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Biomedical subjects

D Lehmann

Publications and source records attributed to D Lehmann.

At least 109 records · Page 6Linked to original sources
PubMed1993

Adaptive segmentation of spontaneous EEG map series into spatially defined microstates.

Space-oriented segmentation can decompose multi-channel EEG map series into time segments characterized by quasi-stationary field map configurations. This assesses the dynamics of the underlying processes as activities of different neural generator ensembles. Our method of space-oriented segmentation describes the scalp field at times of maximal field strength (Global Field Power) by the locations of the centroids of positive and negative map areas. A quantitative measure of the simultaneous distance of the centroid locations evaluates the similarity between consecutive maps. A segment is defined as a sequence of maps that do not differ from each other by more than a present value. Finally, the average centroid locations for each segment are entered into an agglomerative clustering procedure to obtain a set of distinct classes of field configurations. Four records of 16 s of 42-channel resting EEG (band-pass filtered 2-16 Hz) from six subjects were analyzed. Average segment duration was 157.9 ms. Most segments belonged to a small number of classes (from 2 to 6, mean 3.7 classes for 90% of analysis time). The most frequent class showed an anterior-posterior field orientation and covered from 45 to 74% (mean 55% across subjects) of total time, with an average duration of 265 ms. The procedure was also tested using temporally and spatially unstructured data (white noise and randomly shuffled EEG) to ascertain that the methods reflect the spatio-temporal structure of the EEG processes.

Adult↗
PubMed1993

Space-oriented EEG segmentation reveals changes in brain electric field maps under the influence of a nootropic drug.

Map landscape-based segmentation of the sequences of momentary potential distribution maps (42-channel recordings) into brain microstates during spontaneous brain activity was used to study brain electric field spatial effects of single doses of piracetam (2.9, 4.8, and 9.6 g Nootropil UCB and placebo) in a double-blind study of five normal young volunteers. Four 15-second epochs were analyzed from each subject and drug condition. The most prominent class of microstates (covering 49% of the time) consisted of potential maps with a generally anterior-posterior field orientation. The map orientation of this microstate class showed an increasing clockwise deviation from the placebo condition with increasing drug doses (Fisher's probability product, p < 0.014). The results of this study suggest the use of microstate segmentation analysis for the assessment of central effects of medication in spontaneous multi-channel electroencephalographic data, as a complementary approach to frequency-domain analysis.

Adult↗
PubMed1993

Source localization of brain electric field frequency bands during conscious, spontaneous, visual imagery and abstract thought.

This paper addresses the issue of mind-brain correspondence, using a novel way to reduce brain electric field data in the frequency domain to estimates of intracerebral model source locations, and applying this method to brain electric data collected during the 2-s epochs immediately before the randomly solicited reports of spontaneous, conscious, covert experiences from 12 normal volunteers. The mentation reports were classified into visual imagery and abstract thought. The mean locations of the EEG model sources associated with abstract thoughts were generally more anterior and deeper than those of visual imagery, particularly significant for the delta/theta band; the finding was common across subjects. Thus, different brain functional states involving different geometries of activated neural populations exist during conscious, spontaneous, task-free mentations of the visual imagery type and of the abstract thought type.

Acoustic Stimulation↗
PubMed1993

Acquisition and invasiveness of different serotypes of Streptococcus pneumoniae in young children.

Rates of acquisition and mean duration of nasal carriage of different serotypes of Streptococcus pneumoniae have been estimated by fitting a stochastic model to longitudinal carriage data in children from Papua New Guinea. Immunogenicity and two indices of relative invasiveness were determined for each serotype. Immunogenic serotypes were less frequently acquired and were carried for shorter periods, but no relationship between immunogenicity and invasiveness was apparent using either index of invasiveness. Frequent invasion was associated with a high acquisition rate and high frequency and prolonged duration of carriage. Carriage studies can provide a broad indication of which serotypes cause invasive disease but not the proportion of disease due to individual serotypes; some serotypes which cause invasive disease (e.g. serotype 46) are not found even in extensive carriage studies. The antibiotic resistance of carriage organisms, however, does approximate the resistance patterns of invasive organisms and thus may be used to monitor changing patterns of antimicrobial susceptibility in the community.

Antibodies, Bacterial↗
PubMed1993

Levels of anti-pneumococcal antibodies in young children in Papua New Guinea.

