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Biomedical subjects

T Pedersen

Publications and source records attributed to T Pedersen.

At least 55 records · Page 3Linked to original sources

Percutaneous technique for venovenous bypass including a heat exchanger is safe and reliable in liver transplantation.

We have introduced and evaluated several modifications of the conventional venovenous bypass (VVBP) in 29 adult patients undergoing liver transplantation (OLT). A percutaneous technique for insertion of a jugular venous return cannula and a femoral vein cannula was applied. The inferior mesenteric vein (IMV) was used for splanchnic decompression, which facilitated dissection of the recipient liver and allowed portal anastomosis to be performed without disconnecting the portal bypass. A heat exchanger was introduced into the bypass circuit to prevent heat loss. The percutaneous technique prevented complications related to dissection in the axilla and groin. Hemodynamic characteristics corresponded to those found using the traditional technique. Complications related to the VVBP were seen in only one patient in whom the femoral catheter was accidentally introduced into the femoral artery. We conclude that percutaneous cannulas, use of the IMV for splanchnic decompression and the introduction of a heat exchanger offer significant benefits and that they are safe and reliable.

Adult↗

Duraflo II coating of cardiopulmonary bypass circuits reduces complement activation, but does not affect the release of granulocyte enzymes : a European multicentre study.

OBJECTIVE: This study was carried out to: (a) compare complement and granulocyte activation during cardiac operations in patients operated with cardiopulmonary bypass coated with heparin by the Duraflo II method, with activation in patients operated with uncoated circuits; and (b) relate complement, and granulocyte activation to selected adverse effects. METHODS: In a multicentre study among Rikshospitalet, Ullevaal Hospital in Norway and Uppsala University Hospital in Sweden, plasma concentrations of the complement activation products C4b/iC4b/C4c (C4bc), C3b/iC3b/C3c (C3bc), the terminal SC5b-9 complement complex (TCC), and the granulocyte proteins myeloperoxidase and lactoferrin were assessed in two groups of patients undergoing aortocoronary bypass. Seventy-six patients underwent surgery operated with circuits coated by the Duraflo II heparin coating and 75 uncoated circuits. The same amount of systemic heparin was administered to all patients. RESULTS: In both groups a significant increase in C4bc was first seen by the end of operation, from 86.7 +/- 12.5 to 273.0 +/- 277.4 nM in controls and from 86.9 +/- 18.5 to 320.2 +/- 190.5 nM in the control group, confirming previous documentation that the classical pathway is not activated during CPB, but as a consequence of protamin administration. The formation of C4bc did not differ significantly between the two groups. In the uncoated group the C3bc concentration increased from 124.0 +/- 15.3 to a maximum of 1176.1 +/- 64.7 nM (P < 0.01) and in the coated group it increased from 129.8 +/- 16.1 to a maximum of 1019.4 +/- 54.9 nM (P < 0.01) during CPB. Summary values but not peak values differed significantly between the groups. In the uncoated group the TCC concentration increased from 0.52 +/- 0.03 to a maximum value of 8.09 +/- 0.57 AU/ml (P < 0.01) while in the coated group the TCC concentration increased from a baseline of 0.53 +/- 0.03 to a peak value of 5.2 +/- 0.24 AU/ml (P <0.01). The difference between the peak values was statistically significant (P = 0.00002). In both groups a significant increase in myeloperoxidase and lactoferrin release was observed by the end of operation. There was no difference in myeloperoxidase or lactoferrin release between the two groups. TCC levels were compared to the occurrence of perioperative infarction, development of lung or renal failure, postoperative bleeding, time on ventilator and days in hospital. Three patients developed perioperative infarction; the peak levels of TCC were significantly higher in these patients than in the 148 patients that did not develop infarction. The reduction in TCC formation in the heparin-coated group was not associated with differences in any of the other clinical parameters. Few adverse effects occurred in the study. The peak values of C3bc were higher in the patients needing inotropic support that in those who did not, the relevance of this finding remains uncertain. CONCLUSION: It is concluded that the Duraflo II heparin coating reduces complement activation, particularly TCC formation, during CPB, but not the release of specific neutrophil granule enzymes. No certain correlation was established between complement and granulocyte activation and clinical outcome.

