Prognostic impact of the serum levels of soluble CD23 in B-cell chronic lymphocytic leukemia.
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Biomarkers, Tumor↗
Biomedical subjects
B Mohr
Publications and source records attributed to B Mohr.
Short-term effects of behavioral treatment on movement initiation and postural control in Parkinson's disease: a controlled clinical study.
In a controlled clinical study, we investigated the effects of behavioral treatment on postural and gait initiation problems idiopathic Parkinson's disease (PD). Comparable groups of patients received therapy (experimental group, n = 15) and nonspecific psychological treatment (control group, n = 14) for 10 weeks. We monitored various variables reflecting properties of posture and gait initiation by using an optoelectronic motion analyzer (electronic movement analysis system, ELITE). A clinician blind to group membership of the patients assessed PD severity with the United Parkinson's Disease Rating Scale (UPDRS) before and after the treatment period. ELITE measures of postural stability and movement initiation revealed treatment-specific effects. In addition, UPDRS motor scores showed significant improvement only after behavioral treatment. We conclude that behavioral treatment in Parkinson's disease may improve motor disabilities in moderately advanced PD patients.
Aged↗
High-frequency brain activity: its possible role in attention, perception and language processing.
Coherent high-frequency neuronal activity has been proposed as a physiological indicator of perceptual and higher cognitive processes. Some of these processes can only be investigated in humans and the use of non-invasive recording techniques appears to be a prerequisite for investigating their physiological substrate in the healthy human brain. After addressing methodological issues in the non-invasive recording of high-frequency responses, we summarize studies indicating co-occurrence of neuronal synchrony of single cells exhibiting rhythmic activity at high frequencies, oscillations in the local field potential and dynamics in high frequencies recorded using high-resolution electroencephalography (EEG) and magnetoencephalography (MEG). We then review EEG and MEG studies of attention, perception, and language processing in humans indicating that dynamics in the high-frequency range > 20 Hz reflect specific cognitive processes. Types of high-frequency (HF) activity can be distinguished according to their latency after stimulus onset, stimulus-locking, cortical topography and frequency. There appears to be a systematic relationship between specific cognitive processes and types of HF activity. The findings are related to recent theories about the generation of HF activity and their possible role in binding of stimulus features. Dynamics of HF cortical activity reflecting higher cognitive processes can be accounted for based on the assumption that the elements of cognitive processing, e.g. visual objects and words, are organized in the brain as distributed neuronal assemblies with defined cortical topographies generating well-timed spatio-temporal activity patterns.
Arousal↗
Duraflo II coating of cardiopulmonary bypass circuits reduces complement activation, but does not affect the release of granulocyte enzymes : a European multicentre study.
OBJECTIVE: This study was carried out to: (a) compare complement and granulocyte activation during cardiac operations in patients operated with cardiopulmonary bypass coated with heparin by the Duraflo II method, with activation in patients operated with uncoated circuits; and (b) relate complement, and granulocyte activation to selected adverse effects. METHODS: In a multicentre study among Rikshospitalet, Ullevaal Hospital in Norway and Uppsala University Hospital in Sweden, plasma concentrations of the complement activation products C4b/iC4b/C4c (C4bc), C3b/iC3b/C3c (C3bc), the terminal SC5b-9 complement complex (TCC), and the granulocyte proteins myeloperoxidase and lactoferrin were assessed in two groups of patients undergoing aortocoronary bypass. Seventy-six patients underwent surgery operated with circuits coated by the Duraflo II heparin coating and 75 uncoated circuits. The same amount of systemic heparin was administered to all patients. RESULTS: In both groups a significant increase in C4bc was first seen by the end of operation, from 86.7 +/- 12.5 to 273.0 +/- 277.4 nM in controls and from 86.9 +/- 18.5 to 320.2 +/- 190.5 nM in the control group, confirming previous documentation that the classical pathway is not activated during CPB, but as a consequence of protamin administration. The formation of C4bc did not differ significantly between the two groups. In the uncoated group the C3bc concentration increased from 124.0 +/- 15.3 to a maximum of 1176.1 +/- 64.7 nM (P < 0.01) and in the coated group it increased from 129.8 +/- 16.1 to a maximum of 1019.4 +/- 54.9 nM (P < 0.01) during CPB. Summary values but not peak values differed significantly between the groups. In the uncoated group the TCC concentration increased from 0.52 +/- 0.03 to a maximum value of 8.09 +/- 0.57 AU/ml (P < 0.01) while in the coated group the TCC concentration increased from a baseline of 0.53 +/- 0.03 to a peak value of 5.2 +/- 0.24 AU/ml (P <0.01). The difference between the peak values was statistically significant (P = 0.00002). In both groups a significant increase in myeloperoxidase and lactoferrin release was observed by the end of operation. There was no difference in myeloperoxidase or lactoferrin release between the two groups. TCC levels were compared to the occurrence of perioperative infarction, development of lung or renal failure, postoperative bleeding, time on ventilator and days in hospital. Three patients developed perioperative infarction; the peak levels of TCC were significantly higher in these patients than in the 148 patients that did not develop infarction. The reduction in TCC formation in the heparin-coated group was not associated with differences in any of the other clinical parameters. Few adverse effects occurred in the study. The peak values of C3bc were higher in the patients needing inotropic support that in those who did not, the relevance of this finding remains uncertain. CONCLUSION: It is concluded that the Duraflo II heparin coating reduces complement activation, particularly TCC formation, during CPB, but not the release of specific neutrophil granule enzymes. No certain correlation was established between complement and granulocyte activation and clinical outcome.