Anti-pneumococcal polysaccharide antibody (anti-PPS) levels were measured in 153 serum samples collected from children aged between 2 and 47 months living in the highlands of Papua New Guinea (PNG). Fifty-seven of the samples were collected during acute episodes of lower respiratory tract infection (ALRI). Total IgA and IgG increased steadily with age; however, no association was found between the levels of these antibodies and the health status of the child. Total IgM levels showed little relationship to the age of the child but under 12 months of age levels were somewhat higher on average in children with pneumonia. For most of eight pneumococcal serotypes tested, specific IgG levels were found to decline rapidly in the first 6-8 months, reaching a minimum at approximately 12 months of age. Serotype 3 was exceptional in having very low titres in the youngest children. A separate analysis of 24 cord sera suggested that antibodies to this serotype do not usually cross the placenta in PNG. Children with pneumonia tended to have lower levels of specific IgG than healthy controls of the same age. Specific anti-PPS IgA levels were found to increase steadily with age, but were not associated with health status.

Age Factors↗
PubMed1993

Antigenuria in healthy Papua New Guinean children with nasal Haemophilus influenzae type b carriage.

In 100 healthy children under the age of 3 years living in the vicinity of Goroka, Papua New Guinea, the nares were cultured for Haemophilus influenzae type b (Hib), and a urine sample was obtained for measurement of Hib polysaccharide (PS) by ELISA. Hib carriage was detected in nine children and Hib PS was detected in the urine of 11. Hib PS was found in seven of nine Hib nasal carriers compared with four of 91 healthy children without Hib in their nares (p < 0.001). The range of urine antigen concentrations in the two groups was similar (0.6 to 2.7 ng/ml). The relative risk of antigenuria in the carriers, compared with the children with negative nares cultures, was 58 (95% confidence interval, 10.5-324). These data extend previous observations from Hib carriers studied in the United States and show that Hib carriage in children from a developing country is associated with antigenuria. Further studies are needed to determine whether carriers and patients can be differentiated by differences in the magnitude of the concentration of Hib PS excreted in urine.

Antigens, Bacterial↗
PubMed1993

Localization of sources of brain alpha/theta/delta activity and the influence of the mode of spontaneous mentation.

A method is described that accounts for multichannel brain field data (EEG) epochs, after transformation into the frequency domain, by a single oscillating dipole source in terms of phase angles. The method produces a potential distribution for each frequency point ('FFT dipole approximation'). These maps can be subjected to conventional equivalent dipole source fittings in terms of amplitudes. We studied the equivalent source locations for the different temporal EEG frequency bands (delta/theta/alpha) in 12 normal subjects during the collection of reports of spontaneous thoughts. Some of the thought reports were classed into two modes, 'visual imagery' and 'abstract', and the associated equivalent source locations during the 2 s immediately prior to these reports were computed. Different equivalent source locations were found for the different spectral components of the EEG, implying that different neural generator populations generate the different frequencies. Further, the different types of spontaneous thought, i.e. different modes of cortical functioning, were found to be associated with the activity of different neuronal generator sources that operated at the same frequency at different source locations.

Alpha Rhythm↗
PubMed1993

Single doses of piracetam affect 42-channel event-related potential microstate maps in a cognitive paradigm.

We examined whether a single administration of piracetam produces dose-dependent effects on brain functions in healthy young men. In 6 subjects, 42-channel event-related EEG potential maps (ERP) were recorded during a task requiring subjects to watch single digits presented in a pseudorandom order on a screen and to press a button after all triplets of three consecutive odd or even digits. The ERP maps to the three digits of the correctly detected triplets were analyzed in terms of their mapped ERP field configuration (landscape). Different landscapes of the maps indicate different configuration of the activated neural population and therefore reflect different functional microstates of the brain. In order to identify these microstates, adaptive segmentation of the map series based on their landscapes was done. Nineteen time segments were found. These segments were tested for direct effects on brain function of three single doses of piracetam (2.9, 4.8 or 9.6 g) and a placebo given double-blind in balanced order. Piracetam mainly affected the map landscape of the time segments following the triplet's last digit. U-shaped dose-dependent effects were found; they were strongest after 4.8 g piracetam. Since these particular ERP segments are recognized to be strongly correlated to cognitive functions, the present findings suggest that single medium doses of piracetam selectively activate differently located or oriented neurons during cognitive steps of information processing.

Adult↗
PubMed1993

Prevention and reversal of adoptively transferred, chronic relapsing experimental autoimmune encephalomyelitis with a single high dose cytoreductive treatment followed by syngeneic bone marrow transplantation.

