PubMed Health⌕ Search

Biomedical subjects

P Toft

Publications and source records attributed to P Toft.

At least 37 records · Page 2Linked to original sources

The cytokine response in a patient undergoing surgery for an ACTH-producing tumor.

The administration of glucocorticoids has been used to inhibit the cytokine production in patients undergoing cardiac surgery during cardiopulmonary bypass. In this case report the cytokine response in a 43-year-old man undergoing operation for an ACTH-producing lung tumor is presented. There had been clinical symptoms for about 18 months and 8 months before operation elevated serum concentrations of ACTH and cortisol were measured. The patient underwent thoracotomy with removal of the tumor and the cytokine response in relation to surgery was measured as plasma concentrations of IL-1 alpha, IL-6, TNF alpha and TNF beta. With the long-lasting high endogenous glucocorticoid production low or undetectable cytokine levels were expected in this patient. However, a marked and prolonged IL-6 and TNF beta response was measured while IL-1 alpha and TNF alpha were detectable in only a few samples. The cytokine response in this patient was different from the response normally found in patients undergoing major surgery.

Adrenocorticotropic Hormone↗

Expression of adhesion and activation molecules on lymphocytes during open-heart surgery with cardiopulmonary bypass.

Open-heart surgery with cardiopulmonary bypass (CPB) and abdominal surgery are associated with lymphocytopenia. We measured a panel of adhesion and activation molecules on lymphocytes to clarify possible association of CPB with increased expression of these molecules. Eight patients undergoing open-heart surgery and eight with abdominal surgery were studied. The adhesion molecules CD11a/CD18 (LFA-1_, CD11c/CD18 and CD44 and the activation molecules CD25, CD69, CD71 and MHCII were measured, using monoclonal antibodies and flow cytometry. Lymphocytopenia was observed during CPB and for some hours after both open-heart and abdominal surgery. The proportion of CD11a/CD18-positive lymphocytes rose from 67.6 +/- 8% to 86.4 +/- 3% after aortic declamping (p < 0.05). The expression of activation molecules CD25, CD69 and CD71 was unchanged during and after open-heart as well as abdominal operations. Thus CPB was associated with increased expression of the adhesion molecule CD11a/CD18 on lymphocytes, while the expression of activation molecules on lymphocytes was unchanged.

CD18 Antigens↗

Effect of methylprednisolone on the oxidative burst activity, adhesion molecules and clinical outcome following open heart surgery.

Following cardiac surgery with cardiopulmonary bypass (CPB), activated granulocytes may be involved with ischaemia/ reperfusion injury. The purpose of this study was to investigate whether steroids could reduce the oxidative burst activity of granulocytes, the expression of adhesion molecules on granulocytes and improve clinical outcome. Sixteen patients undergoing open heart surgery participated in the study. Eight were randomized to receive methylprednisolone (30 mg/kg intravenously) at the start of anaesthesia while eight patients served as a control group. The oxidative burst was measured flow cytometrically using 123-dihydrorhodamine. A panel of adhesion molecules was measured using monoclonal antibodies. Following CPB the oxidative burst activity and the expression of the adhesion molecule L-selectin more than doubled compared to initial values. There was no difference between the steroid group and the control group regarding the expression of adhesion molecules or the oxidative burst activity. In the steroid group the fluid gain during extracorporeal circulation (ECC) was 683 ml (median) compared to 1488 ml in the control group. Steroids prevented hyperthermia in the postoperative period but did not improve the weaning from the ventilator or reduce the stay in the intensive-care unit. In conclusion, treatment with steroids prevented hyperthermia following open heart surgery with CPB and reduced capillary leak during ECC. Methylprednisolone, however, did not reduce the oxidative burst activity or the expression of adhesion molecules on granulocytes following CPB.

Capillary Leak Syndrome↗

The role of cytokines in cardiac surgery.

Cytokines are a large and rapidly expanding group of polypeptides produced by many different cell types. Increasing interest has been focused on the role of cytokines as mediators of metabolic, immunological and endocrine responses to surgery. The cytokine response in patients undergoing cardiac surgery during cardiopulmonary bypass (CPB) is fairly well-defined and dominated by the proinflammatory cytokines IL-6, TNF alpha and IL-8 and the antiinflammatory cytokine IL-10. Little is known about the cytokine response in patients who develop postoperative complications but CPB with mechanical trauma and blood contact to artificial membranes is definitely an unphysiological state and may contribute to an uncontrollable response similar to that of patients with multiorgan failure and septic shock.

Acute-Phase Reaction↗

Contamination of central venous catheters. The skin insertion wound is a major source of contamination.

