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Biomedical subjects

R Larsen

Publications and source records attributed to R Larsen.

At least 73 records · Page 4Linked to original sources

Total intravenous anaesthesia with propofol and remifentanil in paediatric patients: a comparison with a desflurane-nitrous oxide inhalation anaesthesia.

BACKGROUND: Remifentanil is a new rapid-acting and ultra-short acting mu-opioid receptor agonist with few reports from use in children. Therefore, we compared a propofol-remifentanil-anaesthesia (TIVA) with a desflurane-N2O-anaesthesia (DN) with particular regard to the recovery of characteristics in children. METHODS: 50 children (4-11 yr) scheduled for ENT surgery were randomly assigned to receive TIVA (n = 25) or DN (N = 25). After standardised i.v. induction of anaesthesia in both groups with remifentanil, propofol and cisatracurium, TIVA was maintained with infusion of propofol and remifentanil. Ventilation was with oxygen in air. DN was maintained with desflurane in 50% N20. The administration of volatile and intravenous anaesthetics was adjusted to maintain a surgical plane of anaesthesia. At the end of surgery all anaesthetics were terminated without tapering and early emergence and recovery were assessed. In addition, side effects were noted. RESULTS: Both anaesthesia methods resulted in stable haemodynamics but significantly higher heart rate with desflurane. Recovery did not differ between the groups except for delayed spontaneous respiration after TIVA. Spontaneous ventilation occurred after 11 +/- 03.7 min versus 7.2 +/- 2.8 min (mean +/- SD, TIVA versus DN), extubation after 11 +/- 3.7 min versus 9.4 +/- 2.9 min, eye opening after 11 +/- 3.9 min versus 14 +/- 7.6 min and Aldrete score > or = 9 after 17 +/- 6.8 min versus 17 +/- 7.5 min. Postoperatively, there was a significant higher incidence of agitation in the DN group (80% vs. 44%) but a low incidence (< 10%) of nausea and vomiting in both groups. CONCLUSION: In children, TIVA with remifentanil and propofol is a well-tolerated anaesthesia method, with a lower peroperative heart rate and less postoperative agitation compared with a desflurane-N2O based anaesthesia.

Adenoidectomy↗

E-mail influence messages of type-A scoring managers.

In a study of 158 managers' e-mail influence messages to subordinates, managers' self-reported Type-A scores were positively associated with personal responsibility, legitimate supervisors' authority, and pressure tactics, and negatively correlated with reward from supervisor tactics.

Administrative Personnel↗

Itraconazole maintenance treatment for histoplasmosis in AIDS: a prospective, multicenter trial.

PURPOSE: To study the efficacy and safety of maintenance treatment with itraconazole for disseminated histoplasmosis in patients with AIDS. PATIENTS AND METHODS: This was a prospective, multicenter, open-label study conducted at university-based hospitals participating in the AIDS Clinical Trial Group (ACTG). Forty-six AIDS patients with mild to moderate disseminated histoplasmosis who had successfully completed 12 weeks of induction treatment with itraconazole were treated with itraconazole, 200 mg once daily (42 patients) or 400 mg once daily (4 patients). Patients were followed at monthly intervals with clinical and laboratory assessment for relapse or toxicity. Primary outcome measures were relapse of histoplasmosis and survival. Secondary outcome measures included drug-limiting toxicity and changes in serum and urine Histoplasma polysaccharide antigen (HPA) levels. RESULTS: Two patients relapsed during a median follow-up period of 87 weeks. The 1-year relapse-free rate was estimated to be 95.3% (95% CI, 85.3%-99.7%). One relapse may have been related to poor adherence to treatment and the second to concurrent administration of rifampin. From the start of maintenance treatment, the estimated 1-year survival rate was 73.0% (95% CI, 67.5%-77.9%). Five patients discontinued treatment because of suspected drug toxicity, three of whom had possible or probable hepatotoxicity. Median serum and urine HPA levels declined significantly during treatment. The only patient in whom antigen levels rose >2 U developed clinical relapse 1 week later; antigen levels were unavailable in the other relapsing patient. CONCLUSIONS: Itraconazole, 200 mg daily, is effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. It is generally well tolerated, but clinicians should be alert for drug interactions and possible hepatotoxicity.

