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Biomedical subjects

K Peter

Publications and source records attributed to K Peter.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Continuous peridural analgesia vs patient - controlled intravenous analgesia for pain therapy after thoracotomy].

OBJECTIVES: Continuous epidural analgesia (EA) and patient-controlled intravenous analgesia (PCA) are widely used for postoperative pain control. Studies indicate that both analgesic regimens provide good analgesia after major surgery. However, because of the following reasons it is still unclear whether one of the two modes of application is superior. First, there are conflicting data regarding the differences in pain relief and drug use between epidural and intravenous administration of opioids. Second, in many studies epidural analgesia is performed by a combination of local anaesthetics and opioids. Third, reduced morbidity was observed only in some of the studies, in which epidural analgesia provided better pain relief than systemic opioid supply. Despite these conflicting results, EA with local anaesthetics and fentanyl as well as PCA with piritramid, a highly potent mu-agonist, are routinely used in Germany. The purpose of this study was to compare these two treatments for analgesic efficacy, pulmonary function, incidence of side effects and complications in patients undergoing thoracotomy. METHODS: In this prospective randomized trial 50 patients were included. For postoperative pain control 25 patients (EA group) received thoracic epidural infusion of local anaesthetics (bupivacaine 0.125% or ropivacaine 0,2%) and fentanyl 4,5 microg/ml with a flow rate of 4-10 ml/h. 25 patients received intravenous PCA with piritramid (bolus 2, 5 mg, lock out 15 minutes, maximum of 25 mg/4 h, no background infusion). RESULTS: Analgesia at rest and while coughing, as evaluated by visual analogue scale, was significantly better in the EA group. EA also resulted in superior values of pulmonary function tests, general condition and a lower incidence of sedation and nausea. In contrast, patients with EA reported distinctly more pruritus than patients with PCA. Duration of hospital stay was shorter in the EA group, but this difference did not reach statistical significance. There was one atelectasis in the EA group. No major complications related to EA or PCA were observed. CONCLUSION: In this study EA with local anaesthetics and fentanyl provided superior postoperative pain control and a lower incidence of sedation and nausea compared to intravenous PCA with piritramid, but there was no superiority as to pulmonary complications and duration of hospital stay.

Analgesia, Patient-Controlled↗
PubMed2000

Continuous axillary brachial plexus analgesia with low dose morphine in patients with complex regional pain syndromes.

In this prospective pilot study, nine patients suffering from complex regional pain syndrome of the arm were treated with morphine 0.16 mg h-1 (3.84 mg day-1) applied continuously through an axillary brachial plexus catheter. In all of them an oral analgesic medication including the less potent opioid tramadol had not provided sufficient pain relief. During regional treatment, patients were kept in hospital and physiotherapy was carried out frequently in order to improve strength and function of the affected arm. Pain at rest and during movement as well as grip strength were assessed at first visit, during morphine infusion and at a long-term follow-up visit. All assessments improved significantly during plexus analgesia. There were no major opioid related side-effects. The results from this pilot study indicate that continuous axillary brachial plexus analgesia with low dose morphine might be beneficial in patients suffering from complex regional pain syndrome of the arm.

Adult↗
PubMed2000

HLA-A*0201 restricted CD8+ T-lymphocyte responses to malaria: identification of new Plasmodium falciparum epitopes by IFN-gamma ELISPOT.

