Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data.

Plerixafor was recently approved by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA) to enhance stem cell mobilization for autologous transplant in patients with lymphoma and multiple myeloma. In this study, we present the first European compassionate use experience in mobilization failures, patients who are hardest to remobilize but were not included in registration trials. A total of 56 consecutive patients from 15 centers in Spain and the United Kingdom were included: age 60 (33-69) years; 29 men (32 with myeloma and 24 with lymphoma); 2 lines of previous chemotherapy (1-10); 73 previously failed mobilization attempts with G-CSF (28), chemotherapy plus G-CSF (43) or G-CSF plus SCF(2). Overall, 71% of patients reached ≥ 10 CD34+ cells per µL with plerixafor on day 5 after a 7.6-fold expansion from day 4. A total of 42 patients (75%) collected ≥ 2 × 106, average 3.0 ± 1.7 (0.4-10.6) CD34+ cells per kg with plerixafor plus G-CSF. There were no severe drug-related adverse events. In all, 35 patients (63%) underwent transplant, receiving an average of 3.1±1.2 (1.9-7.7) × 106 CD34+ cells per kg. All patients engrafted neutrophils (day 12; 13.4 ± 0.8; 8-30) and platelets (day 15; 18.5 ± 2.4; 8-33). In our experience, plerixafor offers an effective alternative to collect sufficient CD34+ cells for autologous SCT from patients who fail conventional mobilization methods, with good tolerance and a high success rate.

Diagnostic usefulness of linear and nonlinear quantitative EEG analysis in Alzheimer's disease.

The sensitivity of the EEG in early AD is somewhat limited. In this respect spectral analysis is little better than visual assessment. In this study we address the question whether a new type of EEG analysis derived from chaos theory can improve the sensitivity of the EEG. EEGs were recorded in 15 control subjects and 15 patients with mild AD. The EEG recorded at 02 and 01 during eyes closed and eyes open conditions was subjected to spectral analysis (relative power) and nonlinear analysis (calculation of the correlation dimension D2). AD patients had more relative theta power and impaired reactivity in alpha, delta and theta bands. Also, reactivity of the D2 was impaired in AD subjects. For a specificity of 100%, relative theta power had the highest sensitivity (46.7%). Alpha band reactivity at O1 had a sensitivity of 40% and D2 reactivity at O1 had a sensitivity of 33.3%. Combining theta power with alpha reactivity resulted in a sensitivity of 53.3%; combining theta with D2 reactivity resulted in a sensitivity of 60%. Used in isolation, linear analysis was superior in differentiating AD patients from controls. The best results were obtained by combining linear with nonlinear measures. This approach does not seem practical yet, but deserves further study.

Investigation of EEG non-linearity in dementia and Parkinson's disease.

Many recent studies based on the surrogate data method failed to identify significant non-linearity in the EEG. In this study we examine whether the use of a different embedding method (spatial instead of time delay), and calculation of Kolmogorov entropy (K2) and the largest Lyapunov exponent (L1) in addition to the correlation dimension (D2), can distinguish the EEG form linearly filtered noise. We have calculated D2, L1 and K2 of original EEG epochs and surrogate (phase randomized) data in 9 control subjects, 9 demented patients and 13 Parkinson patients. The correlation dimension D2 and the largest Lyapunov exponent L1 could distinguish between the EEG tracings and the surrogate data. Demented patients had significantly lower D2 and L1 compared to controls. L1 was higher in Parkinson patients than in demented patients. Contrary to other studies that have used the Theiler surrogate data method, we find evidence for non-linearity in normal and abnormal EEG during the awake/eyes closed state. Apparently it is the spatial structure in the EEG that exhibits much of the non-linear structure. Furthermore, non-linear EEG measures show more or less specific patterns of dysfunction in dementia and Parkinson's disease.

Specific patterns of cortical dysfunction in dementia and Parkinson's disease demonstrated by the acceleration spectrum entropy of the EEG.

Acceleration spectrum entropy (ASE) was used to quantify EEG desynchronization, which is related to cortical activation. We investigated the ASE in control and patient groups with dementia (AD) and Parkinson's disease (PD). Both patient groups had significantly lower ASE scores corresponding with less desynchronization in all cortical regions. In the AD group, the ASE was significantly lower in the parietal region. ASE was found to be a sensitive and specific measure for differentiating patient groups with AD and PD from controls and from each other.

Serum anti-GQ1b IgG antibodies recognize surface epitopes on Campylobacter jejuni from patients with Miller Fisher syndrome.

Three patients who had diarrhea prior to the development of Miller Fisher syndrome are presented. Campylobacter jejuni was isolated from stool specimens from all patients. High titers of anti-GQ1b IgG antibodies were demonstrated in the serum of these patients by enzyme-linked immunosorbent assay and thin-layer chromatography overlay. In enzyme-linked immunosorbent assay inhibition studies the anti-GQ1b IgG antibodies bound specifically to whole bacteria of the Miller Fisher syndrome-associated C. jejuni strains. The presence of anti-GQ1b IgG binding epitopes on the surface of the C. jejuni from the patients was not exclusively associated with a specific Penner serotype. It is suggested that anti-GQ1b antibodies are formed during the initial infection that elicits Miller Fisher syndrome. The cross-reactivity of anti-GQ1b IgG antibodies with surface epitopes on Miller Fisher syndrome-associated C. jejuni strains supports the hypothesis of molecular mimicry between bacteria and neural tissue.

Diagnosis of traumatic carotid artery dissection by transcranial Doppler ultrasound: case report and review of the literature.

The clinical course, transcranial Doppler ultrasound (TCD) findings, and angiographic outcome are reported for a patient with a traumatic carotid artery dissection. Transient asymmetrical decreased middle cerebral artery blood flow velocities led to the suspicion of an internal carotid artery (ICA) stenosis. Duplex scanning and angiography subsequently demonstrated an extracranial traumatic ICA dissection in combination with a traumatic saccular aneurysm. These data imply that TCD monitoring has a potential to diagnose not only well established complications of neurotrauma, such as vasospasm and intracranial hypertension, but may also suggest the presence of traumatic extracranial carotid obstructions.

Non-linear dynamical analysis of multichannel EEG: clinical applications in dementia and Parkinson's disease.

The irregular, aperiodic character of the EEG is usually explained by a stochastic model. In this view the EEG is linearly filtered noise. According to chaos theory such irregular signals can also result from low dimensional deterministic chaos. In this case the underlying dynamics is nonlinear, and has only few effective degrees of freedom. In contrast, stochastic models are less efficient, because they require in principle infinite degrees of freedom. Chaotic dynamics in the EEG can be studied by calculating the correlation dimension (D2). Although it has become clear that D2 calculations alone cannot prove chaos, the D2 has potential value as an EEG diagnostic. In this study we investigated whether D2 could be used to discriminate EEGs from normal controls, demented patients and Parkinson patients. We have analyzed epochs (20 channels; 2.5 s) from 52 EEGs (20 controls; 15 patients with dementia; 17 patients with Parkinson's disease). Controls had a mean D2 of 6.5 (0.9); demented patients of 4.4 (1.5), and Parkinson patients of 5.3 (0.9). Both groups were significantly different from controls (p < 0.001). There was a significant positive correlation between D2 and relative power in the beta band (r = 0.81) and a significant negative correlation between D2 and power in the delta (r = -0.60) and theta band (r = -0.37). These results suggest the possible usefulness of multichannel D2 estimation in a clinical setting.