Aged↗
Underestimation of inversion (16) in acute myeloid leukaemia using standard cytogenetics as compared with polymerase chain reaction: results of a prospective investigation.
In order to determine whether the polymerase chain reaction (PCR) is more suitable for the detection of inversion (16) as compared with standard cytogenetics, we prospectively investigated a total of 132 cases of de novo acute myeloid leukaemia (AML) (n = 121) and secondary AML after myelodysplastic syndromes (MDS) (n = 11) using a sensitive and nested PCR procedure to detect the fusion transcripts CBFbeta-MYH11. All patients were recruited within 10 months in an ongoing multicentre AML-trial. In addition, several cases from a retrospective molecular analysis were included. The data were compared with standard cytogenetics performed in a central laboratory. Of the 132 prospective AML cases, five patients (3.7%) harboured inv(16) upon conventional cytogenetics. In all cases fusion transcripts CBFbeta-MYH11 were detected using PCR. In addition in two patients fusion transcripts were detected, although cytogenetics revealed a normal karyotype. In the group of patients analysed retrospectively, four patients harboured fusion transcripts specific for CBFbeta-MYH11; cytogenetics were normal in one case, and could not be evaluated in two cases. These data show that PCR may be a better means to detect inv(16) in AML. Since inv(16) may have prognostic impact in AML, detection of this aberration seems important in the clinical management of AML patients.
Acute Disease↗
Serum levels of soluble CD23, but not soluble CD25, predict disease progression in early stage B-cell chronic lymphocytic leukemia.
Serum levels of the soluble forms of CD23 (sCD23) and CD25 (sCD25) were prospectively analyzed with respect to their prognostic relevance in early stage B-cell chronic lymphocytic leukemia (B-CLL). SCD23 and sCD25 levels were determined in 105 patients with newly diagnosed B-CLL (Binet stage A). In 93 of the patients, these levels were correlated with other already established indicators for risk of disease progression, including the histologic pattern of bone marrow infiltration, lymphocyte doubling time (LDT), and the serum level of thymidine kinase (TK). High serum levels of both sCD23 and of sCD25 were associated with a diffuse bone marrow infiltration, a LDT < or = 12 months, and elevated (>5 U/L) serum TK, respectively. Moreover, examination of the clinical course of 76 untreated patients showed that high levels of sCD23, but not of sCD25, at initial diagnosis were linked with disease progression. Furthermore, in a stepwise Cox regression model, high levels of sCD23 and a short LDT were shown to be strong predictors of progressive disease within the first year of disease presentation. Therefore, it appears to be justified to incorporate sCD23 levels into the risk profile of early stage B-CLL and to take them into account for stratification in risk-adapted treatment strategies.
Biomarkers, Tumor↗
High-frequency cortical responses reflect lexical processing: an MEG study.
