Apolipoprotein E alleles in nonagenarian subjects in the Belfast Elderly Longitudinal Free-living Ageing Study (BELFAST)

The ApoE gene has three alleles coding for the proteins apoE2, apoE3 and apoE4. E4 has been reported to be associated with hypercholesteraemia, ischaemic heart disease, age-related cognitive decline and Alzheimer's disease. Conversely, the E2 allele has been associated with longevity in French centenarians and their siblings. In this study, we have assessed any shift in the ApoE genotypes in nonagenarian subjects from Belfast where there is a high intrinsic incidence of cardiovascular disease. ApoE phenotypes were determined by electrofocusing and immunoblotting in 114 Senieur-approximated subjects >90 years old and compared with 2071 subjects, 30--65 years of age, recruited from the same geographical area by the MONItoring of CArdiovascular trends study group in Belfast (MONICA). The E4 allele was reduced in the nonagenarian group (X(2)=11.1; P=0.0006), the E3 unchanged and E2 frequency was increased (X(2)=4.0; P=0.047). These results suggest that longevity is negatively associated with the E4 allele and may be associated with carriage of E2.     

Trazodone for sleep disturbance after alcohol detoxification: a double-blind, placebo-controlled trial

Background:  Trazodone is a commonly prescribed off-label for sleep disturbance in alcohol-dependent patients, but its safety and efficacy for this indication is unknown.
Methods:  We conducted a randomized, double-blind, placebo-control trial of low-dose trazodone (50 to 150 mg at bedtime) for 12 weeks among 173 alcohol detoxification patients who reported current sleep disturbance on a validated measure of sleep quality or during prior periods of abstinence. Primary outcomes were the proportion of days abstinent and drinks per drinking day over 6-months; sleep quality was also assessed.
Results:  Urn randomization balanced baseline features among the 88 subjects who received trazodone and 85 who received placebo. The trazodone group experienced less improvement in the proportion of days abstinent during administration of study medication (mean change between baseline and 3 months: −0.12; 95% CI: −0.15 to −0.09), and an increase in the number of drinks per drinking day on cessation of the study medication (mean change between baseline and 6 months, 4.6; 95% CI: 2.1 to 7.1). Trazodone was associated with improved sleep quality during its administration (mean change on the Pittsburgh Sleep Quality Index between baseline and 3 months: −3.02; 95% CI: −3.38 to −2.67), but after it was stopped sleep quality equalized with placebo.
Conclusions:  Trazodone, despite a short-term benefit on sleep quality, might impede improvements in alcohol consumption in the postdetoxification period and lead to increased drinking when stopped. Until further studies have established benefits and safety, routine initiation of trazodone for sleep disturbance cannot be recommended with confidence during the period after detoxification from alcoholism.     

Preimplant transthoracic echocardiographic assessment of continuous flow left ventricular assist device

For many patients with end-stage heart failure, heart transplantation is the only remaining option to prolong survival and provide symptom relief. Transthoracic echo is the modality of choice in assessing a patient for potential left ventricular assist device (LVAD) insertion. There are currently no guidelines available, and assessing this specific patient population can prove extremely challenging. As such, an understanding of LVAD mechanism, the important physiological consequences of device implantation together with the related echocardiographic examination is vital to accurately and effectively gauge correct patient selection and also improve implantation success. This review aims to highlight the common devices implanted, how these devices affect cardiac physiology and hemodynamics, and therefore discuss the major echocardiographic variables that should be assessed predevice implantation. (Echocardiography 2012;29:52-58).     

Early changes in white matter pathways of the sensorimotor cortex in premanifest Huntington's disease

Objectives: To investigate the function–structure relationship of white matter within different stages of Huntington's disease (HD) using diffusion tensor imaging (DTI). Experimental design: From the TRACK‐HD study, an early stage HD group and a premanifest gene carrier group (PMGC) were age‐matched to two healthy control groups; all underwent 3‐T MRI scanning of the brain. Region of interest (ROI) segmentation of the corpus callosum, caudate nucleus, thalamus, prefrontal cortex, and sensorimotor cortex was applied, and the apparent fiber pathways of these regions were analyzed. Functional measures of motor, oculomotor, cognition, and behavior were correlated to DTI measures. Principle observations: In PMGC versus controls, higher apparent diffusion coefficient (ADC) was seen in white matter pathways of the sensorimotor cortex (P < 0.01) and in the ROI of corpus callosum (P < 0.017). In early HD, fiber tract analysis showed higher ADC in pathways of the corpus callosum, thalamus, sensorimotor, and prefrontal region (P < 0.01). ROI analysis showed higher diffusivity in the corpus callosum and caudate nucleus (P < 0.017). Motor, oculomotor, cognition, and probability of onset within 2 and 5 years, correlated well with ADC measures of the corpus callosum (P < 0.01 – P < 0.005), sensorimotor (P < 0.01 – P < 0.005), and prefrontal region (P < 0.01). Conclusions: Disturbances in the white matter connections of the sensorimotor cortex can be demonstrated not only in manifest HD but also in premanifest gene carriers. Connectivity measures are well related to clinical functioning. DTI measures can be regarded as a potential biomarker for HD, due to their ability to objectify changes in brain structures and their role within brain networks. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Gender's effect on the efficacy of smoking cessation interventions

Evidence-based guidelines and subsequent studies support the effectiveness of counselling and pharmacotherapy as first-line smoking cessation interventions. Gender is one of many factors that may have an impact on the efficacy of smoking cessation interventions. There is only very limited evidence, however, to answer the question of how gender influences the effectiveness of smoking cessation interventions. Research does suggest that concern about weight gain is related to women's confidence in their ability to stop smoking and this should be kept in mind when designing interventions. In the meantime, any client who indicates a desire to stop smoking should be offered one of the smoking cessation interventions that are already available.     

Blood donation leads to a decrease in natural killer cell activity: a study in normal blood donors and cancer patients

Transfusion-induced immunosuppression has long been known to be beneficial for organ transplantation patients, but recent retrospective studies suggest that blood transfusions may be detrimental for patients with cancer. If autologous blood is used to avoid immunosuppression, the assumption is that the procedure, involving blood donation, is immunologically neutral. In the present study, this assumption was evaluated by monitoring 33 normal blood donors and 16 colorectal cancer patients before and after donation of 1 (500 mL) and 2 units of blood, respectively. The cancer patients belonged to the autologous arm of a randomized trial in which the effects of allogeneic versus autologous blood on cancer prognosis were studied. The patients donated 2 units of blood with an interval of 3 to 4 days between donations. Flow cytometric analysis revealed that blood donation by normal donors and cancer patients had no effect on the proportion of B, T, and natural killer (NK) cells. Only the total number of lymphocytes was significantly decreased in the normal donors on Day 12 after donation. Blood donation had no significant effect on T-cell function assessed by phytohemagglutinin stimulation in normal donors or in cancer patients donating 2 units of blood. A significant depression of NK cell function (88% and 74% of predonation levels) was observed in normal donors on Days 2 and 5 after donation; on Day 12, the activity was again normal. Colorectal cancer patients had a significantly depressed NK cell activity (54% of predonation activity) on Day 12 after the first donation.(ABSTRACT TRUNCATED AT 250 WORDS)