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Biomedical subjects

J R Border

Publications and source records attributed to J R Border.

At least 37 records · Page 2Linked to original sources
PubMed1981

Multiple systems organ failure: IV. Imbalances in plasma amino acids associated with exogenous albumin in the trauma-septic patient.

In a survey study of septic trauma patients, the response of plasma amino acid concentration to albumin infusion was contrasted in survivors (14 patients) and nonsurvivors (11 patients). Plasma albumin levels were maintained at 3 gm/dl by albumin infusion (0-128 gm/day) because of central venous pressure/adequate circulation considerations. Survivors showed no significant increase in plasma essential amino acid concentration as a function of albumin infusion. In nonsurvivors threonine, valine, leucine, phenylalanine, lysine, and histidine all rose significantly (p less than or equal to 0.025) with albumin infusion. Isoleucine (8 residues/molecule albumin), in contrast to leucine (60 residues/molecule) did not increase. As a result, the ratio of isoleucine to leucine (Ile/Leu) decreased with albumin infusion from 0.47 (no albumin infused) to 0.27 (60 gm albumin/day). Survivors did not exhibit a similar response. The low Ile/Leu increased in most nonsurvivors with amino acid infusion from 0.27 (no amino acids) to 0.59 (150 gm amino acids/day). The data strongly suggest that nonsurvivors had an increased rate of albumin catabolism with subsequent amino acid release. Moreover, hypoalbuminemia treated with albumin infusion without amino acid infusion appears to produce a relative isoleucine deficiency which may detrimentally affect protein synthesis.

Accidents, Traffic↗
PubMed1980

Septic autocannibalism. A failure of exogenous nutritional support.

Forty-six patients with surgical sepsis were studied prospectively until death or survival to evaluate the effect of exogenous metabolic support on the observed plasma substrate levels and on the differential endogenous utilization of branch chain amino acids. There were no effects of administered glucose or colloid load. The administered amino acid load had little effect on substrate levels in patients who died; but significantly effected the observed levels of glycine, isoleucine, and methionine in patients who survived. Evidence is presented which suggests that fatal sepsis is associated with an increased release of endogenous valine and isoleucine into plasma, as well as increased plasma levels of tyrosine, proline, and methionine. These abnormalities are highly correlated with the increased levels of plasma alanine and occur at a time when the nonsurviving septic patient manifests a tendency toward reduced oxygen consumption and abnormal vascular tone relations--the septic B state. These data are consistent with the hypothesis that increased muscle protein catabolism is occurring with a differential utilization of branch chain amino acids and increased use of leucine and isoleucine and reduced use of valine. This autocannibalism of muscle mass appears to be the source of the increased plasma alanine and is little influenced by administered amino acid support in the absence of control of the septic process.

Alanine↗
PubMed1980

The systemic septic response: does the organism matter?

The clinical and physiological responses to septicemia were evaluated in 59 patients with 70 septic episodes. All patients were critically ill, had similar ICU support, and had positive blood cultures as well as a clinical infection when studied by dye dilution cardiac outputs. The overall ratio of gram-negative to gram-positive sepsis was 2.6:1.0. Patients with septicemia caused by gram-positive organisms, gram-negative organisms, anaerobes, and fungi had similar fever, leucocyte, and acid-base responses. There were also no statistical differences in any physiological variables between organism group or between specific organisms. After volume loading, all patients exhibited a hyperdynamic cardiovascular response with abnormal vascular tone. Some degree of myocardial depression was a common feature of all forms of bacterial or fungal septicemia. Heart rate was the cardiac variable producing the increased cardiac output in this setting. The exact pathogenesis of the septic response remains undetermined. However, the response appears to be host determined and not peculiar to a specific pathogenic microorganism.

Adult↗
PubMed1980

Primary open reduction and internal fixation of open fractures.

Our experience with primary open reduction with rigid internal fixation of 50 open fractures is presented. Twenty-seven patients had associated major multiple trauma. Twenty fractures were articular and 26 involved 3rd-degree wounds. The infection rate of 4%. A system of staged sequential debridement and wound management is presented. The authors believe this system has contributed to the low infection rate. No secondary amputations occurred. Eighty-two per cent of the patients had good functional results using Charnley's criteria. Fatal post-traumatic cardiopulmonary failure did not occur. The authors feel that early definitive fracture care employing rigid fixation which avoids casts, and allows improved wound management and early mobilization of the multiple-trauma patient, has decreased the cardiopulmonary and metabolic consequences commonly associated with polytrauma patient care.

Adolescent↗
PubMed1979

Monoglyceryl acetoacetate: a ketone body-carbohydrate substrate for parenteral feeding of the rat.

