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Biomedical subjects

F Wagner

Publications and source records attributed to F Wagner.

At least 55 records · Page 3Linked to original sources
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

[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↗
PubMed1997

[Keratometry in dogs: two automatic hand-held keratometers compared].

In human medicine keratometric examinations are an essential tool for the determination of ocular refraction preceeding cataract operations. In dogs the use of manual keratometric methods is not feasible due to the lack of active cooperation. It is therefore necessary to apply autokeratometers which are also utilized in human pediatric patients. In this investigations we compared two portable automated keratometers in respect to their applicability in dogs. 40 dogs, comprising eight clinic beagles and 32 patient-dogs of various breeds were examined awake and under anesthesia using both hand-held keratometers. The horizontal and vertical corneal radius was measured consecutively by one investigator in all dogs and assessed statistically (standard deviation, analysis of regression and Student t-test). Both instruments yielded comparable results in all dogs. Furthermore, they were both tolerated well as they ensure a both rapid and minimal stress-inducing method of keratometry in dogs.

Anesthesia, General↗
PubMed1996

A natural experiment on plant acclimation: lifetime stomatal frequency response of an individual tree to annual atmospheric CO2 increase.

Carbon dioxide (CO2) has been increasing in atmospheric concentration since the Industrial Revolution. A decreasing number of stomata on leaves of land plants still provides the only morphological evidence that this man-made increase has already affected the biosphere. The current rate of CO2 responsiveness in individual long-lived species cannot be accurately determined from field studies or by controlled-environment experiments. However, the required long-term data sets can be obtained from continuous records of buried leaves from living trees in wetland ecosystems. Fine-resolution analysis of the lifetime leaf record of an individual birch (Betula pendula) indicates a gradual reduction of stomatal frequency as a phenotypic acclimation to CO2 increase. During the past four decades, CO2 increments of 1 part per million by volume resulted in a stomatal density decline of approximately 0.6%. It may be hypothesized that this plastic stomatal frequency response of deciduous tree species has evolved in conjunction with the overall Cenozoic reduction of atmospheric CO2 concentrations.

Journal Article↗
PubMed1996

Biological activity of 26-succinylbryostatin 1.

Bryostatin 1, a macrocyclic lactone, has undergone phase I trials as an anticancer agent. Because of the lipid solubility of this compound it must be delivered either in ethanol or in a PET formulation. During the trial, these vehicles caused a large number of treatment-related side effects. We have synthesized the triethanolamine salt of 26-succinylbryostatin 1 and find that this compound is approx. 100-fold more water soluble than bryostatin 1. Because of the potential for clinical use, we have evaluated the biologic activity of this compound. We find that in a concentration-dependent manner 26-succinylbryostatin 1 is capable of activating protein kinase C (PKC) in vitro and displacing [3H]PDBu from PKC. However, at all concentrations tested the activity was less than the parent compound bryostatin 1. Addition of bryostatin 1 but not 26-succinylbryostatin 1 to U937 leukemic cells in culture stimulated a drop in cytosolic PKC, secondary to translocation of PKC to the membrane. Although 26-succinylbryostatin 1 did not stimulate a drop in the cytosolic levels of PKC, addition to U937 cells activated transcription from an AP-1 enhancer construct and c-Jun protein phosphorylation in a similar fashion to bryostatin 1 and differentiation of U937 cells. Unlike bryostatin 1, 26-succinylbryostatin 1 was unable to cause aggregation of human platelets. Although injection of bryostatin-1 into mice carrying B16 melanoma inhibits tumor growth, there was no significant inhibition of melanoma growth when identical doses of 26-succinylbryostatin 1 were injected. Therefore, 26-succinylbryostatin 1 shares some but not all of the pharmacologic properities of bryostatin 1. This compound can activate protein phosphorylation without lowering cytosolic levels of PKC.

Animals↗
PubMed1996

Comparison of the antitumor activity of bryostatins 1, 5, and 8.

Bryostatin 1, a macrocyclic natural lactone isolated from a marine Bryozoan, has undergone phase I testing in humans. Side effects of treatment have included muscle pain and joint aches, a transient decrease in platelets, and the release of tumor necrosis factor alpha (TNF alpha) and IL-6 into the blood stream. In animals, anticancer activity has been demonstrated against murine leukemias, lymphomas, melanomas, and sarcomas. The mechanism of action of this compound depends in part on its ability to activate protein kinase C. To determine the biologic activity and toxicity of other members of the family of bryostatin compounds, we studied the ability of bryostatins 5 and 8 to inhibit the growth of murine melanoma K1735-M2. Bryostatins 1, 5, and 8 induced equivalent inhibition of melanoma growth, but bryostatins 5 and 8 induced less weight loss than bryostatin 1 (P < 0.001). Neither the injection of an antimurine TNF alpha antibody nor an adenovirus, which produces a mutated TNF receptor inhibiting TNF alpha activity, into mice had any effect on either bryostatin-induced weight loss or melanoma tumor growth inhibition. Using a novel competition assay, the levels of bryostatin in the plasma were measured. The approximate half-life (t1/2) of bryostatin was 8.62 min, the clearance (Cl) 3.53 ml/min and the AUC 322.20 nmol/l min. A similar result was obtained with each bryostatin analog. These results suggest that human testing of additional bryostatin analogs may yield compounds with similar antitumor activity but decreased side effects. A novel assay to measure the level of all bryostatins in the plasma of patients undergoing treatment is described.

Animals↗
PubMed1996

Initial steps of sophoroselipid biosynthesis by Candida bombicola ATCC 22214 grown on glucose.

Candida bombicola ATCC 22214 produces the glycolipid sophoroselipid when cultivated on a medium with glucose as the sole carbon source. Under phosphate-limiting conditions the product yield rises from 0.033 to 0.143 and the specific product formation rate rises from 0.004 h-1 to 0.007 h-1. Enhanced sophoroselipid synthesis is initiated by the decline of the specific activities of NAD- and NADP-dependent isocitrate dehydrogenase (EC 1.1.1.41 and 1.1.1.42) to 2% and 0% of the initial activities respectively. Constantly high specific activity of citrate synthase (EC 4.1.3.7) causes an accumulation of isocitrate and citrate in the mitochondria. Both acids are transported into the cytosol where citrate is cleaved by ATP: citrate lyase (EC 4.1.3.8) giving rise to acetyl-CoA, the precursor of fatty acid synthesis. The ATP: citrate lyase is unaffected by different energy charges; the apparent K(m) values for coenzyme A, ATP and citrate are 23 microM, 250 microM and 256 microM respectively. NADPH for fatty acid synthesis might be generated by further metabolism of oxaloacetate, the other product of the citrate-cleaving reaction, by oxidation of the isocitrate by the cytosolic NADP-dependent isocitrate dehydrogenase or via the hexose monophosphate shunt. A possible explanation for sophoroselipid formation during exponential growth is given.

Adenosine Monophosphate↗