The role of antigen specific CD8+ T-lymphocytes in mediating protection against sporozoite-induced malaria has been well established in murine models. In humans, indirect evidence has accumulated suggesting a similar protective role for antigen-specific CD8+ T-lymphocytes. Nevertheless, the low frequency of circulating specific cells together with the lack of sensitive methods to quantify them has hampered the direct assessment of their function. Using a combination of short-term cell culture and IFN-gamma ELISPOT, we studied CD8+ T-lymphocyte responses to a panel of HLA-A*0201 binding peptides. In addition to confirming the response to already described epitopes, we also identified five new CD8+ T-lymphocyte epitopes. These epitopes are presented in pre-erythrocytic stages gene products of Plasmodium falciparum 7G8 strain and correspond to the following protein segments: circumsporozoite (CS) 64-72, 104-113, 299-308 and 403-411; liver stage antigen (LSA-1) repeat region; sporozoite surface protein 2 or thrombospondin related anonymous protein (SSP2/TRAP) 78-88 and 504-513. Four of these peptides are conserved amongst all published sequences of P. falciparum strains. We conclude that the modified IFN-gamma ELISPOT assay is a sensitive technique to monitor antigen-specific CD8+ T-lymphocyte responses in human malaria which may help in the improvement and assessment of the efficacy of malaria subunit vaccines.

Adult↗
PubMed2000

Health-related quality of life and post-traumatic stress disorder in patients after cardiac surgery and intensive care treatment.

OBJECTIVES: Health-related quality of life and patient satisfaction have become important end points in cardiac surgery. Post-traumatic stress disorder has been described in patients with life-threatening heart disease. In this study, we investigated the occurrence of post-traumatic stress disorder in a sample of patients after cardiac surgery and compared health-related quality of life and patient satisfaction between patients with and without evidence of post-traumatic stress disorder. METHODS: We studied 80 patients serially admitted to the intensive care unit after cardiac surgery (bypass grafting, n = 51; aortic valve replacement, n = 29). Health-related quality of life was assessed with the use of the SF-36 Health Status Questionnaire. Post-traumatic stress disorder was measured with a previously validated instrument (the Post-Traumatic Stress Syndrome 10-Questions Inventory), and 20 different aspects of life satisfaction were quantified on a scale ranging from 0 to 10. For measurements of health-related quality of life and post-traumatic stress disorder, age- and gender-comparable healthy individuals, as well as patients with cardiovascular diseases, served as control groups. RESULTS: Patients who had cardiac surgery described high life satisfaction summary scores (156 of a maximum of 200 points) and only small impairments in physical and mental SF-36 summary scores when compared with healthy control groups (median reduction 7.15, P <.05). Patients with evidence of post-traumatic stress disorder (n = 15) reported the lowest SF-36 mental health summary scores when compared with patients without stress disorder (38.3 vs 48.4, P =.004) and rated their life satisfaction lower (121.5 vs 162.0, P =.002). CONCLUSIONS: Patients who have had cardiac surgery demonstrate a high life satisfaction with an acceptable degree of physical and mental health-related quality of life. Impairments in psychosocial function and life satisfaction were found in a subgroup of patients with evidence of post-traumatic stress disorder.

Aged↗
PubMed2000

Urinary iodine concentration follows a circadian rhythm: a study with 3023 spot urine samples in adults and children.

Our overall aim is to monitor iodine supply in a prospective study before and after the September 1998 increase of salt iodide content in Switzerland. Because iodide is supplied by alimentation, we moreover wondered whether urinary iodine concentration (UI) is governed by circadian rhythmicity. Forty-two subjects (18 males and 24 females, including 13 children) collected 3023 urine spots between May 1996 and May 1998, at a rate of three to five samples per month, at any time of the day. The results show that circadian rhythmicity of UI in adults and children was found independent of the individual subject, age, gender, and season. Lowest UI levels were found between 8-11 h. A curve increasing progressively between 12 and 24 h was obtained. UI returned to base-line levels between 21 and 22 h in children only. UI peaks occurred 4-5 h after main meals; children's peaks occurred later than that of adults. Although the existence of a circadian rhythm of UI is probably universal, its profile, however, depends on alimentation. Because nadir of UI is represented by morning spots, this might seem an appropriate collecting period. In view of the significant circadian rhythmicity of UI, studies with restriction of sampling time to morning hours, for example, cannot be directly compared with studies in which urine is sampled all over the day.

