Neurogenic pulmonary edema

Neurogenic pulmonary edema (NPE) is usually defined as an acute pulmonary edema occurring shortly after a central neurologic insult. It has been reported regularly for a long time in numerous and various injuries of the central nervous system in both adults and children, but remains poorly understood because of the complexity of its pathophysiologic mechanisms involving hemodynamic and inflammatory aspects. NPE seems to be under-diagnosed in acute neurologic injuries, partly because the prevention and detection of non-neurologic complications of acute cerebral insults are not at the forefront of the strategy of physicians. The presence of NPE should be high on the list of diagnoses when patients with central neurologic injury suddenly become dyspneic or present with a decreased P(a)o(2)/F(i)o(2) ratio. The associated mortality rate is high, but recovery is usually rapid with early and appropriate management. The treatment of NPE should aim to meet the oxygenation needs without impairing cerebral hemodynamics, to avoid pulmonary worsening and to treat possible associated myocardial dysfunction. During brain death, NPE may worsen myocardial dysfunction, preventing heart harvesting.     

Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this complex process has made antiplatelet therapy the cornerstone of cardiovascular disease management. However, numerous patients will experience a recurrent atherothrombotic vascular event despite adequate antiplatelet therapy. Individual differences in the rate of platelet activation and reactivity markedly influence normal hemostasis and the pathological outcome of thrombosis. Such an individual variability is largely determined by environmental and genetic factors. These are known to either hamper platelets' response to agonists, and thereby mimic the pharmacological modulation of platelet function or mask therapy effect and sensitize platelets. In this article, we reviewed the antiplatelet mechanisms of aspirin and clopidogrel and the possible role of different polymorphisms, which may affect the efficacy of antiplatelet therapy. Heterogeneity in the way patients respond to aspirin and clopidogrel may in part reflect variation in cyclooxygenase (COX)-1, COX-2, glycoprotein (GP) Ib alpha, GP Ia/IIa, GP IIb/IIIa, UGT1A6*2, P2Y₁, P2Y₁₂, CYP2C9, CYP3A4 and CYP3A5 genotypes.     

Social egg freezing: for better, not for worse

The possibility for healthy women to cryopreserve their oocytes in order to counter future infertility has gained momentum in recent years. However, women tend to cryopreserve oocytes at an age that is suboptimal from a clinical point of view--in their late thirties--when both oocyte quantity and quality have already considerably diminished and success rates for eventually establishing a pregnancy are thus limited. This also gives rise to ethical concerns, as the procedure is seen as giving false hope to (reproductively speaking) older women. This study evaluates which measures can be taken to turn social freezing into a procedure that is both clinically and ethically better than the current practice. The main objective of these measures is to convince those women who are most likely to (want to) reproduce at an above-average age to cryopreserve their oocytes at a time when this intervention is still likely to lead to a live birth and to discourage fertility clinics from specifically targeting women who have already surpassed the age at which good results can be expected. The possibility for healthy women to cryopreserve their oocytes in order to counter future infertility has gained momentum in recent years. However, women tend to cryopreserve oocytes at a time that is suboptimal from a clinical point of view - in their late thirties - when both oocyte quantity and quality have already considerably diminished and success rates for eventually establishing a pregnancy are thus limited. This also gives rise to ethical concerns, as the procedure is seen as giving false hope to (reproductively speaking) older women. We evaluate which measures can be taken to turn social freezing into a procedure that is both clinically and ethically better than the current practice and discern three different steps: creating public awareness; offering individualized, age-specific information and counselling; and offering predictive tests such as anti-Müllerian hormone measurements or antral follicle count. The main objective of these measures is to convince those women who are most likely to benefit from social freezing to present themselves before age 35 and to discourage fertility clinics from specifically targeting women who have already surpassed the age at which good results can be expected.     

