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Biomedical subjects

G Ulrich

Publications and source records attributed to G Ulrich.

At least 19 recordsLinked to original sources

[The epistemological problem in neurosciences and its effect on psychiatry].

Currently a comprehensive discipline, neurobiology is the field of examining the essence of mind in contrast to psychophysiology. It is becoming more and more apparent that this aim cannot be satisfied. Neurobiology is hampered by its deeply rooted paradigm of mechanistic materialism. Thus we learn about yet unsolved "hard problems." In order to recognize them as pseudoproblems, we must avoid unprovable metaphysical assumptions such as e.g., treating matter and mind as components of one organism rather than complementary but logically incommensurable means of description. To our physicalistically oriented university psychiatry, reintroducing the subject is of primary importance. At first glance, this would confront us again with unsolvable problems supposedly avoided by the psychiatric 'brain technicians' preferring object-oriented study (neuromaging, receptors). One such question is the 'fact' adverse to physical law of psychophysical interactions: it does not actually represent an insoluble hard problem but is a typical pseudoproblem resulting from false premises.

Germany↗

Drug skin tests in cutaneous adverse drug reactions to pristinamycin: 29 cases with a study of cross-reactions between synergistins.

The present study was made to determine the value of drug skin tests in patients with cutaneous adverse drug reactions (CADRs) due to a synergistin (pristinamycin) and to determine the frequency of cross-reactions between synergistins. 29 patients were referred during the onset of the CADR due to pristinamycin: 18 with maculopapular rash, 9 erythrodermas, 1 angioedema and 1 Stevens-Johnson syndrome. They all had patch tests with pristinamycin and, in most cases, with other synergistins [virginiamycin and dalfopristin-quinupristin (DQ)], prick tests (10 cases) and intradermal tests (IDT) (5 cases). Skin tests with synergistins were positive in 27 cases, patch tests with pristinamycin in 20/29 cases (69%), prick tests with pristinamycin in 3/9 cases on immediate (1 case) or on delayed (2 cases) readings, and IDT with DQ in 4/5 cases. Cross-reactions between synergistins occurred in 9/22 with virginiamycin and in 7/8 cases with DQ. Skin tests with synergistins are useful in investigating CADR due to pristinamycin. Synergistins are composed of 2 chains (1 depsipeptide and 1 macrocyclic lactone) with many structural analogies between all synergistins. According to the chemical structures and our results, it seems advisable to avoid all synergistins in patients with CADR due to pristinamycin.

Adolescent↗

Sensitization to petrolatum: an unusual cause of false-positive drug patch-tests.

We report on an unexpected sensitization to petrolatum diagnosed with the occurrence of multiple nonrelevant and false-positive drug patch-tests performed while investigating a patient suffering from many cutaneous adverse drug reactions. All the positive drug patch-tests were prepared with GILBERT vaseline. This petrolatum reaction is positive as it was tested with five other brands of petrolatums a few months later. As the same petrolatums, but from different batches were tested, patch-tests with GILBERT petrolatum were doubtful, while other petrolatums were positive. White petrolatum is a mixture of semisolid hydrocarbons of the methane series. The sensitizing impurities of petrolatum are polycyclic aromatic hydrocarbons, e.g. phenanthrene derivatives. The purity of petrolatum depends on both the petroleum stock and on the production and packaging methods. Even if rare, contact sensitization to petrolatum can disturb the interpretation of drug patch-tests. It is necessary in the interpretation of drug patch-tests to test both in petrolatum and other vehicles and with all the different petrolatums used in preparing the material for drug patch-tests. So, it is essential to advise the patients sensitized to petrolatum to remove all the topical drugs, such as all the cosmetics, which contain petrolatum in their formulation.

Dermatitis, Contact↗

[Uniformity and diversity of the human image in scientifically oriented human medicine].

Nowadays, hardly anyone would oppose the demand for more rationally based medicine--the catchword here being "evidence-based medicine" (EBM). Anyone trying to comply with this demand will be faced with the question of what is meant by "evidence". It would be false to think that rationality is guaranteed by applying the Galilean method of exact induction. Exact induction aims at objective propositions free of subjectivity. Such propositions are regarded as generally valid, or "true". They lead us toward the transcendent platonic "idea", which is by definition beyond our reach. Exact induction enables us to derive representations of a transcendent idea by means of experimental research. These representations may or may not be useful in actuality, for example in medical therapeutic strategies. Strictly speaking, reproducibility, which is generally taken as proof of a given hypothesis, is not equivalent to identity. Identity implies, among other things, simultaneity.

Artificial Intelligence↗

Decreased level of EEG-vigilance in acute mania as a possible predictor for a rapid effect of methylphenidate: a case study.

