HRT and cardiovascular disease

Conclusions influencing clinical decisions about the effects of hormone replacement therapy (HRT) on cardiovascular disease have undergone major revisions over the last 30 years. Assumptions in the early 1970s that HRT would increase thromboembolic conditions were reversed in the 1980s, when the first formal studies seemed to indicate a cardioprotective effect. The Heart and Estrogen/progestin Replacement Study (HERS) has, however, very recently suggested that HRT does not affect the incidence of coronary heart disease (CHD) one way or the other. These roller-coaster changes of direction have made decisions by doctors and their patients about the long-term use of HRT extremely difficult and need to be replaced by the stability that only further randomised controlled trials (RCTs) can now provide.     

Neurochemical diversity of dystrophic neurites in the early and late stages of Alzheimer's disease

We examined the neurochemical and morphological diversity of abnormal neurites associated with beta-amyloid plaque formation in the early and late stages of Alzheimer's disease. Preclinical Alzheimer's disease was characterised by the presence of abnormal neurites containing either neurofilament or chromogranin A immunoreactivity. All clustered dystrophic neurites in these cases were associated with beta-amyloid plaques. Neurofilament immunoreactive dystrophic neurites in preclinical Alzheimer's disease could be further subclassified into bulb- and ring-like structures, and these abnormal neurites contained both phosphorylated and dephosphorylated neurofilament epitopes. Dystrophic neurites in Alzheimer's disease could be subdivided into predominantly neurofilament, tau, or chromogranin A immunolabeled forms. Some neurofilament immunoreactive neurites had a core region labeled for tau. The neurofilaments of the dystrophic neurites in Alzheimer's disease had the same complement of phosphorylation- and dephosphorylation-dependent epitopes as observed in preclinical cases. Therefore, an abnormal accumulation of variably phosphorylated neurofilaments represent the earliest cytoskeletal alteration associated with dystrophic neurite formation. Furthermore, these data indicate that dystrophic neurites may "mature" through neurofilament-abundant forms to the neurites containing the profoundly altered filaments labeled for tau. The precise morphological and neurochemical changes associated with dystrophic neurite formation suggests that beta-amyloid plaques are causing physical damage to surrounding axons. The resultant axonal sprouting and profound cytoskeletal alterations would follow the chronic stimulation of the stereotypical reaction to such physical trauma.     

Hypotensive ischemic optic neuropathy and peritoneal dialysis.

PURPOSE: To report anterior ischemic optic neuropathy associated with systemic hypotension in a patient undergoing continuous ambulatory peritoneal dialysis. METHODS: Case report. A 58-year-old man undergoing continuous ambulatory peritoneal dialysis developed painless blurred vision in both eyes and bilateral optic disk swelling with an altitudinal field defect in the left eye. Twenty-four-hour ambulatory blood pressure monitoring was requested in addition to other routine investigations. RESULTS: Routine blood pressure measurement in the clinic was 130/86 mm Hg, but ambulatory blood pressure monitoring demonstrated pronounced early morning hypotension with individual readings as low as 91/41 mm Hg. CONCLUSIONS: Renal dialysis can render patients hypotensive, and this may be associated with anterior ischemic optic neuropathy. The overnight drop in blood pressure may not be appreciated with routine blood pressure measurement. Therefore, 24-hour ambulatory blood pressure monitoring should be considered when investigating patients with suspected anterior ischemic optic neuropathy who are undergoing renal replacement.     

In vitro and in vivo studies on the metabolism of tirofiban.

Tirofiban hydrochloride [L-tyrosine-N-(butylsulfonyl)-O-[4-(4-piperidinebutyl)] monohydrochloride, is a potent and specific fibrinogen receptor antagonist. Radiolabeled tirofiban was synthesized with either (3)H-label incorporated into the phenyl ring of the tyrosinyl residue or (14)C-label in the butane sulfonyl moiety. Neither human liver microsomes nor liver slices metabolized [(14)C]tirofiban. However, male rat liver microsomes converted a limited amount of the substrate to a more polar metabolite (I) and a relatively less polar metabolite (II). The formation of I was sex dependent and resulted from an O-dealkylation reaction catalyzed by CYP3A2. Metabolite II was identified as a 2-piperidone analog of tirofiban. There was no evidence for Phase II biotransformation of tirofiban by microsomes fortified with uridine-5'-diphospho-alpha-D-glucuronic acid. After a 1 mg/kg i.v. dose of [(14)C]tirofiban, recoveries of radioactivity in rat urine and bile were 23 and 73%, respectively. Metabolite I and unchanged tirofiban represented 70 and 30% of the urinary radioactivity, respectively. Tirofiban represented >90% of the biliary radioactivity. At least three minor biliary metabolites represented the remainder of the radioactivity. One of them was identified as I. Another was identified as II. When dogs received 1 mg/kg i.v. of [(3)H]tirofiban, most of the radioactivity was recovered in the feces as unchanged tirofiban. The plasma half-life of tirofiban was short in both rats and dogs, and tirofiban was not concentrated in tissues other than those of the vasculature and excretory organs.     

