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Biomedical subjects

S Svensson

Publications and source records attributed to S Svensson.

At least 19 recordsLinked to original sources

Effects of insulin on myocardial uptake of branched chain amino acids soon after cardiac operations.

Infusion of insulin-glucose-potassium is used to support the failing heart after cardiac operations. Although the effects on myocardial uptake of carbohydrates and lipids have been described, the effects on myocardial extraction of amino acids are unknown. This study was undertaken to clarify the effect of insulin-glucose-potassium on the pattern of amino acid uptake/release in myocardial and skeletal muscle after coronary operations. The amino acid uptake/release of the heart and of the leg was studied in 18 patients 1 hour after coronary bypass operations. The patients were randomized to treatment with 25 U of fast-acting insulin as a bolus injection followed by a continuous infusion of 1 U/kg body weight for 1 hour, or to serve as control patients. The hyperinsulinemic "clamp" technique was used to keep blood glucose unchanged during the study. In the insulin-treated group, the arterial concentration of 17 of 22 individual amino acids, including the three branched chain amino acids, decreased, the remainder being unchanged. The amino acid uptake/release of the leg was unchanged. The net myocardial uptake of leucine and isoleucine shifted to a no-uptake/no-release in the insulin-treated group, whereas the no-uptake/no-release of tyrosine and phenylalanine turned into a significant release. A positive correlation was observed between arterial concentration and myocardial uptake/release of the three branched chain amino acids. It is suggested that insulin, by lowering the arterial concentration of leucine and isoleucine, inhibited the myocardial uptake of these amino acids. This may have a negative effect on postoperative myocardial protein balance suggested by the release of tyrosine and phenylalanine.

Amino Acids, Branched-Chain

[Heart transplantation in Denmark. Therapeutic routines and preliminary results].

When the criterion of brain-death was introduced in Denmark on 1.7.1990, the possibility for heart transplantation and other interventions was opened. The first heart transplantation was carried out 3.10.1990 and, during the first year, 28 transplantations were carried out on 27 patients. The therapeutic routines in the department are reviewed and the results obtained after the first year are presented. A total of 33 donors who fulfilled the donor criteria were available. Of these, 28 came to Rigshospitalet, two were sent abroad and suitable recipients could not be found for two. The recipient group consisted of four women and 23 men with an average of 46 years. At the time of writing, on an average 169 days after operation (13-330), 23 out of 27 patients survived in good health and with normal cardiac function. Three patients are still in hospital.

Adult

Myocardial uptake of amino acids and other substrates in relation to myocardial oxygen consumption four hours after cardiac operations.

Myocardial metabolism seems to be markedly abnormal during the first hours of reperfusion after aortic crossclamping. Thus we previously demonstrated no uptake of carbohydrate or lipid substrates 1 hour after coronary operations. Amino acids were the only exogenous substrates taken up by the heart. The aim of the present study was to examine if this metabolic abnormality persisted a few hours later. This was done by measuring coronary sinus blood flow and arterial-coronary sinus differences of oxygen, glucose, free fatty acids, glycerol, lactate, beta-OH-butyrate, and amino acids in a similar group of 19 patients 4 to 5 hours after coronary operations. The results demonstrate a change toward normalization of myocardial free fatty acid use, although the threshold for free fatty acid uptake seemed elevated in comparison with that in the normal postabsorptive state. No correlation was found between free fatty acid uptake and myocardial oxygen consumption. Despite elevated arterial levels of glucose, lactate, pyruvate, and beta-OH-butyrate, no uptake was observed. Myocardial amino acid exchange demonstrated a pattern suggestive of postischemic metabolic adaptation. Several amino acids were extracted, glutamate and branched chain amino acids being the quantitatively most important. The uptake of glutamate and branched chain amino acids correlated with myocardial oxygen consumption, which suggests a direct link to myocardial energy metabolism. Myocardial glutamate uptake seemed to be limited by substrate availability.

3-Hydroxybutyric Acid

The carbohydrate structures of a mouse monoclonal IgG antibody OKT3.

A mouse monoclonal antibody OKT3, of IgG2a isotype, was isolated from hybridoma culture fluid. Sugar analysis showed the presence of sialic acid, galactose, mannose, fucose, and N-acetylglucosamine, i.e. sugars typical for N-glycosidically linked carbohydrate chains. The absence of N-acetylgalactosamine revealed that O-glycosidically linked carbohydrates were not present. The purified antibody was reduced, alkylated, and separated into heavy and light chains, and all carbohydrates were shown to be associated with the heavy chains. The N-linked carbohydrate chains were isolated as alditols using strong alkaline-borohydride degradation and further fractionated on a concanavalin A-Sepharose column and high performance ion exchange chromatography with pulsed amperometric detection. Structural analysis was carried out on the isolated oligosaccharide alditols by chemical analyses, fast atom bombardment mass spectrometry, and 500-MHz 1H NMR spectroscopy. Triantennary and biantenary types of structures were found. The triantennary structures were present as trisialo and tetrasialo forms without fucose; the tetrasialo forms were shown to contain a sequence of Neu5Ac alpha 2-3Gal beta 1-3[Neu5Ac alpha 2-6]GlcNAc beta 1- on one of the branches. The biantennary structures were present as completely sialylated nonfucosylated species and as asialo-, agalacto-, and partially fucosylated structures.

