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Biomedical subjects

F Schneider

Publications and source records attributed to F Schneider.

At least 217 records · Page 12Linked to original sources

[Developmental modalities of septic states. Multiple organ failure syndrome].

Sepsis syndrome occurs when an acute infection results in an host generalized inflammatory response including cytokines production. Death is a frequent and unpredictable sequel of this pathological condition. It may be due either to uncontrolled circulatory failure, or to multiple organ failure. With the advent of nitric oxide in the arena of the most potent vasodilatator agents, we now better understand the mechanisms of low vascular resistance during hyperkinetic septic shock. However a closer understanding of the mechanisms of multiple organ failure is actually required to improve survival rates during severe human sepsis.

Humans↗

Self-regulation of slow cortical potentials in psychiatric patients: alcohol dependency.

Ten unmediated alcohol-dependent male inpatients participated in a Slow Cortical Potential (SCP) self-regulation task utilizing biofeedback and instrumental conditioning. These patients were hospitalized for treatment of alcohol dependency after chronic abuse of alcoholic beverages. Somatic withdrawal symptomatology had occurred recently and the patients were free of any withdrawal symptoms of the autonomic nervous system. Immediately after hospitalization patients were unable to control their SCPs without the reinforcement of immediate feedback across 4 sessions. Seven patients participated in a fifth session an average of 4 months later. Six out of these 7 patients had not had a relapse at the follow-up. In the fifth session these patients were immediately able to differentiate between the required negativity and negativity suppression, whereas the seventh patient, who had relapsed, was unable to control his brain potentials successfully. Results are further evidence that some of the frontocortical dysfunctions in alcohol-dependent patients are reversible. This could covary with a morphological restitution of the cortex.

Adult↗

Plasma cyclic guanosine 3'-5' monophosphate concentrations and low vascular resistance in human septic shock.

OBJECTIVE: To investigate the increase in plasma cyclic GMP (cGMP) concentrations in humans with hyperkinetic septic shock (SS) and to evaluate its relationship to low systemic vascular resistance (SVR). DESIGN: Prospective clinical investigation. SETTING: Medical intensive care unit of a university hospital. PATIENTS: 22 patients with documented SS requiring hemodynamic resuscitation, respiratory support and--in some cases--hemodialysis. MEASUREMENTS AND RESULTS: Hemodynamic data were recorded at admission time and then twice a-day during the following 72 h. We simultaneously measured cyclic GMP, atrial natriuretic peptides (ANP), creatininemia and platelet counts. At admission time, higher plasma cGMP concentrations were observed in patients with SS (11.84 +/- 1.52 pmol.ml-1) than in healthy controls (1.77 +/- 0.18 pmol.ml-1, p < 0.0001), in septicemia patients without circulatory failure (3.28 +/- 0.36 pmol.ml-1, p < 0.005) or in patients with hyperkinetic non-septic shock (3.6 +/- 0.7 pmol.ml-1, p < 0.02). In contrast, there was no significant difference between patients with SS and controls with anuria from non-septic origin. Also ANP concentrations were higher in patients with SS than in others. In addition, cGMP levels correlated negatively with SVR during the first 48 h of the study, and positively with creatininemia later when renal function worsened. However, they did not correlate significantly with ANP. CONCLUSION: These data demonstrate that a significant increase in plasma cGMP concentrations occurs during human SS and that it correlates with the decline in peripheral vascular resistance in the absence, but not in the presence, of severe renal failure. Furthermore, the increase in cGMP levels cannot be ascribed solely to enhanced ANP-induced particulate guanylyl cyclase activity. Thus, our results suggest the occurrence of another endogenous source of cGMP during hyperkinetic SS.

Acute Kidney Injury↗

Galanin receptor activation attenuates norepinephrine release from rat spinal cord slices.