Reading, Demographic, Social and Psychological Factors Related to Pre-adolescent Smoking and Non-smoking Behaviors and Attitudes

The purpose of this study was to examine reading, demographic, social and psychological factors related to pre-adolescent smoking and non-smoking behaviors and attitudes. The school-home humanistic education program was implemented in a large, urban public school system. It stressed responsible decision-making, increased self-esteem and the inter-relationships among the acquisition of knowledge of the consequences of smoking, personal feelings, family relationships and behavior. The results showed that family involvement was necessary to affect smoking attitudes and behaviors. Of all the variables studied, reading had a most pervasive relationship. Peer influence and self-esteem also were related to smoking knowledge, smoking attitude, future smoking intentions and the "purchase" of cigarettes. Two of several conclusions drawn from the results are: 1. Family involvement is necessary to affect attitudes and behaviors. 2. Health education research that does not investigate the relationship between program outcomes and reading achievement may be misleading.     

高效液相色谱法测定小儿磨积片中橙皮苷的含量

目的:建立以高效液相色谱法测定小儿磨积片中橙皮苷含量的方法。方法:色谱柱为SpherisorbC18,流动相为甲醇-冰醋酸-水(25∶4∶71),检测波长为283nm,流速为2·0ml/min,柱温为50℃,灵敏度为0·16AUFS,进样量为20μl。结果:橙皮苷进样量在0·024μg~1·2μg范围内与峰面积积分值呈良好的线性关系(r=0·9999),平均回收率为99·1%(RSD=0·8%)。结论:本方法简便、快捷,灵敏度及准确度高,可为小儿磨积片质量控制提供依据。     

Organ slice viability extended for pathway characterization: an in vitro model to investigate fibrosis.

Liver slice viability is extended to 96 h for rat, expanding the use of this in vitro model for studying mechanisms of injury and repair, including pathways of fibrosis. The contributing factors to increased organ slice survival consist of the use of a preservation solution for liver perfusion and slice preparation, obtaining rats that are within the weight range of 250-325 g, placing a cellulose filter atop the titanium mesh roller-insert to support the slice, and maintaining the slices in an optimized culture medium which is replaced daily. The liver slices remain metabolically active, synthesizing adenosine triphosphate (ATP), glutathione, and glycogen, and exhibit preserved organelle integrity and slice morphology. Slice preparation results in 2-cut surfaces which likely triggers a repair and regenerative response. The fibrogenic pathways are evident by the activation of stellate cells, the proliferation of myofibroblast-like cells, and an increased collagen deposition by 48 h. Markers indicative of activated stellate cells, alpha-smooth muscle actin, collagen 1a1, desmin, and HSP47 are substantiated by real time-PCR. Increased staining of alpha-smooth muscle actin initially around the vessels and by 72-96 h in the tissue is accompanied by increased collagen staining. Microarray gene expression revealed extracellular matrix changes with the up-regulation of cytoskeleton, filaments, collagens, and actin genes; and the down-regulation of genes linked with lipid metabolism. The improvements in extending liver slice survival, in conjunction with its three-dimensional multi-cellular complexity, increases the application of this in vitro model for investigating pathways of injury and repair, and fibrosis.     

A simple decision analytic solution to the comparison of two binary diagnostic tests

One of the most basic biostatistical problems is the comparison of two binary diagnostic tests. Commonly, one test will have greater sensitivity, and the other greater specificity. In this case, the choice of the optimal test generally requires a qualitative judgment as to whether gains in sensitivity are offset by losses in specificity. Here, we propose a simple decision analytic solution in which sensitivity and specificity are weighted by an intuitive parameter, the threshold probability of disease at which a patient will opt for treatment. This gives a net benefit that can be used to determine which of two diagnostic tests will give better clinical results at a given threshold probability and whether either is superior to the strategy of assuming that all or no patients have disease. We derive a simple formula for the relative diagnostic value, which is the difference in sensitivities of two tests divided by the difference in the specificities. We show that multiplying relative diagnostic value by the odds at the prevalence gives the odds of the threshold probability below which the more sensitive test is preferable and above which the more specific test should be chosen. The methodology is easily extended to incorporate combinations of tests and the risk or side effects of a test. Copyright © 2012 John Wiley & Sons, Ltd.