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Biomedical subjects

H Walter

Publications and source records attributed to H Walter.

At least 109 records · Page 6Linked to original sources
PubMed1996

Subtypes of alcoholism and their role in therapy.

In recent years, the term 'chronic alcoholism' has had a meaning that is more descriptive than diagnostic. Several subtypes of alcoholism have been established and are now a necessary tool for studying therapy outcome. Alcohol-dependent patients can be subtyped based on clearly assigned dimensions (e.g. biological, sociological and psychological disturbances). Craving and the underlying disturbance must be treated. The number of pharmacological agents that may reduce alcohol intake has increased recently. We conducted a prospective long-term study based on four subtypes of alcohol-dependent patients to assess the efficacy of acamprosate. Our findings demonstrate that these patient subtypes are relevant to outcome in trials of pharmacological agents. We strongly recommend subtyping alcohol-dependent subjects in future trials, because the usefulness of effective drugs could be overlooked when they are tested in a heterogeneous population.

Alcoholism↗
PubMed1995

Hypnotic catalepsy-induced changes of regional cerebral glucose metabolism.

In an attempt to elucidate the physiological basis of hypnosis, we investigated the changes of whole-brain and regional cerebral glucose metabolism, from a state of resting wakefulness to a hypnotized state with whole-body catalepsy, using positron emission tomography and the 2[18F]fluorodeoxyglucose method in 15 highly hypnotizable adults. Neither the random order of study conditions nor any of the other experimental factors had a measurable effect, and there was no statistically significant global activation or metabolic depression. However, repeated measures analysis of variance revealed a statistically significant heterogeneity of symmetric regional responses: Mainly the occipital areas, including visual and paravisual cortex, became relatively deactivated, while some metabolic recruitment was found in structures involved in sensorimotor functions. The observed pattern of changes of regional cerebral activity corresponds with the shift of attention away from normal sensory input that hypnosis is known to produce.

Adult↗
PubMed1995

A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group.

BACKGROUND: The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism is still a matter of debate. METHODS: We performed a multicenter trial comparing six weeks of oral anticoagulant treatment with six months of such therapy in patients who had a first episode of venous thromboembolism. Anticoagulant therapy consisted of warfarin or dicumarol. Of the 902 patients enrolled, 5 were later excluded because they had congenital protein C deficiency; 443 were randomly assigned to receive six weeks of oral anticoagulant therapy with a targeted international normalized ratio (INR) of 2.0 to 2.85, and 454 were randomly assigned to receive six months of such therapy. The initial diagnoses were confirmed by means of venography in cases of deep-vein thromboses (n = 790) and with perfusion-ventilation scanning or angiography in cases of pulmonary embolism (n = 107); recurrences were confirmed in the same way. RESULTS: After two years of follow-up, there had been 123 recurrences of venous thromboembolism that met the diagnostic criteria, 80 in the six-week group (18.1 percent; 95 percent confidence interval, 14.5 to 21.6) and 43 in the six-month group (9.5 percent; 95 percent confidence interval, 6.8 to 12.2). The odds ratio for recurrence in the six-week group was 2.1 (95 percent confidence interval, 1.4 to 3.1). There was no difference in mortality or the rate of major hemorrhage between the six-week and six-month groups. CONCLUSIONS: Six months of prophylactic oral anticoagulation after a first episode of venous thromboembolism led to a lower recurrence rate than did treatment lasting for six weeks. The difference between the two groups occurred between 6 weeks and 6 months after the start of treatment, and the rates of recurrence remained nearly parallel for 1 1/2 years thereafter.

Anticoagulants↗
PubMed1995

Differential electrophoretic behavior in aqueous polymer solutions of red blood cells from Alzheimer patients and from normal individuals.