Adolescent↗
PubMed2000

Differential regulation by troglitazone of plasminogen activator inhibitor type 1 in human hepatic and vascular cells.

Troglitazone, a novel oral insulin sensitizer, normalizes increased plasma activity of plasminogen activator inhibitor type 1 (PAI-1) in hyperinsulinemic patients such as women with polycystic ovary syndrome and patients with type 2 diabetes mellitus. However, underlying mechanisms have not yet been fully elucidated. Human hepatic and vascular cells, the main sources of circulating PAI-1, were studied in cell culture. In human hepatic cells, PAI-1 accumulated in conditioned medium by 23% within 24 h after exposure to 3 microg/mL troglitazone (P = 0.001). The accumulation depended on the concentration of troglitazone, but not that of insulin (known to stimulate PAI-1 synthesis). By contrast, in human aortic smooth muscle cells, 3 microg/mL troglitazone decreased basal PAI-1 expression by 23% (P = 0.037) and decreased transforming growth factor-beta-induced expression by 34% (P = 0.026). Concomitant insulin had no effect. Tissue-type plasminogen activator was decreased by 38% (P = 0.002). In human endothelial cells, PAI-1 was diminished by 32% (P < 0.001), whereas tissue-type plasminogen activator was unaffected. The results suggest that the reduction in plasma activity of PAI-1 induced by troglitazone in patients may reflect both directly mediated diminution of its elaboration from vessel walls and indirectly mediated reduction of its hepatic synthesis secondary to attenuation of hyperinsulinemia (known to increase the hepatic synthesis of PAI-1).

Aorta↗
PubMed2000

[Therapeutic inhibition of platelets in a acute coronary syndrome and in coronary intervention: mechanisms and clinical results].

Platelets play a crucial role in the pathogenesis of atherosclerosis and especially in the final ischemic consequences such as acute coronary syndromes. Furthermore, platelets are central mediators of acute or subacute complications of coronary interventions. Therefore, therapeutic inhibition of platelet function is of major interest in cardiology. The following review describes three different therapeutic strategies for platelet inhibition and provides a representative overview on the clinical results of studies based on these strategies. First, the mechanism of acetylsalicylic acid is described and the strong meta-analytic data demonstrating a convincing positive clinical effect is discussed. Second, the mode of action of the thienopyridines is described and initial clinical results are discussed. Third, the inhibition of the platelet integrin receptor GP IIb/IIIa is described as a potent way to block the final common pathway of platelet stimulation. The structural description of GP IIb/IIIa is followed by a structural classification of the available GP IIb/IIIa inhibitors. Clinical studies, meanwhile including several thousands of patients, are discussed based on representative examples. Finally, unresolved issues regarding the various GP IIb/IIIa inhibitors, such as differences in receptor affinity and specificity, intrinsic activation and GP IIb/IIIa inhibitor induced thrombocytopenia are, discussed.

Abciximab↗
PubMed2000

Measurement of respiratory impedance by impulse oscillometry--effects of endotracheal tubes.

Impulse Oscillometry is a new, noninvasive method to measure respiratory impedance, i.e. airway resistance and reactance at different oscillation frequencies. These parameters are potentially useful for the monitoring of respiratory mechanics in the critically ill patent with respiratory dysfunction. The endotracheal tube, used to mechanically ventilate these patients, however, represents an additional nonlinear impedance that introduces artifacts into the measurements. The objective of this work was therefore to investigate the effects of clinically available endotracheal tubes on resistance and reactance of an in vitro analogue of the respiratory system. Additionally, the effects of decreasing the compressible gas volume in this experimental model, as a simulation of decreased lung capacity and compliance, was investigated. Impulse oscillometric measurements of the test analogue gave highly reproducible results with and without an endotracheal tube. The tubes had significant influence on the measurement of the test object at all frequencies investigated. Changes of low frequent reactance were negligible - at least if repetitive measurements of the same system are performed - for realistic measurement of airway resistance, a correction of the tube impedance or measurement of the pressure distal of the tube is required. Resistance increased and low frequent reactance decreased significantly with decreasing gas volume. These changes were of magnitudes higher than the variations due to the introduction of the endotracheal tubes. Our results suggest that changes of respiratory reactance measured with impulse oscillometry may be used as a monitoring parameter in intubated patients.

