TIMI risk score underestimates prognosis in unstable angina/non-ST segment elevation myocardial infarction

OBJECTIVES: To determine the value of the TIMI risk score in the individual risk stratification of patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). BACKGROUND: TIMI risk score is a validated tool to identify groups of patients at high risk for major cardiac events. Its prognostic value in individual patients with current diagnostic tools and therapy is unknown. METHODS: TIMI risk score was assessed in patients with UA/NSTEMI admitted to six Belgian hospitals and related to clinical outcome at 30 days. RESULTS: Of the 500 patients enrolled, 49.4% were placed in the low TIMI risk group (score = 0-3) and 50.6% in the high-risk group (score = 4-7). Multivariate analysis identified raised cardiac markers and invasive strategy, but not high TIMI risk score as independent predictors of death and new myocardial infarction (MI). Moreover, the incidence of death and MI in the low TIMI risk group with positive cardiac markers was not lower than in the high TIMI risk group with positive markers: 15.1% versus 17.8% (P = 0.7). CONCLUSIONS: TIMI risk score is of limited value for individual risk stratification. The presence of positive cardiac markers (troponin) appears to be a more powerful prognostic marker.     

Accumulation of flotillin-1 in tangle-bearing neurones of Alzheimer's disease

The protein flotillin-1 is associated with the 'lipid rafts', that is, membrane microdomains that are enriched in cholesterol and sphingolipids. We compared flotillin-1 immunoreactivity in the hippocampus, amygdala and isocortex (Brodmann area 22) of six controls and 13 Alzheimer's disease (AD) cases (10 sporadic and three familial). A diffuse labelling of the neuropil was observed in most of the samples. The intensity of this labelling was not correlated with the density of neurofibrillary tangles (NFT) or of senile plaques. Some neuronal cell bodies were diffusely labelled in patients as in controls. Immunostained granular bodies were found in the cell body of a few neurones. The density of neuronal profiles containing large granular bodies (diameter > or =2 microm) was significantly higher in AD cases and was correlated with the density of NFTs in the three regions that were studied. Sections stained by double immunofluorescence methods and examined with confocal microscopy suggested that flotillin-1 accumulated most often in tangle-bearing neurones (76% of flotillin-1-positive neurones contained a NFT). Flotillin-1 immunoreactivity, even when found in a tangle-bearing neurone, was not colocalized with tau protein indicating that the two proteins were not in close contact and probably in different subcellular compartments. Flotillin-1-positive granular bodies were also found in neurones containing Pin1-positive vesicles but were not colocalized with them. Flotillin-1 immunoreactivity was colocalized with cathepsin D, a lysosomal marker. These data indicate that flotillin-1, a marker of rafts, accumulates in lysosomes of tangle-bearing neurones in the course of AD.     

Human chorionic gonadotropin and growth factors at the embryonic-endometrial interface control leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) secretion by human endometrial epithelium

BACKGROUND: The elucidation of the molecular mechanisms by which the embryo contributes to its implantation is an area of extensive research. The main objective of this study was to investigate the pattern of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) secretion by human endometrial epithelium, and their regulation by human chorionic gonadotropin (hCG) and other growth factors present at the embryonic-endometrial interface. METHODS: Endometrial epithelial cells (EEC) were isolated from biopsies collected at both proliferative and secretory phases of fertile women. RESULTS: HCG (1-50 IU/ml) increased LIF secretion by EEC cultures derived from follicular phase (up to 285+/-75%) or from secretory phase (up to 212+/-16%). In contrast, hCG reduced IL-6 secretion by EEC in both phases. The hCG/LH receptor gene was transcribed by EEC as evidenced by RT-PCR. Insulin-like growth factors 1 and 2 increased LIF secretion by EEC. Transforming growth factor beta1 stimulated LIF and reduced IL-6 secretion. CONCLUSIONS: Through hCG, the blastocyst may be involved in the control of its implantation (via an increase of proimplantatory LIF) and tolerance (via an inhibition of proinflammatory IL-6). Other growth factors present at the embryonic-endometrial interface are also involved in the control of LIF and IL-6 endometrial secretion.