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Biomedical subjects

F Wagner

Publications and source records attributed to F Wagner.

At least 37 records · Page 2Linked to original sources

The optimal radiologic method for assessing spinal canal compromise and cord compression in patients with cervical spinal cord injury. Part II: Results of a multicenter study.

STUDY DESIGN: A multicenter, retrospective study using computed tomographic and magnetic resonance imaging data to establish quantitative, reliable criteria of canal compromise and cord compression in patients with cervical spinal cord injury. OBJECTIVES: To develop and validate a radiologic assessment tool of spinal canal compromise and cord compression in cervical spinal cord injury for use in clinical trials. SUMMARY OF BACKGROUND DATA: There are few quantitative, reliable criteria for radiologic measurement of cervical spinal canal compromise or cord compression after acute spinal cord injury. METHODS: The study included 71 patients (55 men, 16 women; mean age, 39.7 +/- 18.7 years) with acute cervical spinal cord injury. Causes of spinal cord injury included motor vehicle accidents (n = 36), falls (n = 20), water-related injuries (n = 8), sports (n = 5), assault (n = 1), and farm accidents (n = 1). Canal compromise was measured on computed tomographic scan and T1- and T2-weighted magnetic resonance imaging, and cord compression at the level of maximum injury was measured on T1- and T2-weighted magnetic resonance imaging. All films were assessed by two independent observers. RESULTS: There was a strong correlation of canal compromise and/or cord compression measurements between axial and midsagittal computed tomography, and between axial and midsagittal T2-weighted magnetic resonance imaging. Spinal canal compromise assessed by computed tomography showed a significant although moderate correlation with spinal cord compression assessed by T1- and T2-weighted magnetic resonance imaging. Virtually all patients with canal compromise of 25% or more on computed tomographic scan had evidence of some degree of cord compression on magnetic resonance imaging, but a large number of patients with less than 25% canal compromise on computed tomographic scan also had evidence on magnetic resonance imaging of cord compression. CONCLUSIONS: In patients with cervical spinal cord injury, the midsagittal T1- and T2-weighted magnetic resonance imaging provides an objective, quantifiable, and reliable assessment of spinal cord compression that cannot be adequately assessed by computed tomography alone.

Adolescent↗

Information theoretical performance measure for associative memories and its application to neural networks.

We present a general performance measure (information loss) for associative memories based on information theoretical concepts. This performance measure can be estimated, provided that mean values of observables have been determined for the associative memory. Then the estimation guarantees a minimal association quality. The formalism allows the application of the performance measure to complex systems where the relation between input and output of the associative memory is not explicitly known. Here we apply our formalism to the Hopfield model and estimate the storage capacity alpha(c) from the numerically determined information loss. In contrast to other numerical methods the whole overlap distribution is taken into account. Our numerical value alpha(c)=0.1379(4) for the storage capacity in the Hopfield model is below numerical values obtained previously. This indicates that the consideration of small remnant overlaps lowers the storage capacity of the Hopfield model.

Artificial Intelligence↗

Prevention of initial perfusion failure during xenogeneic ex vivo liver perfusion by selectin inhibition.

BACKGROUND: Endothelial cell activation triggered by xenoreactive antibodies and complement products is the main feature of discordant xenograft rejection. The contribution of early cell-mediated mechanisms to this rejection process is poorly understood, and the function of adhesion molecules in xenogeneic cell interactions in vivo is unclear. The aim of the study was to investigate the role of selectins in mediating cell-dependent initial perfusion failure and functional restrictions in xenoperfused guinea pig (GP) livers. METHODS: Isolated GP livers were hemoperfused in a flow-constant, recirculating perfusion system via the portal vein. Microhemodynamic parameters such as sinusoidal perfusion rate and leukocyte flux were analyzed using intravital fluorescence microscopy. Hepatic oxygen consumption and bile production, as well as liver enzymes, potassium level, and numbers of white blood cells and platelets in the perfusate, were determined. The GP livers were perfused either with GP blood (control perfusion), with unmodified rat blood (xenoperfusion), or with rat blood treated with the selectin-blocking polysaccharide Fucoidin. RESULTS: A significant sinusoidal perfusion failure was observed in the xenoperfusion group, which was accompanied by distinct signs of a functional restriction-like reduced oxygen consumption, bile production, and increased perfusion pressure. However, there were significantly fewer impairments in the Fucoidin group. Furthermore, fewer platelets were trapped and a smaller number of stagnant leukocytes were observed in this group. CONCLUSION: Fucoidin did not suppress complement activation during xenoperfusion. Considering that Fucoidin inhibits the selectin-dependent interactions among white blood cells, platelets, and sulfate-containing proteoglycans on the surface of vascular endothelium, these findings suggest an important role for early cellular interactions in the development of organ failure during xenogeneic rejection.