About one third of manic patients show a decreased Electroencephalographic Vigilance Level (EVL). In two patients with recurrent manias the hypothesis was tested that the EEG may be used to predict the therapeutic response to methylphenidate. Patient A (with a decreased EVL) responded rapidly to methylphenidate with a considerable reduction of symptoms and a clear increase of EVL, whereas patient B (normal EVL) did not show any change, neither clinically nor in the EEG.

Bipolar Disorder↗

Mechanisms underlying neuronal death induced by chromogranin A-activated microglia.

The neurotoxic effects of activated microglia in neurodegenerative diseases are well established. We recently provided evidence that chromogranin A (CGA), a multifunctional protein localized in dystrophic neurites and in senile plaques, induces an activated phenotype and secretion of neurotoxins by rat microglia in culture. In the present study, we focused on the mechanisms underlying neuronal degeneration triggered by CGA-activated microglia. We found that neuronal death exhibits apoptotic features, characterized by the externalization of phosphatidylserine and the fragmentation of DNA. Microglial neurotoxins markedly stimulate the phosphorylation and activity of neuronal p38 mitogen-activated protein kinase and provoke the release of mitochondrial cytochrome c, which precedes apoptosis. Inhibition of p38 kinase with SB 203580 partially protects neurons from death induced by CGA-activated microglia. Furthermore, neurons are also protected by Fas-Fc, which antagonizes the interactions between the death receptor Fas and its ligand FasL and by cell-permeable peptides that inhibit caspases 8 and 3. Thus, CGA triggers the release of microglial neurotoxins that mobilize several death-signaling pathways in neurons. Our results further support the idea that CGA, which is up-regulated in many neuropathologies, represents a potent endogeneous inflammatory factor possibly responsible for neuronal degeneration.

Animals↗

Quantitative assessment of dynamic electroencephalogram (EEG) organization as a tool for subtyping depressive syndromes.

Up until now, no subclassification of affective psychoses has been validated biologically. This follows unavoidably from a research practice of defining diagnostic subtypes in consensus conferences and only thereafter allowing their validation. There is evidence that electroencephalograms (EEG) may be a useful tool in psychiatry, provided that the relevant information is extracted. Our EEG quantification procedure aims at an assessment of both the amount and range of variation of spontaneous changes of topographical alpha-power distribution, developing within a certain period of recording under resting conditions. Our measures were designed to characterize the dynamic organization of the EEG. This is quite obviously an eyeball evaluation but it has nevertheless been neglected in research. The study design was done retrospectively. Included were inpatients with a primary depressive disorder. Main exclusion criteria were an age older than 62 years and psychotropic drugs other than antidepressants. The psychopathology and other clinical data were routinely assessed within three days after admission by the AMDP documentation. An EEG was also routinely performed at admission. We made use of robust, generally known non-parametric statistics. Those patients who exhibited a dynamically rigid EEG are especially prone to recurrences, have a relative late onset of their illness, and show an acute symptomatology characterized by organic-like features. The findings lend support to our contention that the quantitative assessment of the dynamics of the EEG-Gestalt allows the delimitation of a clinically important subtype that is characterized both cross-sectionally and in long-term respects.

Adolescent↗

Chromogranin A induces a neurotoxic phenotype in brain microglial cells.

Chromogranin A (CGA) belongs to a multifunctional protein family widely distributed in secretory vesicles in neurons and neuroendocrine cells. Within the brain, CGA is localized in neurodegenerative areas associated with reactive microglia. By using cultured rodent microglia, we recently described that CGA induces an activated phenotype and the generation of nitric oxide. These findings led us to examine whether CGA might affect neuronal survival, expression of neurofilaments, and high affinity gamma-aminobutyric acid uptake in neurons cultured in the presence or absence of microglial cells. We found that CGA was unable to exert a direct toxic effect on neurons but provoked neuronal injury and degeneration in the presence of microglial cells. These effects were observed with natural and recombinant CGA and with a recombinant N-terminal fragment corresponding to residues 1-78. CGA stimulated microglial cells to secrete heat-stable diffusible neurotoxic agents. CGA also induced a marked accumulation of nitric oxide and tumor necrosis factor-alpha by microglia, but we could not establish a direct correlation between the levels of nitric oxide and tumor necrosis factor-alpha and the neuronal damage. The possibility that CGA represents an endogenous factor that triggers the microglial responses responsible for the pathogenesis of neuronal degeneration is discussed.

Animals↗

[Use of flow cytometry for HLA B27 phenotyping: study of a HLA B7/HLA B27 double marker technique].