In a prospective controlled trial we compared the rates of catheter-tip contamination in central venous catheters inserted with or without skin contact. The study was designed so that each patient was their own control. All patients had a single-lumen central venous catheter and a Swan-Gantz sheet inserted through the skin. A Swan-Gantz catheter was inserted and retracted through the sheet thus avoiding contact with skin or subcutaneous tissue. Catheter-tip cultures were performed on removal of catheters. Thirty-three Swan-Gantz catheters were cultured and all were sterile. In the corresponding 33 sheets 16 (48.6%) yielded bacterial growth. Four of the sheets showed growth of more than 15 cfu. In the 26 single-lumen catheters, eight (30.8%) catheter-tips grew bacteria, and four of them had more than 15 colonies. The study supports the theory that the skin-insertion wound is a major source of catheter-contamination.

Adult↗

Changes in lymphocyte subpopulations and adhesion/activation molecules following endotoxemia and major surgery.

Major surgery as well as endotoxin-induced sepsis is accompanied by lymphocytopenia in peripheral blood. The purpose of this study was to investigate the redistribution of lymphocyte subpopulations and adhesion/activation molecules on lymphocytes. Twenty-four rats were included in the investigation. Eight rats received an intraperitoneal injection of E. coli endotoxin (2 mg kg-1), eight rats had a sham operation performed while eight rats received isotonic saline and served as a control group. Blood samples were obtained by making an incision in the tail before and 2 and 5 h after surgery or administration of endotoxin or saline. After isolation of lymphocytes by gradient centrifugation, flow-cytometric immunophenotyping was performed using CD2, CD3, CD4, CD8, CD11/CD18, CD20, CD44 and MHC II monoclonal antibodies. Endotoxemia and surgery were both accompanied by increased serum cortisol, lymphocytopenia, and a decrease in CD2, CD3 and CD4 lymphocytes. Only endotoxemia was followed by a decrease in CD8, CD11/CD18 and CD44 lymphocytes in peripheral blood. Our results show that several of the changes in lymphocyte subpopulations following surgery and sepsis are associated with increased serum cortisol. Sepsis is, in addition, accompanied by an upregulation of adhesion receptors.

Animals↗

Optimum time for neostigmine administration to antagonize vecuronium-induced neuromuscular blockade.

We followed the recovery time course in 46 patients antagonized by neostigmine (0.036 mg kg-1) at different levels of vecuronium-induced neuromuscular blockade ranging from post-tetanic count 1 to train-of-four ratio 0.4 and in 15 patients during spontaneous recovery. Non-linear regression curve fit analyses showed that the optimal time for neostigmine administration was when the first twitch in the train of four (T1) was between 1% and 10%. Visual analyses of the scattergram in which the level of block, when neostigmine was given, was plotted against total recovery time (the time elapsed from administration of the last dose of vecuronium to train-of-four ratio 0.7) gave the same result. The reduction in total recovery time achieved by neostigmine was 32.6 min (SE diff. 6.0 min). To achieve the optimum effect, neostigmine must therefore be given 32.6 min plus the required time for peak effect of neostigmine (5.3-7.1 min), i.e. 37.9-39.7 min, before train-of-four ratio 0.7 is reached. During spontaneous recovery this corresponds to a T1 between 1% and 15%.

Adult↗

[Artificial respiration in patients with acute severe asthma. Mode of ventilation and survival].

The purpose of the study was to register the treatment, mode of ventilation and mortality of patients with acute severe asthma treated with intermittent positive pressure ventilation (IPPV) in a Danish intensive care unit (ICU) during a ten-year period. Fifty-seven patients underwent ventilation on 78 occasions. Fifty-three patients were ventilated with controlled hypoventilation and low PEEP, while four patients were treated with high PEEP. One of the 53 patients receiving controlled hypoventilation and two of the four patients who received high PEEP developed a pneumothorax. All the patients were treated with intravenous steroid and infusion of a beta 2-agonist. Eighty-eight point three per cent received an infusion of theophylline whereas only 16.9% were treated with inhalation of a beta 2-agonist. Eight patients already had irreversible brain damage due to cardiac arrest before arrival to the ICU. Seven of these patients died due to brain damage. All the patients who reached the ICU without brain damage survived. After discharge from the hospital increased mortality was observed among these patients. Some of the patients died due to underestimation from doctors as well as patients of the severity of the asthma. Patients with acute severe asthma requiring IPPV should be ventilated with controlled hypoventilation. A high PEEP is associated with an increased risk of barotrauma. Continuing education of doctors and patients is necessary to increase the use of objective airflow measurement.

