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Biomedical subjects

L Lindgren

Publications and source records attributed to L Lindgren.

At least 127 records · Page 7Linked to original sources

Pharmacokinetics of glycopyrronium in uraemic patients.

We studied the pharmacokinetics of glycopyrronium in 11 uraemic patients undergoing cadaveric renal transplantation and in seven ASA I control patients undergoing general surgery. Glycopyrronium 4 micrograms kg-1 was given i.v. before induction of anaesthesia. Blood and urine samples were collected for up to 24 h for measurement of glycopyrronium concentrations using a radioreceptor assay. Volume of distribution in the elimination phase (V beta) was similar in both groups, the elimination half-life (T1/2 beta) was longer (P < 0.05), area under the plasma concentration-time curve (AUC) larger (P < 0.01) and plasma clearance (CI) smaller (P < 0.01) in the uraemic patients. In 3 h, mean 0.7 (range 0-3)% and 50 (21-82)% of glycopyrronium was excreted in the urine in the uraemic and healthy patients, respectively (P < 0.001). The 24-h renal excretion was 7 (0-25)% in uraemic and 65 (30-99)% in control patients (P < 0.001). We conclude that the elimination of glycopyrronium is severely impaired in uraemic patients.

Glycopyrrolate↗

Effect of atropine on the QT interval and T-wave amplitude in healthy volunteers.

Prolongation of the QT interval of the ECG represents an imbalance in cardiac autonomic function and may predict cardiac arrhythmia. Vagal activity protects against prolongation of the QT interval which may be associated with flattening of the T-wave of the ECG. The changes in QT interval, T-wave amplitude and respiratory sinus arrhythmia (RSA) were studied after i.v. administration of atropine 20 micrograms kg-1 or placebo to 10 healthy volunteers in a cross-over study. After atropine, a decrease in RSA occurred in all volunteers, but remained at baseline values after placebo. Corrected QT interval (QTc) increased from 410 (20) ms to 454 (11) ms (P < 0.001) 5 min after atropine and remained prolonged for the entire study period (60 min). The T-wave flattened significantly (measured as R:T ratio) up to 30 min, without any changes in the R-wave. No changes in the ECG occurred with placebo.

Adult↗

Increases in hemodynamic variables and catecholamine levels after rapid increase in isoflurane concentration.

BACKGROUND: Ventilation of the lungs with isoflurane in nitrous oxide and oxygen has been shown to increase the plasma concentration of norepinephrine. Whether this increase is related to the tachycardia and increased arterial blood pressures, seen following a sudden increase in the concentration of isoflurane, was tested in humans. METHODS: Twenty-two healthy patients in whom the trachea was intubated were given 15 min of stable isoflurane-O2-air anesthesia [end-tidal concentration of isoflurane (ETIso) of 1.3%] (baseline). Patients were then randomly allocated to one of two groups. For 13 "IsoHigh" patients, the inspired concentration of isoflurane was increased abruptly. In those patients, the ETIso was kept at 2.6% for 10 min, i.e., until the end of the study, after which the depth of anesthesia was reduced. For nine "IsoLow" control patients, the ETIso level of 1.3% was continued until the end of the study. Heart rate, arterial pressures, catecholamine levels, and end-tidal concentration of CO2 were recorded at baseline and at 1, 1.5, 2, 4, 6, and 10 min after increase in isoflurane. RESULTS: IsoHigh patients showed significant increases in heart rate (40% from 84.6 to 118.1 beats/min), systolic arterial pressure (SAP, 23%, from 96.4 to 118.3 mmHg), and diastolic arterial pressure (DAP, 30%, from 53.9 to 70.0 mmHg); all three variables peaked at 2 min. Significant increases occurred also in norepinephrine levels (80%, from 0.342 to 0.615 ng/ml) and in end-tidal concentration of CO2 (from 4.22% to 4.43%), both of which peaked at 4 min. Epinephrine levels did not increase significantly, although significant differences were seen between IsoHigh and IsoLow patients during the trial. IsoLow patients had no changes in these variables. CONCLUSIONS: A sudden increase in isoflurane concentration is associated with a transient but clinically significant increase in heart rate, arterial pressures, and norepinephrine concentration.

Adult↗

Isoflurane inhibits muscle fasciculations caused by succinylcholine in children.