The monoglyceride of acetoacetate was prepared from diketene and glycerol. The resulting mixture was composed of nearly equal amounts of 1- and 2-monoacetoacetin. This mixture was tested as a parenteral energy substrate by continuous intravenous infusion into the rat. This glyceride provided 71% of the daily energy for 7 consecutive days. Other groups were either fed ad libitum or fed ad libitum and supplemented with intravenous glucose isoenergetic to monoacetoacetin. All three groups had similar daily non-protein energy intake, and the two supplemented groups ate less protein than normal rats. All three groups gained weight similarly although the glucose group tended to gain fastest and the monoacetoacetin group tended to gain slowest. The rates were not significantly different. At the end of 7 days, the glucose group was hyperglycemic and the monoacetoacetin group was hyperketonemic compared to normal fed rats. The only significant differences among the livers was the small size found for the glucose group. Hepatic compositions were similar. It was concluded from these data that intravenous monoacetoacetin can support weight gain in rats and is a potential alternative to glucose as an energy source in parenteral nutrition.

Acetoacetates↗
PubMed1979

Proline metabolism in sepsis, cirrhosis and general surgery. The peripheral energy deficit.

Proline metabolism was prospectively evaluated in patients with surgical sepsis, cirrhosis, and elective surgical procedures. Significant correlations were found in the septic patients. Proline levels were an excellent indicator of mortality and correlated positively with lactate levels. Lactate and proline were inversely related to total peripheral resistance and oxygen consumption. In septic patients who expired: the metabolites involved in the hepatic pathways of proline degradation were elevated in proportion to proline; lactate, glutamate and proline were directly related to pyruvate; lactate/pyruvate ratios were constant; proline, glutamate, ammonia, ornithine, lactate and pyruvate levels were inversely proportional to oxygen consumption and total peripheral resistance. The primary defects in sepsis seem to be metabolic; there are very strong correlations in time between physiology and metabolism; the metabolic abnormality seems to be a progressive energy-fuel deficit, possibly from a progressive inhibition of substrate entry into the Krebs cycle.

Citric Acid Cycle↗
PubMed1979

Correlations between metabolic and cardiopulmonary measurements in patients after trauma, general surgery, and sepsis.

Simultaneous longitudinal hormonometabolic-physiologic (cardiopulmonary) profiles were measured in 14 nonseptic trauma/general surgery (T/GS) patients and in ten patients with Gram-negative abdominal surgical sepsis. The physiologic state classification system was used as the frame of reference. There were no response differences between the T and GS groups: they had A State responses. The sepsis (S) patients initially had exaggerated A State responses with significant changes in glucose, fat, amino acid, and glucagon plasma levels relative to T/GS. The S patients who survived (four) demonstrated profiles as in T/GS. The S patients who expired (six) progressively evolved an unbalanced, hyperdynamic B State response with progressive elevations of glucose, lactate, aromatic and branched-chain amino acids and glucagon, and low ketone bodies. There is definite correlation over time between metabolic and physiologic responses; the physiologic responses reflect the metabolic responses; the metabolic responses are consistent with a peripheral energy-fuel deficit.

Adult↗
PubMed1979

The physiologic recovery trajectory as the organizing principle for the quantification of hormonometabolic adaptation to surgical stress and severe sepsis.

Preoperative and serial postoperative clinical, cardiovascular, physiologic, and metabolic studies were carried out on 86 patients undergoing coronary artery bypass surgery (CABG); and 48 patients undergoing abdominal general surgical procedures (GSEL). Multivariable statistical analysis of these data showed the patients to be in different physiologic states and to manifest several types of recovery trajectories that could not be discerned on clinical grounds alone. The CABG patients followed one of three types of cardiogenic recovery trajectories. In contrast, GSEL patients show a normal recovery trajectory different from all CABG types. When sepsis develops, and exaggerated stress response (A state) occurs, with increased oxygen consumption and a pattern of amino acids, fat, and glucose breakdown products, which is heightened but similar to the response of nonseptic GSEL patients. With progression of sepsis severity, an unbalanced hyperdynamic recovery trajectory (B state) develops in which a decrease in oxygen consumption is associated with increases in the aromatic amino acids tyrosine, tryptophane, and phenylalanine; and decreases in the branched-chain amino acids, leucine and isoleucine. Triglycerides rise as keto acids fall, but both lactate and pyruvate rise. Glucagon is persistently high, regardless of insulin levels. The quantifiably different physiologic recovery trajectories reflect altered hormone and metabolic states and imply different responses to therapy.

Abdomen↗
PubMed1979

Physiological and metabolic correlations in human sepsis. Invited commentary.

The septic response in man appears to be a disease in which the infecting agent induces a state of disordered metabolic control in the host. The abnormal regulation of metabolic pathways causes a diversion of substrate utilization toward gluconeogenesis and ketone body formation and a reduction in oxidative energy-producing metabolism. This state of metabolic insufficiency is reflected in the pattern of cardiorespiratory, vascular, and physiological compensation. The precise magnitude of the resultant physiological compensation and its rate and direction of change can be quantified by the use of physiological state trajectories which also reflect the magnitude of underlying metabolic derrangements. The prognostic and therapeutic implications of these changes are discussed.

Amino Acids↗
PubMed1978

Plasma concentrations and tissue uptake of free amino acids in dogs in sepsis and starvation: effects of glucose infusion--some effects of low alimentation.