Airway Resistance↗
PubMed1999

Platelet function during and after thrombolytic therapy for acute myocardial infarction with reteplase, alteplase, or streptokinase.

BACKGROUND: Changes in platelet aggregation (PA) and platelet surface receptor expression induced by thrombolytic therapy for acute myocardial infarction may influence the rate of initial reperfusion and early reocclusion. METHODS AND RESULTS: In the RAPID-1 (Reteplase Angiographic Phase II International Dose-finding study), RAPID-2 (Reteplase vs Alteplase Patency Investigation During myocardial infarction), INJECT (INternational Joint Efficacy Comparison of Thrombolytics), and GUSTO-3 (Global Use of Strategies To Open occluded coronary arteries) trials, 126 patients were enrolled in a single center. Patients were treated with either conventional alteplase (100 mg/180 min; n=15), accelerated alteplase (100 mg/90 min; n=21), reteplase 10+10-U double bolus (n=50), reteplase 10+5-U double bolus (n=15), reteplase 15-U single bolus (n=15), or streptokinase (1.5 MU/60 min; n=10). PA (after stimulation with ADP), P-selectin expression and fibrinogen binding to glycoprotein (GP) IIb/IIIa (determined by flow cytometry with and without stimulation with ADP), and levels of soluble P-selectin, prothrombin fragments F1 and F2, thrombin-antithrombin complexes (TAT), and antithrombin III (ATIII) were determined. PA decreased significantly at 1 and 2 hours in patients treated by 10+10-U reteplase or by streptokinase. Fibrinogen binding to platelet GP IIb/IIIa followed a similar pattern. Significant thrombin generation and significantly elevated thrombin levels during thrombolysis were reflected by increased F1 and F2 fragments and TAT levels in all treatment groups. ATIII levels decreased significantly during thrombolytic therapy. CONCLUSIONS: A decrease in PA in patients treated by reteplase or streptokinase compared with alteplase could be observed in the early phase. Double bolus (10+10 U) reteplase and streptokinase resulted in lower PA at 1 and 2 hours than therapy with accelerated alteplase. Total fibrinogen and fibrinogen binding to GP IIb/IIIa tended to be lower during the first 2 hours after reteplase than after accelerated alteplase.

Double-Blind Method↗
PubMed1999

Heparin inhibits ligand binding to the leukocyte integrin Mac-1 (CD11b/CD18).

BACKGROUND: The clinical benefits of heparin reach beyond its anticoagulative properties. Recently, it has been described that leukocytes adhere on immobilized heparin mediated by the integrin Mac-1 (CD11b/CD18, alphaMbeta2, or CR3). Because inhibition of this versatile adhesion molecule could explain various aspects of the beneficial clinical effects of heparin, we evaluated whether soluble heparin modulates Mac-1 function in vitro and in vivo. METHODS AND RESULTS: Binding of unfractionated heparin to Mac-1 on PMA-stimulated monocytes and granulocytes was directly demonstrated in flow cytometry, whereas no binding of heparin was detected on unstimulated leukocytes. Unfractionated heparin inhibited binding of the soluble ligands fibrinogen, factor X, and iC3b to Mac-1. Adhesion of the monocytic cell line THP-1 and of peripheral monocytes and granulocytes to immobilized ICAM-1 was impaired by unfractionated heparin, to the same extent as with inhibition of Mac-1 by monoclonal antibodies such as c7E3. Low-molecular-weight heparin also inhibits binding of fibrinogen to Mac-1. Additionally, flow cytometry of whole blood preparations of patients treated with unfractionated heparin revealed an inhibitory effect of heparin on the binding of fibrinogen to Mac-1 that correlates (n= 48, r=0.63, P<0.001) to the extent of prolongation of the activated partial thromboplastin time. CONCLUSIONS: We describe a pharmacologically relevant property of heparin that may contribute to its benefits in clinical use. The binding of heparin to Mac-1 and the resulting inhibition in binding of Mac-1 ligands may directly modulate coagulation, inflammation, and cell proliferation.

