Should we begin with statin therapy in acute coronary syndrome?

Acute coronary syndrome (ACS) constitutes a unique syndrome with a distinct pathophysiology: rupture of the fibrous cap of unstable atherosclerotic plaques in coronary arteries resulting in subsequent platelet deposition and a thrombus formation that completely or partially occludes the artery. Remarkable therapeutic advances in the treatment of ACS have been made during the past decade with antiplatelet and antithrombotic therapy. However, these therapies alone do not appear to completely stabilize the unstable plaque. Results from several clinical trials suggest that early administration of a statin following an ACS may reduce both short-term and longterm adverse outcomes such as subsequent cardiovascular mortality, myocardial infarction and revascularization. The potential mechanisms of benefit include improvements in endothelial function and vasomotion, reduction of platelet aggregability and thrombus formation, fibrinolytic and antioxidant activity as well as reduction of inflammation within plaques, reducing matrix degradation due to reduction of macrophage metalloproteinase production and increasing collagen content. Based upon the current knowledge, it might be concluded that patients hospitalized for ACS should be given a statin and the treatment should be initiated as soon as possible.     

Non-cholinergic basal forebrain neurons project to the contralateral basal forebrain in the rat

Following injections of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) or the fluorescent tracer fluoro-gold into the magnocellular preoptic area and the horizontal limb of the diagonal band, retrogradely labelled neurons were found in the homotopic region of the contralateral basal forebrain. Labelled fibers apparently arising from these neurons travelled in the stria medullaris and the habenular commissure to terminate in the contralateral basal forebrain. Although the neurons retrogradely labelled with fluoro-gold in the contralateral basal forebrain were similar in size to choline acetyltransferase (ChAT)-immunoreactive neurons, and were intermingled with them, none was ChAT-positive. WGA-HRP injections into the nucleus basalis magnocellularis did not result in retrograde labelling in the contralateral basal forebrain. These findings suggest that non-cholinergic neurons may serve as a direct link between the two sides of selective magnocellular basal forebrain regions.     

Estrogen receptor immunocytochemistry for preoperative determination of estrogen receptor status on fine-needle aspirates of breast cancer

Fine-needle aspirates (FNAs) of 84 primary breast carcinomas were analyzed immunocytochemically for estrogen receptor (ER) using (ER-ICA) monoclonal antireceptor antibodies. ER-ICA in FNAs was concordant to ER-ICA in histologic biopsies in 87% (P less than 0.0001). In most of the carcinomas, biochemically determined ER status also correlated to ER-ICA. There was no false positive ER-ICA in FNAs compared with ER-ICA in histologic biopsies. In 11 FNAs, ER-ICA was negative, whereas it showed positivity in histologic specimens. The most frequent contributing factors to false negative ER-ICAs of FNAs were ER-ICA-low results in histologic biopsies, a prominent stroma component in these tumors, and low cellularity of FNAs. The biochemical ER values in these cases never exceeded 90 fmol/mg protein. In a minority of cases, false negative results were inexplicable.     

Molecular characterization of BCL6 breakpoints in primary diffuse large B-cell lymphomas of the central nervous system identifies GAPD as novel translocation partner

Primary central nervous system lymphomas (PCNSL) constitute diffuse large B-cell lymphomas arising in and remaining confined to the brain. Little information is available on cytogenetic changes in PCNSL, and recurrent chromosomal translocations have not yet been identified. Fluorescence in situ hybridization (FISH) of a series of 13 PCNSL from immunocompetent patients revealed 3 cases with signal patterns of a BCL6-specific probe suggesting a breakpoint in this oncogene locus in chromosome band 3q27. Here, we describe cloning of the translocation breakpoints by long-distance inverse polymerase chain reaction (LDI-PCR) in 2 of these tumors. Both breakpoints affected the first intron of BCL6. In one PCNSL, the HSPCA (HSP90A) gene in 14q32.31 was identified as BCL6 partner. In the second lymphoma, the gene encoding glyceraldehyde-3-phosphate dehydrogenase (GAPD) on 12p13.31 was detected as a hitherto unknown partner of BCL6. Our results suggest translocation-mediated BCL6 oncogene activation as a so far unknown pathogenetically relevant mechanism in PCNSL.     

Cytokines and T cells in host defense

Soluble and cell-bound ligands profoundly influence the differentiative fate of lymphocytes during an immune response. Recent advances have been made in understanding the role of cytokine signals and costimulatory signals in the regulation of T cell responses associated with resistance or susceptibility to infection. There has also been recent progress in defining the requirements for the generation and maintenance of immunologic memory, a critical component of adaptive immunity.     

Extracorporeal treatment for refractory hyperlipidemia

Radical, non-pharmacological, methods of treatment should never be used until it has first been shown that conventional therapy either fails to control hyperlipidemia or cannot be tolerated by the patient. In general, the use of extracorporeal techniques will be restricted to patients with severe familial hypercholesterolemia, although occasionally they may be resorted to in other categories of hyperlipidemia. Seven different procedures are available today for routine clinical practice: unselective plasma exchange, semi-selective double filtration and its modifications as well as the highly selective procedures of immunoadsorption, chemo-adsorption onto dextran sulfate, heparin induced LDL precipitation lipoprotein(a) column, and LDL hemoperfusion (direct adsorption of lipids--DALI). Large-scale regression studies were performed with five highly selective treatment modalities. Control coronary angiograms obtained after about two years of treatment showed that atherosclerotic plaques on coronary arteries had not enlarged or had even been reduced in 80% to 90% of patients.     

Encystation of Giardia lamblia leads to expression of antigens recognized by antibodies against conserved heat shock proteins.

During in vitro encystation, Giardia lamblia expresses several stage-specific proteins which are recognized in immunoblots by antisera raised against antigens from three different pathogens. The antigens belong to two different families of conserved stress proteins: (i) HSP60 purified from Legionella pneumophila and recombinant HSP60 from Mycobacterium bovis BCG and (ii) recombinant HSP70 from Plasmodium falciparum.