AIDS-Related Opportunistic Infections↗

High-performance liquid chromatographic analysis of Peptide T in rabbit plasma with on-line column enrichment.

The present paper describes the development of a simple and sensitive analytical method for quantification of Peptide T (PT) in rabbit plasma, using standard analytical equipment and on-line column enrichment, without prior extraction, clean-up or derivatization. The analytical procedure was found to be accurate, precise and linear. The accuracy was 100% (range 97-103%) and the mean precision was 8% (range 3-14%) for all (n=6) concentrations (0, 15, 50, 100 and 200 ng/ml). The total recovery was found to be approximately 80%, and it was found to be dependent upon the injection rate onto the extraction column. The correlation between added and found concentrations was 0.9982, and the limit of detection was estimated to be around 5 ng/ml. The method is therefore found to be suitable for bioavailability studies, involving Peptide T, in rabbits.

Administration, Intranasal↗

Role of platelet-activating factor in hepatocellular Ca2+ alterations during hemorrhagic shock.

A role of the potent proinflammatory Ca2+ agonist platelet-activating factor (PAF) on hepatocellular Ca2+ homeostasis and oxidant injury was investigated, since Ca2+ dysregulation has been demonstrated as a pivotal pathomechanism causing hepatic dysfunction during hemorrhagic or septic shock. In anesthetized male Sprague-Dawley rats, blood was withdrawn to a mean arterial blood pressure of 40 mm Hg for 60 min. Rats were resuscitated with 60% of shed blood and threefold the shed blood volume of lactated Ringers' (shock group). After 60 min of resuscitation, hepatocytes were isolated by portal collagenase perfusion. Hepatocellular Ca2+ uptake (Caup2+), initial rate of Ca2+ influx (Cain2+), and membrane Ca2+ flux (Caflux2+) were determined using 45Ca2+ incubation techniques. Hepatocyte oxidant injury was fluorometrically determined by thiobarbituric acid reactive substances. Caup2+ (3.37 +/- 0.15 vs. 2. 53 +/- 0.08 nmole Ca2+/mg protein), Cain2+ (0.42 +/- 0.1 vs. 0.27 +/- 0.02 nmole Ca2+/mg protein/min), and Caflux2+ (31.3 +/- 4.3 vs. 16.9 +/- 2.4 pmole Ca2+/mg/min) significantly increased in the untreated shock group compared to untreated sham-operated rats (P < 0.05). The specific PAF receptor antagonist BN52021 given 5 min before (5 mg/kg b.w.) and continuously during resuscitation (5 mg/kg/hr) significantly reduced Caup2+ in the shock group (2.73 +/- 0.2; P < 0.01) and prevented hepatocyte lipid peroxidation (shock: 91.9 +/- 1; shockBN52021: 66.7 +/- 2 nmole/mg wet weight; P < 0.01). These data suggest that platelet-activating factor plays a pivotal role in promoting hepatocyte Ca2+ overload during hemorrhagic shock by releasing Ca2+ agonistic mediators and inducing oxidative membrane alterations both of which are capable of enhancing cellular Ca2+ influx.

Animals↗

[Deferoxamine-conjugated hydroxyethyl starch reduces reperfusion injury to the liver following hemorrhagic shock].