Aged↗

Lp(a) lipoprotein level predicts survival and major coronary events in the Scandinavian Simvastatin Survival Study.

The Scandinavian Simvastatin Survival Study (4S) was a double-blind, randomized placebo-controlled multi-centre clinical trial of long-term Simvastatin therapy in patients with coronary heart disease who had total cholesterol levels between 5.5 and 8.0 mmol/l, comprising 4444 patients, equally distributed to a Simvastatin and a placebo group. Patients achieved a significant 30% relative reduction in overall mortality with Simvastatin therapy through a 42% relative reduction in coronary heart disease mortality. Lp(a) lipoprotein levels in Scandinavian coronary heart disease patients were strikingly higher than in healthy controls. Numbers of deaths in the Simvastatin group differed significantly between quartiles of Lp(a) lipoprotein levels, the reduction in deaths being most pronounced in the second (next to lowest) quartile. Subjects with major coronary events had significantly higher Lp(a) lipoprotein levels than subjects without such events, in all groups. The relationship between Lp(a) lipoprotein level and total mortality as well as between Lp(a) lipoprotein level and major coronary events was significantly different from zero, in logistic regression analyses. The findings show that Lp(a) lipoprotein predicts major coronary events as well as death in secondary prevention with Simvastatin. This prospective study provides independent confirmation that a high Lp(a) lipoprotein level is a significant coronary heart disease risk factor.

Adult↗

The effect of citalopram in panic disorder.

BACKGROUND: Citalopram is a serotonin reuptake inhibitor which has been demonstrated to be highly selective and with a superior tolerability profile to the classical tricyclic antidepressants. This study was designed to test whether there was any difference in efficacy in the management of panic disorder (PD) between citalopram and placebo. METHOD: This was a double-blind, placebo and clomipramine controlled, parallel group eight-week study. A total of 475 patients with PD, with or without agoraphobia, were randomised to treatment with either placebo, clomipramine 60 or 90 mg/day, or citalopram 10 or 15 mg/day, or 20 or 30 mg/day, or 40 or 60 mg/day. Doses were increased over the first three weeks, stabilised during the fourth week and fixed between weeks five and eight. RESULTS: Treatment with citalopram at 20 or 30 mg, 40 or 60 mg and clomipramine were significantly superior to placebo, judged by the number of patients free of panic attacks in the week prior to the final assessment. All rating scales examined suggested that citalopram 20 or 30 mg was more effective than citalopram 40 or 60 mg. CONCLUSION: The most advantageous benefit/risk ratio for the treatment of PD was associated with citalopram 20 or 30 mg/day.

Adolescent↗

Effects on complement, granulocytes and platelets of a leukocyte-depletion filter during in vitro extracorporeal circulation.

In an in vitro study, extracorporeal circuits equipped with either a leukocyte-depleting filter (n = 5) or a standard arterial-line filter (n = 5) were perfused for 120 minutes with fresh human whole blood. Leukocyte activation, leukocyte and platelet counts and complement activation were studied. Significant reduction of leukocyte and platelet counts and significant activation of leukocytes and of platelets were found in both groups, but without significant intergroup difference for any parameter after 120 minutes of perfusion. The leukocyte-depleting filters, however, were somewhat more effective in removing leukocytes during the initial 30 minutes of circulation.

Complement System Proteins↗

[Interruptions of physicians' work at hospitals. A threat to quality?].

When the working hours of junior doctors at a medical clinic were reduced from 44 to 40.7 hours per week a questionnaire was distributed to the doctors themselves and to the different categories of nurses to find out how this change had affected the schedule for investigation and treatment of the patient, care of the patient, discharge from hospital, and collaboration with other health professionals. In the opinion of doctors and nurses alike, the reduced working hours had led to delays in investigation of patients, poorer care, problems in connection with discharge from hospital, and poorer collaboration with other professional groups. It could well be difficult to achieve normal working hours for junior doctors in hospitals with patients under continuous treatment without this having av decided negative effect on continuity of treatment.

