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J H Shaw

Publications and source records attributed to J H Shaw.

At least 109 records · Page 6Linked to original sources

Influence of beta-hydroxybutyrate infusion on glucose and free fatty acid metabolism in dogs.

We have investigated the effect of infusion of DL-beta-hydroxybutyrate (BOHB) (30 mumol X kg-1 X min-1) on glucose and free fatty acid (FFA) metabolism by means of the primed constant infusion of [U-14C]glucose and [1,2-13C]palmitic acid. The role of the hormonal response to the ketone infusion was assessed by controlling the hormone levels pharmacologically. In one group hormones were not controlled, while in the other two groups insulin and glucagon were maintained at constant levels by infusion of somatostatin, insulin, and glucagon at constant rates. In one of these hormonally controlled groups, combined alpha- and beta-adrenergic blockade was also employed. BOHB infusion increased total ketone concentration approximately 10-fold and, when hormones were not controlled, induced a significant increase in glucagon concentration. Regardless of hormonal status, elevation of the ketone levels decreased the rate of glucose production and FFA appearance. Glucose oxidation decreased in proportion to the reduction in the rate of glucose uptake in all groups. When sympathetic activity was not blocked an increase in the percent of FFA uptake oxidized enabled the percent CO2 production from FFA oxidation to remain constant despite the decrease in FFA uptake. However, when sympathetic activity was blocked the increase in the percent of FFA uptake oxidized observed in the other groups was prevented. We conclude from these studies that an elevation in ketone levels directly affects glucose and FFA metabolism independent of changes in insulin and glucagon levels and sympathetic activity.

3-Hydroxybutyric Acid↗

Isotopic determination of amino acid-urea interactions in exercise in humans.

We recently reported that in light exercise (30% VO2max) the oxidation of [1-13C]leucine was significantly increased but the rate of urea production was unchanged (J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 52: 458-466, 1982). We have therefore tested three possible explanations for this apparent incongruity. 1) We infused NaH13CO3 throughout rest and exercise and found that, although altered bicarbonate kinetics in exercise resulted in greater recovery of 13CO2, the difference between rest and recovery was small compared with the increase in the rate of 13CO2 excretion during exercise when [1-13C]leucine was infused. 2) We infused [15N]leucine and isolated plasma urea N to determine directly the rate of incorporation of the 15N. During exercise there was no increase in the rate of 15N incorporation. Simultaneously, we infused [2,3-13C]alanine and quantified the rate of incorporation of 15N in alanine. We found that [15N]alanine production from [15N] leucine more than doubled in exercise, and by deduction, alanine production from other amino acids also doubled. 3) We tested our previous assumption that [1-13C]leucine metabolism in exercise was representative of the metabolism of other essential amino acids by infusing [1-13C] and [alpha-15N]lysine throughout rest and exercise. We found that the rate of breakdown of lysine during exercise was not increased in a manner comparable to that of leucine. Thus, these data confirm our original findings that leucine decarboxylation is enhanced in light exercise but urea production is unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

Effect of substrate intake and physiological state on background 13CO2 enrichment.

The natural enrichment of 13C in energy substrates varies, and this variation must be taken into account when stable isotopic tracers are used in metabolic studies. This is conventionally accomplished by measuring background samples taken before the tracer infusion begins and subtracting these values from postinfusion values. Whereas this approach is satisfactory if no perturbation occurs between the collection of the background samples and the collection of postinfusion sample, the data presented in this paper show that any change in the metabolic state can significantly alter the background enrichment of expired CO2. This study not only confirmed that the introduction of natural energy sources may alter the background enrichment of CO2, but we also found that changes in substrate oxidation induced by different physiological states, such as exercise, can cause significant changes in expired CO2 enrichments. Conclusions from studies in which oxidation of substrates were measured by means of a 13C tracer but potential changes in background enrichments were not accounted for must, therefore, be reassessed.

Animals↗

Energy and substrate kinetics and oxidation during ketone infusion in septic dogs: role of changes in insulin and glucagon.

