Electrochemotherapy for Colorectal Cancer with Commonly Used Chemotherapeutic Agents in a Mouse Model

We examined here the usefulness of electrochemotherapy against colorectal cancer (CRC) using a mouse model. Electropermeabilization profoundly increased the sensitivity of murine CRC, Colon 26, and MC38 cells to bleomycin (BLM) but not to 5-fluorouracil (5-FU) or to cisplatin (CDDP) in vitro. In vivo experiments revealed that electrochemotherapy with 5-FU, CDDP, or BLM was much more effective against CRC compared with the treatment of the drug alone. Electrochemotherapy with BLM or CDDP exhibited profound antitumor effects on subcutaneously established CRC in mice, and complete tumor regression was observed in five and four of eight animals, respectively. Electrochemotherapy with 5-FU also had an impact on CRC development, and complete cure was observed in one of eight animals. Subsequent analyses revealed that electropermeabilization significantly increased intratumoral amounts of BLM and CDDP but not 5-FU. These results indicate that electrochemotherapy may be a promising treatment modality against CRC.     

Assessment of Anxiety in Older Adults: A Reliability Generalization Meta-Analysis of Commonly Used Measures

We conducted a reliability generalization meta-analysis of the 12 most commonly used measures of anxiety in older adults aged 65 and older. Of the 136 articles considered for inclusion, only 24% of published studies reported reliability coefficients from their original data collection. We used 63 reliability coefficients from 51 articles and 16,183 individuals to provide internal consistency reliability estimates for this meta-analysis. We present the average score reliabilities for each of the 12 measures, characterize the variance in score reliabilities across studies, and consider sample and study characteristics that are predictive of score reliability. We discuss the importance of considering factors specific to the assessment of older adults (e.g., the frequency of a comorbid medical condition) as well as the importance of conducting sample specific reliability analyses. Recommendations are provided for researchers and clinicians choosing a measure of anxiety for use with older adults.     

Development and validation of the Mayo Clinic Bowel Prep Tolerability Questionnaire

BackgroundBowel cleansing is paramount for colonoscopy quality. Unfortunately, an adequate bowel preparation is often limited by side effects and/or patient's intolerance to bowel preparation solutions. Comparisons among different preparations are limited by the lack of validated instruments designed to assess patient's tolerability.AimTo develop and validate a simple, comprehensive instrument to assess bowel preparation tolerability in patients undergoing colonoscopy.MethodsDevelopment and validation by phases: Phase I (bibliographic search and questionnaire design); Phase II (assessment of content validity and modification of the questionnaire); Phase III (assessment of reproducibility, final validation, and definitive version of the questionnaire).ResultsThe initial draft of the questionnaire was generated based on a systematic literature review and feedback from a panel of consultants. Content validity was tested in a focus group of 25 patients undergoing colonoscopy. Patients’ suggestions were reviewed by the research team and a second draft of the questionnaire was generated. Final validation and reproducibility were successfully tested (agreement: 86–100%, kappa: 0.77–1.00) in a convenience sample of 100 patients undergoing bowel preparation with different cleansing solutions.ConclusionThe Mayo Clinic Bowel Prep Tolerability Questionnaire is a simple, comprehensive instrument suitable to evaluate the tolerability of various types of bowel preparations.     

Brazilian Portuguese Validated Version of the Cardiac Anxiety Questionnaire

Background

Cardiac Anxiety (CA) is the fear of cardiac sensations, characterized by recurrent anxiety symptoms, in patients with or without cardiovascular disease. The Cardiac Anxiety Questionnaire (CAQ) is a tool to assess CA, already adapted but not validated to Portuguese.

Objective

This paper presents the three phases of the validation studies of the Brazilian CAQ.

Methods

To extract the factor structure and assess the reliability of the CAQ (phase 1), 98 patients with coronary artery disease were recruited. The aim of phase 2 was to explore the convergent and divergent validity. Fifty-six patients completed the CAQ, along with the Body Sensations Questionnaire (BSQ) and the Social Phobia Inventory (SPIN). To determine the discriminative validity (phase 3), we compared the CAQ scores of two subgroups formed with patients from phase 1 (n = 98), according to the diagnoses of panic disorder and agoraphobia, obtained with the MINI - Mini International Neuropsychiatric Interview.