Meaningful words and matched pseudowords, such as moon vs. noom, are of equal perceptual complexity, but invoke different cognitive processes. To investigate high-frequency cortical responses to these stimuli, biomagnetic signals were recorded simultaneously over both hemispheres of right-handed individuals listening to words and pseudowords. Consistent with earlier EEG studies, evoked spectral responses recorded from the left hemisphere revealed depression of spectral power in the low gamma band (around 30 Hz) after pseudowords but not after words. Similar differences between stimulus categories were present in the beta range. These results indicate that distinct patterns of high-frequency cortical responses correspond to the different cognitive processes invoked by words and pseudowords. It is hypothesized that differential high-frequency cortical responses signal the activation or activation failure of distributed Hebbian cell assemblies representing words and other elements of cognitive processing.
Adult↗
P3 and contingent negative variation in Parkinson's disease.
Patients with idiopathic Parkinson's syndrome, most of them in early stages of the disease, and matched healthy controls participated in a continuous performance task while their EEGs were recorded from 15 electrodes. During preparation of movements, a contingent negative variation (CNV) maximal at central and posterior sites was visible. This CNV was reduced in the patient population. A large P3-like positive deflection occurred after go and no-go stimuli that called for execution (go) or suppression (no-go) of a button press. Compared to healthy controls, the positive wave in Parkinson patients was significantly reduced after go stimuli and maximally attenuated when no-go stimuli had indicated to suppress the motor response. In contrast, P3 amplitudes after irrelevant "ignore' stimuli was not significantly reduced in the patients. These results are interpreted in the framework of a model of striatal function postulating (i) that populations of cortical and striatal neurons form distributed functional units (Hebbian cell assemblies), and (ii) that mutual inhibition between such cortico-striatal cell assemblies is mediated by the neostriatum, the forebrain structure primarily affected in Parkinson's disease.
Behavior↗
Multiple simultaneous stimulus presentation facilitates lexical processing.
Bilateral presentation of two copies of the same word leads to faster lexical decisions compared to unilateral presentation alone (bilateral gain). This has implications for theories of interhemispheric interaction, because it suggests that, under certain conditions, both hemispheres cooperate rather than inhibit each other or act independently. Experiment 1 confirmed that the bilateral gain is word-specific and does not occur for pseudowords. Whereas the bilateral gain proved to be present for words of different word frequencies, results of Experiment 2 suggest that it is slightly stronger for high-frequency words compared to words of lower frequencies. Experiment 3 revealed that higher numbers of stimuli (two versus four copies of the same word/pseudoword) presented at the same time lead to an additional improvement of word processing. These results support a neurobiological model of word representation assuming that words are cortically represented in widely distributed interhemispheric cell assemblies. Summation of activity in such assemblies leads to faster and more reliable ignition of the network.
Adult↗
The concept of transcortical cell assemblies: a key to the understanding of cortical lateralization and interhemispheric interaction.
According to Hebb, elements of higher cognitive processes, such as concepts, words and mental images, are realized in the brain as cortical cell assemblies, i.e. large and strongly connected neuron populations that form functional units. Neurons belonging to such assemblies may be scattered over wide cortical areas, and some cell assemblies may even comprise neurons of both hemispheres (transcortical assemblies). If full activation (ignition) of an assembly leads to fast circulation of neuronal activity in the assembly, this process should be visible in high-frequency cortical responses. Some evidence will be reviewed that cell assembly ignition indeed leads to changes in high-frequency cortical responses which can be recorded in the EEG and MEG. Within the cell assembly-framework, the question of cortical laterality translates into the question of how neurons of transcortical assemblies are balanced between the hemispheres. This approach allows for different degrees of laterality. Recent evidence is summarized that the degree of laterality indeed differs between language units. For example, the cortical representation of certain words appears to be strongly lateralized to the left hemisphere while those of others are less lateralized. If neurons of both hemispheres are part of one assembly bihemispheric processing should lead to a processing advantage compared to processing in the dominant hemisphere alone. The latter appears to be the case for lexical processing, as revealed by recent behavioral studies. In conclusion, the cell assembly-framework suggests a more fine-grained description of the issue of cortical laterality; it is not appropriate to ask whether "modules" supporting higher cortical functions are located either in the left or right hemisphere. Rather, it appears fruitful to ask how the neurons of transcortical cell assemblies are balanced between the hemispheres.
Brain Mapping↗
Complex cytogenetic and immunophenotypic aberrations in a patient with Sezary syndrome.