Animals

Trauma metabolism and the heart: studies of heart and leg amino acid flux after cardiac surgery.

Flux of plasma amino acids was measured across the heart and the leg (reflecting mainly skeletal muscle) in 18 patients 1 hour after completion of aorto-coronary bypass surgery. There was a net loss of amino acids from the leg (-324.9 +/- 39 nmol/min/100 ml tissue) while amino acid flux across the heart was not statistically different from zero. There were however positive intertissue correlations between leg and myocardial flux of tyrosine and most other amino acids, suggesting that protein metabolism of both tissues were affected in the same catabolic direction by the trauma response. Alanine and glutamine accounted for 50% of the amino acid release from the leg, which is in accordance with observations in association with other types of trauma. Alanine and glutamine also dominated amino acid release from the heart. Glutamate and aspartate were taken up by both tissues. The principal difference between the tissues was a myocardial uptake of leucine and isoleucine, in contrast to a leg release.

Adult

Development of quinolone-imipenem cross resistance in Pseudomonas aeruginosa during exposure to ciprofloxacin.

Selection and regrowth of ciprofloxacin-resistant variants, which were present in low frequencies in the initial inoculum, were seen when large inocula of Pseudomonas aeruginosa were incubated with ciprofloxacin. These variants showed cross resistance to other quinolones. In 8 of 13 strains tested, ciprofloxacin selected imipenem-resistant variants in a similar way to imipenem. The opposite phenomenon of ciprofloxacin-imipenem cross resistance after exposure to imipenem was not detected. None of the ciprofloxacin-resistant variants showed cross resistance to aztreonam, piperacillin, or tobramycin. These findings indicate that widespread and uncritical use of ciprofloxacin gives a potential risk of development of resistance in P. aeruginosa not only to quinolones but also to another unrelated useful agent, imipenem. In vitro evaluation of this phenomenon in isolates from patients with P. aeruginosa infections may be justified, since strains differ in development of quinolone-imipenem cross resistance after ciprofloxacin exposure.

Aminoglycosides

Trauma metabolism and the heart. Uptake of substrates and effects of insulin early after cardiac operations.

In a controlled, randomized study the myocardial uptake/release of individual free fatty acids, glucose, lactate, pyruvate, alanine, and glycerol was studied 1 hour after completion of coronary operations. The effects of insulin were evaluated by means of a hyperinsulinemic "clamp" technique. No significant uptake of free fatty acids was found despite markedly elevated arterial concentrations (mean +/- standard error of the mean, 2.01 +/- 0.19 mmol.L-1), oleic acid, together with palmitic and linoleic acid, constituting 80% of the total plasma free fatty acid level. Insulin treatment (1 unit.kg bw-1.hr-1) prevented a further increase of the plasma free fatty acid level, observed concomitantly in the control group. Insulin affected all individual free fatty acids similarly. Changes in plasma free fatty acid levels occurring during the study and the corresponding myocardial uptake correlated (rS = 0.50 to 0.81). No significant uptake or release of glucose, lactate pyruvate, and glycerol occurred, whereas a myocardial release of alanine was seen. The heart and the concomitant leg uptake/release of glucose (rS = 0.40, p less than 0.05) and lactate (rS = 0.67, p less than 0.01) correlated. A substantial uptake of glucose was achieved and a more positive myocardial balance was obtained for alanine, lactate, and pyruvate with insulin. The changes in heart and the concomitant leg uptake/release correlated (glucose, rS = 0.62, p less than 0.01; lactate, rS = 0.64, p less than 0.01; pyruvate, rS = 0.71, p less than 0.01). It is concluded that the myocardial uptake of substrates during the first hours after coronary surgery is markedly abnormal with no uptake of free fatty acids or carbohydrates. These changes can be explained to some extent by the insulin resistance of trauma metabolism and can be modified by insulin treatment.

Adult

Structural analysis of the carbohydrate chains of a mouse monoclonal IgM antibody.

