Symptom patterns, duration and responses in newly diagnosed patients with heart failure

This study investigated the symptom patterns and duration and associated predictors occurring prior to first heart failure (HF) admission. Data from the Managing Cardiac Function (MACARF) program from January to December 2007 were reviewed in relation to preadmission symptoms and contacts with health professionals. Patients (n = 242) were aged 78.7 years (SD 12 years), male (54%) and married (45%). Patients experienced up to seven symptoms (Mean 2.7, SD 1.4) for a median of 4.47 days (range 1-7) before admission, most commonly increased dyspnoea on exertion (88%), and for the shortest duration chest discomfort. Less than half (48%) contacted a health professional before hospitalization, most often a general practitioner (37%). The duration patients experienced before presenting to hospital was increased if they presented during business hours (beta = 2.68) or the evening (beta = 1.88) (and therefore less from midnight to 8:30 am), or with a change in symptom (beta = 1.4), whereas duration was reduced by chest discomfort (beta = -2.01) and older age (beta = -0.07). There is a significant time window during which patients and health professionals may detect and act on worsening HF symptoms. Newly diagnosed patients with HF need support to recognize and respond to these symptoms to avoid hospital admission.     

MR imaging of the nasopharynx and floor of the middle cranial fossa. Part I. Normal anatomy

The normal anatomy of the nasopharynx and floor of the middle cranial fossa was analyzed with magnetic resonance (MR) imaging. MR images from five healthy volunteers were correlated with whole-organ cryomicrotome sections from three cadavers. Anatomic connections exist between the paranasopharyngeal spaces and the surface structures of the skull base. These anatomic connections include the intimate relationship between the eustachian tube and the pharyngobasilar fascia, the attachment of the muscles of mastication and deglutition to the skull base, and vascular and nervous structures in the foramina. The inherent contrast between the soft tissues of the nasopharynx and related structures and the bone of the floor of the middle cranial fossa allowed excellent visualization of these anatomic connections.     

Antibodies to oxidized lipoproteins and their relationship to myocardial infarction

The inflammatory process and autoimmunity in the form of antibodies to oxidized LDL are important factors in the formation of the atherosclerotic plaque. We examined the time relationship of oxidized lipoprotein antibodies to the acute oxidative stress of myocardial infarction (MI). We also examined the relationship of C-reactive protein, an index of inflammation, and therefore of free radical production, to oxidized low-density lipoprotein (LDL) antibodies. We examined five groups of patients in a cross-sectional study: group 1, within 48 h of MI; group 2, two days to 1 week; group 3, 1-4 weeks; group 4, 1-3 months; and group 5, 3-6 months post MI. Nine patients with high antibody levels were re-examined 12 months after their first assessment. Malondialdehyde (MDA)-LDL and MDA-HDL antibodies were determined by an ELISA method. The highest MDA-LDL antibodies were found within 48 h of MI, but there was no significant difference in MDA- HDL antibodies between the groups. When 9/10 patients with LDL antibodies greater than the mean of 2.7 were re-examined 1 year later, there was a significant decrease in the mean antibody levels (5.2 +/- 1.7 vs. 3.2 +/- 0.6, p < 0.02). There was no correlation between antibodies to MDA-LDL and antibodies to MDA-HDL. There was a positive correlation between serum HDL cholesterol and antibodies to MDA-LDL (r = 0.4, p < 0.02) and a positive correlation between serum triglycerides and MDA-HDL antibodies (r = 0.39, p < 0.02). Acute MI appears to be associated with significantly higher C-reactive protein and antibodies to MDA-LDL, suggesting a possible acceleration of the atherosclerotic process immediately prior to MI.      

Complications of automatic implantable cardioverter defibrillators: radiographic, CT, and echocardiographic evaluation

Automatic implantable cardioverter defibrillators (AICDs) were studied in three groups: (a) Serial radiographs were reviewed in 51 clinic patients. Twenty of 96 (21%) AICD patches distorted with time. (b) Thirty-six postoperative computed tomographic (CT) scans of asymptomatic patients revealed that pericardial fluid collections were frequent during the month after surgery but rare beyond that. Echocardiography was insensitive for these collections. CT also demonstrated dense fibrosis around some distorted patches, months after surgery. (c) Five other patients with pericardial infection had distorted patches, and the four studied with CT had fluid beneath their patches. (d) A case of constrictive pericarditis had distorted patches but was not diagnosed with CT. The authors conclude that distorted patches may indicate postoperative complications and that CT is the imaging modality of choice.     

