Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or granulocyte-colony-stimulating factor: implications for yield of hematopoietic progenitor cell collections

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN and METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage– colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU- GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G- CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies.     

Catecholaminergic Innervation of the Human Dura Mater Involved in Headache

The catecholaminergic innervation of cranial dura mater in humans was studied by examining several dural zones (vascular, perivascular, intervascular) in different regions (basal, calvarial, occipital, frontal, tentorial, parietal, temporal).
The results demonstrate that catecholaminergic nerve fibers are present in human cranial dura mater and that these fibers, after exposure to formaldehyde vapors, show the specific fluorescence of catecholamines.
There are more dural catecholaminergic nerve fibers in the basal region than in the calvarial region. Moreover, these nerve fibers are more abundant in the perivascular dural zone than in the intervascular zone.
We hypothesize that these catecholaminergic nerve fibers may be involved in headache.     

健胃愈疡颗粒干预下大鼠胃溃疡黏膜乳癌相关肽和血小板活化因子的表达及与胃黏膜疏水性的相关性研究

目的:观察对胃溃疡复发有较好疗效的健胃愈疡颗粒对溃疡黏膜乳腺癌相关肽和血小板活化因子表达的影响,分析其可能的作用机制。方法:实验于2005-07/2006-07在湘雅医院中心实验室完成。SD大鼠110只,雌雄各半,随机抽签法分为5组,即正常对照组、假手术组、雷尼替丁组、健胃愈疡组,各20只;模型组30只。以Okabe改良法复制大鼠实验性胃溃疡,假手术组仅以生理盐水代替乙酸注入玻管内。造模后24h,雷尼替丁组、健胃愈疡组大鼠分别灌服盐酸雷尼替丁和健胃愈疡颗粒(药物组成为:柴胡、党参、白芍、延胡索、白芨、珍珠层粉、青黛、甘草,湖南湘雅制药有限公司生产)药液10mL/kg,分别相当于2.70,1.62g/kg,1次/d。假手术组、模型组灌服蒸馏水10mL/kg。10d后各组中随机取出10只大鼠剖腹取胃(处死前大鼠禁食24h),90d时将模型组20只大鼠再分为模型复发组和模型非复发组,各10只;除正常对照组、假手术组、模型非复发组大鼠腹腔内注射生理盐水外,其余各组大鼠腹腔内注射白细胞介素1,1μg/kg;在注射48h,大鼠禁食24h后,剖腹取胃。观察其对胃溃疡大鼠胃黏膜氨基己糖及磷脂含量、溃疡指数和胃黏膜血流的影响,并用RT-PCR观察乳癌相关肽乳癌相关肽和血小板活化因子表达的变化。结果:实验动物110只,全部进入结果分析。①模型组10,92d胃黏膜血流均低于正常对照组(P<0.01);健胃愈疡组同期胃黏膜血流均高于模型组(P<0.01)。②健胃愈疡组和雷尼替丁组10d溃疡指数均低于模型组(P<0.01,P<0.05);模型复发组、健胃愈疡组和雷尼替丁组92d溃疡指数均高于模型组(P<0.01);健胃愈疡组10,92d溃疡指数及复发率均低于雷尼替丁组(P<0.05,P<0.01)。③模型组10,92d氨基己糖和磷脂含量均低于正常对照组(P<0.01)。健胃愈疡组10,92d氨基己糖和磷脂含量均高于模型组和雷尼替丁组(P<0.01)。溃疡指数与氨基已糖、磷脂含量呈负相关(r=-0.957,-0.960,P<0.01)。④健胃愈疡组和雷尼替丁组10d乳癌相关肽mRNA表达较正常组和假手术组提高,血小板活化因子mRNA的表达下调(P<0.01),健胃愈疡组两指标表达变化较雷尼替丁组显著(P<0.01);模型复发组、健胃愈疡组和雷尼替丁组92d乳癌相关肽mRNA、血小板活化因子mRNA的表达同组10d比较差异无显著性意义(P>0.05);模型组乳癌相关肽mRNA、血小板活化因子mRNA的表达同组10d比较差异有显著性意义(P<0.01)。结论:健胃愈疡颗粒可提高乳癌相关肽mRNA及下调血小板活化因子mRNA的表达,影响胃黏膜氨基己糖及磷脂含量,可能是其促进溃疡愈合的机制之一。     

体外膜肺氧合技术支持治疗期间患者血乳酸浓度及其预后

目的:探讨体外膜肺氧合支持治疗患者血乳酸浓度的变化和预后。方法:于2004-12/2006-09在中国医学科学院阜外心血管病医院因脱离体外循环困难的心脏外科术后患者、扩张性心肌病和冠状动脉粥样硬化性心脏病发生心源性休克的患者共40例进行了体外膜肺氧合支持治疗,按年龄和存活预后分为4组:成人存活组、成人死亡组、儿童存活组、儿童死亡组。分析4组的治疗效果,分别抽取各组患者体外膜肺氧合建立时、体外膜肺氧合运转6h、运转中间时点、停机前6h、停机时的血乳酸浓度。结果:①体外膜肺氧合支持治疗患者40例,成人组26例,20例脱机,16例生存,10例死亡,脱机率76.9%,生存率61.5%;儿童组14例,7例脱机,5例生存,9例死亡,脱机率50.0%,生存率35.0%。②成人或儿童存活组的乳酸浓度都与死亡组有明显差别,存活组血乳酸浓度明显低于死亡组,其中建立和运转6h、中间时点的差异有显著性意义(P<0.05),其余2个时点的差异有非常显著性意义(P<0.001)。组内与建立时比较,中间时点、停止前6h、停止时差异均有显著性意义(P<0.001),血乳酸浓度逐渐降低。结论:经体外膜肺氧合支持治疗的患者,血乳酸浓度明显下降,脱机时血乳酸仍高的患者预后不良。     

