[Familial pulmonary veno-occlusive disease with a composite biallelic heterozygous EIF2AK4 mutation]. / Une maladie veino-occlusive pulmonaire familiale avec mutation biallélique hétérozygote composite d'EIF2AK4.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Heritable and sporadic forms have been distinguished. Hypoxemia, profound reduction in the diffusion of carbon monoxide and haemodynamic confirmation of pre-capillary pulmonary hypertension are the major diagnostic criteria. Thoracic CT scanning and a response to pharmaceutical therapy provide additional information to confirm the diagnosis. A 52-year-old patient, three of whose siblings had pulmonary hypertension, was admitted with dyspnoea, malaise and palpitations. Right heart catheterisation confirmed pre-capillary pulmonary hypertension. A search for an EIF2AK4 mutation was carried out, and this showed a composite biallelic heterozygous mutation compatible with the diagnosis of familial PVOD, identical to that showed in one of his brothers. Given the signs of severity of the disease and the diagnosis of PVOD, whose response to pharmaceutical therapy is often poor, the patient was placed on a waiting list for lung transplantation. Despite a similar diagnosis in 3 brothers and follow-up proposed 11 years before the diagnosis, pulmonary hypertension appeared within a few weeks and led immediately to a severe clinical situation. Annual clinical and echocardiographic monitoring had been strongly advised to the patient, but had not allowed diagnosis at a mild or moderate stage of the disease. This clinical case shows that the identification of factors predicting the development of heritable PVOD at a pre-symptomatic stage is an important issue for clinical research.

Validation of a nomogram to predict the risk of cancer in patients with intraductal papillary mucinous neoplasm and main duct dilatation of 10 mm or less.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is premalignant pancreatic lesion. International guidelines offer limited predictors of individual risk. A nomogram to predict individual IPMN malignancy risk was released, with good diagnostic performance based on a large cohort of Asian patients with IPMN. The present study validated a nomogram to predict malignancy risk and invasiveness of IPMN using both Eastern and Western cohorts. METHODS: Clinicopathological and radiological data from patients who underwent pancreatic resection for IPMN at four centres each in Eastern and Western countries were collected. After excluding patients with missing data for at least one malignancy predictor in the nomogram (main pancreatic duct diameter, cyst size, presence of mural nodule, serum carcinoembryonic antigen and carbohydrate antigen (CA) 19-9 levels, and age). RESULTS: In total, data from 393 patients who fit the criteria were analysed, of whom 265 were from Eastern and 128 from Western institutions. Although mean age, sex, log value of serum CA19-9 level, tumour location, main duct diameter, cyst size and presence of mural nodule differed between the Korean/Japanese, Eastern and Western cohorts, rates of malignancy and invasive cancer did not differ significantly. Areas under the receiver operating characteristic (ROC) curve values for the nomogram predicting malignancy were 0·745 for Eastern, 0·856 for Western and 0·776 for combined cohorts; respective values for the nomogram predicting invasiveness were 0·736, 0·891 and 0·788. CONCLUSIONS: External validation of the nomogram showed good performance in predicting cancer in both Eastern and Western patients with IPMN lesions.

