Impact of adolescent GluA1 AMPA receptor ablation in forebrain excitatory neurons on behavioural correlates of mood disorders

Glutamatergic dysfunctions have recently been postulated to play a considerable role in mood disorders. However, molecular mechanisms underlying these effects have been poorly deciphered. Previous work demonstrated the contribution of GluA1-containing AMPA receptors (AMPAR) to a depression-like and anxiety-like phenotype. Here we investigated the effect of temporally and spatially restricted gene manipulation of GluA1 on behavioural correlates of mood disorders in mice. Here we show that tamoxifen-induced GluA1 deletion restricted to forebrain glutamatergic neurons of post-adolescent mice does not induce depression- and anxiety-like changes. This differs from the phenotype of mice with global AMPAR deletion suggesting that for mood regulation AMPAR may be particularly important on inhibitory interneurons or already early in development.     

Variations of the renal function parameters in rectal cancer patients with a defunctioning loop ileostomy

Purpose

The objective of this study is to investigate the impact of the temporary loop ileostomy on renal function and also to assess the factors associated with the change in renal function observed between the index surgery (the moment of the radical surgical procedure) and the closure of the ileostomy (the moment of the secondary surgical act of suppression of the ileostomy).

Methods

A total of 69 rectal cancer patients from a single referral surgical unit who had a loop ileostomy during low anterior resection of the rectum were included in this study. Serum creatinine levels were evaluated, and estimated glomerular filtration rate (eGFR) was calculated prior to index surgery and closure of the ileostomy.

Results

During this time interval, there was a significant decrease in eGFR levels (mean difference ??4.5 mL/min/1.73 m², 95% CI ??7.8 to ??1.3 mL/min/1.73 m²), and also a significant increase in the serum creatinine values (mean difference 0.07, 95% CI 0.02–0.12 mg/dL). The eGFR decrease was more pronounced in diabetic patients, in those with a baseline Charlson Comorbidity Index score?≥?1 or in those that received chemotherapy. In a multivariable regression analysis, the use of neoadjuvant chemotherapy was the only variable significantly associated with the change in eGFR levels between the two surgical interventions.

Conclusion

Renal function impairment is an important event that the surgeon has to take into consideration when deciding upon opting for a loop ileostomy to temporarily defunction a colorectal anastomosis.

     

New modified Achilles tendon allograft for treatment of chronic patellar tendon ruptures following total knee arthroplasty

Introduction

Patellar tendon rupture is an infrequent but debilitating lesion. Several surgical repairs have been suggested for patellar tendon rupture. Our aim is to propose a modified technique from the classic Achilles allograft procedure.

Materials and methods

Five consecutive patients diagnosed with chronic patellar tendon rupture following total knee arthroplasty (TKA) were included in the presented study. All patients were operated with a modified Achilles allograft technique, dividing the Achilles tendon into two bundles and overcrossing these through the distal part of the quadricipital tendon.

Results

All patients regained their extension mechanism and have discontinued using crutches. No complications were observed.

Conclusions

The modified Achilles allograft has shown to be a safe, time-reducing repair for chronic patellar tendon ruptures following TKA, and should be considered as an alternative surgical repair.     

Cumulative impact of cardiovascular risk factors on regional left ventricular function and reserve: progressive long-axis dysfunction with compensatory radial changes

