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Biomedical subjects

K Jaeger

Publications and source records attributed to K Jaeger.

At least 37 records · Page 2Linked to original sources

Bacterial lipases from Pseudomonas: regulation of gene expression and mechanisms of secretion.

Lipases from Pseudomonas bacteria are widely used for a variety of biotechnological applications. Overexpression in heterologous hosts like Escherichia coli failed to produce enzymatically active lipase prompting to study the molecular mechanisms underlying the regulation of lipase gene expression and secretion. The prototype lipase from P. aeruginosa is encoded in a bicistronic operon which is transcribed from two different promotors, one of which depends on the alternative sigma factor RpoN (sigma(54)). Recently, a two-component regulatory system was identified as an element controlling transcription of the lipase operon. P. aeruginosa lipase is secreted via a type II pathway. The cytoplasmic prelipase contains a 26 amino acid N-terminal signal sequence mediating secretion across the inner membrane via the Sec-machinery. In the periplasm, lipase folds into an enzymatically active conformation assisted by its specific intermolecular chaperone Lif and by unspecific accessory folding catalysts including Dsb-proteins which catalyze the formation of a disulfide bond. Enzymatically active and secretion-competent lipase is finally transported through a complex secretion machinery consisting of 12 different Xcp-proteins of which XcpQ forms a pore-like structure in the outer membrane allowing the release of lipase into the extracellular medium. Biotechnologically important lipases from Burkholderia glumae and P. alcaligenes also use such a type II secretion pathway whereas lipases from P. fluorescens and Serratia marcescens, which lack a typical signal sequence are secreted via a type I pathway. Future challenges to produce Pseudomonas lipases may include artificial up-regulation of lipase gene transcription and construction of more efficient expression strains in which both folding and secretion of lipase are optimized.

Gene Expression Regulation, Bacterial↗

Tracheal injury as a sequence of multiple attempts of endotracheal intubation in the course of a preclinical cardiopulmonary resuscitation.

Management of the difficult airway requires an appropriate approach based on personal clinical experiences. For every physician involved in rescue and emergency medicine, it is important to know the difficult airway algorithm and be familiar with alternative techniques of managing the difficult airway. We report a case of tracheal injury caused by multiple attempts at intubating the trachea. Based on current knowledge, apart from surgical equipment for cricothyroidotomy the laryngeal mask airway (LMA) and the Combitube (ETC) should be available on any ambulance vehicle staffed by an emergency physician. In future, blind intubation through the intubating laryngeal mask airway (ILMA) could offer a new opportunity.

Cardiopulmonary Resuscitation↗

[In Process Citation]

Early post-operative infections remain the most important cause of morbidity and mortality in patients following orthotopic liver transplantation (OLTx). Since polymorphonuclear neutrophils (PMNs) are one of the major determinants of antimicrobial defence, the alteration of their functions may influence the outcome of infection in these patients. Ciclosporin predominantly used as immunosuppressive drug following organ transplantation inhibits superoxide anion production during respiratory burst (RB) of PMNs. Growth factors have been shown to modulate the RB of PMNs in healthy volunteers. It has been examined whether PMNs from patients under immunosuppression following OLTx can be primed by in vitro administration of interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF), and granulocyte colony stimulating factor (G-CSF). For flow-cytometric evaluation, leukocytes were obtained as supernatant following sedimentation and were incubated with IL-3 (500 U ml-1), IL-3 and GM-CSF (500 U ml-1), or IL-3 and G-CSF (500 U ml-1). The RB was measured by intracellular oxidation of non-fluorescent dihydrorhodamine to green fluorescent rhodamine after induction of phorbol 12-myristate 13-acetate (PMA) or a combination of tumour necrosis factor alpha (TNF-alpha) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). Following stimulation with PMA, the RB of patients following OLTx could be increased significantly after priming with the combination of IL-3/G-CSF (p < 0.03); following stimulation with TNF-alpha/FMLP the RB could be increased significantly by IL-3 (p < 0.01), IL-3/G-CSF (p < 0.002), and IL-3/GM-CSF (p < 0.002). Regarding the clinical administration of IL-3, GM-CSF and G-CSF following OLTx, the role of these cytokines for prophylaxis or treatment of early postoperative infections should be further investigated.