UNLABELLED: Deferoxamine is known to reduce the iron-dependent generation of toxic oxygen-derived radicals during reperfusion of ischaemic tissue. The present study investigates the antioxidative properties of a deferoxamine-conjugated hydroxyethyl starch solution and its effects on the hepatic microcirculation in a haemorrhagic-shock rat model. METHODS: Anaesthetized Sprague-Dawley rats were tracheotomized, prepared for invasive haemodynamic monitoring, and subject to haemorrhagic shock (MAP = 40 mmHg during 60 min). The animals were resuscitated blood-free with lactated Ringer's (RILA, n = 10), gelatin (GELA, n = 10), hydroxyethyl starch (HES, n = 10), or deferoxamine-conjugated HES (DFO, n = 8) solution (MAP > or = 70 mmHg). After 1 h of resuscitation the hepatic microcirculation was investigated by intravital microscopy, the glutathione concentration was measured in liver homogenate, and the thiobarbituric acid reactive substances (TBARS) were determined as markers of lipid peroxidation. RESULTS: Resuscitation resulted in restoration of MAP to > or = 70 mmHg within a short time. The volume required to stabilise the arterial pressure during 1 h of resuscitation was significantly less in the DFO group compared with HES, GELA, and RILA. Significantly higher glutathione levels in liver homogenate as well as decreased TBARS levels were observed in the DFO group. The shock-induced increase of leukocyte adhesion in liver sinusoids was significantly attenuated by DFO. CONCLUSION: DFO significantly attenuates shock-induced oxidative stress, thereby reducing the early inflammatory reaction and improving the hepatic microcirculation.

Animals↗

[Remifentanil with propofol or isoflurane. A comparison of the recovery times after arthroscopic surgery].

OBJECTIVES: Due to its unique pharmacokinetics, the new esterase-metabolised opioid remifentanil results in rapid post-anesthesia recovery. The aim of this clinical investigation was to compare recovery times after remifentanil anaesthesia in combination with hypnotic concentrations of either propofol or isoflurane. Dosages used in the study protocol were based on recommendations by the pharmaceutical manufacturer. METHODS: Patients (ASA status I-II) scheduled for elective arthroscopy were included in this trial. Without premedication in the morning, anaesthesia was induced identically in both groups: remifentanil bolus (1 microgram/kg), start of remifentanil-infusion (0.5 micrograms/kg/min), followed immediately by propofol (ca. 2 mg/kg). For maintenance of anaesthesia remifentanil (0.25 micrograms/kg/min) was combined with either a propofol infusion of 0.1 mg/kg/min or 0.5 MAC isoflurane (= 0.6 vol. %) in O2/air. Anaesthetic delivery was discontinued simultaneously with termination of surgery and recovery times were recorded. RESULTS: A total of 40 patients were studied at random in two groups of 20 each with comparable demographic data and anaesthetic technique (Tables 1 and 2). In both groups emergence was very rapid. Recovery times were significantly shorter for remifentanil-isoflurane than for remifentanil-propofol (Table 3): spontaneous ventilation 5.1 vs 8.1 min (P < 0.05), extubation 5.5 vs 8.6 min (P < 0.02), post-anaesthesia recovery score > or = 9 of 10 points 6.2 vs 11.3 min (P < 0.01), and arrival at PACU 16.2 vs 19.2 min (P < 0.01). Mild to moderate shivering was noted in 40% of all patients (9 cases following isoflurane, 7 following propofol). CONCLUSIONS: Using the manufacturer's recommended dosages, emergence after remifentanil anaesthesia is more rapid with 0.5 MAC isoflurane than with 0.1 mg/kg/min propofol. These results are most probably due to the different pharmacological properties of both co-anaesthetics, especially the applied dosages, and to different interactions with remifentanil. Present clinical experience suggests that a further dose reduction, especially for propofol, is possible. For both remifentanil groups emergence was remarkably rapid between return of consciousness and the awake state (on-off phenomenon), which might contribute to post-anaesthesia safety.

Adult↗

[Organ specific expression pattern of a carbon monoxide generating stress protein (hemoxygenase-1/heatshock protein 32) following hemorrhagic shock].

