Obesity is Associated with Genetic Variants That Alter Dopamine Availability

Human and animal studies have implicated dopamine in appetite regulation, and family studies have shown that BMI has a strong genetic component. Dopamine availability is controlled largely by three enzymes: COMT, MAOA and MAOB, and by the dopamine transporter SLC6A3, and each gene has a well-characterized functional variant. Here we look at these four functional polymorphisms together, to investigate how heritable variation in dopamine levels influences the risk of obesity in a cohort of 1150, including 240 defined as obese (BMI ≥ 30). The COMT and SLC6A3 polymorphisms showed no association with either weight, BMI or obesity risk. We found, however, that both MAOA and MAOB show an excess of the low-activity genotypes in obese individuals ( MAOA: χ²= 15.45, p = 0.004; MAOB: χ²= 8.05, p = 0.018). Additionally, the MAOA genotype was significantly associated with both weight (p = 0.0005) and BMI (p = 0.001). When considered together, the 'at risk genotype' - low activity genotypes at both the MAOA and MAOB loci - shows a relative risk for obesity of 5.01. These results have not been replicated and, given the experience of complex trait genetics, warrant caution in interpretation. In implicating both the MAOA and MOAB variants, however, this study provides the first indication that dopamine availability (as opposed to other effects of MAOA) is involved in human obesity. It is therefore a priority to assess the associations in replication datasets.     

Acute recognition and management of congestive heart failure

The acute recognition and management of CHF is challenging. A basic understanding of the determinants of cardiac performance and myocardial O2 consumption along with the pathophysiology of CHF is essential knowledge for the physician undertaking to treat this serious disorder. The basic value of the patient history and physical examination along with assessment of noninvasive tests remains unquestioned, but in addition much relevant and sophisticated information can be gained by invasive hemodynamic monitoring. The cardiopulmonary profile generated by such monitoring allows the physician to use specific hemodynamic and circulatory data for the purpose of manipulating these variables favorably for the heart and circulation. A wide array of therapeutic options is currently available, but, in general, respiratory support and pharmacotherapy are the mainstays of treatment. The traditional agents like digitalis and diuretics have assumed a lesser role during the last decade because of the availability of potent new vasodilator and inotropic agents. In addition, certain mechanical, procedural, and surgical options can be used if circumstances are urgent. In the final analysis, physicians who manage these patients must possess strong cognitive skills but also the clinical reflexes to carry them out: for every hemodynamic and circulatory action, they must be prepared to counter quickly and decisively with a clinical reaction which utilizes these principles to optimize cardiac function. It is hoped that the strategies presented in this article will allow them to perform in such a manner.     

Genetics of epilepsy: epilepsy research foundation workshop report.

The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians to consider progress, issues and strategies for harnessing genetics to improve the understanding and treatment of the epilepsies. General principles were considered, including the fundamental importance of clear study design, adequate patient numbers, defi ned phenotypes, robust statistical data handling, and follow-up of genetic discoveries. Topics where some progress had been made were considered including chromosomal abnormalities, neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics were reviewed. Principles and limitations of collaboration were discussed. Presentations and their matched discussions are produced here. There was optimism that further genetic research in epilepsy was not only feasible, but might lead to improvements in the lives of people with epilepsy.     

A method of repair for quadriceps tendon or patellar ligament (tendon) ruptures without cast immobilization. Preliminary report

The quadriceps tendon and patellar tendon (ligament) were repaired with a Dacron vascular graft used as a tension suture material. In cases of quadriceps tendon ruptures, the Dacron graft is passed transversely through the patellar ligament just below the patella and crossed transversely at the level of the musculotendinous junction with two loops applying tension to the tendon, which brings the tendon ends together by creating a solid structure. In cases of patellar ligament ruptures, the Dacron graft is passed through a hole in the tibia posteriorly to the tibial tuberosity instead of through the patellar ligament below the patella. This technique enables early mobilization on the first day after surgery. The technique was first tested on six dogs with severed quadriceps tendons and patellar ligaments that were repaired with this suture method. All of the animals recovered from surgery and walked and ran normally on the repaired legs within 27 days and with only mild limping after 17 days. The technique was then used on six patients, four with complete quadriceps tendon rupture and two with complete tear (avulsion) of the patellar ligament (tendon). In all of the patients, excellent surgical results were obtained and leg immobilization was virtually eliminated. Physical therapy was prescribed the first day after surgery. The rehabilitation period was significantly reduced.     

COSTING ACUTE MYOCARDIAL INFARCTION IN NEW SOUTH WALES,AUSTRALIA, BASED ON INCIDENCE RATHER THAN PREVALENCE METHODS

Estimating the economic costs of a disease is an important prerequisite to determining the costs and benefits of various preventive programs. For preventive programs, incidence-based costing is a more appropriate means of estimation than is prevalence-based costing. In this study the cost of acute myocardial infarction (AMI) in New South Wales has been estimated using an incidence-based approach. The calculated cost of AMI in 1979 was $301.0 million, made up of $32.3 million as direct costs and $268.7 million as indirect costs. In a sensitivity analysis, the cost was shown to be most sensitive to the incidence of AMI, the discount rate, and the assumption of a wage for housework. Both the direct costs and indirect costs per case are substantially higher in the United States than in Australia, and this reflects higher physician charges, higher hospital costs, and in the case of indirect costs, higher average weekly earnings.     

Soul City: a sustainable edutainment vehicle facilitating social change

This paper outlines the programming model employed by the Soul City Institute for Health and Development Communication, a South African NGO, in using ‘edutainment’ to facilitate social change. The paper refers to the intersection of this model and current thought on health promotion and various social change theories. It also discusses key challenges and factors contributing to sustainability over 12 years.     

Breast reconstruction by tissue expansion for congenital and burn deformities

We have used tissue expanders to treat 10 patients with breast deformities, 2 the result of burns and 8 congenital in origin. The expanders are placed in the subglandular plane and expanded incrementally until the desired amount of growth is obtained. In patients with congenital deformities, the desired size of the reconstructed breast (implant size) is determined during the expansion phase. Reconstructions of the nipple-areola complex are done either at the time of the exchange or as separate procedures. Patients with burn deformities present a variety of problems not seen with the congenital deformities. The expander is placed in the subglandular plane and filled to the desired volume. We have noted a marked permanent softening of the scar and grafts encasing the breast, which persists after the expander is removed and the breast reconstructed. The interval between expansion and definitive reconstruction is delayed for several months to allow scar softening to take place. If the parenchyma is not burned and pedicle tissue is not required, the expander can be deflated and the skin coverage observed to determine if it will remain soft. If it does, the expander can be removed and the breast reconstructed. In patients who require pedicle coverage in the reconstruction and who have unburned scar surrounding the breast, massive overexpansion is carried out. The pedicle skin is used to resurface the breast after removal of the appropriate areas of scar and skin grafts. In all burned patients, the inframammary fold must be reconstructed if the breast is to be protuberant. The nipple-areola complex also requires reconstruction. To date there has been great acceptance by patients with both congenital and burn deformities; however, we believe that tissue expansion techniques offer possibilities that have not as yet been fully explored.