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.

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.

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.

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.

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.

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.

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.

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.

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.

We took arthroscopy to be the ‘gold standard’, and we undertook a systematic review of MRI and arthroscopy in the diagnosis of internal derangements of the knee. We used Coleman scoring methodology to identify scientifically sound articles in a reproducible format.

MRI is highly accurate in diagnosing meniscal and anterior cruciate ligament (ACL) tears. It is the most appropriate screening tool before therapeutic arthroscopy. It is preferable to diagnostic arthroscopy in most patients because it avoids the surgical risks of arthroscopy. The results of MRI differ for medial and lateral meniscus and ACL, with only 85% accuracy.

Study design characteristics should also be taken into account whenever a study on MRI assessing its diagnostic performance is designed or reviewed.

II, systematic review of level II studies.

We identified 200 potentially relevant studies from 1966 to June 2006 and eliminated 187 studies that did not fulfil the objectives of the study. We identified 13 studies with echocardiographic assessment of heart adaptation following variation in training loads in elite or subelite endurance-trained athletes. We performed a meta-analysis by studying the changes in the left ventricular end-diastolic (LVEDD), left ventricular end-systolic (LVESD), left ventricular posterior wall (LVPW) and interventricular septum thickness (IVST) dimensions induced by training.

A significant positive overall effect size on echocardiographic outcomes was found following training, using the fixed effect model on LVPW, LVEDD, LVESD and IVST. LVPW and LVEDD were significantly higher following training.

Studies reported an increase in LVEDD and LVPW, following endurance training. However, the heterogeneity of the studies and the sensitivity of echocardiography technique can be two reasons, for which the results do not allow to state unequivocally that the adaptation to endurance training of highly trained hearts stems from increments of diastolic diameter of the left ventricle and lateral wall of the left ventricle (LVPW).

We conducted a comprehensive literature search using Medline, Embase, Cochrane, CINAHL and Google Scholar. The bibliographies of papers were also examined. All relevant articles in peer-reviewed journals were retrieved except those not mentioning outcomes, case reports, review of literature and letters to editors. Two authors independently scored the quality of the studies using a modified Coleman Methodology Score with 10 criteria which allow critical analysis of the design and implementation of a particular study. The results are recorded as a final score between 0 and 100. We collected data for year of publication, type of study, patient numbers, surgical method, follow-up, complications and patient satisfaction.

Thirty-six studies met our inclusion criteria giving details of 6434 HAs, 78.5% (4031) of which were implanted using MIHA techniques. The only statistically significant outcome was a reduction in length of hospital stay (P = 0.02). With no significant difference noted between the two groups with respect to operating time, blood loss, dislocation and revision rates, neurological injury and incidence of peri-operative fracture, patient selection and surgeons' experience may have had a significant effect on outcome. For instance, studies reporting outcomes on an average patient age of 48 years had significantly different results to one reporting on patients with a mean age of over 70 years. Scores were predominantly low for quality of the studies, with patient number, follow-up time and validated outcome measures being the weakest areas.

At present, there is still a lack of quality evidence to advocate the expansion of MIHA. The better designed studies suggest that it should even be limited further to recognized expert centres. The complication rates and learning curve may be altered by changes in training and adapting surgical techniques. We emphasize the need for meticulous design in future studies comparing the outcomes of these two procedures.

This review provides a brief summary of our current understanding of the epidemiology, clinical presentation and therapeutic approaches of what is termed ‘the HIV-associated lipodystrophy syndrome’ and of HIV-associated lipid and glucose metabolic abnormalities. Other metabolic associations including lactic acidosis, HIV-associated bone disease and the effect of the virus on other endocrine pathways are outside the scope of this article.

A bibliographic search was performed using Entrez Pubmed^®, edition 2.0, by the National Library of Medicine for articles only in the English language using Boolean operators and the terms ‘HIV, HAART, lipodystrophy, lipoatrophy, lipohypertrophy, hyperlipidemia, diabetes and metabolism, cost of illness’. The Program and Abstract Books of the 8th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV (September 24–26, 2006, San Francisco, USA), the 4th International AIDS Society Conference on HIV Pathogenesis (July 22–25, 2007, Sydney, Australia) and the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (September 17–20, Chicago, USA) were searched for relative abstracts. Previous publications were used to identify further references. Approximately 1400 articles and abstracts were identified of which 104 were selected for review.

