Editor's Choice
This quarter British Medical Bulletin has another excellent varied set of reviews on topics which are new or unusual in emphasis.The first on ‘Clinical applications of musculoskeletal tissue engineering’ (page 7) by Roberts, Howard, Buttery and Shakesheff at the University of Nottingham in the UK looks at an increasingly exciting area of work.
They make the point that current surgical techniques for the repair of the musculoskeletal system can be often limited by the availability, quality and quantity of materials, such as grafts to effect repair. This has led to the exploration and development of novel methods of intervention based on tissue engineering and regenerative medicine. They review the successes and investigations that are happening to date in the field of musculoskeletal tissue engineering. This is based on an extensive literature search and research performed by the authors.
Owing to the constraints surrounding certain surgical techniques and restrictions on their use, novel procedures are required for the repair and regeneration of some of the damaged tissues. The choice of cell type has caused much debate within the tissue engineering field. However, it is widely accepted that currently only autologous primary/adult stem cells are fit for transplantation, until such time that optimized differentiation and selection protocols exist for embryonic stem cells. The current results of the clinical cases utilizing tissue-engineered constructs for bone and cartilage repair provide insights for improving these techniques, thus allowing treatments to become increasingly viable. There is a need better to understand the integration of scaffolds and cell populations into the target tissue. This should provide vital information influencing scaffold manufacturing procedures and cell selection in future.
There follows a paper on ‘Circadian abnormalities, molecular clock genes and chronobiological treatments in depression’ (page 23) by Bunney and Potkin from the University of California.
They state that a long-standing challenge in the treatment of depression is the development of a rapidly acting antidepressant. Conventional antidepressants typically require 2–8 weeks for clinical remission. In contrast, chronobiological interventions such as sleep deprivation treatment dramatically reduce depressive symptoms within 24–48 h in 40–60% of depressed subjects. It is hypothesized that fast-acting treatments for depression may alter circadian rhythms through chronobiological mechanisms relevant to clock gene function.
They provide us with a bibliographic review identifying more than 1000 clinical papers published over a 40-year period. They found that a large body of clinical data reports that sleep, temperature, hormone and mood changes in depression are consistent with disturbances in circadian-related processes. However, consensus has not been achieved in terms of defining underlying chronobiological mechanisms for optimal methods to produce rapid and sustained antidepressant responses to circadian interventions. It is hoped that, in future, chronobiological augmentation using combinations of sleep deprivation with light therapy and/or sleep phase advance in medicated patients will support a clinical strategy for accelerating and sustaining rapid antidepressant responses.
There follows two papers related to problems in children. The first of these is on ‘Sports injuries in children’ (page 33) by Shanmugam and Maffulli from Keele University in the UK.
They state that sports injuries in children affect both growing bone and soft tissues, and can result in damage of growth mechanisms with subsequent lifelong growth disturbance. Their clinical review examines the incidence and distribution, physiology, injury characteristics and the prevention modalities in greater detail.
A literature search found that, during growth, there are significant changes in the biomechanical properties of bone. In young athletes, as bone stiffness increases and resistance to impact diminishes, sudden overload may cause bones to bow or buckle. Fractures that initially unite with some deformity can completely remodel, and the remodelled bone may appear totally normal in later life. Most injuries in childrens' sports are minor and self-limiting, suggesting that children and youth sports are safe. Training programmes should take into account children's physical and psychological immaturity, so that growing athletes can adjust to their own body's changes.
There follows a review by Matyka at Warwick Medical School in the UK on ‘Diabetes in childhood – epidemiological and clinical aspects’ (page 59).
She makes the point that the global obesity epidemic has raised concerns about the risk of a tide of Type 2 diabetes (T2DM) in childhood. The review looks at the recent data on the epidemiology of this problem as well as the clinical concerns. A review of 16 paediatric studies suggest that, although T2DM is now more widely reported in childhood, the numbers are still reasonably small, although the data do suggest that ethnicity is an important risk factor.
There are emerging data on what appears to be a significant risk of both microvascular and macrovascular complications. In youth-onset T2DM, the most appropriate management remains unclear. Currently, adult guidelines for management of T2DM are being extrapolated to the adolescent population with T2DM, and studies are underway to examine the pharmacological management of childhood T2DM. More data are necessary on the exact prevalence of T2DM among a variety of populations to provide a greater understanding of the risk factors for T2DM and provide indications for screening. In the meantime, great emphasis needs to be placed on obesity prevention if we are to protect the health of future generations of children.
The next review by Hjerrild, Mortensen and Gravholt from the Aarhus University Hospital in Denmark is on ‘Turner syndrome and clinical treatment’ (Page 77).
They show that Turner syndrome is a genetic disorder associated with abnormalities of the X chromosome, occurring in about 50 per 100 000 liveborn girls. It is usually associated with reduced adult height, gonadal dysgenesis and low concentrations of female sex steroids leading to premature ovarian failure and infertility. Average intellectual performance is within the normal range. Treatment with growth hormone (GH) during childhood and adolescence allows a considerable gain in adult height. Short stature homeobox gene (SHOX) deficiency explains some of the phenotypic characteristics in TS, principally short stature. Puberty has to be induced in most cases, and female sex hormone replacement therapy (HRT) is given during the adult years. Morbidity and mortality is increased, especially due to the risk of dissection of the aorta and other cardiovascular diseases, as well as the risk of T2DM, osteoporosis and thyroid disease.