Journal Article↗

Anaesthesiological and criterial care aspects regarding the treatment of patients with arteriovenous malformations in interventional neuroradiology.

In recent years, the neuroradiological treatment of cerebral and spinal arteriovenous malformations (AVMs) has undergone significant evolution and improvement. Endovascular embolisation procedures of AVMs are mainly performed under general anaesthesia. Different pathophysiological characteristics of patients with AMVs must be considered for the choice of the anaesthetic procedures. Anaesthesiological management must aim at maintaining stable intracranial haemodynamics; thus, the drugs used must be evaluated according to their effects on brain perfusion, brain metabolism, and intracranial pressure. Rapid recovery to normal central nervous functions should be obtained postoperatively. Close-meshed neurological surveillance should be exercised in order to detect immediately any alteration of neurological state. In summary, anaesthesiological management of interventional neuroradiology is based on the same well-established principles as anaesthesia in neurosurgery.

Anesthesia, General↗

Anaesthesia with propofol decreases FMLP-induced neutrophil respiratory burst but not phagocytosis compared with isoflurane.

Propofol has been reported to produce a dose-dependent inhibition of phagocytosis and superoxide anion production during the respiratory burst (RB) of polymorphonuclear cells (PMNs) in vitro. In this randomized, blinded study, these two parameters were compared during propofol or isoflurane anaesthesia in patients undergoing elective interventional embolization of cerebral arterio-venous malformations. Anaesthesia was performed with continuous intravenous propofol 6-8 mg kg-1 h-1 (n = 15) or isoflurane 0.8-1.0% end tidal (n = 15). Heparinized blood was drawn before, and 2 and 4 h after induction of anaesthesia. The RB in isolated leucocytes was measured with the fluorescent dye rhodamine after ex vivo induction by Escherichia coli or tumour necrosis factor alpha/N-formyl-methionyl-leucylphenylalanine (TNF-alpha/FMLP). Phagocytosis was carried out in whole blood after incubation with fluorescein isothiocyanate (FITC)-labelled, opsonized E. coli and also measured with a flow cytometer. The two groups were similar in terms of biometric data and haemodynamic responsiveness. After 4 h of propofol or isoflurane anesthesia, the mean (SD) phagocytosis of E. coli was 93.2% (7.0%) and 94.3% (9.2%), respectively, of that before anaesthesia. The percentage of PMN with RB activity following TNF-alpha/FMLP stimulation was significantly reduced after 2 h (80.9% (24.2%); P < 0.05) and 4 h (53.7% (27.3); P < 0.05) of anaesthesia with propofol compared with the values before induction. This effect of propofol anaesthesia was significantly different from the effect of isoflurane anaesthesia. In contrast to published in vitro results, 4 h of anaesthesia with propofol did not reduce the phagocytotic capacity of human blood PMN more than isoflurane anaesthesia.

Adolescent↗

Procalcitonin in fever of unknown origin after liver transplantation: a variable to differentiate acute rejection from infection.

OBJECTIVE: Does procalcitonin (PCT) differentiate between infection and rejection after liver transplantation in patients with fever of unknown origin? DESIGN: Open prospective trial. SETTING: Transplant intensive care unit at a university hospital. PATIENTS: Forty patients after liver transplantation. INTERVENTIONS: Liver biopsy for the diagnosis of rejection and transcutaneous aspiration cytology for monitoring of lymphocyte activation. MEASUREMENTS: Procalcitonin from EDTA plasma, Acute Physiology and Chronic Health Evaluation II, and sepsis score. RESULTS: Eleven patients experienced an infectious complication resulting in an increase in PCT concentrations (2.2-41.7 ng/mL). Eleven patients had a rejection episode; none of these patients showed a rise in PCT concentrations. The statistical difference between PCT concentrations in rejection and infection was significant (p<.05) on the day of diagnosis. CONCLUSION: PCT allows for differentiation between rejection and infection in patients with fever of unknown origin. Elevation of PCT plasma concentrations develops early postoperatively from operation trauma, and in the case of fever of unknown origin, with no rise in PCT, a rejection may be suspected.

APACHE↗

[Carbon monoxide poisoning].