Results

A 2-factor solution was the most interpretable (46.4% of the variance). Subscales were named "Fear and Hypervigilance" (n = 9; alpha = 0.88), and "Avoidance", (n = 5; alpha = 0.82). Significant correlation was found between factor 1 and the BSQ total score (p < 0.01), but not with factor 2. SPIN factors showed significant correlations with CAQ subscales (p < 0.01). In phase 3, "Cardiac with panic" patients scored significantly higher in CAQ factor 1 (t = -3.42; p < 0.01, CI = -1.02 to -0.27), and higher, but not significantly different, in factor 2 (t = -1.98; p = 0.51, CI = -0.87 to 0.00).

Conclusions

These results provide a definite Brazilian validated version of the CAQ, adequate to clinical and research settings.     

氯吡格雷用于动脉粥样硬化血栓栓塞性疾病的安全性和耐受性观察

目的观察氯吡格雷对动脉粥样硬化血栓栓塞性疾病病人的安全性和耐受性。方法入选21岁~75岁有动脉粥样硬化病变的病人共20例,且病情稳定在1个月以上。服用氯吡格雷75mg/d,持续12周,观察其服药依从性、血压、心率、肝肾功能、血尿粪常规的变化及不良事件的发生情况。结果入选时尿红细胞、大便隐血均为阴性,收缩压(133.6±19.8)mmHg,舒张压(82.4±9.6)mmHg,心率(73.2±7.9)/min;血红蛋白(135.7±9.2)g/L,白细胞(6.3±0.98)×109/L,中性粒细胞0.62±0.03,血小板(203.4±40.0)×109/L;尿素氮6.1mmol/L±1.4mmol/L,肌酐82.3μmol/L±16.2μmol/L;谷丙转氨酶30.4U/L±11.2U/L,谷草转氨酶27.9U/L±6.3U/L。1例受试者因皮疹退出研究,另19例完成12周随访,服药依从性为95.0%。在2周、4周、8周、12周时随访血压、心率、肝肾功能指标等,较入选时均无统计学意义,未见任何白细胞或中性粒细胞显著下降。12周随访时2例病人出现尿红细胞阳性;未见大便隐血者;无脑出血、消化道出血等严重出血事件发生,1例病人出现皮下淤斑,3例病人出现轻至中度过敏反应。结论氯吡格雷用于动脉粥样硬化血栓栓塞性疾病病人耐受性好,且较为安全。     

Comparison of Commonly Used Assays for the Detection of Microalbuminuria

There are a variety of methods for assessing urinary albumin excretion, extending from the very low-range microalbuminuria to higher ranges extending into macroalbuminuria or proteinuria. The recommendation for the initial screening of a new patient is to use a urine dipstick to assess for microalbuminuria. If positive, a spot urine for albumin:creatinine should be measured and reassessed annually. All patients with kidney disease, diabetes, or hypertension and metabolic syndrome should be screened for albuminuria. New methodologies using high-performance liquid chromatography are much more sensitive and specific when compared with older methods of detection and may prove very useful for earlier identification of high-risk patients. This is important since studies have shown that albuminuria levels below the microalbuminuria range, determined by conventional methodologies in uncomplicated essential hypertensive men, are associated with an adverse cardiovascular and metabolic risk profile. High performance liquid chromatography methodology, in contrast to older studies, detects all intact albumin and enables clinicians to assess disease severity and monitor therapeutic effectiveness with confidence in the accuracy of the microalbuminuria data reported to them.     