The recently reported phenomenon that red blood cells (RBC) from Alzheimer disease (AD) patients and normal individuals, which have identical electrophoretic mobilities (EPM) in phosphate-buffered saline (PBS), have different EPM in appropriately selected polymer solutions, has been further explored. Of a number of in vitro treatments to which AD and normal RBC were subjected prior to EPM measurements in bottom phase (from a dextran-poly(ethylene glycol) (PEG) aqueous phase system) only trypsin eliminated the difference. Thus, the differential polymer interaction between AD and normal RBC, thought to be the basis for their dissimilar EPM, can be abolished by appropriate proteolytic modification of the cell surfaces and suggests protein as a source of difference. Because young and old RBC from normal individuals, which have the same EPM in PBS, have different EPM in certain polymer solutions, and the RBC from AD patients have been reported to age abnormally, we also compared the young and old RBC subpopulations from these two sources. By the criterion of cell electrophoresis in polymer solutions the differences between AD and normal RBC and between young and old RBC are distinct. The EPM of AD and normal RBC differ in bottom phase or PEG but not in dextran solution; while the EPM of young and old RBC differ predominantly in dextran. We speculate that since the observed difference in EPM of RBC from AD patients and normals depends on protein(s) yet is anticoagulant-related (being obtained only when blood is collected in citrate or oxalate) it might be the result of an interaction (Ca(2+)-mediated?) between the surfaces of these cells and protein component(s) of their respective, compositionally differing sera.

Alzheimer Disease↗
PubMed1995

Phase separation in cytoplasm, due to macromolecular crowding, is the basis for microcompartmentation.

The macromolecular diversity and concentrations in the fluid phase of cytoplasm constitute conditions necessary and sufficient for aqueous phase separation. Consequences of phase separation in cytoplasm, including its 'compartmentation', are inferred from analogies with the physicochemical properties of aqueous two-phase systems and with the partitioning behavior of biomaterials in them.

Animals↗
PubMed1995

Immunohistochemical analysis of nm23 protein expression in malignant bone tumors.

Expression levels of nm23 protein in 72 malignant bone tumors comprising 41 osteosarcomas, 22 chondrosarcomas, 6 Ewing's sarcomas, and 2 malignant fibrous histiocytomas were examined immunohistochemically, using anti-nm23 protein polyclonal antibody, and compared with 51 cases of benign bone tumors or tumor-like lesions. Malignant bone tumors showed significantly higher nm23 protein expression than benign bone tumors or tumor-like lesions (P < 0.0001). In chondrosarcoma, nm23 expression increased in high-grade tumors (grade I versus grade II and III: P = 0.0229). In the cases of osteosarcoma, however, grade IV osteosarcomas showed decreased expression of nm23 compared with grade III tumors (P = 0.0122). There was no significant relationship between nm23 expression and histological type. nm23 expression had no correlation with metastatic potential in osteosarcoma, although the therapy was not uniform in our cases. Furthermore, in 6 cases of osteosarcoma and 1 case of Ewing's sarcoma, there was no clear tendency for a decrease of nm23 in the metastatic sites compared with primary sites, as reported in breast cancer. These results showed that, in contrast to reports on breast cancer and experimental models, nm23 protein expression in human bone tumors may be associated with malignant potentiality, except in cases of osteosarcoma.

Adolescent↗
PubMed1995

beta-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo.