Animals↗

Analysis of the microcirculation during xenogeneic liver perfusion in the guinea pig--rat model. The contribution of leukocytes to the rejection process.

Since the main feature of hyperacute rejection is a disturbance of the xenograft's microcirculation, we analyzed microhemodynamic parameters during xenogeneic hemoperfusion of the guinea pig (GP) liver and investigated the contribution of leukocytes to the rejection process using intravital fluorescence microscopy. Isolated GP livers were hemoperfused via the portal vein in a recirculating system with a constant flow of 1 ml/min per g liver. In contrast to isogeneic perfusion with heparinized GP blood, a disturbance in the microcirculation was observed during xenogeneic perfusion using heparinized rat blood, with significantly higher values of perfusion pressure, reduced sinusoidal perfusion rates, and a larger number of stagnant leukocytes. A complete breakdown of the microcirculation, with the highest values of perfusion pressure and the smallest perfusion index, was associated with 100% accumulated leukocytes when rat blood was anticoagulated with sodium citrate. Almost isogeneic perfusion values were obtained when fucoidin, which inhibits L-selectin-dependent cell interaction, was added to heparinized rat blood. These data indicate that leukocyte-endothelial cell interaction contributes to xenogeneic rejection.

Animals↗

Microhemodynamics and leukocyte sequestration after pulmonary ischemia and reperfusion in rabbits.

OBJECTIVE: Investigation of leukocyte sequestration in alveolar capillaries and of microhemodynamic changes after pulmonary ischemia/reperfusion injury. METHODS: The kinetics of leukocyte passage and the hemodynamics in pulmonary microcirculation were investigated in 16 rabbits by intravital microscopy. Mean red blood cell velocity and the number of sticking leukocytes were measured in pulmonary arterioles, venules, and capillaries after 1 hour of tourniquet ischemia and 10 minutes and 1 hour after reperfusion. RESULTS: The decrease of red blood cell velocity after reperfusion was associated with a largely increased heterogeneity of blood flow. Immediately after the onset of blood flow, sequestered leukocytes were found in all microvascular segments. An increased number of leukocytes was present in arterioles, venules, and alveolar capillaries 10 minutes and 1 hour after reperfusion. Concomitantly, width of alveolar septa was increased while arterial oxygen tension was reduced, indicating the development of interstitial pulmonary edema. CONCLUSION: Leukocytes are sequestered after pulmonary ischemia and reperfusion not only in alveolar capillaries but also in arterioles and venules, and they may contribute to the development of reperfusion edema.

Animals↗

Percutaneous dilatational tracheostomy: results and long-term outcome of critically ill patients following cardiac surgery.

BACKGROUND: Tracheostomy is widely regarded as the method of choice for long-term airway control in critically ill patients. The advantages of tracheostomy have to be balanced against the surgical risks of conventional surgical tracheostomy. However, the alternative technique of percutaneous dilatational tracheostomy (PDT) has been associated with fewer procedure-related complications. METHODS: The results of PDT following cardiac surgery were investigated in a prospective study (1/1995-9/1997). The procedure of Ciaglia (1985), a modified Seldinger technique, was performed under endoscopic guidance in 88 patients, 30 women and 58 men, with a mean age of 56.6+/-14.5 years. RESULTS: PDT was successfully performed in all cases after a mean of 14.6+/-9.0 days of translaryngeal intubation. No serious procedural complications occurred; a minor hemorrhage occurred in 12 patients and a cuff defect in 2 patients. 49 patients (55.7%) were weaned from mechanical ventilation, and 45 patients (51.1%) were decannulated after a mean tracheostomy duration of 18.9+/-27.2 days. 38 patients died of their underlying disease while still being mechanically ventilated. A total of 20 postprocedural complications were observed in 15 patients: stomal infection (7), minor hemorrhage (4), tracheal stenosis (3), tube displacement (2), delayed wound healing (2), soft-tissue hemorrhage (1), and organ hemorrhage (1). During long-term follow-up a good functional and cosmetic result could be documented in the majority of 35 patients. CONCLUSIONS: PDT can be performed safely in patients following cardiac surgery as a bedside technique with a low incidence of procedural and postprocedural complications and an acceptable functional and cosmetic long-term outcome. Further studies are needed to define the optimal timing of PDT after translaryngeal intubation.

