Patency of the infarct-related coronary artery — a pertinent factor in late recovery of myocardial fatty acid metabolism among patients receiving thrombolytic therapy?

The decrease in mortality among patients receiving thrombolytic therapy for myocardial infarction is greater than would be expected from the improvement in left ventricular contractile function alone; thus some additional advantage of recanalization of the infarctrelated coronary artery probably exists. Changes in the post-infarction myocardial metabolic state with respect to artery patency have not been studied with a gamma camera previously. A single-photon emission tomography scan using the fatty acid analogue para-¹²³I-iodophenylpentadecanoic acid was performed at rest before hospital discharge on nine patients with first anterior myocardial infarction. All patients had received intravenous thrombolytic therapy at the beginning of the insult. The semiquantitative analysis of the left ventricle included a total of 44 segments in each patient. The test was repeated 3 months later, with the patients divided into two groups: six patients had an angiographically patent left anterior descending coronary artery (group A), and three an occluded artery (group B). In group A the number of myocardial segments with abnormal (<70% of maximum) fatty acid uptake was initially 20.2±4.7 (mean±SD) and was reduced to 11.3±6.1 during the follow-up (95% confidence interval of the decrease 16.0–1.7 segments). In group B the number of these aberrant segments was fairly constant (21.7±13.1, initial test, and 21.3±13.3, retest). Our preliminary results suggest that even when thrombolytic therapy fails to prevent myocardial infarction, myocardial fatty acid metabolism has a better change of recovering if the relevant coronary artery has regained its patency. This finding emphasizes the need for further study to establish whether a direct link exists between myocardial metabolic state and patient survival after infarction.     

Lens opacity in patients with hypercholesterolemia and ischaemic heart disease

Lens opacity studies were performed using an electronic Lens Opacity Meter (Interzeag Opacity Lensmeter 701) in a population (n = 321) with ischaemic heart disease. These patients are participating in a trial targetting at the reduction of mortality and incidence of myocardial infarction using a cholesterol-lowering drug, simvastatin. A separate study to evaluate the reliability of the method showed good reproducibility. Repeated measurements after a short time-interval (2–10 days) gave statistically lower opacity values either due to a change in lens transparency or perhaps a change in pigment and cell dispersion in the acqueous caused by repeated mydriasis. Lens opacity values showed a highly significant positive correlation to age. Serum cholesterol, systolic blood pressure and smoking habits showed no significant correlations to the levels of lens opacity when adjustments for age were made.Abbreviations HMG-CoA hydroxy-methylglutarylcoenzyme A - 4S Scandinavian Simvastatin Survival Study - LOM lens opacity meter     

Activated Protein C Reduces Graft Neutrophil Activation in Clinical Renal Transplantation

We studied the role of endogenous activated protein C (APC), the major physiological anti-coagulant with concomitant anti-inflammatory properties, on ischemia/reperfusion (I/R) in 45 patients participating in a larger trial comparing three immunosuppressive protocols in cadaveric renal transplantation: perioperative anti-thymocyte globulin (ATG, Fresenius AG, Bad Homburg, Germany), perioperative basiliximab and conventional triple therapy. Blood samples for assessing plasma APC, protein C, and lactoferrin concentrations, neutrophil CD11b and L-selectin expressions and blood leukocyte differential counts were obtained preoperatively and before reperfusion from central venous cannula, complemented with simultaneous samples from iliac artery and graft vein for calculation of transrenal differences (Delta) of study parameters at 1 and 5 min after reperfusion. Unlike basiliximab or conventional therapy groups, ATG infusion induced a substantial increase in plasma APC concentration (119 [88-144]% before infusion vs. 232 [85-1246]% after infusion, p<0.001), resulting in renal graft sequestration of APC at 1 min after reperfusion (Delta=-72 [-567 to 12]%, p<0.001). Graft APC consumption was associated with transrenal reduction of neutrophil activation markers (L-selectin r=0.7, p=0.01; lactoferrin r=-0.6, p=0.02; CD11b r=-0.8, p=0.001), and with both warm (r=0.6, p=0.01) and cold ischemia time (r=0.6, p=0.02) and donor age (r=0.6, p=0.01). These findings suggest that APC has an anti-inflammatory role in I/R injury in clinical renal transplantation.     

Improved learning of Riemannian metrics for exploratory analysis.

We have earlier introduced a principle for learning metrics, which shows how metric-based methods can be made to focus on discriminative properties of data. The main applications are in supervising unsupervised learning to model interesting variation in data, instead of modeling all variation as plain unsupervised learning does. The metrics are derived by approximations to an information-geometric formulation. In this paper, we review the theory, introduce better approximations to the distances, and show how to apply them in two different kinds of unsupervised methods: prototype-based and pairwise distance-based. The two examples are self-organizing maps and multidimensional scaling (Sammon's mapping).     

