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Biomedical subjects

D Lehmann

Publications and source records attributed to D Lehmann.

At least 91 records · Page 5Linked to original sources

[Evidence of Cryptosporidium in children with symptomatic enteritis from the Leipzig administrative area 1987-1992].

From 1987 to 1992 stool samples of 3235 diarrheic children at the age from 1 to 14 years in the Leipzig district were examined for Cryptosporidium spp. In 58 patients (= 1.8%) oocysts have been detected. Most of the positive children (= 81%) were less than 7 years old. A seasonal increasing of prevalence was observed in August and in the following months. According to anamnestic informations of treating physicians all patients were immunocompetent. The clinical symptomatology comprised diarrhoea, vomiting, fever and stomach ache. Animal contacts were known in 52% of the patients. Stool examinations for diagnosis of Cryptosporidium are recommended in unclear diarrhoeas, also in immunocompetent patients. The role of Cryptosporidium spp. as opportunists in immunodeficiency is especially commented.

Animals↗

Immunomodulation of experimental autoimmune myasthenia gravis with linomide.

Linomide, a synthetic immunomodulator, increases natural killer (NK) activity and markedly activates several lymphocyte populations in both experimental animals and humans. It has been shown to ameliorate the autoimmune manifestations of lupus-like disease in MRL/lpr mice and the clinical and pathological signs of acute and chronic-relapsing experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. We examined the effect of linomide (100 mg/kg/day; administered in drinking water) on rabbits and rats with experimental autoimmune myasthenia gravis (EAMG). Following immunization with Torpedo acetylcholine receptor (AChR), all control rabbits developed clinical signs of severe weakness and exhibited a decrement of muscle action potential upon repetitive stimulation. In contrast, mild signs of weakness appeared in only two of five linomide-treated rabbits, with EMG borderline positive in one of them. Booster immunization with Torpedo AChR induced severe relapse and death in two EAMG control rabbits, whereas the two linomide-treated animals remained free of myasthenic symptoms. The serum level of antibodies against both Torpedo and rat AChR were markedly suppressed in the linomide-treated animals. Similar inhibition of clinical signs of EAMG was observed in the EAMG rat model. Furthermore, the in vitro proliferative response of lymph node cells to Torpedo AChR and the purified protein derivative of Mycobacterium tuberculosis was significantly lower in the linomide-treated EAMG rats than in the controls. Linomide may constitute a new immunomodulating agent for the treatment of myasthenia gravis.

Adjuvants, Immunologic↗

Oral administration of the oxidant-scavenger N-acetyl-L-cysteine inhibits acute experimental autoimmune encephalomyelitis.

The prevention of acute experimental autoimmune encephalomyelitis (EAE) by N-acetyl-L-cysteine (NAC), a potent free radical scavenger, is described. Administrated ad libitum to SJL/J mice at a dosage of 0.2-2 mg/ml in drinking water from the day of the encephalitogenic injection, the agent significantly inhibited the induction of acute EAE. The improvement in clinical condition was dose-dependent. A complete protective effect required administration of the agent at an early stage. Examination of lymphocytes from NAC-treated EAE mice showed that at early stages (days 9 and 15) post encephalitogenic injection the anti-oxidant enhanced the specific lymphocyte proliferative response to the immunizing antigens. Examination of the mitogenic stimulation of lymphocytes from naive animals in the presence of NAC in vitro indicated that the scavenger enhanced the stimulative effect of LPS in a dose-dependent manner. The immunomodulative capacity of the anti-oxidant NAC suggests that free radicals are involved in the pathogenesis of acute EAE.

Acetylcysteine↗

Low resolution electromagnetic tomography: a new method for localizing electrical activity in the brain.