Chest radiography: a survey of techniques and exposure levels currently used

In diagnostic radiology, the routine measurement of exposure levels for a reference patient is an important part of an effective quality assurance program. In the United States, chest radiography is the most frequent examination and has the lowest exposure level of all radiologic examinations. We estimated the amount of exposure an average patient received from both manual and automatic exposure-controlled radiographic techniques by using a "patient-equivalent" chest phantom during measurements. A densitometric procedure was used to assess processor performance. The mean exposure from 194 chest systems was 20 mR (5.16 X 10(-5) C/kg); the mean film density, 1.38; and the mean processing speed, 108. It is interesting to note that a wide range of radiographic techniques, processing conditions, and screen-film speeds are currently being used. With the information given in our study, investigators can begin to identify the problems that lead to unusual exposure levels and, perhaps, poor image quality.     

Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study

Background

Increased circulating levels of hemostatic factors as well as anemia have been associated with increased risk of cardiovascular disease (CVD). Known associations between hemostatic factors and sequence variants at genes encoding these factors explain only a small proportion of total phenotypic variation. We sought to confirm known putative loci and identify novel loci that may influence either trait in genome-wide association and linkage analyses using the Affymetrix GeneChip 100K single nucleotide polymorphism (SNP) set.

Methods

Plasma levels of circulating hemostatic factors (fibrinogen, factor VII, plasminogen activator inhibitor-1, von Willebrand factor, tissue plasminogen activator, D-dimer) and hematological phenotypes (platelet aggregation, viscosity, hemoglobin, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin concentration) were obtained in approximately 1000 Framingham Heart Study (FHS) participants from 310 families. Population-based association analyses using the generalized estimating equations (GEE), family-based association test (FBAT), and multipoint variance components linkage analyses were performed on the multivariable adjusted residuals of hemostatic and hematological phenotypes.

Results

In association analysis, the lowest GEE p-value for hemostatic factors was p = 4.5*10^-16 for factor VII at SNP rs561241, a variant located near the F7 gene and in complete linkage disequilibrium (LD) (r² = 1) with the Arg353Gln F7 SNP previously shown to account for 9% of total phenotypic variance. The lowest GEE p-value for hematological phenotypes was 7*10^-8 at SNP rs2412522 on chromosome 4 for mean corpuscular hemoglobin concentration. We presented top 25 most significant GEE results with p-values in the range of 10^-6 to 10^-5 for hemostatic or hematological phenotypes. In relating 100K SNPs to known candidate genes, we identified two SNPs (rs1582055, rs4897475) in erythrocyte membrane protein band 4.1-like 2 (EPB41L2) associated with hematological phenotypes (GEE p < 10^-3). In linkage analyses, the highest linkage LOD score for hemostatic factors was 3.3 for factor VII on chromosome 10 around 15 Mb, and for hematological phenotypes, LOD 3.4 for hemoglobin on chromosome 4 around 55 Mb. All GEE and FBAT association and variance components linkage results can be found at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007

Conclusion

Using genome-wide association methodology, we have successfully identified a SNP in complete LD with a sequence variant previously shown to be strongly associated with factor VII, providing proof of principle for this approach. Further study of additional strongly associated SNPs and linked regions may identify novel variants that influence the inter-individual variability in hemostatic factors and hematological phenotypes.

     

NONMEM法分析肾移植患者环孢素A的群体药动学

用HPLC和FPIA法(单克隆抗体)测定全血中环孢素A(CsA)浓度,收集临床60例肾移植患者牛奶送服CsA后浓度数据281点,应用NONMEM程序一步法估算其群体药动学参数,并定量地分析体重、年龄、性别,长期用药对清除率的影响。按口服吸收一室开放模型估算的群体药动学参数为:清除率CL(L·h^-1)、表现分布容积V_d(L)和口服吸收速率常数K_a(h^-1)分别等于59.8,227及1.28,其个体间变异Q_CL(%),Q_VL(%)及Q_Ka(%)分别为30.27,29.02和75.10,浓度观察值与模型预测值的残差变异Q_E(%)等于31.19固定效应与CL的定量关系为:以体重的0.03倍加法调整,男性较女性患者增加4.31,长期用药患者下降12.7。