Background: The risk factors that contribute to atherosclerosis also predict clinical heart failure, but it is unclear how they affect myocardial function. Aims were to assess if major cardiovascular risk factors cause subclinical myocardial dysfunction in asymptomatic subjects. Methods: We measured regional left ventricular (LV) function at rest and during dobutamine stress echocardiography in 246 subjects (54 ± 12 years, 54% men) analyzed in five groups according to the presence of six risk factors (diabetes, hypertension, obesity, dyslipidemia, smoking, and family history; age was similar in the five groups). LV longitudinal function was assessed from the mean velocities of four basal segments, and radial function from the velocities of the basal posterior wall. Results: Risk factors did not affect LV ejection fraction, but longitudinal systolic velocity decreased progressively with the number of risk factors, at rest (6.8 ± 1.3 vs. 6.2 ± 1.6 vs. 5.8 ± 1.5 vs. 5.4 ± 1.3 vs. 5.3 ± 1.3 cm/sec, for the five groups, respectively) and at peak stress (14.3 ± 3.3 vs. 12.9 ± 3.2 vs. 11.8 ± 3.4 vs. 11.3 ± 2.6 vs. 11.1 ± 2.3 cm/sec) (both P < 0.0001). Radial systolic velocity increased according to the number of risk factors (P < 0.01). By multivariate regression, determinants of reduced longitudinal systolic velocity at rest were body mass index, diastolic blood pressure, age, and fasting plasma glucose (r = 0.57, r²= 0.32, P < 0.0001). Conclusion: Asymptomatic subjects have impaired LV long‐axis function at rest and during stress, according to their number of major cardiovascular risk factors. Global LV systolic function is maintained by compensatory increases in radial function. These changes provide new targets for preclinical diagnosis and for monitoring responses to preventive strategies. (Echocardiography 2011;28:813‐820)     

The role of ventricular–arterial coupling in cardiac disease and heart failure: assessment,clinical implications and therapeutic interventions. A consensus document of the European Society of Cardiology Working Group on Aorta & Peripheral Vascular Diseases,European Association of Cardiovascular Imaging,and Heart Failure Association

Ventricular–arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent diagnostic and prognostic value and may be used to refine riskstratification and monitor therapeutic interventions. Traditionally, VAC is assessed by the non‐invasive measurement of the ratio of arterial (Ea) to ventricular end‐systolic elastance (Ees). With disease progression, both Ea and Ees may become abnormal and the Ea/Ees ratio may approximate its normal values. Therefore, the measurement of each component of this ratio or of novel more sensitive markers of myocardial (e.g. global longitudinal strain) and arterial function (e.g. pulse wave velocity) may better characterize VAC. In valvular heart disease, systemic arterial compliance and valvulo–arterial impedance have an established diagnostic and prognostic value and may monitor the effects of valve replacement on vascular and cardiac function. Treatment guided to improve VAC through improvement of both or each one of its components may delay incidence of heart failure and possibly improve prognosis in heart failure. In this consensus document, we describe the pathophysiology, the methods of assessment as well as the clinical implications of VAC in cardiac diseases and heart failure. Finally, we focus on interventions that may improve VAC and thus modify prognosis.     

Delineation of small mobile tumours with FDG-PET/CT in comparison to pathology in breast cancer patients

Purpose

Various segmentation methods for 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) images were correlated with pathological volume in breast cancer patients as a model of small mobile tumours.

Methods

Thirty women with T2–T3/M0 breast invasive ductal carcinoma (IDC) were included prospectively. A FDG-PET/CT was acquired 4 ± 3 d before surgery in prone and supine positions, with/without respiratory gating. The segmentation methods were as follows: manual (Vm), relative (Vt%) and adaptive (Va) standard uptake value (SUV) threshold and semi-automatic on CT (Vct). Pathological volumes (Vpath) were measured for 26 lesions.

Results

The mean (±SD) Vpath was 4.1 ± 2.9 mL, and the lesion displacements were 3.9 ± 2.8 mm (median value: 3 mm). The delineated VOIs did not vary with the acquisition position nor with respiration, regardless of the segmentation method. The Vm, Va, Vct and Vt% methods, except Vt30%, were correlated with Vpath (0.5 < r < 0.8). The Vt50% and Vm were the most accurate methods (mean ± SD: 0.0 ± 1.6 mL and +0.6 ± 1.8 mL, respectively), followed by the Vct method.

Conclusions

When compared with pathology, small lesions (diameter <50 mm) with limited respiratory displacement (i.e., breast or apical lung lesions) are best delineated on FDG-PET/CT using a 50% SUVmax threshold. The acquisition position and respiratory gating did not modify the delineated volumes.