The cocaine analogue 2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (beta-CIT) is a potent ligand for both dopamine- and serotonin uptake sites which in its 123I labeled form can be used for single photon emission computerized tomography (SPECT). It was demonstrated previously by SPECT-studies in non-human primates that 123I-beta-CIT binds to dopamine transporters in the striatum and to serotonin transporters in hypothalamus and midbrain. The aim of the present study was to compare 123I-beta-CIT binding in the brain stem of normal controls and a group of subjects under treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram. 123I-beta-CIT-SPECT was performed in 12 depressed patients under 20 mg (n = 5), 40 mg (n = 6) and 60 mg (n = 1) citalopram daily, in one untreated depressed patient and in 11 controls at regular time intervals up till 24 hours p.inj. A highly significant reduction of beta-CIT binding was found in an area including mesial thalamus, hypothalamus, midbrain and pons in patients under citalopram compared to controls (44.1 +/- 14.4 vs. 82.3 +/- 18.6cpm's/mCi x kg body weight; specific binding 4 hrs p.inj.; p = 0.0001). No differences were seen between the high and low dose group and no changes were found in the striatum. 123I-beta-CIT binding in the brain stem and striatum in one untreated depressed patient fell within the range of control values. To our knowledge this is the first report directly demonstrating the effect of a selective serotonin uptake inhibitor in the brain in humans in vivo. SPECT measurements of serotonin uptake sites in patients with depression and other psychiatric disorders might provide better insights into the pathophysiology of these disorders and into mechanisms of drug action.

Adult↗
PubMed1995

Cytokine production by phytohemagglutinin-stimulated human blood cells: effects of corticosteroids, T cell immunosuppressants and phosphodiesterase IV inhibitors.

The ability of dexamethasone and prednisolone (corticosteroids), FK506 and cyclosporin A (T cell immunosuppressants), and of nitraquazone and rolipram (phosphodiesterase IV inhibitors) to inhibit cytokine production by stimulated human blood was investigated. Heparinized human blood obtained from normal healthy volunteers was stimulated with phytohemagglutinin (PHA) in the presence or absence of drug. After different incubation times, supernatant levels of interleukin (IL)-2, IL-5, granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon gamma (IFN-gamma) were quantified by ELISA. Dexamethasone strongly inhibited the production of IL-5 (IC50 = 0.004 microM), was less potent against IL-2 and IFN-gamma (IC50 = 0.02-0.05 microM) and showed a relatively weak effect against GM-CSF (IC50 = 0.6 microM). Similarly prednisolone potently suppressed IL-5 generation (IC50 = 0.05 microM), displayed a more modest activity on IL-2 and IFn-gamma (IC50 = 0.2-0.3 microM) and exerted only partial effects (43% inhibition at 1 microM) on GM-CSF). FK506 strongly suppressed the production of IL-2 (IC50 = 0.01 microM) and GM-CSF (IC50 = 0.03 microM), but was inactive (< 30% inhibition at 1 microM) against IL-5 and IFN-gamma. Similarly, cyclosporin A reduced the generation of IL-2 (IC50 = 0.4 microM) and GM-CSF (IC50 = 0.6 microM) while barely affecting the other two cytokines. Nitraquazone and rolipram were most active in reducing the production of IL-5 (IC50 = 0.8 and 1.3 microM, respectively), while their potency against IL-2, GM-CSF and IFN-gamma was 3-6 times lower, with IC50's between 2.4 and 8.0 microM. These data indicate that corticosteroids, T cell immunosuppressants and phosphodiesterase IV inhibitors affect cytokine production by PHA-stimulated human blood cells in a differential and "pharmacotypical'' manner.

Adrenal Cortex Hormones↗
PubMed1995

Synchronous multifocal bone sarcomas--a case report and molecular pathologic investigation.

A case of a 54-year-old woman is described who developed synchronously two malignant bone tumors: a dedifferentiated chondrosarcoma in the olecranon and a malignant fibrous histiocytoma (MFH) in the lower tibia. The anaplastic part of the dedifferentiated chondrosarcoma revealed an MFH-like pattern. Myogenous differentiations were not observed in the anaplastic sarcoma cells. The MFH in the tibia showed a storiform-pleomorphic pattern. Single tumor cells showed positivity for M-actin and desmin pointing to myogenous differentiation. DNA-cytophotometry of the dedifferentiated chondrosarcoma showed an aneuploid stem cell line. The MFH in the tibia did not reveal aneuploid stem cells. Staining for p53 protein was negative in both tumors. SSCP analysis and sequencing of the p53 gene in both tumors revealed in the dedifferentiated chondrosarcoma a mutation in exon-8 with the transversion from G to T in codon 294 resulting in a substitution of a stop codon for GLU. The mutation was not observed in the MFH. From these immunohistologic, DNA-cytometric and molecular biologic investigations, we consider it probable that the tumor in the lower tibia is a second highly malignant bone tumor and not the metastasis of the dedifferentiated portion of the dedifferentiated chondrosarcoma in the olecranon.

