Guar gum and similar soluble fibers in the regulation of cholesterol metabolism: Current understandings and future research priorities

The hypocholesterolemic effects associated with soluble fiber consumption are clear from animal model and human clinical investigations. Moreover, the modulation of whole-body cholesterol metabolism in response to dietary fiber consumption, including intestinal cholesterol absorption and fecal sterol and bile acid loss, has been the subject of many published reports. However, our understanding of how dietary fibers regulate molecular events at the gene/protein level and alter cellular cholesterol metabolism is limited. The modern emphasis on molecular nutrition and rapid progress in ‘high-dimensional’ biological techniques will permit further explorations of the role of genetic polymorphisms in determining the variable interindividual responses to soluble fibers. Furthermore, with traditional molecular biology tools and the application of ‘omic’ technology, specific insight into how fibers modulate the expression of genes and proteins that regulate intestinal cholesterol absorption and alter hepatic sterol balance will be gained. Detailed knowledge of the molecular mechanisms by which soluble fibers reduce plasma cholesterol concentrations is paramount to developing novel fiber-based “cocktails” that target specific metabolic pathways to gain maximal cholesterol reductions.     

Patterns and predictors of early recurrence in postmenopausal women with estrogen receptor-positive early breast cancer

Previous studies suggest that disease recurrence peaks at around 2 years in patients with early stage breast cancer (EBC), but provide no data regarding recurrence type. This retrospective analysis aimed to identify early recurrence types and risk factors in estrogen receptor-positive (ER+) EBC patients treated with adjuvant tamoxifen following breast cancer surgery. Postmenopausal women diagnosed with ER+ EBC from 1995 to 2004 were evaluated. Annual hazard ratios (HR) for recurrence at different sites were calculated. Time-dependent Cox regression analysis was used to identify predictors of recurrence within 2.5 years of diagnosis, including factors that were more strongly predictive of early than later recurrence. Of 3,614 patients evaluated, 476 developed recurrence during the 5-year median follow-up. Cumulative recurrence rates at 2.5 years (95% confidence interval) were: overall 6.3% (5.5–7.1), locoregional 1.1% (0.7–1.5), contralateral 0.5% (0.3–0.7), and distant 4.8% (4.0–5.6). The annual HR of overall recurrence peaked at 2 years (4.3% per annum). The majority of this peak represented distant recurrence (3.4% per annum). In Cox regression analysis, tumor size and grade, lymph node involvement, lymphovascular invasion, and symptomatic presentation were significant independent predictors of early recurrence. Age at diagnosis was independently predictive of recurrence within 2.5 years of diagnosis but not later recurrence. This study identified an early recurrence peak at 2 years, most of which were distant recurrences. Implementing an aromatase inhibitor after an initial 2–3 years of tamoxifen fails to address this early peak of distant recurrence and the potential breast cancer-associated mortality.     

Theoretical and methodological considerations in the measurement of spasticity

Purpose: To discuss the measurement of spasticity in the clinical and research environments, make recommendations based on the SPASM reviews of biomechanical, neurophysiological and clinical methods of measuring spasticity and indicate future developments of measurement tools. Method: Using the results of the systematic reviews of the biomechanical, neurophysiological and clinical approaches, methods were evaluated across three dimensions: (1) validity, reliability and sensitivity to change; (2) practical quality such as ease of use and (3) qualities specific to the measurement of spasticity, for example ability to be applied to different muscle groups. Methods were considered in terms of applicability to research and clinical applications. Results: A hierarchy of measurement approaches was identified from highly controlled and more objective (but unrelated to function) to ecologically valid, but less objective and subject to contamination from other variables. The lack of a precise definition of spasticity may account for the problem of developing a valid, reliable and sensitive method of measurement. The reviews have identified that some tests measure spasticity per se, some phenomena associated with spasticity or consequential to it and others the effect of spasticity on activity and participation and independence. Conclusions: Methods appropriate for use in research, particularly into the mechanism of spasticity did not satisfy the needs of the clinician and the need for an objective but clinically applicable tool was identified. A clinical assessment may need to generate more than one 'value' and should include evaluation of other components of the upper motor neurone syndrome. There is therefore a need for standardized protocols for 'best practice' in application of spasticity measurement tools and scales.     

Meniscus tears of the knee: prospective evaluation with CT

A total of 209 patients underwent prospective axial computed tomography (CT) examinations of the knee to evaluate the ability of this technique to identify and characterize knee menisci in patients believed to have meniscus tears. Of the 359 knees examined, 105 subsequently underwent arthrography, arthroscopy, or arthrography and arthroscopic surgery. In this group, the sensitivity of CT was 88.5%, specificity was 95.5%, and accuracy was 91.5%. Although axial CT is a sensitive and effective method for the detection and characterization of tears involving the medial and lateral menisci, purely horizontal or nondisplaced peripheral tears may be difficult to demonstrate.     

