Quantitative autoradiography of 5-HT1D and 5-HT1E binding sites labelled by [H]5-HT, in frontal cortex and the hippocampal region of the human brain

In human cortex and hippocampus area, [³H]5-HT (5 nM) labels 5-HT_1A, 5-HT_1D and 5-HT_1E sites. After masking 5-HT_1A receptors by 0.1 μM 8-OH-DPAT, the binding displaced by 0.1 μM 5-CT presumably represented 5-HT_1D sites and the remaining binding 5-HT_1E sites. In frontal cortex, 5-HT_1A receptors represented the main binding in layers II and VI and a lower fraction on other layers. 5-HT_1D and 5-HT_1E sites, were more homogeneously distributed in layers II to VI (21–34% of specific [³H]5-HT binding). 5-HT_1E sites were of similar affinities (K_D close to 6–8 nM) in the cortical layers II to VI. In CA1 field of hippocampus, (pyramidal layer, stratum radiatum, molecular layer), CA2 and dentate gyrus, 5-HT_1A receptors represented the major fraction, 5-HT_1D sites a significant fraction and 5-HT_1E a minor fraction of the specific [³H]5-HT binding. In CA3–CA4 fields, 5-HT_1A receptors were less densely present, 5-HT_1D sites were predominant and 5-HT_1E sites represented a significant fraction (27%). The highest densities of 5-HT_1E sites have been measured in subiculum, where 5-HT_1A, 5-HT_1D, and 5-HT_1E binding sites were equally represented and in entorhinal cortex where 5-HT_1E sites represented the major binding in layer III. They were also present in layers II and IV (29 and 24%) and, to a lesser extent, in layers V and VI. 5-HT_1A sites were predominant in layer VI, II and V and were less abundant in other layers. 5-HT_1D were homogeneously present in layers II, III, IV and were present in low amounts in other layers. No 5-HT_1E were detected in choroid plexus, where [³H]5-HT was dramatically reduced by mesulergine (5-HT_2C receptors). No significant displacement of [³H]5-HT by mesulergine was measured in other structures.     

Emergence of disinhibition-induced synchrony in the CA3 region of the guinea pig hippocampus in vitro

Suppressing inhibition mediated by GABA_A receptors induces rhythmic bursts of synchronous firing in the CA3 region of the hippocampus. Extracellular and intracellular records were made from guinea pig hippocampal slices to examine the emergence of this synchrony. We found that application of GABA_A receptor antagonists initiated a sequence of changes in the activity of the CA3 neuronal population. First, the frequency of firing detected in multiunit records increased. Then, firing began to oscillate with increases followed by decreases in firing that occurred at intervals of 0.5–2 s. The coherence of the rhythmic activity at a single site increased with time, and discharges at distant sites in the CA3 region became correlated. Fluctuations in firing were associated with extracellular field potentials. Finally, epileptiform events associated with large field potentials began to recur at intervals of 5–10 s. The onset of fully synchronous events was sudden and correlated with a large increase in the amplitude of the field potential. Thus the CA3 population can express states of partial population synchrony preceding the onset of epileptiform discharges. A similar activity was induced and maintained by applying low doses of GABA_A receptor antagonists. Intracellular records suggest that inhibitory signalling mediated by GABA_B receptors contributes to the emergence of this activity. States of partial synchrony in the CA3 region exposed to GABA_A receptor antagonists therefore depend on alternating periods of firing, presumably dependent on excitatory synaptic mechanisms, and silence, mediated in part by the activation of GABA_B receptors.     

Transjugular intrahepatic portosystemic shunt before abdominal surgery in cirrhotic patients: a retrospective, comparative study.

Surgery in cirrhotic patients is associated with high morbidity and mortality related to portal hypertension and liver insufficiency. Therefore, preoperative portal decompression is a logical approach to facilitate abdominal surgery and hopefully to improve postoperative survival. The present study evaluated the clinical outcomes of 18 patients (mean age 58 years) with cirrhosis (seven alcoholics and 11 nonalcoholics) who underwent transjugular intrahepatic portosystemic shunt (TIPS) placement before antrectomy (n=5), colectomy (n=10), small-bowel resection (n=1), pancreatectomy (n=1) and nephrectomy (n=1). TIPS was performed a mean (+/-SD) of 72+/-21 days before surgery and induced a marked mean decrease in portohepatic gradient from 21.4+/-3.9 mmHg to 8.4+/-3.4 mmHg. Cirrhotic patients (n=17) who underwent elective abdominal surgery without preoperative TIPS placement were used as the control group. Both groups were matched for age, etiology of cirrhosis, indications for surgery, type of surgery and coagulation parameters. The mean Pugh score was significantly higher in the TIPS group (7.7 versus 6.2). No significant differences were observed for operative blood loss, postoperative complications, duration of hospitalization and one-month (83% versus 88%) or one-year (54% versus 63%) cumulative survival rate. Analysis using the Cox proportional hazards model showed that neither TIPS placement nor preoperative Pugh score were independent predictors for survival. The present study suggests that preoperative TIPS placement does not improve postoperative evolution after abdominal surgery in cirrhotic patients with good or moderately impaired liver function.     

