Proposal for revision of the French bioethics law of July 29, 1994

The president of the joint-academy working group (National Academy of Medicine and the National Academy of Pharmacy) will present the group's proposals for a revision of the 1994 French bioethics laws to the Parliamentary Office for the evaluation of scientific and technological choices in view of a new examination of the laws by the Parliament in 1999.     

Plasticity at hippocampal to prefrontal cortex synapses: dual roles in working memory and consolidation

The involvement of the hippocampus and the prefrontal cortex in cognitive processes and particularly in learning and memory has been known for a long time. However, the specific role of the projection which connects these two structures has remained elusive. The existence of a direct monosynaptic pathway from the ventral CA1 region of the hippocampus and subiculum to specific areas of the prefrontal cortex provides a useful model for conceptualizing the functional operations of hippocampal-prefrontal cortex communication in learning and memory. It is known now that hippocampal to prefrontal cortex synapses are modifiable synapses and can express different forms of plasticity, including long-term potentiation, long-term depression, and depotentiation. Here we review these findings and focus on recent studies that start to relate synaptic plasticity in the hippocampo-prefrontal cortex pathway to two specific aspects of learning and memory, i.e., the consolidation of information and working memory. The available evidence suggests that functional interactions between the hippocampus and prefrontal cortex in cognition and memory are more complex than previously anticipated, with the possibility for bidirectional regulation of synaptic strength as a function of the specific demands of tasks.     

Dysfunctional regulation of alphaCaMKII and syntaxin 1B transcription after induction of LTP in the aged rat

Syntaxin 1B and alphaCaMKII are two genes that are upregulated after the induction of LTP and appear to underlie different mechanisms of synaptic plasticity. alphaCaMKII is directly implicated in strengthening the synapses that have been modified, whereas syntaxin 1B has been implicated in a mechanism for the propagation of synaptic plasticity within neural circuits. In these experiments we have investigated whether the regulation of these genes is altered after the induction of LTP in aged rats. We found, three hours after the induction of LTP in the dentate gyrus, that aged rats could be subgrouped into those in which LTP was maintained and those in which LTP had decayed back to basal levels. Both genes were upregulated in young adult rats, whereas there was a differential pattern of LTP-induced expression in the aged rats. Dendritic alphaCaMKII was upregulated in aged rats only when LTP was maintained. In contrast, regulation of syntaxin 1B and alphaCaMKII was absent in the granule cell bodies of the aged rats regardless of whether LTP was maintained or not. These results suggest that molecular mechanisms implicated in two aspects of hippocampal synaptic plasticity malfunction during normal ageing and therefore may have some contributory role in the decline in memory function routinely observed in ageing.     

Role of computed tomographic scanning of the thorax prior to bronchoscopy in the investigation of suspected lung cancer

BACKGROUND: Fibreoptic bronchoscopy (FOB) is the usual initial investigation of choice in patients with suspected endobronchial carcinoma, but it is often non-diagnostic. Once a positive diagnosis has been made, many patients undergo staging by computed tomographic (CT) scanning to assess the extent of the disease and its suitability for radical treatment. To determine whether initial CT scanning before FOB is a cost effective way of reducing subsequent unnecessary or unhelpful invasive diagnostic procedures, a study was undertaken in 171 patients with suspected endobronchial carcinoma. METHODS: A randomised two group study was performed with all patients undergoing an initial CT staging scan. In group A the CT scans were reviewed before FOB, allowing cancellation or a change to an alternative invasive procedure if considered appropriate. In group B all patients proceeded to FOB with the bronchoscopist blinded to the result of the CT scan until after the procedure. RESULTS: In group A six of 90 patients (7%) required no further investigations as the CT scan was either normal, consistent with benign disease, or consistent with widespread metastatic disease. Of the remainder, bronchoscopy was diagnostic in 50 of 68 (73%) in group A compared with 44 of 81 (54%) in group B (p = 0.015). Overall, a positive diagnosis was made after a single invasive investigation in 64 of 84 patients (76%) in group A compared with only 45 of 81 patients (55%) in group B (p = 0.005). Only seven of 90 patients (8%) in group A required more than one invasive investigation compared with 15 of 81 patients (18.5%) in group B. In patients with malignancy, bronchoscopy was more likely to be diagnostic in group A (50 of 56 patients (89%)) than in group B (44 of 62 (71%); p = 0. 012), and the diagnosis was more frequently made on the initial invasive investigation (group A, 63 of 70 (90%); group B, 44 of 62 (71%); p = 0.004). Because of the lower number of invasive procedures performed in group A than in group B, the cost of performing CT scans before FOB in all patients in group A would have equated to a projected cost of performing CT scans in 60% of patients after FOB in group B. CONCLUSIONS: Performing initial CT thoracic scans before bronchoscopy in patients with suspected endobronchial malignancy is a cost effective way of improving diagnostic yield from invasive diagnostic procedures and occasionally may obviate the need for any further investigation.     

Retinal vasculitis in lupic disease

Three cases of retinal vasculitis in SLE-type diseases are reported. The first was central retinal vein occlusion occurring during clinical remission of SLE in a 55 year old black female. Prednisone maintenance therapy was unchanged and visual loss rapidly regressed with heparin therapy. The second case was a 33 year old black female in whom SLE was discovered following relapsing bilateral optic neuritis. A progressive visual improvement was obtained with high dose of prednisone (1 mg/kg/day). The third cas was a 17 year old white girl with retinal vasculitis. She had an unclassified connective tissue disease inaugurated by optic neuritis at the age of 10. High dose prednisone (1 mg/kg/day) was effective on the visual loss. Retinal vasculitis lesions in SLE and their therapy are reviewed.     

Prevention of venous thromboembolism following cardiac, vascular or thoracic surgery

In the absence of thromboprophylaxis, coronary artery bypass graft surgery (CABG), intrathoracic surgery (thoracotomy or video-assisted thoracoscopy), abdominal aortic surgery and infrainguinal vascular surgery are high-risk surgeries for the development of venous thromboembolic events (VTE). The incidence of VTE following surgery of the intrathoracic aorta, carotid endarterectomy or mediastinoscopy is unknown. Data from the litterature are lacking to draw evidence-based recommandations for venous thromboprophylaxis after these three types of surgeries, and the following guidelines are but experts'opinions (Grade D recommendations). Thromboprophylaxis is recommended after CABG (Grade D), with either subcutaneous (SC) low molecular weight heparin (LMWH) or SC or intravenous (i.v.) unfractioned heparin (UH) (PTT target = 1.1-1.5 time control value) (both grade D). This may be combined with the use of intermittent pneumatic compression device (Grade B). After valve surgery. The anticoagulation recommended to prevent valve thrombosis is sufficient in order to prevent VTE. We recommend thromboprophylaxis with either LMWH or low dose UH to prevent VTE after aortic or lower limbs infrainguinal vascular surgery (both grade B and D). Vitamine K antagonists (VKA) are not recommended in this indication (Grade D). We recommend thromprophylaxis following intrathoracic surgery via thoracotomy or videoassisted thoracoscopy (grade C). Either subcutaneous LMWH or subcutaneous or i.v. low dose UH may be used (Grade C). Efficacy of intermittent pneumatic compression device has been demonstrated in a study (grade C). VKA are not recommended (grade D). No further recommendation regarding the duration of thromboprophylaxis after these three types of surgeries can be made.