Encainide—An updated safety profile

The safety of encainide has been evaluated using retrospective analyses of the Bristol-Myers Supraventricular and Ventricular Arrhythmias data base and of the Post-Marketing Adverse Experience Report data and prospective analyses of the Cardiac Arrhythmia Suppression Trial (CAST), the Cardiac Arrhythmia Pilot Study (CAPS), and the Ventricular Tachycardia/Heart Disease and Boston studies. CAST, a randomized, placebo-controlled study in patients with a history of myocardial infarction with asymptomatic or minimally symptomatic ventricular arrhythmias, showed that sudden death or nonfatal cardiac arrest occurred more frequently on encainide (24/418, 5.7%) than on placebo (7/416, 1.7%). The highest sudden death/cardiac arrest rates were found in patients with a left ventricular ejection fraction of less than 0.30, those with a ventricular premature beat count of more than 50/hr and those with a myocardial infarction of more than 90 days. Similar sudden death/cardiac arrest rates were seen in the flecainide-treated group of the study but not in the moricizine-treated group. A retrospective analysis of the data collected from a similar cohort of patients in the Bristol-Myers data base showed a 1-year cumulative incidence of 10.2% in patients with a history of myocardial infarction. A retrospective analysis of mortality data in patients with supraventricular arrhythmias (301 patients) showed this to be slightly lower than in a matched sample of the general U.S. population. The sudden death mortality in the Ventricular Tachycardia/Heart Disease and Boston studies were similar to those reported with other antiarrhythmic agents. Abnormal laboratory findings caused four patients to be discontinued prematurely, but there have been no reported cases of any blood dyscrasias. Thus, there are currently no data showing that patients with symptomatic reentry supraventricular and life-threatening ventricular arrhythmias are at increased risk with encainide therapy. Encainide should be reserved for those patients who are refractory or intolerant to other antiarrhythmic agents. Encainide is not indicated in patients with symptomatic ventricular arrhythmias and structural heart disease. In patients without structural heart disease and symptomatic ventricular arrhythmias, the benefit and risks of encainide therapy should be carefully considered before it is prescribed.     

无定形结晶对UP-50全自动尿沉渣分析仪测定红细胞和管型的影响

目的 探讨无定形结晶对全自动尿沉渣分析仪测定红细胞和管型的影响.方法 随机收集我院门诊病人的2131例新鲜尿首先做常规分析(干化学 沉渣),然后在室温放置,将在两小时内变混浊的84例标本摇匀后再重复上述试验,并进行离心镜检确证为无定形结晶,对其同一份标本的无定形结晶析出前后所测得的红细胞和管型进行比较分析.结果 无定形结晶析出后比析出前对UF-50全自动尿沉渣分析仪测定红细胞计数和管型计数有明显的升高.结论 无定形结晶对全自动尿沉渣分析仪测定红细胞和管型是有一定的影响.     

Allergen-induced mediator release tests

The diagnosis of allergic reactions in clinical practice is based on both clinical history and the determination of specific immunoglobulin E (IgE), either in the serum or on skin mast cells. However, for various reasons, identification of the causative factors is not possible in all the cases. Moreover, not all allergies are IgE-dependent. In an attempt to find sensitive, specific and cost-effective methods to investigate hypersensitivity reactions, in vitro tests were developed at a very early stage. Allergen-induced mediator release assays analyze the mediator released from effector cells, mainly peripheral blood cells, when stimulated in vitro with serial dilutions of the putative allergens. Described initially as research tools, they could well become diagnostic tests. However, relatively few high quality reports have been published so far. In this review, we will detail allergen-dependent histamine, tryptase, arachidonic acid metabolite, e.g. cysteinyl leukotrienes and 15-hydroxyeicosatetraenoic mediator release tests.     

Psychometric properties of the CAST and SDS scales in young adult cannabis users

Aim

To assess the validity of two cannabis use severity scales among young cannabis users and to evaluate their ability to detect Substance Use Disorders (SUD).