The incidence and intensity of muscle fasciculations as well as the occurrence of cardiac arrhythmias following succinylcholine were evaluated in 36 premedicated children (1.0-5.7 years) after intravenous induction with thiopentone or after inhalation induction with isoflurane (3.75 vol-% in 70% nitrous oxide in oxygen). The study was randomized. In the thiopentone group, fasciculations were seen in all children and in the isoflurane group in 5 of 18 children (P < 0.001). The median of the duration of fasciculations was 15 s with a minimum of 5 s and maximum of 36 s (1st quartile 9 s and 3rd quartile 20 s) in the thiopentone group and 0 (0-15) s with a 1st quartile of 0 and a 3rd quartile of 3 s in the isoflurane group (P < 0.001). No cardiac arrhythmias were noted in either group. In conclusion, isoflurane in nitrous oxide inhibits succinylcholine-induced muscle fasciculations in children.

Anesthesia, Inhalation↗

Changes in the T-wave amplitude of ECG during isoflurane anaesthesia.

R/T-wave amplitude ratio of electrocardiogram (ECG), heart rate (HR) and systolic arterial pressure (SAP) were recorded in 15 patients awake, at 1 minimal alveolar concentration of isoflurane before and during surgery, and in deep anaesthesia (electroencephalogram burst suppression) during surgery. R/T-wave amplitude ratio and HR were sensitive to both surgery and changes in the level of isoflurane anaesthesia; induction of anaesthesia, skin incision and the rapid increase in the concentration of isoflurane all significantly decreased the T-wave amplitude, without influence on the R-wave. Changes in the T-wave amplitude correlated directly to HR. SAP increased at skin incision and decreased when the anaesthesia was deepened. The authors conclude that the R/T-wave amplitude ratio of ECG provides a reliable method for monitoring the sympathetic tone during isoflurane anaesthesia.

Adult↗

Atropine abolishes electroencephalogram-associated heart rate changes without an effect on respiratory sinus arrhythmia during anaesthesia in humans.

Heart rate fluctuates with the electroencephalogram burst suppression pattern during anaesthesia: increasing at burst onset and decreasing at suppression. Heart rate also oscillates with positive pressure ventilation. The effects of atropine on these heart rate changes were studied in 12 patients during isoflurane anaesthesia and positive pressure ventilation at a frequency of 6 cycles min-1. Four additional patients served as controls. A bolus dose of atropine (20 micrograms kg-1 intravenously) abolished the electroencephalogram-correlated heart rate changes; however, the amplitude of respiratory sinus arrhythmia was not changed after atropine. The control mechanism of the burst suppression pattern in electroencephalogram also affects parasympathetic heart rate control. The control mechanisms of respiratory sinus arrhythmia during anaesthesia with positive pressure ventilation differ from those during spontaneous breathing awake.

Adult↗

Improving radioimmonotargeting of tumors. Variation in the amount of L6 MAb administered, combined with an immunoadsorption system (ECIA).

Extracorporeal immunoadsorption (ECIA) is a new method for the selective removal of circulating radiolabeled monoclonal antibodies (MAb) from plasma to increase the uptake in tumor versus normal tissues (T/N-ratio). To ascertain whether the amount of MAb affects T/N ratios immediately and 24 h after ECIA, we used a rat model with two tumor sites--one intramuscular (im) and one below the subrenal capsule (SR). Extracorporeal immunoadsorption was done with an avidin-agarose column after injection of 125I-labeled biotinylated L6 MAb. The animals received 10, 50 or 250 micrograms of L6 only (controls), or followed by ECIA. The efficacy of the procedure in removing plasma activity was 80-95%. For both tumor sites, the highest T/N-ratios were obtained with 10 micrograms L6. All T/N-ratios significantly improved for SR tumors by a factor ranging from 3.2 (lung) to 12.6 (bone marrow). The T/N-ratios were still elevated 24 h after ECIA. Injection of larger amounts of MAb, probably causing a higher degree of tumor saturation, will not necessarily improve the T/N ratio after ECIA.

Adenocarcinoma↗

A general, extracorporeal immunoadsorption method to increase the tumor-to-normal tissue ratio in radioimmunoimaging and radioimmunotherapy.