Animals↗
PubMed1999

Platelet activation as a potential mechanism of GP IIb/IIIa inhibitor-induced thrombocytopenia.

The blockade of the platelet integrin glycoprotein (GP) IIb/IIIa has proved to be an effective antiplatelet therapy. Profound thrombocytopenia has repeatedly been described as an adverse effect in patients treated with GP IIb/IIIa inhibitors, but its mechanism has not been elucidated yet. With use of flow cytometry, the activation status of platelets was monitored in 26 patients presenting with acute myocardial infarction who were treated with the GP IIb/IIIa inhibitor abciximab alone or in combination with the fibrinolytic agent reteplase. Fibrinogen and PAC-1 (a GP IIb/IIIa activation-specific monoclonal antibody) binding, as well as P-selectin expression on unstimulated platelets were constant in 25 patients throughout a follow-up of 7 days. In 1 patient (D.F.), the percentage of platelet-binding fibrinogen increased from 2.2% to 17.8%, for PAC-1 from 2.8% to 13.2%, and for P-selectin expression from 10.2% to 58.3% 10 minutes after the start of treatment. Furthermore, D.F. had a decrease in single platelet count in ethylenediaminetetraacetic acid-, citrate-, and heparin-anticoagulated and native blood. Blood films revealed platelet aggregates. In vitro testing of D.F.'s blood 2 and 4 weeks after initial admission demonstrated a reinduction of fibrinogen and PAC-1 binding to platelets, an increase of P-selectin expression, and formation of platelet aggregates following exposition of platelets to abciximab in vitro. In summary, this report describes the induction of platelet activation by a GP IIb/IIIa inhibitor in vivo and reinduction in vitro in direct association with thrombocytopenia. Platelet activation by GP IIb/IIIa inhibitors may be one potential mechanism for GP IIb/IIIa inhibitor-induced thrombocytopenia.

Abciximab↗
PubMed1999

Effects of mutations in the cytoplasmic domain of integrin beta(1) to talin binding and cell spreading.

Integrins are transmembrane proteins linking the extracellular matrix or certain cell-cell contacts to the cytoskeleton. To study integrin-cytoskeleton interactions we wanted to relate talin-integrin interaction to integrin function in cell spreading and formation of focal adhesions. For talin-binding studies we used fusion proteins of glutathione S-transferase and the cytoplasmic domain of integrin beta(1) (GST-cytobeta(1)) expressed in bacteria. For functional studies chimeric integrins containing the extracellular and transmembrane parts of beta(3) linked to the cytoplasmic domain of beta(1) were expressed in CHO cells as a dimer with the alpha(IIb) subunit. Point mutations in the amino acid sequence N(785)PIY(788) of beta(1) disrupted both the integrin-talin interaction and the ability of the integrin to mediate cell spreading. COOH-terminal truncation of beta(1) at the amino acid position 797 disrupted its ability to mediate cell spreading, whereas the disruption of talin binding required deletion of five more amino acids (truncation at position 792). A synthetic peptide from this region of beta(1) (W(780)DTGENPIYKSAV(792)) bound to purified talin and inhibited talin binding to GST-cytobeta(1). The ability of the mutants to mediate focal adhesion formation or to codistribute to focal adhesions formed by other integrins correlated with their ability to mediate cell spreading. These results confirm the previous finding that a talin-binding site in the integrin beta(1) tail resides at or close to the central NPXY motif and suggest that the integrin-talin interaction is necessary but not sufficient for integrin-mediated cell spreading.