Aged↗

Organs from animals for man.

In the following review some of the problems of xenotransplantation shall be discussed, based on the few experimental data available so far and on reports in the literature describing investigations which may be of importance for xenotransplantation. The impact of gravity on the upright posture of man versus almost all other mammals, the dysfunction between enzymes and hormones in different species and the lack of interactions between interleukins, cytokines and vasoactive substances will be taken into consideration. The question must be asked whether different levels of carrier molecules or serum proteins play a role in the physiological network. Even though the development of transgenic animals or other imaginative manipulations may lead to the acceptance of any type of xenografted organ, it has to be established for how long the products of the xenografts are able to act in the multifactorial orchestra. We are far from understanding xenogeneic molecular mechanisms involved in toxicity, necrosis and apoptosis or even reperfusion injury and ischemia in addition to the immediate mechanisms of the hyperacute xenogeneic rejection. Here, cell adhesion, blood clotting and vasomotion collide and bring micro- and macrocirculation to a standstill. All types of xenogeneic immunological mechanisms studied so far were found to have a more serious impact than those seen in allogeneic transplantation. In addition we are now only beginning to understand that so-called immunological parameters in allogeneic mechanisms act also in a true physiological manner in the xenogeneic situation. These molecular mechanisms occur behind the curtain of hyperacute, accelerated, acute or chronic xenograft rejection of which only some folds have been lifted to allow glimpses of part of the total scene. Other obstacles are likely to arise when long-term survival is achieved. These obstacles include retroviral infections, transfer of prions and severe side effects of the massive immunosuppression which will be needed. Moral, ethical and religious concerns are under debate and the species-specific production of proteins of the foreign donor species developed for clinical use suddenly appears to be a greater problem than anticipated.

Animals↗

Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up. Results of the third National Acute Spinal Cord Injury randomized controlled trial.

OBJECT: A randomized double-blind clinical trial was conducted to compare neurological and functional recovery and morbidity and mortality rates 1 year after acute spinal cord injury in patients who had received a standard 24-hour methylprednisolone regimen (24MP) with those in whom an identical MP regimen had been delivered for 48 hours (48MP) or those who had received a 48-hour tirilazad mesylate (48TM) regimen. METHODS: Patients for whom treatment was initiated within 3 hours of injury showed equal neurological and functional recovery in all three treatment groups. Patients for whom treatment was delayed more than 3 hours experienced diminished motor function recovery in the 24MP group, but those in the 48MP group showed greater 1-year motor recovery (recovery scores of 13.7 and 19, respectively, p=0.053). A greater percentage of patients improving three or more neurological grades was also observed in the 48MP group (p=0.073). In general, patients treated with 48TM recovered equally when compared with those who received 24MP treatments. A corresponding recovery in self care and sphincter control was seen but was not statistically significant. Mortality and morbidity rates at 1 year were similar in all groups. CONCLUSIONS: For patients in whom MP therapy is initiated within 3 hours of injury, 24-hour maintenance is appropriate. Patients starting therapy 3 to 8 hours after injury should be maintained on the regimen for 48 hours unless there are complicating medical factors.

Activities of Daily Living↗

Nitric oxide inhalation in the treatment of right ventricular dysfunction following left ventricular assist device implantation.

BACKGROUND: Following left ventricular assist device (LVAD) implantation in end-stage heart failure, the management of right ventricular dysfunction presents a therapeutic problem unresolved by conventional drug therapy (catecholamines, nitrates, and prostacyclin). This study was performed to investigate the effects of supplemental inhalation of nitric oxide (NO), a selective pulmonary vasodilator, postoperatively and prospectively. METHODS AND RESULTS: Intraindividual dose titration of NO was performed (0 to 40 ppm) according to a standardized protocol. Thereafter treatment was continued with the individually most effective dose of NO (25 to 40 ppm). In 8 consecutive male patients presenting with right ventricular dysfunction postoperatively, a significant dose-dependent improvement in hemodynamic function was observed: pulmonary vascular resistance decreased from 336+/-110 to 210+/-59 dynes x s x cm(-5) (P<.0001), cardiac index rose from 2.0+/-0.4 to 2.7+/-0.4 L x min(-1) x m(-2) (P<.003) at 40 ppm; doses of >20 ppm were effective in increasing cardiac index (P<.05). With continuous NO inhalation up to 48 hours, pulmonary vascular resistance decreased further to 155+/-33 dynes x s x cm(-5) (P<.0001) as the cardiac index increased to 3.3+/-0.6 L x min(-1) x m(-2) (P<.003). Pulmonary artery pressure decreased (P<.0001) as did systemic vascular resistance with hemodynamic improvement (P<.01). Central venous pressure and mean arterial pressure remained unchanged. Right ventricular ejection fraction at transesophageal echocardiography increased from 24+/-7% to 44+/-7% (P<.01) at the end of the study, and right ventricular end-diastolic volume decreased (P<.05). Weaning from NO therapy was successful at 2 to 8 days, and all patients were extubated. Right ventricular function remained stable thereafter. CONCLUSIONS: In the treatment of right ventricular dysfunction following LVAD implantation, inhalation of NO markedly decreased right ventricular afterload by its selective vasodilating effects on the pulmonary circulation without producing systemic hypotension; this merits further evaluation.