ANTECEDENTES: La neoplasia mucinosa papilar intraductal (intraductal papillary mucinous neoplasm, IPMN) es una lesión pancreática premaligna. Las guías internacionales incluyen un número limitado de factores predictivos de riesgo individual. Para predecir el riesgo individual de malignidad del IPMN se ha propuesto un nomograma con un buen rendimiento diagnóstico, basado en una gran cohorte de pacientes asiáticos con IPMN. Este estudio validó el nomograma para predecir el riesgo de cáncer y de invasión de la IPMN utilizando cohortes tanto orientales como occidentales. MÉTODOS: Se recogieron datos clínico-patológicos y radiológicos de pacientes en los que se realizó una resección de páncreas por IPMN en 4 centros en países orientales y en 4 centros de países occidentales. Se excluyeron los pacientes en los que en el nomograma faltaba ≥ 1 factor(es) predictivo(s) de malignidad (diámetro del conducto pancreático principal, tamaño del quiste, presencia de nódulo mural, niveles séricos de CEA y CA19-9, y edad). RESULTADOS: En total, se analizaron datos de 393 pacientes que cumplían con los criterios de inclusión, de los cuales 265 eran de centros orientales y 128 de centros occidentales. Aunque la edad media, el sexo, el valor logarítmico del nivel sérico de CA19-9, la localización del tumor, el diámetro del conducto principal, el tamaño del quiste y la presencia de un nódulo mural difirieron entre las cohortes de Corea/Japón y las cohortes oriental y occidental, las tasas de malignidad y de cáncer invasivo no fueron significativamente diferentes. Las áreas bajo la curva operativa del receptor (area under the receiver operating curve, AUC) que mostró el nomograma para predecir la malignidad fueron: cohorte oriental: 0,745; cohorte occidental: 0,856 y cohortes combinadas: 0,776; y para predecir la invasión tumoral fueron: cohorte oriental: 0,736; cohorte occidental: 0,891, y cohortes combinadas: 0,788. CONCLUSIÓN: La validación externa del nomograma mostró un buen rendimiento en la predicción de cáncer, tanto en pacientes orientales como occidentales con lesiones IPMN.

Motoric cognitive risk syndrome and mortality: results from the EPIDOS cohort.

BACKGROUND AND PURPOSE: Cognitive impairment, slow walking speed and motoric cognitive risk syndrome (MCR) have separately been associated with an increased risk for mortality in the short term. The aim of the study was to examine the association of MCR and its components [i.e. subjective cognitive complaint (SCC) and slow walking speed] with short-, medium- and long-term mortality in older community-dwellers. METHODS: In all, 3778 participants from the Epidémiologie de l'Ostéoporose (EPIDOS) study were selected. MCR was defined as the combination of slow walking speed and SCC in participants without major neurocognitive disorders. Deaths were prospectively recorded using mail, phone calls, questionnaires and/or the French national death registry at 5, 10, 15 and 19 (end of follow-up period) years. RESULTS: Over the follow-up of 19 years, 80.5% (n = 3043) participants died. Slow walking speed and MCR were associated with mortality [hazard ratio (HR) 1.20 with P = 0.004 for slow walking speed and HR = 1.26 with P = 0.002 for MCR at 10 years; HR = 1.27 with P ≤ 0.001 for slow walking speed and HR = 1.22 with P = 0.001 for MCR at 15 years; HR = 1.41 with P ≤ 0.001 at 19 years for slow walking speed and MCR]. There was no association between SCC and mortality. Kaplan-Meier distributions of mortality showed that participants with MCR and slow walking speed died earlier compared to healthy participants and those with SCC (P < 0.001). CONCLUSIONS: Slow walking speed and MCR were associated with an increased risk for mortality at the medium and long term, whereas no association was found with SCC.

[VIVOPTIM: Feedback of an e-Health experimental program of primary prevention of cardiovascular risk on 30 to 70 years old volunteers]. / VIVOPTIM : retour d'expérience d'un programme expérimental de e-santé et de prévention primaire du risque cardiovasculaire global chez des sujets volontaires âgés de 30 à 70 ans.

Today by the e-health and the telemedicine, many people are more and more interested by the improvement of disease knowledge on cardiovascular diseases and associated risk factors, personalized self management support follow-up and e-Health monitoring. MGEN is a not-for-profit complementary health insurance gave itself the ways to use the new digital tools in health. MGEN developed an original and personalized program VIVOPTIM for the primary prevention of the cardiovascular risks for their members. The VIVOPTIM Pilot program is based upon digital services and was experimented by November 2015 to December, 2017 with 8000 members of the MGEN, from 30 to 70 years old and resident in two French areas (Occitanie and Bourgogne Franche-Comté). The assessment of the experiment VIVOPTIM e -health program was positive for the personalized cardiovascular support and for their health. Therefore, the MGEN generalized the VIVOPTIM program of cardiovascular prevention, to the whole France on July 11th, 2018.