C-reactive protein induces pro- and anti-inflammatory effects, including activation of the liver X receptor alpha, on human monocytes

Non-specific markers of inflammation such as C-reactive protein (CRP) are associated statistically with an increased risk of atherosclerosis through mechanisms that have not yet been fully elucidated. We investigated the effects of CRP on several aspects of human monocyte biology, a cell type involved in the initiation and progression of atherosclerosis. Blood monocytes isolated from healthy men and premenopausal women (n = 9/group) were exposed to purified CRP (25 microg/ml) for 12 hours. Changes in gene expression were analyzed using a custom-made array containing oligonucleotide sequences of 250 genes expressed by activated monocytes and confirmed by quantitative PCR. CRP increased significantly the expression of the cytokines interleukin (IL)-1alpha, IL-1beta and IL-6, and the chemokines GRO-alpha, GRO-beta and IL-8. CRP also displayed anti-inflammatory effects through upregulation of liver X receptor (LXR) alpha and activin receptor expression, and down-regulation of alpha 2-macroglobulin expression. Increased LXRalpha mRNA expression in both monocytes and the monocytic cell lineTHP-1 was associated with increased LXRalpha protein expression and nuclear translocation, as well as increased ABCA1 mRNA expression, a target gene of LXRalpha. Western blot analysis revealed CRP-induced nuclear translocation of NF-kappaB and activation of p42/44, MAP and Akt kinases. CRP-induced LXRalpha mRNA expression was inhibited by anti-CD64 (FcgammaRI) antibodies and by p42/44 and PI3 kinase inhibitors. This hypothesis-generating study demonstrates that CRP modulates the expression of genes that contribute to both pro- and anti-inflammatory responses in human monocytes. Among these novel anti-inflammatory effects, we show clearly that CRP activates the LXRalpha pathway.     

Subarachnoid haemorrhage: epidemiology, genomic, clinical presentation

Subarachnoid haemorrhage (SAH) accounts for 1 to 7% of all strokes. In France, the range of incidence of SAH varies between 3 and 8/100,000 inhabitants. Global mortality lies around 40%, including 70% during the first week. The size of more than 90% of all aneurysms is less than 10 mm. In more than 90% of the patients; SAH is sporadic and a familial screening is warranted only after SAH occurring in 2 first-degree relatives. The main risk factors of SAH are tobacco, arterial hypertension and alcohol abuse. Genetic susceptibility may exist: it could involve several genes, the expression of which would characterize pathophysiological pathways implicated in the disease. This could be identified using genomic technique of microarrays, which could explore all the genome, simply using a sample of peripheral venous blood. For example, in the future, this approach could help to identify patients who are at high risk to develop vasospasm after SAH.     

Effects of CRL 41034 on the adrenergic neuroeffector interaction in the canine saphenous vein

Experiments were designed to determine the effect of CRL 41034, a buflomedil analogue, on the adrenergic responsiveness of canine veins. Rings of saphenous vein (without endothelium) were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution at 37 degrees C. CRL 41034 produced a concentration-dependent inhibition of the contractions evoked by the alpha adrenergic agonists norepinephrine, phenylephrine and UK 14304 which was insensitive to the blockade of neuronal uptake by cocaine. CRL 41034 was more potent in inhibiting the concentration-dependent contractions evoked by UK 14304 than those by phenylephrine and the antagonism it caused against the response to UK 14304 fulfilled the criteria for competitivity. CRL 41034, at 10(-5) M significantly depressed, and at 10(-4) M abolished the contractions induced by electrical stimulation of the adrenergic nerves and those evoked by the indirect sympathomimetic amine tyramine. Strips of canine saphenous vein were superfused after incubation with [3H] norepinephrine. During sympathetic nerve activation, CRL 41304 increased the stimulation-evoked overflow of [3H] norepinephrine and 3-methoxy-4-dihydroxyphenylglycol; in the presence of rauwolscine the compound only increased the stimulation-evoked overflow of 3,4-dihydroxyphenylglycol. These experiments suggest that the major vascular effects of CRL 41034 in canine veins are blockade of alpha 2-adrenoceptors on vascular smooth muscle, and inhibition of prejunctional alpha 2-adrenoceptors on adrenergic nerve endings.