Evaluation of chromosomal abnormalities by clg-FISH and association with proliferative and apoptotic indexes in multiple myeloma

Eighty-six newly diagnosed multiple myeloma (MM) patients from a public hospital of São Paulo (Brazil) were evaluated by cIg-FISH for the presence of del(13)(q14), t(4;14)(p16.3;q32) and del(17)(p13). These abnormalities were observed in 46.5, 9.3, and 7.0% of the patients, respectively. In order to identify the possible role of del(13)(q14) in the physiopathology of MM, we investigated the association between this abnormality and the proliferative and apoptotic indexes of plasma cells. When cases demonstrating t(4;14)(p16.3;q32) and del(17)(p13) were excluded from the analysis, we observed a trend towards a positive correlation between the proportion of cells carrying del(13)(q14) and plasma cell proliferation, determined by Ki-67 expression (r = 0.23, P = 0.06). On the other hand, no correlation between the proportion of cells carrying del(13)(q14) and apoptosis, determined by annexin-V staining, was detected (r = 0.05, P = 0.69). In general, patients carrying del(13)(q14) did not have lower survival than patients without del(13)(q14) (P = 0.15), but patients with more than 80% of cells carrying del(13)(q14) showed a lower overall survival (P = 0.033). These results suggest that, when del(13)(q14) is observed in a high proportion of malignant cells, it may have a role in determining MM prognosis. Another finding was a statistically significant lower overall survival of patients with t(4;14)(p16.3;q32) (P = 0.026). In the present study, almost half the patients with t(4;14)(p16.3;q32) died just after diagnosis, before starting treatment. This fact suggests that, in São Paulo, there may be even more patients with this chromosomal abnormality, but they probably die before being diagnosed due to unfavorable socioeconomic conditions. This could explain the low prevalence of this chromosomal abnormality observed in the present study.     

Heart rate variability (HRV) in adolescent females with anxiety disorders and major depressive disorder

Aim: The aim of this study was to investigate heart rate variability (HRV) in a clinical sample of female adolescents with anxiety disorders (AD) and/or major depressive disorder (MDD) compared with healthy controls and to assess the effect of selective serotonin reuptake inhibitors (SSRI) on HRV. Methods: Heart rate variability was measured in adolescent female psychiatric patients with AD and/or MDD (n = 69), mean age 16.8 years (range: 14.5–18.4), from 13 out‐patient clinics and in healthy controls (n = 65), mean age 16.5 years (range: 15.9–17.7). HRV was registered in the sitting position during 4 min with no interventions. Results: Logarithmically transformed high frequency HRV (HF), low frequency HRV (LF) and standard deviation of inter beat intervals (SDNN) were lower in the clinical sample compared with the controls (Cohen’s d for HF = 0.57, LF = 0.55, SDNN = 0.60). This was not explained by body mass index, blood pressure or physical activity. Medication with SSRI explained 15.5% of the total variance of HF, 3.0% of LF and 6.5% of SDNN. Conclusions: Adolescent female psychiatric patients with AD and/or MDD show reduced HRV compared with healthy controls. Medication with SSRI explained a part of this difference.     

Gender differences on benefits and risks associated with oral antithrombotic medications for coronary artery disease

Introduction: Despite the significant advances in the pharmacological and interventional management of patients with cardiovascular disease (CVD) over the last decades, cardiovascular mortality remains the leading cause of death. Large randomized clinical trials have investigated the efficacy and safety of different antithrombotic medications in patients with CVD. Although female gender is generally underrepresented in these clinical trials, most analyses clearly indicate that both men and women may accrue therapeutic benefits from antithrombotic management strategies.

Areas covered: This review aims to provide a comprehensive and focused update on gender-related comparative clinical studies of antithrombotic therapies in patients suffering from CVD.

