Associations between trunk, leg and total body adiposity with arterial stiffness

BackgroundObesity and arterial stiffness are associated, but fat distribution patterns may be more strongly related to arterial stiffness than general obesity because of the possible increased inflammation associated with increased abdominal adiposity. The aims of this study were to examine whether fat patterning is associated with arterial stiffness, and determine whether these associations are mediated by low-grade inflammation.MethodsAdult participants from the Fels Longitudinal Study (228 males and 254 females) were assessed for brachial-ankle pulse wave velocity (BaPWV) to determine arterial stiffness. Dual energy X-ray absorptiometry was used to estimate fat percentage of the trunk and legs (e.g., TRUNKFAT% and LEGFAT%). High-sensitivity C-reactive protein (hs-CRP) levels were assayed as a general marker of inflammation. General linear regression analyses were used.ResultsBaPWV was positively associated with TRUNKFAT% (r = 0.44 in men and r = 0.38 in women), whereas it was inversely related to LEGFAT% (r = -0.40 in men and r = -0.39 in women). In multiple regression analyses, each SD increase in TRUNKFAT% was associated with an ~1.03 m/s increase in BaPWV in both men and women. Each SD increase in LEGFAT% was related to a similar magnitude of decrease (1.03 m/s) in BaPWV in both sexes. The relationships of TRUNKFAT% and LEGFAT% with BaPWV were attenuated slightly when including hs-CRP in the models, but remained significant.ConclusionsWe found that trunk and leg fat are related to BaPWV in opposite directions when total body adiposity was accounted for. However, the associations between regional fat patterning and arterial stiffness did not appear to be mediated by low-grade inflammation.American Journal of Hypertension, 2012; doi:10.1038/ajh.2012.92.     

白花蛇舌草-半枝莲药对组分对结肠腺癌Lovo细胞生物学行为的影响

摘要:目的　探讨白花蛇舌草-半枝莲药对组分对结肠腺癌Lovo细胞增殖、侵袭、迁移和凋亡的影响及作用机制。方法　将白花蛇舌草、半枝莲按质量1∶1进行3次煎煮,获得水提物,后取适量浸膏用石油醚回流脱脂,再以乙酸乙酯进行多次萃取,获得白花蛇舌草-半枝莲药对组分,并计算得率。实验分为对照组（正常培养Lovo细胞）、白花蛇舌草-半枝莲药对组分低剂量组（10 mg/L）、中剂量组（30 mg/L）及高剂量组（50 mg/L）。通过噻唑蓝比色法（MTT）检测各组细胞培养24、48、72 h后的增殖抑制率。各组细胞培养48 h后,流式细胞仪检测细胞周期分布;Transwell实验检测细胞侵袭能力;划痕实验检测细胞迁移能力;TUNEL法检测细胞凋亡情况;Western blot法检测Grb2相关结合蛋白1（Gab1）、血管内皮生长因子受体2（VEGFR-2）、磷脂酰肌醇3-激酶（PI3K）、苏氨酸激酶（Akt）、基质金属蛋白酶-9（MMP-9）、B淋巴细胞瘤-2基因（Bcl-2）、Bcl-2相关X蛋白（Bax）蛋白表达情况。结果　化学萃取后的白花蛇舌草-半枝莲药对中主要含有对羟基苯乙酮、野黄芩苷、木犀草素和芹菜素4种化合物,组分得率为0.61%。与对照组相比,低、中、高剂量组细胞增殖抑制率升高,G1期肿瘤细胞比例增加,细胞凋亡指数增高,侵袭细胞数和划痕闭合率明显减小（均P＜0.05）,细胞中Gab1、VEGFR-2、PI3K、Akt、MMP-9、Bcl-2蛋白表达降低,Bax表达升高（均P＜0.05）,且存在剂量依赖性。结论　白花蛇舌草-半枝莲药对组分可抑制结肠腺癌Lovo细胞的增殖,降低其迁移和侵袭能力,诱导细胞凋亡,其机制可能与抑制Gab1/VEGFR-2/PI3K/Akt信号通路活化有关。     

The floating cardiac fat pad—sign of occult pneumothorax

Pneumothoraces are a possible sequela of chest trauma with potential morbidity and mortality if not recognized and treated promptly. A portable supine chest radiograph is frequently the first radiologic study performed in the setting of trauma. While large pneumothoraces can be readily recognized on these radiographs, smaller pneumothoraces are missed in up to 15 % of trauma patients. There are many radiographic signs of occult pneumothoraces, and we are presenting a new radiographic sign of occult pneumothorax. The floating cardiac fat pad sign occurs when pleural air collects anteriorly and superiorly in the most non-dependent portion of the chest lifting the pericardial fat pad off the diaphragm. Lung markings are still seen surrounding the pericardial fat pad due to the inflated lower lobe of the lung resting dependently. Rapid and accurate identification of pneumothoraces is critical but often difficult on chest radiographs. Although there are many existing radiographic signs for identification of pneumothorax, prospective identification of small pneumothoraces is still relatively poor. Here, we describe an additional sign which aides in the detection of pneumothoraces, the floating cardiac fat pad. When present, this should prompt further evaluation with chest CT or upright chest radiograph.     

Meta-analysis of retrojugular versus antejugular approach for carotid endarterectomy

Introduction

The retrojugular approach for carotid endarterectomy (CEA) has been reported to have the advantages of shorter operative time and ease of dissection, especially in high carotid lesions. Controversial opinion exists with regard to its safety and benefits over the conventional antejugular approach.

Methods

A systematic review of electronic information sources was conducted to identify studies comparing outcomes of CEA performed with the retrojugular and antejugular approach. Synthesis of summary statistics was undertaken and fixed or random effects models were applied to combine outcome data.

Findings

A total of 6 studies reporting on a total of 740 CEAs (retrojugular approach: 333 patients; antejugular approach: 407 patients) entered our meta-analysis models. The retrojugular approach was found to be associated with a higher incidence of laryngeal nerve damage (odds ratio [OR]: 3.21, 95% confidence interval [CI]: 1.46–7.07). No significant differences in the incidence of hypoglossal or accessory nerve damage were identified between the retrojugular and antejugular approach groups (OR: 1.09 and 11.51, 95% CI: 0.31–3.80 and 0.59–225.43). Cranial nerve damage persisting during the follow-up period was similar between the groups (OR: 2.96, 95% CI: 0.79–11.13). Perioperative stroke and mortality rates did not differ in patients treated with the retrojugular or antejugular approach (OR: 1.26 and 1.28, 95% CI: 0.31–5.21 and 0.25–6.50).

Conclusions

Currently, there is no conclusive evidence to favour one approach over the other. Proof from a well designed randomised trial would help determine the role and benefits of the retrojugular approach in CEA.     

Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.     

Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.