Thoracic outlet syndrome: evaluation with CT

Diagnosis of the thoracic outlet syndrome is often difficult, particularly in patients without osseous abnormalities on plain radiographs. The radiographic and computed tomographic (CT) findings were reviewed from 27 patients with thoracic outlet syndrome and 21 normal subjects. The plain radiographs and CT scans were assessed by two independent observers without awareness of the clinical history. Fifteen patients with thoracic outlet syndrome had osseous abnormalities (anomalous cervical ribs; abnormally long, drooping C-7 transverse processes) identifiable on plain radiographs. CT did not provide further diagnostic information in the patients with abnormal radiographs. Eight of 12 patients (66%) with normal plain radiographs had abnormal findings on CT scans, consisting of impingement of the C-7 transverse process on the scalene triangle or anteromedial aspect of the middle scalene muscle. Only two of 21 control patients (9.5%) displayed this CT abnormality (P less than .01). CT may be useful in patients with symptoms suggestive of thoracic outlet syndrome and no osseous abnormalities on plain radiographs.     

The analysis of very small samples of repeated measurements II: A modified Box correction

There is a need for appropriate methods for the analysis of very small samples of continuous repeated measurements. A key feature of such analyses is the role played by the covariance matrix of the repeated observations. When subjects are few it can be difficult to assess the fit of parsimonious structures for this matrix, while the use of an unstructured form may lead to a serious lack of power. The Kenward–Roger adjustment is now widely adopted as a means of providing an appropriate inferences in small samples, but does not perform adequately in very small samples. Adjusted tests based on the empirical sandwich estimator can be constructed that have good nominal properties, but are seriously underpowered. Further, when such data are incomplete, or unbalanced, or non‐saturated mean models are used, exact distributional results do not exist that justify analyses with any sample size. In this paper, a modification of Box's correction applied to a linear model‐based F‐statistic is developed for such small sample settings and is shown to have both the required nominal properties and acceptable power across a range of settings for repeated measurements. Copyright © 2010 John Wiley & Sons, Ltd.     

N-乙酰半胱氨酸对脑死亡状态巴马小型猪肾脏结构、功能与核转录因子κB表达的影响

目的：观察核转录因子κB活性抑制剂N-乙酰半胱氨酸对脑死亡状态下巴马小型猪肾脏结构、功能与核转录因子κB mRNA其蛋白表达的影响，以期提高脑死亡供肾的肾移植效果。方法：实验于2003—08／2004—12在河南省实验动物中心及河南省病理学重点实验室完成。①实验分组及方法：将15只巴马小型猪按随机数字表法分为3组（n=5），即脑死亡组、N-乙酰半胱氨酸组及对照组。脑死亡组和N-乙酰半胱氨酸组均应用改进的缓慢间断颅内加压法建立脑死亡模型，脑死亡组不行药物干预；N-乙酰半胱氨酸组分别于初次确认脑死亡后1h，12h给予N-乙酰半胱氨酸。对照组动物麻醉后仅行开颅与开关腹手术。②实验评估：分别于首次判定脑死亡后3，6，12，18和24h检测动物血清中尿素氮、肌酐、白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平。于脑死亡后3，6，12及24h开腹取相同部位肾组织，苏木精-伊红染色后观察肾组织结构变化，应用免疫组化染色观察核转录因子κB蛋白的表达水平，应用反转录-聚合酶链反应法检测核转录因子κB mRNA动态变化。结果：15只猪均进入结果分析。①自首次判定脑死亡后12h开始，脑死亡组和N-乙酰半胱氨酸组尿素氮和肌酐水平逐渐升高（P〈0．05），相同时间点比较N-乙酰半胱氨酸组显著低于脑死亡组（P〈0．05）。②自首次判定脑死亡3h开始，脑死亡组及N-乙酰半胱氨酸组白细胞介素1β、白细胞介素6、肿瘤坏死因子α逐渐升高（P〈0．05），相同时间点比较N-乙酰半胱氨酸组显著低于脑死亡组（P〈0．05）。③自脑死亡后3h开始，脑死亡组及N-乙酰半胱氨酸组肾组织NF-κB mRNA其蛋白表达水平逐渐升高（P〈0．05），相同时间点比较N-乙酰半胱氨酸组显著低于脑死亡组（P〈0．05）。④N-乙酰半胱氨酸组和脑死亡组动物脑死亡后12h可见肾脏结构变化，N-乙酰半胱氨酸组变化程度明显轻于脑死亡组。结论：N-乙酰半胱氨酸可能通过抑制核转录因子κB mRNA其蛋白的表达，减少炎症介质的释放，从而保护脑死亡状态下肾脏的功能及结构，提高脑死亡供肾肾移植效果。