Acute tolerance to ethanol using drug discrimination and open-field procedures in rats

This study examined the phenomenon of acute tolerance to ethanol (ETOH) using drug discrimination learning (DDL), and open-field (OF) procedures. In DDL, rats were trained to discriminate between ETOH (1.2 g/kg) and saline. Doses of ETOH lower (0.6 and 0.9 g/kg), or higher (1.8 and 2.4 g/kg) than the training dose were tested to examine possible influence of ETOH pretreatment doses on the expression of acute tolerance. To assess concentrations of ETOH in the organism, a rebreathed air procedure was used. Equal concentrations after different ETOH doses were achieved by postponing the tests until sufficient time had elapsed. Only doses of ETOH higher than the training dose produced acute tolerance in the DDL procedure. For the response-time data no acute tolerance was observed. In the OF experiment, the occurrence of acute tolerance was examined for different spontaneous behaviours in drug-naive animals. At equal ETOH concentrations, the group examined during the descending phase of intoxication (1.8 g/kg, 60 min post-injection), reared significantly more than the group tested during the ascending phase (1.5 g/kg, 10 min post-injection). Other OF behaviours did not differ significantly between the two time intervals. Thus, it is suggested that acute tolerance is seen both in ETOH naive and in ETOH pre-exposed rats. However, in DDL acute tolerance was observed only when doses higher than the training dose of ETOH were evaluated.     

Absence of association between an intercellular adhesion molecule 1 gene E469K polymorphism and Alzheimer's disease in Finnish patients

Increased expression of intercellular adhesion molecule 1 (ICAM1), a protein known to contribute to inflammatory responses, has been detected in the brain tissue of patients with Alzheimer's disease (AD) and animals modelled to mimic AD or Parkinson's disease (PD). ICAM1 may, thus, be implicated in the pathogenesis of these disorders. Our purpose was to investigate whether genetic variants of the ICAM1 gene have a role in causing susceptibility to AD and/or PD. We genotyped the E469K polymorphism of ICAM1 in 196 AD, 52 PD and 202 control patients of Finnish origin. The distributions of the genotype and allele frequencies of the polymorphism did not differ significantly between the AD, PD or the control patients. We therefore conclude that the E469K polymorphism of ICAM1 is not a risk factor for AD or PD.     

C-reactive protein in population samples

The significance of C-reactive protein (CRP) was studied in three different sets of specimens. Raised levels (greater than 10 mg/l) were detected in 2.0% of 380 healthy blood donors from whom two blood specimens, taken at an interval of half a year, were tested. Except for two cases, only one of the two specimens was positive. Raised levels were found three times as frequently (in 6.6%) in a random middle-aged population sample consisting of 531 subjects. More than 40% of the raised levels could be connected to acute respiratory infections, and about 20% to smoking. Five of the 35 subjects (14%) in the population sample with elevated CRP had rheumatoid arthritis. The third set of sera comprised pre-illness specimens from 22 subjects who developed rheumatoid arthritis a few months to five years later. Although it had previously been proved that the majority of these sera contained rheumatoid factors, the CRP concentration was increased in one specimen only.     

Subtyping of hepatitis B surface antigen by radioimmunoassay.

A solid-phase radioimmunoassay used for HBsAg screening of blood donors at the Finnish Red Cross Blood Transfusion Service (FRC-RIA) was modified for subtyping of HBsAg. The anti-HBs coated test tubes of FRC-RIA served as the solid-phase anti-HBs. Monospecific ¹²⁵I-labelled antibodies were prepared by absorption of the labelled anti-HBs used in FRC-RIA with partially purified HBsAg coupled to Sepharose 4B.Labelled anti-y detected 4 ng/ml of ay antigen and 160 ng/ml of ad antigen; the reagent was 40 times more sensitive for the homologous subtype. Labelled anti-d detected 3 ng/ml of ad antigen, but it did not bind to ay antigen. Thus, anti-d was completely monospecific. The standard FRC-RIA was only about 5 times more sensitive than the subtype RIA; 96% of HBsAg positive blood donor samples screened by FRC-RIA could by subtyped by RIA.The important feature of this method is the absorption of the antibodies in the presence of carrier protein after radioactive labelling. This has certain advantages: (1) No extra radioactive labelling is needed for subtyping, because the labelled anti-HBs of standard RIAs for HBsAg can be utilized. (2) Small amounts of labelled monospecific antibodies can be prepared at a time, which promotes economical use of reagents. (3) Only crude antigen preparation (e.g. polyethyleneglycol precipitate from plasma) is needed for the absorption of antibodies.