Recognition of a positive MLR within 4 hours using a carrier free electrophoresis system

Summary Indicator cells — tanned, surface stabilized sheep erythrocytes — were incubated for 1 h in supernatants of 3 h MLCs. Their electrophoretic mobility was measured by an analytical, carrier free electrophoresis system. The change in their mobility compared with an appropriate control was calculated in per cent and correlated with the conventional measured MLR-cpm. The correlation of the two quantities is statistically highly significant (p<0.01). Furthermore, the difference of the electrophoretic mobility values of the group of HLA-D-identical and the groups of HLA-D-haploidentical or -different donors is significant beyond the 1 level (p<0.0005). Our method enables, therefore recognition of a positive or negative MLC after only 4 h. Typing for HLA-D-determinants seems to be possible. This could be of great importance for histocompatibility testing and organ transplantation.     

Robotic Assistance System for Cone-Beam Computed Tomography-Guided Percutaneous Needle Placement

CardioVascular and Interventional Radiology - The study aimed to evaluate a new robotic assistance system (RAS) for needle placement in combination with a multi-axis C-arm angiography system for...     

Role of allogeneic transplantation in chronic myeloid leukemia

The use of allogeneic hematopoietic stem cell transplantation for the treatment of chronic myeloid leukemia (CML) patients has changed dramatically during the past decade. It was the standard of care for all younger CML patients with a compatible donor before the introduction of imatinib. It is used now as a rescue treatment for patients for whom tyrosine kinase inhibitors have failed. Both treatments, tyrosine kinase inhibitors and allogeneic transplantation, are very powerful and able to control the disease in the long-term. It is therefore of great importance to know the place of each therapy and to integrate allogeneic hematopoietic stem cell transplantation in a risk-adapted way into the treatment plan of each individual patient.     

Prognostic impact of karyotypic findings in childhood acute lymphoblastic leukaemia: a Nordic series comparing two treatment periods. For the Nordic Society of Paediatric Haematology and Oncology (NOPHO) Leukaemia Cytogenetic Study Group

The prognostic impact of acquired chromosome abnormalities was evaluated in a population-based consecutive series of 768 children (< 15 years of age) with acute lymphoblastic leukaemia (ALL). The study cohort included all cases of cytogenetically abnormal childhood ALL diagnosed between 1986 and 1997 in the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden). The probability of event-free survival (pEFS) for the total cohort was 0. 72 +/- 0.02. When comparing the two treatment periods of July 1986 to December 1991 and January 1992 to December 1997, a better survival was seen for the latter time period (pEFS of 0.69 +/- 0.02 vs. 0.76 +/- 0.02, P = 0.05). Hypodiploidy with less than 45 chromosomes, t(9;22)(q34;q11) and 11q23 translocations were associated with a dismal outcome during the whole study period (pEFS of 0.57 +/- 0.12, 0.41 +/- 0.14 and 0.37 +/- 0.10 respectively). The poor prognostic influence of 11q23 rearrangements seemed to be restricted to infants and older children (> 10 years), who differed significantly from children aged 1-10 years in this regard (P < 0. 01). Patients with t(9;22)-positive ALL seemed to benefit from allogeneic bone marrow transplantation in first remission (P = 0.05). The pEFS for children with t(1;19)(q23;p13)-positive ALL was intermediate (0.63 +/- 0.17), with a tendency to a better outcome for patients with the unbalanced variant der(19)t(1;19). Hyperdiploid ALL patients, subdivided into moderate hyperdiploidy (47-51 chromosomes), massive hyperdiploidy (52-60 chromosomes) and cases in the tri-/tetraploid range (> 60 chromosomes) had the best outcome in the last treatment period (pEFS of 0.81 +/- 0.06, 0.80 +/- 0.04 and 0.88 +/- 0.07 respectively), unless t(1;19), t(8;14), t(9;22) or 11q23 translocations were present. In a multivariate analysis including white blood cell (WBC) count, immunophenotype, age, mediastinal mass, central nervous system involvement and leukaemia karyotype, only WBC and modal chromosome number were shown to be significant independent risk factors (P < 0.01).     

Cytogenetics of secondary myelodysplasia (sMDS) and acute nonlymphocytic leukemia (sANLL)

