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.     

肝癌介入诊疗中DSA血流动力学参数分析初步探讨

目的探讨肝癌TACE介入栓塞前肝动脉造影图像上癌灶、癌旁肝组织、背景肝组织之间血流动力学相关参数的差异性。方法本组共34例,男28例,女6例,均为经临床诊断原发性肝癌后第一次行介入诊疗。介入栓塞治疗前均先行肝固有动脉插管造影,采用高压注射器团注对比剂（370mgl／m1）15ml,流率5ml／s,注射后延时0．5s曝光,以4帧／s（fps）帧率持续采集图像15s,获取60（4x15）幅图像。图像处理采用自主开发的图像处理软件DSAanalysis1．0。分别在癌灶的肿瘤染色区、癌旁肝组织及背景肝组织等区域各选定兴趣区（ROI）,并生成各区域ROI的时间一密度曲线（TDC）,对各TDC进行定量分析,获得与血流动力学相关的参数并对比,相关的参数包括：视频密度增量峰值（AXPV）、达峰时间（TP）、显影持续时间（TD）、TDC升支及降支最大斜率（KmaxU及KmaxD）。结果癌灶、癌旁肝组织、背景肝组织的TD分别为12．97s±0．89、7．75s±0．89、4．99s±0．37;KmaxD分别为36．0s^-1±8．2、90．8s^-1±24．3和142．6S^-1±26．4s。癌灶、癌旁肝组织、背景肝组织的TD及KmaxD两两对比均具有显著性的差异（P〈0．01）。而其他参数三者之间差异无统计学意义（P〉0．05）。结论通过对DSAanalysis1．0软件获得的TDC进行分析,可获得与血流动力学相关参数值,其中TD、KmaxD可在一定程度上反映癌灶、癌旁肝组织及背景肝组织的血流动力学差异。     

Anatomical reconstruction of the lateral ligaments using Gracillis tendon in chronic ankle instability; a new technique

Background

Many surgical technique have been described to assess the outcome of anatomical reconstruction of the lateral ligaments using Gracillis tendon. This technique aims to restore the stability of the ankle by reconstruction of the talofibular ligament (ATFL) and the calcaneofibular ligament (CFL) using the Gracillis tendon.

Methods

From January 2004 to February 2008; inclusive, 16 patients; 11 male and 5 female, underwent an anatomic reconstruction of the lateral ankle ligament for chronic ankle instability. Their ages ranged from 18 to 29 giving a mean age of 25 years. Patients were then subjected to radiologic and clinical assessments for a period of at least 33.5 months. For pain scoring the Americans Orthopaedic Foot and Ankle Society (AOFAS) scores were used; whilst subjective symptom was evaluated using the Olerud and Molander ankle scoring system.

Results

All patients returned for the final evaluation and subjective excellent or good results were recorded on self-assessment, pain scores, AOFAS and Karissons scores. Additionally Olerud and Molander ankle scoring was also done. During the final follow-up, the mean post-operative AOFAS score was 96 (range 80–100), the Visual analog score was 6 (range 0–4), Karissons score was 94.7 (range 80–100) and last but not least Olerud and Molander score was 87.5 (range 70–100). It was noted that the ankle range of motion was not affected by lateral ankle reconstruction. The talar tilt was reduced from a mean of 12–4° (p < 0.0001) and the anterior drawer was reduced from a mean of 11–4 mm (p < 0.001) by the ankle ligament reconstruction.

Conclusion

Anatomical reconstruction of the lateral ligaments of chronic ankle instability using Gracillis tendon graft resulted in successful results, excellent ankle stability, significant reduction in pain and negligible loss of ankle and hind foot motion.     

Hand,foot and mouth disease in China: evaluating an automated system for the detection of outbreaks

Objective

To evaluate the performance of China’s infectious disease automated alert and response system in the detection of outbreaks of hand, foot and mouth (HFM) disease.

Methods

We estimated size, duration and delay in reporting HFM disease outbreaks from cases notified between 1 May 2008 and 30 April 2010 and between 1 May 2010 and 30 April 2012, before and after automatic alert and response included HFM disease. Sensitivity, specificity and timeliness of detection of aberrations in the incidence of HFM disease outbreaks were estimated by comparing automated detections to observations of public health staff.

Findings

The alert and response system recorded 106 005 aberrations in the incidence of HFM disease between 1 May 2010 and 30 April 2012 – a mean of 5.6 aberrations per 100 days in each county that reported HFM disease. The response system had a sensitivity of 92.7% and a specificity of 95.0%. The mean delay between the reporting of the first case of an outbreak and detection of that outbreak by the response system was 2.1 days. Between the first and second study periods, the mean size of an HFM disease outbreak decreased from 19.4 to 15.8 cases and the mean interval between the onset and initial reporting of such an outbreak to the public health emergency reporting system decreased from 10.0 to 9.1 days.

Conclusion

The automated alert and response system shows good sensitivity in the detection of HFM disease outbreaks and appears to be relatively rapid. Continued use of this system should allow more effective prevention and limitation of such outbreaks in China.     