The proper dose of HRT with female sex steroids has not been established and, likewise, benefits and/or drawbacks from HRT have not been thoroughly evaluated. In most countries, the transition period from paediatric to adult care is especially vulnerable. Treatment recommendations are based on expert opinion and are unfortunately not evidence based, although more areas, such as GH treatment for increasing height, are well founded. Proper care during adulthood needs to be studied, since most morbidity is amenable to proper care. Turner syndrome is a condition associated with a number of diseases and conditions that need the attention of a multi-disciplinary team.
Next, we have another review related to sports medicine; ‘Doping in competition or doping in sport?’ (page 95) by Lippi, Franchini and Guidi from Verona in Italy.
They make the point that competitive athletes have used drugs since ancient times, and they will probably continue to use unfair and harmful substances in future, because their motivation to win, along with the idea of glory and money, will probably overcome their fear of health and legal risks. The authors systematically searched for papers on the topic. The phenomenon of doping is found to be complex and multifaceted. It involves a number of causes and factors that do not originate solely in the athletic field. It is observed in all ages and levels of competition, and it concerns all sports, even the most unpredictable.
The high number of athletes testing positive during anti-doping controls attests that the current strategy may be adequate to unmask most (but not all) doping practices, but it is probably ineffective at preventing athletes from using dope and to modify this upsetting trend. Since doping parallels the use of medications, food supplements, alcohol and social drugs, a reinforced preventive policy is thought to be advisable. The current anti-doping policy should be replaced with a more efficient and practical strategy to identify and monitor abnormal and harmful deviations of biochemical and haematological profiles.
There follows an update on ‘Parkinson's disease’ (page 109) by Davie at the Royal Free Hospital in London.
He makes the point that Parkinson's disease (PD) is one of the most common neurodegenerative disorders. He systematically searched the literature to find that there have been significant recent advances in the understanding of the pathogenesis of the disease. There has also been a greater realization that the disorder may be associated with significant non-motor disturbances in addition to the more commonly recognized motor complications.
Although there is growing circumstantial evidence, it remains to be proven whether any of the current treatments for PD have a neuroprotective effect. Although there is no cure, there are several management options for the early treatment of PD. As the disease progresses, further treatment options are available; however, the management of late stage motor complications and non-motor symptoms remain particularly challenging and will benefit from further clinical research.
Lastly, a review on that most important of subjects ‘The treatment of post-menopausal osteoporosis’ (Page 129) by Cole, Dennison and Cooper from Southampton in the UK.
They make the point that osteoporosis has a huge impact on public health, through increased morbidity, mortality and economic costs associated with resultant fractures. The lifetime incidence of any fracture in 50 year olds in Britain is 40% for women and 13% for men. The annual cost of osteoporosis is £1.7 billion in the UK alone. The goal is to evaluate and identify those who are at risk of osteoporotic fractures in order to start preventative and therapeutic measures to reduce their risk of fracture. Their article reviews the data from randomized controlled trials for the current therapeutic agents available in the UK. It also reviews new trial data for promising osteoporosis therapies in particular denosumab, a monoclonal antibody against receptor activator for nuclear factor KB (RANK) ligand.
Bisphosphonates are the current recommended first line treatments for patients with osteoporosis. There are a number of patients where bisphosphonates are contraindicated. Under these circumstances it is important that clinicians have access to alternative treatments. The long-awaited National Institute for Health and Clinical Excellence (NICE) technology appraisals for both primary and secondary prevention and the clinical guidelines will clarify this. Treatment decisions should be based on risk factors and pharmaceutical intervention given to those with the highest risks. Future studies are required to look at these agents in combination to see whether anti-fracture efficacy can be improved.
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Related articles in BMB:
- Clinical applications of musculoskeletal tissue engineering
- Scott J. Roberts, Daniel Howard, Lee D. Buttery, and Kevin M. Shakesheff
BMB 2008 86: 7-22.[Abstract] [FREE Full Text] - Circadian abnormalities, molecular clock genes and chronobiological treatments in depression
- Jennifer N. Bunney and Steven G. Potkin
BMB 2008 86: 23-32.[Abstract] [FREE Full Text] - Sports injuries in children
- Chezhiyan Shanmugam and Nicola Maffulli
BMB 2008 86: 33-57.[Abstract] [FREE Full Text] - Type 2 diabetes in childhood: epidemiological and clinical aspects
- K. A. Matyka
BMB 2008 86: 59-75.[Abstract] [FREE Full Text] - Turner syndrome and clinical treatment
- Britta E. Hjerrild, Kristian Havmand Mortensen, and Claus H. Gravholt
BMB 2008 86: 77-93.[Abstract] [FREE Full Text] - Doping in competition or doping in sport?
- Giuseppe Lippi, Massimo Franchini, and Gian Cesare Guidi
BMB 2008 86: 95-107.[Abstract] [FREE Full Text] - A review of Parkinson's disease
- C. A. Davie
BMB 2008 86: 109-127.[Abstract] [FREE Full Text] - Update on the treatment of post-menopausal osteoporosis
- Zoë Cole, Elaine Dennison, and Cyrus Cooper
BMB 2008 86: 129-143.[Abstract] [FREE Full Text]
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