Specific medications and medication classes increase the lipoatrophy and lipodystrophy risk. A change of treatment strategy might be beneficial in improving adipose tissue deposition. The effects of HIV on metabolism offer new insights into cardiovascular disease pathogenesis.

We conduct a narrative review of neuroscientific studies focused on the role of emotion in morality. Specifically, we describe evidence implicating the ventromedial prefrontal cortex (VMPC), a brain region known to be important for emotional processing.

Functional imaging studies demonstrate VMPC activation during tasks probing moral cognition. Studies of clinical populations, including patients with VMPC damage, reveal an association between impairments in emotional processing and impairments in moral judgement and behaviour.

Considered together, these studies indicate that not only are emotions engaged during moral cognition, but that emotions, particularly those mediated by VMPC, are in fact critical for human morality.

The literature was reviewed to assess the role of EUS in cancer staging.

EUS is an integral part of the staging of many upper gastrointestinal cancers as well as rectal and lung cancer and has been shown to be cost-effective. It can be used to confirm malignancy in suspicious lesions as well as to identify and confirm nodal or metastatic spread. It has been used to re-stage cancers following chemoradiotherapy, but results are disappointing. Future developments are discussed, which may include using EUS-guided delivery of anti-tumour agents directly into tumours.

Relevant literature was reviewed with regards to the different dyes and techniques used for the detection of SLN in breast cancer.

Highest identification rates and lowest false negative rates are achieved by using the combined blue dye and radiocolloid technique with pre-operative imaging using a gamma camera. There is a well-recognized learning curve to successfully perform SLN biopsy.

The concept of SLN has been well validated and is the standard of care in early breast cancer. A multidisciplinary approach and structured training is the key to the successful introduction of the technique.

The largest and most inclusive forensic database in the world, the UK National DNA database (NDNAD), leads the worldwide trend towards greater inclusivity. The performance of the NDNAD, criteria for inclusion, legislative framework and plans for integrating forensic databases across Europe are discussed. Comparisons are drawn with UK biobank that has started collecting DNA samples linked to medical records and, unlike the NDNAD, requires informed consent from volunteers, allows withdrawal of samples and only includes adults. The potential uses of research into genes associated with violent and ‘antisocial’ behaviour are discussed in the context of an increasing degree of surveillance in the UK.

It should not be assumed that the benefits of forensic databases will necessarily override the social and ethical costs, regardless of changes to the criteria for inclusion or the permitted uses of samples and profiles. The expansion of forensic databases raises issues of relevance to the medical profession.

This paper suggests that policies to increase patient choice require a significant investment in terms of restructuring primary-care services to allow them to happen, as well as to present relevant information to patients, but that patients may not want to make choices about where and what type of treatment they receive for the most part, being content with having a larger say in when they are treated.

We conducted a narrative review summarizing epidemiological data on medication-related adverse events in elderly people, considering various known causes of such events and suggesting practical ways in which prescribing can be made safer for high-risk populations.

There is an increasing recognition that a relatively high proportion of ADEs in the elderly may be preventable. Systems issues have been found to play a particularly powerful role in this context, resulting in several promising approaches to address the problem.

Relatively simple system changes have the potential to reduce the burden associated with medication-related adverse events in the elderly.

This article will review the requirements and strategies for successful MoAb therapy and the clinical experience in a range of lymphoid malignancies. On the basis of substantial experience of antibodies, such as rituximab and alemtuzumab, as single agents, there is now evidence from randomized trials that the addition of antibodies to chemotherapy improves efficacy and prolongs progression free and overall survival for patients with follicular and diffuse large B-cell lymphomas.

The trials of the next decade will address issues such as the optimal strategies and timing for clinical use, the role of radio- and immuno-conjugates and, finally, what other potential molecules, such as those influencing cell growth and death, may be targeted.