The aim of this study was to investigate a new extracorporeal immunoadsorption method to improve tumor-to-normal tissue ratios in radioimmunoimaging (RII) and radioimmunotherapy (RIT). We have developed and investigated a general method using biotinylated antibodies and an agarose-avidin column for extracorporeal immunoadsorption. The studies were made in an animal model and extracorporeal immunoadsorption (ECIA) was performed 24 or 48 hr after the injection of 125I-labeled biotinylated antibodies. In athymic rats, heterotransplanted with human malignant melanoma, 90%-95% of the circulating activity was removed with ECIA. The tumor-to-normal tissue ratios at 24 hr was increased 4 times (from 1.2 to 5.1) in the liver, 2.5 times (0.7 to 1.8) in the lung, 4 times (1 to 4) in the kidneys and 4 times (1.4 to 5) in the bone marrow. Whole body activity was reduced by 40%-50%. Tumor-to-organ ratios at 48 hr were increased 3.5 times (from 1.5 to 5.2) in the liver, 2 times (0.9 to 1.7) in the lung, 3 times (1.3 to 3.8) in the kidneys and 4 times (1.4 to 5.5) in the bone marrow. Whole body activity was reduced by 35% when ECIA was performed 48 hr after injection. This study proves that an important reduction in background activity, and thereby an improvement in the tumor-to-background ratio, can be achieved by using this generally applicable, biotin-avidin ECIA method. For RII, the improved ratio increases the possibilities of detecting tumors and metastases in blood-rich organs. For RIT, the procedure may lead to a decreased absorbed dose to bone marrow and other critical organs.

Animals↗

Alpha-human-ANP response to preanesthetic volume expansion and subsequent renal transplantation in diabetic and nondiabetic uremic patients.

alpha-Human atrial natriuretic peptide (ANP) concentrations were measured in 11 diabetic patients with uremia and in 16 nondiabetic uremic controls undergoing renal transplantation after preanesthetic volume expansion with 1000 ml saline solution within 10 min. Two diabetic and seven nondiabetic patients received grafts from living donors and the rest from cadaveric donors. Volume expansion induced a significant increase in the cardiac filling pressures (P less than 0.001), which were kept at that level especially at declamping, which was preceded by mannitol infusion. The baseline mixed venous ANP levels were significantly higher in the diabetic (252 +/- 6 pg/ml) than in the nondiabetic group (103 +/- 14 pg/ml; P less than 0.05). In the nondiabetic group, ANP increased to 177 +/- 40 pg/ml as a response to volume loading (P less than 0.05); it was not clearly changed in the diabetic group. Arterial ANP increased from 267 +/- 55 to 343 +/- 75 pg/ml in the diabetic group (P less than 0.05 and from 102 +/- 17 to 147 +/- 31 pg/ml in the nondiabetic group (P less than 0.05). During transplantation, mixed venous ANP decreased to 125 +/- 55 pg/ml in the diabetic and to 80 +/- 10 pg/ml in the nondiabetic group (P less than 0.001). About 30% of circulating ANP was taken up by the transplant irrespective of postoperative graft function. Two patients in each group showed delayed diuresis requiring postoperative dialysis therapy (22% of all cadaveric transplantations). ANP levels at declamping had no correlation to the outcome of kidney function.

Adult↗

Cardiac arrhythmias and myocardial ischemia after thoracotomy for lung cancer.

The records of 598 patients undergoing a thoracic surgical procedure for lung cancer from 1975 through 1989 were reviewed for occurrence of cardiac arrhythmias and myocardial ischemic events. Atrial tachycardias occurred in 16% (94/598); atrial fibrillation was preponderant (87%), followed by supraventricular tachycardia and atrial flutter. Patients with recurrent episodes of dysrhythmias had a significantly higher mortality rate than those without episodes or with a single episode only (17% versus 2.4%; p less than 0.01). Transient ischemic electrocardiographic changes were documented in 23 patients (3.8%) and myocardial infarction in 7 (1.2%). An abnormal preoperative exercise test result and intraoperative hypotension were strongly associated with both dysrhythmia and ischemia (p less than 0.01). Pneumonectomy, ischemic changes on the electrocardiogram, and cardiac enlargement were also associated with arrhythmias (p less than 0.01). A weaker association (p less than 0.05) was found between postoperative arrhythmias and old myocardial infarction (greater than 6 months), arterial hypertension, and heart failure. Pulmonary function had no predictive value in this respect. A history of angina or old myocardial infarction was predictive of transient postoperative myocardial ischemia but not myocardial infarction. Despite improved anesthetic and monitoring techniques and more frequent use of the intensive care unit postoperatively in the last decade, the incidence of arrhythmias after thoracotomy has not decreased. More effective prevention is needed, particularly for patients with defined preoperative and perioperative risk factors.