Bone Neoplasms↗
PubMed1995

Expression of growth factors and their receptors in human osteosarcomas. Immunohistochemical detection of epidermal growth factor, platelet-derived growth factor and their receptors: its correlation with proliferating activities and p53 expression.

The expression of both epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), and of their receptors (EGFR and PDGFR) was immunohistochemically examined in 37 cases of osteosarcoma. Furthermore, immunostaining for p53 protein and Ki-67 antigen by MIB-1 was carried out and compared with the above results. EGFR (81%) expressed more often than EGF (51%) and the expression of EGF and EGFR, and PDGF and PDGFR were recognized in 49% and 38%, respectively. In eleven cases (30%), the expression of both growth factors and their receptors was combined. Anaplastic osteosarcoma showed higher MIB-1 index than osteoblastic and fibroblastic subtypes (P < 0.05). High grade osteosarcomas (G3 and G4) revealed higher MIB-1 index compared with low grade tumors (G1 and G2). PDGF positive tumors (MIB-1 index: 20.0) showed significantly higher proliferation compared with PDGF negative tumors (MIB-1 index: 6.5) (P < 0.01). Five out of 37 cases (13.5%) showed positive immunoreaction for p53. There was no correlation of p53 status with MIB-1 index and the expression of growth factors or their receptors. Our results suggest that PDGF expression may be an important mediator of cell proliferation control, via an autocrine mechanism, in human osteosarcoma.

Antibodies, Monoclonal↗
PubMed1995

[Assessment of experimentally-induced pain effects and their elimination by hypnosis using pupillometry studies].

Hypnotherapeutical technique were often used for control of pain. However, an objective examination of this phenomenon was seldom carried out. The aim of the study was the psychophysiological objectivation of the effect of experimental induced pain and the elimination of pain by means of hypnosis. 22 healthy volunteers (11 female and 11 male) aged between 22 and 35 years participated in the study. In the 1st phase of the experiment static pupillometry was carried out before randomized presentation of a light stimulus (143 lux, 0.3 sec) and of a pain stimulus (coldness-spray, -50 degrees C, 0.5 sec) respectively. Afterwards the dynamic pupillary measurement was done. Additionally the Fourier analyses of pupillary oscillations reflecting central nervous activation during the static measurement (25,6 sec) was calculated. In the 2nd phase the subjects were investigated by means of the same techniques during hypnosis with specific suggestions for elimination of pain. Under light condition as well as after induction of pain an autonomic deactivation could be observed during hypnosis. Furthermore under pain condition a central deactivation could also be found, reflecting the depth of the hypnosis and the reduced perception of pain.

Adult↗
PubMed1995

[Ethanol-independent methanol elimination in chronic alcoholics].

72% of a collective of chronic alcoholics (DSM-III-R, ICD 9), who were admitted under the influence of alcohol in order to undergo alcohol withdrawal, showed a serum methanol concentration (SMC) above 10 mg/l. This level is usually considered to be the one for the detection of regular alcohol consumption. The SMC values were considerably higher in cases where alcoholic beverages with a higher methanol content were consumed rather than the ones lower in methanol. In the majority of patients a decrease of the methanol concentration could only be detected once an individually varying limit concentration of ethanol (0-0.62 g/kg) was reached. There were, however, a few exceptions where the elimination of methanol independent from the ethanol concentration could be seen. Contrasting the general collective, these 'ethanol independent' methanol eliminators showed a much higher serum level of ethanol and methanol at the time of admission. As a sign of addiction, all patients showed increased beta 60 values for ethanol and preferred high proof beverages, which at the same time have high methanol contents.