Carbon monoxide (CO) is a product of incomplete burning of coals and carbon compounds and is a gas without any typical taste, colour or smell. Defective radiators or gas pipes, open fireplaces, fires and explosions are sources of unintended CO production and inhalation. CO bonds with haemoglobin much more readily than oxygen does. CO toxicity causes impaired oxygen delivery and utilisation at cellular level. It affects different sites within the body, but has its most profound impact on the organs with the highest oxygen requirement. CO concentration and the intensity and duration of inhalation determine the extent of intoxication. Following basic life support, assisted or controlled ventilation with 100% oxygen is essential during emergency care. Hyperbaric oxygenation (HBO) is the preferred therapeutic option for releasing CO from its binding to haemoglobin. It has been shown that CO may cause lipid peroxidation and leukocyte-mediated inflammatory changes in the brain, a process that may be inhibited by HBO. Patients with neurological symptoms including loss of consciousness and expectant mothers should undergo HBO treatment, no matter how high their CO levels are. Neonates and in-utero fetuses are more vulnerable due to the natural leftward shift of the dissociation curve of fetal haemoglobin, a lower baseline pO2 and carboxyhaemoglobin levels at equilibration that are 10-15% higher than maternal levels. Physicians need to be aware of the potential occurrence of this life threatening hazard so that appropriate emergency treatment can be administered and fatalities prevented.

Brain↗

Organoapatite growth on an orthopedic alloy surface.

We report here a method to coat orthopedic metals with the artificial bone material organoapatite. The growth of organoapatite on titanium alloy surfaces of foils and porous cylinders involves sequential preadsorption of poly(L-lysine) and poly(L-glutamic acid) on metal, followed by exposure to organoapatite-precipitating solutions. The organoapatite characterization of the coating was carried out by transmission electron microscopy, electron diffraction, scanning electron microscopy, energy-dispersive X-ray scattering, powder X-ray diffraction, FT-IR, and elemental analysis. The preadsorbed poly(amino acids) in the form of a self-assembled bilayer of oppositely charged macromolecules can lead to a surface coverage of titanium alloy in the range of 70-90%. The deposition mechanisms could involve the surface capture of embryonic crystals and the nucleation of apatite on the bilayer. Bioabsorbable organoapatite could serve as a tissue-engineering scaffold for bone regeneration into porous implants.

Apatites↗

Effect of magnetic resonance imaging on human respiratory burst of neutrophils.

It is known that low intensity magnetic fields increase superoxide anion production during the respiratory burst of rat peritoneal neutrophils in vitro. We investigated whether the high intensity magnetic fields (1.5 T) during magnetic resonance imaging can influence the human neutrophil function under in vivo conditions. Blood samples were obtained from 12 patients immediately before and after magnetic resonance imaging (mean time 27.6(+/-11.4 min)). The induced respiratory burst was investigated by the intracellular oxidative transformation of dihydrorhodamine 123 to the fluorescent dye rhodamine 123 via flow cytometry. The respiratory burst was induced either with phorbol 12-myristate 13-acetate, Escherichia coli, N-formyl-methionyl-leucylphenylalanine or priming with tumor necrosis factor followed by FMLP stimulation. There was no significant difference between the respiratory burst before and after magnetic resonance imaging, irrespective of the stimulating agent. Short time exposure to a high intensity magnetic field during magnetic resonance imaging seems not to influence the production of radical species in living neutrophils.

Adult↗

GM-CSF increases in vitro the respiratory burst of human neutrophils after liver transplantation.

OBJECTIVE: Superoxide production by polymorphonuclear neutrophils (PMNs) under cyclosporin A (CsA) therapy following kidney transplantation is impaired. We investigated if the respiratory burst of PMNs is similarly depressed in patients undergoing CsA treatment following orthotopic liver transplantation (OLTx). Additionally, the in vitro influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the superoxide anion production was examined during the respiratory burst. PATIENTS: 10 patients after OLTx and 10 healthy blood donors (control group). MEASUREMENTS AND RESULTS: PMNs were stimulated with bacteria (Escherichia coli) or a combination of tumour necrosis factor alpha (TNFalpha) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). The respiratory burst was measured by oxidation of non-fluorescent dihydrorhodamine to the fluorescent rhodamine by means of flow cytometry. No differences in respiratory bursts from OLTx patients compared to those from healthy blood donors could be seen. Under TNFalpha/FMLP stimulation, the respiratory burst was significantly increased after in vitro incubation with GM-CSF (500 U ml(-1)) in patients following OLTx (from 58.2 to 74.5 %) as well as in the control group (from 47.4 to 61.9%). CONCLUSIONS: Our results demonstrate that superoxide production is not impaired under CsA treatment following OLTx. The respiratory burst of these patients' PMNs can even be augmented by GM-CSF in vitro.