Aged↗

Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and peroperative fentanyl.

The effects of the new, highly selective alpha 2-adrenergic agonist, dexmedetomidine, were studied in a randomized, placebo-controlled, double-blind trial in 24 ASA I patients. Dexmedetomidine 0.6 micrograms kg-1 or saline was given i.v. 10 min before induction of anaesthesia. The required dose of thiopentone was significantly (P less than 0.001) smaller in the dexmedetomidine group (mean 4.4 (sd 0.9) mg kg-1) than in the control group (6.9 (1.6) mg kg-1), and the drug attenuated the cardiovascular responses to laryngoscopy and tracheal intubation. The concentration of noradrenaline in mixed venous plasma was smaller in the dexmedetomidine group during all phases of induction (P less than 0.01). During surgery, fentanyl was required in a dose of 0.5 (0.6) mg kg-1 and 2.8 (2.6) mg kg-1 in the dexmedetomidine and control groups, respectively (P less than 0.001). During 2 h postoperative follow-up, oxycodone 0.06 (0.06) mg kg-1 and 0.16 (0.1) mg kg-1 (P less than 0.05) was given to the two groups respectively.

Adrenergic alpha-Agonists↗

Topical anaesthesia of the nasal mucosa for fibreoptic airway endoscopy.

We have compared four methods of topical anaesthesia of the nostril for fibreoptic airway endoscopy in a randomized study with 31 unpremedicated volunteers, each serving as his or her own control. Lignocaine spray, EMLA cream, three cotton swabs soaked in 4% lignocaine solution, or 2% lignocaine gel was applied in a nostril for 3 min. Application of lignocaine spray was rated as the most unpleasant and EMLA cream the least unpleasant. Spray and gel caused an increase in arterial pressure. Anaesthesia of the mucosa, tested by passing a bronchoscope through the nose to the oropharynx was best with lignocaine spray or gel. Gel or EMLA, but not the local anaesthetic applied with swabs, obscured vision. When slight obscurity of vision is not a problem, local anaesthetic gel is recommended for anaesthesia of the nasal mucosa. Premedication or sedation is recommended for all the methods described here.

Administration, Topical↗

Pharmacokinetics of propofol and haemodynamic changes during induction of anaesthesia in uraemic patients.

The pharmacokinetics of an i.v. bolus of propofol 2 mg kg-1 were studied in 10 uraemic patients undergoing renal transplantation and in seven healthy controls matched for age, weight and duration of anaesthesia. Haemodynamic changes during induction of anaesthesia were recorded in the uraemic and in 10 healthy control patients. Pharmacokinetic variables were similar in uraemic and control patients; mean elimination half-lives were 1638 (SD 340) min and 1714 (842) min, respectively. Induction of anaesthesia with propofol was preceded by fentanyl 3 micrograms kg-1. After administration of propofol over 60 s, systolic arterial pressure decreased by 19 (12)%, and by 24 (11)% in the adequately volume loaded uraemic and healthy patients, respectively. Propofol caused a marked peripheral vasodilatation in all patients. A moderate increase in systolic arterial pressure after intubation was statistically significant only in the control patients (P less than 0.01). We conclude that, in terms of pharmacokinetics and haemodynamic changes, propofol may be used safely for the induction of general anaesthesia in uraemic patients.

Adult↗

The effect of amrinone on recovery from severe bupivacaine intoxication in pigs.