Among HLA-associated diseases, the strong association between HLA B27 and ankylosing spondylitis (AS) allows to perform HLA B27 typing for the diagnosis of this disease. The technique described: double immunostaining anti-HLA B7/HLA B27 on whole blood samples and analysis by flow cytometry is a rapid method for the detection of HLA B27 antigen. We have compared the results obtained with those of the TERASAKI microlymphocytotoxicity reference method on a population of 300 patients. The absence of false negative results indicates that this test is suitable for AS screening. The use of two monoclonal antibodies proves to be effective in eliminating cross reactions described with HLA B7 flow cytometric techniques using single monoclonal antibody. This technique allows to restrict the use of microlymphocy-totoxicity to patients presenting with both HLA B7 and B27 positive reactivities.

Antibodies, Monoclonal↗

Elevated levels of complement components C5 and C9 and decreased antitrypsin activity in the serum of patients with X-linked vacuolated myopathy.

We have recently reported a French family presenting with an X-linked vacuolated myopathy. Here we show that levels of complement components C5 and C9 are elevated in the serum of these patients. Moreover, antitrypsin activity is decreased in the serum of the patients. Taken with the deposition of membrane attack complex encountered in muscle tissue, these results emphasize the role of complement in the pathogenesis of this rare muscular disorder.

Complement C5↗

Chromogranin A triggers a phenotypic transformation and the generation of nitric oxide in brain microglial cells.

Chromogranin A is an ubiquitous 48,000 mol. wt secretory protein stored and released from many neuroendocrine cells and neurons. In human brain, chromogranin A is a common feature of regions that are known to be affected by various neurodegenerative pathologies such as Alzheimer's, Parkinson's and Pick's diseases. Brain degenerative areas are generally infiltrated by activated microglial cells, the resident macrophage cell population within the central nervous system. Here, we report that both recombinant human chromogranin A and chromogranin A purified from bovine chromaffin granules trigger drastic morphological changes in rat microglial cells maintained in culture. Microglial cells exposed to chromogranin A adopted a flattened amoeboid shape and, this change was associated with an accumulation of actin in the subplasmalemmal region, as observed by immunocytochemistry and confocal laser microscopy. In single microglial cells loaded with indo-1, chromogranin A elicited a rapid and transient increase in [Ca2+]i which preceded the reorganization of actin cytoskeleton. The activity of nitric oxide synthase was estimated by measuring the accumulation of nitrite in the culture medium. Both recombinant human chromogranin A and bovine chromogranin A triggered an important accumulation of nitrite comparable to that induced by lipopolysaccharide, a well-known activator of microglia. The effect of chromogranin A was dose dependent, inhibited by N omega-nitro-L-arginine methyl ester, a competitive inhibitor of nitric oxide synthase, and by cycloheximide, an inhibitor of protein synthesis. These findings suggest that chromogranin A induces an activated phenotype of microglia, and thus may have a role in the pathogenesis of neuronal degeneration in the brain.

Actins↗

Femoral stress fracture.

The following case report describes the history of a high school football player who complained of right anterior thigh pain, which worsened during the season. The team orthopedic surgeon made an initial diagnosis of a right rectus femoris strain. The athlete was treated and improved quickly. One week later, his condition worsened and he reported signs and symptoms similar to those experienced initially. A follow-up examination by the orthopedic surgeon revealed a femoral stress fracture to the proximal one-third (medial side) of the right femur. We describe the athlete's clinical findings, diagnostic tests, and rehabilitation program. We also discuss the pathophysiology and treatment principles relevant to the management of a femoral shaft stress fracture. The athlete has recovered and has returned to full athletic activity with no complications.

Journal Article↗

[Health promotion and prevention as responsibilities of the established physician--status and current deficits].

General practitioners have been questioned by the Society of panel doctors of Bavaria about the status, deficiencies and the future focus of prevention in the medical office. The results of this questionnaire was compared to similar studies from Niedersachsen and Switzerland. From these results, conclusions should be drawn for initiatives of the medical self-administration to improve the preventive out-patient care. Written questionnaires with a semi-structured form for all of the 1067 general practitioners in the district Oberfranken of the Society of panel doctors of Bavaria. Response 33.7%. Descriptive analysis of the answers and development of a list of priorities of further education in preventive medicine. Comparison of the results with questionnaires in German language. Preventive care plays an important role in the medical practice. However, the status of prevention has currently a lower importance as it would be appropriate. This is caused by unsatisfactory honorary, lack of further education, and lack of time for an adequate consultation. It was recommended that the medical self-administration should offer more further education about preventive medicine. In all three cited studies, first of many topics, where there was a need for further education, was nutrition followed by withdrawing from smoking and protection from infections.

Ambulatory Care↗

Immunocytochemical localization of protein kinases Yes and Src in amoeboid microglia in culture: association of Yes kinase with vimentin intermediate filaments.