Participants

241 volunteers (18–25 years), with a wide spectrum of cannabis use in the last 12 months.

Measurements

The Cannabis Abuse Screening Test (CAST) and Severity of Dependence Scale (SDS) were self-administered. The Psychiatric Interview for Substance and Mental Disorders (PRISM) was used as gold standard for cannabis use disorders according to DSM-IV. Reliability and validity were assessed for two different CAST coding algorithms (b—binary and f—full) and for the SDS. In addition, the cannabis use diagnostic criteria contained in the PRISM were grouped to approximate forthcoming proposed DSM-V criteria to further evaluate these scales.

Findings

26.6% (95% CI: 21.0–32.2) of the subjects met criteria for cannabis dependence, and 49.0% (95% CI: 42.7–55.3) for cannabis use disorders. For both scales internal consistency (Cronbach's alpha > 0.71) and test–retest intraclass correlation coefficients (> 0.80) were good. The score 12 in the CAST-full discriminated better than others between presence and absence of dependence (27.0%; 95% CI: 21.4–32.6) while the score for discrimination of SUD was 9 (51.5%; 95% CI: 45.1–57.8). For the SDS the values were 7 (22.0%; 95% CI: 16.8–27.2) and 3 (64.7%; 95% CI: 58.7–70.8), respectively. According to proposed DSM-V criteria, for moderate and severe addiction the values for the CAST-f were 7 (68.5%; 95% CI: 62.5–74.3) and 12 (27%; 95% CI: 21.3–32.6) and for the SDS, 3 (65.0%; 95% CI: 58.7–70.8) and 7 (22%; 95% CI: 17.0–34.3), respectively.

Conclusions

The CAST and SDS applied to young cannabis users are reliable and valid measures to detect cannabis use disorders when compared to both DSM-IV and proposed DSM-V criteria.     

The Caries Assessment Spectrum and Treatment (CAST) index: rational and development

Serious difficulties in reporting results were encountered when using ICDAS II and PUFA separately in an epidemiological survey in a child population in Brazil. That necessitated the development of a comprehensive but pragmatic caries assessment index. This publication describes the rationale, development and content of a novel caries assessment index. Strengths and weaknesses of ICDAS II, PUFA and other indices were analysed. The novel caries index developed for use in epidemiological surveys is termed 'Caries Assessment Spectrum and Treatment' (CAST). 'Spectrum' indicates what is considered the main strength of the new index - its usefulness in describing the complete range of stages of carious lesion progression: from no carious lesion, through caries protection (sealant) and caries cure (restoration) to lesions in enamel and dentine, and the advanced stages of carious lesion progression in pulpal and tooth-surrounding tissue. CAST combines elements of the ICDAS II and PUFA indices, and the M- and F-components of the DMF index. A DMF score can easily be calculated from the CAST score, thereby enabling retention of the use of existing DMF scores. The CAST index for use in epidemiological surveys is very promising. It should be validated and its reliability and usefulness be tested in different age groups in different countries and cultures.     

The Caries Assessment Spectrum and Treatment (CAST) instrument: its reproducibility in clinical studies

