Incremental value of myocardial perfusion scintigraphy in prognosis and outcomes of patients with coronary artery disease

The concept of incremental value in prognosis and outcome of patients with coronary artery disease is important to the field of noninvasive imaging. Because these tests are expensive, they should be held to the standard of demonstrating a statistical improvement over the information provided by clinical assessment and treadmill testing. Responding to the demand for cost-effective applications of myocardial perfusion scintigraphy, a large amount of research has recently been devoted to defining specific patient subsets in which incremental value exists for scintigraphy. Subsets thus far demonstrated to benefit incrementally include those men and women referred for possible coronary artery disease, with known coronary artery disease, and after percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, unstable angina, or recent infarction. Incremental cost savings also apply to these subsets except for patients with normal ECGs at rest and less than 15% likelihood for significant coronary artery disease.     

Centromere-linkage analysis and consolidation of the zebrafish genetic map

The ease of isolating mutations in zebrafish will contribute to an understanding of a variety of processes common to all vertebrates. To facilitate genetic analysis of such mutations, we have identified DNA polymorphisms closely linked to each of the 25 centromeres of zebrafish, placed centromeres on the linkage map, increased the number of mapped PCR-based markers to 652, and consolidated the number of linkage groups to the number of chromosomes. This work makes possible centromere-linkage analysis, a novel, rapid method to assign mutations to a specific linkage group using half-tetrads.     

Depletion of hepatic 3'-phosphoadenosine 5'-phosphosulfate (PAPS) and sulfate in rats by xenobiotics that are sulfated

Sulfation is considered a high-affinity but low-capacity conjugation mechanism that is limited by the availability of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), the cosubstrate for sulfation. Salicylamide, phenol and 1-naphthol are all known substrates for the sulfation reaction. This study was conducted to determine whether the xenobiotics that are sulfated when administered to rats will lower hepatic PAPS and its precursor, sulfate. Urinary sulfate excretion was reduced 85% to 95% by these compounds. Hepatic PAPS was reduced 73%, 39%, and 87% by salicylamide, phenol and naphthol, respectively, 2 hr after administration of 2 mmol/kg. These compounds also decreased serum sulfate concentrations by 45% to 86% and lowered hepatic sulfate concentrations. In summary, these studies demonstrate that salicylamide, phenol and 1-naphthol lower hepatic PAPS and sulfate concentrations, as well as serum sulfate concentrations. These findings imply that increased sulfation, as a result of the sulfation of xenobiotics, results in depletion of hepatic PAPS concentrations, possibly because the utilization of PAPS by the sulfotransferases exceeds its generation via sulfate activation. Thus the capacity-limited sulfation of high dosages of xenobiotics appears to be due to the reduced availability of hepatic PAPS, which in turn is limited by the availability of sulfate.     

The use of nonhomologous scatchard analysis in the evaluation of ligand-protein interactions

Scatchard plots are widely used for the graphical presentation of receptor-ligand binding data. When a combination of labelled and unlabelled ligand molecules is used in a binding assay, equations for Scatchard plots are readily available if the labelled and unlabelled ligands have similar binding affinities. In this article, Everardus van Zoelen, Roel Kramer, Herman van Moerkerk and Jacques Veerkamp present mathematical equations to obtain the binding characteristics of an unlabelled ligand in a Scatchard plot, which has a dissociation equilibrium constant different from that of the labelled ligand used.     

MR of the heart under pharmacologic stress

Magnetic resonance imaging is one method for assessing cardiac function and perfusion at rest and under stress conditions. In this article, the potential of stress magnetic resonance imaging for evaluating ischemic heart disease is reviewed, and technical aspects of some developments that may contribute to comprehensive magnetic resonance imaging assessment of heart disease under rest and stress are discussed.     

Psychological stress, occurrence of cancer and cause-specific mortality]

Psychological stress has been claimed to contribute to the onset of cancer and to increase mortality from a number of nonmalignant diseases. We investigated the effect of a genuine psychological stressor, i.e. cancer in a child, on the incidence of cancer and mortality from nonmalignant diseases of 11,231 parents in a Danish nationwide population-based study. The children were identified from records in the Danish Cancer Registry for the period 1943-1985; their parents were identified from population registers. Overall, 1665 parental malignancies were diagnosed from the date the cancer of the child was reported through 1992, as compared with 1702 expected from national incidence rates, to yield standardized incidence ratios of 1.0 (95% confidence interval, 0.9-1.0) for all parents, 1.0 for mothers and 1.0 for fathers. No excess mortality was seen from causes associated with allergic illness, autoimmune conditions, chronic illness or changes in behaviour. Our data provide no support for the hypothesis of an association between psychological stress and the incidence of cancer or mortality from nonmalignant diseases. We conclude that the human organism is highly adaptable, even to extreme psychological stress.     

Serum endothelin and atrial natriuretic peptide in cirrhotic patients with ascites and hepatorenal syndrome

BACKGROUND: The pathogenesis of cirrhotic ascites and hepatorenal syndrome remains unresolved. The involvement of both endothelin-1 and atrial natriuretic peptide have recently been suggested. This study investigated the concentrations of serum endothelin and atrial natriuretic peptide in cirrhotic patients. METHODS: Seven healthy subjects and 31 cirrhotic patients were studied. Cirrhotic patients were divided into three groups: Group I, 16 cirrhotic patients without ascites; Group II, 10 cirrhotic patients with ascites, but without hepatorenal syndrome; and Group III, five cirrhotic patients with hepatorenal syndrome and ascites. Their sera were analyzed for endothelin-1 and atrial natriuretic peptide concentrations. RESULTS: Cirrhotic patients with ascites, Group II and Group III, had higher plasma endothelin-1 concentrations (15.9 +/- 2.3 pg/ml and 24 +/- 2.1 pg/ml, respectively) than normal subjects and compensated cirrhotics (3.8 +/- 0.7 pg/ml and 6.4 +/- 1.1 pg/ml, respectively); p < 0.001). Atrial natriuretic peptide concentrations were also significantly higher in cirrhotic patients than in normal subjects (p < 0.025). Plasma endothelin-1 concentration had a negative correlation with creatinine clearance (r = -0.65, p < 0.001), as did atrial natriuretic peptide concentrations (r = -0.44, p = 0.012). Plasma endothelin-1 correlated significantly with atrial natriuretic peptide concentrations (r = 0.38, p = 0.035). CONCLUSIONS: Both endothelin-1 and atrial natriuretic peptide concentrations were elevated in cirrhotic patients with ascites and hepatorenal syndrome. Endothelin-1 may have a negative impact on renal function. Our data also suggested that impaired responsiveness rather than impaired secretion of atrial natriuretic peptide is responsible for sodium retention in cirrhotic patients with ascites.