The plasma concentrations of substrates, together with transhepatic and transgut balances, have been studied in six control and eight septic awake fasted dogs. Four severely ill septic dogs (typically fluid in chest and/or abdomen, extensive peritonitis, respiratory difficulties) had high concentrations of threonine, glycine, tyrosine, lysine, histidine, tryptophan, and triglycerides (p less than or equal to 0.05). The other septic dogs (less severely ill) showed fewer and less pronounced alterations in the plasma substrates (aspartate and tryptophan were elevated, p less than or equal to 0.05). The infusion of glucose increased the concentration of glucose, lactate, and pyruvate and depressed the concentrations of most amino acids in both normal and septic dogs. Threonine, asparagine, glutamine, leucine, isoleucine, alpha-aminobutyrate, and tyrosine were significantly depressed in the severely ill septic dogs (p less than or equal to 0.05). In the normal dogs most amino acids were removed by the liver, with alanine accounting for approximately 40% of the total. Glutamine removal was negligible. In the septic dogs hepatic removal of amino acids was variable; livers of two severely ill septic dogs did not remove amino acids. In the control dogs glucose infusion (0.015--0.017 g/kg/min) tended to lower hepatic removal of amino acids. Hepatic dye removal in the septic dogs was always very poor. In the gut glutamine was removed and alanine, glutamate, glycine, and ammonia produced, but the overall sum of amino acid uptake was negligible in both the control and septic dogs. The ratio of tryptophan to the sum of valine, isoleucine, leucine, tyrosine, and phenylalanine concentrations was greatly elevated in all septic dogs in which it was measured. The free concentrations of amino acids in the liver, heart, and muscle tissues were grossly elevated in the low intravenous alimented septic state relative to the fasted normal state, whereas the tissue concentrative ability as measured by nonmetabolizable amino acids, alpha-aminoisobutyrate and cycloleucine, was not similarly increased. Sepsis clearly alters plasma and tissue concentrations, and in some instances hepatic uptake of amino acids.

Amino Acids↗
PubMed1978

Intravenous feeding of the rat with short chain fatty acid esters. II. Monoacetoacetin.

Acetoacetic acid is oxidized independent of carnitine transport into the cell mitochondria and its monoglyceride is a water soluble compound. The latter was examined as an intravenous nutrient. The monoglyceride of acetoacetic acid was prepared from the acid anhydride, diketene, and glycerol and was found to be totally miscible with water. The nutritional properties of monoacetoacetin were investigated by continuous intravenous infusion of 25 or 50 g/kg body weight per day into ad libitum fed rats. The response of these animals was compared to normal and food restricted rats. All experimental animals survived the 7 day study period in good health and were free of detectable physiological and behavioral abnormalities. The test rats demonstrated weight gain dependent on the infusion rate while on an inadequate spontaneous oral food intake diet. Ketonuria, hyperketonemia and monoglyceride excretion in the urine accompanied the infusion of monoacetoacetin and were dependent on the infusion load. At 50 g/kg per day total plasma ketones were found to be comparable with the infusion load. At 50 g/kg per day total plasma ketones were found to be comparable with the maximum level obtained in fasted rats, but the acetoacetate concentration was relatively higher than in fasting. This was consistant with ketosis derived from the hydrolysis of the monoglyceride. It was concluded from these results that monoacetoacetin might be an asset for intravenous nutrition.

Acetoacetates↗
PubMed1978

Influence of intermittent hyperglycemic glucose levels on the phagocytosis of microorganisms by human granulocytes in vitro.

Repeated brief exposures to glucose in concentrations of 0.8 g/100 ml significantly depresses in vitro phagocytic ingestion of opsonized Gram-positive and Gram-negative bacteria by human peripheral polymorphonuclear granulocytes (PMN's), while the same concentration of L-aminoacid mixtures (Freamine) under the same conditions has no influence on it.

Blood Glucose↗
PubMed1977

Intravenous feeding of the rat with short chain fatty acid esters. I. Glycerol monobutyrate.

Intravenous nutrition was investigated using butyric acid because it is oxidized independent of carnitine transport into the cell mitochondria. This carnitine independent fatty acid, in the form of water soluble monobutyrin, was continuously infused into rats for seven days at 27 g monobutyrin per kilogram of body weight per day and provided half the daily energy requirement. All experimental animals survived the alimentation in good health and were free of detectable physiological and behavioral abnormalities. The intravenous infusion depressed the test animals spontaneous food intake to half their preinfusion level. These experimental rats still demonstrated continuous weight pain in contrast to weight loss by pair-fed controls. At decapitation, the monobutyrin infused rats had hepatic glycogen levels three times that of the controls, along with lower soluble hepatic protein, and normal lipid and water content. The plasma acetoacetate was also elevated in experimental rats. It was inferred from these results that monobutyrin was hydrolyzed, and the metabolites were oxidized by the rat. It is concluded from these observations that monobutyrin produces no obvious toxic affects during short infusion periods and provides calories for the rat when given intravenously.

Animals↗
PubMed1977

Recent advances in the management of trauma.

Delivery of the most up-to-date trauma care requires a well-trained team of four physicians and four nurses to carry out the initial management of a single major injury patient (Border et al, 1975). Ventilatory insufficiency, circulatory insufficiency, and wounds must all be treated promptly and simultaneously.

Cardiovascular Diseases↗