Cyclosporine↗

Neutrophil respiratory burst following liver transplantation: in vitro effects of granulocyte colony-stimulating factor.

Early postoperative infections and septic complications are predominant causes of morbidity and mortality in patients following orthotopic liver transplantation (OLTx). Prophylactic granulocyte colony-stimulating factor (G-CSF) administration after OLTx was found to decrease the number of sepsis episodes and sepsis-related mortality. Since polymorphonuclear neutrophils (PMNs) are one of the major determinants of antimicrobial defense, alteration of their functions may influence the development of sepsis in these patients. Therefore, we investigated in vitro whether or not priming with G-CSF affects the neutrophils' respiratory burst (RB) in immunosuppressed liver-transplanted patients. Venous blood was drawn from liver allograft recipients (n=12) between the 5th and 15th day postoperatively. Patients without clinical signs of infection or rejection were included in this study. Leukocytes were obtained as supernatant following sedimentation and incubated with 1000 IE ml-1 G-CSF. The RB was measured by the intracellular oxidation of non-fluorescent dihydrorhodamine to the fluorescent rhodamine by flow cytometry. The results were expressed as a percentage of increasing stimulation compared to the control responses, which are made up of the percentage of cells with RB reaction after stimulation with phorbol ester (PMA), bacteria (E. coli), or the combination of a cytokine (TNF-alpha) and a bacterial peptide (FMLP) in the absence of G-CSF. In vitro priming with G-CSF resulted in significantly increased activity of the RB after PMA (from 71.7% to 85.6%) and TNF-alpha/FMLP (from 58.4% to 72.7%) stimulation. These data demonstrate that G-CSF in vitro augments the RB of PMNs, thereby suggesting a possible therapeutic role for G-CSF as immunomodulating agent during bacterial and fungal infections following OLTx.

Flow Cytometry↗

[Quality of life after breast reduction-plasty].

We have investigated the improvement in the quality of life in 384 breast reduction patients within a seven-year postoperative follow-up. Through the use of a questionnaire (recall of n = 223 patients), we sought to establish the patient's most compelling reason for seeking this surgical procedure. In addition, the effect of the operation on the patient's quality of life was investigated. Preoperatively, the main complaint was pain in the shoulder girdle in 77% of the patients, followed by 67% patients suffering from lower and thoracic back pain symptoms, whereas 51% defined mastodynia as their primary complaint. 95% of the patients noted a remarkable improvement in the quality of their professional and social lifes. 94% were able to specify this improvement as an increase in the feeling of self-esteem, 53% showed up with amelioration of selfconfidence. 95% of the patients felt that the breast reduction had a positive influence on their sexual behaviour and personal relationships. Our study reveals that breast reduction surgery offers not only an aesthetic improvement but also the relief of preoperative pain and discomfort, leading to important improvements in the patient's quality of life.

Adolescent↗

[Value of the laryngeal mask in emergency care--a survey of North German emergency physicians].

In clinical routine, the laryngeal mask airway (LMA) has proved an alternative to both endotracheal intubation and mask ventilation. In a survey among North German emergency physicians, aspects such as doctors' acquaintance with the LMA, the degree of ist distribution, its use and its potential benefits under non-hospital emergency conditions were evaluated. Seventeen per cent (n = 162) of physicians responded to the questionnaire, 75% of them (n = 122) anaesthetists. Although 73% (n = 119) were familiar with the use of the LMA from clinical experience, and again 73% would welcome having LMA use and application as part of the training of non-academic members of ambulance teams, only 24% (n = 37) of the responding doctors have an LMA on their emergency ambulances and merely twelve (7.4%) physicians reported actually using the LMA, one of them unsuccessfully. Sixty-three per cent considered the LMA the first-choice alternative in an unexpected "can't-ventilate-can't-intubate" situation. Use of the LMA should be extended in emergency medicine especially as its application is relatively easy to learn in clinical routine.

Attitude of Health Personnel↗