This paper briefly outlines the history of research on the recently dead, before critically exploring
1. In what sense can we harm the dead?
2. What are the justificatory arguments for employing family or parental consent for medical research on dead relatives?
The controversy surrounding harm in relation to research on dead bodies largely depends on how dead people are perceived. That is,
1. As Cadavers
2. As Ante-mortem persons
3. By Significant others
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.
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.
This review focuses on the mechanism of action of the DNA repair protein, O6-methylguanine-DNA methyltransferase (MGMT) and its exploitation in cancer therapy and reviews the current literature.
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. In addition, MGMT overexpression in haematopoietic stem cells has been shown in animal models to protect normal cells against the myelosuppressive effects of chemotherapy: this strategy has also entered clinical trials.
MGMT inhibitors enhance the myelotoxic effect of O6-alkylating drugs and therefore reduce the maximum-tolerated dose of these agents. Retroviral vectors used for chemoprotective gene therapy are associated with insertional mutagenesis and leukaemia development.
The results of ongoing preclinical and clinical research involving various aspects of MGMT modulation should provide new prospects for the treatment of glioma, melanoma and other cancer types.
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.
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.
There is an accumulating body of evidence from clinical genetics and animal work that suggests some epigenetic processes may also be labile.
A number of these 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 to assess the contribution of gene–environment interactions to brain function.
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. Here, we 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.
The review summarizes the achievements to date and the present areas of stem cell investigations in the ophthalmic field, based on a literature search and knowledge gained by the authors' work in the subject.
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, a 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.
There is need to understand the cell requirements and environmental conditions that may promote functional integration and long-term survival of stem cells within the diseased retina. At present, this constitutes a major area of research.
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. 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.
We reviewed the relevant English language literature in relation to gastric cancer with particular reference to the role of Helicobacter pylori. We summarize what is known of the epidemiology, aetiology and pathogenesis of gastric cancer. We also describe current approaches to the detection and management of early gastric cancer and discuss the prevention strategies.
H. pylori is the most important aetiological risk factor for this cancer, and the pathogenesis involves the combined effects of host genetics, bacterial virulence and environmental factors.
Although 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.
Gastric cancer is now arguably one of the most understood malignancies, and real progress is being made towards eradicating this global killer. Much work still needs to be done to define the optimal approach for eradicating the causative agent, namely H. pylori infection.
Mountain biking is a fast, exciting adventure sport with increasing numbers of participants and competitions.
A search of PubMed, Medline, CINAHL, DH data, and Embase databases was performed using the following keywords: mountain, biking and injuries. This revealed 2 review articles, 17 case controlled studies, 4 case series and 5 case reports. This review summarises the published literature on mountain biking injuries, discusses injury frequency and common injury mechanisms.
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 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.
A narrative review of selected literature.
Quality of life is described often with both objective and subjective dimensions. The majority of the 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. Although there are no cultural differences in the subjective dimension of quality of life, in the objective dimension such differences exist. 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.
Age-related macular degeneration (AMD) is a leading cause of blind registration in Western Europe and the third leading cause of blindness worldwide.
The management of AMD is discussed 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 (PDT), but these have largely been superseded by agents which block the action of vascular endothelial growth factor (anti-VEGF agents). Current preventative strategies involve cessation of smoking and use of specific nutritional supplements to reduce the risk of developing nAMD.
There have been exciting advances in the treatment of nAMD and increased understanding of the genetics and pathogenic mechanisms involved will hopefully lead to the development of new therapies in the future.
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 (ACHD), we reviewed the most common congenital heart defects and discussed 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.
The present article summarizes key clinical information on ACHD for the benefit of physicians who are not specialized in this field.
Research efforts and education strategies are greatly needed in order to optimize the care of patients with ACHD.