Anaesthesia in the obese patient

Obesity is an increasing problem and its burden on healthcare resources is well documented. This article gives an overview of the physiological and pharmacological considerations when anaesthetizing the obese patient. It will look at key aspects of assessing obese patients, and planning and delivering a safe anaesthetic to them. Special areas of focus include correct drug dosing, as well as equipment, monitoring and environmental aspects involved in delivering the anaesthetic.     

Multiple isolated aneurysms in a case of "burned out" Takayasu aortitis

Takayasu aortitis (TA) is a chronic inflammatory disease predominantly seen in young Asian women. The disease is idiopathic and largely affects the aorta and its major branches. The basic pathologic changes in TA are fibrosis and subsequent occlusion of the large arteries. TA is classically termed "pulseless" disease, with manifestations during the occlusive stage including limb ischemia, renovascular hypertension, and heart failure. Arterial dilation and aneurysm are largely unappreciated manifestations of TA, but they occur in as many as 32% of affected patients. We report chronic "burned out" TA in a 23-year-old Hispanic woman with isolated aneurysms of the descending thoracic aorta, abdominal aorta, and common iliac arteries, without occlusive disease.     

Selective dorsal rhizotomy: long-term experience from Cape Town

Introduction Given the large number of cerebral palsy patients who have undergone selective dorsal rhizotomy in the past two decades, it is clearly imperative that the clinical community be provided with objective and compelling evidence of the long-term sequelae of the procedure. Materials and methods In the early 1980s, Peacock in Cape Town shifted the site of the rhizotomy from the conus medullaris to the cauda equina, and in the past 25 years, more than 200 children have been operated on. We have studied the incidence of spinal deformities after multiple-level laminectomy and recorded a 20% incidence of isthmic spondylolysis or grade-I spondylolisthesis. We have also conducted a long-term prospective gait analysis study on a cohort of 14 ambulatory patients who were operated on in 1985. Results Ten years after surgery, our patients had increased ranges of motion that were within normal limits. Step length was significantly improved, although cadence was unchanged postoperatively and was significantly less than normal age-matched control subjects. Discussion We have recently tracked down all 14 patients from the original cohort and are currently completing a 20-year prospective follow-up analysis of their neuromuscular function and gait. Our preliminary data suggest that selective dorsal rhizotomy is not only an effective method for alleviating spasticity but it also leads to long-term functional benefits.     

An innovative cycling exergame to promote cardiovascular fitness in youth with cerebral palsy

Objective: To evaluate the effects of an internet-platform exergame cycling programme on cardiovascular fitness of youth with cerebral palsy (CP). Methods: In this pilot prospective case series, eight youth with bilateral spastic CP, Gross Motor Functional Classification System (GMFCS) level III, completed a six-week exergame programme. Outcomes were obtained at baseline and post-intervention. The primary outcome measure was the GMFCS III-specific shuttle run test (SRT-III). Secondary outcomes included health-related quality of life (HQL) as measured by the KIDSCREEN-52 questionnaire, six-minute walk test, Wingate arm cranking test and anthropomorphic measurements. Results: There were significant improvements in the SRT-III (t?=??2.5, p?=?0.04, d?=?0.88) post-intervention. There were no significant changes in secondary outcomes. Conclusion: An exergame cycling programme may lead to improvement in cardiovascular fitness in youth with CP. This study was limited by small sample size and lack of a comparison group. Future research is warranted.     

Glucagon-like peptide-1 receptor dimerization differentially regulates agonist signaling but does not affect small molecule allostery

The glucagon-like peptide-1 receptor (GLP-1R) is a family B G protein-coupled receptor and an important drug target for the treatment of type II diabetes, with activation of pancreatic GLP-1Rs eliciting glucose-dependent insulin secretion. Currently, approved therapeutics acting at this receptor are peptide based, and there is substantial interest in small molecule modulators for the GLP-1R. Using a variety of resonance energy transfer techniques, we demonstrate that the GLP-1R forms homodimers and that transmembrane helix 4 (TM4) provides the primary dimerization interface. We show that disruption of dimerization using a TM4 peptide, a minigene construct encoding TM4, or by mutation of TM4, eliminates G protein-dependent high-affinity binding to GLP-1(7-36)NH₂ but has selective effects on receptor signaling. There was <10-fold decrease in potency in cAMP accumulation or ERK1/2 phosphorylation assays but marked loss of intracellular calcium mobilization by peptide agonists. In contrast, there was near-complete abrogation of the cAMP response to an allosteric agonist, compound 2, but preservation of ERK phosphorylation. Collectively, this indicates that GLP-1R dimerization is important for control of signal bias. Furthermore, we reveal that two small molecule ligands are unaltered in their ability to allosterically modulate signaling from peptide ligands, demonstrating that these modulators act in cis within a single receptor protomer, and this has important implications for small molecule drug design.     

The Role of Facial Feedback in the Modulation of Clinically-Relevant Ambiguity Resolution

Two experiments investigated the effect of facial expressions on clinically-relevant ambiguity resolution in a nonclinical sample. Experiment 1 investigated the effect of negative facial feedback (frowning) on a basic threat-interpretation bias procedure using a homophone spelling task and found that participants in a frowning condition interpreted significantly more threat/neutral homophones as threats than did participants in a neutral control condition. Experiment 2 investigated how frowning affected interpretation of bodily sensations. The findings indicated that participants in the frowning condition generated fewer positive consequences for bodily sensation scenarios and also rated the imagined bodily sensations as more negative and more of a cause for health concern. These effects could not simply be explained by differences in self-reported mood or by demand characteristics. These findings suggest that facial expressions have a moderating effect on the cognitive processes that contribute to clinically-relevant ambiguity resolution, and this has implications for clinical interventions.     

Studies of women eating diets with different fatty acid composition. III. Fatty acids and prostaglandin synthesis by platelets and cultured human endothelial cells.

The aim of this study was to determine how plasma fatty acids (FA) of subjects eating either a diet designed to match the US diet consumed in 1974 in fat content and composition in accord with the HANES I survey (US74) or a diet modified to meet the US Dietary Goal Recommendations (MOD) are altered, and how the changes affect platelet thromboxane (TXB2) synthesis, and prostacyclin (PGI2) and prostaglandin E2 (PGE2) synthesis by cultured human endothelial cells. Following a period of recorded self-selected diets, 10 women ate the US74 diet for 4 weeks, changing to the MOD diet for the next 4 weeks (sequence 1), and 10 ate the MOD diet followed by the US74 diet (sequence 2). Plasma triglycerides, free FA, platelet FA composition, and red blood cell phospholipids responded to the change from self-selected to controlled diets, but differences in responses were not seen between US74 and MOD diets. Red blood cell total FA did not respond to dietary changes. Under collagen but not thrombin stimulation, platelet TXB2 synthesis was correlated with platelet arachidonate concentration but not serum cholesterol. Endothelial cells were isolated from umbilical cord veins and incubated for 72 hours with a 20% medium of the women's plasma. In sequence 1 (high saturated FA to high polyunsaturated fatty acids), but not in 2 (reverse order), plasma from subjects eating the MOD diet decreased (p less than 0.05) basal and thrombin-stimulated PGI2 and PGE2 synthesis by the cells. These cells had a higher content of linoleic acid than cells from subjects eating the US74 diet. Thus, our study suggests that an increase in the intake of linoleic acid from 4.8 to 7.6 en% decreases PGI2 and PGE2 synthesis by human endothelial cells, and supplementation of the diet with linoleic acid has a longer period of effectiveness than its decrease in the diet.