Administration, Inhalation↗

Primary structure of a new phosphocholine-containing glycoglycerolipid of Mycoplasma fermentans.

The chemical structure of a novel phosphocholine-containing glycoglycerolipid, the major polar lipid in the cell membrane of Mycoplasma fermentans PG18, was investigated by chemical analyses, gas-liquid chromatography-mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, as well as one- and two-dimensional homo- and heteronuclear NMR spectroscopy and identified as 6'-O-(3"-phosphocholine-2"-amino-1"-phospho-1", 3"-propanediol)-alpha-D-glucopyranosyl-(1'-->3)-1,2-diacyl-glycerol (MfGL-II). Palmitate (16:0) and stearate (18:0), in a 3.6:1 molar ratio, constitute the major fatty acids present. MALDI-TOF mass spectrometry revealed two major pseudomolecular ions at m/z 1049.5 [MI + H]+ and 1077.3 [MII + H]+ representing a dipalmitoyl as the major component and a palmitoyl-stearoyl structure as a minor component. This is the first report of 2-amino-1,3-propanediol-1,3-bisphosphate present in a natural product. This glycoglycerolipid is the second phosphocholine-containing glycoglycerolipid found in M. fermentans.

Fatty Acids↗

Antibody response to MfGL-II, a phosphocholine-containing major lipid of Mycoplasma fermentans membranes.

The choline-containing phosphoglycolipid, MfGL-II, is the major polar lipid of Mycoplasma fermentans PG18. Anti-MfGL-II antisera raised in rabbits using the purified MfGL-II as an immunogen were employed in immunogold electron microscopic and immunofluorescence studies showing that MfGL-II is uniformly distributed and exposed on the cell surface of M. fermentans cells. The specificity of the antibodies was determined by immunostaining of lipid extracts separated by thin layer chromatography. The antibodies recognize lipids specific to M. fermentans but did not cross-react with lipid extracts of M. penetrans, M. capricolum, M. gallisepticum or Acholeplasma laidlawii. As phosphocholine almost completely abolished antibody interaction with MfGL-II in an ELISA assay it is suggested that the anti-MfGL-II repertoire is composed primarily of anti-phosphocholine antibodies. The anti-MfGL-II antisera inhibit the attachment of M. fermentans to Molt-3 lymphocytes suggesting that MfGL-II plays a major role in M. fermentans-host cell interaction.

Animals↗

Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study.