A chronic relapsing form of experimental autoimmune encephalomyelitis (CR-EAE) was induced in SJL/J mice by adoptive transfer of lymph node cells (LNC) sensitized to guinea pig myelin basic protein (GMBP). We examined the efficacy of high dose immunosuppressive regimens (cyclophosphamide [CY] 300 mg/kg or total body irradiation [TBI] 900 cGy) followed by syngeneic bone marrow transplantation (SBMT) in prevention and treatment of already established CR-EAE. Treatment with TBI and SBMT on day 5 after the induction of CR-EAE, just before the onset of clinical signs, completely inhibited the appearance of the paralytic signs. The same treatment, applied 4 d after the clinical onset of the disease, led to a significant regression of the paralytic signs and to a total inhibition of spontaneous relapses during a follow-up period of 2 mo. Challenge of mice with GMBP+CFA 78 d after the passive induction of CR-EAE induced a relapse of the disease 7 d later in almost all of the untreated mice; in contrast, the same challenge given to TBI+SBMT-treated mice caused a delayed relapse (30 d later) in only a minority (3/7) of the challenged mice. In vitro lymphocytic proliferative responses to GMBP and purified protein derivative were significantly lower in TBI/SBMT-treated mice before and after the GMBP challenge, although these mice were fully immunocompetent, as evidenced by their normal lymphocytic proliferation to concanavalin A (ConA) and the FACS analysis of their lymphocytic subpopulations. A similar beneficial therapeutic effect was observed in mice treated with CY followed by SBMT, after the onset of CR-EAE. Our results could support possible clinical applications of similar therapeutic strategies, involving acute immunosuppression followed by stem cell transplantation and retolerization of the reconstituting immune cells in life-threatening neurological and multisystemic autoimmune diseases.

Animals↗
PubMed1992

Prevention of experimental autoimmune encephalomyelitis and induction of tolerance with acute immunosuppression followed by syngeneic bone marrow transplantation.

Experimental autoimmune encephalomyelitis (EAE) is an inducible autoimmune disease widely used as a model of the acute/relapsing stage of multiple sclerosis. In the present study we examined the effect of acute immunosuppression induced by total body irradiation (TBI) (900 to 1100 centigray (cGy)) or by a single high dose of cyclophosphamide (CY) (300 mg/kg), followed by syngeneic bone marrow transplantation (SBMT), on the development of EAE in SJL/J mice. EAE was induced in SJL/J mice by immunization with spinal cord homogenate in adjuvant. Treatment with TBI (900 cGy) and SBMT on day 6 postimmunization caused a delayed onset and a marked reduction in the incidence and severity of EAE. A higher dose of irradiation (1100 cGy) or the administration of CY followed by SBMT completely abrogated the development of paralysis. None of the 21 mice treated with CY and SBMT, and only 1 of 7 mice treated with TBI (1100 cGy) and SBMT developed clinical signs of EAE during a period of 3 months. Furthermore, mice treated with CY and SBMT became resistant to rechallenge with the same encephalitogenic inoculum. In addition, the lymphocytes obtained from these mice did not proliferate in vitro in response to myelin basic protein or tuberculin-purified protein derivative, unlike lymphocytes from immunized but untreated animals. This absence of reactivity was not associated with alterations in the proportion of the L3T4 and Lyt-2 T-cell subsets nor with a loss in T cell competence as evidenced by the full response of lymphocytes to the T cell mitogen Con A and to a nonrelevant Ag (OVA). Our results indicate that the elimination of effector lymphocytes either by myeloablative doses of CY or ionizing irradiation followed by rescue with SBMT inhibits the development of the autoimmune process in EAE and leads to induction of tolerance to the immunizing Ag by newly developing lymphocytes. This approach of combining immunoablation and reconstitution with autologous bone marrow transplantation may be applicable in the treatment of life-threatening neurologic autoimmune diseases.

Animals↗
PubMed1992

Randomized double blind trial of Ambroxol for the treatment of respiratory distress syndrome.

In order to test the ability of Ambroxol to improve the clinical course of respiratory distress syndrome and to reduce the incidence of complications a multicentre, randomized, placebo-controlled double-blind trial was conducted. Entry was limited to infants with a birth weight below 1500 g. A total of 179 neonates were enrolled, but 31 were later excluded because they had other diseases. Of the remaining 148 babies, 74 received Ambroxol (birth weight 1190 +/- 216 g; gestational age 29.1 +/- 1.9 weeks) and 74 placebo (birth weight 1168 +/- 216 g; gestational age 28.9 +/- 1.9 weeks). In the Ambroxol group 23 (31%) and in the placebo group 27 (37%) infants died during the first 5 months of life. In 28 day-survivors Ambroxol was able to significantly improve the PaO2/FiO2 ratio, mean airway pressure, phospholipid profile of tracheal effluent and pulmonary mechanics of spontaneously breathing infants. In addition, the incidences of bronchopulmonary dysplasia (29% vs 54%), intraventricular haemorrhage (25% vs 44%) and postnatally acquired pneumonia (15% vs 36%) were significantly reduced in the Ambroxol group as compared to the control group. No adverse events attributed to the Ambroxol treatment were reported.

