British Medical Bulletin Advance Access originally published online on February 21, 2008
British Medical Bulletin 2008 85(1):1-5; doi:10.1093/bmb/ldn010
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Editor's Choice
Once again the British Medical Bulletin presents an extraordinarily wide range of excellent reviews by experts.
First, we have an review on ‘Research on the recently dead: an historical and ethical examination’ (Pages 7–16) by Tomasini from the University of Central Lancashire and Lancaster University.
This paper briefly outlines the history of research on the recently dead, before critically exploring in what sense can we harm the dead and the arguments for employing family or parental consent for medical research on dead relatives? He makes the point that the controversy surrounding harm in relation to research on dead bodies largely depends on how dead people are perceived.
Controversy over whether we need to have consent from significant others (bereaved relatives) depends on the weight we give to the bereaved and their experience of the dead. Understanding this is timely in developing research and is relevant to the issue of consent around organ donation for transplants.
Next a paper on ‘O6-methylguanine-DNA methyltransferase inactivation and chemotherapy’ (Pages 17–33) by Verbeek, Southgate, Gilham and Margison from the University of Manchester.
They show that alkylating agents are frequently used in the chemotherapy of many types of cancer. This group of drugs mediates cell death by damaging DNA and therefore, understandably, cellular DNA repair mechanisms can influence both their antitumour efficacy and their dose-limiting toxicities. The review focuses on the mechanism of action of the DNA repair protein, O6-methylguanine-DNA methyltransferase (MGMT) and its exploitation in cancer therapy.
MGMT can provide resistance to alkylating agents by DNA damage reversal. Inhibition of tumour MGMT by pseudosubstrates to overcome tumour resistance is under clinical evaluation. MGMT overexpression in haematopoietic stem cells has been shown in animal models to protect normal cells against the myelosuppressive effects of chemotherapy: this strategy is being tested in clinical trials. Tissue and tumour specific approaches to the modulation of MGMT together with other DNA repair functions and in combination with immuno- or radiotherapy are promising strategies to improve alkylating agent therapy.
Further genetic approaches in relation to medicine is explored in a review of ‘Epigenetics; what is it and why is it important to mental disease?’ (Pages 35–45) by Isles and Wilkinson from Cardiff University.
The chemical marking of the DNA and surrounding histone proteins represent some of the means by which gene expression is controlled. Many of these epigenetic modifications are pre-programmed, and are an important part of the control of development. A number of studies have demonstrated that the epigenetic status of genes can be altered through environmental events such as in vitro culture of embryos and exposure to toxins, sometimes resulting in disease.
More routine variations in life events may also be encoded by changes in the epigenetic status of genes and, as such, these processes may provide a mechanism mediating interplay between genes and the environment, including the now recognized idea of gene–environment interactions. The significance of epigenetics for mental disease is becoming increasingly clear. It is important that the techniques developed to analyse the epigenome are now applied to the study of the molecular basis of mental disease in order to assess the contribution of gene–environment interactions to brain function.
There follows a review on ‘Ocular regeneration by stem cells—present status and future prospects’ (Pages 47–61) by Limb and Daniels from the Institute of Ophthalmology, London.
Advances in the stem cell field provide much hope for the use of these cells in the regeneration of ocular tissue damaged by diseases for which no treatments are yet available. They discuss the current status and limitations on the application of stem cells to ocular therapies, and consider the future prospects for their use in the restoration of vision. Their review summarizes the achievements to date and the present areas of stem cell investigations in the ophthalmic field.
Owing to its accessibility, the cornea constitutes an easy anatomical target for stem cell regeneration. On this basis, limbal epithelial stem transplantation is the only ocular cell-based therapy already in use in the clinical setting. Regeneration of the retina and less accessible and complex neural tissue, currently constitutes a major challenge. Investigations into the potential use of stem cells for retina regeneration have generated variable data and no therapies have yet been designed for human treatments. Despite the present limitations, it has been progressively accepted that various stem cells may have potential use for the development of cell-based therapies to restore retinal function.
After this we find a review on ‘Bicuspid aortic valve and its impact on sports activity’ (Pages 63–85) by De Mozzi, Longo, Galanti and Maffulli from Keele University School of Medicine, Rome and Florence.
They make the point that the bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. Complications associated with BAV include aortic stenosis and regurgitation, infective endocarditis and aortic dilation and dissection. BAV may be associated with other cardiovascular anomalies, mainly aortic coarctation. The early identification of BAV is of paramount importance but the justification of the more appropriate diagnostic methods still an area of debate. A normally functioning BAV usually does not represent a limit for practising sport.
However, the stress of regular and intense exercise on an abnormal aortic valve may favour its early deterioration and accelerate the development of complications. Therefore, athletes with BAV warrant regular follow-up which should include echocardiographic assessment at least every year. The eligibility for participation and ability to continue to practise competitive sports in athletes with BAV cannot be generalized, but needs to be individualized depending on age, severity of lesions and type of sport.
There follows a clinical review on ‘Gastric cancer’ (Pages 87–100) by Lochhead and El-Omar from Aberdeen University.
They state that gastric cancer remains a major cause of mortality and morbidity worldwide and the total number of gastric cancer cases is predicted to rise as a result of population growth and ageing. The pathogenesis of gastric cancer represents a paradigm for microbially induced and inflammation-driven malignancies and understanding this will be the best means of defeating this cancer.
