Transcatheter coil occlusion of residual shunt in a patient with recurrent cryptogenic stroke after PFO percutaneous closure.

A significant association has been suggested between a residual shunt and the risk of cerebral ischemic recurrences after transcatheter patent foramen ovale (PFO) closure. We report the use of a detachable coil to treat a residual shunt in a patient who had a recurrent cerebral ischemic event after transcatheter closure of a PFO.     

Positron emission tomography scanning in the assessment of patients with lymphoma

BACKGROUND: The detection of lymphoma by computed tomography (CT) scanning is known to be improved by positron emission tomography (PET) and/or gallium scanning, although the direct comparative accuracy of these imaging modalities remains a subject of ongoing review. AIMS: The aim of the present study was to compare PET scanning with conventional imaging (CT and/or gallium scanning) in patients with lymphoma. METHODS: A retrospective study of 38 patients (25 men; 13 women; median age 39.5 years; range 18.0-81.0 years) who had had PET scans (24 scans at initial staging and 46 scans at restaging, including suspected disease relapse) was carried out. Thirty-one concurrent gallium scans had been performed. Disease was validated with clinical follow up or biopsy. RESULTS: The sensitivities of PET and CT at initial staging were 96 and 71%, respectively. PET identified additional sites of disease compared with CT in 29% of patients. Of the 15 patients who had had all three imaging modalities, the sensitivities of PET, CT and gallium were 93, 67 and 87%, respectively. At treatment completion, the positive predictive values of PET, CT and gallium scans for relapse given a residual mass were 100, 33 and 0%, respectively (P = 0.006 for PET and CT comparison). The negative predictive values of PET, CT and gallium were 76, 0 and 70%, respectively (P-value not significant). In suspected disease relapse, PET results changed management in 50% of patients. CONCLUSION: Compared with CT and gallium scans, PET has superior accuracy in staging and restaging, and its greatest value lies in its positive predictive value for relapse in patients with residual masses.     

中药防风抑制小鼠胃肠运动的实验观察

[目的]观察不同浓度的防风对正常小鼠小肠推进及胃排空的抑制作用。[方法]清洁级昆明小鼠60只,随机分为对照（NS）组和5个防风组,每组10只,NS组予0.85%NaCl,5个防风组分别以5、10、15、20、25 g/kg剂量,灌胃后30 min处死小鼠,观察各组的小肠推进率和胃残留率。[结果]防风各组均对小鼠小肠推进和胃排空有一定程度的抑制作用,其中5、101、5 g/kg剂量组小肠推进率与NS组比较差异有统计学意义（P〈0.05）,15 g/kg组作用最强;5、10、25 g/kg剂量组胃排空率与NS组比较差异有统计学意义（P〈0.05）,而15、20 g/kg剂量组与NS组比较差异无统计学意义。[结论]防风有抑制小鼠小肠推进的作用,在5-15 g/kg范围内效果随剂量的增大而增强,在〉15-25 g/kg范围内随剂量的增大而减小;防风对胃排空也有不同程度的抑制,在5-15 g/kg范围内抑制作用随剂量的增大而减小,在〉15-25 g/kg范围内随剂量的增大而增强。     

Post-transplantation tumour load in bone marrow, as assessed by quantitative ASO-PCR, is a prognostic parameter in multiple myeloma

High-dose therapy (HDT) and autologous transplantation prolongs remission duration and survival in multiple myeloma (MM), but relapse still occurs at a median of 2 years post-HDT. In order to investigate whether the number of residual tumour cells in the bone marrow (BM) after transplantation can predict the duration of response, a quantitative allele-specific oligonucleotide polymerase chain reaction (qASO-PCR) assay was used to measure tumour load in BM at 3-6 months post-HDT in 67 patients. The method of maximally selected log-rank statistics was used to test for the existence of a cut-off value in the BM tumour load data set. A cut-off value with respect to progression-free survival (PFS) was identified (P = 0.001). The estimated threshold for placing patients into a "good" or "bad" prognostic group was 0.015% (n = 22 and 38 respectively) with a median PFS of 64 months vs. 16. Multivariate analysis showed grouping by PCR result to be an independent prognostic factor for PFS (estimated hazard ratio after shrinkage, 3.91). This study identifies for the first time a threshold of the post-HDT tumour load with prognostic significance for PFS in MM. Quantitative molecular assessment thus may help to identify those patients who are in need of further treatment early after autologous transplantation.     