We have investigated the response of glucose and free fatty acid (FFA) kinetics and oxidation to betahydroxybutyrate (BOHB) infusion (30 mumol/kg X min) in both normal and Escherichia coli septicemic conscious dogs. In both the septic and control groups, experiments were performed in which hormone levels were allowed to change in response to the BOHB infusion, and in which the infusion of somatostatin, insulin, and glucagon were used to hold those hormone levels constant and sympathetic activity was blocked by the infusion of propranolol and phentolamine. In the nonseptic groups, the infusion of BOHB decreased both glucose production and FFA appearance (RaFFA) independent of the hormonal status. Glucose oxidation decreased in proportion to the decrease in production and uptake. FFA oxidation decreased only when hormones were controlled. In contrast, the infusion of BOHB in septic dogs did not suppress either glucose production or RaFFa, irrespective of the hormonal status. Substrate oxidation again corresponded to the rate of appearance of the substrate. We conclude that in normal dogs, ketones act directly as metabolic regulators to decrease the appearance of both glucose and FFA in the plasma, but do not directly affect the ability of the animal to oxidize these substrates. In sepsis, the normal regulatory actions of ketones appear to be lost.

Animals↗

A conscious septic dog model with hemodynamic and metabolic responses similar to responses of humans.

We have developed a conscious septic dog model suitable for in vivo tracer studies. Dogs weighing 10 to 20 kg underwent general anesthesia followed by the insertion of long-term arterial, venous, and portal cannulas and the formation of a long-term tracheostomy. After 7 to 10 days of convalescence, the animals were fed in the morning and 4 hours later 10(10) live Escherichia coli organisms were infused intra-arterially over approximately 30 minutes. One hour later a second dose of 5 X 10(9) bacteria was given, again over 30 minutes. Resuscitation was provided by infusion of 1000 ml of lactated Ringer solution over 3 hours. Twenty-four hours after the induction of sepsis the animals were hemodynamically stable and suitable for study. Cardiac output was increased from the control value of 185 +/- 35 ml/kg X min to 308 +/- 44 ml/kg X min in the septic animals. Heart rate was increased from 98 +/- 10 to 125 +/- 5 beats/min, and arterial pressure was not significantly altered. We employed indirect calorimetry and primed constant infusions of both radioactive and stable isotopes to assess a variety of metabolic parameters. The metabolic rate was increased approximately 25%, and the energy for this increase was primarily provided by the increased oxidation of both free fatty acids and triglyceride. The release of free fatty acids was approximately three times greater than the control value, and triglyceride synthesis increased 500%. The oxidation rate of free fatty acids and the fatty acids contained in very low density lipoproteins-triglyceride increased 40% and 900%, respectively. Glucose production was maintained at approximately the control value, and the rate of glucose oxidation (as measured with 14C-glucose) was also not significantly altered. The plasma insulin concentration was moderately elevated, and plasma glucagon concentration was five to six times greater than the control value. Plasma catecholamine levels were increased significantly. This model is suitable for the performance of metabolic studies in sepsis. The induction of a hyperdynamic septic state in less than 24 hours avoids the complications of starvation and dehydration frequently seen in the various peritonitis and abscess models. Most importantly, the model is predictable in its time course and reproducibly creates a situation that hormonally, hemodynamically, and metabolically resembles what is commonly seen in humans with sepsis.

Animals↗

Renal oncocytoma. A review of the literature and report of an unusual multicentric case.

Renal oncocytoma is a rare tumour of the kidney composed exclusively of large polygonal cells with eosinophilic, granular cytoplasm. Ultrastructurally they are distinguished by the presence of large numbers of mitochondria and histochemically by abundant oxidative enzymes and adenosine triphosphate. Macroscopically these tumours are usually light brown in colour and commonly exhibit a dense central area of fibrous scarring, with fibrous trabeculae extending from this central zone in a stellate fashion. Renal oncocytomas are commoner in males than females (sex ratio 2:1) and although the age range at presentation is wide, there is a peak incidence in the seventh decade. The prognosis following surgical removal is excellent, despite the fact that many of these tumours are large. Invasion of the perirenal fat and the renal vein and metastatic spread to regional lymph nodes is documented, but death from metastatic disease is rare. The great majority of renal oncocytomas reported are solitary. We describe a multicentric renal oncocytoma, the sixth so far reported.

Adenoma↗

Plasmid content of Streptococcus faecalis strain 39-5 and identification of a pheromone (cPD1)-induced surface antigen.