Galanin and norepinephrine both act on sensory neurons in the rat spinal cord dorsal horn. We looked for the effects of galanin on the basal and electrically-evoked release of [3H]norepinephrine from slices of the dorsal spinal cord. 0.1 to 1.0 microM reduced the basal efflux by maximal 10% and the stimulation-evoked release in a concentration-related manner by maximal 27%. In the presence of 0.1 microM galanin receptor antagonist (M-15) reduction of basal efflux persisted but significant effects on the stimulation-evoked release were no longer observed. The antagonist, given alone, was without effect on the release. Thus galanin can reduce the stimulation-evoked norepinephrine release from spinal cord dorsal horn nerve terminals by an action on galanin receptors, however, the release seems not to be tonically inhibited by galanin.

Animals↗

Analysis of antibody response to the measles virus using synthetic peptides of the fusion protein. Evidence of non-random pairing of T and B cell epitopes.

The measles virus induces a life-long immune response associated with antibodies specific for the fusion protein. To map the linear immunodominant recognition sites of the fusion (F) protein of the measles virus, we have reacted a complete set of 108 overlapping pentadecapeptides with purified IgG obtained from donor sera with elevated anti-measles titers. The antibodies recognized about 20% of the peptides and generated a characteristic binding pattern, defining about 6 or 7 distinctive regions (31-75; 111-145; 151-165; 191-215; 271-320; 421-440; 481-530) which include the major hydrophobic segment (111-145) of the intersubunit region and the C-terminal Cys-cluster region. The binding sites were located in close proximity of the few experimentally defined T cell epitopes. This pairing of T and B cell epitopes was corroborated by computer-assisted T cell prediction. The significance of a non-random association of T and B cell epitopes for processing and presentation is discussed. It is speculated that in long-term immunity against measles (F protein), B cells of the same sIg specificity play an important role both as antigen presenting cells and as antibody producing cells. In contrast to human sera from late convalescent donors, mouse and rabbit MV antisera with high neutralizing titers as well as neutralizing MV-F specific monoclonal antibodies did not react with the peptides.

Adult↗

The serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine facilitates noradrenaline release from rat spinal cord slices and inhibits monoamine oxidase activity.

1. The influences of the purported serotonergic agonist 5-methoxy-N,N-dimethyltryptamine (MeODMT) on noradrenaline release and metabolism were investigated in a rat spinal cord release model and a monoamine oxidase (MAO) assay. 2. MeODMT inhibited the basal outflow of tritium from rat spinal cord slices preincubated with [3H]noradrenaline and enhanced the electrically-evoked overflow. 3. Effects on basal outflow were not observed, when monoamine oxidase (MAO) was inhibited by pargyline. Effects on the evoked overflow were not observed in the presence of metitepine or phentolamine. 4. Preferential inhibition by MeODMT of MAO A-type enzyme activity was found in a direct assay. 5. The results provide evidence for two different effects by which MeODMT reinforces noradrenergic neurotransmission in the rat spinal cord: facilitation of stimulation-evoked noradrenaline release and inhibition of noradrenaline metabolism by MAO inhibition.

Animals↗

Analysis of the neutralizing antibody response to the measles virus using synthetic peptides of the haemagglutinin protein.

Infection or immunization with measles virus induces a protective immune reaction including neutralizing antibodies against the haemagglutinin and fusion protein. The reactivity of the polyclonal IgG response of sera obtained from late convalescent donors was studied, using overlapping 15mer peptides covering the complete sequence of the measles virus haemagglutinin. Most sera reacted with a similar set of peptides generating a characteristic binding pattern. The reactive peptides correspond to a region mediating cell hemolysis (aa310-325), to regions which serve as targets to neutralizing antibodies and to a putative transmembrane region (aa35-58). The latter region contains also a human T-cell epitope providing evidence of a non-random association of T- and B-cell epitopes. We also immunized different strains of mice and rabbits with measles virus. In contrast to the human sera, animal sera with strong neutralizing activities did not react with any of the H-protein peptides. The mostly weak reactivities with the linear sequences contrast with the strong neutralizing activities of the human or animal antibodies, suggesting that these primarily recognize the fusion protein or conformational epitopes of the haemagglutinin protein.

Adult↗

Novel antibody coating of a magnetizable solid phase for use in enzyme immunoassays.