Age effect on the prediction of risk of prolonged length hospital stay in older patients visiting the emergency department: results from a large prospective geriatric cohort study.

BACKGROUND: With the rapid growth of elderly patients visiting the Emergency Department (ED), it is expected that there will be even more hospitalisations following ED visits in the future. The aim of this study was to examine the age effect on the performance criteria of the 10-item brief geriatric assessment (BGA) for the prolonged length of hospital stay (LHS) using artificial neural networks (ANNs) analysis. METHODS: Based on an observational prospective cohort study, 1117 older patients (i.e., aged ≥ 65 years) ED users were admitted to acute care wards in a University Hospital (France) were recruited. The 10-items of BGA were recorded during the ED visit and prior to discharge to acute care wards. The top third of LHS (i.e., ≥ 13 days) defined the prolonged LHS. Analysis was successively performed on participants categorized in 4 age groups: aged ≥ 70, ≥ 75, ≥ 80 and ≥ 85 years. Performance criteria of 10-item BGA for the prolonged LHS were sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], likelihood ratios [LR], area under receiver operating characteristic curve [AUROC]). The ANNs analysis method was conducted using the modified multilayer perceptron (MLP). RESULTS: Values of criteria performance were high (sensitivity> 89%, specificity≥ 96%, PPV > 87%, NPV > 96%, LR+ > 22; LR- ≤ 0.1 and AUROC> 93), regardless of the age group. CONCLUSIONS: Age effect on the performance criteria of the 10-item BGA for the prediction of prolonged LHS using MLP was minimal with a good balance between criteria, suggesting that this tool may be used as a screening as well as a predictive tool for prolonged LHS.

Precipitants of Delirium in Older Inpatients Admitted in Surgery for Post-Fall Hip Fracture: An Observational Study.

BACKGROUND: Hip fractures precipitate several acute adverse outcomes in elderly people, thus leading to chronic adverse outcomes. OBJECTIVES: The objective of our study was to examine the clinical characteristics associated with incident delirium in community dwelling elderly individuals who have a hip fracture. DESIGN: Retrospective observational cohort study. SETTING: Data was collected from an academic tertiary hospital affiliated with McGill University. PARTICIPANTS: 114 elderly individuals who were above 65 years of age, who underwent surgery for a fractured hip. MEASUREMENTS: The main outcome variable was incident delirium, which was assessed by chart reviews of notes and observations recorded by nurses and physicians when patients were admitted post operatively to the surgical unit. Covariates included age, sex, length of stay, delay to surgery, number of medical comorbidities, number of medications and hip fracture location, and were extracted from medical records. Baseline mobility and functional status, preoperative cognitive impairment, postoperative complications, regular psychotropic medications, psychotropic medications in hospital, and location of discharge were also assessed through chart review. RESULTS: The results demonstrated that 17.5% of participants with a diagnosis of delirium had a longer length of hospitalization (p = 0.01), a lower baseline functional status (p = 0.03) and pre-operative cognitive impairment (p = 0.01). Patients receiving new psychotropic medications in hospital were more likely to have delirium (OR = 4.6, p = 0.01) which was independent of pre-operative cognitive impairment. CONCLUSION: We have shown that an association exists between psychotropic medication prescription and incident delirium in patients with hip fractures, even when adjusting for cognitive impairment. Hence, the prescription of psychotropic drugs should be judicious in these patients so as minimize the risk of adverse outcomes.

Falls Risk Prediction for Older Inpatients in Acute Care Medical Wards: Is There an Interest to Combine an Early Nurse Assessment and the Artificial Neural Network Analysis?