Ambroxol↗
PubMed1992

Localization of the sources of EEG delta, theta, alpha and beta frequency bands using the FFT dipole approximation.

FFT dipole approximation and 3-dimensional dipole modelling were used to determine the locations of the equivalent dipole model sources of the delta, theta, alpha, beta-1 and beta-2 frequency bands in 13 normal subjects during resting. From each subject, 2 successive data sets were analysed, each consisting of 10 epochs of 2 sec randomly collected during 30 min. ANOVAs showed that over subjects, the source locations of EEG frequency bands differed significantly in the vertical and antero-posterior dimensions. Results of data set 2 confirmed those of data set 1. The source of delta was deepest and most anterior, theta more posterior and less deep, alpha most posterior and highest on the vertical dimension, beta-1 deeper and slightly more anterior than alpha, and beta-2 again more anterior and deeper than beta-1. Thus, the depth of source location was not linearly related to temporal frequency. The sources of all 5 bands were oriented in the sagittal direction; delta mean fields had steeper gradients anteriorly, alpha and beta-1 posteriorly. The power map for any frequency was well described by a single phase angle. The results indicate that the different EEG frequency bands during a given EEG epoch are generated by neural populations in different brain locations.

Adult↗
PubMed1992

Chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE): treatment and induction of tolerance, with high dose cyclophosphamide followed by syngeneic bone marrow transplantation.

We examined the effect of acute immunosuppression with high dose cyclophosphamide (CY), followed by syngeneic T-cell-depleted bone marrow transplantation (SBMT) on chronic-relapsing autoimmune encephalomyelitis (CR-EAE) induced in SJL/J mice by immunization with mouse spinal cord homogenate (MSCH) in adjuvant. Treatment of mice on day 9 post immunization, before the appearance of clinical signs of the disease, delayed the onset of paralysis, but did not affect its clinical course. Treatment on day 2-3 after the first clinical signs led to complete regression of the disease. During a period of 3 months, only one of the 15 mice treated after the the onset of CR-EAE relapsed, as compared to a total of 21 relapses in the 15 untreated animals. A rechallenge with MSCH in adjuvant on day 78 after immunization induced a severe relapse in all untreated mice, with 78% mortality; in contrast, only 25% of mice treated with CY and SBMT relapsed when similarly rechallenged. Lymphocytes from mice treated with CY and SBMT showed reduced in vitro proliferative responses to myelin basic protein (GMBP) and PPD, even after the rechallenge with MSCH. Our results show that high dose CY for elimination of immunocompetent lymphocytes, followed by SBMT rescue, suppresses CR-EAE and induces tolerance to the immunizing antigens. These results may encourage attempts to apply a similar therapeutic principle in life-threatening human neurological autoimmune diseases.

Animals↗
PubMed1992

42-channel potential map series to visual contrast and stereo stimuli: perceptual and cognitive event-related segments.

Event-related potential maps to perceptual (stimulus type) and cognitive (stimulus relevance) manipulations were studied in 12 healthy volunteers using 42-channel mapping. Perceptual manipulation used three types of visual stimuli: rectangles constituted by: (1) contrast; (2) different densities of monocular Dynamic Random Dots (Flat DRD); and (3) different binocular disparities of Dynamic Random Dots (Stereo DRD). Cognitive manipulation within each stimulus type consisted of presenting the rectangles horizontally and vertically, one of the two with a probability of 33%, and requesting the subjects to count and thus attend to the 'rare' rectangles. Spatial characteristics of the maps were analyzed; this allowed conclusions about the generating sources. The map series were adaptively segmented using the minima points of the grand mean Global Field Power curve. Segment strength (Global Field Power) and segment landscape (locations of extreme potentials) were assessed. Stimulus type had effects from 78 to 310 ms, stimulus relevance was effective from 210 to 1000 ms. In the 78-174 ms segment, Stereo DRD and Flat DRD stimuli produced similar map landscapes, while contrast stimuli produced different map landscapes. Attended and ignored stimuli produced contrary effects on landscapes at 210-310 ms as compared to those at 310-546 ms, indicative of different neural populations activated by attention processes during these late event-related potential segments. Interaction between perceptual and cognitive manipulation occurred at 210-310 ms when perceiving stereo stimuli and attending to relevant monocular visible stimuli produced similar map landscapes, suggesting a common brain resource during this segment for automatic figure perception and voluntary attention. The observed functional differences of the segments contribute to the identification of global functional microstates of brain electric activity.

