Editor's Choice
This edition of the British Medical Bulletin contains the usual wide range of review articles, from genetics to community care. There are two reviews on imaging, two on public health problems and two reviews on important clinical problems.
Moving through the reviews in our traditional manner, from those with the most theoretic content to those with most practical (though they all contain a great deal of both), we have first a review by Eamonn Maher in Birmingham (UK) on the Genetics of phaeochromocytoma (page 141).
At the end of the 20th Century, inherited phaeochromocytoma was generally considered to account for about 10% of all cases. He shows that recent advances examining the genetics of phaeochromocytoma susceptibility have revealed a much larger inherited contribution to its pathogenesis has been recognized. The identification of individuals with phaeochromocytoma susceptibility disorders (e.g. von Hippel-Lindau disease, succinate dehydrogenase subunit mutations, multiple endocrine neoplasia type 2 and neurofibromatosis type 1) is important because it may be possible to reduce the morbidity and mortality from phaeochromocytoma and other relevant tumours in affected individuals and their at risk relatives. Recent studies have provided clues to the molecular pathogenesis of phaeochromocytoma development in families and suggest that this differs from that seen in sporadic non-inherited cases.
The identification of germline mutations in succinate dehydrogenase subunit genes (SDHB and SDHD) in patients with familial and sporadic phaeochromocytoma has significantly increased estimates of the frequency of inherited phaeochromocytoma. Furthermore investigations of the molecular mechanisms of inherited phaeochromocytoma have suggested that Mendelian disorders predisposing to phaeochromocytoma share a common defect in programmed cell death during normal development.
Our next review, by Peter Karran at the Cancer Research UK London Research Institute is about Thiopurines, DNA damage, DNA repair and therapy-related cancer (page 153).
He states that the thiopurines, azathioprine, 6-mercaptopurine and 6-thioguanine are at the centre of a success story of chemotherapy. They are effective immunosuppressants and anti-cancer agents and are prescribed increasingly to treat inflammatory diseases. Although their metabolism has been studied in detail, the optimal use of thiopurines has been guided predominantly by clinical experience and the precise molecular events that underlie their therapeutic activity have remained unclear. The aim of this review is to examine some of the properties of the thiopurines and relate them to possible therapeutic mechanisms. In particular, it considers the contribution that DNA substitution by 6-thioguanine makes to their effects as well as some of the possible harmful reactions that DNA 6-thioguanine might undergo. The increased chemical reactivity of DNA 6-thioguanine underlies its cytotoxic effects and is an important contributor to the anti-leukaemic effects of the thiopurines. However the same enhanced reactivity may contribute to the increased risk of acute myeloid leukaemia and skin cancer in thiopurine-treated organ transplant patients.
The next two papers look at different approaches to imaging. The first is a general review by Jonathan Berry and Gary Cook from the Royal Marsden Hospital in Surrey on Positron emission tomography in oncology (page 171).
They make the point that increasing access to positron emission tomography-computed tomography (PET-CT) has resulted in a shift towards functional imaging, being the primary tool in the assessment of viable tumour in oncology patients. In this review, they discuss the basic principles of the evolving technology and the radio-isotopes it employs. The main clinical applications of PET-CT are reviewed and some of the limitations of the technique are highlighted. Finally, they offer an insight into possible future developments and how these modify current practice. In a short space of time, PET–CT has established itself as an essential component in the assessment of malignancy. There is little doubt that as understanding of PET–CT grows among the medical community as a whole, indications for PET–CT will grow.
The second on imaging by Henneman, Schuijf, van der Wall and Bax from the Department of Cardiology in Leiden, The Netherlands is a general review on Non-invasive anatomical and functional imaging for the detection of coronary artery disease (page 187).
They say that coronary artery disease (CAD) is still an important cause of morbidity and mortality in the Western world and that the gold standard for assessing significant coronary artery stenosis is invasive coronary angiography. However several disadvantages of the technique in combination with the fact that a substantial number of patients referred for conventional angiography appear free from significant stenosis have led to the pursuit of non-invasive imaging modalities for the diagnosis of CAD. The traditional methods for this purpose are gated single-photon emission computed tomography, position emission tomography, (contrast) stress echocardiography and cardiac magnetic resonance (CMR). These techniques can be characterized as functional imaging techniques as they detect ischaemia. Although the presence of a flow-limiting stenosis can be adequately ruled out with these techniques, atherosclerosis cannot be visualized with functional techniques. For this purpose, non-invasive coronary angiography techniques (computed tomography and CMR) are currently under development. The purpose of the review is to provide readers with an overview of the currently used imaging methods for detecting CAD.