BACKGROUND: Identification of the risk of falls is important among older inpatients. This study aims to examine performance criteria (i.e.; sensitivity, specificity, positive predictive value, negative predictive value and accuracy) for fall prediction resulting from a nurse assessment and an artificial neural networks (ANNs) analysis in older inpatients hospitalized in acute care medical wards. METHODS: A total of 848 older inpatients (mean age, 83.0±7.2 years; 41.8% female) admitted to acute care medical wards in Angers University hospital (France) were included in this study using an observational prospective cohort design. Within 24 hours after admission of older inpatients, nurses performed a bedside clinical assessment. Participants were separated into non-fallers and fallers (i.e.; ≥1 fall during hospitalization stay). The analysis was conducted using three feed forward ANNs (multilayer perceptron [MLP], averaged neural network, and neuroevolution of augmenting topologies [NEAT]). RESULTS: Seventy-three (8.6%) participants fell at least once during their hospital stay. ANNs showed a high specificity, regardless of which ANN was used, and the highest value reported was with MLP (99.8%). In contrast, sensitivity was lower, with values ranging between 98.4 to 14.8%. MLP had the highest accuracy (99.7). CONCLUSIONS: Performance criteria for fall prediction resulting from a bedside nursing assessment and an ANNs analysis was associated with a high specificity but a low sensitivity, suggesting that this combined approach should be used more as a diagnostic test than a screening test when considering older inpatients in acute care medical ward.

The spectrum of pre-dementia stages: cognitive profile of motoric cognitive risk syndrome and relationship with mild cognitive impairment.

BACKGROUND AND PURPOSE: Motoric cognitive risk (MCR) syndrome is a pre-dementia syndrome. There is little information on the cognitive profile of individuals with MCR syndrome and its overlap with mild cognitive impairment (MCI) syndrome. This study aimed to examine and compare the cognitive performance of non-demented older community dwellers with and without MCR and MCI syndromes. METHODS: A total of 291 non-demented individuals were selected from the Gait and Alzheimer Interactions Tracking study, which is a cross-sectional study. All participants were referred to a memory clinic. Individuals with and without MCR were separated into those with and without MCI. Cognitive performance was measured using the scores of the Mini Mental Status Examination, Frontal Assessment Battery, Free and Cued Selective Reminding Test, Trail Making Test part A and B, and Stroop test. RESULTS: The prevalence of MCI was 40.1% and that of MCR was 18.2%, with a higher prevalence of MCI in MCR group compared with the non-MCR group (47.2% vs. 39.5%). Individuals with MCR and MCI syndromes had poorer cognitive performance in all domains compared with those without MCR (P < 0.005), except for the ratio part III: part I of the Stroop test (P = 0.345). The association between cognitive performance and MCR syndrome was worse on the Mini Mental Status Examination score [effect size, -0.57 (95% confidence interval, -1.02 to -0.12)] and Trail Making Test part B [effect size, 0.59 (95% confidence interval, 0.14-1.04)] in individuals with MCR and MCI syndromes. CONCLUSIONS: Motoric cognitive risk syndrome is associated with low global cognitive performance. Association of MCR and MCI syndromes is characterized by a worse cognitive performance.

Neoadjuvant therapy and vascular resection during pancreaticoduodenectomy: shifting the survival curve for patients with locally advanced pancreatic cancer.