Sezary syndrome is defined as the leukemic variation of cutaneous T-cell lymphomas. Here we describe the cytogenetic pattern of peripheral T-cells of a 50-year-old male patient suffering from this disease. We used Giemsa-banding (G-banding) technique and a fluorescence in situ hybridization (FISH) assay to determine cytogenetic changes affecting 15 different chromosomes. The cells displayed an abnormal hypodiploid karyotype with a prominent insertion located at the short arm of chromosome 1. Unbalanced translocations were observed involving chromosomes 4 and 14. Besides other abnormalities we detected a 6q- deletion. These multiple genetic changes may reflect the high aggressivity of the neoplastically transformed T-cell population and the poor response to chemotherapeutic treatment.
Aneuploidy↗
Complement activation during and after open-heart surgery is only marginally affected by the choice of fluid for volume replacement.
Forty patients undergoing CPB for coronary artery surgery, using a standardized technical setting, were randomized to receive either Ringer's acetate, dextran 70 (Macrodex), polygeline (Haemaccel) or albumin 4% for volume replacement during and after surgery. The choice of fluid did not affect early complement activation (C3 activation products). Higher values of the terminal complement complex (TCC) were found only at the end of the operation in patients receiving polygeline. There were no differences between any two of the four groups during the postoperative course. The use of blood transfusion or autotransfusion and the degree of haemodilution and hypothermia did not affect complement activation. We conclude that complement activation in association with open-heart surgery is only marginally affected by the choice of fluid for volume replacement.
Adult↗
Fluid balance and pulmonary functions during and after coronary artery bypass surgery: Ringer's acetate compared with dextran, polygeline, or albumin.
The effects on fluid balance, pulmonary functions and economics were evaluated in a randomized comparison of one colloid free and three colloid containing fluid regimens, for 48 hours during and after coronary artery bypass (CAB) surgery. A standard regimen for anaesthesia, extracorporeal circulation and monitoring was used. Only Ringer's acetate (RAc) was used as priming solution for extracorporeal circulation. Forty patients were randomized to receive either RAc, polygeline 35 mg.ml-1 (Haemaccel), dextran 70 (Macrodex) 60 mg.ml-1, or albumin 40 mg.ml-1 in saline whenever fluid volume was needed to stabilize haemodynamics. At the end of the operation, fluid retention was significantly lower in patients receiving polygeline and dextran 70, compared with patients receiving RAc. At 48 hours, however, there were no differences in cumulative fluid balance. Patients in the colloid groups postoperatively had a higher serum colloid osmotic pressure (s-COP), but a higher net lung capillary filtration pressure (delta P) only on the second postoperative day than the RAc group. However, this did not adversely affect intrapulmonary venous admixture, arterial oxygen tension, or time on respirator in the RAc group compared with the colloid groups. The most expensive colloid fluid regimen (albumin) cost about 230 US$ more per patient than the RAc fluid regimen. We conclude that Ringer's acetate for volume replacement to stabilize haemodynamics during and after CAB surgery is associated with increased fluid retention only during the intraoperative period, compared with dextran 70 or polygeline, and with a lower serum colloid osmotic pressure and net lung capillary filtration pressure postoperatively, compared with all three colloid groups. This does not affect pulmonary functions adversely.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Interhemispheric cooperation during lexical processing is mediated by the corpus callosum: evidence from the split-brain.
If two copies of a meaningful word are tachistoscopically presented simultaneously in both visual half-fields of normal subjects the word will be processed more rapidly and more accurately compared to unilateral presentation (bilateral gain). The word-specific bilateral gain may be due to excitatory transcallosal connections within interhemispheric cell assemblies corresponding to words. In this case, the bilateral gain should be absent in split-brain patients. L.B., a split-brain patient, performed a lexical decision task with words and non-words presented in the left visual field, the right visual field, or in both visual fields simultaneously. As predicted, bilateral presentations did not improve performance compared to unilateral presentation in the right visual field. This result suggests that transcallosal connections play a significant role in lexical processing.
Adult↗
Lexical decision after left, right and bilateral presentation of function words, content words and non-words: evidence for interhemispheric interaction.