OBJECTIVE: To compare the efficacy of methylprednisolone administered for 24 hours with methyprednisolone administered for 48 hours or tirilazad mesylate administered for 48 hours in patients with acute spinal cord injury. DESIGN: Double-blind, randomized clinical trial. SETTING: Sixteen acute spinal cord injury centers in North America. PATIENTS: A total of 499 patients with acute spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS) centers within 8 hours of injury. INTERVENTION: All patients received an intravenous bolus of methylprednisolone (30 mg/kg) before randomization. Patients in the 24-hour regimen group (n=166) received a methylprednisolone infusion of 5.4 mg/kg per hour for 24 hours, those in the 48-hour regimen group (n=167) received a methylprednisolone infusion of 5.4 mg/kg per hour for 48 hours, and those in the tirilazad group (n=166) received a 2.5 mg/kg bolus infusion of tirilazad mesylate every 6 hours for 48 hours. MAIN OUTCOME MEASURES: Motor function change between initial presentation and at 6 weeks and 6 months after injury, and change in Functional Independence Measure (FIM) assessed at 6 weeks and 6 months. RESULTS: Compared with patients treated with methylprednisolone for 24 hours, those treated with methylprednisolone for 48 hours showed improved motor recovery at 6 weeks (P=.09) and 6 months (P=.07) after injury. The effect of the 48-hour methylprednisolone regimen was significant at 6 weeks (P=.04) and 6 months (P=.01) among patients whose therapy was initiated 3 to 8 hours after injury. Patients who received the 48-hour regimen and who started treatment at 3 to 8 hours were more likely to improve 1 full neurologic grade (P=.03) at 6 months, to show more improvement in 6-month FIM (P=.08), and to have more severe sepsis and severe pneumonia than patients in the 24-hour methylprednisolone group and the tirilazad group, but other complications and mortality (P=.97) were similar. Patients treated with tirilazad for 48 hours showed motor recovery rates equivalent to patients who received methylprednisolone for 24 hours. CONCLUSIONS: Patients with acute spinal cord injury who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone is initiated 3 to 8 hours after injury, patients should be maintained on steroid therapy for 48 hours.

Adolescent↗

Interruption of Escherichia coli heat-stable enterotoxin-induced guanylyl cyclase signaling and associated chloride current in human intestinal cells by 2-chloroadenosine.

Diarrhea induced by Escherichia coli heat-stable enterotoxin (STa) is mediated by a receptor guanylyl cyclase cascade. The present study establishes that an intracellular nucleotide-dependent pathway disrupts toxin-induced cyclic GMP (cGMP) production and the associated chloride (Cl-) flux that underlie intestinal secretion. Incubation of Caco 2 human intestinal epithelial cells with the nucleoside analog 2-chloroadenosine (2ClAdo) resulted in a concentration- and time-dependent inhibition of toxin-induced cGMP production. Inhibition of cGMP production correlated with the metabolic conversion of 2ClAdo to 2-chloroadenosine triphosphate. The effect of 2ClAdo did not reflect activation of adenosine receptors, inhibition of adenosine deaminase, or modification of the binding or distribution of STa receptors. Guanylyl cyclase activity in membranes prepared from 2ClAdo-treated cells was inhibited, in contrast to membranes from cells not exposed to 2ClAdo, demonstrating that inhibition of guanylyl cyclase C (GCC) was mediated by a noncompetitive mechanism. Treatment of Caco 2 cells with 2ClAdo also prevented STa-induced Cl- current. Application of 8-bromo-cGMP, the cell-permeant analog of cGMP, to 2ClAdo-treated cells reconstituted the Cl- current, demonstrating that inhibition of Cl- flux reflected selective disruption of ligand stimulation of GCC rather than the chloride channel itself. Thus, the components required for adenine nucleotide inhibition of GCC signaling are present in intact mammalian cells, establishing the utility of this pathway to elucidate the mechanisms regulating ST-dependent guanylyl cyclase signaling and intestinal fluid homeostasis. In addition, these data suggest that the adenine nucleotide inhibitory pathway may be a novel target to develop antisecretory therapy for enterotoxigenic diarrhea.

2-Chloroadenosine↗

Control and quality assurance in anaesthesia with a PDMS.

This paper presents preliminary results of our experience, over the past three and half years, with an on-line data management system in the OR that charts and documents all features relevant to anaesthesia. We achieved two goals with this system: 1) There has been a considerable improvement in the quantity and quality of documentation, and 2) we have been able to contain costs within our department, despite an increase in workload, by the continuous audit of the quality process in our specialty. Finally we learned that the quality assurance features that we documented and later analyzed, revealed rather conflicting and disappointing results. We believe that this is at least partly due to the reluctance of our staff to accept the concept of quality assurance and quality control in our field.

Anesthesiology↗

[Combined 3-in-1 sciatic block. Prilocaine 500 mg vs. 650 mg].

The objective of the study was to investigate the clinical effectiveness of increasing the dosage of prilocaine for a combined 3-in-1/sciatic nerve block from 500 to 650 mg (open study with 29 patients compared with 30 patients from a former study) and to validate these findings in a second stage (randomised study comparing two groups of 30 patients each). Not only was clinical effectiveness improved by increasing the dose to 650 mg, but methaemoglobinaemia and toxicity were not relevant problems. With the higher dosage, development of the block was slightly faster (onset and completion); there were fewer unsatisfactory blocks; and clinically relevant plasma levels of methaemoglobin did not occur.

Adolescent↗