Postoperative Cognitive Dysfunction in Middle-aged Patients

Background: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent.

Methods: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living.

Results: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months.     

Role of oxidative stress,angiogenesis and chemo-attractant cytokines in the pathogenesis of ischaemic protection induced by remote ischaemic conditioning: Study of a human model of ischaemia-reperfusion induced vascular injury

Aims

We explored the effect of remote ischaemic conditioning (RIC) on endothelial function and on circulating mediators.

Female Genital Arousal: A Focus on How Rather than Why

Archives of Sexual Behavior -     

Reducing Ventral Tegmental Dopamine D2 Receptor Expression Selectively Boosts Incentive Motivation

Altered mesolimbic dopamine signaling has been widely implicated in addictive behavior. For the most part, this work has focused on dopamine within the striatum, but there is emerging evidence for a role of the auto-inhibitory, somatodendritic dopamine D2 receptor (D2R) in the ventral tegmental area (VTA) in addiction. Thus, decreased midbrain D2R expression has been implicated in addiction in humans. Moreover, knockout of the gene encoding the D2R receptor (Drd2) in dopamine neurons has been shown to enhance the locomotor response to cocaine in mice. Therefore, we here tested the hypothesis that decreasing D2R expression in the VTA of adult rats, using shRNA knockdown, promotes addiction-like behavior in rats responding for cocaine or palatable food. Rats with decreased VTA D2R expression showed markedly increased motivation for both sucrose and cocaine under a progressive ratio schedule of reinforcement, but the acquisition or maintenance of cocaine self-administration were not affected. They also displayed enhanced cocaine-induced locomotor activity, but no change in basal locomotion. This robust increase in incentive motivation was behaviorally specific, as we did not observe any differences in fixed ratio responding, extinction responding, reinstatement or conditioned suppression of cocaine, and sucrose seeking. We conclude that VTA D2R knockdown results in increased incentive motivation, but does not directly promote other aspects of addiction-like behavior.     

Lipopolysaccharides,but not Angiotensin ll,lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Angiotensin II (Ang II) might induce pro‐inflammatory effects directly in the vascular wall independently of its haemodynamic effects. The aim of our study was to investigate the putative direct pro‐inflammatory and vasomotor effects of Ang II and compare to those of lipopolysaccharides (LPS) in mouse isolated mesenteric resistance‐sized arteries (MRA) supported by experiments in cultured human primary endothelial and vascular smooth muscle cells. Results showed that 24‐hr organ culture of mouse MRA with 10 nM Ang II had, unlike 100 ng/mL LPS, no effects on IL‐6 or MCP‐1 secretion, VCAM1 mRNA expression or endothelial function, while Ang II significantly decreased maximal vasomotor responses to phenylephrine. In support, 24‐hr organ culture of mouse MRA significantly suppressed Agtr1a mRNA and augmented Tlr4 mRNA along with attenuated vasomotor responses to Ang II. Moreover, contrary to LPS and TNF‐α, Ang II and [Sar1]‐Ang II had no concentration‐ or time‐dependent effects on IL‐6 and MCP‐1 secretion in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMC). AGTR1 or AGTR2 mRNA expression was undetectable in HUVEC, whereas HASMC expressed only AGTR1 mRNA. In summary, contrary to previous studies and the observed effects of LPS, we could not demonstrate direct vascular pro‐inflammatory effects of Ang II ex vivo or in vitro. As indicated by our results, down‐regulation or desensitization of AT₁R during culture may explain our findings.     

Dual contrast in computed tomography allows earlier characterization of articular cartilage over single contrast

Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non-ionic agents. However, osteoarthritis-related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual-energy computed tomography technique allows the simultaneous determination of the partitions of iodine-based cationic (CA4+) and gadolinium-based non-ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non-ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual-energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P < .05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent.     

Alternative therapies for localized prostate cancer

Prostate cancer is the leading malignancy in men; an increase in detected localized prostate cancers is expected in the years to come. Radical prostatectomy, although effective, is associated with a considerable morbidity. The aim of minimal invasive alternative treatment options should be equal efficacy, but a decrease in side effects. Cryosurgical ablation of the prostate, brachytherapy, high-intensity focused ultrasound, and radiofrequency interstitial tumor ablation were evaluated after a literature review from a MEDLINE search (1966-2002). When compared with treatments in the 1960s and 1970s, increased safety is observed in all of the alternative treatments available today. Sophisticated technology, including the latest ultrasonography devices for exact planning and monitoring of treatment, contributes largely to this safety. Five-year results of cryosurgical ablation of the prostate show a prostate-specific antigen lower than 1 ng/ mL in 60% of the cases; in the third generation, there are no long-term data available on cryosurgical ablation of the prostate. Recent outcome data of brachytherapy come close to results of radical prostatectomy series. Brachytherapy is the only true alternative at this point in time. Highintensity focused ultrasound and radiofrequency interstitial tumor ablation are promising new technologies that have proven to be able to induce extensive necrosis; however, follow-up is too short to determine their definite places in the treatment of prostate cancer.