This paper presents a new method for localizing the electric activity in the brain based on multichannel surface EEG recordings. In contrast to the models presented up to now the new method does not assume a limited number of dipolar point sources nor a distribution on a given known surface, but directly computes a current distribution throughout the full brain volume. In order to find a unique solution for the 3-dimensional distribution among the infinite set of different possible solutions, the method assumes that neighboring neurons are simultaneously and synchronously activated. The basic assumption rests on evidence from single cell recordings in the brain that demonstrates strong synchronization of adjacent neurons. In view of this physiological consideration the computational task is to select the smoothest of all possible 3-dimensional current distributions, a task that is a common procedure in generalized signal processing. The result is a true 3-dimensional tomography with the characteristic that localization is preserved with a certain amount of dispersion, i.e., it has a relatively low spatial resolution. The new method, which we call Low Resolution Electromagnetic Tomography (LORETA) is illustrated with two different sets of evoked potential data, the first showing the tomography of the P100 component to checkerboard stimulation of the left, right, upper and lower hemiretina, and the second showing the results for the auditory N100 component and the two cognitive components CNV and P300. A direct comparison of the tomography results with those obtained from fitting one and two dipoles illustrates that the new method provides physiologically meaningful results while dipolar solutions fail in many situations. In the case of the cognitive components, the method offers new hypotheses on the location of higher cognitive functions in the brain.

Brain↗

Seroepidemiology of cryptosporidiosis in children in Papua New Guinea and Australia.

Enzyme immunoassays (EIA) were used to measure serum antibodies to Cryptosporidium in four immunocompetent adults with recent proven cryptosporidial infection, 379 healthy children and 73 adult volunteers in Melbourne, Australia, and 205 children in Papua New Guinea (PNG) (47 healthy children; 158 with pneumonia). Antibodies peaked 3-6 weeks after infection and fell to baseline within a few months. A high level (5000 EIA units/ml) or a significant change between paired sera, of IgG or IgM, were taken as evidence of recent infection and found in 24% of PNG children and in 8% of children and 5% of adults in Melbourne. Among PNG children with pneumonia who had high cryptosporidial antibody levels, those with measles (6/8) were significantly more likely (P = 0.002) to have diarrhoea than the remainder (4/28). Symptomatic cryptosporidiosis may be associated with transient immune suppression due to viral infection. This study indicates that serological surveys can contribute to an understanding of the epidemiology of cryptosporidosis.

Adult↗

Analyses of 94 consecutive spinal cord injury patients using ASIA definition and modified Frankel score classification.

Serial neurological examinations were analysed on 94 consecutive spinal cord injury (SCI) patients admitted for rehabilitation to the Swiss Paraplegic Center at the Clinic Balgrist Zurich, Switzerland between 1987 and 1992. Patients' data were examined adopting ASIA and modified Frankel definitions in order to compare the two classifications in terms of consistency and prognostic value. The modified Frankel definition was subdivided into five categories (A, B, C, D and E). On admission (discharge) 43 (37) patients were classified as Frankel A, 23 (11) patients in group B, 26 (42) patients in group C, 2 (2) patients as Frankel D and 0 (2) patients in group E. A qualitative analysis of the results on the base of a maximal score of 100 points (A = 0, B = 25, C = 50, D = 75 and E = 100 points) suggested a mean score improvement from 21.5 (+/- 22.5) to 29.0 (+/- 26.3) or 7.5 (+/- 7.1), regarding all 94 patients during follow up (admission/discharge). The median improvement was one modified Frankel grade (A/B to B/C). No detailed assessments were yielded concerning motor and sensory functions. Using ASIA definition, a continuous numerical score of motor and sensory function was observed. Recovery during follow up was determined by detailed motor and sensory function. For all 94 patients (quadriplegics and tetraplegics), the average motor recovery according to the ASIA definition was 9.4 (+/- 9.6). The mean ASIA motor score improved from 52.2 (+/- 17.3) on admission to 61.6 (+/- 17.9) on discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Immunoglobulin G antibody responses to polyvalent pneumococcal vaccine in children in the highlands of Papua New Guinea.