The next review by Cooper, Barreto and Rodrigues; a group from the St Georges in London, Bahia in Brazil, with contacts in Ecuador and the London School of Hygiene and Tropical Medicine is another general review but with a conceptual model to guide the investigation of possible causal associations in Human allergy and geohelminth infections (page 203).
They state that geohelminth infections and allergic disease are major public health problems and there is evidence in developing countries that they are associated. Although there is an extensive literature of the relationship between geohelminth infections and allergy, there is little consensus on whether the association is causal and if so, whether geohelminth infections increase or decrease the risk of allergy. An explanation for the conflicting findings of epidemiological studies is that geohelminths decrease the risk of allergy in areas of high infection prevalence and conversely increase the risk of allergy in areas of low prevalence. Chronic geohelminth infections are inversely associated with allergy and anthelmintic treatment may increase the prevalence of allergy. In this paper they review studies that have investigated the relationship between geohelminths and allergy, discuss the relevance of prevalence and timing of geohelminth infections and propose a conceptual model to define relevant scientific questions in future human and animal studies.
From infectious disease we move to another public health problem; the possible sequelae of chemical exposure. This review by Finlay Dick in Aberdeen is on Parkinson's disease and pesticide exposures (page 219).
He undertook a systematic review of the literature on the subject and showed that many studies have found an association between pesticides and Parkinson's Disease (PD), but no one agent has been consistently identified. Those implicated include organochlorine insecticides, maneb and paraquat. One meta-analysis of pesticide exposure and PD found an almost doubling of risk in those exposed. Associations with specific agents may be confounded by exposure to other pesticides, making it difficult to identify the causative agent. He concludes that the available evidence indicates that pesticides are associated with PD, but further research is needed to identify long-term biomarkers of exposure, improve methods for estimating pesticide-exposure and undertake prospective cohort studies of pesticide-exposed workers.
Our next reviewer, James Acheson from Moorfields Eye Hospital and the National Hospital for Neurology and Neurosurgery in London looked at Idiopathic intracranial hypertension and visual function (page 233). He gives an overview of the literature and provides internal audit data.
Idiopathic intracranial hypertension is a relatively common condition with an incidence up to 19/100,000 people/year in the high-risk group of obese women in reproductive age range. It causes headaches with papilloedema. Detailed investigations are required to exclude other causes of raised intracrainal pressure. The condition may be self-limiting or enter a chronic phase with significant morbidity because of headache and visual loss. The management of hypertension is initially medical, utilizing a combination of managed weight reduction and diuretic therapy. Cerebrospinal fluid (CSF) diversion surgery may be required to stabilize vision. Options include neurosurgical shunting by lumbar-peritoneal of ventriculo-peritoneal routes or by optic nerve sheath fenestration or both. High category evidence from randomized trials to guide management decisions is lacking. This review sets out to guide current best practice.
Finally we have a review by Helen Killaspy at the Royal Free and University College London Medical School on a vital piece of health policy for mentally ill people; the move From the asylum to community care (page 245) and its present status.
This is a systematic review of research and policy on community care. Her search of the literature returned 349 titles in total. Inclusion criteria were quality and relevance to other specialties. Policy material was included to illustrate the socio-political context of the development of community services. It was found that community care was consistently associated with greater patient satisfaction and quality of life across specialties. It was not a cheaper alternative to hospital care. The disadvantages of the policy include the exodus of experienced inpatient staff to community settings and the development of alternative institutions in the non-statutory sector. She concludes that the increased interest in community care for other groups, especially physical health problems should learn from the experience of the mental health services.
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Related articles in BMB:
- Genetics of phaeochromocytoma
- Eamonn R. Maher
BMB 2006 79-80: 141-151.[Abstract] [FREE Full Text] - Thiopurines, DNA damage, DNA repair and therapy-related cancer
- Peter Karran
BMB 2006 79-80: 153-170.[Abstract] [FREE Full Text] - Positron emission tomography in oncology
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BMB 2006 79-80: 171-186.[Abstract] [FREE Full Text] - Non-invasive anatomical and functional imaging for the detection of coronary artery disease
- M. M. Henneman, J. D. Schuijf, E. E. van der Wall, and J. J. Bax
BMB 2006 79-80: 187-202.[Abstract] [FREE Full Text] - Human allergy and geohelminth infections: a review of the literature and a proposed conceptual model to guide the investigation of possible causal associations
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BMB 2006 79-80: 219-231.[Abstract] [FREE Full Text] - Idiopathic intracranial hypertension and visual function
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