Expert opinion: Current evidence supports the understanding of a similar therapeutic effect between genders with signals of an increased risk of bleeding in women. However, important gaps in evidence exist due to the overall limited percentage of women that have been enrolled in randomized controlled trials. A greater awareness of gender-related issues in antithrombotic therapy should be promoted among physicians and further evidence from large clinical trials looking at the safety and efficacy balance of different antithrombotic strategies in women is warranted.     

Effect of low doses of cannabidiolic acid and ondansetron on LiCl-induced conditioned gaping (a model of nausea-induced behaviour) in rats

Background and Purpose

To determine the minimally effective dose of cannabidiolic acid (CBDA) that effectively reduces lithium chloride (LiCl)-induced conditioned gaping reactions (nausea-induced behaviour) in rats and to determine if these low systemic doses of CBDA (5–0.1 μg·kg⁻¹) relative to those of CBD could potentiate the anti-nausea effects of the classic 5-hydroxytryptamine 3 (5-HT₃) receptor antagonist, ondansetron (OND).

Experimental Approach

We investigated the efficacy of low doses of CBDA to suppress acute nausea, assessed by the establishment of conditioned gaping to a LiCl-paired flavour in rats. The potential of threshold and subthreshold doses of CBDA to enhance the reduction of nausea-induced conditioned gaping by OND were then determined.

Key Results

CBDA (at doses as low as 0.5 μg·kg⁻¹) suppressed nausea-induced conditioned gaping to a flavour. A low dose of OND (1.0 μg·kg⁻¹) alone reduced nausea-induced conditioned gaping, but when it was combined with a subthreshold dose of CBDA (0.1 μg·kg⁻¹) there was an enhancement in the suppression of LiCl-induced conditioned gaping.

Conclusions and Implications

CBDA potently reduced conditioned gaping in rats, even at low doses and enhanced the anti-nausea effect of a low dose of OND. These findings suggest that combining low doses of CBDA and OND will more effectively treat acute nausea in chemotherapy patients.     

Formulating causal questions and principled statistical answers

Although review papers on causal inference methods are now available, there is a lack of introductory overviews on what they can render and on the guiding criteria for choosing one particular method. This tutorial gives an overview in situations where an exposure of interest is set at a chosen baseline (“point exposure”) and the target outcome arises at a later time point. We first phrase relevant causal questions and make a case for being specific about the possible exposure levels involved and the populations for which the question is relevant. Using the potential outcomes framework, we describe principled definitions of causal effects and of estimation approaches classified according to whether they invoke the no unmeasured confounding assumption (including outcome regression and propensity score-based methods) or an instrumental variable with added assumptions. We mainly focus on continuous outcomes and causal average treatment effects. We discuss interpretation, challenges, and potential pitfalls and illustrate application using a “simulation learner,” that mimics the effect of various breastfeeding interventions on a child's later development. This involves a typical simulation component with generated exposure, covariate, and outcome data inspired by a randomized intervention study. The simulation learner further generates various (linked) exposure types with a set of possible values per observation unit, from which observed as well as potential outcome data are generated. It thus provides true values of several causal effects. R code for data generation and analysis is available on www.ofcaus.org , where SAS and Stata code for analysis is also provided.     

The anti-nausea effects of CB1 agonists are mediated by an action at the visceral insular cortex

BACKGROUND AND PURPOSE

Conditioned gaping reactions reflect nausea-induced behaviour in rats. Cannabinoid 1 receptor (CB₁) agonists interfere with the establishment of nausea-induced conditioned gaping; however, it is not known if their effects are mediated by an action at peripheral or central CB₁ receptors.

EXPERIMENTAL APPROACH

We utilized the conditioned gaping model of nausea to evaluate the effect of peripheral and central administration of the peripherally restricted CB₁ agonist, CB13, on the establishment of LiCl-induced gaping in rats. We further evaluated the ability of HU-210 administered to the gustatory insular cortex (GIC) or visceral insular cortex (VIC) to interfere with LiCl-induced conditioned gaping and determined if this effect was mediated by CB₁ receptors.