Expression of poliovirus receptor-related proteins PRR1 and PRR2 in acute myeloid leukemia: first report of surface marker analysis, contribution to diagnosis, prognosis and implications for future therapeutical strategies

Poliovirus receptor-related (PRR) proteins belong to the Nectin-adhesion molecules' group, are expressed on endothelial cells and on CD34(+) stem cells and mediate the organization of endothelial and epithelial junctions. There is evidence to suggest, that those receptors could have a role in leukemia. We have studied the expression of PRR molecules PRR1 and PRR2 on mononuclear bone marrow (BM) cells of 55 patients with acute myeloid leukemia (AML) at first diagnosis by FACS-analysis using directly Phycoerythrin-labeled markers (PRR1 clone R1.302.12; PRR2 clone R2.477.1) in combination with other Fluorescein conjugated antibodies to evaluate the blast phenotype in AML. The leukemic gate included blasts and residual monocytes and lymphocytes. A case was defined as positive, if more than 20% of the gated cells expressed the regarding receptor. We could demonstrate, that on average 35% PRR1(+) or 45% PRR2(+) cells in AML were found. Within FAB-types we observed a high PRR1 expression in cases with M3 and M4 and lowest expressions in M0 and M5; a high PRR2 expression was found in cases with M3, M4, M5 and M1 and lowest expressions in M0 and M2. Separating our patients' cohorts in cytogenetic risk groups we could detect a significant higher proportion of PRR1(+) cases (73% vs. 25% of cases, P = 0.009) or PRR1(+) cells (57% vs. 18% of cases, P = 0.001) in the cytogenetic favorable risk vs. poor risk group (75% vs. 32% PRR2(+) cases). Moreover cut-off-values with a maximum probability for a significant differentiation between cases with higher or lower levels of these markers could be found: cases with >78% PRR1(+) and cases with >77% PRR2(+) cells were characterized by a tendency for longer relapse free survival times. Qui-square analyses showed, that 3 of 4 cases with FAB-type M3 (P = 0.03) or a favorable karyotype (P = 0.04) were found in the group with >7% PRR1(+) cells, due to only few cases available a similar correlation, however, could not be found in cases with >78% PRR2(+) cells. We can conclude, that blasts in AML regularly express PRR1 and PRR2. Cases with a high expression of PRR1 or PRR2 are characterized by a more favorable prognosis. With respect to the individual PRR-status the benefit of biological response modifiers as priming agents, differentiation mediators or factors influencing cellular metabolisms inducing factors can be discussed under a new point of view.     

Quality of leucoreduced red blood cell concentrates: 5 years of follow-up in France

BACKGROUND: Since 1998, prestorage leucoreduction of all cellular blood components has been made mandatory in France. The French blood service needed to follow the data on the quality of the blood components prepared by blood centres. MATERIAL AND METHODS: Quality control (QC) data were submitted to a central data bank by each blood centre. The data were stratified by preparation method for analysis of key performance criteria - residual white blood cell (WBC) and total haemoglobin content. The red blood cell (RBC) preparation processes and the methods for measuring haemoglobin content and residual WBC count were those routinely employed by blood centres. Each year, more than 15,500 RBCs were tested. RESULTS: Red blood cells had a mean haemoglobin content between 53.6 and 54.9 g/unit depending on the year (2001 to 2005). The requirement of 40 g/unit was reached for about 99% of units. The haemoglobin content was influenced by the preparation process: 56.8 +/- 6.9 vs. 50.6 +/- 5.6 g/unit in average for whole blood filtration or RBC filtration, respectively. Apheresis RBCs exhibited a reduced variability (51.8 +/- 3.1 g/unit). The median residual WBC count remained low (0.046 to 0.057 x 10(6) WBCs/unit), and the percentage of RBC units exceeding the 1 x 10(6) WBCs/unit cut-off ranged from 1.5 to 0.6% depending on the year. A seasonal pattern was observed, with a significant increase (P < 0.001) of the median residual WBC count and of the percent of non-conforming units during the summer months. CONCLUSION: Our QC data suggest an overall compliance with the standard. Our data bank is useful to inform on the performance of leucoreduced RBC preparation processes carried out with market available devices.     