Total but not resting energy expenditure is increased in infants with ventricular septal defects

OBJECTIVE: The purpose of this study was to determine the effect of left-to-right shunting on the resting energy expenditure (REE), total energy expenditure (TEE), and energy intake in a group of 3- to 5-month-old infants with moderate to large unrepaired ventricular septal defects (VSDs) compared with age-matched, healthy infants. METHODS: Eight infants with VSDs and 10 healthy controls between 3 to 5 months of age participated in the study. Indirect calorimetry was used to measure REE and the doubly-labeled water method was used to measure TEE and energy intake. An echocardiogram and anthropometric measurements were performed on all study participants. Daily urine samples were collected at home for 7 days. Samples were analyzed by isotope ratio mass spectrometry. Data were compared using analysis of variance. RESULTS: No significant differences were found in REE (VSD, 42.2 +/- 8.7 kcal/kg/d; control, 43.9 +/- 14.1 kcal/kg/d) or energy intake (VSD, 90.8 +/- 19.9 kcal/kg/d; control, 87.1 +/- 11.7 kcal/kg/d) between the groups. The percent total body water was significantly higher in the VSD infants and the percent fat mass was significantly lower. TEE was 40% higher in the VSD group (VSD, 87.6 +/- 10.8 kcal/kg/d; control, 61.9 +/- 10.3 kcal/kg/d). The difference between TEE and REE, reflecting the energy of activity, was 2.5 times greater in the VSD group. CONCLUSIONS: REE and energy intake are virtually identical between the two groups. Despite this, infants with VSDs have substantially higher TEE than age-matched healthy infants. The large difference between TEE and REE in VSD infants suggests a substantially elevated energy cost of physical activity in these infants. These results demonstrate that, although infants with VSDs may match the energy intake of healthy infants, they are unable to meet their increased energy demands, resulting in growth retardation.     

Reduced inspiratory flow attenuates IL-8 release and MAPK activation of lung overstretch.

Lung overstretch involves mechanical factors, including large tidal volumes (VT), which induce inflammatory responses. The current authors hypothesised that inspiratory flow contributes to ventilator-induced inflammation. Buffer-perfused rabbit lungs were ventilated for 2 h with 21%, O2+5%, CO2, positive end-expiratory pressure of 2-3 cmH2O and randomly assigned to either: 1) normal VT (6 mL x kg(-1)) at respiratory rate (RR) 30, inspiration:expiration time ratio (I:E) 1:1, low inspiratory flow 6 mL x kg(-1) x s(-1); 2) large VT (12 mL x kg(-1)) at RR 30, I:E 1:1, high inspiratory flow 12 mL x kg(-1) x s(-1) (HRHF); 3) large VT at RR 15, I:E 1:1, low inspiratory flow 6 mL x kg(-1) x s(-1) (LRLF); or 4) large VT at RR 15, I:E 1:2.3, high inspiratory flow 10 mL x kg(-1) x s(-1) (LRHF). Physiological parameters, tumour necrosis factor (TNF)-alpha, interleukin (IL)-8 and activation of mitogen-activated protein kinases (extracellular signal-regulated kinase (ERK)1/2, p38 and stress-activated protein kinase (SAPK)/ c-Jun N-terminal kinase (JNK)) were measured. HRHF increased weight gain, perfusate IL-8 and phosphorylation of ERK1/2, p38 and SAPK/JNK. These responses were absent during LRLF but present during LRHF. Changes in TNF-alpha were small. Tissue IL-8 and phospho-ERK1/2 staining was localised primarily to smooth muscle, adventitia and bronchial epithelium within larger bronchioles and arterioles. These results indicate that mild overstretch of perfused lungs during high inspiratory flow enhances inflammatory signalling by cells in lung regions most affected by strong turbulent airflow.     

中西医结合治疗老年高脂血症

目的：探讨中西医结合治疗高脂血症的临床疗效。方法：符合高脂血症标准的老年患者120例，随机分为A、B2组各60例，A组采用益肾化淤、利湿化浊为主的中药及西药辛伐他汀片治疗；B组则单纯用辛伐他汀片治疗。治疗前及治疗4周后2组均行全套血脂水平测定。结果：与B组比较，A组血清总胆固醇（TC）及甘油三酯（TG）均明显下降，HDL明显上升（均P〈0．05）；A组临床控制率明显高于B组（P〈0．05）；治疗后A组患者未见肝功能损害，B组转氨酶及转肽酶轻度异常，2例。停药3个月后，A组复发率低于B组（2．2％、8．8％，P〈0．05）。结论：中西医结合治疗老年高脂血症的临床效果明显优于单一的一种治疗方法，值得临床进一步推广应用。     

Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization

Human factor VIII(FVIII) inhibitors are pathologic, circulating antibodies that inactivate FVIII. We have examined the location of epitopes on the FVIII protein for inhibitors from hemophilia A and nonhemophilic individuals. The inhibitors were of type I or type II in the kinetics of their inactivation of FVIII. A cDNA clone of human FVIII was used to express defined FVIII protein fragments in Escherichia coli for immunoblotting with inhibitor plasma. An epitope for 18 heavy-chain inhibitors was localized to the aminoterminal 18.3 Kd of the A2 domain. Two of these inhibitors also recognized an epitope located between A1 and A2 domains. Similarly, an epitope for 23 light- chain inhibitors was localized to the C2 domain. Weaker epitopes for 13 of the same inhibitors within the C1 and C2 domains were also observed. Four of the 23 inhibitors in addition bound strongly to the A3 domain. Most inhibitors (22 of 23) were neutralized in vitro only by the FVIII fragments to which they bound on immunoblots; however, one inhibitor that was neutralized by a fragment containing the A1 domain did not bind to it on immunoblots. Conversely, 3 of 3 inhibitors that bound to the A3 domain and 5 of 15 that bound to the A2 domain were not neutralized by the corresponding fragments. The epitope specificity of an inhibitor did not depend on its source or type. Our results show that FVIII inhibitors bind to limited areas within the heavy and light chains of FVIII. Some inhibitor plasmas contain additional antibodies that may not be inhibitory.