A new caries assessment instrument, the Caries Assessment Spectrum and Treatment (CAST), was developed. It covers carious lesion progression from no lesion, sealants and restorations to lesions in enamel and dentine, advanced stages in pulpal and tooth‐surrounding tissues, and tooth loss owing to dental caries, in nine codes. The objective of this study was to determine the reproducibility of the CAST instrument in primary and permanent dentitions, using three age groups. Two epidemiological surveys were conducted in Brazil, covering three age groups: 2–6‐year‐old and 6–9‐year‐old children and 19–30‐year‐old adults. Four trained and calibrated examiners performed the examinations. Reproducibility was calculated for intra‐ and inter‐examiner at surface and tooth levels and expressed as unweighted kappa‐coefficient value (κ) and percentage of agreement (Po) for CAST codes (0–7) and for the categories healthy (0–2) versus diseased (3–7), and non‐cavitated (0–3) versus cavitated (4–7) teeth. Using CAST codes (0–7) for the 2–6‐year‐old age group in primary dentitions, inter‐examiner consistency was κ  =  0.74 and Po was 98.3%. In the 6–9‐year‐old age group in primary dentitions, inter‐examiner consistency ranged from κ  =  0.68 to κ  =  0.86 and Po was ≥93.7%. In the 19–30‐year‐old age group inter‐examiner consistency was κ  =  0.87 and Po was 94.1%. The reproducibility of the CAST instrument for use in the primary dentition of 2–6‐year olds and of 6–9‐year olds was ‘substantial’ to ‘almost perfect’. The reproducibility for its use in the permanent dentition of 19–30‐year olds was ‘almost perfect’. The CAST instrument can reliably be applied in epidemiological studies covering these ages.     

Barriers to antibody therapy in solid tumors,and their solutions

Antibody drugs have become the mainstream of cancer treatment due to advances in cancer biology and Ab engineering. However, several barriers to Ab therapy have also been identified. These include various mechanisms for Ab drug resistance, such as heterogeneity of antigen expression in tumor cells and reduction in antitumor immunity due to expression diversity, polymorphism of Fc receptors (FcR) in effector cells, and reduced function of effector cells. Countermeasures to each resistance mechanism are being investigated. This review focuses on barriers that impede the delivery of Ab drugs due to features of the solid tumor microenvironment. Unlike hematological malignancies, in which the target tumor cells are in blood vessels, clinical solid tumors contain cancer stroma, which interferes with the delivery of Ab drugs. In addition, the cancer mass itself interferes with the penetration of Ab drugs. In this article, I will consider the etiology of cancer stroma and propose a new Ab drug development strategy for solid cancer treatment centering on cancer stromal targeting (CAST) therapy using anti-insoluble fibrin Ab-drug conjugate (ADC), which can overcome the cancer stroma barrier. The recent success of ADCs, chimeric antigen receptor T cells (CAR-Ts), and Bi-specific Abs is changing the category of Ab drugs from molecular-targeted drugs based on growth signal inhibition to cancer-specific targeted therapies. Therefore, at the end of this review, I argue that it is time to reorient the concept of Ab drug development.     

The INMA—INfancia y Medio Ambiente—(Environment and Childhood) project: More than 10 years contributing to environmental and neuropsychological research

Background

In 2003 the INMA—INfancia y Medio Ambiente (Environment and Childhood) project, a Spanish national network of birth cohorts including more than 3500 participants, was set up with the aim to assess the health impacts of pre- and postnatal environmental exposures on children. The project has published more than 60 papers on maternal and environmental factors related to neuropsychological development in children, one of the main research interests within the project. With the present review, we evaluate the evidence provided by the INMA project on this topic and discuss how the data can contribute to cover the challenges that children’s environmental health research will face in the coming years.

Magnetic resonance angiography and vascular corrosion casting as tools in biomedical research: application to transgenic mice modeling Alzheimer's disease

Abstract

In vivo imaging technologies are presently receiving considerable attention in the biomedical and pharmaceutical research areas. One of the principal imaging modalities is magnetic resonance imaging (MRI). The multiparametric nature of MRI enables anatomical, functional and even molecular information to be obtained non-invasively from intact organisms at high spatial resolution. Here we describe the use of one MRI modality, namely angiography (MRA), to non-invasively study the arterial vascular architecture of APP23 transgenic mice modeling Alzheimer's disease. Because the spatial resolution of the technique is limited, the in vivo studies are complemented by a powerful analysis of the vasculature using vascular corrosion casting. Both techniques revealed age-dependent blood flow alterations and cerebrovascular abnormalities in these mice. Our experience suggests that MRA complemented by cast analysis are important tools to describe vascular alterations and test new therapy concepts in animal models of AD. Furthermore, being non-invasive, MRA can also be applied to studies in patients suffering from this disease.