BACKGROUND: Neoadjuvant therapy and vascular resection may offer patients with locally advanced pancreatic cancer potential cure. METHODS: We reviewed medical records of patients with ductal adenocarcinoma who underwent pancreaticoduodenectomy (PD) from 1992 through 2011. We identified patients who received neoadjuvant therapy (NA+) or required vascular resection (VR+) for locally advanced disease and compared outcomes to those who did not. RESULTS: Of the 643 patients who were initially explored, 506 (143 NA+ and 363 NA- patients) ultimately underwent PD. There were no significant differences in R0 resection or morbidity. Mortality was higher in the NA+ versus NA- group (7.0 vs 3.0 %, p = 0.04). More NA+ patients underwent PD VR+ (p < 0.001). Among VR+ patients, neoadjuvant therapy resulted in significantly lower R1 resection. Among resected patients, survival of NA+ patients was significantly longer than both NA- patients (27.3 vs 19.7 months, p < 0.05) and patients abandoned because of locally advanced disease. Age, tumor grade, lymph node ratio, and R1 resection were independent predictors of poor survival. CONCLUSIONS: Neoadjuvant therapy and vascular resection offer patients with locally advanced pancreatic cancer the chance for cure with acceptable morbidity and mortality. These patients have improved survival over patients deemed locally inoperable by traditional criteria.

The non-invasive and automated detection of bovine respiratory disease onset in receiver calves using infrared thermography.

Bovine respiratory disease complex (BRD) causes considerable economic loss and biosecurity cost to the beef industry globally and also results in significant degradation to the welfare of affected animals. The successful treatment of this disease depends on the early, timely and cost effective identification of affected animals. The objective of the present study was to investigate the use of an automated, RFID driven, noninvasive infrared thermography technology to determine BRD in cattle. Sixty-five calves averaging 220 kg were exposed to standard industry practices of transport and auction. The animals were monitored for BRD using conventional biometric signs for clinical scores, core temperatures, haematology, serum cortisol and infrared thermal values over 3 weeks. The data collected demonstrated that true positive animals for BRD based on a gold standard including core temperature, clinical score, white blood cell number and neutrophil/lymphocyte ratio displayed higher peak infrared thermal values of 35.7±0.35 °C compared to true negative animals 34.9±0.22 °C (P<0.01). The study also demonstrated that such biometric data can be non-invasively and automatically collected based on a system developed around the animal's water station. It is concluded that the deployment of such systems in the cattle industry would aid animal managers and practitioners in the identification and management of BRD in cattle populations.

Possible involvement of programmed cell death pathways in the neuroprotective action of polyphenols.

One of the hallmarks of Alzheimer's disease is the accumulation of senile plaques composed of extra-cellular aggregates of beta-amyloid (Aß) peptides. It is well established that at least in vitro, Aß triggers apoptotic cell death via the activation of caspase-dependent and -independent cell death effectors, namely caspase-3 and apoptosis inducing factor (AIF), respectively. Epidemiological studies have reported that elderly people have a lower risk (up to 50%) of developing dementia if they regularly eat fruits and vegetables and drink tea and red wine (in moderation). Numerous studies indicate that polyphenols derived from these foods and beverages account for the observed neuroprotective effects. In particular, we have reported that polyphenols extracted from green tea (i.e. epigallocatechin gallate or EGCG) and red wine (i.e. resveratrol) block Aß-induced hippocampal cell death, by at least partially inhibiting Aß fibrillisation. It has been shown that polyphenols may also modulate caspase-dependent and -independent programmed cell death (PCD) pathways. Indeed, polyphenols including resveratrol, EGCG and luteolin significantly inhibit the activation of the key apoptotic executioner, caspase-3 and are able to modulate mitogen-activated protein kinases known to play an important role in neuronal apoptosis. Moreover, it has been reported that polyphenols may exert their anti-apoptotic action by inhibiting AIF release from mitochondria, thus providing new mechanism of action for polyphenols. This review aims to update the current knowledge regarding the differential effects of polyphenols on PCD pathways and discuss their putative neuroprotective action resulting from their capacity to modulate these pathways.

Two-stage operative cytoreduction and intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma: Operative morbidity and mortality in phase I and II trials.