Novel kinds of magnetizable particles have been prepared using the interaction between the complexing groups of phosphonic acid and polyvalent metal ions on the surface of Fe3O4 particles. After modification of monoclonal and polyclonal antibodies by the bifunctional chelating agent 2-(4-diazophenyl)-1-hydroxyethane-1,1-bisphosphonic acid, antibodies were immobilized at a ratio of 5-10 mg antibody molecules per ml Fe3O4 particles without loss of immunological reactivity. Very sensitive and fast immunoenzymometric assays for the quantitative determination of human interferon-alpha 1 and mouse immunoglobulins were developed using such particles. The advantages of the method include immobilization of proteins on magnetizable carriers without chemical modification of the carrier and the short assay time compared to conventional immunoenzymometric assays.

Animals↗

L-arginine induces relaxation of small mesenteric arteries from endotoxin-treated rats.

The effect of arginine (Arg) was studied on norepinephrine- (1 microM) precontracted small mesenteric arteries removed from rats treated with E. coli lipopolysaccharide (LPS). The addition of L- (but not D-) Arg (1 mM) relaxed, within 3 min, the small mesenteric arteries from LPS-treated but not from control rats, the maximal relaxation (65.3 +/- 11%) being reached with less than 100 microM L-Arg. NG-Nitro-L-arginine methyl ester (1 mM) and methylene blue (10 microM) restored contractions to the level reached before addition of L-Arg. These results show that LPS induces the production of an L-Arg-derived, nitric oxide-like, relaxing factor in small mesenteric arteries.

Animals↗

Political economy of hospital financing.

In this paper we tried to explain the recent reform in the law of financing German hospitals. We first described five basic types of hospital payment systems which were available as alternatives to the decision on the reform in the early 1980s. In the next step we identified five concerned interest groups whose actions certainly had a great influence on the legislative process. We proposed a simple theoretical model to examine how these groups of actors evaluated the different payment systems. After deriving a preference ranking for each actor, we confronted these rankings with the respective revealed preferences, which could be inferred from their official statements towards the reform. It could also be shown that quite often the actual statements deviated strongly from the theoretically expected preferences because all groups were engaged in a highly interactive lobbying game. In the last step we compared these preferences to the actual outcome of the legislation and found that all groups have at least partly realized their targets. So in contrast to the typical results of interest group theory, the differences in bargaining power do to appear to have led to a solution which unambiguously benefits some groups of actors at the expense of others. It has to be repeated that the empirical analysis was limited to statements from the interest groups in the pre-legislative stage of the whole process. From this point the most promising procedure would appear to be the step-by-step analysis of the statements of the groups during the legislative process as well. This would give the researcher a chance to evaluate whether or not the theoretical hypotheses can be confirmed, whether or not our simple theoretical model is an appropriate way to understand the behavior of the affected groups and what was finally responsible for the outcome of the legislation. Therefore this paper should be seen as a first attempt to apply the framework of public choice theory to the field of health care financing and to demonstrate that much more research is needed.

Budgets↗

Influence of short-chain fatty acids on the production of spiramycin by Streptomyces ambofaciens.

The addition of short-chain fatty acids stimulates the production of spiramycin by Streptomyces ambofaciens cultivated on dextrins and ammonium chloride. The fatty acids were activated by two enzymatic systems. The first system (acyl-CoA synthetases) was present only during the exponential phase. The second system (acylkinases coupled with acylphosphotransferases) was synthesized during the growth phase and during the stationary phase, in which spiramycin production started. Short-chain fatty acids induced the synthesis of acylkinases and acylphosphotransferases. Added at the beginning of cultures, they increased the specific activity of these enzymes during the exponential growth phase. Added at the early stationary phase, the specific activity of these enzymes and of the spiramycin production increased. Excess ammonium in the culture considerably lowered the specific activity of acylkinases synthesized in the stationary phase, when spiramycin production started. This ammonium effect can be reduced by the addition of short-chain fatty acids.

Acetate Kinase↗

Role of endothelium in the response of the vein wall to magnesium withdrawal.