Continuity of Patient Care↗

Release of soluble tumour necrosis factor alpha receptors during and after paediatric cardiopulmonary bypass. Correlation with haemodynamic and clinical variables.

The release of cytokines during cardiopulmonary bypass (CPB) may contribute to haemodynamic alternations encountered after open heart surgery. Regulatory mechanisms exist and include soluble cytokine receptors. We have measured blood levels of tumour necrosis factor (TNF) and its soluble receptor (TNFsr) during and after open heart surgery in children. Correlation analysis to haemodynamic and clinical variables was performed. Using immunoassays the authors registered a significant increase in plasma levels of TNFsr with peak levels 2 h post-operatively at a level of 1702 +/- 170 pg/ml. The concentration of TNFsr remained significantly elevated until 48 h postoperatively but TNF was not significantly elevated. An inverse correlation existed between peak TNFsr and mean arterial pressure (rho = -0.827, P < 0.05), between TNFsr and cardiac index (rho = -0.8, P < 0.05), between TNFsr and left ventricular stroke work index (rho = -0.983, P < 0.01), between TNFsr and weight (rho = -0.85, P < 0.05) and between TNFsr and body surface area (rho = -0.867, P < 0.05). The authors demonstrate that the smallest children experienced the highest TNFsr concentration post-operatively. Furthermore cardiac performance, expressed as cardiac index and left ventricular stroke work index, correlated inversely to peak TNFsr level post-operatively.

Cardiopulmonary Bypass↗

Release of interleukin-8 and calprotectin during and after paediatric cardiopulmonary bypass with and without ultrafiltration.

Release of calprotectin and interleukin-8 (IL-8), changes in leukocyte counts and subsets and influence of extracorporeal ultrafiltration were evaluated during and after cardiopulmonary bypass (CPB) in 18 children undergoing open-heart surgery for congenital heart anomalies. Ultrafiltration was used in nine cases and nine were controls. Calprotectin concentration rose after start of CPB, peaking 48 hours postoperatively, with no significant intergroup difference. Positive correlation was found between duration of CPB and calprotectin (peak level and accumulated total). Circulating IL-8 was detected in all patients perioperatively, peaking at wound closure in the ultrafiltration group and at termination of bypass in the controls. CPB duration correlated significantly to peak level and accumulated total of IL-8. Seven of nine ultrafiltrate samples contained IL-8 at levels similar to the plasma concentration. Changes in white cell counts were mainly attributable to neutrophils. The two subgroups did not differ significantly in neutrophil counts. Neutropenia found after 10 minutes of CPB was replaced by neutrophilia, with maximal values postoperatively. Calprotectin and IL-8 thus were released into the circulation during CPB in children. Ultrafiltration did not affect the plasma concentrations of these substances, and only IL-8 was detected in the ultrafiltrate.

Calcium-Binding Proteins↗

Ultrafiltration after cardiopulmonary bypass in children: effects on hemodynamics, cytokines and complement.

OBJECTIVES: The purpose of the study was to evaluate the clinical and hemodynamic effect of intraoperative extracorporeal ultrafiltration (UF) and its potential in reducing the plasma concentration of circulating cytokines and complement activation products following open heart surgery in children. METHODS: Eighteen children with congenital heart disease were prospectively randomized into a control group (n = 9) and a group who underwent UF (n = 9). Serial plasma samples for measurements of circulating cytokines (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF), and its soluble receptor (sTNF receptor)), and complement factors (C3 activation products (C3a and C3bc) and terminal complement complex (TCC)) were obtained before, during and up to 48 h after cardiopulmonary bypass (CPB). A pulmonary artery thermodilution catheter was introduced preoperatively for hemodynamic monitoring. RESULTS: Postoperative hemodynamics were similar in both groups. Plasma levels of IL-6, sTNF receptors, C3a, C3bc and TCC increased significantly perioperatively (P < 0.01) in both groups. TNF was detected transiently in 16 patients perioperatively and in 4 of the 9 ultrafiltrate samples in concentrations similar to the plasma levels. Complement activating products were not detected in the ultrafiltration samples except for small amounts of C3a in two cases. Compared to the control group the plasma levels of C3a, C3bc and TCC were unaffected by the ultrafiltration procedure. The level of IL-6 and sTNF receptors increased significantly after 15 min of UF but there was no significant difference between the two groups postoperatively. CONCLUSIONS: In this study no clinical or hemodynamic effect was registered after UF. TNF and C3a were occasionally detected in the ultrafiltrate but we were unable to demonstrate reduction of these or any of the other markers tested in the group subjected to ultrafiltration.