A mouse monoclonal IgM antibody, directed against human blood group B determinant, was isolated from hybridoma culture growth medium. Chemical analysis indicated presence of N- and O-linked oligosaccharides. The N- and O-linked carbohydrate chains were liberated using two different conditions of reductive alkaline degradation. Structural analysis was carried out on the isolated chains using chemical analysis, 500-MHz 1H-NMR spectroscopy and fast-atom-bombardment mass spectrometry. The following composite structures of the N-linked chains were found: (formula; see text) where R = OH for biantennary structures and R = Neu5Ac alpha 2-3Gal beta 1-4 GlcNAc beta 1- or Neu5Ac alpha 2-3Gal beta 1-3[Neu5Ac alpha 2-6]GlcNAc beta 1- for triantennary structures. The O-linked oligosaccharides, found in the light chains, were shown to have the structure Neu5Ac alpha 2-3Gal beta 1-3GalNAc. The native IgM antibody could be separated on a concanavalin-A-Sepharose column into two subfractions, differing in the presence of a high-mannose-type oligosaccharide.

ABO Blood-Group System

Synthesis of Gal beta 1-3GlcNAc and Gal beta 1-3GlcNAc beta-SEt by an enzymatic method comprising the sequential use of beta-galactosidases from bovine testes and Escherichia coli.

Gal beta 1-3GlcNAc (1) and Gal beta 1-3GlcNAc beta-SEt (2) were synthesized on a 100 mg scale by the transgalactosylation reaction of bovine testes beta-galactosidase with lactose as donor and N-acetylglucosamine and GlcNAc beta-SEt as acceptors. In both cases the product mixtures contained unwanted isomers and were treated with beta-galactosidase from Escherichia coli which has a different specificity, under conditions favouring hydrolysis, yielding besides the desired products, monosaccharides and traces of trisaccharides. The products were purified to greater than 95% by gel filtration, with a final yield of 12% of 1 and 17% of 2, based on added acceptor. In a separate experiment Gal beta 1-6GlcNAc beta-SEt (3) was synthesized by the transglycosylation reaction using beta-galactosidase from Escherichia coli. No other isomers were detected. Compound 3 was purified by HPLC.

Animals

Insulin as a vasodilating agent in the first hour after cardiopulmonary bypass.

To study the vasodilating effect of insulin after termination of ECC in aortocoronary bypass surgery, 21 patients were randomized to treatment with 7.5 U of fast-acting insulin/kg b.w. as a bolus injection followed by continuous infusion of 15 U/kg b.w. for 1 hour, or to serve as controls. Insulin administration was begun when the last proximal anastomosis had been completed. Cardiac output and central pressures were monitored for 1 hour after termination of ECC. Systemic vascular resistance in both groups was lower at the end of ECC than before surgery (reduction 39% in the controls, 51% in the insulin-treated group). During the following hour the peripheral resistance increased significantly in the controls (from 20 +/- 2 to 29 +/- 2 mmHg X min X m2/l), but no change was found in the insulin group. It is concluded that insulin can maintain a low vascular resistance after aortocoronary bypass surgery.

Adult

Glucose and lactate balances in heart and leg after coronary surgery: influence of insulin infusion.

Glucose and lactate balances in leg (representing mainly skeletal muscle) and heart were studied 1 hour after aortocoronary bypass surgery and insulin treatment. Seventeen men were randomized to receive 25 U fast-acting insulin as a bolus injection, followed by continuous infusion of 1 U/kg b.w. for 1 hour, or to serve as controls. In the leg a small glucose uptake was found while the lactate balance was negative. During the study period the lactate release increased further in the control group. In the myocardium no significant extraction of glucose or lactate could be demonstrated. Insulin treatment resulted in a fivefold increment of leg glucose uptake and in significant myocardial glucose uptake. Myocardial lactate balance was also improved by insulin treatment, with fractional extraction increased from 6 to 21%. It is concluded that myocardial carbohydrate metabolism is restricted in the early period after cardiac surgery, and that this seems to result from insulin resistance induced by the surgical trauma.

Adult

The effect of insulin on the leg and splanchnic balance of glucose and gluconeogenic substrates after cardiac surgery.

The effect of insulin and glucose infusion on the leg and splanchnic balance of glucose and the gluconeogenic substrates lactate, pyruvate, alanine and glycerol was studied in 13 patients directly after cardiac surgery. Insulin was infused continuously at a rate of 1.0 Unit/kg/hr during 1 hour. Sixteen patients served as a control group and received no insulin and glucose infusion. A significant increase in arterial lactate concentration in both the control group (from 1.40 +/- 0.19 to 1.68 +/- 0.24 mmol/l p less than 0.01) and the insulin group (from 1.58 +/- 0.27 to 2.07 +/- 0.22 mmol/l, p less than 0.05) was observed. The arterial pyruvate concentration was significantly increased (from 0.075 +/- 0.019 to 0.105 +/- 0.021 mmol/l, p less than 0.01) and glycerol was significantly decreased (from 0.15 +/- 0.03 to 0.12 +/- 0.03 mmol/l, p less than 0.05) during the insulin and glucose infusion. The alanine concentration was unchanged in both groups. Insulin and glucose infusion was followed by an increased leg uptake of glucose (from 0.15 +/- 0.14 to 1.06 +/- 0.16 mmol/min/100 ml, p less than 0.05), and by a changed splanchnic glucose balance (from -8.2 +/- 2.8 to +4.0 +/- 1.2 mmol/kg/min, p less than 0.01). A net leg release and at the same time a net splanchnic uptake of all gluconeogenic substrates was observed. The insulin and glucose infusion did not significantly change either the splanchnic balance or the leg balance of the gluconeogenic substrates.