AIMS: The standard of care for diffuse malignant peritoneal mesothelioma involves operative cytoreduction and intraperitoneal chemotherapy. Most centers favor aggressive operative cytoreduction, accepting high morbidity and mortality. In our trials, patients underwent less extensive cytoreduction followed by prolonged intraperitoneal chemotherapy. Patients underwent a second cytoreduction with heated intraperitoneal chemotherapy. We hypothesized this would result in lower operative morbidity and mortality with similar survival. METHODS: Hospital records, discharge summaries, microbiology, radiography, and office records were retrospectively reviewed to supplement a prospective database. 30-day morbidity and mortality were categorized, and classified according to the Clavien methodology. RESULTS: 47 first and 39 second operations were performed with 13% and 26% morbidity, respectively. Mortality was 2%. Infections comprised 59% of the morbidity. Inclusive of both operations, formal peritonectomy was performed in 16% of patients, resection of isolated lesions in less than half, and only 19% had a visceral organs other than the spleen resected. At the completion of the protocol, only 3% of patients had visible intraperitoneal disease. The mean total length of stay for both operations combined was 16 ± 23 days. Overall median survival was 54.9 months, and median survival for the epithelioid subtype was 70.2 months. CONCLUSIONS: A two-stage cytoreduction with intraperitoneal chemotherapy offers median survival comparable to one-stage protocols, with relatively low morbidity, mortality, visceral resections and length of stay despite two operations. This series supports that our protocol is a feasible and safe approach.

[Clinical practices appraisal]. / Evaluation des pratiques professionnelles.

Beyond a social and professional requirement, assessing physician practices has become a legal obligation. The success of this assessment, i.e., its utility for the quality of the healthcare provided to patients requires that it be integrated into routine medical procedure.

[Clinical governance]. / La gouvernance clinique.

The direction of health organisations requires the coordination of diversified competencies, notably in administration, management and care. In France, for university hospitals, the law (decree) of 1958 is pivotal. Other approaches have been developed in other countries, depending on their history, traditions, and the organisation of their respective health care systems. These models can enlighten our current reflexions at a time when in France, the question of a new definition of governance for university hospitals is raised.

Localization and modulation of calcitonin gene-related peptide-receptor component protein-immunoreactive cells in the rat central and peripheral nervous systems.

Calcitonin gene-related peptide (CGRP) is widely distributed in the central and peripheral nervous system. Its highly diverse biological activities are mediated via the G protein-coupled receptor that uniquely requires two accessory proteins for optimal function. CGRP receptor component protein (RCP) is a coupling protein necessary for CGRP-receptor signaling. In this study, we established the anatomical distribution of RCP in the rat central and peripheral nervous system and its relationship to CGRP immunoreactivity. RCP-immunoreactive (IR) perikarya are widely and selectively distributed in the cerebral cortex, septal nuclei, hippocampus, various hypothalamic nuclei, amygdala, nucleus colliculus, periaqueductal gray, parabrachial nuclei, locus coeruleus, cochlear nuclei, dorsal raphe nuclei, the solitary tractus nucleus and gracile nucleus, cerebellar cortex, various brainstem motor nuclei, the spinal dorsal and ventral horns. A sub-population of neurons in the dorsal root ganglia (DRG) and trigeminal ganglia were strongly RCP-IR. Overall, the localization of RCP-IR closely matched with that of CGRP-IR. We also determined whether RCP in DRG and dorsal horn neurons can be modulated by CGRP receptor blockade and pain-related pathological stimuli. The intrathecal injection of the antagonist CGRP(8-37) markedly increased RCP expression in the lumbar DRG and spinal dorsal horn. Carrageenan-induced plantar inflammation produced a dramatic bilateral increase in RCP expression in the dorsal horn while a partial sciatic nerve ligation reduced RCP expression in the ipsilateral superficial dorsal horn. Our data suggest that the distribution of RCP immunoreactivity is closely matched with CGRP immunoreactivity in most of central and peripheral nervous systems. The co-localization of RCP and CGRP in motoneurons and primary sensory neurons suggests that CGRP has an autocrine or paracrine effect on these neurons. Moreover, our data also suggest that RCP expression in DRG and spinal cord can be modulated during CGRP receptor blockade, inflammation or neuropathic pain and this CGRP receptor-associated protein is dynamically regulated.