OBJECTIVE: Recent evidence suggests a possible role for Haeme oxygenase (HO)-derived carbon monoxide (CO) in the regulation of vascular tone through elevation of cyclic 3'-5' guanosine monophosphate (cGMP). Previous work from our laboratory has shown that blockade of the HO pathway by tin-protoporphyrin-IX (SnPP) after resuscitation from hemorrhage leads to a specific and profound increase in portal resistance while neither systemic nor hepatic arterial resistance are affected. We therefore investigated the organ-specific expression pattern of the stress-inducible protein haeme oxygenase-1/heat shock protein 32 after haemorrhage and resuscitation. MATERIALS AND METHODS: After approval of the protocol by the local review board, male Sprague-Dawley rats (n = 6/group) were anaesthetised with pentobarbitone, instrumented for assessment of central haemodynamics and subjected to haemorrhagic hypotension (40 mm Hg for 1 h) followed by resuscitation with 60% shed blood and Ringer's solution or a time-matched sham protocol. Samples of liver, spleen, kidney intestine, aorta, and lungs were harvested 5 h after the onset of resuscitation and subjected to Western-blot analysis using a specific anti-rat HO-1/hsp 32 antibody (StressGen, Sidney, Canada). RESULTS: Resuscitation with shed blood/Ringer's solution restored central haemodynamics and acid-base status while significant haemodilution was observed. Haemorrhage and resuscitation led to strong induction of HO-1 in the liver and slight induction in aortic tissue, while no increase in steady-state protein levels was observed in the other organs studied. CONCLUSION: These results suggest a specific contribution of the HO/CO pathway to maintenance of low hepatic portal resistance in vivo in a clinically relevant model of haemorrhagic shock and adequate resuscitation.

Animals↗

Automated image analysis applied to the odontoblast-predentine region in undemineralized sections of human permanent third molars.

A computerized histomorphometric analysis was made by Karnovsky-fixed, hydroxethylmethacrylate embedded and toluidine blue/pyronin-stained sections to determine: (1) the two-dimensional size of the coronal odontoblasts given by their cytoplasm:nucleus ratio; (2) the ratio between the number of coronal odontoblasts and dentinal tubules; and (3) the relation between odontoblast size and adjacent predentine. All conditions were measured in relation to three well-defined sectioning profiles of the dentinal tubules. The sections were randomly taken from 10 unerupted and erupted third-molar crowns. Sixty-three photomicrographs (x100), equally distributed among the three sectioning profiles, were scanned in a high-resolution scanner to produce images for the analysis. After initial user interaction for the description of training classes on one image, an automatic segmentation of the images with respect to odontoblast cell nuclei, cytoplasm and background was computed by statistical discriminant analysis. In longitudinal profiles of the dentinal tubules the cytoplasm:nucleus ratio in erupted teeth was 3.1 +/- 0.54, and the mean of the odontoblast cell:dentinal tubule ration was 1.19 +/- 0.20. Analysis of cytoplasm:nucleus ratio and the adjacent predentine in relation to the chosen sectioning profiles disclosed that there was less variation in the predentine measurements in the longitudinal sections. Thus, in future two-dimensional studies of the odontoblast-predentine region only longitudinal sectioning profiles should be analysed. The use of advanced image processing on undemineralized tooth sections provides a rational foundation for further work on the reactions of the odontoblasts to external injuries including dental caries.

Analysis of Variance↗

Role of nitric oxide in the regulation of the hepatic microcirculation in vivo.