Imatinib in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia: current status and evolving concepts

Until recently, progress in the treatment of patients with Ph(+) acute lymphoblastic leukaemia (ALL) has been limited, and long-term survival, even with high-dose intensified chemotherapy, is rare. Allogeneic stem cell transplantation is potentially curative, but treatment-related mortality and rate of disease recurrence are substantial. With the advent of the ABL-selective tyrosine kinase inhibitor STI571 (imatinib mesylate, Glivec), it has become apparent that the understanding of crucial leukaemogenic pathways at the molecular level can lead to the development of specific and selective agents. In recent clinical trials, imatinib has demonstrated significant anti-leukaemic efficacy in patients with advanced Ph(+) ALL, in conjunction with a remarkably favourable safety profile. Clinical resistance to imatinib develops rapidly, highlighting the limitations of using imatinib as a single agent; however, the value of imatinib as an element of treatment has become apparent. Resistance mechanisms have already been identified that will enable the development of rational strategies to prevent or overcome resistance. On the basis of available clinical results, combinations of imatinib with established anti-leukaemic agents, as well as with novel, molecularly targeted treatment modalities, will need to be evaluated in advanced Ph(+) ALL. Incorporation of imatinib in the first-line treatment of de novo Ph(+) ALL and in the setting of minimal residual disease is a promising therapeutic approach which is currently being studied in clinical trials. Better understanding of targeted therapies, including strategies based on recruitment of host immune functions, as well as the prudent use of active chemotherapy agents, may eventually improve the outlook for patients with Ph(+) ALL.     

Limited efficacy of nintedanib for idiopathic pleuroparenchymal fibroelastosis

BackgroundThe antifibrotic agent nintedanib has been reported to effectively prevent the decline in forced vital capacity (FVC) in a broad range of interstitial lung diseases. However, the efficacy of nintedanib against idiopathic pleuroparenchymal fibroelastosis (iPPFE) remains unclear.MethodsWe retrospectively examined patients with idiopathic PPFE or idiopathic pulmonary fibrosis (IPF) who received nintedanib for more than 6 months. We evaluated annual changes in %FVC, radiological PPFE lesions, and body weight before and during nintedanib treatment. To investigate radiological PPFE lesions, we examined the fibrosis score, which was defined as the mean percentage of the high attenuation area in the whole lung parenchyma using three axial computed tomography images.ResultsOverall, 15 patients with iPPFE and 27 patients with IPF were included in the present study. In patients with IPF, the annual rate of decline in %FVC was significantly lower during nintedanib treatment than that before treatment (?2.01%/year [?7.64 to 3.21] versus ?7.64%/year [?10.8 to ?4.44], p = 0.031). Meanwhile, in patients with iPPFE, the annual rate of decline in %FVC during nintedanib treatment was higher than that before treatment (?18.0%/year [?21.6 to ?12.7] versus ?9.40%/year [?12.3 to ?8.23], p = 0.109). In addition, nintedanib treatment failed to inhibit the annual rate of increase in fibrosis score in patients with iPPFE (6.53/year [1.18–15.3] during treatment versus 2.70/year [0.27–12.2] before treatment, p = 0.175).ConclusionsNintedanib efficacy may be limited in patients with iPPFE.     

Lobar distribution of non-emphysematous gas trapping and lung hyperinflation in chronic obstructive pulmonary disease

BackgroundLung hyperinflation in chronic obstructive pulmonary disease (COPD) is closely associated with emphysema and non-emphysematous gas trapping, termed functional small airway disease (fSAD), on inspiratory and expiratory computed tomography (CT). Because the cranial-caudal emphysema distribution affects pulmonary function and fSAD may precede emphysema on CT, we tested the hypothesis that lobar fSAD distribution would affect lung hyperinflation differently in COPD with minimal and established emphysema.MethodsThe volume percentages of fSAD and emphysema (fSAD% and Emph%) over the upper and lower lobes were measured using inspiratory and expiratory CT in 70 subjects with COPD. Subjects were divided into those with minimal and established emphysema (n = 36 and 34) using a threshold of 10% Emph% in the whole lung.ResultsIn the minimal emphysema group, fSAD% in the upper and lower lobes was positively correlated with functional residual capacity (FRC) and residual volume to total lung capacity ratio (RV/TLC), and the correlation of fSAD% with RV/TLC was greater in the lower lobes. Conversely, in the established emphysema group, fSAD% in the upper and lower lobes was correlated with RV/TLC, but not with FRC. In multivariate analysis, fSAD% in the lower lobes, but not in the upper lobes, was associated with RV/TLC in subjects with minimal emphysema after adjusting for age, smoking status, and bronchodilator use.ConclusionNon-emphysematous gas trapping in the upper and lower lobes has a distinct physiological effect, especially in COPD with minimal emphysema. This local evaluation might allow sensitive detection of changes in lung hyperinflation in COPD.