Adult↗
PubMed1992

Delineation of tissue damage mechanisms in experimental autoimmune encephalomyelitis (EAE). I. Cell detachment and lysis induced by encephalitogenic CD4+ T lymphocytes.

Myelin basic protein (MBP) reactive CD4+ T lymphocytes, capable of inducing experimental autoimmune encephalomyelitis (EAE), were examined for their ability to damage target cells of central nervous system (CNS) origin. Damage was assessed by monitoring detachment of adherent astrocytes from substratum and astrocyte lysis. MBP-specific, but non-encephalitogenic CD4+ T cells mediated astrocyte detachment but not lysis. However, encephalitogenic CD4+ T cell lines were more efficient in causing astrocyte detachment and could also cause astrocyte lysis. The detachment and lytic activities of the MBP-reactive T cell lines tested were often independent of the presence of specific antigen, and were not restricted to syngeneic major histocompatibility (MHC) antigens. MBP often augmented the detaching and, if lytic, lytic activities of these T cells. The encephalitogenic CD4+ T cells also detached and lysed allogeneic 'bystander' fibroblasts in the presence of unlabelled syngeneic astrocytes, suggesting the involvement of a soluble mediator(s). Although MBP is essential for the initiation of EAE, the presence of MBP on cells of CNS origin, such as astrocytes and oligodendrocytes, does not appear to be necessary for their damage by MBP-specific CD4+ T cells. Immune CD4+ T cells, which penetrate the CNS, may disorganize brain tissue structure by lysing astrocytes directly and by damaging other brain cells indirectly by soluble mediators. Thus cellular detachment, in addition to cell lysis, mediated by MBP-specific CD4+ cells may contribute to EAE pathogenesis.

Animals↗
PubMed1992

Bacterial agents protect against autoimmune disease. I. Mice pre-exposed to Bordetella pertussis or Mycobacterium tuberculosis are highly refractory to induction of experimental autoimmune encephalomyelitis.

Infectious agents have often been implicated in the etiology of autoimmune diseases. Here we show that bacteria may also play a role in resistance to autoimmune diseases. SJL/J and (SJL/J x BALB/c)F1 mice are genetically susceptible to induction of experimental autoimmune encephalomyelitis (EAE), a murine model for human demyelinating autoimmune diseases such as multiple sclerosis. We studied the effect of several bacteria on the development of EAE and found that exposure of SJL/J or (SJL/J x BALB/c)F1 mice to Mycobacterium tuberculosis or Bordetella pertussis consistently rendered mice highly refractory to subsequent induction of the disease. Other bacteria such as Escherichia coli, Shigella and Staphylococcus aureus were found to be less effective, or were protective only if specific immunization procedures were used. Furthermore, M. tuberculosis and B. pertussis were protective irrespective of the route of administration and minute amounts (as low as 0.5 micrograms) of M. tuberculosis were sufficient to protect EAE-susceptible mice against induction of the disease. Interestingly, these bacteria, which are commonly used to promote development of EAE, conferred the highest degree of protection against the disease. The M. tuberculosis-induced protection was found to be associated with active suppression mechanisms mediated by T lymphocytes capable of transferring protection to naive syngeneic mice. These findings indicate that certain bacteria may protect against the development of autoimmune diseases. These results also suggest the potential use for still-unidentified bacterial agents in the manipulation of certain autoimmune diseases.

Animals↗
PubMed1992

Epidemiology of acute respiratory tract infections, especially those due to Haemophilus influenzae, in Papua New Guinean children.

Acute lower respiratory tract infections (ALRI) are the most common cause of death in Papua New Guinean children. Haemophilus influenzae and Streptococcus pneumoniae are almost universally carried in the nasopharynx from a young age and commonly cause disease. While most H. influenzae isolates from blood and cerebrospinal fluid are serotype b, other serotypeable and nonserotypeable H. influenzae are more frequently isolated in Papua New Guinea than in developed countries. Low levels of antipneumococcal antibody, malnutrition, and upper respiratory carriage of invasive pneumococcal serotypes are associated with increased risk of ALRI. An oral H. influenzae vaccine given to adults with chronic bronchitis reduced the bacterial load in sputum and may thereby help reduce transmission of bacteria in the community. The efficacy of conjugate H. influenzae type b vaccine in preventing pneumonia must be determined in developing countries; vaccines against other types of H. influenzae will also be needed to control pneumonia and meningitis.

Acute Disease↗