Expression of calcitonin gene-related peptide, substance P and protein kinase C in cultured dorsal root ganglion neurons following chronic exposure to mu, delta and kappa opiates.

The mechanisms involved in morphine tolerance are poorly understood. It was reported by our group that calcitonin gene-related peptide (CGRP)-like immunoreactivity (IR) was increased in the spinal dorsal horn during morphine tolerance [Ménard et al. (1996) J. Neurosci. 16, 2342-2351]. More recently, we observed that it was possible to mimic these results in cultured dorsal root ganglion (DRG) neurons allowing for more detailed mechanistic studies [Ma et al. (2000) Neuroscience 99, 529-539]. The aim of the present series of experiments was to further validate the DRG cell culture model by establishing which subtypes of opioid receptors are involved in the induction of CGRP in cultured rat DRG neurons, and to examine the signaling pathway possibly involved in the induction of CGRP-like IR following repeated opiate treatments. Other neuropeptides known to be expressed in DRG neurons, such as substance P (SP), neuropeptide Y (NPY) and galanin, were investigated to assess specificity. Following treatment with any of the three opioid agonists (mu, DAMGO; delta, DPDPE; kappa, U50488H), the number of CGRP- and SP-IR cultured DRG neurons increased significantly, and in a concentration-dependent manner, with the effects of kappa agonist being less pronounced. NPY and galanin were not affected.Double-immunofluorescence staining showed that the three opioid receptors were co-localized with both CGRP- and SP-like IR.Protein kinase C (PKC)-like IR was found to be significantly increased following a repetitive treatment with DAMGO. Double-immunofluorescence staining showed the co-localization of PKCalpha with CGRP- and SP-IR in cultured DRG neurons. Moreover, a combined treatment with DAMGO and a PKC inhibitor (chelerythrine chloride or Gö 6976) was able to block the effects of the opioid on increased CGRP-like IR. These data suggest that the three opioid receptors may be involved in the induction of CGRP and SP observed following chronic exposure to opiates, and that PKC probably plays a role in the signaling pathway leading to the up-regulation of these neuropeptides. These findings further validate the DRG cell culture as a suitable model to study intracellular pathways that govern changes seen following repeated opioid treatments possibly leading to opioid tolerance.

[Evaluation of continuing medical training in private sector French cardiologists in 1999]. / Evaluation des pratiques de formation médicale continue des cardiologues libéraux francais en 1999.

The authors present the results of a retrospective national enquiry which took place in 1999 and was mailed and faxed to the 3,800 cardiologists practising in the private sector in order to assess the different types of continuous, individual and collective postgraduate training which they had benefited from in the preceding 12 months. The data was analysed by comparison with that obtained from an individualized representative sample in a panel of private sector cardiologists. The results were then compared with the criteria of a yardstick proposed by the National Committee of Continuous Medical Education of 1997, according to the April 25th 1996 decree. The meeting of these criteria would require carrying out 114,000 to 76,000 hour-equivalents of continuous education whereas the present offer is about 100,000 hour-equivalents. The different forms of individual or collective training were compared in the 327 questionnaires which were exploitable following adhesion to the French Society of Cardiology, to the Cardiologists' Union, to local cardiological societies, by age, gender and type of practice. The average number of annual hours of collective education was 52.2 +/- 60.1 hours (25% quartile = 25 hours, 75% = 60 hours). The average value of hours of individual education was 89.7 +/- 89.3 hours (25% quartile = 25 hours; 75% = 120 hours). This evaluation indicates that about 15% of cardiologists practising in the private sector have inadequate continuous medical education and that 68% would satisfy the criteria laid down in 1997. Moreover, the present offer would seem to be adequate providing the criteria of accreditation have been met.