KEY RESULTS

Central, but not peripheral, CB13 suppressed LiCl-induced conditioned gaping. Central administration of the potent CB₁ agonist, HU-210, delivered to the VIC, but not the GIC, suppressed the establishment of LiCl-induced gaping reactions, but not LiCl-induced suppression of hedonic reactions or conditioned taste avoidance. This pattern of results suggests that HU-210 delivered to the VIC prevented LiCl-induced nausea, but not learning per se. The suppression of LiCl-induced conditioned gaping by HU-210 was mediated by CB₁ receptors because it was prevented by co-administration of CB₁ antagonist/inverse agonist, AM-251, into the VIC. A high dose of AM-251 (20 µg) administered alone into the VIC did not produce conditioned gaping reactions.

CONCLUSIONS AND IMPLICATIONS

The nausea-relieving effects of CB₁ agonists, but not the nausea-inducing effects of CB₁ inverse agonists, are mediated, at least in part, by their action at the VIC in rats.     

Food safety in hospital: knowledge,attitudes and practices of nursing staff of two hospitals in Sicily,Italy

Background  

Food hygiene in hospital poses peculiar problems, particularly given the presence of patients who could be more vulnerable than healthy subjects to microbiological and nutritional risks. Moreover, in nosocomial outbreaks of infectious intestinal disease, the mortality risk has been proved to be significantly higher than the community outbreaks and highest for foodborne outbreaks. On the other hand, the common involvement in the role of food handlers of nurses or domestic staff, not specifically trained about food hygiene and HACCP, may represent a further cause of concern.     

Bacteremia during double-contrast barium enema examination

Forty-five patients undergoing double-contrast barium enema examinations were studied to identify the incidence of transient bacteremia associated with the examination. Blood cultures were obtained immediately prior to the examination and at 5, 10, and 20 minutes after the start of the examination. Blood samples were cultured in both aerobic and anaerobic media, and four of these cultures were positive for organisms that are common skin contaminants. No bacteremia was identified from enteric pathogens. The data herein suggest that patients with cardiac valvular disease are not at greater risk of bacteremia during double-contrast barium enema examinations.     

Radiological assessment of dysphagia with endoscopic correlation

Four hundred fifty consecutive patients with dysphagia were evaluated radiologically over a 14-month period; 127 of these (28.2%) were also examined endoscopically. The most common abnormality seen was dysmotility (34%), followed by hiatal hernia, benign stricture, and esophagitis. Correlation with endoscopy was generally good. Radiologic study demonstrated all cases of esophageal malignancy; radiologic/endoscopic correlation was also strong in patients with moderate or severe esophagitis, though the radiologist had some difficulty detecting mild inflammation. Endoscopy failed to demonstrate some benign strictures. Radiologic study was relatively accurate in detecting significant organic disease; most motility disorders were not detected by endoscopy. For these reasons, as well as lower cost, increased convenience, and patient comfort, radiologic assessment is recommended as the primary method of evaluating patients with dysphagia.     

口服Carvedilol治疗心力衰竭多中心研究(MOCHA)

标题　Ｃａｒｖｅｄｉｌｏｌ对慢性心力衰竭患者左心室功能的改善和存活的提高呈剂量相关性作者　ＢｒｉｓｔｏｗＭＲ，ＧｉｌｂｅｒｔＥＭ，ＡｂｒａｈａｍＷＴ，等　　Ｃｉｒｃｕｌａｔｉｏｎ１９９６，９４：２８０７～２８１６　　研究疾病：充血性心力衰竭。目的：对Ｃａｒｖｅｄｉｌｏｌ治疗慢性心力衰竭患者剂量－疗效特征进行评价。　　设计：随机、双盲、安慰剂对照的多中心研究，剂量效应关系研究。病人资料：共３４５名心力衰竭患者，年龄１８～８５岁，左室射血分数≤０－３５，心力衰竭症状时间≥３月，研究前所有患者必须用利…