Function words, content words and pronounceable non-words (pseudowords) were presented tachistoscopically either in the left or the right visual field or with identical copies flashed simultaneously to both visual half-fields. Consistent with earlier studies [10], function words were found to show a right visual field advantage, whereas for content words the right visual field advantage was absent. Compared to either of the unilateral modes of presentation, bilateral presentation of identical word stimuli improved accuracy and latency significantly. The bilateral (Bi) advantage was largest for content words, and was also highly significant for function words in both latency and accuracy. The Bi gain was absent for non-words (significant interaction of Wordness x Visual Field). These results indicate that the lexicons of the left and right hemisphere can "collaborate" rather than inhibit each other or act independently when processing the same linguistic stimuli. Our findings are consistent with the view that the neuronal counterparts of words are Hebbian cell assemblies consisting of strongly connected excitatory neurons of both hemispheres. Since function words show a right visual field advantage in addition to their Bi gain, their assemblies are likely to have most of their neurons located in the left hemisphere. Neuronal assemblies corresponding to content words may be less strongly lateralized.
Adolescent↗
Recombinant human erythropoietin in patients with myelodysplastic syndrome and myelofibrosis.
In a dose titration study we tested the efficacy and tolerance of recombinant human erythropoietin (rhEPO) in 10 patients with myelodysplasia (MDS) and 2 patients with idiopathic myelofibrosis. Patients with a haemoglobin level < 100 g/l were treated as out-patients for 12 weeks with daily doses ranging from 30 U/kg body weight (BW) up to 240 U/kg BW in non-responders. Of the 10 patients with MDS, 6 were suffering from refractory anaemia with sideroblasts (RAS) and 4 from refractory anaemia with an excess of blasts. The median age was 73 years (range 41-81). Two patients with RAS responded with a rise in haemoglobin concentration to > 130 g/l. They had not been transfusion-dependent prior to treatment. Both patients had relatively low serum concentrations of immunoreactive EPO. There was neither a rise in haemoglobin nor a reduction in transfusion dependence in any of the other patients. It may be concluded that rhEPO is possibly effective in a subgroup of MDS patients where the disease is less advanced. None of the transfusion-dependent patients benefited.
Adult↗
Multiple drug resistance gene expression in human renal cell cancer is associated with the histologic subtype.
Overexpression of p170 glycoprotein, the product of the multiple drug resistance (mdr) gene, has been associated with resistance to various cytotoxic drugs used in the treatment of human neoplasms. Normal renal epithelial cells express p170 as a function of their secretory capacity. Because renal cell carcinomas (RCC) respond poorly to chemotherapeutic regimens, p170 expression was studied in primary RCC. Such expression was measured in 40 human RCC and normal kidney tissues using immunohistochemical staining with the monoclonal antibody C-219. Staining intensities of the whole tumor and of different areas of the cryostat sections were transformed into digital numbers using an algorithm designed for this purpose. In most tumors, an inhomogeneous staining pattern and a correlation between grade of differentiation and C-219 immunoreactivity was observed. A comparison of the tumors according to their histopathologic subtypes showed clear differences. The means (range) of the staining intensities of the different types of RCC: clear cell carcinoma Grade 1 (n = 3), 2.0 (2.0 to 2.0); clear cell carcinoma Grade 2 (n = 19), 0.8 (0.0 to 2.9); clear cell carcinoma Grade 3 (n = 5), 0.1 (0.0 to 0.2); tubular carcinoma (n = 4), 2.0 (2.0 to 3.0); anaplastic carcinoma (n = 8), 0.05 (0.0 to 0.2); oncocytoma (n = 1), 0.0 (0.0 to 0.0); and normal kidney (n = 40), 0.5 (0.0 to 2.0). The differences between anaplastic, clear cell, and tubular carcinoma were significant (P less than 0.001 by Kruskal-Wallis test). In addition, the difference between the three subgroups of clear cell carcinoma was significant (P less than 0.01). It was concluded that the histopathologic subtypes of RCC correlate with the degree of mdr gene expression, as determined by staining with the C-219 monoclonal antibody.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Results of 6 1/2 years of heart transplantation at Rikshospitalet].
We discuss our experience from 6 1/2 years of orthotopic heart transplantation at Rikshospitalet (the National Hospital). 112 grafts were performed on 109 patients (19 women and 90 men), mean age 47 years (range 14-63). In the first nine patients the immunosuppressive regimen consisted of cyclosporine A and prednisolone, and in the last 100 azathioprine was added (triple medication). There was no operative mortality. 21 patients died, giving an 81% cumulative survival, with a significantly better prognosis among those who received triple immunosuppressive regimen. The main complications were rejection, infection and arrhythmia. Since our main problem was rejection it is concluded that careful supervision, concentrated on as few cardiologists as possible, and a liberal indication for myocardial biopsy, are decisive for the prognosis.
Adolescent↗