A Comparison of Agents Used to Manage Type 2 Diabetes Mellitus

In patients with type 2 diabetes mellitus, the traditional method of initiating therapy with a sulfonylurea and increasing the dosage until maximum levels are reached before adding an insulin-sensitizing agent has persisted and should be re-evaluated. Similarly, the current practice of starting therapy with one agent and increasing to maximum dosage before adding a second agent, rather than starting with combination therapy, also needs to be addressed. There is much evidence to suggest that initiating therapy with lower doses of two agents that have complementary effects can increase the overall efficacy and decrease the incidence of adverse effects. Clearly, there is a need for a paradigm shift away from the traditional approach of therapy using insulin secretagogues to a more pathophysiologic approach using an insulin-sensitizing agent, such as the thiazolidinediones. The thiazolidinediones have been shown to reduce insulin resistance, improve the ability of beta-cells to produce insulin, and decrease cardiac risk factors. By reducing insulin resistance, improving glycemic control, and preserving beta-cell function with a thiazolidinedione early in the course of therapy, it is likely that durable glycemic control will be achieved and both microvascular and macrovascular complications may be reduced. Furthermore, early use of an insulin-sensitizing agent either alone or incombination is expected to improve both acute and long-term outcomes in patients with type 2 diabetes.     

颈动脉粥样硬化兔造模的常用方法

兔颈动脉粥样硬化狭窄模型制备的方法很多,包括内膜空气干燥法、球囊损伤法、颈总动脉套环法、直流电刺激颈动脉外膜法、幽门螺杆菌感染法、显微缝合法、放射处理法、液氮损伤法、化学烧灼法等,不同的造模方式颈动脉粥样硬化狭窄形成的机制及病理特点各不相同。本文重点介绍颈动脉粥样硬化兔模型的制作方法及其优、缺点。     

A modification of the Health Assessment Questionnaire for the spondyloarthropathies

A functional status measure was developed by adding 5 items to the Health Assessment Questionnaire (HAQ-S), and compared to anthropometric measures of spinal mobility. Forty-four patients with spondylitis were evaluated by the HAQ-S and measures of spine flexibility (finger-to-floor, Smythe test, neck rotation, and chest expansion). Modification of the HAQ raised the mean difficulty score by 29% from 0.38 (SD = 0.49) to 0.49 (SD = 0.51), indicating increased ability to capture functional limitations. Neck rotation correlated most strongly with the HAQ-S score (r = -0.57), which suggests an important role for this measure in clinical management and followup of spondylitis.     

部分冠心病常用中药对鸡胚尿囊膜的促血管生成作用研究

目的探讨部分冠心病常用中药对鸡胚尿囊膜血管生成的影响及代表药物的量效关系。方法制备鸡胚绒毛尿囊膜模型(CAM),分别以生理盐水和碱性成纤维生长因子(bFGF)为阴性和阳性对照,以血管指数为观察指标,比较所选药物的促血管生成作用,并选取作用显著者作为代表中药,研究不同浓度时对血管生成的影响。结果红景天和降香的血管指数值比较突出(P<0.01),采用不同药物浓度发现红景天中等剂量时血管生成最多,而降香的剂量和血管生成近似线性关系。结论红景天和降香具有良好的促血管生成作用,呈现独有的量效曲线。     

Misapplications of Commonly Used Kidney Equations: Renal Physiology in Practice

Equations for estimating GFR, quantifying urinary protein excretion, and assessing renal sodium handling are widely used in routine nephrology and general medical and surgical practice. If these equations are applied in circumstances inconsistent with the clinical situations for or extrapolated beyond the limits in which they were validated, clinicians can come to erroneous conclusions, which could be detrimental for patient care. This review uses clinical vignettes to demonstrate some of the common pitfalls that clinicians may encounter in the use of these equations and considers the physiologic principles underlying their use. Equations for assessing aspects of renal function should only be used in specific clinical situations, if the underlying assumptions regarding their calculations and values are satisfied.As physicians, we use equations to quantify physiologic and pathologic processes, such as measurement of renal function, estimation of proteinuria, and assessment of sodium handling, which are difficult to measure directly. Often, we do so without regard to the situation in which these formulas were initially derived and validated. By ignoring these important limitations, we may arrive at erroneous conclusions, risking compromise of the medical care we deliver to our patients. We use four case presentations to discuss common clinical settings in which the use and results of these equations may prove invalid.     

常用家庭电子血压计示值重复性和准确度的研究

目的:对常用家庭电子血压计示值重复性和准确度进行再评估.方法:选择中国人民解放军空军特色医学中心高血压和心内科门诊患者140例,以水银血压计测量3次的血压平均值为真实血压水平,依据《JJG692-2010无创自动测量血压计检定规程》和听诊法对患者使用的140台家庭电子血压计进行示值重复性和准确度再评估.结果:140台家...     