Adult↗
PubMed1994

Cell partitioning in two-polymer aqueous phase systems and cell electrophoresis in aqueous polymer solutions. Human and rat young and old red blood cells.

It has recently been found that electrophoresis in solutions of appropriately selected polymers in phosphate-buffered saline (PBS) can differentiate between some closely related cell populations which have identical electrophoretic mobilities (EPM) in PBS (e.g., human young and old red blood cells (RBC); RBC from Alzheimer patients and normal individuals). The EPM differences detected in polymer solutions are most likely a consequence of cell- and polymer-specific interactions. Aspects of the relation between the electrophoresis in aqueous polymer solutions of native and in vitro treated young and old RBC (from human and rat) and their partitioning in a charge-sensitive dextran-poly(ethylene glycol) (PEG) aqueous phase system (i.e., a system with a Donnan potential between the phases, top phase positive) have been examined further and are discussed. Unlike the behavior of RBC from Alzheimer patients and normal individuals in which an EPM difference can be detected in PEG solutions but not in dextran, differences in EPM between human young and old RBC are detectable in solutions of either polymer. Selected enzyme treatments of human young and old RBC or their fixation with aldehyde eliminates the EPM differences in dextran; while neuraminidase treatment or formaldehyde fixation of rat young and old RBC retains EPM differences in dextran between these cells. In these latter cases partitioning differences are also in evidence and are in the same direction as the cells' relative EPM (i.e., old RBC < young RBC). The earlier hypothesis that cell partitioning is 'more sensitive' than cell electrophoresis in detecting differences in surface charge between cells bears reexamination because human young and old RBC, which cannot be differentiated by single-tube partitioning in a charge-sensitive phase system, have different EPM in polymer solutions. The difference between these cells can be detected by partitioning but only by use of a multiple-extraction procedure. It is then found to be in a direction similar to the cells' relative EPM in dextran (i.e., human old RBC > young RBC). Rat young and old RBC have different partitions (rat old RBC < young RBC) and different EPM (also rat old RBC < young RBC). Thus, while cell partitioning in a charge-sensitive dextran-PEG aqueous phase system and cell electrophoresis in polymer solution seem to reflect, at least with these cell subpopulations, qualitatively analogous differences in surface properties (in that increasing partitions and EPM are concomitant), there are instances in which either of these physical measurements discerns surface differences which escape detection by the other.

Aging↗
PubMed1994

Cell partitioning in two-polymer aqueous phase systems and cell electrophoresis in aqueous polymer solutions. Red blood cells from different species.

A correlation, with some exceptions, between the partitioning behavior of red blood cells (RBCs) from different species in charge-sensitive dextran-poly(ethylene glycol) (PEG) aqueous phase systems and their relative electrophoretic mobilities (EPMs) in phosphate-buffered saline (PBS) has previously been reported. This relationship has now been further probed by carrying out RBC electrophoresis in media (i.e., dextran-rich bottom or PEG-rich top phases) more closely approximating the environment in which RBC partitioning takes place to see whether a better correlation would ensue. The ratios of viscosity-corrected EPMs of different species' RBCs in (diluted) dextran-rich or PEG-rich phases/EPMs of the respective species' RBCs in PBS differ for a number of species, and from each other, reflecting thereby differences in kind (i.e., dextran or PEG) and nature of polymer interaction with these RBCs. There is a general tendency for EPMs in any of the tested media to correlate with both the cells' relative partition ratios as well as with their relative EPMs in one of the other media. However, examination of the behavior of different species' RBCs taken two species at a time indicates that their relative EPMs in any two suspending media or in one suspending medium and partitioning often differ. Thus, both the cell partition ratio and the cell EPMs obtained in polymer media must, at least in some cases, reflect surface properties other than or in addition to the charge reflected by EPM measurements in PBS or saline. Cell electrophoresis in polymer solutions thereby provides an additional parameter for discriminating between surface properties of certain closely related cell populations.

