Interleukin-6 -174 G/C promoter polymorphism and effects of fenofibrate and simvastatin on inflammatory markers in hypercholesterolemic patients.

To evaluate whether the interleukin-6 (IL-6) -174 G/C polymorphism might alter the effects of micronized fenofibrate or simvastatin therapy on inflammatory markers, we measured IL-6, C-reactive protein, CD40 ligand, adhesion molecules, P-selectin and monocyte chemoattractant protein-1 in hypercholesterolemic patients both before and after a 30-day treatment. Serum IL-6 levels were significantly higher in patients with the GC or CC genotypes (P=0.04). The presence of the C allele was associated with greater absolute reduction of IL-6 levels (P=0.04) following fenofibrate treatment. There was no significant association between the -174 G/C IL-6 polymorphism and the effects of simvastatin treatment. A relationship between the -174 G/C IL-6 polymorphism and the anti-inflammatory action of fenofibrate reported might be useful in the optimization of the treatment regimen in patients receiving this class of drugs.     

Correction of head movement on PET studies: comparison of methods.

Head movement presents a continuing problem in PET studies. Head restraint minimizes movement but is unreliable, resulting in the need to develop alternative strategies. These include frame-by-frame (FBF) realignment or use of motion tracking (MT) during the scan to realign PET acquisition data. Here we present a comparative analysis of these 2 methods of motion correction. METHODS: Eight volunteers were examined at rest using (11)C-raclopride PET with the radioligand administered as a bolus followed by constant infusion to achieve steady state. Binding potential (BP) was estimated using the ratio method during 2 periods of the scan at steady state. Head movement was compensated by using coregistration between frames (FBF) and 3 methods using MT measurements of head position acquired with a commercially available optical tracking system. RESULTS: All methods of realignment improved test-retest reliability and noise characteristics of the raw data, with important consequences for the power to detect small changes in radiotracer binding, and the potential to reduce false-positive and false-negative results. MT methods were superior to FBF realignment using coregistration on some indices. CONCLUSION: Such methods have considerable potential to improve the reliability of PET data with important implications for the numbers of volunteers required to test hypotheses.     

Youth Tobacco Access and Possession Policy Interventions: Effects on Observed and Perceived Tobacco Use

This study evaluated the effects of tobacco Purchase, Use and Possession (PUP) laws on student perceptions of adolescent tobacco use within towns and schools. Twenty‐four towns were randomly assigned into two conditions, the experimental condition (E PUP) involved efforts to increase both PUP law enforcement and reduce minors' access to commercial sources of tobacco, whereas the control condition (C) focused only on efforts to reduce minors' access to commercial sources of tobacco. A hierarchical linear modeling analytical approach was selected due to the multilevel data and nested design. The present study found that over time, youth in the experimental PUP condition observed less youth tobacco usage at school and in their town, and perceived lower rates of tobacco among their peers at school and among friends than youth in the control condition. The findings suggest that PUP law enforcement might be used to strengthen community norms against youth tobacco use.     

Fatal thromboembolic complications following assault in a subject with an abdominal aortic aneurysm

A 62-year-old male with no significant medical history developed thromboembolic complications in the lower limbs shortly after an assault which involved punching and kicking to the trunk. Laparotomy revealed intra-abdominal injuries and an abdominal aortic aneurysm. Death from multi-organ failure and sepsis occurred 9 days post-injury. The discussion concentrates on blunt force trauma to the abdominal aorta, specifically on causation, mechanisms of injury and complications.     

Results of non-operative treatment following hip fracture compared to surgical intervention

We followed all consecutive hip fracture patients admitted between 2004 and 2006, identified cases in which the intention was to treat non-operative and compared their functional outcome and mortality with a similar cohort treated surgically over the same period. We recorded length of hospital stay, place of discharge, pre and post-fracture mobility and residence, 30 days and 1 year mortality, re-admission due to same fracture and delayed surgery. The group treated surgically was recruited and matched for age, gender, pre and post-fracture mobility, mental confusion and independence. 25 patients were treated non-operative. 22 patients treated surgically over the same time period matched the patient characteristics of the non-operative arm. The mean hospital stay was 13 days in both groups. There were 4 extra-capsular fractures (3 displaced) and 21 intra-capsular fractures (5 displaced) in the non-operative arm and 11 extra-capsular fractures and 9 intra-capsular fractures in the surgically treated arm. 4 patients from the non-operative treatment group underwent late surgery because of persisting hip pain 20 days-2 months after the index event (2 cannulated screws, 1 hemiarthroplasty, 1 total hip arthroplasty). 11 patients in the surgical treatment arm underwent dynamic screw fixation, 1 had cannulated screw, 1 had total hip replacement and 7 had hemiarthroplasty. 14 of the non-operative treated patients were mobile independently or with aid before fracture but only 9 patients retained their pre-fracture mobility following treatment, compared to 16 patients pre-fracture and 11 patients post-fracture after surgery. 16 patients treated non-operative were living independently prior to injury but only 7 went back to their own residence. Of the operatively treated patients 14 patients were living independently and 10 patients went back to their previous residence. 1 month and 1 year mortality in the non-operative treated group was 4/21 and 7/21 respectively compared to 1/20 and 5/20 in the operative fixation group. There was no statistically significant difference in mobility, residence or mortality between the two groups (Fisher exact test, p > 0.05). Non-operative management after hip fracture is suitable for medically unfit patients and does not result in statistically significant difference in functional outcome or mortality compared to patients treated surgically.     

Ultrastructural evidence for the uptake of a neurotoxic snake venom phospholipase A2 into mammalian motor nerve terminals

A mutant form of ammodytoxin A, a neurotoxic phospholipase A₂ from the venom of the long nosed viper Vipera ammodytes ammodytes, was prepared by site-directed mutagenesis, conjugated to a nanogold particle and inoculated into the antero-lateral aspect of one hind limb of female mice. Eight hours later the mice were killed, the soleus muscles of both ipsi- and contra-lateral hind limbs were removed, exposed to a silver enhancing medium and then prepared for transmission electron microscopy. Silver-enhanced particles were subsequently found concentrated in the peri-synaptic area, particularly within the synaptic gutter and the deep synaptic folds, and in many cases had been taken up into the cytoplasm of the terminal boutons of the motor axon. The results suggest that the presynaptic neurotoxicity of snake venom phospholipases A₂ involves several components of the neuromuscular apparatus, including intracellular organelles of the motor nerve terminal.     

Community pharmacy services to optimise the use of medications for mental illness: a systematic review

The objective of this systematic review was to evaluate the impact of pharmacist delivered community-based services to optimise the use of medications for mental illness. Twenty-two controlled (randomised and non-randomised) studies of pharmacists' interventions in community and residential aged care settings identified in international scientific literature were included for review. Papers were assessed for study design, service recipient, country of origin, intervention type, number of participating pharmacists, methodological quality and outcome measurement. Three studies showed that pharmacists' medication counselling and treatment monitoring can improve adherence to antidepressant medications among those commencing treatment when calculated using an intention-to-treat analysis. Four trials demonstrated that pharmacist conducted medication reviews may reduce the number of potentially inappropriate medications prescribed to those at high risk of medication misadventure. The results of this review provide some evidence that pharmacists can contribute to optimising the use of medications for mental illness in the community setting. However, more well designed studies are needed to assess the impact of pharmacists as members of community mental health teams and as providers of comprehensive medicines information to people with schizophrenia and bipolar disorder