76 cases of secondary myelodysplasia (sMDS) and acute non-lymphocytic leukemia (sANLL) were cytogenetically analyzed. Among the 36 sMDS patients, 13 (36%) had only normal karyotypes whereas 23 (64%) displayed clonal chromosomal abnormalities. The most common aberrations were -7, 5q-, -5, and +8. In 10 patients (43% of the cytogenetically aberrant cases), clones with only one anomaly, mostly 5q- or -7, were found. Of the 40 sANLL patients, normal karyotypes were detected in 10 (25%). Among the 30 (75%) abnormal cases, the most frequent aberrations were -7, -5, +8, 7q-, -17, and +21. 12 patients (40%) had clones with single abnormalities, most often -7. In 4 sANLL patients cytogenetically unrelated clones were detected. A survey of all previously published secondary hematologic neoplasias reveals that the most frequent abnormalities in sMDS are -7 (41%), 5q- (28%), and -5 (11%), followed by der(21q), +8, 7q-, der(12p), t(1;7), -12, -17, der(17p), der(3p), der(6p), and -18. Clones with single aberrations have been found in 45% of the cases and cytogenetically unrelated clones have been described in 6%. The most common abnormalities in sANLL are -7 (38%), 5q- (17%), -5 (15%), +8 (13%), and -17 (11%), followed by der(3q), der(11q), der(12p), -21, 7q-, -18, der(3p), der(17p), +21, der(21q), der(6p), and -16. 38% of the sANLL patients have had clones with only one aberration and 3% have had unrelated clones. The frequencies of these nonrandom abnormalities in sMDS and sANLL are thus remarkably similar - the only exception appears to be 5q-, which is more common in sMDS. Also the mean number of abnormalities per case is similar - 5.3 in sMDS and 5.6 in sANLL. When the incidences of characteristic cytogenetic abnormalities were correlated with the type of previous therapy, -7 was found to be more frequent in sMDS and sANLL patients who had been exposed to chemotherapy whereas 5q- was associated with previous exposure to ionizing radiation in sMDS patients.     

Four phase 1 trials to evaluate the safety and pharmacokinetic profile of single and repeated dosing of SCO‐101 in adult male and female volunteers

SCO‐101 (Endovion) was discontinued 20 years ago as a new drug under development against sickle cell anaemia. Data from the phase 1 studies remained unpublished. New data indicate that SCO‐101 might be efficacious as add‐on therapy in cancer. Thus, we report the results from the four phase 1 trials performed between 2001 and 2002. Adult volunteers received SCO‐101 or placebo in four independent trials. Adverse events were recorded, and SCO‐101 was determined for pharmacokinetic analysis. Ninety‐two volunteers completed the trials. The most remarkable adverse effect was a transient and dose‐dependent increase in unconjugated bilirubin. Plasma SCO‐101 elimination was approximately log linear, with apparent oral clearances of between 315 and 2103 mL/h for single doses, and between 121 and 2433 mL/h at steady state following oral administration. There was a marked decrease in clearance with increasing dose, and for repeated dose versus single dose. T_max was greater, and C_max and AUC_∞ were lower in the fed state compared to the fasted state. Exposure was equivalent in males and females and for African Americans and Caucasians. In conclusion, SCO‐101 appears to be a safe drug with a predictable PK profile. Its efficacy as add‐on to standard anticancer drugs has yet to be defined.     

A mechanical microconnector system for restoration of tissue continuity and long-term drug application into the injured spinal cord

Complete transection of the spinal cord leaves a gap of several mm which fills with fibrous scar tissue. Several approaches in rodent models have used tubes, foams, matrices or tissue implants to bridge this gap. Here, we describe a mechanical microconnector system (mMS) to re-adjust the retracted spinal cord stumps. The mMS is a multi-channel system of polymethylmethacrylate (PMMA), designed to fit into the spinal cord tissue gap after transection, with an outlet tubing system to apply negative pressure to the mMS thus sucking the spinal cord stumps into the honeycomb-structured holes. The stumps adhere to the microstructure of the mMS walls and remain in the mMS after removal of the vacuum. We show that the mMS preserves tissue integrity and allows axonal regrowth at 2, 5 and 19 weeks post lesion with no adverse tissue effects like in-bleeding or cyst formation. Preliminary assessment of locomotor function in the open field suggested beneficial effects of the mMS. Additional inner micro-channels enable local substance delivery into the lesion center via an attached osmotic minipump. We suggest that the mMS is a suitable device to adapt and stabilize the injured spinal cord after surgical resection of scar tissue (e.g., for chronic patients) or traumatic injuries with large tissue and bone damages.     

Stimulus transformation into motor action: Dynamic graph analysis reveals a posterior‐to‐anterior shift in brain network communication of older subjects

Cognitive performance slows down with increasing age. This includes cognitive processes that are essential for the performance of a motor act, such as the slowing down in response to an external stimulus. The objective of this study was to identify aging‐associated functional changes in the brain networks that are involved in the transformation of external stimuli into motor action. To investigate this topic, we employed dynamic graphs based on phase‐locking of Electroencephalography signals recorded from healthy younger and older subjects while performing a simple visually‐cued finger‐tapping task. The network analysis yielded specific age‐related network structures varying in time in the low frequencies (2–7 Hz), which are closely connected to stimulus processing, movement initiation and execution in both age groups. The networks in older subjects, however, contained several additional, particularly interhemispheric, connections and showed an overall increased coupling density. Cluster analyses revealed reduced variability of the subnetworks in older subjects, particularly during movement preparation. In younger subjects, occipital, parietal, sensorimotor and central regions were—temporally arranged in this order—heavily involved in hub nodes. Whereas in older subjects, a hub in frontal regions preceded the noticeably delayed occurrence of sensorimotor hubs, indicating different neural information processing in older subjects. All observed changes in brain network organization, which are based on neural synchronization in the low frequencies, provide a possible neural mechanism underlying previous fMRI data, which report an overactivation, especially in the prefrontal and pre‐motor areas, associated with a loss of hemispheric lateralization in older subjects.