Acute Disease↗

Contamination of central venous catheters: use of infusion-lines does not increase catheter-contamination.

In a prospective controlled trial we compared the rates of intraluminal contamination between the two lumens of a double-lumen central venous catheter. One lumen was used for repeat infusions and injections, and the other was permanently connected to a slow infusion of 0.9% NaCl. The study was designed so that the patient was his own control. Twenty-eight catheters were examined and comparison with catheter-tip cultures was performed in 24. Intraluminal culture was performed 67-77 h after insertion of the catheter and catheter-tip culture was performed on removal of the catheter. The contamination rate from catheter-tips was 20.8%, which is acceptable compared with other studies. There was only one positive intraluminal culture in each group (3.6%), and thus no correlation was found between contamination rate and the number of times the infusion-line had been interrupted for use. As for catheter-tip contamination, we found no correlation between infusion of blood-products or parenteral nutrition and contamination rates.

Blood Transfusion↗

Redistribution of granulocytes during adrenaline infusion and following administration of cortisol in healthy volunteers.

Major surgical procedures induce an endocrine metabolic stress response characterized by increased secretion of adrenaline and cortisol. Furthermore, surgical stress is accompanied by granulocytosis in peripheral blood. The granulocytosis may be due to increased adrenaline and cortisol secretion. The purpose of this study was to investigate the redistribution of granulocytes during adrenaline infusion and following administration of cortisol. Granulocytes were isolated from peripheral blood from eight healthy volunteers, labelled with indium-111-tropolene and reinjected. The distribution of granulocytes was imaged by using a gamma camera and calculated with an interfaced computer three times during a control period and three times during a corresponding hour af adrenaline infusion 0.05 micrograms kg b.w.-1 min-1. The distribution was then measured every second h for another 6-h control period and then for 6 h following administration of cortisol 3.6 mg kg b.w.-1. Infusion of adrenaline resulted in granulocytosis in peripheral blood and a reduction of radioactivity of the spleen to 83.0% of the initial value. The effect of adrenaline on the bone marrow was negligible. Cortisol administration was followed by granulocytosis and decreased radioactivity of both the spleen (81.5%) and the bone marrow (79.8%). It is concluded that the spleen is an active immunological organ as both adrenaline and cortisol induces efflux of granulocytes from the spleen. The cortisol induced efflux of granulocytes from the bone marrow explains that granulocytosis also occurs in splenectomized patients after major surgery.

Adult↗

The redistribution of granulocytes following E. coli endotoxin induced sepsis.

Infusion of endotoxin elicits granulocytopenia followed by increased numbers of granulocytes in peripheral blood. The purpose of this study was to investigate the redistribution and sequestration of granulocytes in the tissues following E. coli endotoxin induced sepsis. From 16 rabbits granulocytes were isolated, labelled with Indium and reinjected intravenously. Eight rabbits received an infusion of E. coli endotoxin 2 micrograms kg-1 while eight received isotonic saline. The redistribution of granulocytes was imaged with a gamma camera and calculated with a connected computer before and 2 and 6 hours after infusion of endotoxin or saline. Serum cortisol and interleukin-1 beta were measured. In another seven rabbits, respiratory burst activity and degranulation of granulocytes were measured prior to and from 5 min to 6 hours after infusion of E. coli endotoxin 2 micrograms kg-1 BW. Following infusion of endotoxin, the number of granulocytes in peripheral blood decreased from 2.44 to 0.064 x 10 l-1 two hours later. Within 5 min after infusion the overall oxidative burst of the peripheral blood granulocytes was increased and the granularity had decreased. Serum cortisol and interleukin-1 beta increased significantly. The radioactivity of labelled cells in the bone marrow and spleen decreased to 83.1% and 91.6% of initial values. At the same time there was a transient sequestration of labelled granulocytes in the lungs reaching 117.6% of initial values. The radioactivity of the liver increased continuously to 118.4%. The results indicate that endotoxin induces an efflux in activated granulocytes from peripheral blood, bone marrow and spleen to the lungs and liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Redistribution of granulocytes in patients after major surgical stress.

Major surgery induces a stress response characterized by granulocytosis in peripheral blood, and increased secretion of adrenaline and cortisol. The purpose of this study was to investigate the redistribution of granulocytes in response to major surgical stress. Granulocytes were isolated from eight surgical patients and eight healthy volunteers, labelled with Indium-111-tropolone, and reinjected. The distribution of granulocytes was imaged with a gamma camera and calculated by an interfaced computer before surgery and at 2, 4 and 6 h after the end of surgery. The volunteers served as a control group. In the hours after surgery the radioactivity of the area around the surgical field increased to 410.7% of initial values, while the radioactivity of the spleen decreased to 77.5%. In conclusion, the spleen constitutes a readily mobilizable source of granulocytes. This in vivo model demonstrates pronounced postoperative efflux of granulocytes to the area around the surgical field within hours.