Complete absence of magnesium has a two-fold effect on the arterial tone: direct smooth muscle contraction and relaxation via endothelium-derived relaxing factor (EDRF) release. In the present study performed on a systemic vein we investigated (1) which of these effects dominates following reduction of magnesium concentration from 1.2 mM to 0.8 and 0.4 mM and (2) whether the vessel segments asymmetrically respond when the magnesium concentration is reduced on either the intra- or extraluminal side. The effects of reducing magnesium concentration on both the isometric tension of isolated ring preparations and the diameter of isolated, perfused and superfused feline femoral veins were investigated. In noradrenaline-precontracted rings, rapid decreases in the extracellular magnesium concentration from 1.2 mM to 0.8 and 0.4 mM caused relaxation, whereas total omission of magnesium returned the tone to the level of the initial tone induced by noradrenaline. Both in the presence of haemoglobin (5 x 10(-6) M), and in vessels without endothelium, lowering the magnesium concentration caused a dose-dependent elevation of the noradrenaline-induced tone. In perfused and superfused noradrenaline-contracted vein segments, each reduction of extraluminal magnesium concentration caused contraction of the vessels, regardless of whether the endothelium was intact or not. A decrease in intraluminal magnesium concentration did not alter the diameter of the vessel when the endothelium was intact, but caused contraction when the endothelium was disrupted. The results of the present study demonstrate that both the reduction of magnesium concentration or its complete absence cause an EDRF-mediated relaxation and a directly mediated smooth muscle contraction in the femoral vein of the cat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Self-regulation of slow cortical potentials in psychiatric patients: schizophrenia.

Slow cortical potentials (SCPs) are considered to reflect the regulation of attention resources and cortical excitability in cortical neuronal networks. Impaired attentional functioning, as found in patients with schizophrenic disorders, may covary with impaired SCP regulation. This hypothesis was tested using a self-regulation paradigm. Twelve medicated male schizophrenic inpatients and 12 healthy male controls received continuous feedback of their SCPs, during intervals of 8 s each, by means of a visual stimulus (a stylized rocket) moving horizontally across a TV screen. The position of the feedback stimulus was a linear function of the integrated SCP at each point in time during the feedback interval. Subjects were required to increase or reduce negative SCPs (referred to pretrial baseline) depending on the presentation of a discriminative stimulus. The correct response was indicated by the amount of forward movement of the feedback stimulus and by monetary rewards. Schizophrenics participated in 20 sessions (each comprising 110 trials), while controls participated in 5 sessions. Compared with the healthy controls, schizophrenics showed no significant differentiation between negativity increase and negativity suppression during the first sessions. However, in the last 3 sessions, patients achieved differentiation similar to controls, demonstrating the acquisition of SCP control after extensive training.

Adult↗

Self-regulation of slow cortical potentials in psychiatric patients: depression.

Findings on depressive patients indicate that depressives have electrophysiological characteristics similar to those of schizophrenics, in that they exhibit reduced Contingent Negative Variation (CNV) amplitudes and more distinct Postimperative Negative Variations (PINVs) than normal controls. In a biofeedback experiment, 8 medicated male inpatients with the DSM III-R diagnosis of "Bipolar Disorder, Depressive," and "Major Depression" demonstrated no impairment in the self-regulation of Slow Cortical Potentials (SCP) in comparison to schizophrenics in terms of increasing and suppressing negativity. Continuous visual SCP feedback is presented to the patient as a horizontally moving rocket in a video game format. The direction changes of the rocket represented SCP changes at each point in time, recorded by the central EEG (based on the pretrial baseline). Depressives demonstrated SCP self-regulation across 20 sessions, although with many between-and-within variations. The 8 male controls were unable to regulate their SCPs across 5 sessions. This result contradicts other findings of our laboratory on normal controls. Motivational factors and insufficient operant reinforcement (financial reward) may have facilitated this effect.

Adult↗

Methylene blue increases systemic vascular resistance in human septic shock. Preliminary observations.