The immunoglobulin G (IgG) antibody responses to a pneumococcal polysaccharide vaccine were examined for 480 children aged 3 months to 5 years and living in Tari, Southern Highlands Province, Papua New Guinea. Antipneumococcal IgG to the seven serotypes most frequently causing invasive disease (types 2, 5, 6B, 7F, 14, 19F, and 23F) was measured by an enzyme-linked immunosorbent assay in serum collected before vaccination and 1 and 6 months after vaccination. Prevaccination antibody levels fell rapidly after 3 months of age and remained low throughout the first 2 years of life. One month after vaccination, geometric mean titers of antipneumococcal IgG to serotypes 2, 7F, 23F, and 5 were at least twice those of antibodies in nonvaccinated children of the same age from the ages of 5, 6, 9, and 12 months onwards, respectively; postvaccination antibody responses to serotypes 6B, 14, and 19F rose gradually during the second year of life. Elevated antibody titers to serotypes 2 and 7F were maintained 6 months after vaccination. Thus, young Papua New Guinean children are capable of mounting a good immune response to some pneumococcal capsular polysaccharides from a young age, and the antibody responses to capsular polysaccharides are consistent with studies in developed countries. However, in Papua New Guinea, the serogroup distribution of invasive disease matches the immunogenic components of the pneumococcal polysaccharide vaccine more closely than in developed countries, a fact which helps to explain the results of controlled trials in Papua New Guinea, in which this vaccine prevented death and severe morbidity from pneumonia in young children.

Age Factors↗

Diazepam and sulpiride effects on frequency domain EEG source locations.

Effects of an anxiolytic (diazepam; n = 13) and an antipsychotic (sulpiride; n = 6) on the location of EEG model sources in the frequency domain were studied in normal volunteers in 19-channel eyes-closed EEG before and 1, 15, 30, 45 and 60 min after i.v. injections. Ten 2-second epochs from each recording were subjected to the fast Fourier transformation (FFT) Dipole Approximation which results in a single-source (in terms of phase angle) potential distribution map for each frequency point. Three-dimensional model dipole sources were fitted into the maps. Differences in source location before and after injection were computed, and differences between drugs were evaluated. The source location in the beta band shifted significantly more towards superior and anterior areas after diazepam than sulpiride, most prominently in the first minute after injection; during this time, conventional beta band power was significantly increased after diazepam versus sulpiride at all recording sites. The results demonstrate that the FFT dipole approximation adds direct 3-dimensional topographical information to power spectral results in pharmaco-EEG.

Adult↗

Inoculation of BCL1 lymphoma cells into CSJL/J F1 mice inhibits acute experimental autoimmune encephalomyelitis.

T cell vaccination, which protects rodents against experimental autoimmune encephalomyelitis (EAE), has been shown to induce anti-idiotypic response in the T cell compartment. CD5 B cells (B1 cells) are the main source of natural autoantibodies, and are often characterized by high idiotypic connectivity. In this study we examined the possibility that idiotypic connectivity in the B cell compartment may also play a role in the regulation of EAE. We inoculated CSJLF1 mice (H-2d,s) with a CD5 B cell line, the BCL1 lymphoma cells (H-2d), and subsequently induced EAE. The injection of as few as 1,000 BCL1 lymphoma cells significantly blocked the development of EAE. Injection of CD5-negative myeloma cells (SP2) had no effect on the pathogenesis of the disease. Unlike control animals, lymphocytes from BCL1 lymphoma-injected mice significantly proliferate in response to interleukin-5, a growth factor to CD5 B cells. The proliferative response of lymphocytes from BCL1 inoculated mice to mitogenic stimulation was rather unchanged, indicating that no general immunosuppression has been induced by inoculating BCLJ lymphoma. These experiments suggest that CD5 B cells may be involved in the regulation of EAE.

Acute Disease↗

Treatment of chronic-relapsing experimental autoimmune encephalomyelitis with the synthetic immunomodulator linomide (quinoline-3-carboxamide).

Linomide is a synthetic immunomodulator that enhances natural killer cell activity and significantly activates several lymphocytic cell subpopulations in both experimental animals and humans. In this study we examined the effect of linomide (80 mg per kg per day in drinking water) on mice with chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE), a T-cell-mediated organ-specific autoimmune disease that resembles human multiple sclerosis. None of the mice (n = 17) that were treated with linomide from day 7 after disease induction developed any clinical or histopathological signs of CR-EAE, as compared to 19 of 20 untreated controls that were severely paralyzed and had extensive demyelinating lesions in the central nervous system. Linomide-treated animals were also resistant to an induced attack by a booster injection with a murine spinal cord homogenate. When administered to mice exhibiting severe clinical signs of paralysis, linomide inhibited both spontaneous and induced relapses. Linomide treatment protected mice from passively induced CR-EAE as well, when given from the day of injection with myelin-basic-protein-specific lymphocytes. Lymphocytes obtained from linomide-treated mice had a reduced in vitro proliferative response to the myelin basic protein and to the tuberculin purified protein derivative, whereas the mitogenic response to concanavalin A was not affected. Natural killer cell and lymphokine-activated killer cell activities were enhanced. These results suggest that linomide regulates autoimmunity in the absence of systemic immunosuppression. Since linomide is very well tolerated in experimental animals and humans, it might be used in the treatment of multiple sclerosis.