Cardiopulmonary Bypass↗

[Death under anesthesia. Definition, causes, risk factors and prevention].

Death associated with anaesthetic procedures is rare, 1-4 deaths per 10,000 anaesthesias. However, each case gives rise to discussion about causality and who is to blame. Prospective studies are few, and comparison between them is difficult because of the use of different definitions of anaesthesia related death. A critically ill patient with impaired function of multiple organs seems to be at a higher risk of anaesthesia related death than a more healthy patient. However, no study has so far identified preoperative risk factors of anaesthesia related death. This is probably due to the low incidence of anaesthesia related death. The most common causes of anaesthesia related deaths are: 1) circulatory failure due to hypovolaemia in combination with overdosage of anaesthetic agents such as thiopentone, opioids, benzodiazepines or regional anaesthesia; 2) hypoxia and hypoventilation after for instance undetected oesophageal intubation, difficult intubation, technical failure in the anaesthetic equipment, or aspiration of gastric content, 3) anaphylactoid reactions including malignant hyperthermia, and 4) human negligence such as lack of vigilance or errors in the administration of drugs and in the maintenance and control of the anaesthetic equipment. We discuss the importance of continuing education for anaesthesiologists, development of a standard for surveillance during anaesthesia and quality control of the anaesthetic procedure with registration of undesired incidents. National registration of serious incidents will make it possible to determine the incidence of serious complications and death associated with anaesthesia. Hopefully this registration will provide information about causality and thereby facilitate prevention and improve patient safety during anaesthesia.

Anesthesia↗

[Persistent pulmonary hypertension in a newborn infant treated with extracorporeal membrane oxygenation].

Extracorporeal membrane oxygenation is a recent addition to our therapeutic arsenal in infants with life-threatening respiratory failure. We have treated a neonate with persistent pulmonary hypertension secondary to meconium aspiration with veno-arterial extracorporeal membrane oxygenation. Both conventional, pressure-controlled ventilation and high-frequency jet ventilation having failed, extracorporeal membrane oxygenation was life-saving for this infant. A clotting episode in the extracorporeal membrane oxygenation circuit resulted in focal as well as global ischemic changes in the brain. In spite of this complication the child was found to be normal upon neurodevelopmental evaluation at one year of age. Extracorporeal membrane oxygenation is a high-technology therapy which should probably be centralized to only one to two units in Norway. It may be life-saving for selected patients who do not respond to other forms of therapy, but the risk of sequelae is not insignificant.

Critical Illness↗

Trials of lipid-lowering therapy in secondary prevention of coronary heart disease.

The Scandinavian Simvastatin Survival Study showed that a 35% decrease in LDL-cholesterol was accompanied by a 42% reduction in coronary mortality. Even if the period of time is longer than 1 year for the divergence of survival curves in the simvastatin and placebo groups there are reasons to believe that the beneficial effect of lipid lowering is rapid. The effect may be mediated by stabilization of lipid-rich coronary lesions or by effects on endothelium. Lipid-lowering studies in the acute stage of coronary heart disease are suggested.

Anticholesteremic Agents↗

Complement activation and release of tumour necrosis factor alpha, interleukin-2, interleukin-6 and soluble tumour necrosis factor and interleukin-2 receptors during and after cardiopulmonary bypass in children.