Contribution of corticospinal tract damage to cortical motor reorganization after a single clinical attack of multiple sclerosis

The objectives of this study were to assess whether cortical motor reorganization in the early phase of multiple sclerosis (MS) is correlated with the clinical presentation and with specific damage to the corticospinal tract. Twenty patients with clinically isolated syndrome (CIS) and serial MR findings indicative of MS were selected. In 10 patients the CIS was hemiparesis (group H), and in 10 patients the CIS was optic neuritis (group ON). There were no significant differences in age, disease duration, total T2 lesion load (LL), and total T1 LL between group H and group ON. Ten age-matched healthy subjects served as controls (group C). All subjects were submitted to fMRI during a sequential finger-to-thumb opposition task of the right hand. Group H showed a significantly higher EDSS score and T1 LL calculated along the corticospinal tract than group ON. Three-group comparison by ANOVA showed significantly higher activation in group H than in the other two groups (P < 0.001). Significant foci were located in the sensory-motor cortex (BA 1-4), the parietal cortex (BA 40), the insula of the ipsilateral hemisphere, and the contralateral motor cortex (BA 4/6). Group ON showed, although at a lower level of significance (P < 0.01), higher activation of the contralateral motor-related areas than group C. Multiple regression analysis showed that T2 and T1 LL along the corticospinal tract and time since clinical onset positively correlated with activation in motor areas in both cerebral hemispheres (P < 0.005). Total T2 LL positively correlated with activation in motor areas in the contralateral hemisphere (P < 0.005). Total T1 LL and EDSS did not show any significant correlation. More severe specific damage to the motor pathway in patients with previous hemiparesis may explain the significantly higher involvement of ipsilateral motor areas observed in group H than in group ON. Furthermore, the significant correlation between the time since clinical onset and activation in motor areas suggests that cortical reorganization develops gradually in concomitance with the subclinical accumulation of tissue damage.     

Bilateral periventricular nodular heterotopia with amniotic band syndrome

The amniotic (constriction) band syndrome is characterized by distal ring constrictions, intrauterine amputations, and acrosyndactyly. External constriction by amniotic bands is the generally accepted mechanism: early amniotic rupture leads to formation of mesodermal fibrous strands that constrict, entangle, and amputate distal portions of limbs. Etiology is heterogeneous. Anecdotal cases involving central nervous system abnormalities (e.g., acrania, anencephaly, polymicrogyria, congenital bilateral perisylvian syndrome, neuronal heterotopia, septo-optic dysplasia, and spinal cord tethering) have been reported. We describe a 9-year-old girl with typical features of constriction band syndrome localized to the lower limbs who had also profound mental retardation and drug-resistant epilepsy associated with bilateral periventricular nodular heterotopia (a brain malformation of neuronal migration and proliferation caused by mutations in the X-linked filamin 1 gene [FLN1] on chromosome Xq28). The karyotype was normal, as was mutational screening for FLN1. The occurrence of bilateral periventricular nodular heterotopia in the context of amniotic band syndrome is novel (chance occurrence of both: 0.000004%).     

Topiramate in frontal lobe epilepsy

BACKGROUND: Frontal lobe epilepsy (FLE) is a type of epilepsy that is difficult to treat and there are few studies about the use of topiramate (TPM). AIM OF THE STUDY: To evaluate the efficacy and tolerability of TPM monotherapy in FLE. METHODS: The study group consisted of 55 (33 male; 22 female) patients. TPM was administered as a first drug (n = 16) or converted after previous treatment (n = 39). All patients were followed every 3 months for at least 1 year. The patients were subdivided into two groups: 'newly diagnosed' patients and 'difficult-to-treat' patients. RESULTS: Overall, all patients completed the 1-year study. At the end of follow-up, 10 patients showed disappearance of seizures and 33 patients showed improvement in seizure frequency. In particular, among the newly diagnosed patients 6/16 patients showed complete cessation of seizures and 5/16 patients showed very good response; in the other group, 4/39 patients showed complete cessation and 4/39 patients showed a very good response. No patients of both groups had worsening of seizures. No treatment-limiting adverse events associated with TPM were reported. CONCLUSIONS: TPM is effective in newly diagnosed patients with FLE; TPM can be considered for the treatment of FLE.     

Levetiracetam monotherapy for children and adolescents with benign rolandic seizures.

To assess the efficacy, tolerability and safety of Levetiracetam (LEV) therapy, we identified 21 (15 male; 6 female) patients with a history of benign epilepsy with centrotemporal spikes (BECTS), with and without secondarily generalization in children and adolescents aged between 5.0 and 12.1 years. LEV was administered as a first drug (number of patients=9) or converted after previous treatment with other AEDs (number of patients=12). The patients were subdivided into two groups: "newly diagnosed" patients and "converted" patients. Patients were followed up for 12 months and all patients were able to continue on LEV treatment. At the end of follow-up (12 months), all patients were seizure free or showed a reduction of seizures >50%. LEV dosage ranged from 1000 to 2500mg/daily. Overall, 100% of patients completed the 12 months study, without any important side effect. Somnolence and irritability occurred in two (9.5%) patients. Our results support findings that LEV monotherapy is effective and well tolerated in children with BECTS. Prospective, large, long-term double-blind studies are needed to confirm these findings.