Adjuvants, Immunologic↗

Dimensional complexity of EEG brain mechanisms in untreated schizophrenia.

The dimensional complexity of left temporal-parietal and parietal-occipital electroencephalographic (EEG) recordings was assessed by computing the correlation dimension during 20 sec in six recording conditions from 15 first-episode acute schizophrenics before medication, 12 other medication-free individuals clinically and socially remitted after a first schizophrenic episode, 17 medication-free neurotics and 17 controls. The correlation dimension of the temporal-parietal EEG differed between groups [analysis of variance (ANOVA)] (p < 0.004), whereas neurotics (different from schizophrenics at p < 0.002) and remitted schizophrenics showed intermediate values. There was no overall significant difference between groups in the parietal-occipital EEG. Differences of the correlation dimension of the temporal-parietal versus the parietal-occipital EEG were significant between groups (ANOVA p < 0.05); first-episode schizophrenics differed from controls (p < 0.002) and remitted patients (p < 0.08). Increased dimensional complexity of schizophrenic EEG was found in one of two examined brain regions. The higher dimensional complexity of functional brain mechanisms in schizophrenics versus normals is reminiscent of the loosened organization of thought, and of suggestions of certain superior abilities in the patients.

Acute Disease↗

Inhibition of acute, experimental autoimmune encephalomyelitis by the synthetic immunomodulator linomide.

Linomide (LS-2616, quinoline-3-carboxamide) is a synthetic immunomodulator that stimulates natural killer cell activity and activates several lymphocytic subpopulations in experimental animals and humans. In this study we determined the effect of oral treatment with linomide on the development of experimental autoimmune encephalomyelitis, an animal model for immune-mediated human demyelinating disorders. Experimental autoimmune encephalomyelitis was induced in SJL/J mice and in an outbred strain of rats (Sabra) by subcutaneous injection of spinal cord homogenate in adjuvant followed by inoculation with Bordetella pertussis. Linomide was administered in drinking water, at an estimated dose of 50 to 100 mg/kg/day. None of the linomide-treated mice (0/41) and Sabra rats (0/15) developed any clinical or pathological signs of experimental autoimmune encephalomyelitis, whereas almost all control animals (48/53 and 18/19, respectively) were severely paralyzed and 64.5% died from the disease. Lymphocytes obtained from linomide-treated animals had reduced in vitro proliferative responses to guinea pig myelin basic protein, proteolipid protein of the myelin, and tuberculin-purified protein derivative, unlike antigen-independent proliferation which was rather unaffected. Natural killer cell activity (tested by a cytotoxic assay on radiolabeled YAC-1 target cells) was significantly enhanced in mice treated with linomide. Our results indicate that modulation of the immune system with linomide leads to complete inhibition of experimental autoimmune encephalomyelitis in the absence of systemic immunosuppression. Linomide could therefore be of use in future clinical trials for the treatment of human autoimmune demyelinating disorders.

Adjuvants, Immunologic↗

Protection against autoimmune disease by bacterial agents. II. PPD and pertussis toxin as proteins active in protecting mice against experimental autoimmune encephalomyelitis.