Cardiovascular collapse following intravascular bupivacaine may be resistant to treatment. The effect of amrinone on recovery from bupivacaine-induced severe cardiovascular depression was evaluated in 20 pigs (13-26 kg) in a placebo-controlled randomized double-blind study. Under 0.7% isoflurane anesthesia at FIO2 0.21, 0.5% bupivacaine 2 mg.kg-1.min-1 was infused until mean arterial pressure was 40% of the baseline. Cardiac output and heart rate decreased 75% and 50% from the baseline, respectively. The total dose of bupivacaine was 17 +/- 6 (SD) mg.kg-1 in the control and 19 +/- 5 mg.kg-1 in the amrinone group, resulting in mean plasma concentrations of 42 +/- 6 and 53 +/- 19 micrograms.ml-1, respectively. A bolus of amrinone 4 mg.kg-1 (n = 10) was given immediately after cardiovascular depression, followed by an infusion of 0.6 mg.kg-1.min-1. The control animals received corresponding volumes of physiologic saline (n = 10). After cardiovascular depression, the lungs were ventilated with FIO2 1.0 without anaesthetics or sympathomimetic support. Electric activity of the heart ceased in all control animals in 3.9 +/- 2 min after cardiovascular depression despite atropine and external cardiac compression. All animals in the control group and 5 of 10 animals in the amrinone group were given atropine (P less than 0.01). The animals receiving amrinone survived without cardiac compression (P less than 0.0001). During bupivacaine infusion, all animals developed burst suppression in the electroencephalogram. At the time of cardiovascular depression, in 8 of 10 control and in 6 of 10 amrinone animals, the electroencephalogram was isoelectric.(ABSTRACT TRUNCATED AT 250 WORDS)

Amrinone↗

IgE antibodies to Pityrosporum orbiculare and Staphylococcus aureus in patients with very high serum total IgE.

Serum IgE antibodies were detected with the radioallergosorbent test (RAST) to a panel of allergens which included Pityrosporum orbiculare, Candida albicans, Trichophyton rubrum, Cladosporium herbarum, Staphylococcus aureus, animal dander, deciduous tree pollens, grass pollens and foods in 81 consecutive patients with total IgE greater than or equal to 3000 kU/l. Data on atopic and infectious disease characteristics were collected by a questionnaire. IgE antibody concentrations to P. orbiculare were significantly higher than to the other fungi and of the same magnitude as those to animal danders and pollens. High levels of P. orbiculare IgE antibodies were associated with current eczema, especially when it was the only atopic manifestation and demanding specialist care. IgE antibodies to P. orbiculare had the best explanatory value for current eczema in logistic regression analysis. Head-neck-face dermatitis was also associated with high levels of specific IgE to the yeast. IgE antibodies to S. aureus were detected in few patients and at low concentrations. Six patients had a history of systemic staphylococcal infections and presented a clinical picture, which was very similar to the hyperimmunoglobulinaemia E syndrome. Among the six were the two cases with the highest levels of IgE antibodies to S. aureus. The demonstration of high levels of IgE antibodies to P. orbiculare, which is a major part of human normal skin microflora, suggests that allergy to this yeast plays an important pathogenic role in eczema.

Adolescent↗

Ketamine anaesthesia in a patient with septic shock.

A 71-year-old male patient was operated on in a septic state (tachycardia, hypotonia, fever peaks, disorientation) because of an occluding tumour of the biliary tract. Ketamine was used as the main anaesthetic. Mean arterial pressure increased markedly and diuresis started during the anaesthesia. The inotropic support (dopamine, dobutamine, noradrenaline) could be reduced. Ketamine anaesthesia seemed to have a beneficial haemodynamic effect in septic shock.

Aged↗

Alfentanil inhibits muscle fasciculations caused by suxamethonium in children and in young adults.

The effect of alfentanil on suxamethonium-induced muscle fasciculations was studied in a double-blind study in 34 children (mean age 6.8 years) and in 30 adults (mean age 20 years). After pretreatment with either alfentanil 50 micrograms kg-1 or saline, each patient was anaesthetized with a sleep dose of thiopental followed by suxamethonium 1.5 mg kg-1 for endotracheal intubation. Compared to the control groups, alfentanil significantly decreased the intensity of visible muscle fasciculations caused by suxamethonium. In children, the duration of muscle fasciculations was shorter in the alfentanil than in the control group. In adults, the intensity rather than the duration of fasciculations was attenuated by alfentanil. The inhibition of fasciculations caused by alfentanil was also demonstrated in children in the surface electromyogram recorded on the biceps. There was no circulatory response to endotracheal intubation in the groups pretreated with alfentanil.

Adolescent↗