Amoeboid microglia isolated from primary cultures of neonatal rat brain correspond to a transient form of activated microglia, a resident population of macrophage-like cells. In order to understand the molecular aspects of microglial activation, we have studied amoeboid microglia in primary culture for the presence of Yes and Src protein tyrosine kinases, two kinases which have been implicated in signal transduction process during monocyte/macrophage activation. Immunofluorescence with an antibody raised against the peptide from unique N-terminal domains of Yes and Src demonstrated that Yes and Src kinases are enriched in perinuclear areas of amoeboid microglia. In addition, the antibody to c-yes peptide had a cytoplasmic distribution which coincided with the distribution of vimentin-containing intermediate filaments. Preadsorption of anti-c-yes antibody with an excess of antigenic peptide inhibited anti-c-yes immunofluorescence, while vimentin immunofluorescence remained unchanged. Double immunofluorescence images analyzed with the two-dimensional intensity distribution program (2-D scattered histograms) on Zeiss confocal scanning laser microscope demonstrate the colocalization of c-yes with vimentin. The extent of colocalization was more prominent after exposure of intact cultured microglia to dibutyryl cyclic AMP (dBcAMP), or to phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) or to okadaic acid, an inhibitor of protein phosphatases. The findings suggest that vimentin might serve as molecular support for Yes kinase and, since previous studies have shown that vimentin in amoeboid microglia is one of the major protein substrates of serine/threonine protein kinases, this function could be regulated by phosphorylation.

Animals↗

Bacterial endotoxin induces [Ca2+]i transients and changes the organization of actin in microglia.

We have employed amoeboid microglia purified from primary cultures of neonatal rat brain to examine the effect of bacterial lipopolysaccharide (LPS), a potent activator of immune cells, on intracellular calcium concentration ([Ca2+]i) in brain macrophages. In single brain macrophages loaded with indo 1, pulse administration of LPS elicited a rapid and transient increase in [Ca2+]i. From a total of 70 cells examined, all responded to LPS with a similar [Ca2+]i transient, indicating a good homogeneity of the cell population with regard to the LPS response. It was concluded that the rise of cytosolic [Ca2+]i originated from intracellular stores because the response to LPS occurred similarly in the presence or in the absence of extracellular Ca2+. A second administration of LPS to the same cells resulted in a second but reduced [Ca2+]i transient. In contrast to the first response to LPS, this second response was totally dependent on the presence of Ca2+ in the extracellular medium. The first response to LPS was strongly inhibited by ruthenium red and could be suppressed in a reversible manner by preincubating the cells with caffeine in the absence of Ca2+ in the extracellular medium. These results indicate that caffeine-sensitive intracellular Ca2+ stores may be the major source of Ca2+ in the response of brain macrophages to LPS. The possible release of Ca2+ from phosphatidylinositol(3,4,5)-trisphosphate (IP3)-sensitive stores in brain macrophages was also evaluated by stimulating cells with the IP3-mobilizing agonist histamine. Brain macrophages were heterogeneous with regard to the histamine response since histamine induced a [Ca2+]i rise in only 30% of cells examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Acute vs. chronic EEG effects in maprotiline- and in clomipramine-treated depressive inpatients and the prediction of therapeutic outcome.

Patients treated with the norepinephrine uptake inhibitor maprotiline showed an opposite tendency between acute and chronic effect of EEG. Whereas the acute effect indicated a decrease upon EEG vigilance, the chronic effect indicated an increase. Under clomipramine which acts upon different transmitter systems in a complex, up to now not fully understood way, acute and chronic EEG effects could not be differentiated.

Adult↗

Electroencephalographic response prediction of antipsychotic drug treatment in acutely ill patients and of long-term prophylactic treatment with lithium salts.

The use of the EEG as a pharmacotherapeutic response predictor is still hampered by the largely unsolved problem of extracting the relevant information from the recording in a theory-guided manner and by the likewise largely underestimated fact of pathobiological heterogeneity in diagnostically homogenous groups of patients. Instead of the usual group-statistical designs that rely solely on homogenous psychopathology, we advocate a strategy of single case studies, performed as comprehensive as possible and giving special attention to the baseline condition. It is only a certain number of such single case studies that afford an empirical data base for meaningfully applicating statistical procedures.

Acute Disease↗

["Neuroadaptation" in long-term cannabis abuse. A clinical and electroencephalographic case study].

This report is about electroencephalographic changes in a twenty-eight year old patient with longterm heavy cannabis use. He was admitted to our hospital after he had developed a depressive-apathetic syndrome. Two days after the last cannabis-intake, the patient had recovered from initial psychopathology and his EEG was completely inconspicuous at this day. Some days later however the patient's behavior became increasingly impulsive and unstable, while his EEG showed a marked disturbed regulation of vigilance. In the following weeks his impulsiveness became less and his EEG returned to normal. We suggest that these alterations may reflect a discontinuation of the initial neuroadaption of the central nervous system to the drug.

Adult↗