BACKGROUND/AIMS: Nitric oxide (NO) is an important mediator in the regulation of vascular tone. However, no data exist on the physiological role of NO in the regulation of the hepatic microcirculation. This study was designed to evaluate the role of NO in the hepatic microcirculation in vivo under physiological conditions. METHODS: The hepatic microcirculation was investigated in anesthetized rats by intravital fluorescence microscopy after injection of fluorescein-isothiocyanate-labeled erythrocytes. Following assessment of baseline sinusoidal perfusion, animals were randomly treated with L-NMMA (n=6), L-arginine (n=6), nitroprusside sodium (NPS, n=5) or a comparable volume of NaCl (n=4). Drugs were given through a portal vein catheter at three doses (Dx), each followed by intravital microscopy. L-NMMA was given: 5 mg/kg (D1), 25 mg/kg (D2), 50 mg/kg (D3); L-arginine 30 mg/kg (D1), 150 mg/kg (D2), 300 mg/kg (D3); and NPS continuously 80 microg x kg(-1) x h(-1). RESULTS: L-NMMA induced a significant increase of mean arterial blood pressure (MAP) (114 vs. 129 mm Hg; p<0.05). In contrast, MAP of NPS-treated animals decreased (107 vs. 91 mm Hg; p<0.01) whereas MAP of animals receiving L-arginine did not significantly differ. Sinusoidal blood flow revealed dose-dependent changes: L-NMMA significantly decreased perfusion of sinusoids (D1: 65%, D2: 57%, D3: 50% of baseline, p<0.05). Injection of L-arginine increased the sinusoidal flow even with the lowest dose (D1: 137%, D2: 133%, D3: 123%, p<0.05). Continuous infusion of NPS had little effect on sinusoidal blood flow at the first and second times of microscopy but sinusoidal blood flow was significantly increased at the third time (D1: 103%, D2: 106%, D3: 122%). CONCLUSIONS: Inhibition of NOS results in a dose-dependent disturbance of the hepatic microcirculation despite significantly increased MAP, whereas L-arginine increases the sinusoidal blood flow. The results indicate an important role for NO in the regulatory mechanisms of hepatic sinusoidal perfusion under physiological conditions.

Animals↗

Total intravenous anaesthesia using propofol, gamma-hydroxybutyrate or midazolam in combination with sufentanil for patients undergoing coronary artery bypass surgery.

Total intravenous anaesthesia (TIVA) using propofol, gamma-hydroxybutyrate (GHB) or midazolam in combination with sufentanil was investigated in 45 patients undergoing coronary artery bypass grafting (CABG). Anaesthesia was induced with sufentanil, etomidate and pancuronium. After endotracheal intubation, anaesthesia was continued with sufentanil (2 micrograms kg-1 h-1) for all patients. Patients were randomized to receive supplementary propofol (2 mg kg-1 h-1, n = 15), gamma-hydroxybutyrate (20 mg kg-1 h-1, n = 15) or midazolam (0.06 mg kg-1 h-1, n = 15). Haemodynamic measurements were performed after induction and at various times in the pre-bypass period. In the propofol group, a significant decrease in heart rate (HR 12% +/- 3%), cardiac index (CI 23% +/- 4%), mean arterial pressure (MAP 16% +/- 3%) and left ventricular stroke work index (LVSWI 17% +/- 4%) occurred until sternotomy was performed. With the exception of cardiac index, both midazolam and gamma-hydroxybutyrate produced similar haemodynamic effects: cardiac index was temporarily decreased (19% +/- 4%) by midazolam and remained unchanged after gamma-hydroxybutyrate. In both groups, sternotomy was followed by temporary hypertension, associated with a significant rise in systemic vascular resistance. No electrocardiographical signs of ischaemia were observed in any patient. In the case of propofol and midazolam, gamma-hydroxybutyrate showed adequate haemodynamic stability especially after induction of anaesthesia and may also be a suitable agent for total intravenous anaesthesia in patients with coronary artery disease. However, during sternotomy, supplementary administration of opioids was required.

Aged↗

The addition of clonidine to prilocaine for intravenous regional anaesthesia.

