vascularized similarly to full-thickness adult skin grafts. Grafted skin contained relatively more blood than did the corresponding normal skin. Reconstituted freeze dried allogeneic skin grafts contained virtually no blood, a phenomenon possibly analogous to the 'no reflow' phenomenon of microsurgery. The inferior vascularization of non-mammalian xenografts is more plausibly explained on the basis of defective self recognition than as representing a reaction to foreign determinants. These results do not necessarily indicate that one type of graft is better than another in clinical practice. But if the beneficial effects of temporary skin grafts do indeed depend on their capacity to become vascularized, fresh skin appears preferable to reconstituted freeze dried skin.

Animals↗
PubMed1986

Response to glucose infusion in humans: role of changes in insulin concentration.

We have used the primed-constant infusion of stable isotopes of glucose ([6,6-d2]glucose), alanine([3-13C] alanine), and urea ([15N2]urea) to investigate their kinetic interrelationships in normal volunteers in the postabsorptive state and during the infusion of unlabeled glucose at two rates. Each glucose infusion was tested with and without the simultaneous infusion of somatostatin (S), insulin (I), and glucagon (G) to clamp those hormonal levels. When glucose was infused at 1 mg X kg-1 X min-1, endogenous glucose production was suppressed almost exactly 1 mg X kg-1 X min-1, regardless of whether S plus I plus G were infused. The 4 mg X kg-1 X min-1 glucose infusion suppressed endogenous glucose production, both with and without hormonal control. The plasma concentration of glucose also increased to the same extent during the 4 mg X kg-1 X min-1 infusion in both protocols, which indicated that the spontaneous insulin response to the glucose infusion (an increase from 11 +/- 2 to 24 +/- 3 microU/ml) did not stimulate the peripheral clearance of glucose. The high rate of glucose infusion, both with or without hormonal control, stimulated alanine flux and inhibited urea production. These results indicate that glucose, per se, is an important direct controller of normal metabolic interactions of endogenous alanine, glucose, and urea kinetics.

Adult↗
PubMed1986

Role of changes in insulin and glucagon in glucose homeostasis in exercise.

This experiment was performed to determine if plasma glucose homeostasis is maintained in normal human volunteers during light exercise (40% maximal oxygen consumption [VO2 max]) when changes in insulin and glucagon are prevented. Hormonal control was achieved by the infusion of somatostatin, insulin, and glucagon. Glucose kinetics and oxidation rates were determined with stable isotopic tracers of glucose, and by indirect calorimetry. Two different rates of replacement of insulin and glucagon were used; in one group, insulin was clamped at 19.8 +/- 2.6 microU/ml (high-insulin group), and in the other group insulin was clamped at 9.2 +/- 1.3 microU/ml (low-insulin group). Glucagon was maintained at 261 +/- 16.2 and 124 +/- 6.4 pg/ml, respectively, in the high-insulin and low-insulin groups. Without hormonal control, plasma glucose homeostasis was maintained during exercise because the increase in glucose uptake was balanced by a corresponding increase in glucose production. When changes in insulin and glucagon were prevented, plasma glucose concentration fell, particularly in the high-insulin group. Glucose uptake increased to a greater extent than when hormones were not controlled, and glucose production did not increase sufficiently to compensate. The increase in glucose uptake in the hormonal control groups was associated with an increased rate of glucose oxidation. When euglycemia was maintained by glucose infusion in the hormonal control subjects, the modest increase in glucose production that otherwise occurred was prevented. It is concluded that during light exercise there must be a reduction in insulin concentration and/or an increase in glucagon concentration if plasma glucose homeostasis is to be maintained. If such changes do not occur, hypoglycemia, and hence exhaustion, may occur.

Blood Glucose↗
PubMed1985

Response to glucose and lipid infusions in sepsis: a kinetic analysis.

The kinetics and oxidation of glucose and free fatty acid (FFA) metabolism were assessed in control and Escherichia coli septicemic dogs by using primed, constant infusions of U-14C-glucose and 1,2, 13C-palmitic acid. In the controls, the infusion of glucose suppressed endogenous glucose production completely, whereas, in the septic dogs, only a 30% suppression of glucose production occurred. The ability of the septic dogs to oxidize endogenous or exogenous glucose was decreased significantly. The basal rate of appearance of FFA was significantly higher in the septic dogs, but their ability to oxidize FFA was comparable to that of the control dogs; therefore, the basal rate of FFA oxidation was higher in the septic dogs. These studies indicate that septic dogs have a decreased capacity to oxidize glucose, but that they retain their ability to oxidize long-chain fatty acids. Because the rate of lipolysis was increased in sepsis, lipid was the predominate energy substrate in this septic model.

Animals↗
PubMed1985

Complete nucleotide sequence of macrolide-lincosamide-streptogramin B-resistance transposon Tn917 in Streptococcus faecalis.

Streptococcus faecalis transposon Tn917 was cloned in Escherichia coli on plasmid vector pBR325. The erythromycin resistance determinant of Tn917 was not expressed in the E. coli background. The nucleotide sequence of Tn917 was determined and found to be 5,257 base pairs in length. Six open reading frames (ORFs) were identified and designated 1 through 6 (5' to 3'); all were on the same DNA strand. A region exhibiting strong homology with known promoters was identified upstream from ORF1. ORFs 1 to 3 were virtually identical to the previously sequenced erythromycin resistance determinant on Streptococcus sanguis plasmid pAM77. At the 3' point, where the homology between Tn917 and pAM77 ends, was a 20-base-pair region about 80% homologous with a component of the res site of Tn3. The amino acid sequence of ORF4 showed homology with other site-specific recombination enzymes, including approximately 30% homology with the resolvase of Tn3. Contained within Tn917 was a directly oriented 73-base-pair duplication of the left terminus. The Tn917 sequence revealed that antibiotic-enhanced transposition might be due to extension of transcription from the resistance-related genes (in ORFs 1 to 3) into transposition genes (in ORFs 4 to 6). Transcription analyses resulted in data consistent with this interpretation.