Aged

Emergency treatment of rupture of the proximal anastomosis of an infected thoracoabdominal aortic graft with bleeding into a postpneumonectomy empyema cavity.

The thoracic part of a huge thoracoabdominal aortic aneurysm was resected. A prosthetic graft was implanted between the descending aorta and the iliac arteries. The celiac, superior mesenteric, and the renal arteries were connected to the aortic prosthesis with two bifurcation grafts. A life-threatening hemorrhage into an empyema cavity occurred postoperatively. An emergency two-stage procedure was employed involving: (1) exclusion of the infected intrathoracic segment and exclusion of an infected sutured aortic stump; (2) subsequent removal of necrotic and infected tissue, including the excluded segment of the aorta and the graft in a second operation. The patient recovered and is now well and works full-time. Angiography 3 years after the operation shows that all anastomoses are patent. A scheme of management of these rare cases is proposed.

Adult

Management of postinfarction ventricular septal rupture.

Thirty-five patients were operated on for ventricular septal rupture after acute myocardial infarction (AMI). The overall operative mortality rate was 46%. Hemodynamic and clinical stability was achieved in 14 patients preoperatively. They were operated on after 4 weeks or more. Late development of cardiac failure was the main cause of an operative mortality rate of 21%. From a surgical point of view there are no reasons to delay the operation of these patients for more than 4-8 weeks. The operative mortality rate among 21 patients in cardiogenic shock was 62%. The present study shows, however, that it was possible to save lives by emergency operation of patients who otherwise would have died of cardiogenic shock. The time-interval from diagnosis to surgical treatment, and the preoperative condition of the patients appeared to be important prognostic factors. The location of the myocardial infarction did not significantly influence the prognosis in this series. The 19 long-term survivors returned to normal life, although 8 of them had a small residual shunt. More than half of the patients, who were examined, had multivessel disease. The operative mortality rate for those patients without concomitant coronary artery bypass grafting (CABG) was 80%. Technical failures and some new surgical principles are presented. The indications for IAPB and coronary angiography are discussed as well as the optimum time for surgical repair. The clinical course varies greatly and calls for a differentiated approach to treatment. A plan for surgical management of these patients is suggested.

Aged

Iron, zinc and folate status during pregnancy and two months after delivery.

Iron, zinc and folate statuses of 45 women were determined during pregnancy around 12, 20, 28, 32 and 36 weeks, and again 2 months after delivery. Analyses of plasma ferritin, Hb, MCV, folate and zinc in plasma and whole blood were performed. Iron supplementation was recommended from mid-pregnancy but 13 of the participants did not use the iron supplements. This group had significantly decreased levels of plasma ferritin and MCV at the end of pregnancy, but none developed anemia. Two months post partum the plasma ferritin of the unsupplemented group had normalized and was in the same range as in the supplemented group. The concentrations of zinc in plasma and whole blood and the calculated levels of red cells were low even at the first examination around 12 weeks of gestation, compared with non-pregnant women. Throughout the course of pregnancy the plasma zinc levels continued to decrease, while the whole blood and red cell levels showed a significant rise. At term of gestation almost half the women had subnormal plasma folate levels (L. casei), which persisted during the post partum follow-up. The corresponding value for red cell folate was 10% below normal values at term and 30% subnormal 2 months after parturition. These findings stress the importance of extending the observation period to include also the lactating period, in order to judge the need for folate supplementation.

Adult

Structural studies on the O-glycosidically linked carbohydrate chains of glucoamylase G1 from Aspergillus niger.

Glucoamylase G1 from Aspergillus niger contains an unusual type of carbohydrate-protein linkage, involving mannose O-glycosidically linked to serine and threonine. The majority of the neutral oligosaccharides of glucoamylase G1 are located in a region of about 70 amino acid residues which carries about 35 oligosaccharide units [(1983) Carlsberg Res. Commun. 48, 517-527]. Structural analysis was performed on the O-linked carbohydrates of a tryptic fragment from glucoamylase G1 comprising the segment characterized by a high degree of glycosylation. The carbohydrate structures released by trifluoroacetolysis were elucidated using sugar analysis, methylation analysis, mass spectrometry, chromium trioxide oxidation, digestion with alpha-mannosidase and 1H-NMR spectroscopy. The following structures could be identified. (formula; see text)

Aspergillus niger