The effect of the addition of clonidine 2 micrograms kg-1 to prilocaine 0.5% for intravenous regional anaesthesia (IVRA) in the arm was investigated in 56 healthy patients using a randomized, double-blind study. The characteristics of the sensory and motor block, quality of analgesia, development of post-operative pain sensations and haemodynamic variables were studied in three groups (IVRA with prilocaine, IVRA with prilocaine and clonidine, IVRA with prilocaine and systemic application of clonidine at tourniquet release). There were no significant differences between the groups concerning the onset and recovery characteristics of sensory and motor blockade, post-operative pain or side effects. In those patients receiving clonidine, mean arterial pressure decreased significantly (24-28%, respectively) after tourniquet release, while heart rate remained unchanged. Clonidine as an adjunct to prilocaine seems to be of limited benefit during and after intravenous regional anaesthesia.

Adrenergic alpha-Agonists↗

Antiproliferative effect of fermented milk on the growth of a human breast cancer cell line.

In vivo and in vitro studies have shown an antitumor activity of Lactobacilli in colon cancer, and some epidemiologic studies have indicated a reduced risk of breast cancer in women who consume fermented milk products. We studied the direct effect of milk fermented by five bacteria strains (Bifidobacterium infantis, Bifidobacterium bifidum, Bifidobacterium animalis, Lactobacillus acidophilus, and Lactobacillus paracasei) on the growth of the MCF7 breast cancer cell line. Our results showed a growth inhibition induced by all fermented milks, even though B. infantis and L. acidophilus were the most effective (85% inhibition after 9 days). The antiproliferative effect was not related to the presence of bacteria in fermented milk, and neither whole milk (crude or ultrahigh temperature sterlizied) nor its main fractions (lactalbumin or beta-lactoglobulin fraction) affected cell growth. Our findings suggest the presence of an ex novo soluble compound produced by lactic acid bacteria during milk fermentation or the microbial transformation of some milk components in a biologically active form. Although the mechanism of the antitumor activity is not clear, the present study suggests the potentiality offered by fermented milk as producers of compounds with antiproliferative activity useful in the prevention and therapy of solid tumors like breast cancer.

Animals↗

Recombinant N-terminal fragment of bactericidal/permeability increasing protein (rBPI21) prevents shock-induced microcirculatory alterations in the liver.

OBJECTIVE: To investigate the effects of the recombinant 21-kilodalton N-terminal fragment of recombinant bactericidal and permeability increasing protein (rBPI21) on leukocyte adhesion and the hepatic microcirculation after hemorrhagic shock. DESIGN: Prospective, randomized, blinded, and placebo-controlled experimental study. SETTING: University research laboratory. SUBJECTS: Anesthetized Sprague-Dawley rats, weighing 220 to 250 g. INTERVENTIONS: Rats were subjected to 60 mins of hemorrhagic shock and subsequent resuscitation to sufficiently restore systemic circulation. The microcirculation of the liver was investigated by intravital fluorescence microscopy 5 hrs after hemorrhagic shock. Four shock groups were compared with a sham-control group. Shock groups received either rBPI21 (10 mg/kg) or placebo either before or after shock period. MEASUREMENTS AND MAIN RESULTS: No differences were observed in hemodynamic, respiratory, or metabolic parameters between the shock groups. However, the hepatic microcirculation showed severe deterioration 5 hrs after shock, indicated by significantly narrowed sinusoids in all shock groups compared with controls (8.5 +/- 0.3 microm vs. 10.0 +/- 0.4 pm). Leukocyte adhesion was markedly increased to comparable values in both placebo groups (619 cells/mm2 and 644 cells/mm2; sham, 168 cells/mm2). Neutralization of endotoxin by administration of rBPI21 before or after shock resulted in plain reduction of pathologic leukocyte-endothelial interaction (138 cells/mm2 and 85 cells/mm2). CONCLUSION: The results support the hypothesis that endotoxin induces microcirculatory alterations after shock, and further suggest a potentially beneficial role of rBPI21 in the treatment of posttraumatic endotoxin-induced inflammatory reactions.

Animals↗