Amino Acid Sequence↗
PubMed1985

Glucose and FFA kinetics in sepsis: role of glucagon and sympathetic nervous system activity.

We have assessed the role of glucagon and sympathetic nervous system (SNS) activity on glucose and palmitate kinetics and oxidation in the conscious dog infused with live Escherichia coli bacteria by means of the simultaneous primed constant infusion of [1,2-13C]palmitate and [U-14C]-glucose. The basal rate of glucose production in septic dogs and controls was similar. However, when the glucagon concentration was selectively decreased in the septic animals by the appropriate infusion of somatostatin (S), insulin (I), and glucagon (G), the rate of glucose production decreased significantly, whereas in control animals S + I + G infusion had no effect on glucose kinetics. When alpha- and beta-adrenergic blockade was added to the infusion, the rate of glucose production decreased further and hypoglycemia developed in the septic dogs, whereas in the controls both glucose production and concentration increased. The basal rate of appearance of palmitate was increased in the septic dogs (P less than 0.01). S + I + G had no effect on palmitate appearance in either group, and sympathetic blockade caused a significant decrease in palmitate appearance in both groups of dogs. The rates of oxidation of both glucose and palmitate was related directly to their availability in plasma. Thus, in sepsis, glucagon and SNS activity play important roles in the mobilization of glucose and palmitate into the plasma and therefore in the overall state of energy metabolism.

Animals↗
PubMed1985

Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion.

The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with [2-3H]glycerol and [1-14C]palmitic acid, was used to trace VLDL kinetics and oxidation, and [1-13C]palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. We conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis.

Animals↗
PubMed1985

Assessment of alanine, urea, and glucose interrelationships in normal subjects and in patients with sepsis with stable isotopic tracers.

The kinetic interactions among glucose, alanine, and urea metabolism were studied in both normal volunteers and in patients with sepsis by means of a primed, constant infusion of stable isotopes. In the normal volunteers, infusion of glucose at 4 mg/kg/min suppressed total glucose production, the rate of gluconeogenesis from alanine, and the production of urea, despite an increase in the rate of release and uptake of alanine. When the glucose infusion rate was increased to 8 mg/kg/min, the production of urea decreased further, even though gluconeogenesis from alanine was already suppressed by the first infusion. This additional N-sparing effect was explainable by an increase in glucose oxidation. In the patients with sepsis the basal rates of production of glucose and urea were elevated significantly. Glucose infusion (4 mg/kg/min) decreased hepatic glycogenolysis but not gluconeogenesis from alanine or urea production. At the glucose infusion rate of 8 mg/kg/min, glucose oxidation increased in the patients and urea production decreased. Thus in patients with sepsis a higher rate of glucose infusion is necessary to achieve nitrogen-sparing effects than is necessary in controls because of a lack of suppressibility of gluconeogenesis. Because of continued glucose production during glucose infusion, hyperglycemia commonly develops during glucose infusion in sepsis. However, this effect does not necessarily indicate a complete inability of the patient with sepsis to benefit nutritionally from infused glucose, as we observed no decrement in the ability to oxidize infused glucose.

Adult↗
PubMed1984

Glucose production in the perfused dog liver: effect of free fatty acids and ketones.

The perfused rat liver model has been used widely for the past 30 years to investigate various aspects of hepatic metabolism. Certain aspects of the regulation of glucose production, however, are different in rats and in higher mammals. A method for perfusing dog livers in situ has been developed. It is easier to perform and to standardize than previously described techniques, and enables the direct effect of various substances on glucose production to be tested. This new approach has been used to assess the influence of ketones and albumin-bound free fatty acids (FFA) on total hepatic glucose output. In contrast to the response generally observed in the rat, it was found that an increased availability of FFA or ketones caused a net decrease in glucose output from the dog liver. Thus, perfusion of the dog liver is a feasible technique that is particularly useful because the responses in rats and dogs are not always the same.

3-Hydroxybutyric Acid↗
PubMed1984

Inhibitory effect of plasma free fatty acids on glucose production in the conscious dog.

We have previously reported that, in conscious, unrestrained dogs in which insulin and glucagon levels were clamped pharmacologically, combined alpha- and beta-adrenergic blockade resulted simultaneously in a fall in plasma free fatty acid (FFA) levels and an increase in glucose production. In this study we have tested the hypothesis that the increase in glucose production observed in the previous study was due to the fall in plasma FFA concentration. Glucose production was measured by means of the primed-constant infusion of [6-3H]- and/or [U-14C]glucose, and insulin and glucagon were clamped at constant levels by means of the infusion of somatostatin, insulin, and glucagon. When no attempt was made to control the FFA levels, combined alpha- and beta-adrenergic blockade significantly decreased plasma FFA levels, and this was associated with a significant increase in the rate of glucose production. However, the glucose production response to adrenergic blockade was entirely prevented by the clamping of FFA levels at a high, constant value by the infusion of a 10% lipid emulsion (Liposyn) and heparin. We conclude that basal adrenergic activity is important in the mobilization of fat but does not directly influence glucose production. Further, there is an inhibitory effect of FFA on glucose production that is unmasked during hormonal control and alpha- and beta-adrenergic blockade.

Animals↗