C3 activation products, terminal complement complex (TCC), and cytokines including interleukins 6 and 2 (IL-6, IL-2) and tumour necrosis factor-alpha (TNF), and the soluble IL-2 and TNF receptors were determined serially during and up to 48 h after open heart surgery in children. Significant increases were noted in soluble TNF and IL-2 receptor levels postoperatively (p < 0.05). No significant increase over preoperative levels was seen in the cytokines, except for IL-6 which was significantly increased postoperatively (p < 0.01), reaching a maximum 2 h postoperatively. C3 activation products and TCC levels increased significantly after weaning from cardiopulmonary bypass (p < 0.05). The IL-6 response lagged behind the complement activation. We found a significant correlation between duration of cardiopulmonary bypass and IL-6 levels 48 h postoperatively (r = 0.852, p < 0.05). We conclude that the concentration of complement activation products, IL-6 and the soluble TNF and IL-2 receptors are significantly increased after open heart surgery in children. The cytokine receptor response probably reflects some sort of regulatory mechanism.

Cardiopulmonary Bypass↗

Activation of the fibrinolytic, coagulation and plasma kallikrein-kinin systems during and after open heart surgery in children.

Activation of the fibrinolytic, coagulation and plasma kallikrein-kinin systems may be responsible for some of the coagulation disorders and inflammatory sequelae seen after extracorporeal circulation. The activation pattern of these systems was studied in 10 children undergoing open heart surgery with extracorporeal circulation. Blood samples were drawn serially before, during and up to 48 h after surgery. The heparin injection induced a significant elevation of plasmin (PL) (p < 0.05) which stayed elevated during extracorporeal circulation. Antiplasmin (AP) values were reduced at wound closure, while the levels were significantly elevated 48 h postoperatively (p < 0.05). alpha 2-antiplasmin-plasmin (APP) increased significantly perioperatively peaking 10 min after the initiation of cardiopulmonary bypass (p < 0.05). The coagulation markers thrombin-antithrombin (TAT) and the prothrombin fragment F1 & 2 increased significantly, peaking at wound closure and at termination of bypass respectively (p < 0.05). Plasma kallikrein (KK) values increased significantly with subsequent decreased levels of prekallikrein (PKK) and kallikrein inhibitor (KKI) after heparin injection. The KK level stayed elevated during cardiopulmonary bypass (CPB). The proenzyme functional inhibition index (PFI index), defined as the sum of deviations from the control values for proenzyme and functional inhibition values of the coagulation, fibrinolytic and plasma kallikrein-kinin systems, correlated significantly to the duration of cardiopulmonary bypass (p < 0.05). We conclude that open heart surgery in children activates the fibrinolytic, coagulation and plasma kallikrein-kinin systems.

Antifibrinolytic Agents↗

[Cardiac risk in surgery. A review and guidelines for risk evaluation and reduction of cardiac risk in general surgery].

Cardiac complications occur with an incidence of 2-6% and are a main cause (15-20%) of mortality after non-cardiac surgery. Cardiac risk should be determined and reduced by treatment preoperatively and by an intraoperative and postoperative care that has been adjusted to the increased risk. This review provides recommendations concerning risk evaluation and management.

Heart Diseases↗

IS1032 from Acetobacter xylinum, a new mobile insertion sequence.

IS1031 elements constitute a family of related insertion sequences (IS) in Acetobacter xylinum strains. A new IS1031-related element, IS1032, was isolated from A. xylinum ATCC 23770. Southern hybridization analysis showed that one or more sequences similar to IS1032 are present in most of the A. xylinum strains examined. In addition, one copy was detected in Acetobacter aceti ATCC 15973. The transposition of IS1032 was evident from the appearance of an extra insertion in a spontaneous exopolysaccharide-negative mutant of A. xylinum ATCC 23770. IS1032 consists of 916 bp and has imperfect terminal inverted repeats of 14 bp (IR-Left) and 16 bp (IR-Right). A 3-bp target sequence is duplicated upon insertion. IS1032 displays a single open reading frame, encoding a putative 276-amino-acid protein sharing 58% identity with the corresponding protein encoded by IS1031. Thus, IS1032 is a member of the IS1031 family in A. xylinum. A striking degree of nucleotide sequence similarity between IS1032 and ISRm4 from Rhizobium meliloti was found. Furthermore, the IS1031-family transposases also display stretches of amino acid sequence similarities with putative transposases encoded by IS elements from other species.

Amino Acid Sequence↗