We report the hemodynamic improvements induced by intravenous methylene blue (MB), a guanylate cyclase inhibitor, in 2 patients with hyperdynamic septic shock treated with norepinephrine (NE) infusion, mechanical ventilation and hemodialysis. MB injection augmented the low vascular resistance, mean arterial pressure and induced a slight decrease of cardiac index, without any change of heart rate and pulmonary artery wedge pressure. Plasma cyclic GMP levels decreased without a significant change of atrial natriuretic factor levels. MB (2 mg.kg-1) induced a longer lasting improvement of circulatory failure without deleterious side effects, but did not prevent the occurrence of delayed multiorgan failure or subsequent death. These data suggest that in patients, severe sepsis-induced loss of vascular responsiveness to NE involves activation of soluble guanylate cyclase, possibly stimulated by enhanced nitric oxide production. Furthermore, these observations support the concept that pharmacological blockade of guanylate cyclase may improve hemodynamics but not survival rates.

Adult↗

The effects of neuroleptics on facial action in schizophrenic patients.

This paper describes the influence of neuroleptic therapy on facial action in drug-naive schizophrenics. In a comparative study of medicated and unmedicated schizophrenic patients, the coordinates of 12 small light-reflecting points, attached to subjects' faces, were computer-recorded and analyzed automatically during a semi-standardized clinical interview. In addition, facial activity in videotaped interviews was coded using the Facial Action Coding System (FACS). Each sample group comprised of eight patients with the DSM-III-R diagnostic criteria "schizophrenia" or "schizophreniform disorder". Subjects were studied on two occasions, one shortly after admission to the hospital, the other three weeks later. Group 1 was unmedicated during the first session, whereas group 2 was medicated throughout the study. Three weeks after the start of medication, at the second interview, both recording methods showed a reduction in facial activity and facial expression across all subjects in group 1. The facial action of patients in group 2, however, remained unchanged.

Adult↗

Heterogeneity of linear B cell epitopes of the measles virus fusion protein reacting with late convalescent sera.

B cell epitopes of the measles virus fusion protein were mapped, by reacting sera from late convalescent donors with synthetic overlapping pentadecapeptides, segments covering the whole F protein sequence. Unselected individual sera recognized 7 to 20% of the total sequence. Cumulation of the binding patterns of 30 sera identified eight to 10 clusters of antibody-binding peptides spread over most of the sequence. The B cell epitopes included regions of transition between the more hydropathic (including the N-terminal end of the F1 and F2 protein) and hydrophilic sequences. When the regions of antibody binding were compared with the predicted secondary structure of the F protein, no detectable pattern became apparent. Exposed sequences as well as sequences hidden in the viral membrane or in the protein core of both the F1 and F2 polypeptides were recognized by the antibodies. The heterogeneity of the binding patterns was not merely dependent on the anti-measles virus titre. The importance of antibodies recognizing linear epitopes of the measles virus fusion protein for the immune protection is presently not known.

Adult↗

Dexamethasone-induced gastric mucosal damage in the rat: possible role of platelet-activating factor.

1. The aim of the present experiments was to study the possible role of platelet-activating factor (PAF) in mediating gastric mucosal damage induced by dexamethasone in the rat by measuring gastric tissue levels of PAF during dexamethasone-treatment and by investigating the effects of specific PAF receptor antagonists on dexamethasone-induced gastric lesions. PAF-like bioactivity extracted from the rat glandular stomach was determined by a platelet aggregation assay. 2. Dexamethasone treatment (0.4-4 mg kg-1, daily for 1-6 days) produced time- and dose-dependent damage to the glandular mucosa of the stomach as characterized by extensive, uniform hyperaemia with multiple, focal petechiae and erosions. 3. These changes were accompanied by a time-, and dose-dependent increase in PAF content of the glandular stomach. Control rat stomach contained small amounts of PAF (0.14 +/- 0.04 ng per g wet weight), which increased over 40 fold in response to dexamethasone treatment (4 mg kg-1, daily for 6 consecutive days). The presence of PAF-like material in the stomach extract was ascertained by thin-layer chromatography, high performance liquid chromatography and by alkaline hydrolysis. 4. Pretreatment of the animals with one or other of the structurally unrelated PAF receptor antagonists, BN 52021 (10 mg kg-1, i.p.) or BN 50727 (1 mg kg-1, i.p.) significantly reduced dexamethasone-induced gastric damage. In these animals neither petechiae nor erosions were observed. 5. These observations suggest that PAF is a likely endogenous mediator of glucocorticoid-induced gastric mucosal damage in the rat.

Animals↗