Streptococcus faecalis 39-5 is a haemolytic, bacteriocinogenic strain harbouring six plasmids. One of these plasmids, pPD1 (36.4 MDal) determines a bacteriocin and encodes a conjugative response to the sex pheromone cPD1 excreted by recipient (plasmid-free) strains. The pheromone response is characterized by the formation of mating aggregates of donors (responders) with recipients. Aggregation required the presence of phosphate and divalent cations and was inhibited by agents or conditions that destroy protein structure. Aggregation was postulated to be due to synthesis of a new proteinaceous molecule on the donor cell surface. Referred to as 'aggregation substance', such a material was identified and found to exhibit antigenic properties not associated with uninduced cells; it could be detected by immunoelectron microscopy. Aggregation substance could be extracted from induced cells but not uninduced cells as demonstrated by crossed immunoelectrophoresis. Antibody raised against the aggregation substance controlled by pPD1 cross-reacted with aggregation substance determined by other plasmid systems which respond to pheromones unrelated to cPD1.

Animals↗

Energy metabolism in trauma and sepsis: the role of fat.

There seems little doubt that there are signals for the increased mobilization of fat in shock, trauma, and sepsis. Whether those signals are reflected by an actual increase in mobilization is dependent on many variables including cardiovascular status. A hypothetical scheme based on our own experiments in the hyperdynamics phases of response to burn injury and to sepsis is presented in Figure 8. According to this scheme, catecholamines stimulate lipolysis in the adipose tissue, resulting in the release of glycerol and FFA into the plasma at increased rates. The glycerol is cleared by the liver and converted into glucose--a process stimulated by, among other things, glucagon. Some of the increased flux of FFA is also cleared by the liver, whereupon the fatty acids are incorporated into VLDL and released again into the plasma. The increased FFA levels also exert a dampening effect on the factors stimulating hepatic glucose production. At the periphery, plasma FFA as well as VLDL fatty acids are taken up at an increased rate. The tissues are attuned to the oxidation of fat, and as a consequence most of the energy production is derived from fat oxidation. The increased fatty acids exert an inhibitory effect on the complete oxidation of glucose, so although glucose may be taken up at an accelerated rate, the relative contribution of glucose oxidation to total energy production may fall. Rather than being completely oxidized, pyruvate is reduced to lactate and released into the plasma at an accelerated rate. The lactate then contributes to the production of glucose in the liver, completing a cyclical process called the Cori Cycle. Although all aspects of this scheme are supported by data highlighted in this paper, it certainly must be an oversimplification of the overall response of substrate metabolism to trauma and sepsis. It is presented for the purpose of highlighting the potential role of fat as a controller of the metabolic response, and to suggest that the enhanced mobilization and oxidation of fat is one of the fundamental responses to stress.

Animals↗

Hepatobronchial fistula caused by hydatid disease. The Dunedin experience 1952-79.

Despite intensive hydatid control measures in New Zealand, hepatopulmonary fistula resulting from infection by the echinococcus granulosus still occurs. Although the patients may quickly become debilitated from coughing bile and pus and associated septic complications, appropriate surgical therapy is usually effective. The exact diagnosis may be obscure, but it is helped by a high index of suspicion. A retrospective study of eight patients seen over a 27-year period is presented, and principles of management are outlined. Where biliary hypertension is not present adequate evacuation of the intrahepatic cysts, obliteration of the cyst space, freeing of the adherent lung, and closure of the pulmonary fistula(e) usually give satisfactory long-term results. Pulmonary lobectomy or segmental resection is seldom required.

Adult↗

Villous adenomas of the duodenum.

Two cases of villous adenoma of the duodenum are presented. One patient had two lesions in the first part of the duodenum, this being only the second report of multiple villous adenomas of the duodenum. One patient was totally asymptomatic and his villous adenoma was diagnosed radiologically during investigation of anaemia, while the second patient had his two villous adenomas discovered incidentally during surgery for a bleeding leiomyosarcoma of the stomach. The two duodenal adenomas in the second patient had been missed on the barium study.

Adenoma↗

Perforated jejunal diverticulum due to foreign body.

Inflammation is the commonest cause of jejunal diverticulum perforation. Perforation from foreign body is a clinical rarity, with only two cases documented. A third case of perforation due to foreign body is presented with a brief review of the literature.

Diverticulum↗