Helicobacter pylori is the most important aetiological risk factor and the pathogenesis involves the combined effects of host genetics, bacterial virulence and environmental factors. While most accept that removing Helicobacter could prevent gastric cancer, there are still no definitive trials to prove this concept. There is also some anxiety about the long-term effects of removing such a prevalent chronic infection from large sections of the population. Overall, gastric cancer is now arguably one of the most understood malignancies and real progress is being made towards eradicating this global killer.
Next a piece on sports medicine: ‘Mountain biking injuries’ (Pages 101–112) by Carmont from the University Hospital of North Staffordshire.
Mountain biking is a fast exciting adventure sport with increasing numbers of participants and competitions. A search of the literature using keywords of mountain, biking and injuries revealed 2 review articles, 17 case-controlled studies, 4 case series and 5 case reports. This review summarizes the published literature on mountain biking injuries, discusses injury frequency and common injury mechanisms.
He concludes that riders are quick to adopt safety measures. Helmet usage is now increasingly common and handlebar adaptations have been discontinued. Although the sport has a reputation for speed and risk with research and awareness, injury prevention measures are being adopted making the sport as safe as possible.
The next review is about measuring the ‘Quality of life in older ages’ (Pages 113–126) by Netuveli and Blane from Imperial College, London.
The quality of life of elderly people has become relevant with the demographic shift that has resulted in greying of population. There are indications that concepts and concerns related to quality of life in older ages are different from the general population. The majority of elderly people evaluate their quality of life positively on the basis of social contacts, dependency, health, material circumstances and social comparisons.
Adaptation and resilience might play a part in maintaining good quality of life. Two major factors to be considered with regard to quality of life in old age are dementia and depression. With all other influences controlled, ageing does not influence quality of life negatively; rather a long period of good quality of life is possible. Therefore, the maintenance and improvement quality of life should be included among the goals of clinical management.
Next a review on another problem of older people; ‘Age-related macular degeneration’ (Pages 127–149) by Cook, Patel and Tufail from Moorfields Eye Hospital, in London.
Age-related macular degeneration (AMD) is a leading cause of blind registration in Western Europe and the third leading cause of blindness worldwide. They discuss the management of AMD with a review of current and new treatments.
Although there is no treatment for advanced dry AMD (geographic atrophy), there have been considerable advances in the management of neovascular AMD (nAMD). Established therapies for nAMD include laser photocoagulation and photodynamic therapy, but these have largely been superseded by agents which block the action of vascular endothelial growth factor (anti-VEGF agents). Increased understanding of the genetics and pathogenic mechanisms involved will hopefully lead to the development of new therapies in the future.
Finally, we have a review of ‘Adult congenital heart disease’ (Pages 151–180) by Bédard, Shore and Gatzoulis from the Royal Brompton Hospital, and Imperial College, London.
During the past decades, health care of patients born with congenital heart disease (CHD) has improved substantially, leading to a growing population of adult survivors. Using the recently published and relevant data on adult CHD, the authors review the most common congenital heart defects and discuss important related issues.
Adults with CHD most often require specialized medical or surgical care in a tertiary centre. However, this population also need local follow-up; general practitioners and other specialists therefore have to face the complexity of their disease. Management of pregnancy, non-cardiac surgery, arrhythmias and endocarditis prophylaxis may be challenging in patients with CHD and should be adapted to their condition.
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Related articles in BMB:
- Research on the recently dead: an historical and ethical examination
- F. Tomasini
BMB 2008 85: 7-16.[Abstract] [FREE Full Text] - O6-Methylguanine-DNA methyltransferase inactivation and chemotherapy
- Barbara Verbeek, Thomas D. Southgate, David E. Gilham, and Geoffrey P. Margison
BMB 2008 85: 17-33.[Abstract] [FREE Full Text] - Epigenetics: what is it and why is it important to mental disease?
- Anthony R. Isles and Lawrence S. Wilkinson
BMB 2008 85: 35-45.[Abstract] [FREE Full Text] - Ocular regeneration by stem cells: present status and future prospects
- G. Astrid Limb and Julie T. Daniels
BMB 2008 85: 47-61.[Abstract] [FREE Full Text] - Bicuspid aortic valve: a literature review and its impact on sport activity
- Paola De Mozzi, Umile Giuseppe Longo, Giorgio Galanti, and Nicola Maffulli
BMB 2008 85: 63-85.[Abstract] [FREE Full Text] - Gastric cancer
- Paul Lochhead and Emad M. El-Omar
BMB 2008 85: 87-100.[Abstract] [FREE Full Text] - Mountain biking injuries: a review
- Michael R. Carmont
BMB 2008 85: 101-112.[Abstract] [FREE Full Text] - Quality of life in older ages
- Gopalakrishnan Netuveli and David Blane
BMB 2008 85: 113-126.[Abstract] [FREE Full Text] - Age-related macular degeneration: diagnosis and management
- H. L. Cook, P. J. Patel, and A. Tufail
BMB 2008 85: 127-149.[Abstract] [FREE Full Text] - Adult congenital heart disease: a 2008 overview
- Elisabeth Bédard, Darryl F. Shore, and Michael A. Gatzoulis
BMB 2008 85: 151-180.[Abstract] [FREE Full Text]
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