3T3 Cells↗
PubMed1999

Efficient endocytosis of the cystic fibrosis transmembrane conductance regulator requires a tyrosine-based signal.

We previously demonstrated that the cystic fibrosis transmembrane conductance regulator (CFTR) is rapidly endocytosed in epithelial cells (Prince, L. S., Workman, R. B., Jr., and Marchase, R. B. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 5192-5196). To determine the structural features of CFTR required for endocytosis, we prepared chimeric molecules consisting of the amino-terminal (residues 2-78) and carboxyl-terminal tail regions (residues 1391-1476) of CFTR, each fused to the transmembrane and extracellular domains of the transferrin receptor. Functional analysis of the CFTR-(2-78) and CFTR-(1391-1476) indicated that both chimeras were rapidly internalized. Deletion of residues 1440-1476 had no effect on chimera internalization. Mutations of potential internalization signals in both cytoplasmic domains reveal that only one mutation inhibits internalization, Y1424A. Using a surface biotinylation reaction, we also examined internalization rates of wild type and mutant CFTRs expressed in COS-7 cells. We found that both wild type and A1440X CFTR were rapidly internalized, whereas the Y1424A CFTR mutant, like the chimeric protein, had approximately 40% reduced internalization activity. Deletions in the amino-terminal tail region of CFTR resulted in defective trafficking of CFTR out of the endoplasmic reticulum to the cell surface, suggesting that an intact amino terminus is critical for biosynthesis. In summary, our results suggest that both tail regions of CFTR are sufficient to promote rapid internalization of a reporter molecule and that tyrosine 1424 is required for efficient CFTR endocytosis.

Amino Acid Sequence↗
PubMed1999

[In Process Citation]

Intensive care medicine for both surgical and medical patients has a common scientific and clinical basis. In critically ill patients the medical conditions are complex and can be managed only by specialists thoroughly trained in intensive care medicine. Therefore, surgeons as well as anesthesiologists must have a detailed theoretical and clinical knowledge of intensive care medicine. Surgical training places the emphasis on operative skills, while intraoperative management of the patient by the anesthesiologist calls for skills involved in intensive care medicine. Interdisciplinary cooperation between specialists is essential to improve the quality of intensive care medicine further. The cooperation that already exists between surgeons and anesthesiologists makes closer collaboration in the future a logical step.

Journal Article↗
PubMed1999

Comparison of five sedation scoring systems by means of auditory evoked potentials.

OBJECTIVE: To review five sedation scoring systems and to determine their correlation with an objective method for assessing the level of sedation by means of auditory evoked potentials (AEP) in critically ill patients. DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit in a university hospital. PATIENTS: Ninety-five consecutive patients requiring sedation during intensive care therapy. MEASUREMENTS AND RESULTS: Previous studies have shown that auditory evoked potentials, especially latencies of the midlatency component N(b), could serve as an indicator of depth of anaesthesia. In the present study we used this electrophysiological method to evaluate sedation during intensive care therapy. Changes in latency of peak N(b) were compared with various levels of sedation assessed by five established sedation scoring systems. As in anaesthesia, latencies of N(b) increased with increasing depth of sedation. Among the scoring systems, the one developed by Ramsay correlated best with changes in N(b) latency (r2=0.68). The coefficient of determination, r2, of the other scores ranged from 0.56 to 0.61. CONCLUSION: For the assessment of sedation, several scoring systems have been introduced into clinical practice, but the differentiation of deeper sedation levels, especially, remains poor. In this study we compared auditory evoked potentials, as an objective method with which to assess the level of sedation, with five different sedation scoring systems. In comparison with changes in latency of the midlatency component N(b), Ramsay's sedation score showed the closest correlation. Objective electrophysiological monitoring is desirable during long-term sedation.

APACHE↗