The literature was reviewed with regard to the concept of VCI and its incidence, pathophysiological substrate, clinical features and management.

A change in the diagnostic paradigm from the current Alzheimer-based definition of vascular dementia to VCI will allow the earlier identification of cases and will identify a different population from that recognized using the current criteria for vascular dementia.

Case identification at the earliest possible stage affords the greatest opportunity for treatment that may slow the rate of progression.

Laser refractive surgery is now a safe and effective alternative to glasses or contact lenses.

Because refractive surgery is an area of rapidly developing technology, the relative benefits of the different surgical options remain uncertain.

Controlled trials are needed to provide better guidance as to the relative merits of the different surgical options. Better interventions are required to minimize the biological response after laser surface treatment to eliminate the need for mechanical cutting of a flap for laser in situ keratomileusis. An effective surgical treatment for presbyopia is awaited.

We highlight the main physical symptoms encountered in metastatic prostate cancer and their management. We also introduce the UK Department of Health's ‘End-of-Life Care Programme’. This initiative intends to improve the lives and deaths of all patients with incurable disease and should be a priority for all health care professionals, within any setting.

Clearly, we have addressed the management of metastatic prostate cancer within the UK setting, though any of these government initiatives may provide a resource and framework in other countries.

Orthopaedic clinic.

Randomized trials were identified from a current search of The Cochrane Bone, Joint and Muscle Trauma Group specialized register of trials, the Cochrane Central Register of Controlled Trials, MEDLINE and reference lists of articles and dissertations. We included 10 trials that randomized 948 participants to SWT or placebo or treatment control. For each trial, two independent reviewers assessed the methodological quality and extracted data. Methodological quality criteria included appropriate randomization, allocation concealment, blinding, number lost to follow-up and intention-to-treat analysis.

Conflicting results of the 10 studies were found. There was considerable heterogeneity in terms of methodological quality; treatment regimen; patient selection and follow-up period, precluding pooled analyses. Instead, individual trial results were described in the text. Only six trials had a high-quality methodology. Two independent high-quality randomized placebo-controlled trials (196 participants) reported significant success of SWT over placebo (65 versus 28%; 61 versus 29%). Design of both trials included enrolment of chronic recalcitrant patients only; 1500–2000 shocks of low-energy flux density (0.1 mJ/mm²) applied to the site of maximal discomfort (clinical focusing) in weekly intervals; no use of local anaesthesia and main follow-up at least 3 months after the last application. Three other independent high-quality trials (406 participants) did not find any benefit of SWT over placebo (32 versus 33%; 35 versus 34%; 39 versus 31%). In these three trials, study designs deviated from the design described earlier, enrolling acute patients or applying SWT under local anaesthesia or expanding the application intervals to 4 weeks, while reducing the main follow-up to 4 weeks.

With current studies heterogeneous in terms of the duration of the disorder; type, frequency and total dose of SWT; period of time between SWT; type of management and control group; timing of follow-up and outcomes assessed, a pooled meta-analysis of SWT for lateral elbow tendinopathy was considered inappropriate. In a qualitative systematic per-study analysis identifying common and diverging details of 10 randomized-controlled trials, evidence was found for effectiveness of shock wave treatment for tennis elbow under well-defined, restrictive conditions only.

We searched the literature for relevant studies. Most of the published studies in these fields have used 434 and 915 microwave diathermy, as these wavelengths are most effective.

Hyperthermia induced by microwave diathermy into tissue can stimulate repair processes, increase drug activity, allow more efficient relief from pain, help in the removal of toxic wastes, increase tendon extensibility and reduce muscle and joint stiffness. Moreover, hyperthermia induces hyperaemia, improves local tissue drainage, increases metabolic rate and induces alterations in the cell membrane.

The biological mechanism that regulates the relationship between the thermal dose and the healing process of soft tissues with low or high water content or with low or high blood perfusion is still under study. Microwave diathermy treatment at 434 and 915 MHz can be effective in the short-term management of musculo-skeletal injuries.