Bordetella pertussis and Mycobacterium tuberculosis, routinely used to promote the development of autoimmune disease, were recently reported to also be effective in inducing protection against an autoimmune disease. Thus, we previously demonstrated that SJL/J and (SJL/J x BALB/c)F1 mice that are genetically susceptible to experimental autoimmune encephalomyelitis (EAE) become highly refractory to the induction of the disease following their exposure to B. pertussis and M. tuberculosis. In the present study, the pertussis toxin (PT) from B. pertussis and the purified protein derivative (PPD) of M. tuberculosis, were found to be sufficient to fully protect against EAE and thus may be the major bacterial components responsible for conferring protection. The 65-kDa heat-shock protein played only a marginal role in the protection against EAE induced by these bacteria. Both PT and PPD were protective when given before, but not after, the encephalitogenic challenge, and minute amounts (5-50 ng) emulsified in oil were sufficient to confer long-lasting resistance to EAE. The effect of PT or PPD on EAE differed from that of mitogens or bacterial superantigens, suggesting that their protection ability was not attributable merely to mitogenic or superantigenic properties. The mechanism of protection is not yet clear. Preliminary studies revealed a complex mechanism of protection whereby PPD and PT may operate differently. Thus, only PPD-induced, but not PT-induced, protection was transferrable by CD4+ T lymphocytes bearing an alpha beta T cell antigen receptor. Neither PT nor PPD had a protective effect on EAE mediated by preformed pathogenic T lymphocytes and it is most likely that they exert their protection by affecting the development of such T lymphocytes. How bacteria such as B. pertussis and M. tuberculosis can either enhance the development of an autoimmune disease or protect against the disease is not yet clear. However, identifying PT and PPD as the bacterial components active in protection may allow a better understanding of the modulatory effects of bacteria and point to the potential use of such bacterial products in immunomodulation of autoimmune diseases.

Animals↗

EEG reactivity in high and low symptomatic schizophrenics, using source modelling in the frequency domain.

A dipole localization method in the frequency domain was used (FFT Dipole Approximation) to assess spatial differences in the spectral EEG reactivity (orienting response) between high and low symptomatic schizophrenics. Frequency bands of interest were determined empirically by comparing the two dichotomized patient groups with two matched control groups. Evidence for a correlation between EEG reactivity and severity of schizophrenic symptomatology was found, especially in the higher beta frequency range (16-25.5 Hz). Opposite effects were found in the two beta ranges of 20.5-22.5 Hz and 23.0-25.5 Hz, supporting the hypothesis that different EEG frequency bands have specific functional significances and that these bands are not necessarily those that are conventionally selected.

Adaptation, Physiological↗

Global dimensional complexity of multi-channel EEG indicates change of human brain functional state after a single dose of a nootropic drug.

Viewing the multi-channel EEG as a sequence of momentary field maps corresponds to the concept of a trajectory in K-dimensional state space (K = number of channels). This approach permits a quantitative, single value measure of complexity of the brain state trajectory, the global correlation dimension that describes the ensemble characteristics of all recorded channels. In 5 normal volunteers, 4 records of 16-channel resting EEG were obtained during each of 4 randomized sessions (double blind design) after a single dose of placebo or 2.9 g or 4.8 g or 9.6 g piracetam. The global correlation dimension of a 40 sec epoch from each record was estimated, using 50 computational runs with 8192 point pairs. The results were combined for the two intermediate doses and averaged over repeated records. The dimensionality decreased from placebo (median = 5.89) to low dose (median = 5.72) to high dose (median = 5.59), significant in a Friedman ANOVA at P < 0.02, with significant differences between placebo vs. high and low vs. high dose. Thus, the subtle change of brain global functional state after a single dose of piracetam is reflected by the non-linear measure of global dimensional complexity of the multi-channel EEG.

Adult↗

Data-determined window size and space-oriented segmentation of spontaneous EEG map series.

For the segmentation of series of momentary potential distribution maps into epochs of quasi-stable landscape (brain electric microstates), the maps are reduced to extracted landscape descriptors. Changes of the descriptors over time are recognized as segment terminators. The selection of the descriptors' tolerated variance (the window size) determines the result. We present a window-determining function which allows a data-driven determination of the optimal window size, based on equal weight given to the recognition of similarity and dissimilarity between maps. Segmentations based on two map descriptors (locations of extreme potentials and centroids) were used on 211 two-second map epochs from 8 normal subjects for validation of the window-determining function and to establish normative data. Using the data-determined window sizes for segmentation, the mean duration of the obtained microstates across subjects did not differ between descriptors (144 and 143 msec, respectively). Random permutation of the maps in time produced significantly shorter segments, ensuring that the segmentation disclosed real properties of the original data and not artifacts of the procedure.

Adult↗