Animals↗
PubMed1994

A neuromagnetic study of the functional organization of the sensorimotor cortex.

Movement-related neuromagnetic fields from eight healthy human subjects were investigated in a Bereitschaftspotential paradigm. The three conditions studied were right-sided mouth, index finger and foot movement. The neuromagnetic field patterns corresponding to the motor field and the movement-evoked field I were analysed using a moving dipole model. For both components a somatotopic organization was found: the estimated dipole locations for the mouth were more lateral and those for the foot more medial than the estimated dipole positions for the index finger movement. With regard to possible clinical applications, e.g. non-invasive mapping of the sensorimotor cortex and studies of plasticity of the motor function, the present results suggest that the investigation of movement-evoked field I for the index finger condition is most likely to yield further results.

Adult↗
PubMed1994

Synergy between cyclosporin A and a monoclonal antibody to B7 in blocking alloantigen-induced T-cell activation.

Costimulatory signals are absolutely required for T-cell activation after T-cell receptor/major histocompatibility complex-peptide interaction. So far, the best-known candidate essential costimulatory signal is mediated by interaction of CD28 on T cells with B7 on antigen-presenting cells. Using an allogeneic B7+ Epstein-Barr virus-transformed B-cell line as stimulator, we found that addition of a monoclonal antibody (MoAb) to B7 that efficiently blocks B7-CD28 interaction only partially inhibited proliferation and interleukin-2 (IL-2) production in primary and secondary mixed lymphocyte reactions (MLR), whereas the generation of cytotoxic T lymphocytes (CTL) was not affected. Inhibition of primary or secondary MLR-induced T-cell activation with cyclosporin A (CsA) at nontoxic concentrations also was never complete. However, the combination of CsA and anti-B7 MoAb B7-24 synergistically blocked allogeneic B cell-induced T-cell proliferation, IL-2 production, and CTL generation. These data suggest that the mere blockage of B7-CD28 interaction during allotransplantation will be insufficient to prevent rejection or graft-versus-host disease. However, low CsA concentrations, when combined with an agent blocking B7-CD28 interaction, can potentially achieve complete immunosuppression.

Abatacept↗
PubMed1994

A case of pure red cell aplasia: follow-up on different immunosuppressive regimens.

A 66-year-old patient was admitted to our hospital in January 1992 for further evaluation of severe normocytic anemia. Hemoglobin (Hb) was 3.5 g/dl, reticulocyte count 1%. Bone marrow showed a nearly complete lack of red cell precursors, thus favoring the diagnosis of acquired pure red cell aplasia (PRCA). Immunosuppressive therapy with prednisolone was started but had to be supplemented with azathioprine because of a further rapid decrease in Hb to 3.7 g/dl after an initial transfusion of 6 U red blood cells. However, with this regimen a renewed decrease in Hb to 6.6 g/dl was noted, and further transfusions were required. Therefore therapy was switched to cyclosporine A (CyA) while tapering off prednisolone. Four months after the initial diagnosis a positive parvovirus B19 IgM antibody was found. After the failure of hematological remission with three immunosuppressive regimens a course of high-dose intravenous immunoglobulins (IVIG) was administered in July 1992. Six weeks after IVIG therapy a peak hemoglobin concentration of 12.3 g/dl was noted, and further transfusion was not required. CyA was tapered off in October 1992. One month later CyA was reinstituted because of a relapse of PRCA but was unsuccessful until January 1993. At this time immunosuppressive CyA therapy was discontinued because of a periodontal abscess. In February 1993 a second IVIG infusion was given, and a second remission of PRCA was noted, showing an increase in hemoglobin up to 14.5 g/dl by November 1993. At the last follow-up visit in February 1994 our patient was still in complete hematological remission.

Aged↗