Implications of Periprocedural Myocardial Biomarker Elevations and Commonly Used MI Definitions After Left Main PCI

ObjectivesThe aim of this study was to: 1) assess the relationship of different thresholds of creatine kinase–myocardial band (CK-MB) and cardiac troponin with subsequent mortality; and 2) evaluate the prognostic significance of periprocedural myocardial infarction (PMI) according to various definitions of myocardial infarction in patients with left main (LM) coronary artery disease.BackgroundThe magnitude of postprocedural biomarker elevation representing a clinically meaningful PMI after percutaneous coronary intervention (PCI) is controversial.MethodsA total of 4,013 consecutive patients undergoing LM PCI at a single center from January 2004 to December 2016 were enrolled. CK-MB and cardiac troponin I (cTnI) were routinely collected at baseline and at frequent intervals between 8 and 48 hours after PCI. The primary and secondary outcomes were the covariate-adjusted 3-year rates of cardiovascular (CV) and all-cause mortality, respectively.ResultsThe 3-year rate of CV mortality progressively increased with higher peak CK-MB values. CV mortality was first independently predicted by postprocedural CK-MB 3 to 5 times the upper reference limit (URL) (adjusted hazard ratio [aHR]: 2.93; 95% confidence interval [CI]: 1.02-8.40), whereas all-cause death was independently predicted only by CK-MB ≥ 10 × URL (aHR: 3.25; 95% CI: 1.37-7.70). In contrast, no level of peak postprocedural cTnI was associated with CV or all-cause death. PMI by the Society for Cardiovascular Angiography and Interventions (SCAI), Academic Research Consortium-2 (ARC-2), and fourth universal definition of myocardial infarction (UDMI) occurred in 1.3%, 3.1%, and 5.1% of patients, respectively. The SCAI definition was significantly associated with 3-year CV mortality (aHR: 4.93; 95% CI: 1.92-12.69) and all-cause mortality (aHR: 3.11; 95% CI: 1.33-7.27), whereas the ARC-2 and fourth UDMI definitions were not.ConclusionsIn a large cohort of consecutive patients undergoing LM PCI, intermediate (≥3 × URL) and high (≥10 × URL) levels of peak postprocedural CK-MB independently predicted 3-year CV and all-cause mortality, respectively, whereas even large elevations of post-PCI cTnI did not. The SCAI definition (but not the ARC-2 or fourth UDMI) of PMI was independently associated with mortality after LM PCI.     

The Assessment of Burden of COPD (ABC) Scale: A Reliable and Valid Questionnaire

The newly developed Assessment of Burden of COPD (ABC) scale is a 14-item self-administered questionnaire which measures the physical, psychological, emotional and/or social burden as experienced by patients with chronic obstructive pulmonary disease (COPD). The ABC scale is part of the ABC tool that visualises the outcomes of the questionnaire. The aim of this study was to assess the reliability and construct validity of the ABC scale. This multi-centre survey study was conducted in the practices of 19 general practitioners and 9 pulmonologists throughout the Netherlands. Next to the ABC scale, patients with COPD completed the Saint George Respiratory Questionnaire (SGRQ). Reliability analyses were performed with data from 162 cases. Cronbach's alpha was 0.91 for the total scale. Test-retest reliability, measured at a two week interval (n = 137), had an intra-class correlation coefficient of 0.92. Analyses for convergent validity were performed with data from 133 cases. Discriminant and known-groups validity was analysed with data from 162 cases. The ABC scale total score had a strong correlation with the total score of the SGRQ (r = 0.72, p < 0.001) but a weak correlation with the forced expired volume in 1 second predicted (r = -0.28, p < 0.001). Subgroups with more severe disease, defined by GOLD-stage, frequency of exacerbations, activity level and depression scored statistically significantly (p < 0.05) worse on almost all domains of the ABC scale than the less severe subgroups. The ABC scale seems a valid and reliable tool with good discriminative properties.