Adult↗

Anthropometric variables as predictors for duration of action of vecuronium-induced neuromuscular block.

To identify the best anthropometric predictor for duration of action of neuromuscular block and to propose a better dosing regimen for vecuronium in obese patients, we studied 67 female patients (body weight 45-126 kg) anesthetized with thiopental, fentanyl, droperidol, and nitrous oxide. Twelve different anthropometric variables were evaluated as predictors for duration of action. Simple and multiple linear, least-squares, regression analyses were used. The predictors with the greatest correlation coefficients for duration of action of the vecuronium induction dose (100 micrograms/kg) were percentage of ideal body weight (%IBW) r2 = 0.389, P = 0.0001) and body mass index (r2 = 0.379, P = 0.0001). Body weight alone was also correlated to duration of action, but the r2 value was less (r2 = 0.312, P = 0.0001). The most significant predictors of the first supplementary dose of vecuronium (33 micrograms/kg) were the sum of subscapularis and suprailiac skin folds divided by surface area (r2 = 0.264, P = 0.0001) and %IBW (r2 = 0.261, P = 0.0001). We conclude that %IBW, the body mass index, and the sum of subscapularis and suprailiac skin folds divided by the surface area are the best predictors of duration of action of a vecuronium neuromuscular block.

Adult↗

[Combined spinal-epidural anesthesia for cesarean section].

A retrospective review was undertaken of 61 consecutive cases of combined spinal and epidural block for caesarean section during the period from 27.3.1988 to 13.12.1991. It was found that combined spinal and epidural block was sufficient in 90% of the cases. In 10% it was necessary to give intravenous analgetic supplementation. A high frequency of intermittent hypotension (75%) was found and 15% developed postdural puncture headache. It is concluded that combined spinal and epidural anaesthesia for caesarean section combine the advances of spinal and epidural anaesthesia. However, smaller or Sprotte spinal needles must be used and more vigorous efforts made to avoid hypotension.

Adult↗

[Hyperthyroidism and heart disease. Is thyrotoxic cardiomyopathy a disease entity?].

Cardiac symptoms have a prominent position in hyperthyroidism. The basic haemodynamic change is an increased cardiac output due to an increased stroke volume and an increased heart rate. Dyspnoea and palpitations are frequent symptoms. ECG-changes such as atrial fibrillation, sinus tachycardia, prolonged atrioventricular conduction and ST-segment changes are seen, but such changes are unspecific. Chest X-ray and echocardiographic studies are often normal, but cardiomegaly and ventricular hypertrophy are seen. The cardiac and non-cardiac symptoms of hyperthyroidism may in part be related to an increased sympathoadrenal activity. The thyroid hormones also exert a direct effect on the heart. Treatment includes specific anti-thyroid medication, beta-blocking agents, digoxin, diuretics and possibly anticoagulant therapy. Congestive heart failure, ventricular hypertrophy and arrhythmia are most commonly seen if other cardiac abnormalities are already present. The existence of thyrotoxic cardiomyopathy as an independent disease is illustrated by two case histories, which also demonstrate the reversibility of this condition.

Adult↗

The concentration of N-acetyl aspartate, creatine + phosphocreatine, and choline in different parts of the brain in adulthood and senium.

The fully relaxed water signal was used as an internal standard in a STEAM experiment to calculate the concentrations of the metabolites: N-acetyl aspartate (NAA), creatine + phosphocreatine (Cr + PCr), and choline (Cho) containing compounds in four different parts of the brain in two age groups of healthy volunteers (20-30 yr, n = 8) and (60-80 yr, n = 8). Furthermore, T1 and T2 relaxation time of the metabolites and signal ratios: NAA/Cho, NAA/Cr + PCr, and Cho/Cr + PCr at TE = 272 msec were calculated. The experiments were carried out using a Siemens Helicon SP 63/84 wholebody MR-scanner at 1.5 T. In the younger age group, the concentration of NAA was significantly higher in the occipital part than in the other three parts of the brain. No significant regional variation was found for any other metabolite concentration. There was a significantly higher concentration of NAA in the occipital part of the brain in the younger age group compared to the older one. No significant regional or age dependent variation was found concerning the T1 and T2 relaxation times.

Adult↗