Does Preoperative Coronary Angioplasty Improve Perioperative Cardiac Outcome?

Background: Percutaneous coronary intervention (PCI) is performed in patients with coronary artery disease who are undergoing major noncardiac procedures to reduce perioperative cardiac morbidity and mortality. However, the impact of this approach on postoperative outcome remains controversial.

Methods: The authors analyzed a cohort of 1,152 patients after abdominal aortic surgery in which 78 patients underwent PCI. A propensity score analysis was performed. Also, using a logistic regression model, the authors determined variables associated with a severe postoperative coronary event or a death in patients without PCI. Then, in patients with PCI, they compared the expected and observed outcome.

Results: Five variables (age > 75 yr, blood transfusion > 3 units, repeated surgery, preoperative hemodialysis, and previous cardiac failure) independently predicted (with 94% correctly classified) a severe postoperative coronary event, and five variables (age > 75 yr, repeated surgery, previously abnormal ST segment/T waves, previous hypertension, and previous cardiac failure) independently predicted (with 97% correctly classified) postoperative death. In the PCI group, the observed percentages of patients with a severe postoperative coronary event (9.0% [95% confidence interval, 4.4-17.4]) or death (5.1% [95% confidence interval, 2.0-12.5]) were not significantly different from the expected percentages (8.2 and 6.9%, respectively). When all patients were pooled together, the odds ratios of PCI were not significant. The propensity score analysis provided a similar conclusion.     

Cystic fibrosis mortality trends in France.

BACKGROUND: In 1992 France set up a national cystic fibrosis observatory (Observatoire national de la mucoviscidose, ONM) to monitor the state of health of patients on an annual basis. Using the ONM data, this study estimates the main indicators for life expectancy and assesses the total number of cystic fibrosis patients. METHODS: The data for the years 1994 to 2003 are divided into 3-year periods. Life tables are drawn up for these periods, from which mean and median lengths of life are determined. Using the most recent life table, the number of births in 2003 and the incidence of the disease, the total population of patients can be estimated, assuming a stationary population. RESULTS: In 2001-2003, life expectancy at birth of patients registered with the ONM was 39.1 years and median length of life was 36.4 years. These results, substantially better than those of 1994-1996, are linked to improved conditions of patient inclusion in the ONM database, to improvements in their healthcare, but also to the limitations of the life tables. Based on the 2003 data, the total theoretical number of patients is 6490, and coverage by the ONM database is thus 63.2%. CONCLUSIONS: These provisional results demonstrate the need to convert the ONM observatory into a registry providing exhaustive coverage of all patients.     

Automated three-dimensional analysis of histological and autoradiographic rat brain sections: application to an activation study.

Besides the newly developed positron emission tomography scanners (microPET) dedicated to the in vivo functional study of small animals, autoradiography remains the reference technique widely used for functional brain imaging and the gold standard for the validation of in vivo results. The analysis of autoradiographic data is classically achieved in two dimensions (2D) using a section-by-section approach, is often limited to few sections and the delineation of the regions of interest to be analysed is directly performed on autoradiographic sections. In addition, such approach of analysis does not accommodate the possible anatomical shifts linked to dissymmetry associated with the sectioning process. This classic analysis is time-consuming, operator-dependent and can therefore lead to non-objective and non-reproducible results. In this paper, we have developed an automated and generic toolbox for processing of autoradiographic and corresponding histological rat brain sections based on a three-step approach, which involves: (1) an optimized digitization dealing with hundreds of autoradiographic and histological sections; (2) a robust reconstruction of the volumes based on a reliable registration method; and (3) an original 3D-geometry-based approach to analysis of anatomical and functional post-mortem data. The integration of the toolbox under a unified environment (in-house software BrainVISA, http://brainvisa.info) with a graphic interface enabled a robust and operator-independent exploitation of the overall anatomical and functional information. We illustrated the substantial qualitative and quantitative benefits obtained by applying our methodology to an activation study (rats, n=5, under unilateral visual stimulation).     

Scoring and psychometric properties of the Eye-Drop Satisfaction Questionnaire (EDSQ), an instrument to assess satisfaction and compliance with glaucoma treatment

Background  

The objective of this study was to ascertain the scoring and assess the psychometric properties of the Eye-Drop Satisfaction Questionnaire (EDSQ), a 43-item Patient-Reported Outcome instrument developed to assess patients' satisfaction and compliance with glaucoma treatment.